Microbiota influences host exercise capacity via modulation of skeletal muscle glucose metabolism in mice.
The microbiota enhances exercise performance and regulates host physiology and energy metabolism by producing beneficial metabolites via bacterial fermentation. In this study, we discovered that germ-free (GF) mice had a reduced capacity for aerobic exercise as well as low oxygen consumption rates and glucose availability. Surprisingly, GF mice showed lower body weight gain and lower fat mass than specific pathogen-free (SPF) mice. Therefore, we hypothesized that these paradoxical phenotypes could be mediated by a compensatory increase in lipolysis in adipose tissues owing to impaired glucose utilization in skeletal muscle. Our data revealed that gut microbiota depletion impairs host aerobic exercise capacity via the deterioration of glucose storage and utilization. The improved browning ability of GF mice may have contributed to the lean phenotype and negatively affected energy generation. These adaptations limit obesity in GF mice but impede their immediate fuel supply during exercise, resulting in decreased exercise performance.


Chlamydia and Gonorrhea Incidence and Testing Among Patients in the Human Immunodeficiency Virus Outpatient Study (HOPS), 2007-2017.
Although chlamydia (CT) and gonorrhea (GC) infections are increasing in the United States, there are limited data on their incidence, testing rates, and associated risk factors among persons living with HIV (PLWH), including by anatomic site among men who have sex with men (MSM). We analyzed 2007-2017 medical records data from Human Immunodeficiency Virus (HIV) Outpatient Study (HOPS) participants in care at 9 HIV clinics. We calculated CT (and GC) incidence and testing rates and assessed associations with sociodemographic and clinical factors using log-linear regression. Among 4727 PLWH, 397 had 881 CT infections and 331 had 861 GC infections, with an incidence of 2.95 and 2.88 per 100 person-years, respectively. From 2007 to 2017, incidence and testing rates increased by approximately 3.0- and 1.9-fold for CT and GC, respectively. Multivariable factors associated with incident CT (GC) included younger age, MSM, and prior diagnoses of sexually transmitted diseases (STDs). Among 1159 MSM, 583 (50.3%) had 844 CT and 843 GC tests during 2016-2017, and 26.6% of tests were 3-site (urethra, rectum, and pharynx), yielding the highest rates of CT (GC) detection. Multivariable factors associated with CT (GC) testing included younger age, non-Hispanic/Latino black race, and having prior STDs. Recent CT and GC incidence and testing increased among PLWH; however, only half of MSM were tested for CT or GC during 2016-2017 and less than a third of tests were 3-site. To promote sexual health and STD prevention among PLWH who are MSM, research regarding the added value of CT and GC testing across 3 anatomic sites is needed.


Hyperemesis gravidarum complicated by Wernicke's encephalopathy.
Wernicke's encephalopathy is usually associated with alcohol abuse, but can also occur with hyperemesis gravidarum. The effect of delay in thiamine replacement on fetal outcomes is unknown. We present a case of this complication. A primipara with hyperemesis was admitted for mental status changes in her 14th week of pregnancy. Physical examination revealed a lethargic patient with ophthalmoplegia, ataxia, and hyporeflexia. Parenteral thiamine therapy was started. The patient improved rapidly although the ataxia persisted. A spontaneous abortion occurred 2 weeks later. Wernicke's encephalopathy can complicate hyperemesis gravidarum. Early thiamine replacement may decrease the chances of spontaneous abortion.


Cardiac capillary hemangioma: a case report and brief review of the literature.
Among primary cardiac tumors, hemangiomas are relatively rare, with a reported incidence of 2.8%. To date, less than 100 cases have been reported in literature. We report the case of a 61-year-old woman who complained from chest discomfort since 3 years and in whom transthoracic echocardiography revealed a pedunculated tumor in the left ventricle. The tumor was successfully resected and its histopathological examination revealed a capillary hemangioma. The patient had an uneventful recovery without any complication.


