Low Levels of Low-Density Lipoprotein Cholesterol and Mortality Outcomes in Non-Statin Users.
We aimed to test the association between low-density lipoprotein cholesterol (LDL-C) and cardiovascular disease (CVD), cancer, and all-cause mortality in non-statin users. A total of 347,971 subjects in Kangbuk Samsung Health Study (KSHS.57.4% men, mean follow up: 5.64 ± 3.27 years) were tested. To validate these associations, we analyzed data from another cohort (Korean genome and epidemiology study, KoGES, 182,943 subjects). All subjects treated with any lipid-lowering therapy and who died during the first 3 years of follow up were excluded. Five groups were defined according to baseline LDL-C concentration (<70, 70-99, 100-129, 130-159, ≥160 mg/dL). A total of 2028 deaths occurred during follow-up in KSHS. The lowest LDL-C group (LDL < 70 mg/dL) had a higher risk of all-cause mortality (HR 1.95, 1.55-2.47), CVD mortality (HR 2.02, 1.11-3.64), and cancer mortality (HR 2.06, 1.46-2.90) compared to the reference group (LDL 120-139 mg/dL). In the validation cohort, 2338 deaths occurred during follow-up. The lowest LDL-C group (LDL < 70 mg/dL) had a higher risk of all-cause mortality (HR 1.81, 1.44-2.28) compared to the reference group. Low levels of LDL-C concentration are strongly and independently associated with increased risk of cancer, CVD, and all-cause mortality. These findings suggest that more attention is needed for subjects with no statin-induced decrease in LDL-C concentrations.


Expression of G protein-coupled receptor 30 in the hamster ovary: differential regulation by gonadotropins and steroid hormones.
The nongenomic actions of estradiol-17beta are mediated by transmembrane estrogen receptors. Recently, G protein-coupled receptor 30 (GPR30) has been suggested to be a transmembrane estrogen receptor that can mediate rapid and transcription-independent estradiol-17beta signaling in different cell types. However, the expression, regulation, or biological relevance of GPR30 in the ovary remains unknown. We examined the expression and hormonal regulation of GPR30 mRNA and protein in hamster ovarian cells during the estrous cycle and after hypophysectomy and hormone replacement. GPR30 protein expression was high in the theca, appreciable in the granulosa, but low in luteal cells. GPR30 protein levels in granulosa and theca cells increased steadily with the development of preantral and antral follicles, respectively. GPR30 mRNA and protein levels increased significantly on diestrous (d 3 of the estrous cycle), but decreased on d 4 at 1600 h after the LH surge. GPR30 mRNA levels increased significantly after hypophysectomy. Although steroid treatment failed to alter ovarian GPR30 mRNA levels, either FSH or LH effectively reduced the levels. Interestingly, the decrease in GPR30 mRNA corresponded to a marked increase in the receptor protein levels. FSH treatment, either alone or together with LH, resulted in a marked increase in GPR30 immunostaining in granulosa cells. LH alone significantly increased immunostaining in theca cells. These results suggest that GPR30 is expressed in the membrane of hamster granulosa and theca cells, and the expression is regulated by gonadotropins. The unique pattern of GPR30 expression suggests that gonadotropin-regulated follicular cell functions may involve GPR30 activity.


Refractory hypercalcemia in an infant secondary to talc pleurodesis resolving after renal transplantation.
Talc pleurodesis is the definitive therapy of recurrent pneumothorax and has not been associated with metabolic complications. We report an anephric male infant who developed severe hypercalcemia 6 months following talc pleurodesis for recurrent peritoneal dialysis-related hydrothorax. The etiology of hypercalcemia was related to persistently elevated 1,25-dihydroxyvitamin D(3) (1,25[OH]2D) levels. The source appeared to be the extrarenal production of 1,25(OH)2D from macrophages in a large thoracic talc granuloma. Hypercalcemia was controlled with a combination of a low calcium diet, low calcium dialysis, ketoconazole and hydroxychloroquine, but elevated 1,25(OH)2D levels persisted. At 32 months of age the child underwent renal transplantation with alemtuzumab pre-conditioning. The hypercalcemia resolved immediately, with normalization of serum 1,25(OH)2D levels and without hypercalciuria. This case demonstrates that hypercalcemia is a potential complication of talc pleurodesis from the extrarenal production of 1,25(OH)2D and that alemtuzumab, a monoclonal antibody directed against the CD52 antigen (which is expressed on almost all macrophages), may have a role in the treatment of hypercalcemia associated with granulomatous conditions.


Limitations of Kr-81m for quantitation of ventilation scans.
Predictions of Kr-81m behavior in the lungs have been based on a single-compartment model of well-mixed gas. To determine the validity of this model, anesthetized, paralyzed dogs were ventilated mechanically over a wide range of ventilations with Kr-81m in the inspirate. Averaged data obtained from 1.5- to 2-min images were compared with the model's predictions. Krypton-81m concentration appeared more linearly related to ventilation than the model predicts. This suggests that the Kr-81m may not be distributed to the entire resident gas volume or that its distribution changes with lung volume. Estimation of end-expiratory volume (FRC)--based on the tidal volume and the maximum-to-minimum count ratio over the lung during gated acquisitions--underestimated the true FRC by about 40%. The magnitude of error depended upon the combination of tidal volume and frequency and the inspiratory time. Thus, Kr-81m does not mix well with resident lung gas, and the well-mixed, single-compartment model is not a good predictor of Kr-81m behavior in the lung.


Promoting cessation resources through cigarette package warning labels: a longitudinal survey with adult smokers in Canada, Australia and Mexico.
Health warning labels (HWLs) on tobacco packaging can be used to provide smoking cessation information, but the impact of this information is not well understood. Online consumer panels of adult smokers from Canada, Australia and Mexico were surveyed in September 2012, January 2013 and May 2013; replenishment was used to maintain sample sizes of 1000 participants in each country at each wave. Country-stratified logistic Generalised Estimating Equation (GEE) models were estimated to assess correlates of citing HWLs as a source of information on quitlines and cessation websites. GEE models also regressed having called the quitline, and having visited a cessation website, on awareness of these resources because of HWLs. At baseline, citing HWLs as a source of information about quitlines was highest in Canada, followed by Australia and Mexico (33%, 19% and 16%, respectively). Significant increases over time were only evident in Australia and Mexico. In all countries, citing HWLs as a source of quitline information was significantly associated with self-report of having called a quitline. At baseline, citing HWLs as a source of information about cessation websites was higher in Canada than in Australia (14% and 6%, respectively; Mexico was excluded because HWLs do not include website information), but no significant changes over time were found for either country. Citing HWLs as a source of information about cessation websites was significantly associated with having visited a website in both Canada and Australia. HWLs are an important source of cessation information.


Chimpanzees (Pan troglodytes) detect strange body parts: an eye-tracking study.
This study investigated chimpanzee body representation by testing whether chimpanzees detect strangeness in body parts. We tested six chimpanzees with edited chimpanzee body pictures in eye-tracking tasks. The target body parts were arms or legs. For either target, there were four conditions: "normal" condition as control, where all bodies were normal; "misplaced" condition, where one arm or one leg was misplaced to an incorrect body location in each picture; "replaced by a chimpanzee part" condition, where one arm or one leg was replaced by a chimpanzee leg or arm, respectively, in its original place in each picture; and "replaced by a human part" condition, where one arm or one leg was replaced by a human arm or leg in each picture. Compared to the looking times toward the normal parts, chimpanzees had significantly longer looking times toward the human arms or legs. The looking times toward the misplaced parts were also longer than the normal parts, but the difference just failed to meet significance. These results indicate more interests toward strange body parts, compared to typical parts, suggesting that chimpanzees might have a body representation that is sufficiently sensitive to detect these aspects of strangeness.


Recommendations for a culturally relevant Internet-based tool to promote physical activity among overweight young African American women, Alabama, 2010-2011.
Innovative approaches are needed to promote physical activity among young adult overweight and obese African American women. We sought to describe key elements that African American women desire in a culturally relevant Internet-based tool to promote physical activity among overweight and obese young adult African American women. A mixed-method approach combining nominal group technique and traditional focus groups was used to elicit recommendations for the development of an Internet-based physical activity promotion tool. Participants, ages 19 to 30 years, were enrolled in a major university. Nominal group technique sessions were conducted to identify themes viewed as key features for inclusion in a culturally relevant Internet-based tool. Confirmatory focus groups were conducted to verify and elicit more in-depth information on the themes. Twenty-nine women participated in nominal group (n = 13) and traditional focus group sessions (n = 16). Features that emerged to be included in a culturally relevant Internet-based physical activity promotion tool were personalized website pages, diverse body images on websites and in videos, motivational stories about physical activity and women similar to themselves in size and body shape, tips on hair care maintenance during physical activity, and online social support through social media (eg, Facebook, Twitter). Incorporating existing social media tools and motivational stories from young adult African American women in Internet-based tools may increase the feasibility, acceptability, and success of Internet-based physical activity programs in this high-risk, understudied population.


Enhancement of Corneal Visibility in Optical Coherence Tomography Images with Corneal Opacification.
To establish and to rank the performance of a corneal adaptive compensation (CAC) algorithm in enhancing corneal images with scars acquired from three commercially available anterior segment optical coherence tomography (ASOCT) devices. Horizontal B-scans of the cornea were acquired from 10 patients using three ASOCT devices (Spectralis, RTVue, and Cirrus). We compared ASOCT image quality (with and without CAC) by computing the intralayer contrast (a measure of shadow removal), the interlayer contrast (a measure of tissue boundary visibility), and the tissue/background contrast (a measure of overall corneal visibility). All six groups (Spectralis, RTVue, Cirrus, Spectralis+CAC, RTVue+CAC, and Cirrus+CAC) were ranked according to a global performance index that averaged all contrast quantities. CAC provided mean intralayer contrasts improvement for all devices (all P < 0.05). Mean tissue/boundary contrasts were also improved for Spectralis and Cirrus (both P < 0.001). Mean interlayer contrasts were increased for Spectralis (P = 0.011) only. When comparing global performance indices, all CAC groups outperformed their corresponding baseline groups significantly. RTVue performed best without CAC, but Spectralis+CAC was ranked first. ASOCT images of corneal scars may be enhanced by CAC through shadow removal, improved tissue boundary visibility, and enhanced corneal visibility against the image background. RTVue produces the finest baseline images but the best image quality can be achieved by applying CAC to Spectralis images. CAC could enhance visibility of corneal images with scars acquired from commercially available ASOCT devices and could aid preoperative planning of patients for ophthalmic procedures.


