Surgical management of dysthyroid optic neuropathy: A systematic review.
There is currently no recommendation on the optimal surgical management for dysthyroid optic neuropathy (DON). The aim of this study is to systematically review the surgical management of DON and its outcome on visual acuity (VA). MEDLINE, Cochrane Library, and clinicaltrials.gov REVIEW METHODS: A systematic review of studies about the surgical management of DON was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Articles were included if preoperative and postoperative VA in logMAR (Logarithm of the Minimum Angle of Resolution) were available. Fifteen articles were included in the study accounting for 669 orbits. The mean VA improvement was of 0.44 logMAR overall, 0.41 logMAR for 1-wall, 0.41 logMAR for 2-wall, and 0.55 logMAR for 3-wall decompressions. The mean reduction in exophthalmos was 4.9 mm overall, 4.3 mm for 1-wall, 4.54 mm for 2-wall, and 6.02 for 3-wall decompressions. The mean new onset diplopia (NOD) rate was 19.84% overall, 19,12% for 1-wall, 20.75% for 2-wall, and 19.83% for 3-wall decompressions. The results are limited due to the high number of biases in the included studies. It seems that 3-wall decompression offers the best VA improvement and proptosis reduction although also the highest NOD and complications rate. Two-wall balanced decompression or 1-wall inferomedial decompression seems to be effective with less morbidity.


Alcohol withdrawal delirium - diagnosis, course and treatment.
Delirium tremens represents the most severe complication of alcohol withdrawal syndrome and, in its complications, significantly increases the morbidity and mortality of patients. Alcohol withdrawal delirium is characterized by features of alcohol withdrawal itself (tremor, sweating, hypertension, tachycardia etc.) together with general delirious symptoms such as clouded consciousness, disorientation, disturbed circadian rhythms, thought processe and sensory disturbances, all of them fluctuating in time. The treatment combines a supportive and symptomatic approach. Benzodiazepines in supramaximal doses are usually used as drugs of choice but in some countries such as the Czech Republic or Germany, clomethiazole is frequently used as well. A computer search of the all the literature published between 1966 and December 2012 was accomplished on MEDLINE and Web of Science with the key words "delirium tremens", "alcohol withdrawal", "treatment" and "pharmacotherapy". There were no language or time limits applied. When not early recognized and treated adequately, delirium tremens may result in death due to malignant arrhythmia, respiratory arrest, sepsis, severe electrolyte disturbance or prolonged seizures and subsequent trauma. Owing to these possible fatalities and other severe unexpected complications, delirium tremens should be managed at an ICU or wards ensuring vital signs monitoring. In symptomatic treatment, high doses of benzodiazepines, especially lorazepam, diazepam and oxazepam are considered the gold standard drugs. Supportive therapy is also of great importance.


Tuberoinfundibular peptide of 39 residues decreases pain-related affective behavior.
Tuberoinfundibular peptide of 39 residues (TIP39) is a recently identified parathyroid hormone 2 receptor ligand. Their CNS distributions suggest potential involvement in neuroendocrine, limbic and sensory processing functions. Herein we investigate the analgesic and antinociceptive actions of brain delivery of TIP39 in adult male rats. Intracerebroventricular (i.c.v.) TIP39 did not change hot-plate paw withdrawal latency or formalin test behavioral responses. TIP39 partially reversed tactile withdrawal hypersensitivity following carageenan administration. In the place/escape avoidance paradigm (PEAP), which evaluates affective components of responses to noxious stimuli by presenting a choice between a naturally preferred environment paired with stimulation of a carrageenan sensitized paw and a less preferred environment paired with stimulation of a less sensitive paw, TIP39 decreased the apparent aversiveness of sensitive paw stimulation. Because acute sensory thresholds were unaffected by TIP39, and the effects of i.c.v. TIP39 were opposite in direction from previously described effects of intrathecal TIP39, this suggests that TIP39 may modulate an affective component of nociception within the brain.


Food insecure student clients of a university-based food bank have compromised health, dietary intake and academic quality.
University and college students in wealthy countries may be vulnerable to financial food insecurity. If food insecure students have suboptimal health, their ability to learn and excel in their education could be compromised. This Canadian study examined the relationship of food security status to diet and self-perceived health and academic quality among students receiving emergency food hampers from the Campus Food Bank at University of Alberta. A convenience sample of 58 students completed a survey. Of participating students, 10.3% were food secure, 44.8% were moderately food insecure and 44.8% were severely food insecure. Overall, 32.8% rated their general health as fair/poor, 27.6% rated their mental health as fair/poor and 60.3% indicated at least one adverse academic outcome of not having enough money for food. Compared to other participating students, students with severe food insecurity had a greater likelihood of fair/poor general health (odds ratios (OR) 4.03, 95% confidence intervals (CI) 1.10-14.78); fair/poor mental health (OR 4.96, 95% CI 1.28-19.19); being unable to concentrate in class or during an exam (73.1% vs 40.6%, χ2 = 6.12, P = 0.013); relying on food hampers (34.6% vs 9.7%, χ2 = 5.57, P = 0.018); and, consuming fewer daily fruits, vegetables and legumes (2.12 vs 2.97 cup equivalents, P = 0.009). Food insecurity compromises students' health, diet and academic quality. Campus food banks are not the solution to student hunger. Governmental and university-based programmes and policies are needed to improve the food security situation of university students.


Overnight basal insulin requirements in insulin dependent diabetics.
Programming open loop insulin delivery systems makes necessary the knowledge of patients insulin needs. It is frequently postulated that insulin needs increase at the end of the night in relation to the rise in cortisol secretion. According to this hypothesis is it justified to speed up the insulin infusion rate in the early morning? This question was addressed by studying insulin infusion rate by an artificial pancreas during the night in 12 C. peptide negative insulin dependent diabetics. They were connected to the artificial pancreas from 8 a.m. to 10 a.m. the next morning while on their habitual diabetic diet and slept as usual from 11 p.m. to 7 a.m. approximately. From 11 p.m. to 7 a.m. mean insulin infusion rate was 21.5 +/- 3.3 mU/Kg/h representing 15.6 +/- 1.6% of the dose delivered in 24 hours. Blood glucose was stable around 85 mg/dl. No significant differences were observed in the hourly insulin infusion rate during the night period, in spite of a slight tendency to a rise (from 21.1 +/- 2.8 to 22.1 +/- 2.6 mU/kg/h) tendency to a rise (from 21.1 +/- 2.8 to 22.1 +/- 2.6 mU/kg/h) after 4 a.m. On the basis of these results obtained in patients sleeping as usual it does not appear useful to envisage a systematic acceleration of insulin infusion rate by continuous delivery systems in the early morning.


A seven-m6A regulator-related CpG site-based prognostic signature for endometrial carcinoma.
Endometrial carcinoma (EC) has become a common gynecologic malignancy with a high mortality. The m6A regulators have been identified to be closely associated with multiple human cancers including EC. However, the CpG methylation signature related to m6A regulators in EC remains unclear. The methylation profiles of EC patients including cancer samples and adjacent normal samples were obtained from The Cancer Genome Atlas (TCGA) database. The CpG sites in 20 m6A regulators were identified. Univariate Cox regression and LASSO Cox regression analysis were used to screen key CpG sites which were located at m6A regulators and significantly related to the prognosis of EC. The predictive model for EC prognosis was constructed, and multivariate Cox regression analysis was applied to explore whether the risk score derived from the model could function as an independent signature for EC prognosis. Meanwhile, a nomogram model was constructed by combing the independent prognostic signatures for prediction of the long-term survival in EC patients. A total of 396 CpG sites located at 20 m6A regulators were identified. A specific predictive model for EC prognosis based on 7 optimal CpG sites was constructed, which presented good performance in prognosis prediction of EC patients. Moreover, risk score was determined to be an independent signature both in the training set and validation set. By bringing in three independent prognostic factors (age, risk score, and TNM stage), the nomogram was constructed and could effectively predict the 3- and 5-year survival rates of EC patients. Our study suggested that the CpG sites located at m6A regulators might be considered as potential prognostic signatures for EC patients.


Readiness for smoking cessation in coronary heart disease patients across Europe: Results from the EUROASPIRE III survey.
Readiness for smoking cessation is an important predictor of quit attempts and cessation success. We aimed to investigate the prevalence and correlates of readiness for smoking cessation in coronary heart disease (CHD) patients. The EUROpean Action on Secondary and Primary Prevention by Intervention to Reduce Events III (EUROASPIRE III) survey is a cross-sectional study conducted in 2006-2007 among CHD patients <80 years of age from 22 European regions. Patients were interviewed on average 15 months after hospital admission for an acute coronary event or procedure. Readiness for smoking cessation was assessed using the smoking stages of change (SSC) short form questionnaire. Breath carbon monoxide was measured to validate self-reported non-smoking. Among 2585 patients who were smoking prior to hospital admission, 25.6%, 16.8%, 8.1%, 5.6% and 44.0% were in the precontemplation (no intention to quit), contemplation (thinking of quitting), preparation (planning to quit), action (having quit within six months) and maintenance (having quit more than six months ago) stages, respectively. Significant multivariable correlates of advancement in SSC showed positive associations of older age and attended cardiac rehabilitation and negative associations of severe depressive symptoms, longer smoking duration and environmental tobacco smoke (ETS) exposure. One-quarter of CHD patients across Europe who were smoking prior to hospitalisation have no intention to quit, and an additional quarter is thinking of quitting or planning to quit. Patients who are younger, do not attend cardiac rehabilitation, have severe depressive symptoms, have been smoking for longer periods of time and are exposed to ETS may need to be specifically targeted in cessation interventions.


An epidemiology of homicidal deaths due to rifled firearms in Peshawar Pakistan.
To determine the pattern of homicidal deaths caused by rifled weapons in Peshawar as regards the parameters of age, gender, place of occurrence and the number and location of injuries on the body. Descriptive study. The study was conducted at the Department of Forensic Medicine and Toxicology, Khyber Medical College, Peshawar, from June 2005 to February 2006. The subjects were selected from victims presenting for autopsy at the Department of Forensic Medicine and Toxicology, Khyber Medical College, Peshawar. One hundred cases were selected where the weapon of offence was a rifled weapon and the manner of death was homicide on the basis of the police inquest, the autopsy and an interview with the relatives of the victim. After the autopsy, the findings were tabulated and analyzed. Homicides predominantly occurred in young males residing in a rural locality. The peak incidence was between 20-29 years in males and in females the age group most prone was 30-39 years. Male to female ratio was 6:1. The chest (33.8%) followed by the head and abdomen were the areas primarily targeted. High velocity automatic weapons are primarily being used to kill young people in rural areas. Prevention can be through strict gun control laws coupled with education and awareness.