Molecular and immunohistochemical comparison between primary gastrointestinal mucosal melanomas and atypical gastrointestinal stromal tumors.
It is sometimes challenging to differentiate between gastrointestinal (GI) mucosal melanoma and gastrointestinal stromal tumors (GISTs) because they share some similarities in histological and molecular features. In this study, we investigated their clinicopathological and molecular features. Four primary GI mucosal melanomas and 4 atypical GISTs resected from 2017 to 2019 were included. Electronic medical records and histology slides were reviewed and, if needed, immunohistochemical stainings were additionally done. Somatic mutations were analyzed using whole exome sequencing (WES) with tumors and matched normal tissues. By immunohistochemistry, GISTs were positive for CD117 (4 of 4), DOG1 (4 of 4), and CD34 (2 of 4). In contrast, melanomas were positive for CD117 (2 of 4), HMB-45 (4 of 4), Melan-A (4 of 4), and S100 protein (3 of 4). Using WES, the KIT mutation was detected in 2 of 4 GISTs and 1 of 4 melanomas, all of which showed strong CD117 immunoreactivity. PDGFRA mutation was detected in 2 of 4 GISTs but 0 of 4 melanomas. TP53, NF1, RB1, TERT, and KMT2D mutations were detected in 1 of 4 melanomas but 0 of 4 GISTs. A patient with KIT-mutated melanoma was treated with Gleevec and has remained disease-free for 1 year. GISTs and GI melanomas have a wide histopathological spectrum. Appropriate ancillary studies can be helpful for proper diagnosis and optimal treatment.


Resilience and social change: Findings from research trends using association rule mining.
This study analyzed the historical development of resilience with respect to multidisciplinary aspects using association rule mining (ARM). ARM is a rule-based machine-learning approach tailored to identify validated relations among multiple variables in a large dataset. This study collected author keywords from all resilience-related literature in the Web of Science database and examined the changes in validated resilience-related topics using ARM. We found that resilience-related research tends to diversify and expand over time. Although topics and their academic fields related to engineering and complex adaptive systems were prominent in the early 2000s, psychosocial resilience and social-ecological resilience have received significant attention in recent years. The increasing interest in resilience-related topics linked to psychological and ecological factors, as well as social system components, can be attributed to the impact of a series of complex and global events that occurred in the late 2000s. Recently, resilience has been conceived as a way of thinking, perspective, or paradigm to address emergent complexity and uncertainty with vague concepts. Resilience is increasingly being regarded as a boundary spanner that promotes communication and collaboration among stakeholders who share different interests and scientific knowledge.


Attribute reduction of SE-ISI concept lattices for incomplete contexts.
Three-way concept analysis in incomplete contexts lays the theory dealing with the data in incomplete contexts, especially three kinds of partially known formal concepts including SE-ISI formal concept, ISE-SI formal concept and ISE-ISI formal concept. Generally speaking, not every attribute is essential in an incomplete context since the purpose of research is different. Thus, we propose four kinds of attribute reduction of SE-ISI concept lattices based on different criteria. Then, we discuss the relationships among the four kinds of attribute reduction, including the relationships among the consistent sets and relationships among the reducts. Finally, based on discernibility matrices and discernibility functions, the approaches to obtaining these attribute reduction are presented.


A quantitative analysis of monochromaticity in genetic interaction networks.
A genetic interaction refers to the deviation of phenotypes from the expected when perturbing two genes simultaneously. Studying genetic interactions help clarify relationships between genes, such as compensation and masking, and identify gene groups of functional modules. Recently, several genome-scale experiments for measuring quantitative (positive and negative) genetic interactions have been conducted. The results revealed that genes in the same module usually interact with each other in a consistent way (pure positive or negative); this phenomenon was designated as monochromaticity. Monochromaticity might be the underlying principle that can be utilized to unveil the modularity of cellular networks. However, no appropriate quantitative measurement for this phenomenon has been proposed. In this study, we propose the monochromatic index (MCI), which is able to quantitatively evaluate the monochromaticity of potential functional modules of genes, and the MCI was used to study genetic landscapes in different cellular subsystems. We demonstrated that MCI not only amend the deficiencies of MP-score but also properly incorporate the background effect. The results showed that not only within-complex but also between-complex connections present significant monochromatic tendency. Furthermore, we also found that significantly higher proportion of protein complexes are connected by negative genetic interactions in metabolic network, while transcription and translation system adopts relatively even number of positive and negative genetic interactions to link protein complexes. In summary, we demonstrate that MCI improves deficiencies suffered by MP-score, and can be used to evaluate monochromaticity in a quantitative manner. In addition, it also helps to unveil features of genetic landscapes in different cellular subsystems. Moreover, MCI can be easily applied to data produced by different types of genetic interaction methodologies such as Synthetic Genetic Array (SGA), and epistatic miniarray profile (E-MAP).