The impact of aging infrastructure and site on facility planning.
Infrastructure analysis should be a basic component of the facility master plan and specific information concerning the site and facility must be collected, evaluated, and analyzed at each phase of development of the master plan. The interpretation of such information can significantly impact the visibility of design solutions, department locations, construction phasing, and costs. This paper identifies the information to be collected, its potential impact on the master plan, and the facility manager's role during the planning process.


A randomised Phase II/III study to evaluate the efficacy and safety of orally administered Oxalobacter formigenes to treat primary hyperoxaluria.
Primary hyperoxaluria (PH) patients overproduce oxalate because of rare genetic errors in glyoxylate metabolism. Recurrent urolithiasis and/or progressive nephrocalcinosis are PH hallmarks and can lead to kidney damage, systemic oxalosis and death. Based on previous studies, we hypothesised that treatment with the oxalate-metabolizing bacterium Oxalobacter formigenes would mediate active elimination of oxalate from the plasma to the intestine of PH patients, thereby reducing urinary oxalate excretion (Uox). The efficacy and safety of O. formigenes (Oxabact™ OC3) were evaluated for 24 weeks in a randomised, placebo-controlled, double-blind study. The primary endpoint was reduction in Uox. Secondary endpoints included change in plasma oxalate (Pox) concentration, frequency of stone events, number of responders, and Uox in several subgroups. Additional post hoc analyses were conducted. Thirty-six patients were randomised; two patients withdrew from placebo treatment. Both OC3 and placebo groups demonstrated a decrease in Uox/urinary creatinine ratio, but the difference was not statistically significant. No differences were observed with respect to change in Pox concentration, stone events, responders' number or safety measures. In patients with estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m2, Pox increased by 3.25 µmol/L in the placebo group and decreased by -1.7 µmol/L in the OC3 group (p = 0.13). After 24 weeks, eGFR had declined to a greater degree in the placebo than in the OC3 group: -8.00 ± 2.16 versus -2.71 ± 2.50; p = 0.01. OC3 treatment did not reduce urinary oxalate over 24 weeks of treatment compared with placebo in patients with PH. The treatment was well tolerated.


Heart failure in COVID-19: the multicentre, multinational PCHF-COVICAV registry.
We assessed the outcome of hospitalized coronavirus disease 2019 (COVID-19) patients with heart failure (HF) compared with patients with other cardiovascular disease and/or risk factors (arterial hypertension, diabetes, or dyslipidaemia). We further wanted to determine the incidence of HF events and its consequences in these patient populations. International retrospective Postgraduate Course in Heart Failure registry for patients hospitalized with COVID-19 and CArdioVascular disease and/or risk factors (arterial hypertension, diabetes, or dyslipidaemia) was performed in 28 centres from 15 countries (PCHF-COVICAV). The primary endpoint was in-hospital mortality. Of 1974 patients hospitalized with COVID-19, 1282 had cardiovascular disease and/or risk factors (median age: 72 [interquartile range: 62-81] years, 58% male), with HF being present in 256 [20%] patients. Overall in-hospital mortality was 25% (n = 323/1282 deaths). In-hospital mortality was higher in patients with a history of HF (36%, n = 92) compared with non-HF patients (23%, n = 231, odds ratio [OR] 1.93 [95% confidence interval: 1.44-2.59], P < 0.001). After adjusting, HF remained associated with in-hospital mortality (OR 1.45 [95% confidence interval: 1.01-2.06], P = 0.041). Importantly, 186 of 1282 [15%] patients had an acute HF event during hospitalization (76 [40%] with de novo HF), which was associated with higher in-hospital mortality (89 [48%] vs. 220 [23%]) than in patients without HF event (OR 3.10 [2.24-4.29], P < 0.001). Hospitalized COVID-19 patients with HF are at increased risk for in-hospital death. In-hospital worsening of HF or acute HF de novo are common and associated with a further increase in in-hospital mortality.


[Rejection and identity].
The author shows that the splitting of identity is reversible if the object relations are strong enough (example: Rahel Varnhagen). The schizophrenic subject escapes into another manner of being in a desperate effort to survive (example: Gregor Samsa in the novel of Kafka). A borderline patient recovers her identity by overcoming a symbiotic relationship with her psychotic mother.


Circadian profile of QT interval and QT interval variability in 172 healthy volunteers.
The limited prognostic value of QT dispersion has been demonstrated in recent studies. However, longitudinal data on physiological variations of QT interval and the influence of aging and sex are few. This analysis included 172 healthy subjects (89 women, 83 men; mean age 38.7 +/- 15 years). Beat-to-beat QT interval duration (QT, QTapex [QTa], Tend [Te]), variability (QTSD, QTaSD), and the mean R-R interval were determined from 24-hour ambulatory electrocardiograms after exclusion of artifacts and premature beats. All volunteers were fully active, awoke at approximately 7:00 AM, and had 6-8 hours of sleep. QT and R-R intervals revealed a characteristic day-night-pattern. Diurnal profiles of QT interval variability exhibited a significant increase in the morning hours (6-9 AM; P < 0.01) and a consecutive decline to baseline levels. In female subjects the R-R and Tend intervals were significantly lower at day- and nighttime. Aging was associated with an increase of QT interval mainly at daytime and a significant shift of the T wave apex towards the end of the T wave. The circadian profile of ventricular repolarization is strongly related to the mean R-R interval, however, there are significant alterations mainly at daytime with normal aging. Furthermore, the diurnal course of the QT interval variability strongly suggests that it is related to cardiac sympathetic activity and to the reported diurnal pattern of malignant ventricular arrhythmias.


Primary and secondary small cell neuroendocrine carcinoma of the larynx: a review.
Primary laryngeal small cell neuroendocrine carcinoma (SCNC) is an unusual malignancy accounting for <0.5% of laryngeal carcinomas. To date, approximately 200 cases of primary and 5 of secondary SCNC of the larynx have been reported. This tumor most often presents in the sixth and seventh decades in men who are heavy cigarette smokers. The lesion may be associated with different paraneoplastic syndromes (ectopic adrenocorticotropic hormone syndrome, Schwartz-Bartter syndrome or syndrome of inappropriate secretion of antidiuretic hormone, and Eaton-Lambert myasthenic syndrome) or with ectopic hormone production. The diagnosis is based essentially on the histologic appearance of the tumor, confirmed by immunocytochemical investigations. Concurrent chemoradiotherapy regimens offer potential for long-term survival. This tumor is biologically aggressive, and the extent of the disease is the most significant independent prognostic factor of survival. The survival rate is similar to that with pulmonary SCNC.


Detraining outcomes with expiratory muscle strength training in Parkinson disease.
Expiratory muscle strength training (EMST) is efficacious for improving maximum expiratory pressure (MEP), cough function, and swallowing safety in Parkinson disease (PD). However, there are no published reports describing detraining effects following EMST in persons with PD. Moreover, there are no published reports describing detraining effects following any behavioral swallowing intervention. Ten participants with PD underwent 3 mo of detraining following EMST. Measures of MEP and swallowing safety were made prior to beginning EMST (baseline), posttreatment (predetraining), and 3 mo postdetraining. Participants demonstrated, on average, a 19% improvement in MEP from pre- to post-EMST. Following the 3 mo detraining period, MEP declined by 2% yet remained 17% above the baseline value. No statistically significant changes were found in swallowing safety from post-EMST to postdetraining period. Following the 3 mo detraining period, seven participants demonstrated no change in swallowing safety, one worsened, and two had improvements. This preliminary study highlights the need for the design of maintenance programs to sustain function following intensive periods of training.


Technique evaluation of foster care in chronic psychiatric disorders.
Foster care received by 178 patients with chronic psychiatric disorders discharged from Hamilton Psychiatric Hospital in the years 1966 through 1969 was studied by technique evaluation. Residents were followed for 3 years by means of health records. The achievement of operational objectives of the program (Homes for Special Care) was compared with two types of outcome--emergency readmission to hospital and discharge to the community. Emergency readmission was associated with rural location of the foster home, inferior quality of the home operator and smaller size (i.e., fewer residents) of the home. Discharge to the community was more common among younger, female residents whose previous psychiatric hospitalization had been relatively brief. In general, prescription audit was not a fruitful way of evaluating quality of health care.


Nanopore-based detection and characterization of yam viruses.
We here assessed the capability of the MinION sequencing approach to detect and characterize viruses infecting a water yam plant. This sequencing platform consistently revealed the presence of several plant virus species, including Dioscorea bacilliform virus, Yam mild mosaic virus and Yam chlorotic necrosis virus. A potentially novel ampelovirus was also detected by a complimentary Illumina sequencing approach. The full-length genome sequence of yam chlorotic necrosis virus was determined using Sanger sequencing, which enabled determination of the coverage and sequencing accuracy of the MinION technology. Whereas the total mean sequencing error rate of yam chlorotic necrosis virus-related MinION reads was 11.25%, we show that the consensus sequence obtained either by de novo assembly or after mapping the MinION reads on the virus genomic sequence was >99.8% identical with the Sanger-derived reference sequence. From the perspective of potential plant disease diagnostic applications of MinION sequencing, these degrees of sequencing accuracy demonstrate that the MinION approach can be used to both reliably detect and accurately sequence nearly full-length positive-sense single-strand polyadenylated RNA plant virus genomes.


Preoperative Evaluation and Optimization for Reconstruction of Segmental Bone Defects of the Tibia.
Reconstruction of segmental bone defects requires a large commitment both on the part of the patient and the physician. Investing in preoperative evaluation and optimization is the only logical way to pursue such an endeavor. Unfortunately, detailed studies regarding segmental bone defects and preoperative factors are relatively lacking owing to the relatively low incidence of the problem. Fortunately, other orthopaedic pathologies (arthritis, ligamentous injuries about the knee) have high prevalence and consistency, allowing detailed analysis of preoperative factors. We review this literature, and that directly involving segmental bone defects when available, to guide surgeons planning segmental bone defect reconstruction.


Antibacterial action of colistin (polymyxin E) against Mycobacterium aurum.
Mycobacterium aurum was susceptible to the antibiotic colistin (polymyxin E),which had an MIC of 5 micrograms/ml and an apparent bactericidal effect at concentrations above 50 micrograms/ml. Treatment of actively growing cells with sublethal concentrations of colistin (15 micrograms/ml) resulted in synchronized cell division once the antibiotic was removed. Under conditions of synchronized cell growth, one cycle of DNA replication lasted 120 min and one cycle of cell division lasted about 180 min. Although the antibiotic treatment during synchronization experiments did not produce apparent changes in the bacterial envelope, it was accompanied by the accumulation of a polysaccharide-like substance in the bacterial cytoplasm which gradually decreased after the removal of antibiotic and by an increase in the number of mesosomes at 3 h after antibiotic removal. This step was closely linked to the doubling time of bacteria. Lethal concentrations of colistin of 50 and 100 micrograms/ml, which caused about 90 and 99% cell death, respectively, produced significant cytoplasmic membrane injuries, patchy appearance of the cell wall outer polysaccharide layer, and little cell lysis. These data indicate that the cytoplasmic membrane is a site of action of colistin and raise a question as to whether an outer bilayer exists in mycobacteria, at least functionally.