Heterodyne detector for measuring the characteristic of elliptically polarized microwaves.
In the present paper, a device is introduced, which is capable of determining the three characteristic parameters of elliptically polarized light (ellipticity, angle of ellipticity, and direction of rotation) for microwave radiation at a frequency of 110 GHz. The device consists of two perpendicular orientated pickup waveguides. A heterodyne technique mixes the microwave frequency down to frequencies on the order of 200 MHz. An oscilloscope is used to determine the relative amplitudes of the electrical fields and the phase shift in between, from which the three characteristic parameters can be calculated. Results from measured and calculated wave characteristics of an elliptically polarized 110 GHz microwave beam for plasma heating launched into the TEXTOR-tokamak experiment are presented. Measurement and calculation are in good agreement.


Vascular regulation of glioma stem-like cells: a balancing act.
Glioblastoma (GBM) are aggressive and therapy-resistant brain tumours driven by glioma stem-like cells (GSCs). GSC behaviour is controlled by the microenvironment, or niche, in which the cells reside. It is well-established that the vasculature is a key component of the GSC niche, which drives maintenance in the tumour bulk and invasion at the margin. Emerging evidence now indicates that the specific properties of the vasculature within these two regions impose different functional states on resident GSCs, generating distinct subpopulations. Here, we review these recent findings, focusing on the mechanisms that underlie GSC/vascular communication. We further discuss how plasticity enables GSCs to respond to vascular changes by interconverting bidirectionally between states, and address the therapeutic implications of this dynamic response.


Assessment of digital panoramic radiography's diagnostic value in angular bony lesions with 5 mm or deeper pocket depth in mandibular molars.
Assessment of alveolar bone level in periodontitis is very important in determining prognosis and treatment plan. Panoramic radiography is a diagnostic tool used to screen patients. The aim of the present study was to assess the diagnostic value of digital panoramic radiography in angular bony defects with 5 mm or deeper pocket depth in mandibular molars. In this cross-sectional study, ninety angular bony defects in mandibular molars teeth with 5 mm or deeper pocket depth were selected in sixty patients with the diagnosis of chronic periodontitis. Before surgery, bone probing was performed. During the surgery, the vertical distance from cementoenamel junction to the most apical part of bony defect was measured using a Williams probe and this measurements were employed as gold standard. This distance was measured on the panoramic radiographs by a Digital Calliper and Digital Ruler. All data were compare dusing independent samples t-test and Pearson's correlation coefficient. No significant difference was found between the results of bone probing and intra-surgical measurements (P = 0.377). The mean defect depth determined by Digital Caliper and Digital Ruler on panoramic radiographs was significantly less than surgical measurements (P < 0.001). The correlation between bone probing and surgical measurements in determining the defect depth was strong (r = 0.98, P < 0.001). Radiographic measurements made by Digital Ruler (r = 0.86), comparing to Digital Caliper (r = 0.79), showed a higher degree of correlation with surgical measurements. Based on this study, bone probing is a reliable method in vertical alveolar bone defect measurements. While the information obtained from digital panoramic radiographs should be used with caution and the ability of digital panoramic radiography in the determination of defect depth is limited.


The potential of kyllinga erecta Schumach and Cyperus rotundus Linn. to remediate soil contaminated with heavy metals from used engine oil in Cameroon.
Contaminated soils are a serious environmental problem in developing countries. Poor disposal of used engine oil from vehicles is a source of soil contamination in Buea, Cameroon. This study was conducted in the University of Buea Teaching and Research Farm to determine the ability of two sedges (Kyllinga erecta Schumach and Cyperus rotundus Linn.) to remediate crop land contaminated with used engine oil. The experiment consisted of the two sedges and the following used oil levels (v/wt): 0, 5, 10, 20, 40 and 60 ml/kg of soil. Control treatments with 0 and 60 ml of used engine oil/kg of soil without the sedges were also included. The plant (roots and shoots) and soil samples were analyzed for heavy metal contents using the Inductively Coupled Plasma Optical Mass Spectrometry analytical package for ultra-low detection and high precision. The root and shoot dry biomass of both sedges decreased with an increase in soil contamination. Cyperus rotundus accumulated high concentrations of Cr (mean = 64.8 ± 19.5 ppm) and Cd (mean =1.2 ± 0.2 ppm) in its roots. Kyllinga erecta had the potential to extract Sn, Cd, Mn, Sr and Mo on soils contaminated with used oil at 60 ml/kg. Cyperus rotundus had phytostabilisation potential for Cd at concentrations of used oil ≤20 ml/kg and Rb at 20 ml/kg. The sedge also had phytoextraction potential for Cr and Rb on soils contaminated with used oil at concentrations up to 20 ml/kg. Therefore, the use of indigenous plants adapted to tropical environments could be a possible option for the sustainable remediation of soils contaminated with heavy metals from used engine oil.


Achalasia of the cardia and multiple endocrine neoplasia 2B.
We report a 34-yr-old patient with multiple endocrine neoplasia 2B and achalasia of the cardia who was successfully treated with pneumatic dilation. The various gastrointestinal manifestations of this syndrome are discussed.


Combined treatment of staghorn calculi by fiberoptic transurethral nephrolithotripsy and extracorporeal shock wave lithotripsy.
Although various strategies have been proposed, the treatment of staghorn calculi is still controversial. We report on the treatment of 27 staghorn calculi using fiberoptic transurethral nephrolithotripsy (f-TUL) combined with extracorporeal shock wave lithotripsy (ESWL). Stones were initially disintegrated by f-TUL as an inpatient procedure. For stone fragmentation, we originally used an electrohydraulic lithotriptor (EHL) but changed to a pulsed-dye laser in 1993. After the stones were disintegrated as much as possible, a double-J ureteral stent was inserted and the patient was discharged. ESWL for the residual fragments was begun on an outpatient basis at 1 or 2 weeks after f-TUL and repeated until the residual fragments were smaller than 4 mm. Since 1989, 27 staghorn calculi in 26 patients have been treated. Among them, 21 were successfully fragmented using this combined treatment regimen. From 3 to 26 ESWL sessions (mean, 8.4 sessions) were required to disintegrate the staghorn calculi. Auxiliary percutaneous endourological procedures were necessary in 2 cases due to ureteral obstruction. The other 4 patients are still receiving ESWL for residual fragments. Urinary tract injury occurred in 2 patients early in this series when an EHL was used, but was managed without any surgical procedures. A fever greater than 38 degrees C developed in 9 patients. Combining f-TUL with ESWL provides an alternative treatment option for staghorn calculi. The use of a small caliber fiberscope (2.6 mm in diameter) and a laser for fragmentation decreased the risk of complications.


5-Iodouracil: structure of a reflection twin.
The crystal structure of 5-iodouracil, C4H3IN2O2, has been determined in the noncentrosymmetric space group P21 on a nonmerohedrally twinned crystal. Both twin components are enantiomorphically pure, but the twin element is a mirror plane perpendicular to c*. The molecular structure is discussed and stacking faults in the two-dimensional packing are proposed as a reason for the twinning.


Distress in significant others of patients with chronic fatigue syndrome: A systematic review of the literature.
The objective of this study was to systematically review existing empirical research assessing levels and correlates of distress in significant others of patients with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). Systematic searches in CINAHL, Web of Science and PsycINFO were conducted in August 2014. The search was repeated in January 2015 to check for newly published articles. Studies published in English with quantitative, qualitative, or mixed designs exploring distress, poor subjective health, poor mental health, reduced quality of life and well-being, and symptoms of depression and anxiety in significant others (>18 years) of children and adults with CFS/ME were included. Quality appraisal of included studies was carried out. Quantitative and qualitative studies were summarized separately. Six articles met eligibility criteria. Two quantitative studies with significant others of adult patients, and one quantitative and two mixed-methods studies with significant others of child patients showed moderate to high levels of distress. One qualitative study (adult patients) found minimal evidence of distress and that acceptance of CFS/ME was related to better adjustment. In the quantitative and mixed-methods studies, significant others who attributed some level of responsibility for symptoms to the patient, or who were female, or whose partners had poorer mental health, had higher levels of distress. The small number of studies to date, the contrary evidence from a qualitative study, and the limited data available on levels of distress in significant others of patients with CFS/ME mean that our conclusion that distress levels are elevated is provisional. We recommend that future qualitative studies focus on this particular topic. Further longitudinal studies exploring correlates of distress within the context of a predictive theoretical model would be helpful. Statement of contribution What is already known on this subject? Chronic fatigue syndrome (CFS/ME) entails considerable economic, social, and personal costs. Uncertainties exist around diagnosis and management. This may lead to particular difficulties for significant others trying to support patients. What does this study add? Few studies have examined distress and its correlates in significant others of people with CFS/ME. Significant others report elevated levels of distress on quantitative measures.


AluI in situ digestion of human alphoid and classical satellite DNA regions: high-resolution digital image analysis of FISH signals from condensed and extended chromatin.
Human lymphocyte chromatin either extended or condensed in interphase nuclei and chromosomes was in situ digested by the restriction endonuclease AluI and then hybridized with alphoid probes specific for chromosome 1 (D1Z5 locus), for chromosome X (DXZ1 locus), and with a classical satellite DNA probe specific for chromosome 9 (D9Z1 locus). Fluorescent hybridization signals were quantified by digital analysis of high-resolution images obtained by a Photo-CD system in an attempt to analyze the differential DNA removal produced by AluI in specific repetitive DNA sequences with known restriction site frequency and distribution. The analysis of area and average pixel grey count of hybridization signals suggests that the greater the degree of chromatin stretching, the higher the accessibility of the probe and/or reporter molecules to the target. Nevertheless, this greater hybridization efficiency does not result in a higher fluorescence intensity due to dispersion of individual signals. Specific repetitive DNA at D9Z1 locus (classical) remained impervious to digestion, while that at DXZ1 (alphoid) was extensively removed, according to the frequency and distribution of restriction sites. Nevertheless, though the restriction sites were at least as frequent as at the DXZ1 locus, DNA at the D1Z5 locus (alphoid) was only partially removed. This indicates that chromatin organization within the C-band partially prevents extraction of alphoid sequences, supporting the hypothesis that alphoid DNA sequences are differentially organized among chromosomes. Overall, the same results were obtained from condensed and extended chromatin, suggesting that higher-order chromatin organization does not influence the in situ DNA cleavage and removal by AluI.