[Stimulating autophagosome formation and inducing mixed cell death in HeLa cells by troglitazone].
To study the effect of troglitazone on autophagy and programmed cell death of HeLa cells. Fluorescence microscopy, electron microscopy, western-blotting and flow cytometry were used. Troglitazone increased the autophagosome formation of HeLa cell as observed by fluorescence and electron microscopy. Immunoblotting further confirmed cell morphology observation upon the reagent stimulating by detecting an enhanced expression of LC3, an autophagic related gene. Besides apoptosis, troglitazone triggered a necrotic cell death in flow cytometry analysis. Troglitazone induced mixed type of cell death in HeLa cells.


Teaching pediatrics residents how to obtain informed consent.
Few physicians view informed consent as a critical component of the physician-patient relationship or as a way to improve individual and population health. We hypothesized that formal education about informed consent would affect first-year pediatrics residents' knowledge and attitudes. Twenty-seven first-year pediatrics residents participated in a randomized controlled trial with a wait-list control group. The one-hour interactive intervention consisted of a lecture, video, and small-group discussion. Outcomes were measured after randomization at baseline and after the intervention group received the intervention. Data were analyzed using multivariate analysis and between and within group t tests. Qualitative data were obtained after the wait-list control group's exposure to the intervention. The quantitative analyses demonstrated that the intervention yielded statistically significant improvements in the measured outcomes. The qualitative analyses confirm the quantitative findings. A formal session on informed consent in the pediatrics residency educational program positively affects residents' knowledge and attitudes about informed consent.


Combining lesional short-contact dithranol therapy of psoriasis with a potent topical corticosteroid.
Since its introduction, the effectiveness of dithranol in treating psoriasis has been unequalled by other topical treatments. Out-patient short-contact dithranol treatment is effective with regard to clinical response rate and relapse rate after 1 year. A drawback, however, is the relatively long treatment duration. To study a dithranol regimen combined with a potent topical corticosteroid with regard to clinical response rate, treatment duration and remission period after clearance. Twelve patients with stable psoriasis vulgaris participated in this study. We treated three comparable psoriasis lesions on the extremities for 39 consecutive days. The first lesion was treated daily with short-contact dithranol cream followed by clobetasol-17-propionate ointment 5 days per week. The second lesion was treated daily with short-contact dithranol cream followed by the vehicle of clobetasol-17-propionate ointment. The third lesion was treated with clobetasol-17-propionate ointment 5 days per week. The patients attended on days 1, 4, 9, 12, 15, 18, 22, 25, 32 and 39 during treatment. We assessed lesional severity scores at each visit and registered the baseline area at the first visit. During the follow up at weeks 2, 4, 6, 10, 14, 19 and 23 we assessed lesional sum scores. We also estimated the area involved in recurrence of the lesion as a percentage of the baseline area. The overall differences between the three treatment curves for the treatment period and follow-up period separately were tested with a likelihood ratio test. Differences between the curves of the sum scores during treatment (P < 0.001) were mainly due to the different time-course of dithranol monotherapy, which showed a slower decrease in sum score. Differences between the linear trends of the sum score (P < 0.001) and the area score P < 0.001) during follow up were due to a different time-course of the combination therapy, which started lower and increased more slowly, suggesting a slower relapse rate with combination therapy. When comparing the follow-up data, it must be kept in mind that the three treatments showed an overall significantly different sum and area score at the start of follow up. Intermittent addition of clobetasol-17-propionate ointment enhanced the antipsoriatic efficacy of short-contact, high-dose dithranol therapy in terms of clearing capacity and treatment duration, without shortening remission duration.