Short burst oxygen therapy after activities of daily living in the home in chronic obstructive pulmonary disease.
Short burst oxygen therapy (SBOT) is widely prescribed in the UK with little evidence of benefit. A study was performed to examine whether SBOT benefits patients when undertaking normal activities at home among those who already use it. Twenty-two patients with chronic obstructive pulmonary disease (COPD) were included in the study. All regularly used SBOT at home and claimed that it helps them. Each patient chose two daily living activities for which they used SBOT for relief of breathlessness. Patients were then randomised to use either an air or oxygen gas cylinder. At least 15 min later the same activity was performed using the other gas cylinder. The same process was then repeated for the second chosen activity. The main endpoints were subjective and objective times to recovery, analysed for each activity separately or taking the average over the two activities. A paired statistical analysis was performed. All patients used SBOT with nasal prongs after exercise. Using the average recovery time over two activities for each patient, the mean objective recovery time was 38 s lower (95% CI -81 to +5) using oxygen and the mean subjective recovery time was 34 s lower (95% CI -69 to +2). Five patients were correctly able to distinguish oxygen from air after both activities and there was a suggestion that their recovery times were shorter than those who did not correctly identify the gases (91 s vs 20 s using objective recovery times, and 80 s vs 22 s using subjective recovery times), although this was a subgroup analysis based on only five patients with non-significant results. There is some evidence that SBOT shortens recovery time after activities of daily living in a selected group of patients with COPD, but the effect is small. There appears to be a subgroup of patients who may benefit to a much greater degree.


[Mechanism of dwarfing effect of tomato (Solanum lycopersicon) seedlings induced by cold-shock treatment under high temperature stress].
To explore the dwarfing mechanism of tomato seedlings induced by cold-shock treatment followed by high temperature, tomato seedlings were subjected to cold-shock treatment once a day at 8:00 with temperature of 5, 10 and 15 °C for 10, 20 and 30 min, respectively, and ethylene production rate was measured. Plant height, ethylene production and gibberellin (GA3) content of the seedlings treated with T10 °C D10 min (cold-shock with 10 °C for 10 min), coupled with utilization of growth regulators, were also evaluated. The results showed that the release of ethylene was increased with the decrease of cold-shock temperature and extension of treatment time. The cold-shock treatment of 5 °C and 30 min had the highest ethylene production rate of 60.3 nL h-1 . g-1, which was 6.5 times of the control. None of ethephon (ETH), silver thiosulphate (STS), GA, or paclobutrazol (PP333) could completely block high ethylene production induced by cold-shock treatment. Tomato seedlings with cold-shock treatment (T10 °C D10 min ) resulted in reduction in GA3 content by 38.1% compared with the value of control (130.6 µg . g-1). Neither ethephon nor STS had significant effect on the dwarfing induced by cold-shock. However, GA3 weakened the dwarfing effect induced by cold-shock treatment (T10 °C D10 min), while PP333 greatly enhanced it. The dwarfing effect by cold-shock treatment of T10 °C D10 min was equivalent to that of application of 4.0 mg . L-1 PP333 based on the seedling height as an evaluation indicator. It was concluded that cold-shock treatment stimulated shoot ethylene production and blocked GA3 synthesis. GA3 played a vital role in dwarfing effect on tomato seedling induced by cold-shock treatment. Cold-shock with 10 °C and duration of 10 min could promote the growth of tomato seedlings with shorter stem and higher dry mass accumulation.


The effects of sampling from a peripheral venous catheter compared to repeated venepunctures on markers of coagulation, inflammation, and endothelial function.
Peripheral venous (PV) catheters are often used for serial blood sampling, but studies suggest that PV catheters increase markers of coagulation activation and inflammation. Whether the increase is caused by irritation of the vessel wall or diurnal variation is unknown. We therefore compared the effects of a PV catheter and repeated venepunctures on markers of coagulation, inflammation, and endothelial function.A PV catheter was inserted at 07:45 in a hand vein in 10 healthy subjects, and blood samples were collected at 8:00, 10:00, 12:00, and 14:00. In the contralateral arm, blood was simultaneously obtained by venepunctures. Measures of coagulation, i.e., activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen, prothrombin fragment 1 + 2 (F1 + 2) and thrombin-antithrombin (TAT), inflammation, i.e., interleukin 6 (IL-6) and C-reactive protein (CRP), and endothelial function, i.e., plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator (tPA), von Willebrand factor (vWF), and tissue factor (TF) were measured in plasma.The concentrations of TAT and F1 + 2 were significantly increased (10:00; p < .01, 12:00; p < .05, and 14:00; p < .01) in PV catheter samples compared with venepuncture samples. There was a minor increase in PT and INR and no increase in APTT, fibrinogen, CRP, PAI-1, tPA, vWF, and TF, with no differences between sampling methods. IL-6 concentrations increased in many PV catheter samples and venepuncture samples, but the response varied between the subjects.Blood collection through a PV catheter induces coagulation activation, whereas endothelial function is not affected. More studies are needed to disclose the effect of blood sampling on IL-6.


Innate lymphoid cells in atherosclerosis.
The family of innate lymphoid cells (ILCs) consisting of NK cells, lymphoid tissue inducer cells and the 'helper'-like ILC subsets ILC1, ILC2 and ILC3 have been shown to have important roles in protection against microbes, regulation of inflammatory diseases and involved in allergic reactions. ILC1s produce IFN-γ upon stimulation with IL-12 and IL-18, ILC2s produce IL-5 and IL-13 responding to IL-33 and IL-25 while ILC3s produce IL-17 and IL-22 after stimulation with IL-23 or IL-1. Although few studies have directly investigated the role for ILCs in atherosclerosis, several studies have investigated transcription factors and cytokines shared by ILCs and T helper cells. In this review we summarize our current understanding of the role of ILC in atherosclerosis and discuss future directions.


Dopamine regulates phosphate uptake by opossum kidney cells through multiple counter-regulatory receptors.
The purpose of this study was to determine the mechanisms of dopamine regulation of phosphate uptake in opossum kidney (OK) cells, a model of proximal renal tubules. Dopamine stimulated cAMP generation and inhibited radiolabeled phosphate uptake into OK cell monolayers by 14.4 +/- 1.8%. The effect of dopamine was transient, as phosphate uptake returned toward control level by 3 h despite the continued presence of dopamine. Pretreatment with pertussis toxin increased dopamine inhibition of phosphate uptake to 25 +/- 3%, increased the duration of the dopamine effect to at least 3 h, and enhanced cAMP generation. In an OK cell clone that overexpressed cAMP phosphodiesterase, dopamine did not inhibit phosphate uptake, but pharmacologic inhibition of protein kinase A activation did not prevent dopamine inhibition of phosphate uptake. A DA1 receptor agonist inhibited phosphate uptake more potently than dopamine (29.5 +/- 1.1%) or a DA2 receptor agonist (7.9 +/- 2%). However, both DA1 and DA2 receptor antagonists completely blocked dopamine inhibition of phosphate uptake. DA1, but not the DA2, antagonists blocked dopamine-stimulated cAMP generation. Treatment with alpha-adrenergic receptor antagonists potentiated dopamine inhibition of phosphate uptake to the same extent as pertussis toxin and was not additive with pertussis toxin. It is concluded that dopamine inhibits phosphate uptake through DA1 and DA2 receptor stimulation by cAMP-dependent and -independent pathways and activates a pertussis toxin-sensitive counter-regulatory pathway that attenuates this response through alpha-adrenergic receptor stimulation.


Current perspectives on revascularization in multivessel ST elevation myocardial infarction.
Up to 50% of patients presenting with ST elevation myocardial infarction (STEMI) are found to have multivessel coronary artery disease. These patients have a worse prognosis compared with the overall STEMI population. Two revascularization strategies are possible for these patients: treating the infarct-related artery percutaneous coronary intervention (IRA-PCI) only or achieving Complete revascularization (CR), either through an immediate multivessel PCI during the index angiography or during a second-staged procedure. Until recently, most clinical data on this issue were derived from observational studies - which all showed a clear advantage to the IRA-PCI over the CR approach. Over the past few years, several groundbreaking randomized trials have suggested that the CR approach may be at least equivalent, and perhaps superior, to the IRA-PCI strategy. This has caused a paradigm shift reflected in the recent US and European guidelines. However, there is still uncertainty on the optimal timing for achieving CR (immediate/during the index admission/during a subsequent elective admission) and several other important issues in terms of revascularization: the extent of revascularization needed to achieve maximal benefit, the optimal means to evaluate the significance of intermediate coronary stenosis in the context of acute myocardial infarction, and the best approach to treat chronic total occlusions have not been thoroughly examined, and are the subject of an ongoing debate.


Osteoclast activation by receptor activator of NF-kappaB ligand enhances the mobilization of hematopoietic progenitor cells from the bone marrow in acute injury.
Osteoclasts (OCLs) are multinucleated cells that are derived from the monocyte/macrophage hematopoietic lineage in response to receptor activator of NF-kappaB ligand (RANKL) activation. They are specialized cells responsible for physiological bone resorption and as well as pathologic bone loss. In addition to their unique ability to resorb bone, OCLs also play a potential role in the mobilization of hematopoietic progenitor cells from the bone marrow (BM), particularly under various stress stimuli (e.g. hypoxia, injury or inflammation). We investigated the effect of activated OCLs on the stem cell niche and whether this leads to mobilization of hematopoietic progenitors. We induced activated OCLs from the RAW264.7 cell line through stimulation with RANKL and we quantified the levels of the stem cell niche component SDF-1 on the osteblasts and CXCR4 on the bone marrow cells (BMCs) by culturing with supernatants from activated OCLs. In addition, we exposed mice to stress by inducing liver injury with CCl4 followed by injecting RANKL to activate OCLs and compared the effect on the mobilization of hematopoietic progenitor cells from the BM. We found that functional OCLs cleaved SDF-1alpha in the osteoblasts and increased CXCR4 expression in the BMCs. Moreover, under stress in vivo, mobilized hematopoietic progenitor cells were significantly increased after RANKL treatment. These results suggest that OCLs might be involved in alteration of the interaction between SDF-1 and CXCR4 leading to mobilization of hematopoietic progenitor cells from the BM.