Novel application of an established technique for removing a knotted ureteric stent.
This report describes a case whereby a ureteric stent became knotted during removal and lodged within the upper ureter. The authors describe a novel minimally invasive technique to remove the knotted ureteric stent using the holmium laser.


NAD+ Precursors and Intestinal Inflammation: Therapeutic Insights Involving Gut Microbiota.
The oxidized form of nicotinamide adenine dinucleotide (NAD+) is a critical metabolite for living cells. NAD+ may act either as a cofactor for many cellular reactions as well as a coenzyme for different NAD+-consuming enzymes involved in the physiological homeostasis of different organs and systems. In mammals, NAD+ is synthesized from either tryptophan or other vitamin B3 intermediates that act as NAD+ precursors. Recent research suggests that NAD+ precursors play a crucial role in maintaining the integrity of the gut barrier. Indeed, its deficiency has been associated with enhanced gut inflammation and leakage, and dysbiosis. Conversely, NAD+-increasing therapies may confer protection against intestinal inflammation in experimental conditions and human patients, with accumulating evidence indicating that such favorable effects could be, at least in part, mediated by concomitant changes in the composition of intestinal microbiota. However, the mechanisms by which NAD+-based treatments affect the microbiota are still poorly understood. In this context, we have focused specifically on the impact of NAD+ deficiency on intestinal inflammation and dysbiosis in animal and human models. We have further explored the relationship between NAD+ and improved host intestinal metabolism and immunity and the composition of microbiota in vivo. Overall, this comprehensive review aims to provide a new perspective on the effect of NAD+-increasing strategies on host intestinal physiology.


Postnatal characterization of cells in the accessory olfactory bulb of wild type and reeler mice.
Olfaction is the most relevant chemosensory sense of the rodents. General odors are primarily detected by the main olfactory system while most pheromonal signals are received by the accessory olfactory system. The first relay in the brain occurs in the olfactory bulb, which is subdivided in the main and accessory olfactory bulb (MOB/AOB). Given that the cell generation time is different between AOB and MOB, and the cell characterization of AOB remains limited, the goal of this work was first, the definition of the layering of AOB/MOB and second, the determination of cellular phenotypes in the AOB in a time window corresponding to the early postnatal development. Moreover, since reelin (Reln) deficiency has been related to olfactory learning deficits, we analyzed reeler mice. First, we compared the layering between AOB and MOB at early embryonic stages. Then, cell phenotypes were established using specific neuronal and glial markers as well as the Reln adaptor protein Dab1 to analyse differences in both genetic backgrounds. There was no apparent difference in the cell phenotypes among AOB and MOB or between wild type (wt) and reeler animals. However, a disruption in the granular cell layer of reeler with respect to wt mice was observed. In conclusion, the AOB in Reln-deficient mice showed similar neuronal and glial cell types being only affected the organization of granular neurons.


[Determination of risperidone in human plasma by liquid chromatography-tandem mass spectrometry].
To develop and validate a liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method for the determination of risperidone in human plasma. Risperidone and the internal standard, diphenhydramine, were isolated from plasma by liquid-liquid extraction with etherdichloromethane (3:2, v/v) , then chromatographed on a Zorbax Extend-C18 column (150 mm x 4.6 mm ID, 5 microm) using a mobile phase consisted of acetonitrile-water-formic acid (40:60: 0.5, v/v), at a flow rate of 0.7 mL x min(-1). A Finnigan TSQ tandem mass spectrometer equipped with atmospheric pressure chemical ionization source was used as detector and was operated in the positive ion mode. Selected reaction monitoring (SRM) using the precursor product ion combinations of m/z 411-->191 and m/z 256-->167 were used to quantify risperidone and diphenhydramine (IS) , respectively. The linear concentration range of the calibration curve for risperidone was 0.025 - 50 microg L(-1). The lower limit of quantification was 0.025 microg x L(-1). The intra- and inter-day relative standard deviation (RSD) across three validation running over the entire concentration range was less than 7.1%. The accuracy was within +/- 3.8%. Each sample was chromatographed within 2.7 min. The method was proved to be rapid, sensitive and suitable for pharmacokinetic investigations of risperidone.


DIP/Dpr interactions and the evolutionary design of specificity in protein families.
Differential binding affinities among closely related protein family members underlie many biological phenomena, including cell-cell recognition. Drosophila DIP and Dpr proteins mediate neuronal targeting in the fly through highly specific protein-protein interactions. We show here that DIPs/Dprs segregate into seven specificity subgroups defined by binding preferences between their DIP and Dpr members. We then describe a sequence-, structure- and energy-based computational approach, combined with experimental binding affinity measurements, to reveal how specificity is coded on the canonical DIP/Dpr interface. We show that binding specificity of DIP/Dpr subgroups is controlled by "negative constraints", which interfere with binding. To achieve specificity, each subgroup utilizes a different combination of negative constraints, which are broadly distributed and cover the majority of the protein-protein interface. We discuss the structural origins of negative constraints, and potential general implications for the evolutionary origins of binding specificity in multi-protein families.


The nature of constant and cyclic force production: unintentional force-drift characteristics.
We explored unintentional changes in forces during performance of constant and cyclic force-production tasks (F-tasks) after visual feedback removal. Based on earlier studies, we expected all force parameters to drop exponentially with time. We also explored possible role of working memory in the force drop phenomena. Healthy subjects performed constant or cyclic isometric F-tasks with the index finger under visual feedback. The cyclic task was paced by a metronome. Removing visual feedback resulted in a consistent force drop in constant F-tasks and a qualitatively similar drift in the mean force in the cyclic F-task. Both were slow with characteristic times of about 10-20 s. In contrast, force amplitude in the cyclic F-task increased quickly (within 1-2 s). When the subjects were asked to stop producing force for 5 s after the visual feedback disappeared and then resume force production, no downward force drift was seen in constant F-tasks, while in cyclic F-tasks, the drift of the mean force was present and an exaggerated increase in force amplitude was also observed. We conclude that while working memory limitations may influence cyclic F-tasks, their role in determining the force drift in constant F-tasks is limited. The results of both experiments are interpreted within the referent configuration hypothesis supplemented with an idea of unintentional drift of referent coordinates (RC-back-coupling) induced by differences between the referent and actual body configurations.


Pethidine binding in whole blood: methodology and clinical significance.
A three-compartment equilibrium dialysis method was developed for the simultaneous and direct determination of drug binding in whole blood and in plasma and of the blood to plasma concentration ratio (b/p). The unbound fraction of pethidine in the blood of six healthy volunteers (0.63, s.d. 0.09, n = 23 determinations) was significantly different from that in the blood of six patients (0.72, s.d. 0.08, n = 24 determinations). There was no significant difference in the b/p of six patients (0.84, s.d. 0.09, n = 24 determinations) and six volunteers (0.90, s.d. 0.14, n = 23 determinations). The observed unbound fraction of pethidine in blood (0.6 to 0.7) was considerably lower than previously reported. As this value for the unbound fraction (0.6 to 0.7) is similar to the reported estimated hepatic extraction ratio of the drug in man, it is proposed that pethidine elimination should be described as 'capacity limited, binding sensitive' rather than 'flow-limited'.


Dileucine-based sorting signals bind to the beta chain of AP-1 at a site distinct and regulated differently from the tyrosine-based motif-binding site.
In previous work, we showed that peptides from endocytosed proteins containing the tyrosine YXXphi sorting motif are recognized by the mu 2 subunit of AP-2, the plasma membrane clathrin adaptor protein complex. This interaction is activated by phosphoinositide lipids that are phosphorylated at the D-3 position of the inositol ring, and is also enhanced by the formation of clathrin-AP-2 coats. Here, we describe the detection of a specific interaction between peptides containing a second sorting motif, the dileucine motif, and AP-1, the clathrin adaptor complex responsible for sorting proteins at the trans-Golgi network (TGN). Surprisingly, the site of dileucine binding is the beta1 subunit, not mu 1. A YXXphi-containing peptide from a protein trafficked within the TGN does bind to mu 1, however. Phosphatidylinositol 3,4-diphosphate and 3,4, 5-triphosphate did not activate the interaction between dileucine-containing peptides and AP-1 but instead inhibited it, and clathrin-AP-1 coat formation did not alter the interaction. Thus, there are at least two physically separate binding sites for sorting signals on APs, which are also regulated independently.


Crustal anisotropy across northern Japan from receiver functions.
Northern Japan is a tectonically active area, with the presence of several volcanoes, and with frequent earthquakes among which the destructive Mw = 8.9-9.0 Tohoku-oki occurred on 11 March 2011. Tectonic activity leaves an imprint on the crustal structures, on both the upper and the lower layers. To investigate the crust in northern Japan, we construct a receiver function data set using teleseismic events recorded at 58 seismic stations belonging to the Japanese National (Hi-net) network. We isolate the signals, in the receiver function wavelet, that witness the presence of anisotropic structures at depth, with the aim of mapping the variation of anisotropy across the northern part of the island. This study focuses on the relation among anisotropy detected in the crust, stresses induced by plate convergence across the subduction zone, and the intrinsic characteristics of the rocks. Our results show how a simple velocity model with two anisotropic layers reproduces the observed data at the stations. We observe a negligible or small amount of signal related to anisotropy in the eastern part of the study area (i.e., the outer arc) for both upper and lower crust. Distinct anisotropic features are observed at the stations on the western part of the study area (i.e., the inner arc) for both upper and lower crust. The symmetry axes are mostly E-W oriented. Deviation from the E-W orientation is observed close to the volcanic areas, where the higher geothermal gradient might influence the deformation processes.