Relationship Between Occupational Noise and Hypertension in Modern Enterprise Workers: A Case-Control Study.
Objective: The association between occupational noise exposure and hypertension is controversial. Thus, we aimed to assess the relationship between occupational noise exposure and hypertension. Methods: This was a case‒control study, and 509 cases and 1,018 controls from an automobile company were included between July and October 2013. Occupational noise exposure was defined as exposure to noise level ≥80 dB(A) (Lex, 8 h) or cumulative noise exposure (CNE) ≥ 80 dB(A)-years. To assess the associations of noise level and CNE with hypertension, univariate and multivariate logistic regression were performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs). The restricted cubic spline function was used to establish dose‒response curves. Results: A noise level ≥80 dB (A) (Lex, 8 h) was significantly associated with hypertension (OR 2.48, 95% CI 1.89-3.24). CNE ≥80 dB (A)-years was significantly associated with hypertension (OR 1.53, 95% CI 1.18-2.00). Nonlinear relationships between noise level, CNE and hypertension were found (p- nonlinear<0.05). Conclusion: Our study suggests that occupational noise exposure is a potential risk factor for hypertension in automobile company workers.


[Discordant manifestation of celiac disease in monozygotic twins].
A monozygous pair of twins with discordant presentation of coeliac disease is reported. The gluten-sensitive enteropathy in one of the twins might have been initiated by a virus infection.


Smooth muscle layer-specific variations in the autonomic innervation of bovine myometrium.
1. To clarify the autonomic innervation regulating longitudinal muscle (LM) and circular muscle (CM) motility in the bovine uterus, functional (nerve stimulation, adrenergic drug responsiveness) and biochemical studies (catecholamine content, radioligand binding) were conducted on parous luteal-phase myometrium. 2. Electrical field stimulation (EFS; 60 V, 0.5-msec duration) caused tetrodotoxin (1 microM)-sensitive contractions in a frequency-dependent manner (0.5-20 Hz) in both LM and CM layers. 3. The EFS-induced LM contractions were potentiated by propranolol and conspicuously decreased by phentolamine, yohimbine, idazoxan or guanethidine, but were unaffected by prazosin or atropine. 4. On the other hand, CM contractions were only slightly decreased by phentolamine, idazoxan, yohimbine and guanethidine, but were insensitive to propranolol, prazosin or atropine. 5. The noradrenaline content in LM was about five times higher than that in CM. 6. Noradrenaline, adrenaline, clonidine, xylazine, UK14,304 and phenylephrine caused concentration-dependent contractions of both smooth muscle layers. 7. Clonidine, UK14,304 and xylazine were more potent contractile agents than noradrenaline and phenylephrine. 8. The contractile response to noradrenaline was competitively antagonized by yohimbine, but not by prazosin. 9. Binding studies using [3H]-prazosin and [3H]-rauwolscine revealed that the bovine myometrium contained both alpha1- and alpha2-adrenoceptors, but the alpha2-type receptor was dominant in both LM (94% of alpha-adrenoceptors) and CM (88%) layers. 10. The distribution of alpha-adrenoceptors was muscle layer-specific; that is, the concentration of alpha1-receptors in LM was the same as in CM, but the concentration of alpha2-receptors in LM was 2.6 times higher than that in CM. 11. The results of the present study indicate that there are layer-specific variations in the functional innervation of the parous bovine myometrium (exclusive adrenergic innervation in LM and adrenergic [minor] plus nonadrenergic, noncholinergic innervation [major] in CM), and that alpha2-adrenoceptors, which were responsive to the excitatory response of endogenous and exogenous noradrenaline, were dominant in both muscle layers of the bovine myometrium.