Phosphoryl Transfer Reaction in RNA: Is the Substrate-Assisted Catalysis a Possible Mechanism in Certain Solvents?
A proton shuttle mechanism for the phosphoryl transfer reaction in RNA, in which a proton is transferred from the nucleophile to the leaving group through a nonbridged oxygen atom of the phosphate, was explored using the MO6-2X density functional method and the solvent continuum model. This reaction is the initial step of the RNA hydrolysis. We used different solvents characterized by their dielectric constant, and, for each of them, we studied the nuclear and electronic relaxation, produced by the solvent reaction field, for the stationary points. Given that RNA has a poor leaving group, the bond breaking corresponds to the rate-determining step. If the O atom is substituted by a S atom, the leaving group is now good, and the rate-determining step is now the nucleophilic attack concerted with the proton transfer. The most relevant result we found is that none of the solvents we studied has a free energy of activation that is smaller than the one in water. This suggests that the enzyme catalysis following this mechanism must be due to the permanent electric field that is created by a preorganized charge distribution but not to the solvent reaction field.


On linear combinations of dichotomizers for maximizing the area under the ROC curve.
In this paper, we propose a method for the linear combination of several dichotomizers aimed at maximizing the area under the receiver operating characteristic (ROC) curve of the resulting classification system. This is particularly suited for real applications where it is difficult to exactly determine the key parameters such as costs and priors. In such cases, the accuracy is not adequate in measuring the quality of a classification system, while the ROC analysis provides the right tools for an appropriate assessment of the classification performance. The proposed approach revealed to be particularly effective with respect to other widespread combination rules both on artificial and real applications.


Genetic determination of plasma lipids and insulin in the Czech population.
To evaluate the association between plasma lipids and insulin and variation in the genes for apolipoproteins (APO) E (CfoI), B (insertion/deletion), C1 (HpaI), and C3 (C-482T, C3238G) in a population-based Czech Slavonic study. In 131 men and 154 women, polymorphisms were investigated using PCR. In the same subjects plasma lipid levels and insulin were measured. In the women, carriers of the e4 allele had higher apoB (p = 0.03) and triglyceride (p = 0.03) compared to e3 homozygotes, whereas in the men, the effect of the e4 allele was seen on total cholesterol (p = 0.02), LDL cholesterol (p = 0.003) and apoB (p = 0.001). Compared with SP27 (insertion) homozygotes of the APOB polymorphism, women SP24 (deletion) homozygotes had higher levels of total (p = 0.003) and LDL cholesterol (p = 0.007) and apoB (p = 0.05). No significant effect was seen in the men. Women homozygous for the APOC3 -482T allele had higher insulin levels than -482C homozygotes (p = 0.03). Men homozygous for APOC3 -482T allele have the highest plasma triglyceride level (p = 0.02). The APOC1 polymorphism exhibited no significant effect on any of the parameters studied. In this sample, variation at the APOE, APOB and APOC3 genes play a role in determining plasma levels of insulin and lipids, and emphasize the importance of gender-associated effects in the genetic determinations.


Using the Panel Study of Income Dynamics To Analyze Housing Decisions, Dynamics, and Effects.
The Panel Study of Income Dynamics (PSID) is the world's longest running household panel survey. It started in 1968 and has followed the same families-and their descendants-for nearly 50 years. PSID was conducted annually from 1968 through 1997 and has been conducted biennially since 1997. As of 2015, 39 waves of data have been collected. In 2015, interviews were completed with more than 9,000 households and information was collected on about 25,000 household members. PSID has achieved high wave-to-wave response rates throughout most of its history. Since the beginning of the study, detailed information has been collected on family composition, income, assets and debt, public program participation, and housing. At the beginning of the recent housing crisis, PSID began collecting information about mortgage distress and foreclosure activity. PSID currently includes several major supplemental studies. The Child Development Supplement and the Transition into Adulthood Supplement collect detailed information about behavior and outcomes among children and young adults in PSID families, such as educational achievement, health, time use, family formation, and housing-related decisions among young adults. PSID data are publicly available free of charge to researchers; some data available only under contract to qualified researchers allow linkage with various administrative databases and include information such as census tract and block of residence that can be used to describe neighborhood characteristics. PSID data have been widely used to study topics of major interest to Cityscape readers, including housing decisionmaking, housing expenditures and financing, residential mobility and migration, and the effects of neighborhood characteristics on a variety of measures of child and family well-being. This article provides an overview of PSID and its housing- and neighborhood-related measures. We briefly describe studies using PSID on housing-related topics. Finally, we point readers to resources needed to begin working with PSID data.


The role of birth cohorts in long-term trends in liver cirrhosis mortality across eight European countries.
Understanding why inequalities in alcohol-related mortality trends by sex and country exist is essential for developing health policies. Birth cohort effects, indicative of differences by generation in drinking, have rarely been studied. This study estimated the relative contributions of birth cohorts to liver cirrhosis mortality trends and compared sex- and country-specific cohort patterns across eight European countries. Time-series analysis of population-level mortality data. Austria, Finland, Hungary, Italy, the Netherlands, Poland, Spain and Sweden; 1950-2011. National populations aged 15-94 years. We modelled country- and sex-specific liver cirrhosis mortality (from national vital registers) adjusting for age, period and birth cohort. Birth cohorts (adjusted for age and period) made statistically significant contributions to liver cirrhosis mortality in all countries and for both sexes (P < 0.001), and more so among women (average contribution to deviance reduction of 38.8%) than among men (17.4%). The observed cohort patterns were statistically different between all but two country pairs (P < 0.001). Sex differences existed overall (P < 0.001), but not in the majority of countries (P > 0.999). Visual inspection of birth cohort patterns reveals birth cohorts at higher risk of liver cirrhosis mortality. The inclusion of the birth cohort dimension improves the understanding of alcohol-attributable mortality trends in Europe. Birth cohorts at higher risk of liver cirrhosis mortality were born during 1935-49 in Sweden and Finland, around 1950 in Austria and the Netherlands and 1960 or later in Hungary, Italy, Poland and Spain.


Hemodynamic and Echocardiographic Comparison of the Lotus and CoreValve Transcatheter Aortic Valves in Patients With High and Extreme Surgical Risk: An Analysis From the REPRISE III Randomized Controlled Trial.
Comparative echocardiographic data on transcatheter aortic valve replacement systems from randomized trials are limited. The REPRISE III trial (Repositionable Percutaneous Replacement of Stenotic Aortic Valve through Implantation of Lotus Valve System - Randomized Clinical Evaluation) is a multicenter, randomized comparison of a mechanically expanded (Lotus) versus self-expanding (CoreValve) transcatheter aortic valve replacement device. This analysis rigorously assesses Doppler-derived valve hemodynamics and the impact on outcomes at 1 year in patients with extreme/high surgical risk treated with Lotus and CoreValve from REPRISE III. REPRISE III includes patients with extreme- and high-risk aortic stenosis. Patients were enrolled at 55 centers. All transthoracic echocardiograms with Doppler were obtained following a standard protocol up to 12 months postimplant and analyzed by a core laboratory. Valve size, mean gradient, aortic valve area, and Doppler velocity index and their impact on clinical outcomes are reported. Additional parameters including paravalvular leak were evaluated using a multiparametric approach. A total of 912 patients were randomly assigned (2:1 ratio; 607 Lotus:305 CoreValve). Median age was 84 years, 51% of the patients were women, and the Society of Thoracic Surgeons score was 6.8±4.1. CoreValve demonstrated lower gradients and larger aortic valve area and Doppler velocity index than Lotus at discharge; the difference decreased in subsequent follow-up up to a year (all P<0.01). Lotus had lower rates of paravalvular leak that persisted over time (P<0.05). Similar outcomes were seen when comparing each valve type by size group (small, medium, large). The hemodynamic differences between valves did not translate into worse clinical outcomes. All-cause mortality was not different between the 2 groups in any of the 3 valve sizes. When comparing patients with normal valve gradients (<20 mm Hg, n=780) with those with abnormal gradients (>20 mm Hg, n=48) in the entire patient population, all-cause mortality was not different. This was also not significant when evaluating each valve type separately. Similarly, there were no differences for aortic valve area >1.1 cm2 or <1.1 cm2 and for Doppler velocity index >0.35 or <0.35 (all P=not significant). Lotus had significantly greater freedom from moderate or severe paravalvular leak and smaller valve area and higher gradients than CoreValve. The hemodynamic differences were not associated with any clinical differences in the composite end point of mortality, disabling stroke, and moderate paravalvular leak or with quality of life at 1 year of follow-up. URL: https://www.clinicaltrials.gov. Unique identifier: NCT02202434.


Cardiovascular diseases among diffuse large B-cell lymphoma long-term survivors in Asia: a multistate model study.
We modeled the clinical course of a cohort of diffuse large B-cell lymphoma (DLBCL) patients with no prior cardiovascular diseases (CVDs) using a multistate modeling framework. Data on 2600 patients with DLBCL diagnosed between 2000 and 2018 and had received chemotherapy with or without radiotherapy were obtained from a population-wide electronic health database of Hong Kong. We used the Markov illness-death model to quantify the impact of doxorubicin and various risk factors (therapeutic exposure, demographic, comorbidities, cardiovascular risk factors, and lifestyle factors which included smoking) on the clinical course of DLBCL (transitions into incident CVD, lymphoma death, and other causes of death). A total of 613 (23.6%) and 230 (8.8%) of 2600 subjects died of lymphoma and developed incident CVD, respectively. Median follow-up was 7.0 years (interquartile range 3.8-10.8 years). Older ages [hazard ratio (HR) for >75 versus ≤60 years 1.88; 95% confidence interval (CI) 1.25-2.82 and HR for 61-75 versus ≤60 years 1.60; 95% CI 1.12-2.30], hypertension (HR 4.92; 95% CI 2.61-9.26), diabetes (HR 1.43; 95% CI 1.09-1.87), and baseline use of aspirin (HR 5.30; 95% CI 3.93-7.16) were associated with an increased risk of incident CVD. In a subgroup of anticipated higher-risk patients (aged 61-75 years, smoked, had diabetes, and received doxorubicin), we found that they remained on average 7.9 (95% CI 7.2-8.8) years in the DLBCL state and 0.1 (95% CI 0.0-0.4) years in the CVD state, if they could be followed up for 10 years. The brief time in the CVD state is consistent with the high chance of death in patients who developed CVD. Other causes of death have overtaken DLBCL-related death after about 5 years. In this Asian population-based cohort, we found that incident CVDs can occur soon after DLBCL treatment and continued to occur throughout survivorship. Clinicians are advised to balance the risks and benefits of treatment choices to minimize the risk of CVD.