Benign Bone Conditions That May Be FDG-avid and Mimic Malignancy.
Positron emission tomography with the radiotracer 18F-fluoro-2-deoxy-d-glucose (FDG) plays an important role in the evaluation of bone pathology. However, FDG is not a cancer-specific agent, and knowledge of the differential diagnosis of benign FDG-avid bone alterations that may resemble malignancy is important for correct patient management, including the avoidance of unnecessary additional invasive tests such as bone biopsy. This review summarizes and illustrates the spectrum of benign bone conditions that may be FDG-avid and mimic malignancy, including osteomyelitis, bone lesions due to benign systemic diseases (Brown tumor, Erdheim-Chester disease, Gaucher disease, gout and other types of arthritis, Langerhans cell histiocytosis, and sarcoidosis), benign primary bone lesions (bone cysts, chondroblastoma, chondromyxoid fibroma, desmoplastic fibroma, enchondroma, giant cell tumor and granuloma, hemangioma, nonossifying fibroma, and osteoid osteoma and osteoblastoma), and a group of miscellaneous benign bone conditions (post bone marrow biopsy or harvest status, bone marrow hyperplasia, fibrous dysplasia, fractures, osteonecrosis, Paget disease of bone, particle disease, and Schmorl nodes). Several ancillary clinical and imaging findings may be helpful in discriminating benign from malignant FDG-avid bone lesions. However, this distinction is sometimes difficult or even impossible, and tissue acquisition will be required to establish the final diagnosis.


Breast cancer in brothers: case reports and a review of 30 cases of male breast cancer.
Two brothers with breast cancer are presented. One died 8 years after diagnosis and the other is presently living at 1 year with metastatic disease. The courses of 28 other previously unreported male patients with carcinoma of the breast are reviewed, and the possibility of male breast carcinoma being metastatic disease from the prostate is discussed. Useful etiologic information might be obtained from following the offspring of male breast cancer patients to see if they are at increased risk of developing the disease.


CURRENT APPRAISAL OF THROMBOLYTIC THERAPY. A CRITICAL REVIEW.
Thrombolytic therapy holds great promise for becoming an important therapeutic adjunct in the treatment of acute vascular occlusions, but such therapy has not reached the stage for general clinical use. The optimum method of administering thrombolytic agents has not yet been determined, and the processes that bring about lysis of clots are incompletely understood. Current theories in this field are reviewed and the suggested modes of therapy and potential complications are discussed.


Analysis of the Relationship between the Expression Levels of Neutrophil Gelatinase-Associated Lipocalin and Cytokine Genes in Bone Marrow.
Background: Recently, various associations of NGAL with several hematological cancers have been reported. However, given that the regulation of NGAL gene expression by cytokines is tissue-specific, NGAL expression in relation to those of cytokine genes has not been analyzed in bone marrow (BM) tissue. The purpose of this study was to analyze the association between NGAL and 48 cytokine gene expression levels in mononuclear cells (MNCs) of BM at the time of diagnosis of hematological malignancy and to explore the expression pattern of NGAL and related cytokine genes in patients with hematological malignancies and controls. Methods: BM MNCs were isolated from 48 patients, who were classified as patients presenting myeloproliferative neoplasm, acute myeloid leukemia, myelodysplastic syndrome, and as controls. NGAL and cytokine genes were analyzed using NanoString. Data on hematological parameters were collected from medical records. Single and multiple regression analyses were performed to analyze relationships. Results: Normalized counts of 26 cytokine genes were related to NGAL normalized counts, while STAT3 and TLR4 normalized counts had the highest explanatory power. The following multiple regression model was developed: NGAL normalized counts=4316.825 + 9.056 × STAT3 normalized counts + 844.226 × IL5 normalized counts + 17.540 × TLR1 normalized counts - 28.206 × TLR2 normalized counts - 42.524 × IRAK4 normalized counts. In the multiple regression analysis, STAT3 and TLR4 normalized counts showed multicollinearity. NGAL, STAT3, IL5, and TLR4 normalized counts showed similar intergroup patterns. Conclusions: NGAL normalized counts was predicted by a multiple regression model, while they showed similar intergroup patterns to STAT3, IL5, and TLR4 normalized counts.


HtpG contributes to Salmonella Typhimurium intestinal persistence in pigs.
Salmonella enterica subspecies enterica serovar Typhimurium (Salmonella Typhimurium) contamination of pork, is one of the major sources of human salmonellosis. The bacterium is able to persist and hide in asymptomatic carrier animals, generating a reservoir for Salmonella transmission to other animals and humans. Mechanisms involved in Salmonella persistence in pigs remain poorly understood. In the present study, we demonstrate that the Salmonella htpG gene, encoding a homologue of the eukaryotic heat shock protein 90, contributes to Salmonella Typhimurium persistence in intestine-associated tissues of pigs, but not in the tonsils. HtpG does not seem to play an important role during the acute phase of infection. The contribution to persistence was shown to be associated with htpG-dependent Salmonella invasion and survival in porcine enterocytes and macrophages. These results reveal the role of HtpG as a virulence factor contributing to Salmonella persistence in pigs.


Radiologists in the United States: demographic, professional, and practice characteristics.
The purpose of this report is to present a statistical portrait of radiologists in the United States based on the 1990 American College of Radiology Manpower Survey. Unlike previous surveys, this survey included radiologists who were not members of the College and was thus more representative of all radiologists. (Approximately three quarters of radiologists are College members.) We examined how the demographic, professional, and practice characteristics of radiologists vary among major groups within the profession. A stratified random sample of 2804 radiologists and nuclear medicine specialists was drawn from the American Medical Association Physician Masterfile, which is the most complete and extensive single source of information on physicians in the United States. Because the total numbers of female radiologists, nuclear medicine specialists, and radiologists less than 35 years old are relatively small, these groups were deliberately "oversampled" (hence the term stratified random sample) to ensure sufficient numbers of responses in these categories for meaningful analysis. A total of 1845 completed questionnaires were received, which yields a response rate of 68% if the questionnaires sent to invalid addresses are excluded. Responses were weighted to make the data representative of all radiologists, despite differences in sampling rates. Findings for professionally active radiologists who completed their training included the following: 94% were certified by the American Board of Radiology, 13% were women, 47% were less than 45 years old, fees for service were the primary remuneration for 62%, and 72% are in practices owned by physician members of the practice. By major activity in radiology, 69% were diagnostic radiology generalists; 11% were radiation oncologists; 18% were diagnostic radiology subspecialists; and 2% were nuclear medicine specialists. A breakdown by age indicated that the age group of radiologists less than 45 years old included more women, diagnostic subspecialists, and persons who had fellowship training than other age groups did. Percentages of diagnostic radiology generalists and solo practitioners were lower among younger radiologists. Radiation oncologists, compared with all others, were the most likely to practice solo or in small groups of two to four members. The subfields with the highest percentages (60% or more) of diagnostic radiologists reporting expertise or proficiency were CT, mammography, and sonography. Among radiologists who were retired, half had retired by the time they were 65 years old. However, a majority of radiologists 65-69 years old were still working, as were 40% of those 70-74 years old. The profession of radiology is changing, with more women, subspecialists, and fellowship-trained radiologists in younger age groups and fewer solo practitioners. Only a small percentage of radiologists are not board certified. Radiologists typically remain professionally active into their late 60s or even beyond.


Scenario-based analysis of traffic-related PM2.5 concentration: Lisbon case study.
Air quality in urban centers constitutes a challenge ahead for most cities. For this reason, the objective of this research work was to evaluate the impacts of changing traffic-related parameters on particulate matter (PM) concentration for several hierarchical street levels using real-world data for the city of Lisbon, Portugal. For that purpose, 2014 data regarding meteorological conditions, traffic volumes, typical vehicle speed, and a vehicle representative of the fleet was used in an air quality dispersion model (CALINE4). The available data allowed building a baseline case for several streets that are representative of the traffic circulation conditions in Lisbon, which was compared with different scenarios: hypothetical introduction of a cordon toll (S1.1 to S1.4) and the implementation of a low emission zone (S2.1 and 2.2). The results indicate that reductions on PM2.5 concentrations from 5 to 42 % may be obtained from the implementation of the scenarios. Overall, this study demonstrates that modeling tools based on real-world data can provide a good approach to study urban policies regarding traffic-related PM exposure. Additionally, implementation of such measures requires an integrated strategy that enables proper enforcement and monitoring, as well as an adequate management of traffic flows between the implementation boundaries.


Synthesis of mayolene-16 and mayolene-18: larval defensive lipids from the European cabbage butterfly.
A tandem Wittig approach has been employed for the synthesis of both (11S,9Z,12Z,15Z)- and (11R,9Z,12Z,15Z)-hydroxyoctadeca-9,12,15-trienoic acid (11-hydroxylinolenic acid, 11-HLA) from (R)-glyceraldehyde acetonide. From (11R)-HLA we have prepared the corresponding palmitic acid and stearic acid esters, mayolene-16 (1) and mayolene-18 (2), insect defensive compounds recently identified from Pieris rapae larvae. In addition, we describe the synthesis of three macrocyclic oligomers (24-26) derived from (11R)-HLA.


Flow field analysis in expanding healthy and emphysematous alveolar models using particle image velocimetry.
Particulates that deposit in the acinus region of the lung have the potential to migrate through the alveolar wall and into the blood stream. However, the fluid mechanics governing particle transport to the alveolar wall are not well understood. Many physiological conditions are suspected to influence particle deposition including morphometry of the acinus, expansion and contraction of the alveolar walls, lung heterogeneities, and breathing patterns. Some studies suggest that the recirculation zones trap aerosol particles and enhance particle deposition by increasing their residence time in the region. However, particle trapping could also hinder aerosol particle deposition by moving the aerosol particle further from the wall. Studies that suggest such flow behavior have not been completed on realistic, nonsymmetric, three-dimensional, expanding alveolated geometry using realistic breathing curves. Furthermore, little attention has been paid to emphysemic geometries and how pathophysiological alterations effect deposition. In this study, fluid flow was examined in three-dimensional, expanding, healthy, and emphysemic alveolar sac model geometries using particle image velocimetry under realistic breathing conditions. Penetration depth of the tidal air was determined from the experimental fluid pathlines. Aerosol particle deposition was estimated by simple superposition of Brownian diffusion and sedimentation on the convected particle displacement for particles diameters of 100-750 nm. This study (1) confirmed that recirculation does not exist in the most distal alveolar regions of the lung under normal breathing conditions, (2) concluded that air entering the alveolar sac is convected closer to the alveolar wall in healthy compared with emphysematous lungs, and (3) demonstrated that particle deposition is smaller in emphysematous compared with healthy lungs.