Is androgen deprivation therapy for prostate cancer associated with cardiovascular disease? A meta-analysis and systematic review.
Androgen deprivation therapy (ADT) is widely being applied in men who suffered from prostate cancer. Whether androgen deprivation therapy (ADT) is associated with an increased risk of developing cardiovascular-related disease is poorly defined. The aim of the present meta-analysis is to explore the relationship between ADT and the risk of cardiac events. MATERIALS AND METHODS: For this systematic review and meta-analysis, we searched databases from inception to April 2019 for randomized controlled trials (RCT) or observational studies that reported data on ADT administration and cardiac event incidence. The connection was evaluated through estimating relative risk ratio (RR) and 95% confidence intervals (CIs). A significantly increased acute myocardial infarction (AMI) was detected in the ADT group compared with the control group (RR = 1.19, 95% confidence interval (CI), 1.02-1.39, P < .05). A significant difference between cardiovascular disease (CVD) and ADT was also observed, with summary RR = 1.25, 95% CI, 1.11-1.40, P < .05. Furthermore, our study also suggested ADT was not related to increased incidence of sudden cardiac death (SCD) (RR = 1.13, 95% CI, 0.92-1.38, P = .24); AMI and CVD were not connected with the duration of ADT (AMI: RR = 1.31; 95% CI, 0.66-2.63, P = .44, for > 5 year group; CVD: RR = 1.12, 95% CI, 0.97-1.30, P = .12, for > 5 year group). In addition, the RR for risk of CVD was 1.28 (95% CI, 1.01-1.62, P < .05) for men with PCa on new hormonal agents. Various ADT modalities have different impact on cardiovascular disease risk in different level. Long-term application of ADT is not associated with increased risk of AMI and CVD. Both abiraterone and enzalutamide could significantly increase the incidence of cardiac events in patients who suffered from prostate cancer. Cautions and periodic cardiovascular elevation are necessary for patients before the ADT starting. Androgen deprivation therapy is associated with increased risk of AMI, CHD, in contrast, this association is not detected in SCD.


Complications of argon laser retinal buckling performed in myopic subjects presenting rhegmatogenous degenerations.
Twenty-two eyes of twenty-two patients suffering from retinal peripheral degenerations underwent preventive equatorial buckling with argon laser photocoagulation. The fellow eye was used as control. We evaluated the effects of laser photocoagulation on corneal sensitivity, on accommodation, on pupillary diameter and light reflex. In the postoperative period, up to the 3rd month, results were significant with respect to the control eye. The mechanisms to which the onset of these undesired alterations is due are discussed.


Salmeterol improves fluid clearance from alveolar-capillary membrane in COPD patients: a pilot study.
The cardiovascular component associated with chronic obstructive pulmonary disease (COPD) plays a major role in disease prognosis, accounting for 25% of the deaths. Experimental and initial clinical data suggest that beta-adrenergic agonists accelerate fluid clearance from the alveolar airspace, with potentially positive effects on cardiogenic and noncardiogenic pulmonary oedema. This pilot study investigated the acute effects of the long-acting beta-2 agonist, salmeterol, on alveolar fluid clearance after rapid saline intravenous infusion by evaluating diffusive and mechanical lung properties. Ten COPD and 10 healthy subjects were treated with salmeterol or placebo 4 h before the patient's mechanical and diffusive lung properties were measured during four non consecutive days, just before and after a rapid saline infusion, or during a similar period without an infusion. In both COPD and healthy subjects, rapid saline infusion with placebo or salmeterol premedication lead to a significant decrease in diffusion capacity for carbon monoxide (DLCO) and forced expiratory volume in 1 s (FEV1). Nonetheless, salmeterol pretreatment lead to a significantly reduced gas exchange impairment caused by saline infusion (-64% of DLCO reduction compared with placebo), whereas it did not affect changes in FEV1. In the control setting with no infusion, we found no significant change in either DLCO or mechanical properties of the lung. Salmeterol appears to provide a protective effect, not related to bronchodilation, against an acute alveolar fluid clearance challenge secondary to lung fluid overload in COPD patients.