Acquired rifampicin resistance during first TB treatment: magnitude, relative importance, risk factors and keys to control in low-income settings.
The incidence of acquired rifampicin resistance (RIF-ADR; RR) during first-line treatment varies. Compare clinically significant RIF-ADR versus primary and reinfection RR, between regimens (daily versus no rifampicin in the continuation phase; daily versus intermittent rifampicin in the continuation phase) and between rural Bangladesh and Kinshasa, Democratic Republic of Congo. From patients with treatment failure, relapse, or lost to follow-up, both the outcome and baseline sputum sample were prospectively collected for rpoB sequencing to determine whether RR was present in both samples (primary RR) or only at outcome (RIF-ADR or reinfection RR). The most frequent cause of RR at outcome was primary RR (62.9%; 190/302). RIF-ADR was more frequent with the use of rifampicin throughout versus only in the intensive phase (difference: 3.1%; 95% CI: 0.2-6.0). The RIF-ADR rate was higher with intermittent versus daily rifampicin in the continuation phase (difference: 3.9%; 95% CI: 0.4-7.5). RIF-ADR after rifampicin-throughout treatment was higher when resistance to isoniazid was also found compared with isoniazid-susceptible TB. The estimated RIF-ADR rate was 0.5 per 1000 with daily rifampicin during the entire treatment. Reinfection RR was more frequent in Kinshasa than in Bangladesh (difference: 51.0%; 95% CI: 34.9-67.2). RR is less frequently created when rifampicin is used only during the intensive phase. Under control programme conditions, the RIF-ADR rate for the WHO 6 month rifampicin daily regimen was as low as in affluent settings. For RR-TB control, first-line regimens should be sturdy with optimal rifampicin protection. RIF-ADR prevention is most needed where isoniazid-polyresistance is high, (re)infection control where crowding is extreme.


Study of out-of-hours visits to children.
Out-of-hours calls made to children by an urban practice were studied over a 12-month period. Out of a total of 1463 out-of-hours visits, 336 were to children, of whom 17 were admitted to hospital. The proportion of the out-of-hours calls which were to children is less than had been expected. This unexpectedly low level of out-of-hours visits to children and the type of conditions encountered should be taken into account when planning vocational training programmes.


Breastfed or bottle-fed: who goes home sooner?
A literature search was conducted to answer the clinical question, "Do premature infants who breastfeed have different oral feeding outcomes compared with those who receive bottles?" The CINAHL, PubMed, and PsycInfo databases were queried for articles published in the past 10 years that reported original research available in English. Two studies specifically addressed a comparison between infants who received exclusive direct breastfeeding, mixed direct breast and bottle, and/or exclusive bottle-feeding. Additional studies were included that addressed oral feeding outcomes specific to either direct breastfeeding (n = 2) or those that grouped bottle and breastfeeding together (n = 3). The findings from these studies indicate that the statement that bottle-feeding leads to sooner discharge is not based in evidence. Although more data are needed to fully understand the differences between direct breastfeeding and bottle-feeding, neonatal intensive care unit staff should be aware of the message they send to breastfeeding families when they encourage the use of bottles over direct breastfeeding.


Feasibility of a concanavalin A-peroxidase labeling method to detect cancerous and precancerous lesions of the uterine cervix.
For the detection of cancerous and precancerous lesions in cervical cytopathology, the feasibility of a concanavalin A-peroxidase labeling procedure was tested and compared with the Papanicolaou method. To this end, the percentage of labeled flattened epithelial cells with a morphologically normal appearance present in cervical cell suspensions was determined. It was found that the mean labeling percentage of the control group was 71% (SD, 11%). The means for mild, moderate, and severe dysplasia groups were, respectively, 54% (SD, 19%), 48% (SD, 13%), and 44% (SD, 16%). The mean for the carcinoma in situ group was 32% (SD,11%), and for the squamous cell carcinoma group 16% (SD, 5%). It appeared that the labeling percentage gradually decreases with increasing atypia of the epithelium as confirmed by histological observation. A complete dissimilarity was found between healthy individuals and cancer patients. In a follow-up study it was found that the mean labeling percentage did not alter in cases of an unchanged stage of disease. A reestablishment of the normal concanavalin A-peroxidase labeling percentage often appeared once the cancerous or precancerous lesion was treated. In conclusion, the concanavalin A-peroxidase labeling method can be considered as a supplementary technique to the Papanicolaou method for the early detection of cervical cancer. It reduces the effect of sampling and screening errors of the Papanicolaou method, and it allows a more objective cytological diagnosis. In addition, it may possess prognostic significance.


Heat-treatment, phytase and fermented liquid feeding affect the presence of inositol phosphates in ileal digesta and phosphorus digestibility in pigs fed a wheat and barley diet.
The aim was to evaluate the effect of heat-treatment, microbial phytase addition and feeding strategy (dry feeding v. fermented liquid feeding) on degradation of phytate (myo-inositol hexakisphosphate, InsP6) and formation and further degradation of lower inositol phosphates (myo-inositol pentakisphosphate-myo-inositol bisphosphate, InsP5-InsP2) at the distal ileum of pigs. Furthermore, the apparent ileal digestibility/degradability (AID) of phosphorus (P), InsP6-P and calcium (Ca) and the apparent total tract digestibility (ATTD) of P and Ca were studied. Pigs were fitted with a T-shaped ileal cannula for total collection of digesta at 2 h intervals during an 8 h sampling period after feeding the morning meal. Each period lasted for 2 weeks: 8 days of adaptation followed by 3 days of total collection of faeces and 3 days of total collection of ileal digesta. The experiment was designed as a 4 × 4 Latin square with four pigs fed four diets. A basal wheat/barley-based diet was fed either as non-heat-treated or heat-treated (steam-pelleted at 90°C). The heat-treatment resulted in an inactivation of plant phytase below detectable level. Diet 1 (non-heat-treated basal diet fed dry); diet 2 (heat-treated basal diet fed dry); diet 3 (as diet 2 but with microbial phytase (750 FTU/kg as fed) fed dry); diet 4 (as diet 3 fed liquid (fermented for 17.5 h nighttime and 6.5 h daytime at 20°C with 50% residue in the tank)). Chromic oxide (Cr2O3) was included as marker and ATTD was determined both by total collection of faeces (ATTDTotal) and Cr2O3 (ATTDCr). InsP6 was completely degraded in diet 4 before feeding resulting in no InsP6-P being present in ileal digesta. InsP6-P concentration in ileal digesta decreased with increasing dietary levels of plant or microbial phytase in pigs fed the dry diets. Consequently, AID and ATTD of P and Ca were greatest for pigs fed diet 4 followed by diets 3, 1 and 2. The ATTD of P depended on the used method as ATTDTotal of P was 72%, 61%, 44% and 34%, whereas ATTDCr of P was 65%, 52%, 38% and 23% for diets 4, 3, 1 and 2, respectively. In all pigs the ileal concentration of InsP5-InsP2-P was extremely small, and thus unimportant for maximisation of ATTD of plant P. In conclusion, fermented liquid feeding with microbial phytase seems to be an efficient approach to improve ATTD of plant P compared with dry feeding. This opens up for further reductions in P excretion.


Off-label use of medications in children undergoing sedation and anesthesia.
Many drugs used for anesthesia and analgesia in children are administered "off-label." We undertook an audit of drugs commonly used for pediatric anesthesia to determine which drugs have United States Food and Drug Administration (FDA) labeling for pediatric use, which drugs are age-restricted, and which have no labeling for pediatric use. We identified drugs administered during anesthesia to pediatric patients from the operating room pharmacy. FDA approval and indications were determined by using the Thomson Micromedex® online database. Drugs without FDA approval for pediatric use were further examined for strength of evidence and strength of recommendation for their listed indications in the database. We then examined the rate of off-label drug administration to patients younger than the age of 18 years between July 1, 2010, and August 31, 2011. One hundred six drugs were identified. Thirty-six (34%) were not FDA-labeled for use in any pediatric age group, 40 (38%) were FDA-labeled for use in all pediatric age groups, and 30 (28%) were FDA-labeled for use in only specific age groups. Drugs were administered off-label in 73.4% of cases. Of those not labeled for any pediatric age group, some were among the most commonly used drugs in pediatric anesthesia, including neostigmine, hydromorphone, and dopamine. Many drugs used for children during anesthesia continue to lack FDA labeling for pediatric use. Off-label use of these drugs is an accepted practice that is considered superior to the alternative of withholding needed medications. Studies are still needed to determine the safety and efficacy of drugs that lack FDA labeling for this vulnerable patient population.


Comparison of two treatment regimens with trilostane in dogs with pituitary-dependent hyperadrenocorticism.
Trilostane is used to treat dogs with pituitary-dependent hyperadrenocorticism (PDH). In our institution, it was initially dosed based on bodyweight (BW) categories, since April 06 it is dosed per kg BW. Our objectives were to compare effectiveness, number of dose adjustments and side effects of the two dose regimens in dogs with PDH. Dogs of group 1 (28 dogs) received trilostane based on BW categories (< 5 kg, 30 mg; 5 - 20 kg, 60 mg and > 20 kg, 120 mg; SID); dogs of group 2 (20 dogs) received 2 - 5 mg/kg SID. Treatment goal was a post-ACTH cortisol of 1 - 2.5 and 1.5 - 5.4 µg/dl in group 1 and 2, respectively. Starting doses were significantly higher in group 1 and stayed higher until re-check at 4 - 7 months. Baseline and post-ACTH cortisol were significantly decreased compared to pre-treatment at all time points in both groups. Significantly more dogs of group 2 (5/20) needed a dose increase at the first re-check and significantly more dogs of group 1 (10/23) a dose reduction at the last re-check. Intermittent discontinuation was necessary in 25 and 10 % of dogs of group 1 and 2, respectively. We conclude that dosing per kg BW results in comparable clinical improvement, decrease in cortisol, but lower risk of side effects.


Pegasus, a small terminal inverted repeat transposable element found in the white gene of Anopheles gambiae.
Pegasus, a novel transposable element, was discovered as a length polymorphism in the white gene of Anopheles gambiae. Sequence analysis revealed that this 535 bp element was flanked by 8 bp target site duplications and 8 bp perfect terminal inverted repeats similar to those found in many members of the Tc1 family. Its small size and lack of long open reading frames preclude protein coding capacity. Southern analysis and in situ hybridization to polytene chromosomes demonstrated that Pegasus occurs in approximately 30 copies in the genomes of An. gambiae and its sibling species and is homogenous in structure but polymorphic in chromosomal location. Characterization of five additional elements by sequencing revealed nucleotide identities of 95% to 99%. Of 30 Pegasus-containing phage clones examined by PCR, only one contained an element exceeding 535 bp in length, due to the insertion of another transposable element-like sequence. Thus, the majority, if not all, extant Pegasus elements may be defective copies of a complete element whose contemporary existence in An. gambiae is uncertain. No Pegasus-hybridizing sequences were detected in nine other anophelines and three culicines examined, suggesting a very limited taxonomic distribution.