[Metallothionein].
Metallothionein is a low-molecular weight protein involved in resistance to toxicity of heavy metals. Recent experimental evidences indicate that metallothionein appears to be a factor in determining the responsiveness of tumor cells to anticancer drugs, such as cisplatin and adriamycin. The resistance of tumor cells having high concentration of metallothionein to cisplatin has been observed in cultured cells and transplanted tumors. On the other hand, increase in metallothionein concentration in normal tissues of tumor-bearing animals prevents side effects of anticancer drugs. Metallothionein may be an important endogenous factor in cancer chemotherapy.


[Prediction and identification of B-cell linear epitopes of hepatitis B e antigen].
To predict and identify B-cell linear epitopes of hepatitis B e antigen (HBeAg). The B-cell linear epitopes of HBeAg were predicted using the software provided by NCBI Database and Immune Epitope Database (IEDB) and synthesized by a solid-phase method followed by conjugation with keyhole limpet hemocyanin (KLH). The KLH conjugates were used for immunization of New Zealand white rabbits, and the immune response of the rabbits was monitored by direct ELISA using a bovine serum albumin conjugate of the predicted epitopes. RESULTS Four new B-cell linear epitopes of HBeAg were identified, namely (1)MDIDPYKEFG(10), (37)LYREALESPEHCSP(50), (74)SNLEDPAS(81) and (127)RTPPAYRPPNAPIL(140). The rabbits immunized with the KLH conjugate showed an antibody titer over 1:512 000. The antisera of B-cell linear epitopes collected could specifically react with HBeAg as shown by ELISA. Four B-cell linear epitopes of HBeAg have been confirmed using bioinformatics methods, which provides new evidence for further functional studies of HBeAg in hepatitis B.


Photon-Induced Near-Field Electron Microscopy of Eukaryotic Cells.
Photon-induced near-field electron microscopy (PINEM) is a technique to produce and then image evanescent electromagnetic fields on the surfaces of nanostructures. Most previous applications of PINEM have imaged surface plasmon-polariton waves on conducting nanomaterials. Here, the application of PINEM on whole human cancer cells and membrane vesicles isolated from them is reported. We show that photons induce time-, orientation-, and polarization-dependent evanescent fields on the surfaces of A431 cancer cells and isolated membrane vesicles. Furthermore, the addition of a ligand to the major surface receptor on these cells and vesicles (epidermal growth factor receptor, EGFR) reduces the intensity of these fields in both preparations. We propose that in the absence of plasmon waves in biological samples, these evanescent fields reflect the changes in EGFR kinase domain polarization upon ligand binding.


Influences of Cutting Speed and Material Mechanical Properties on Chip Deformation and Fracture during High-Speed Cutting of Inconel 718.
The paper aims to investigate the influences of material constitutive and fracture parameters in addition to cutting speed on chip formation during high-speed cutting of Inconel 718. Finite element analyses for chip formation are conducted with Johnson-Cook constitutive and fracture models. Meanwhile, experiments of high-speed orthogonal cutting are performed to verify the simulation results with cutting speeds ranging from 50 m/min to 7000 m/min. The research indicates that the chip morphology transforms from serrated to fragmented at the cutting speed of 7000 m/min due to embrittlement of the workpiece material under ultra-high cutting speeds. The parameter of shear localization sensitivity is put forward to describe the influences of material mechanical properties on serrated chip formation. The results demonstrate that the effects of initial yield stress and thermal softening coefficient on chip shear localization are much more remarkable than the other constitutive parameters. For the material fracture parameters, the effects of initial fracture strain and exponential factor of stress state on chip shear localization are more much prominent. This paper provides guidance for controlling chip formation through the adjustment of material mechanical properties and the selection of appropriate cutting parameters.


Bystander-initiated chest compression-only CPR is better than standard CPR in out-of-hospital cardiac arrest.
Out-of-hospital cardiac arrest has a low survival rate to hospital discharge. Recent studies compared a simplified form of CPR, based on chest compression alone versus standard CPR including ventilation. We performed systematic review and meta-analysis of randomized controlled trials, focusing on survival at hospital discharge. We extensively searched the published literature on out-of hospital CPR for non traumatic cardiac arrest in different databases. We identified only three randomized trials on this topic, including witnessed and not-witnessed cardiac arrests. When pooling them together with a meta-analytic approach, we found that there is already clinical and statistical evidence to support the superiority of the compression-only CPR in terms of survival at hospital discharge, as 211/1842 (11.5%) patients in the chest compression alone group versus 178/1895 (9.4%) in the standard CPR group were alive at hospital discharge: odds ratio from both Peto and DerSimonian-Laird methods =0.80 (95% confidence interval 0.65-0.99), p for effect =0.04, p for heterogeneity =0.69, inconsistency =0%). Available evidence strongly support the superiority of bystander compression-only CPR. Reasons for the best efficacy of chest compression-only CPR include a better willingness to start CPR by bystanders, the low quality of mouth-to-mouth ventilation and a detrimental effect of too long interruptions of chest compressions during ventilation. Based on our findings, compression-only CPR should be recommended as the preferred CPR technique performed by untrained bystander.


Systematic and Comprehensive Review of Clustering and Multi-Target Tracking Techniques for LiDAR Point Clouds in Autonomous Driving Applications.
Autonomous vehicles (AVs) rely on advanced sensory systems, such as Light Detection and Ranging (LiDAR), to function seamlessly in intricate and dynamic environments. LiDAR produces highly accurate 3D point clouds, which are vital for the detection, classification, and tracking of multiple targets. A systematic review and classification of various clustering and Multi-Target Tracking (MTT) techniques are necessary due to the inherent challenges posed by LiDAR data, such as density, noise, and varying sampling rates. As part of this study, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was employed to examine the challenges and advancements in MTT techniques and clustering for LiDAR point clouds within the context of autonomous driving. Searches were conducted in major databases such as IEEE Xplore, ScienceDirect, SpringerLink, ACM Digital Library, and Google Scholar, utilizing customized search strategies. We identified and critically reviewed 76 relevant studies based on rigorous screening and evaluation processes, assessing their methodological quality, data handling adequacy, and reporting compliance. As a result of this comprehensive review and classification, we were able to provide a detailed overview of current challenges, research gaps, and advancements in clustering and MTT techniques for LiDAR point clouds, thus contributing to the field of autonomous driving. Researchers and practitioners working in the field of autonomous driving will benefit from this study, which was characterized by transparency and reproducibility on a systematic basis.


Effects of Salt Concentrations and Nitrogen and Phosphorus Starvations on Neutral Lipid Contents in the Green Microalga Dunaliella tertiolecta.
Dunaliella tertiolecta, a halotolerant alga, can accumulate large amounts of neutral lipid, which makes it a potential biodiesel feedstock. In this study, neutral lipids of D. tertiolecta induced by different salinities or N or P starvation were analyzed by thin-layer chromatography (TLC), flow cytometry (FCM), and confocal laser scanning microscopy (CLSM). High salinities or N or P starvation resulted in a decrease in cell growth and chlorophyll contents of D. tertiolecta. Neutral lipid contents increased markedly after 3-7 days of N starvation or at low NaCl concentrations (0.5-2.0 M). N starvation had a more dramatic effect on the neutral lipid contents of D. tertiolecta than P starvation. Four putative ME isozymes in different conditions can be detected by using isozyme electrophoresis. Two alternative acetyl-CoA producers, ACL and ACS genes, were up-regulated under low salinities and N starvation. It was suggested that low salinities and N starvation are considered efficient ways to stimulate lipid accumulation in D. tertiolecta.


Cucurbitacin B synergistically enhances the apoptosis-inducing effect of arsenic trioxide by inhibiting STAT3 phosphorylation in lymphoma Ramos cells.
Arsenic trioxide (ATO) is a classic apoptosis-inducing agent used to treat acute promyelocytic leukemia. However, the therapeutic effect of ATO is limited in lymphoma, which resists apoptosis possibly due to inappropriate activation of STAT3. Therefore, combination of ATO and STAT3 inhibitor may be a potential strategy to treat lymphoma. Dramatically, Cucurbitacin B (CuB), an effective component of the dichloromethane extraction from Trichosanthes kirilowii Maxim, synergistically eliminated the apoptosis resistance of Burkitt's lymphoma Ramos cells to ATO by inhibiting the phosphorylation of STAT3, followed in turn by downregulation of Bcl-2 and upregulation of Bax. Furthermore, CuB and ATO in combination have no pro-apoptotic effect on normal lymphatic cells, indicating the absence of toxicity to hematological cells. This synergistic effect was further confirmed in nude murine lymphoma model, which exhibited significant apoptosis induction and tumor growth inhibition. Collectively, CuB synergistically enhances the apoptosis-inducing effect of ATO by inhibiting STAT3 phosphorylation in Ramos cells.


Hyaluronidases of the gastrointestinal invasive nematodes Ancylostoma caninum and Anisakis simplex: possible functions in the pathogenesis of human zoonoses.
The gastrointestinal invasive stages of two parasitic nematodes, Ancylostoma caninum and Anisakis simplex, were each found to release in vitro a hydrolytic enzyme that degrades the glycosaminoglycan hyaluronic acid. The parasite hyaluronidases were partially purified by ion-exchange chromatography and biochemically characterized. The hyaluronidase from A. caninum adult worms had a molecular weight of 65,000 and a pH optimum of 6 with activity at neutral pH, while the hyaluronidase from A. simplex larvae had a molecular weight of 40,000 and a pH optimum of 4 with no activity at neutral pH. Both parasite hyaluronidases also degraded the glycosaminoglycan chondroitin sulfate A. Cupric sulfate and high concentrations of sodium chloride were inhibitory. The nematode hyaluronidases are postulated to have a role in tissue histolysis and mucosal invasion; their distinct biochemical properties have relevance to the pathogenesis of the zoonoses anisakiasis and eosinophilic enteritis.