Intramuscular Priming and Intranasal Boosting Induce Strong Genital Immunity Through Secretory IgA in Minipigs Infected with Chlamydia trachomatis.
International efforts in developing a vaccine against Chlamydia trachomatis have highlighted the need for novel immunization strategies for the induction of genital immunity. In this study, we evaluated an intramuscular (IM) prime/intranasal boost vaccination strategy in a Göttingen Minipig model with a reproductive system very similar to humans. The vaccine was composed of C. trachomatis subunit antigens formulated in the Th1/Th17 promoting CAF01 adjuvant. IM priming immunizations with CAF01 induced a significant cell-mediated interferon gamma and interleukin 17A response and a significant systemic high-titered neutralizing IgG response. Following genital challenge, intranasally boosted groups mounted an accelerated, highly significant genital IgA response that correlated with enhanced bacterial clearance on day 3 post infection. By detecting antigen-specific secretory component (SC), we showed that the genital IgA was locally produced in the genital mucosa. The highly significant inverse correlation between the vaginal IgA SC response and the chlamydial load suggests that IgA in the minipig model is involved in protection against C. trachomatis. This is important both for our understanding of protective immunity and future vaccination strategies against C. trachomatis and genital pathogens in general.


Does postural stability affect the performance of eye-hand coordination in stroke survivors?
The aim of this study was to investigate eye-hand coordination in stroke survivors while sitting and standing and its relationship with sensorimotor performance. This was a cross-sectional study conducted at university-based rehabilitation center. Fifteen stroke survivors performed a fast finger-pointing task toward a visual target moving at 10 cm/sec from the contralateral side toward the moving arm in sitting and standing positions. Reaction time, movement time, and pointing accuracy were measured. Anteroposterior, medial-lateral, and total sway were also measured during the standing trials. Several sensorimotor impairments were also measured to correlate with the eye-hand coordination performance. A significantly shorter reaction time was found in the nonparetic than the paretic side when standing, but not when sitting. The movement time of the paretic side was significantly faster when standing when compared with sitting. Fast pointing with the paretic arm significantly increased the total sway path and anteroposterior displacement while standing compared with pointing with the nonparetic arm. Movement time of the paretic arm was negatively correlated with handgrip strength and the strength of the elbow flexors and wrist extensors. The movement time of eye-hand coordination of stroke survivors was affected by postural stability. Correlations were found between pointing performance and several sensorimotor impairments.


Immunohistochemical evaluation of survivin in oral lichen planus and oral squamous cell carcinoma - a retrospective study.
Oral cancer is a multistep process involving enhanced activation of proto-oncogenes. Survivin (anti-apoptotic protein) is one of such proto-oncogenes that contribute to the carcinogenesis by deregulating cell proliferation. Expression of these proteins in cancerous and pre-cancerous lesions helps a better understanding of the etiology, treatment and prognosis. To evaluate qualitative and quantitative expression of survivin in healthy mucosa, oral lichen planus (OLP) and oral squamous cell carcinoma (OSCC). A total of 70 cases of formalin fixed paraffin embedded blocks, of which 20 healthy mucosa, 20 OSCC and 30 OLP were included in the study and stained immunohistochemically using antibodies against survivin monoclonal antibody. 4 μm sections were stained immunohistochemically, both nuclear and cytoplasmic staining was considered as positive for surviving. Positive and negative stained cells were counted with the help of Olympus BX51 rarefaction microscope and were analyzed quantitatively using image analysis pro plus software. Representative fields were randomly selected at 40× high power magnification. Values obtained were evaluated and tabulated for statistical analysis. There was a statistically significant relation between the expressions of survivin among healthy mucosa, OLP, OSCC with a p value of 0.001. Presence of survivin expression in healthy mucosa, OLP and OSCC, which is an inhibitor of apoptosis protein, can be identified as a useful diagnostic tool for the identification of precancerous lesions and conditions which are at higher risk for progression into invasive carcinoma.


Patient-reported Urinary, Bowel, and Sexual Function After Hypofractionated Intensity-modulated Radiation Therapy for Prostate Cancer: Results From a Randomized Trial.
Hypofractionated prostate radiotherapy may increase biologically effective dose delivered while shortening treatment duration, but information on patient-reported urinary, bowel, and sexual function after dose-escalated hypofractionated radiotherapy is limited. We report patient-reported outcomes (PROs) from a randomized trial comparing hypofractionated and conventional prostate radiotherapy. Men with localized prostate cancer were enrolled in a trial that randomized men to either conventionally fractionated intensity-modulated radiation therapy (CIMRT, 75.6 Gy in 1.8 Gy fractions) or to dose-escalated hypofractionated IMRT (HIMRT, 72 Gy in 2.4 Gy fractions). Questionnaires assessing urinary, bowel, and sexual function were completed pretreatment and at 2, 3, 4, and 5 years after treatment. Of 203 eligible patients, 185 were evaluable for PROs. A total of 173 completed the pretreatment questionnaire (82 CIMRT, 91 HIMRT) and 102 completed the 2-year questionnaire (46 CIMRT, 56 HIMRT). Patients who completed PROs were similar to those who did not complete PROs (all P>0.05). Patient characteristics, clinical characteristics, and baseline symptoms were well balanced between the treatment arms (all P>0.05). There was no difference in patient-reported bowel (urgency, control, frequency, or blood per rectum), urinary (dysuria, hematuria, nocturia, leakage), or sexual symptoms (erections firm enough for intercourse) between treatment arms at 2, 3, 4, and 5 years after treatment (all P>0.01). Concordance between physician-assessed toxicity and PROs varied across urinary and bowel domains. We did not detect an increase in patient-reported urinary, bowel, and sexual symptom burden after dose-escalated intensity-modulated prostate radiation therapy using a moderate hypofractionation regimen (72 Gy in 2.4 Gy fractions) compared with conventionally fractionated radiation.


[The otoneurological symptoms in giant adenomas of the hypophysis].
Analysis of the otoneurological symptomatology in 32 patients with hypophyseal tumors showed that they extended most frequently into the sphenoidal sinus, the cells of the ethmoidal sinus, the superoposterior parts of the nose, and the nasopharynx. The focal symptoms of compression of the adjoining parts of the brain (frontal, temporal) were manifested in 11 among 32 cases by olfactory disorders (loss of olfaction in 4 patients, diminished olfaction in 2, olfactory hallucinations in 4 patients, and impaired recognition of odors in 1 patient). Asymmetric action of the tumor on the subcortical structures in the fronto-parietal-temporal parts was manifested by side asymmetry of the experimental nystagmus, complete spatial disorientation of the patient after the rotation test with a false sensation of collapse to the side of the slow phase of nystagmus with vigorous motor compensatory disharmonic deviation of the trunk and limbs in the direction of the rapid nystagmus phase. The effect of the giant hypophyseal tumor on the brain stem was often manifested for a large distance (simultaneously on the diencephalic level, on the level of the midbrain, and in the posterior cranial fossa). Among a group of 32 patients 18 had the decompensated phase of affection of the vestibular apparatus. The effect of the tumor on the diencephalic parts of the brain was attended by sharply intensified vestibulovegetative reactions which should be considered as a stimulation symptom. In giant cell hypophyseal tumors, however, intensification of vestibulovegetative reactions after experimental vestibular tests does not occur in many cases, which is due to death and areactivity of the diencephalo-hypothalamic structures.(ABSTRACT TRUNCATED AT 250 WORDS)


Gender differences in gait kinematics for patients with knee osteoarthritis.
Females have a two-fold risk of developing knee osteoarthritis (OA) as compared to their male counterparts and atypical walking gait biomechanics are also considered a factor in the aetiology of knee OA. However, few studies have investigated sex-related differences in walking mechanics for patients with knee OA and of those, conflicting results have been reported. Therefore, this study was designed to examine the differences in gait kinematics (1) between male and female subjects with and without knee OA and (2) between healthy gender-matched subjects as compared with their OA counterparts. One hundred subjects with knee OA (45 males and 55 females) and 43 healthy subjects (18 males and 25 females) participated in this study. Three-dimensional kinematic data were collected during treadmill-walking and analysed using (1) a traditional approach based on discrete variables and (2) a machine learning approach based on principal component analysis (PCA) and support vector machine (SVM) using waveform data. OA and healthy females exhibited significantly greater knee abduction and hip adduction angles compared to their male counterparts. No significant differences were found in any discrete gait kinematic variable between OA and healthy subjects in either the male or female group. Using PCA and SVM approaches, classification accuracies of 98-100% were found between gender groups as well as between OA groups. These results suggest that care should be taken to account for gender when investigating the biomechanical aetiology of knee OA and that gender-specific analysis and rehabilitation protocols should be developed.


Differential Diagnosis of Asthma and COPD Based on Multivariate Pulmonary Sounds Analysis.
Asthma and chronic obstructive pulmonary disease (COPD) can be confused in clinical diagnosis due to overlapping symptoms. The purpose of this study is to develop a method based on multivariate pulmonary sounds analysis for differential diagnosis of the two diseases. The recorded 14-channel pulmonary sound data are mathematically modeled using multivariate (or, vector) autoregressive (VAR) model, and the model parameters are fed to the classifier. Separate classifiers are assumed for each of the six sub-phases of flow cycle, namely, early/mid/late inspiration and expiration, and the six decisions are combined to reach the final decision. Parameter classification is performed in the Bayesian framework with the assumption of Gaussian mixture model (GMM) for the likelihoods, and the six sub-phase decisions are combined by voting, where the weights are learned by a linear support vector machine (SVM) classifier. Fifty subjects are incorporated in the study, 30 being diagnosed with asthma and 20 with COPD. The highest accuracy of the classifier is 98 percent, corresponding to correct classification rates of 100 and 95 percent for asthma and COPD, respectively. The prominent sub-phase to differentiate between the two diseases is found to be mid-inspiration. The methodology proves to be promising in terms of asthma-COPD differentiation based on acoustic information. The results also reveal that the six sub-phases are not equally pertinent in the differentiation. Pulmonary sounds analysis may be a complementary tool in clinical practice for differential diagnosis of asthma and COPD, especially in the absence of reliable spirometric testing.