Nicotinic acid in nanocontainers. Encapsulation and release from ion exchangers.
The paper is devoted to the study of the ion exchange encapsulation of nicotinic acid in nanocontainers on polymer matrices. Dowex-50 cation exchanger, sulphonated polymer based on metacyclophanoctol, polymer zirconium phosphate, and strongly basic Dowex-1 anion exchanger are used as polymer matrices. It was confirmed that commercial ion exchangers can encapsulate up to 0.64 g of nicotinic acid per gram of polymer. The high elution rate of nicotinic acid from nanocontainers via the ion exchange mechanism makes it possible to achieve the desired pharmacokinetics of drug release in vivo.


Comparison of functional properties of 34% and 80% whey protein and milk serum protein concentrates.
This study compared the functional properties of serum protein concentrate (SPC) with whey protein concentrate (WPC) made from the same milk and with commercial WPC. The experimental SPC and WPC were produced at 34% or 80% protein from the same lot of milk. Protein contents of WPC and SPC were comparable; however, fat content was much lower in SPC compared with WPC and commercial WPC. The effect of drying methods (freeze vs. spray drying) was studied for 34% WPC and SPC. Few differences due to drying method were found in turbidity and gelation; however, drying method made a large difference in foam formation for WPC but not SPC. Between pH 3 and 7, SPC was found to have lower turbidity than WPC; however, protein solubility was similar between SPC and WPC. Foaming and gelation properties of SPC were better than those of WPC. Differences in functional properties may be explained by differences in composition and extent of denaturation or aggregation.


Recent advances in photocatalytic self-cleaning performances of TiO2-based building materials.
TiO2-based photocatalytic building materials can keep the building surface clean, and have decontamination, antibacterial effects and so on, which greatly reduces the maintenance cost and the risk of cleaning work, and these materials have great application potential in pollution and carbon reduction in the future. However, due to the wide band gap of TiO2, the low utilization of solar energy and the instability of super hydrophilicity have always been the difficulties in the field of photocatalysis. Based on the relevant research of TiO2-based photocatalytic materials in recent years, this review summarizes the modification strategies that can effectively improve the photocatalytic activity of TiO2-based photocatalytic materials. At the same time, the influence of complex environmental factors and substrate properties on the self-cleaning behavior of TiO2-based building materials was analyzed. This paper aims to provide effective guidance for the future application of TiO2-based photocatalysts in the construction field, improve people's understanding of photocatalytic building materials (PBM) and photocatalytic self-cleaning characteristics, and provide more possibilities for the extensive application of photocatalysis technology in the construction field, as well as to promote the realization of global carbon neutrality and other strategic goals of pollution and carbon reduction.


Psychological outcomes of patients with screen-detected type 2 diabetes: the influence of time since diagnosis and treatment intensity.
The objective of this study was to investigate how time since diagnosis and treatment intensity influence psychological outcomes in patients with screen-detected type 2 diabetes. A 2 x 2 factorial cross-sectional design was used to examine psychological outcomes in 196 patients with screen-detected diabetes diagnosed 3-33 months previously who were receiving usual care or intensive multifactorial pharmacological treatment. Outcomes included anxiety, depression, diabetes-related distress, perceived seriousness and vulnerability, self-efficacy, and self-care. Multivariate analysis was used to examine variations in outcomes based on time since diagnosis (<1 vs. 2-3 years) and treatment intensity. Most patients reported little distress, low perceived seriousness and vulnerability, high self-efficacy, and low self-care, but outcomes varied considerably across conditions. Time effects were found for perceived vulnerability, which increases significantly with time since diagnosis. Time x treatment interactions were found for anxiety, diabetes-related distress, and self-efficacy; notably, intensively treated patients showed more distress and less self-efficacy in the 1st year, and usual-care patients reported more distress and less self-efficacy 2-3 years after diagnosis. Screen-detected patients generally do not experience much difficulty with their condition in the first few years, but early and intensive treatment can influence patients' psychological outcomes, leading to relatively more anxiety and less self-efficacy in the 1st year after diagnosis but not necessarily improving self-care. This suggests that intensive treatments confront patients with their diabetes earlier on whereas milder treatments may delay confrontation. This finding should be taken into account in the development and timing of psychological interventions for patients with newly diagnosed diabetes.


The prediction of chronic persistent versus intermittent tardive dyskinesia. A retrospective follow-up study.
Relatively little is known about the course of TD in patients continuing to receive neuroleptic medication. In a retrospective follow-up study of 192 patients seen two or more times (average 7.7 visits) over 3-55 months in the Yale Tardive Dyskinesia Clinic, 112 (58%) demonstrated a 'chronic persistent' pattern, the remainder an 'intermittent' pattern. The most important predictors of chronic persistent TD, using multiple logistic-regression analyses, included increased age and the presence of non-orofacial TD at baseline.


Distribution of tetracycline resistance genes in genotypically related and unrelated multiresistant Acinetobacter baumannii strains from different European hospitals.
The presence of tetracycline (TET) resistance genes was investigated in 49 genotypically related and unrelated multidrug-resistant Acinetobacter baumannii (MDRAB) strains from European hospitals including representatives of pan-European clones I and II. Except for one strain, all MDRAB strains displayed resistance to tetracycline (MIC range of 16 to > 512 microg/ml) but were susceptible (MIC < 4 microg/ml) or exhibited intermediate resistance (MIC of 4-8 microg/ml) to minocycline (MIN). In 37 strains, either tet(A) or tet(B) was detected and one of these strains possessed both tet(A) and tet(M). In addition, all MDRAB strains contained the aspecific efflux gene adeB irrespectively of whether they harbored tet genes or not. Repetitive DNA element (rep)-PCR fingerprinting using the (GTG)5 primer [(GTG)5-PCR] revealed that strains previously assigned to pan-European clones I and II were grouped into two separate clusters. In addition, these clusters also contained strains that had not been typed previously, indicating that (GTG)5-PCR is a valuable method for recognizing putative new members of MDRAB clones. Most, but not all, members of clones I and II were linked to the presence of either tet(A) or tet(B) and displayed different levels of TET resistance with MIC values of 32 to > 512 microg/ml and > 512 microg/ml, respectively. Of these two genes only tet(B) encodes an efflux of both TET and MIN, which was reflected by the relatively high MIC values for MIN (4 microg/ml) shown by the majority of the tet(B)-carrying clone II strains as opposed to the low MIC values for MIN (< 1 microg/ml) displayed by most tet(A)-containing clone I strains. Collectively, our phenotypic and genotypic resistance data support the therapeutic evaluation of second-generation tetracyclines like MIN as promising agents for treating MDRAB infections.


INFERENCE OF SPERM COMPETITION FROM BROODS OF FIELD-CAUGHT DROSOPHILA.
In field studies of multiple mating and sperm competition there typically is no experimental control over the number of times that a female mates, the interval between matings, or the genetic identity of multiple fathers contributing to a brood. Irrespective of this complexity, high-resolution molecular markers can be used to assign paternity with considerable confidence. This study employed two highly heterozygous microsatellite loci to assess multiple paternity and sperm displacement in a sample of broods taken from a natural population of Drosophila melanogaster. The large number of alleles present at each of the loci makes it difficult to derive explicit maximum-likelihood estimates for multiple paternity and sperm displacement from brood samples. Monte Carlo simulations were used to estimate maximum-likelihood parameters for the distribution of female remating frequency and the proportion of offspring sired by the second or subsequent mating males. Estimates were made based on genotypes scored at two distinct marker loci because they were found to give statistically homogeneous results. Fitting a Poisson distribution of number of matings, the mean number of males mated by a female was 1.82. The sperm displacement parameter estimated from doubly mated females were 0.79 and 0.86 for the two loci (0.83 for the joint estimate). The overall probability that a multiply mated female will be misclassified as singly mated was only 0.006, which indicates that microsatellites can provide excellent resolution for identifying multiple mating. In addition, microsatellites can be used to generate relatively precise estimates of sperm precedence in brood-structured samples from a natural population.


A young adult male with peripheral artery disease.
A 19-year-old man was admitted with severe symptoms suggestive for bilateral occlusive disease of his lower extremities. Clinical, laboratory, and radiological evaluation established the diagnosis of Buerger's disease. Buerger's disease often poses a diagnostic challenge and requires a high degree of suspicion. Although rare for this patient's young age, it is important that a correct diagnosis is being made, because the disease process can be stopped if the patient stops smoking.


Thermal accumulation and the early development of Ixodes scapularis.
We examined the relationship between the accumulation of thermal energy and the onset of oviposition and eclosion of the northern deer tick, Ixodes scapularis, and explored the usefulness of comparing degree days (DD) required for larval emergence with area-wide National Weather Service (NWS) data to construct maps indicating where the establishment of this vector tick would be climatologically constrained. Initially, the validity of basal temperatures for egg and larval development was confirmed by prolonged incubations of gravid females and eggs at 6 degrees C and 10 degrees C respectively. Next, the number of DD accumulated in situ from the placement of gravid females to oviposition, and from oviposition to larval emergence, were measured using temperature data loggers placed next to fall- and spring-fed ticks held within individual vials under leaf litter in multiple enclosures located in diverse biophysical regions of Maine. Finally, when it was found that total DD to larval emergence, as measured in ambient air above the enclosures, compared favorably with DD accumulated simultaneously at nearby NWS stations, maps were constructed, based on archived NWS data, to demonstrate where temperatures were sufficient to allow the hatching of larvae both within one season and over the last three decades as I. scapularis has advanced into northern New England.


[Metastatic lung adenocarcinoma. Nivolumab as second line treatment: between unresolved issues and promising future. A case report.]
In recent years immunotherapy has become a fundamental part of the treatment of many solid tumors, including non-small cell lung cancer (NSCLC). With the results of trials investigating the role of monoclonal antibodies against immuno-checkpoints in particular, today these drugs have become part of everyday clinical practice, even though many questions still remain unresolved (optimal duration of treatment, prognostic and predictive role of biomarkers, management of immuno-related toxicity). Here we report the case of our patient with diagnosis of metastatic lung adenocarcinoma "non oncogene driven" successfully treated in second line with nivolumab, analyzing the problems and the questions most frequently evidenced during treatment with these new molecules.


Piroxicam cocrystals with phenolic coformers: preparation, characterization, and dissolution properties.
This study explores the preparation and investigation of dissolution properties of piroxicam cocrystals. Differential scanning calorimetry (DSC) was used to determine the capability of resorcinol (RES), methylparaben (MPB), and vanillin (VAN) to form cocrystals with piroxicam (PRX). Generation of cocrystals was attempted by liquid assisted grinding and slurry methods. Cocrystals were characterized by thermal methods, powder X-ray diffraction, and Fourier-transform infrared spectroscopy. Apparent solubility, intrinsic dissolution rate (IDR), and powder dissolution profile of cocrystals were compared with anhydrous piroxicam, piroxicam monohydrate (PRXMH), and previously reported piroxicam-succinic acid cocrystal. Contact angles and particle sizes of the studied solids were also measured. Based on the DSC screening results, we prepared and characterized PRX-RES and PRX-MPB cocrystals. Interestingly, the cocrystals not only failed to improve apparent solubility and IDR of PRX but also showed lower values than PRX that were attributed to induction of phase transformation of PRX to PRXMH. In contrary, cocrystals performed better than PRX in powder dissolution studies. The higher dissolution rates of cocrystals were explained by improved wettability and reduced sizes. This study has highlighted the complexity of solid state properties of cocrystals and has provided new evidence for the in-solution stability issues of cocrystals.


Seasonal patterns in trace elements assessed in toenails.
Seasonal patterns in measured exposure biomarkers can cause measurement error in epidemiological studies. There is little known about the seasonality of trace elements when measured in toenails. Adjusting for such patterns when estimating associations between long-term exposures and health outcomes could be needed to improve precision and reduce bias. Our goal was to assess seasonal patterns in toenail measurements of trace elements. At enrollment, Sister Study participants, who were US residents, removed polish and collected toenail clippings, which were cleaned before analysis. We measured: iron, vanadium, aluminum, chromium, manganese, cobalt, nickel, copper, zinc, arsenic, selenium, molybdenum, cadmium, tin, antimony, mercury, and lead. For a sample of the cohort we fit trigonometric regression models with toenail element measures as the outcome, using sine and cosine functions of the collection day of the year (transformed to an angle) to assess seasonality. Results were replicated in a second sample of women, with measurements done in a separate lab. There was a seasonal association between day of collection and toenail measures for iron, aluminum, vanadium, chromium, manganese, cobalt, arsenic, molybdenum, cadmium, tin, and lead, all of which peaked near mid-August. Seasonal patterns were concordant across the two samples of women. Given the evidence supporting seasonal patterns for 11 of the 17 elements measured in toenails, correcting for seasonality of toenail levels of those trace elements in models estimating the association between those exposures and health outcomes is important. The basis for higher concentrations in toenails collected during the summer remains unknown.


The Role of Autophagy in White Adipose Tissue Function: Implications for Metabolic Health.
White adipose tissue (WAT) is a highly adaptive endocrine organ that continuously remodels in response to nutritional cues. WAT expands to store excess energy by increasing adipocyte number and/or size. Failure in WAT expansion has serious consequences on metabolic health resulting in altered lipid, glucose, and inflammatory profiles. Besides an impaired adipogenesis, fibrosis and low-grade inflammation also characterize dysfunctional WAT. Nevertheless, the precise mechanisms leading to impaired WAT expansibility are yet unresolved. Autophagy is a conserved and essential process for cellular homeostasis, which constitutively allows the recycling of damaged or long-lived proteins and organelles, but is also highly induced under stress conditions to provide nutrients and remove pathogens. By modulating protein and organelle content, autophagy is also essential for cell remodeling, maintenance, and survival. In this line, autophagy has been involved in many processes affected during WAT maladaptation, including adipogenesis, adipocyte, and macrophage function, inflammatory response, and fibrosis. WAT autophagy dysregulation is related to obesity and diabetes. However, it remains unclear whether WAT autophagy alteration in obese and diabetic patients are the cause or the consequence of WAT malfunction. In this review, current data regarding these issues are discussed, focusing on evidence from human studies.


Kinetics of cytotoxicity induced by immunotoxins. Enhancement by lysosomotropic amines and carboxylic ionophores.
The kinetics of cytotoxicity induced by ricin and a series of immunotoxins consisting of ricin A-chain coupled to antibodies against cell-surface antigens has been studied. The inhibition of protein synthesis in cells treated with immunotoxins or ricin occurs after a lag period. The rate of protein synthesis decreases according to a mono-exponential function, indicating a first-order process. With increasing concentration of immunotoxin, a maximal rate of inhibition is reached. The inactivation rate induced by immunotoxins was much slower than that achieved with ricin, even when products were compared on a basis of an identical number of molecules bound per cell, demonstrating the real higher efficacy of ricin. The time required to reduce protein synthesis by 90%, denoted T10, was 1.4-1.6 h with ricin, 60 h with anti-T65 immunotoxin on CEM human T leukemia cells (T65 positive), 65 h with anti-p97 immunotoxin on SK-MEL 28 human melanoma cells (p97 positive), and 20 h with an IgM anti-Thy 1.2 immunotoxin on WEHI-7 mouse T leukemia cells (Thy 1.2 positive). In this latter case, when the IgM antibody was replaced by an IgG anti-Thy 1.2, a 5-fold increase in the inactivation rate was obtained, demonstrating the importance of the binding moiety for the immunotoxins. Lysosomotropic amines such as ammonium chloride, chloroquine, and methylamine and carboxylic ionophores such as monensin, which are known to interfere with the uptake of certain macromolecules, strongly increased the rate of protein synthesis inhibition by all immunotoxins tested and increased 4-50,000-fold the sensitivity of cells to the immunotoxin. Enhancement in the inactivation rate was as much as 7-10-fold when either of these compounds was added, generating T10 values comparable to those of ricin.


Comparison of Heart Rate and Blood Pressure with Toe Pinch and Bispectral Index for Monitoring the Depth of Anesthesia in Piglets.
Determining depth of anesthesia (DOA) is a clinical challenge in veterinary medicine, yet it is critical for the appropriate oversight of animals involved in potentially painful experimental procedures. Here, we investigated various parameters used to monitor conscious awareness during surgical procedures and refined the application of noxious stimuli to anesthetized animals. Specifically we used a common stimulus, a compressive toe pinch (TP), to determine physiologic changes that accompanied a positive or negative motion response in isoflurane-anesthetized piglets. A positive response was defined as any reflexive withdrawal, whereas a negative response was defined as the absence of motion after stimulation. We also assessed the utility of the bispectral index (BIS) for its ability to predict a motion response to TP. The average of BIS values over 1 min (BISmean) was recorded before and after TP. In piglets with a positive response to TP, heart rate (HR), but not blood pressure (BP), increased significantly, but receiver operating characteristic (ROC) analysis revealed that HR was not a sensitive, specific predictor of TP motion response. Both before and after TP, BISmean was a strong predictor of a positive motion response. We conclude that HR and noninvasive BP changes are not clinically reliable indicators of anesthetic depth when assessed immediately after a peripherally applied compressive force as an indicator stimulus; however, BISmean and response TP are acceptable for assessing DOA in piglets maintained under isoflurane anesthesia.


Formulation and Characteristics of Edible Oil Nanoemulsions Modified with Polymeric Surfactant for Encapsulating Curcumin.
Curcumin (Cur) is a beneficial phytochemical with numerous health advantages. However, its limited solubility in oil and poor stability hinder its potential for biomedical applications. In this study, we employed a mixture of food-grade Tween 60, a polymeric surfactant, and Span 60 to adjust the hydrophilic lipophilic balance number (HLBt) and prepared nanoemulsions (NEs) of coconut oil (Cc oil) as carriers for Cur. The effects of HLBt values, surfactant-to-oil ratio, and oil ratio on the physicochemical characteristics of the food-grade oil-NEs were investigated using dynamic light scattering, transmission electron microscopy, differential scanning calorimetry, fluorescence polarization spectroscopy, and viscometry. Increasing the addition ratio of Tween 60 in the NEs, thereby increasing the HLBt, resulted in a reduction in NE size and an improvement in their storage stability. The temperature and size of the phase transition region of the NEs decreased with increasing HLBt. NEs with higher HLBt exhibited a disordering effect on the intra-NE molecular packing of Cc oil. NEs with high HLBt displayed low viscosity and demonstrated nearly Newtonian fluid behavior, while those with lower HLBt exhibited pseudoplastic fluid behavior. Cur was effectively encapsulated into the Cc oil-NEs, with higher encapsulation efficiency observed in NEs with higher HLBt values. Furthermore, the Cur remaining activity was significantly enhanced through encapsulation within stable NEs. The biocompatibility of the Cc oil-NEs was also demonstrated in vitro. In summary, this study highlights the preparation of stable NEs of Cc oil by adjusting the HLBt using Tween 60, facilitating effective encapsulation of Cur. These findings provide valuable insights for the development of Cur carriers with improved solubility, stability, and bioavailability.


Role of Vitamin D Deficiency in Increased Susceptibility to Respiratory Infections Among Children: A Systematic Review.
Vitamin D has several roles in the immune system besides its effects on bone metabolism. Acute respiratory infections are common infections in children. Severe lower respiratory tract infections (LRTIs) even cause death in children, especially in those less than five years of age. Our study aims to examine whether children with vitamin D deficiency are susceptible to respiratory infections and to study the association between vitamin D deficiency and the severity of respiratory infections. We comprehensively searched research articles in PubMed, ScienceDirect, and Cochrane library databases. The main keywords were vitamin D deficiency, respiratory infections, and children. We used Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines to conduct this systematic review. The initial search showed 16,120 papers. A meticulous screening of research articles using the eligibility criteria and quality appraisal tools was done. Finally, 10 research articles qualified for this systematic review, including eight case-control studies, one randomized controlled trial (RCT), and one cohort study. Seven of 10 research studies reviewed found that children with low vitamin D levels are susceptible to respiratory infections. Five studies discussed the severity of respiratory infections and low vitamin D levels. This systematic review concluded that children with low vitamin D levels are prone to developing respiratory infections. But we could not find a conclusive association between the severity of respiratory infections and low vitamin D levels.


[Intrauterine device migration to the bladder: four case reports].
The intrauterine device has been commonly used in our population for many years as contraceptive method. One of the complications is the device migration out of the uterus. One of the most uncommon fait of this migration is the bladder, with few reports on the literature. In this work, four cases are reported with their clinical presentation, study and treatment.