From Neuronal Differentiation of iPSCs to 3D Neuro-Organoids: Modelling and Therapy of Neurodegenerative Diseases.
In the last decade, the advances made into the reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) led to great improvements towards their use as models of diseases. In particular, in the field of neurodegenerative diseases, iPSCs technology allowed to culture in vitro all types of patient-specific neural cells, facilitating not only the investigation of diseases' etiopathology, but also the testing of new drugs and cell therapies, leading to the innovative concept of personalized medicine. Moreover, iPSCs can be differentiated and organized into 3D organoids, providing a tool which mimics the complexity of the brain's architecture. Furthermore, recent developments in 3D bioprinting allowed the study of physiological cell-to-cell interactions, given by a combination of several biomaterials, scaffolds, and cells. This technology combines bio-plotter and biomaterials in which several types of cells, such as iPSCs or differentiated neurons, can be encapsulated in order to develop an innovative cellular model. IPSCs and 3D cell cultures technologies represent the first step towards the obtainment of a more reliable model, such as organoids, to facilitate neurodegenerative diseases' investigation. The combination of iPSCs, 3D organoids and bioprinting will also allow the development of new therapeutic approaches. Indeed, on the one hand they will lead to the development of safer and patient-specific drugs testing but, also, they could be developed as cell-therapy for curing neurodegenerative diseases with a regenerative medicine approach.


Role of "HinCh Score" as a Non-invasive Predictor of Post-endoscopic Retrograde Cholangiopancreatography Cholangitis.
Post-endoscopic retrograde cholangiopancreatography (ERCP) cholangitis (PEC) is associated with increased morbidity and mortality in patients ERCP. The aim of the present study was to analyze the predictors of PEC and to formulate a predictive model for early diagnosis and management. It was a cross-sectional study that was carried out at the Sindh Institute of Urology and Transplantation from September 2019 to June 2021. All patients aged between 18 and 75 years and undergoing ERCP due to obstructive jaundice were included. Patients with altered biliary anatomy, history of hepatobiliary surgery, and concurrent sepsis were excluded. Endoscopic retrograde cholangiopancreatography intervention was performed by an expert gastroenterologist. Laboratory parameters (total leukocyte count, total bilirubin, alanine transaminase) and patient temperature were checked on admission, at 12 hours, 24 hours, and 36 hours after ERCP to document PEC. A total of 349 patients were included in the study. Among them, 176 (50.4%) patients were males. Common bile duct (CBD) stricture was the most common indication of ERCP seen in 148 (42.4%) patients followed by CBD stone and cholangiocarcinoma in 108 (30.9%) and 48 (13.8%) patients, respectively. The most common presenting complaint was jaundice noted in 300 (86%) patients followed by right hypochondrial pain in 280 (80.2%) and weight loss in 194 (55.6%) patients, respectively. Post-ERCP cholangitis developed in 251 (71.9%) patients. On univariate analysis, age >50 years, female gender, right hypochondrial pain, fever, bilirubin >5 mg/dL on admission, CBD stricture on ERCP, TLC of >10,000 cells/L at 12 hours, 24 hours, and 36 hours post-ERCP and rise in ALT >50 IU 24 and 48 hours post-ERCP were significantly associated with PEC. While on multivariate analysis, female gender, bilirubin >5 mg/dL on admission, CBD stricture on ERCP, post-ERCP fever, and rise in TLC of >10000 cells/L at 24 hours post-ERCP were independently associated with PEC. HinCh score was formulated and was found to be significantly associated with the presence of cholangitis. Area under the receiver operating characteristics (AUROC) of HinCh score was 0.74 and at cutoff of ≥4, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of HinCh were 81.67%, 59.18%, 83.67%, and 55.71%, respectively with a diagnostic accuracy of 75.36%. The performance of HinCh score in predicting PEC was accurate in 86% of the patients. However, further studies are needed to validate the score. Ismail H, Yaseen RT, Danish M, et al. Role of "HinCh Score" as a Non-invasive Predictor of Post-endoscopic Retrograde Cholangiopancreatography Cholangitis. Euroasian J Hepato-Gastroenterol 2022;12(1):19-23.


TRPC3 and NALCN channels drive pacemaking in substantia nigra dopaminergic neurons.
Midbrain dopamine (DA) neurons are slow pacemakers that maintain extracellular DA levels. During the interspike intervals, subthreshold slow depolarization underlies autonomous pacemaking and determines its rate. However, the ion channels that determine slow depolarization are unknown. Here we show that TRPC3 and NALCN channels together form sustained inward currents responsible for the slow depolarization of nigral DA neurons. Specific TRPC3 channel blockade completely blocked DA neuron pacemaking, but the pacemaking activity in TRPC3 knock-out (KO) mice was perfectly normal, suggesting the presence of compensating ion channels. Blocking NALCN channels abolished pacemaking in both TRPC3 KO and wild-type mice. The NALCN current and mRNA and protein expression are increased in TRPC3 KO mice, indicating that NALCN compensates for TRPC3 currents. In normal conditions, TRPC3 and NALCN contribute equally to slow depolarization. Therefore, we conclude that TRPC3 and NALCN are two major leak channels that drive robust pacemaking in nigral DA neurons.


Prophylactic antibiotics in orthopaedic surgery.
The use of prophylactic antibiotics in orthopaedic surgery is effective in reducing surgical site infections in hip and knee arthroplasty, spine surgery, and open reduction and internal fixation of fractures. To maximize the beneficial effect of prophylactic antibiotics while minimizing adverse effects, the correct antimicrobial agent must be selected, the drug must be administered just before incision, and the duration of administration should not exceed 24 hours.


Clinical and molecular characteristics of a novel rare de novo variant in PPP2CA in a patient with a developmental disorder, autism, and epilepsy.
PP2A-related (neuro) developmental disorders are a family of genetic diseases caused by a heterozygous alteration in one of several genes encoding a subunit of type 2A protein phosphatases. Reported affected genes, so far, are PPP2R5D, encoding the PP2A regulatory B56δ subunit; PPP2R1A, encoding the scaffolding Aα subunit; and PPP2CA, encoding the catalytic Cα subunit-in that order of frequency. Patients with a pathogenic de novo mutation in one of these genes, in part, present with overlapping features, such as generalized hypotonia, intellectual and developmental delay, facial dysmorphologies, seizures, and autistic features, and, in part, with opposite features, e.g., smaller versus larger head sizes or normal versus absent corpus callosum. Molecular variant characterization has been consistent so far with loss-of-function or dominant-negative disease mechanisms for all three affected genes. Here, we present a case report of another PPP2CA-affected individual with a novel de novo missense variant, resulting in a one-amino acid substitution in the Cα subunit: p.Cys196Arg. Biochemical characterization of the variant revealed its pathogenicity, as it appeared severely catalytically impaired, showed mildly affected A subunit binding, and moderately decreased binding to B/B55, B"/PR72, and all B56 subunits, except B56γ1. Carboxy-terminal methylation appeared unaffected, as was binding to B"'/STRN3-all being consistent with a partial loss of function. Clinically, the girl presented with mild-to-moderate developmental delay, a full-scale IQ of 83, mild dysmorphic facial features, tonic-clonic seizures, and autistic behaviors. Brain MRI appeared normal. We conclude that this individual falls within the milder end of the clinical and molecular spectrum of previously reported PPP2CA cases.


New aspects of HbA1c as a risk factor for cardiovascular diseases in type 2 diabetes: an observational study from the Swedish National Diabetes Register (NDR).
To analyse the association between glycosylated haemoglobin A1c (HbA1c) and cardiovascular disease (CVD) in patients with type 2 diabetes in the Swedish National Diabetes Register (NDR). An observational study of 18 334 patients (age 30-79 years, previous CVD in 18%, baseline HbA1c 5.0-10.9%) who were followed for 6 years (mean 5.6 years) from 1997/1998 until 2003. Hazard ratios per 1% unit increase in baseline or updated mean HbA1c for fatal/nonfatal coronary heart disease (CHD), CVD and total mortality were 1.11-1.13, 1.10-1.11 and 1.09-1.10, respectively (all P < 0.001), adjusted for several risk factors and clinical characteristics in Cox regression. Adjusted 6-year event rates increased with higher baseline or updated mean HbA1c with no J-shaped risk curves, in all patients and also when subgrouping by shorter (mean 3 years) or longer (mean 14 years) diabetes duration, by presence or absence of previous CVD, or by treatment with oral hypoglycaemic agents (OHAs) or insulin. Risk reductions of 20% for CHD and 16% for CVD (P < 0.001) were found in patients with a baseline mean HbA1c of 6.5%, compared to those with a mean level of 7.5%. Compared to OHA-treated patients, insulin-treated patients had an increased risk of total mortality, due almost exclusively to an increased risk of non-CVD mortality, and due less to a weakly significant increased risk of fatal CVD. HbA1c was not associated with non-CVD mortality. This observational study showed progressively increasing risks of CHD, CVD and total mortality with higher HbA1c, and no risk increase at low HbA1c levels even with longer diabetes duration, previous CVD or treatment with either insulin or OHAs. Patients achieving HbA1c <7% showed benefits for risk reduction.


Tuberculosis infection and homelessness in Melbourne, Australia, 1995-1996.
To describe tuberculosis infection among persons experiencing homelessness in inner Melbourne, Australia. Homeless people were surveyed during late 1995 and early 1996. In stage one of the study 284 homeless people from crisis and long-term accommodation sites were recruited by means of stratified, systematic, random sampling. In stage two a convenience sample of 100 homeless people from squats and the streets were recruited. Participants completed a questionnaire and Mantoux testing was performed. A past history of tuberculosis was reported by 3%. Thirty-seven per cent had a Mantoux > or =10 mm; 21% > or =15 mm; and 11% > or =20 mm. A Mantoux > or =15 mm was independently associated with being aged > or =40 years, coming from the accommodated sample, overseas birth, and a past history of tuberculosis. Using logistic regression modelling, a Mantoux > or =15 mm was predicted by being aged > or =40 years, overseas birth, and past history of tuberculosis. Mantoux test results suggest that this group of homeless people had a high prevalence of infection with the tubercle bacillus. Many aspects of the physical and social circumstances of homeless people predispose to reactivation and have the potential to enhance rapid spread should latent infection become active disease.