Comparison of Commercially Available and Laboratory-Developed Assays for In Vitro Detection of SARS-CoV-2 in Clinical Laboratories.
Multiple laboratory-developed tests (LDTs) and commercially available assays have emerged to meet diagnostic needs related to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. To date, there is limited comparison data for these different testing platforms. We compared the analytical performance of a LDT developed in our clinical laboratory based on CDC primer sets and four commercially available, FDA emergency use authorized assays for SARS-CoV-2 (Cepheid, DiaSorin, Hologic Panther, and Roche Cobas) on a total of 169 nasopharyngeal swabs. The LDT and Cepheid Xpert Xpress SARS-CoV-2 assays were the most sensitive assays for SARS-CoV-2 with 100% agreement across specimens. The Hologic Panther Fusion, DiaSorin Simplexa, and Roche Cobas 6800 failed to detect positive specimens only near the limit of detection of our CDC-based LDT assay. All assays were 100% specific, using our CDC-based LDT as the gold standard. Our results provide initial test performance characteristics for SARS-CoV-2 reverse transcription-PCR (RT-PCR) and highlight the importance of having multiple viral detection testing platforms available in a public health emergency.


Implicit Perceptions of Closeness From the Direct Eye Gaze.
Eye gaze plays an important role during social interaction. Specifically, different eye gaze directions may send different functional messages to the observers, who have the capacity to automatically interpret these signals. In the present study, we used the implicit association test (IAT) to investigate whether direct eye gaze sends a functional, automatically perceived signal about non-target interpersonal closeness. Results suggest that the direct gaze strongly signals close relationship, and this association cannot be accounted for by positive valence. The findings suggest that the direct gaze may function to uniquely communicate a generalized closeness without orientation. Discussion focuses on the implications of these findings for social functions of direct gaze during interpersonal interaction and the automatic nature of such associations.


Bone marrow transplantation for leukocyte adhesion deficiency-I: case report.
Leukocyte adhesion deficiency type I (LAD-I) is a rare autosomal recessive immunodeficiency syndrome leading to recurrent bacterial and fungal infections. Bone marrow transplantation offers the only cure. In this report, we describe the course and outcome of bone marrow transplant in a 4 month-old female infant with LAD-I at King Hussein Medical Center, Jordan. A successful matched HLA- related allogeneic bone marrow transplantation was performed. Engraftment was demonstrated on the 12th day. The patient developed Grade III grafts versus host disease (GVHD), veno-occlusive disease of the liver, and late onset hemorrhagic cystitis. She recovered with appropriate immune reconstitution.


Natural Compounds as Antimicrobial Agents.
During the first two decades of this century, conventional antimicrobial compounds have been found out to have more bacterial resistance. What has also been worrying is the rediscovery of the so-called "natural compounds", which in turn have a good name among the average citizen because of the former's plant or animal origin. However, they do not form a well-classified group of substances. This Special Issue consists of five reviews focusing on clinical bacteria applications in food and their specific effects upon virulent bacterial factors. You will also find a research on much needed, new antimicrobials sourced in extreme environments, and secondary metabolites of Burkholderia. This issue includes 12 original research papers which will provide you with an in-depth coverage of the protein extract activity, as well as the activity of other plant extracts, on fighting bacteria, fungi or diarrhea. Their use in broilers or laying eggs for production purposes has also been focused on in order to improve gut microbiota. Last but not least, we should not forget about honey and its effect; Allium sativum-fermented extracts, as well as other "natural" compounds, have been studied in their fight against biofilms. Furthermore, we have also examined the use of essential oils, which are currently used in edibles such as fresh sausages. The present work also deals with other applications such as natural compound derivatives as well as compound mixtures.


Temporal evolution and prognostic significance of postoperative spikes after selective amygdala-hippocampectomy.
The purpose of this study was to quantify the temporal evolution and to determine the prognostic significance of spikes on serial postoperative EEGs after selective amygdala-hippocampectomy. The authors performed postoperative EEGs 4 months, 1 year, and 2 years after surgery in 31 patients with unilateral mesial temporal lobe epilepsy. Spike frequency was determined ipsilateral to the resection (group I, no spikes; group II, 1 to 10 spikes; group III, 11 to 20 spikes; group IV, more than 21 spikes during the 30-minute recording). The temporal evolution of postoperative spike frequency was assessed, and these parameters were correlated with surgical outcome. Twenty-two patients showed spikes on postoperative EEG. Spike frequency decreased over time in 14 patients, while no changes or minimal changes occurred in seven patients, and spike frequency increased in one patient. Nine patients had no spikes. There was no correlation between occurrence, frequency, and temporal evolution of spikes with postoperative seizure control. The authors' results demonstrate a progressive decrease of spike frequency during the postoperative period after selective amygdala-hippocampectomy, although occurrence, frequency, and temporal evolution of postoperative spikes had no implications on surgical outcome.


Evidence of patients' challenges and barriers related to usage of Implanon®: scoping review protocol.
According to the United Nations Trends in Contraceptive Use 2015 report, at least one in ten married or in-union women in most regions of the world has an unmet need for family planning. Family Planning 2020 reports an estimate of almost 134 million married or in-union women of reproductive age who have an unmet need for modern methods of contraception in 2016 in participating countries. Family planning has therefore been highlighted as a global unmet need. Initiatives such as Family Planning 2020 aim to promote contraceptive use through Implanon® contraceptive implant. Implanon® has been reported to be a highly effective form of contraception. However, poor outcomes from users of the Implanon® have been reported in recent studies. The main objective of this review is to map the literature for the evidence on usage of Implanon® in order to reveal challenges and barriers. A scoping review searching evidence on Implanon® use will be conducted. Relevant studies will be identified from 1998 to present. The following databases: PubMed, MEDLINE, EBSCOhost, Google Scholar and Cochrane library will be searched for peer-reviewed literature. We will also search for grey literature in this study area. The eligibility criteria will guide the study selection. A data charting table will be designed to extract information from the literature. The results of this study will be reported by use of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Data will be analysed using thematic analysis and the NVIVO software version 10. The mixed method appraisal tool (MMAT) will be used to assess the quality of included studies. We anticipate finding relevant studies on the use of Implanon®. Evidence gathered from included studies will help us identify gaps in research and help guide future research on Implanon® usage. This information can also help guide implementers and users on challenges and barriers related to use of Implanon®. PROSPERO CRD42017072926 .


Power considerations for clinical trials using multivariate time-to-event data.
Many clinical trials involve the collection of data on the times to occurrence of different types of events, such as different fungal infections in AIDS research, or of recurrences of the same type, such as successive fits in epilepsy research. The multivariate proportional hazards model allows for analysis of this data and software for doing this is now widely available. In this paper, the approximate power of a clinical trial that aims to use such data for comparing two treatments is derived. Special attention is given to the bivariate case, both to show that the approximation works well and to illustrate how various design parameters affect the power of a trial. As with any multivariate data in clinical trials, there are many conceptual issues that should be considered during trial design; the paper closes with a discussion of some of these.


Mathematical approaches to modeling of cortical spreading depression.
Migraine with aura (MwA) is a debilitating disease that afflicts about 25%-30% of migraine sufferers. During MwA, a visual illusion propagates in the visual field, then disappears, and is followed by a sustained headache. MwA was conjectured by Lashley to be related to some neurological phenomenon. A few years later, Leão observed electrophysiological waves in the brain that are now known as cortical spreading depression (CSD). CSD waves were soon conjectured to be the neurological phenomenon underlying MwA that had been suggested by Lashley. However, the confirmation of the link between MwA and CSD was not made until 2001 by Hadjikhani et al. [Proc. Natl. Acad. Sci. U.S.A. 98, 4687-4692 (2001)] using functional MRI techniques. Despite the fact that CSD has been studied continuously since its discovery in 1944, our detailed understandings of the interactions between the mechanisms underlying CSD waves have remained elusive. The connection between MwA and CSD makes the understanding of CSD even more compelling and urgent. In addition to all of the information gleaned from the many experimental studies on CSD since its discovery, mathematical modeling studies provide a general and in some sense more precise alternative method for exploring a variety of mechanisms, which may be important to develop a comprehensive picture of the diverse mechanisms leading to CSD wave instigation and propagation. Some of the mechanisms that are believed to be important include ion diffusion, membrane ionic currents, osmotic effects, spatial buffering, neurotransmitter substances, gap junctions, metabolic pumps, and synaptic connections. Discrete and continuum models of CSD consist of coupled nonlinear differential equations for the ion concentrations. In this review of the current quantitative understanding of CSD, we focus on these modeling paradigms and various mechanisms that are felt to be important for CSD.


Activation of calpain by renin-angiotensin system in pleural mesothelial cells mediates tuberculous pleural fibrosis.
Pleural fibrosis is defined as an excessive deposition of extracellular matrix (ECM) components that results in destruction of the normal pleural tissue architecture. It can result from diverse inflammatory conditions, especially tuberculous pleurisy. Pleural mesothelial cells (PMCs) play a pivotal role in pleural fibrosis. Calpain is a family of calcium-dependent endopeptidases, which plays an important role in ECM remodeling. However, the role of calpain in pleural fibrosis remains unknown. In the present study, we found that tuberculous pleural effusion (TPE) induced calpain activation in PMCs and that inhibition of calpain prevented TPE-induced collagen-I synthesis and cell proliferation of PMCs. Moreover, our data revealed that the levels of angiotensin (ANG)-converting enzyme (ACE) were significantly higher in pleural fluid of patients with TPE than those with malignant pleural effusion, and ACE-ANG II in TPE resulted in activation of calpain and subsequent triggering of the phosphatidylinositol 3-kinase (PI3K)/Akt/NF-κB signaling pathway in PMCs. Finally, calpain activation in PMCs and collagen depositions were confirmed in pleural biopsy specimens from patients with tuberculous pleurisy. Together, these studies demonstrated that calpain is activated by renin-angiotensin system in pleural fibrosis and mediates TPE-induced collagen-I synthesis and proliferation of PMCs via the PI3K/Akt/NF-κB signaling pathway. Calpain in PMCs might be a novel target for intervention in tuberculous pleural fibrosis.