Involvement of Interferon Gamma Signaling in Spinal Trigeminal Caudal Subnucleus Astrocyte in Orofacial Neuropathic Pain in Rats with Infraorbital Nerve Injury.
Trigeminal nerve injury causes orofacial pain that can interfere with activities of daily life. However, the underlying mechanism remains unknown, and the appropriate treatment has not been established yet. This study aimed to examine the involvement of interferon gamma (IFN-γ) signaling in the spinal trigeminal caudal subnucleus (Vc) in orofacial neuropathic pain. Infraorbital nerve (ION) injury (IONI) was performed in rats by partial ION ligation. The head-withdrawal reflex threshold (HWT) to mechanical stimulation of the whisker pad skin was measured in IONI or sham rats, as well as following a continuous intracisterna magna administration of IFN-γ and a mixture of IFN-γ and fluorocitrate (inhibitor of astrocytes activation) in naïve rats, or an IFN-γ antagonist in IONI rats. The IFN-γ receptor immunohistochemistry and IFN-γ Western blotting were analyzed in the Vc after IONI or sham treatment. The glial fibrillary acid protein (GFAP) immunohistochemistry and Western blotting were also analyzed after administration of IFN-γ and the mixture of IFN-γ and fluorocitrate. Moreover, the change in single neuronal activity in the Vc was examined in the IONI, sham, and IONI group administered IFN-γ antagonist. The HWT decreased after IONI. The IFN-γ and IFN-γ receptor were upregulated after IONI, and the IFN-γ receptor was expressed in Vc astrocytes. IFN-γ administration decreased the HWT, whereas the mixture of IFN-γ and fluorocitrate recovered the decrement of HWT. IFN-γ administration upregulated GFAP expression, while the mixture of IFN-γ and fluorocitrate recovered the upregulation of GFAP expression. IONI significantly enhanced the neuronal activity of the mechanical-evoked responses, and administration of an IFN-γ antagonist significantly inhibited these enhancements. IFN-γ signaling through the receptor in astrocytes is a key mechanism underlying orofacial neuropathic pain associated with trigeminal nerve injury. These findings will aid in the development of therapeutics for orofacial neuropathic pain.


Genomic characterization of two Orf virus isolates from Jilin province in China.
Orf virus (ORFV), a typical member of the Parapoxvirus genus within the family Poxviridae, which is the causative agent of Orf, a common epitheliotropic viral disease of sheep, goats, wild ruminants, and humans. In the present study, we sequenced the complete genomic sequences of two ORFV strains (ORFV-SY17, isolated from sheep, and ORFV-NA17, isolated from goat) and conducted the comparative analysis of multiple ORFVs. The complete genomic sequence of ORFV-SY17 was at length of 140,413 bp, including 131 potential open reading frames (ORFs) flanked by inverted terminal repeats (ITRs) of 4267 bp at both ends. The ORFV-NA17 strain displayed the similar genome structure with ORFV-SY17. The whole genomic sequence of ORFV-NA17 strain was 139,287 bp in length and contained 132 ORFs flanked by ITRs of 3974 bp. The overall G+C contents of ORFV-SY17 and ORFV-NA17 genome sequences were about 63.8% and 63.7%, respectively. The ITR sequences analysis showed that ORFV-SY17 and ORFV-NA17 contained the terminal BamHI sites and conserved telomere resolution sequences at both ends of their genome. In addition, comparative analysis of ORFs among ORFV-SY17, ORFV-NA17, and other ORFV strains revealed several sequence variations caused by insertions or deletions, especially in ORFs 005 and 116, which were very likely associated with host species. Phylogenetic analysis based on the complete genome sequences revealed that ORFV-SY17 was genetically closely related to NA1/11 and HN3/12 strains derived from sheep, while ORFV-NA17 was closely related to YX strain derived from goat. The multiple alignment of deduced amino acid sequences further revealed the genetic relationship between host species and genetic variations of ORFV strains. Taken together, the availability of genomic sequences of ORFV-SY17 and ORFV-NA17 strains from Jilin Province will aid in our understanding of the genetic diversity and evolution of ORFV strains in this region and can assist in distinguishing between ORFV strains that originate in sheep and goats.


Intestinal parasites in children and soil from Turbaco, Colombia and associated risk factors.
Objective To determine the frequency of intestinal parasites in children and soil from Turbaco- Colombia and associated risks factors. Methods Analytical study in which 390 children between 2 and 12 years old from 10 neighborhoods of Turbaco were included, whose legal representatives gave informed consent. Three serial samples of feces and 10 soil samples were processed. Risk factors were determined through an interview. Physicochemical and structural characteristics of soils were also evaluated. Results Parasites were found in 30.5 % of children. 162 parasites were observed; the most frequent protozoan was Endolimax nana (30.3 %) and in terms of helminthes, the most frequent was Ascaris lumbricoides (4.9 %). No statistical association between age or sex and intestinal parasites (p>0.05) or between risk factors and intestinal parasites (p>0.05) was found. Low frequencies of intestinal parasites were encountered in soil samples, being more common Entamoeba spp., Giardia spp., and Ascaris lumbricoides. Neighborhoods of Turbaco had sandy dry soil with low content of ions, low conductivity and low organic matter. Conclusion This study showed a low frequency of intestinal parasites in feces and soils. Despite this, pathogenic parasites were found which can affect the health of the population. Besides this, a high percentage of intestinal parasites that are transmitted through feces were detected indicating fecal contamination and low level of hygiene.


The role of coordination compounds in virus research. Different approaches and trends.
This article aims to provide an overview of the studies focused on using coordination compounds as antiviral agents against different types of viruses. We present various strategies so far used to this end. This article is divided into two sections. The first collects the series of designed antiviral drugs based on coordination compounds. This approach has been developed for many years, starting from the 70s with the discovery of cis-platin (cis-DDP). It has been mainly focused on studying the synergistic effect of a wide variety of new compounds obtained by combining metal ions with organic antiviral ligands. Then, we collect various strategies analyzing the coordination compounds interacting with viruses using different processes such as wrapping viruses, rapid detection of RNA or DNA virus, or nanocarriers. These recent and novel insights help to study viruses from other points of view, allowing to measure their physical and chemical properties. We also highlight a section in which the issue of viruses from a disinfection viewpoint is addressed, using coordination compounds as a tool able to control the release of antiviral and biocide agents. This is an emerging and promising field but this approach is actually little developed. We finally provide a section with a general conclusion and perspectives.


Anonymization of DICOM electronic medical records for radiation therapy.
Electronic medical records (EMR) and treatment plans are used in research on patient outcomes and radiation effects. In many situations researchers must remove protected health information (PHI) from EMRs. The literature contains several studies describing the anonymization of generic Digital Imaging and Communication in Medicine (DICOM) files and DICOM image sets but no publications were found that discuss the anonymization of DICOM radiation therapy plans, a key component of an EMR in a cancer clinic. In addition to this we were unable to find a commercial software tool that met the minimum requirements for anonymization and preservation of data integrity for radiation therapy research. The purpose of this study was to develop a prototype software code to meet the requirements for the anonymization of radiation therapy treatment plans and to develop a way to validate that code and demonstrate that it properly anonymized treatment plans and preserved data integrity. We extended an open-source code to process all relevant PHI and to allow for the automatic anonymization of multiple EMRs. The prototype code successfully anonymized multiple treatment plans in less than 1min/patient. We also tested commercial optical character recognition (OCR) algorithms for the detection of burned-in text on the images, but they were unable to reliably recognize text. In addition, we developed and tested an image filtering algorithm that allowed us to isolate and redact alpha-numeric text from a test radiograph. Validation tests verified that PHI was anonymized and data integrity, such as the relationship between DICOM unique identifiers (UID) was preserved.


Stability of liposome encapsulated hemoglobin dispersions.
The demand for artificial blood substitutes in cases of elective surgeries, trauma, and civilian mass catastrophes increases every day. However, few studies have been done to characterize the mechanical stability of blood substitutes, especially liposome encapsulated hemoglobin (LEHb) dispersions. In this work, the stability of LEHb dispersions was investigated by fitting Jung et al.'s liposome size distribution model to experimentally measured LEHb size distributions [6] (produced via extrusion) using asymmetric flow field-flow fractionation coupled with multi-angle static light scattering. The effective bending constant (KB) and radius of curvature (R0) of each liposome dispersion were regressed from the size distribution fits. The model was found to be in agreement with the size distributions of LEHbs extruded through 400, 200 and 100 nm pore diameter membranes, but not in agreement with LEHbs extruded through 80 and 50 nm pore diameter membranes. Although the magnitude of KB fluctuated, we deduced a general trend for KB to decrease with decreasing pore diameter, and increasing initial Hb concentration. LEHbs extruded through 400nm pore diameter membranes were stabilized by the spontaneous curvature effect, while those extruded through 80 and 50 nm pore diameter membranes were mostly stabilized by thermal undulations, regardless of the initial Hb concentration. For LEHb dispersions extruded through 200 and 100 nm pore diameter membranes, there was a transition of stabilization mechanism from spontaneous curvature to thermal undulations with increasing initial Hb concentration. Taken together, these results suggest that moderate Hb encapsulation might actually impart better mechanical stability to LEHb dispersions extruded through 200 and 100 nm pore diameter membranes.


[Quality of life in dementia, opinions among people with dementia, their professional caregivers, and in literature].
Different definitions of quality of life (QOL) are found in the literature. This raised the question which domains are viewed as really important by persons with dementia. In an explorative study the opinions of persons with dementia (community-dwelling and living in nursing homes), were compared to those of professional carers and instruments for QOL in dementia. Data were gathered through interviews, focus groups and literature study. Most QOL-domains mentioned as important by persons with dementia were also acknowledged by carers and in measurement instruments. Some domains, however, were not mentioned by the carers ('sense of aesthetics', 'financial situation', 'being useful' and 'spirituality'), or not selected in the measuring instruments ('security and privacy', 'self-determination and freedom', 'being useful' and 'spirituality'). This indicates differences in perspectives on quality of life between persons with dementia, professional caregivers and researchers. Subsequently it was studied to what degree professionals focus on the QoL-domains that persons with dementia consider essential. Caregivers working on 29 units and 3 day care facilities of 13 nursing homes and in 12 meeting centers filled out a questionnaire (N = 374). They reported to focus at least to some degree on most domains considered important by persons with dementia. However, little attention was paid to the domains 'financial situation' and 'being useful'. Professionals offering daytime activities focused more than 24-hour care staff on 'attachment', 'enjoyment of activities', 'sense of aesthetics', and 'being useful'. This article is a translation and merging of 1) Dröes et al. Quality of life in dementia in perspective; an explorative study of variations in opinions among people with dementia and their professional caregivers, and in literature. Dementia: The International Journal 2006; 5 (4): 533-558, and 2) Gerritsen et al. Differences in perspective: do professional caregivers focus on the Quality of life domains that are important for people with dementia? American Journal of Alzheimer's Disease and Other Dementias 2007; 22:176-183.