Gene-based genome-wide association study identified 19p13.3 for lean body mass.
Lean body mass (LBM) is a complex trait for human health. To identify genomic loci underlying LBM, we performed a gene-based genome-wide association study of lean mass index (LMI) in 1000 unrelated Caucasian subjects, and replicated in 2283 unrelated Caucasians subjects. Gene-based association analyses highlighted the significant associations of three genes UQCR, TCF3 and MBD3 in one single locus 19p13.3 (discovery p = 6.10 × 10-5, 1.65 × 10-4 and 1.10 × 10-4; replication p = 2.21 × 10-3, 1.84 × 10-3 and 6.95 × 10-3; combined p = 2.26 × 10-6, 4.86 × 10-6 and 1.15 × 10-5, respectively). These results, together with the known functional relevance of the three genes to LMI, suggested that the 19p13.3 region containing UQCR, TCF3 and MBD3 genes was a novel locus underlying lean mass variation.


Ovulation induction in polycystic ovary syndrome: No. 242, May 2010.
To review current non-pharmacologic and pharmacologic options for ovulation induction in women with polycystic ovary syndrome (PCOS). This guideline reviews the evidence for the various options for ovulation induction in PCOS. Ovulation, pregnancy and live birth rates, risks, and side effects are the outcomes of interest. Published literature was retrieved through searches of Medline using appropriate controlled vocabulary and key words. Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. Grey (unpublished) literature was identified through searching the websites of health technology assessment and of health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The evidence gathered was reviewed and evaluated by the Reproductive Endocrinology and Infertility Committee of the Society of Obstetricians and Gynaecologists of Canada. The quality of evidence was quantified using the Canadian Task Force on Preventive Health Care. Benefits include weight reduction and improvements in ovulation, pregnancy, and live birth rates. Potential harms include medication side effects and multiple pregnancies. These guidelines have been reviewed and approved by the Reproductive Endocrinology and Infertility Committee of the SOGC.


Facial Paralysis in a Babylonian Plaque.
A terra cotta plaque [LMU 2551] from the Neo-Babylonian period (c.629-539 BCE), housed in the museum of the Archaeology Center at Loyola Marymount University, Los Angeles, is a representation of right peripheral facial paralysis. Ancient representations of pathology are rare and often difficult to identify. This is particularly true of Assyrian-Babylonian cultures where, despite numerous surviving medical texts, artistic examples of disease are almost non-existent. Precise caliper measurements and archaeological analysis of LMU 2551 were used to confirm the authors' hypothesis. The facial distortions portrayed in LMU 2551 are not accidental. Measurements show a pronounced asymmetry of the lower face where the length from the mid-philtrum to the oral commissure and from the lateral edge of the ala nasi to the mid-ipsilateral nasolabial fold are twice as long in the left than in the right side. The left eye is closed, whereas the right is widely open. The described plaque is among the oldest representations of facial paralysis on record. It correlates with contemporary Babylonian texts describing neurological disorders but its function is unknown.


Case report: Long-term outcome post-heart transplantation in a woman with Fabry's disease.
Fabry's disease is an X-linked recessive disorder that results from the deficiency of alpha-galactosidase A and causes the accumulation of globotriaosylceramide (Gb3) in different tissues. It leads to a rare form of cardiomyopathy which may be complicated by end-stage heart failure and need to heart transplant. Our group described the first case of heart transplant in a woman with cardiomyopathy secondary to Fabry's disease about 12 years ago. There was uncertainty in regards to the possibility of recurrence of the disease as previously documented in kidney transplant recipients and long-term outcomes. In this report, 14 years after transplant, this woman is still alive and there is no evidence of Fabry's disease in any of the endomyocardial biopsies. Heart transplantation can be recommended for Fabry's patients with end-stage cardiomyopathy.


[Posterior interosseous nerve palsy. A series of 18 cases and literature review].
Posterior interosseous nerve palsy is a rare syndrome frequently unrecognized, while the clinical presentation is characteristic: finger extension paresis associated with wrist extension in radially deviated position. Here, we assessed our results of surgical treatment. A 20-year retrospective study was carried out in our unit. Analysis of causes and an assessment of postoperative functional outcome were performed. Our study was compared with literature data. Eighteen cases were treated with a predominance in men manual workers. The etiology of the posterior interosseous nerve palsy was tumor in four cases, traumatic in two cases, iatrogenic in two cases and idiopathic in ten cases. In seven of these ten cases, compression under the arch of the extensor carpi radialis brevis was found. The postoperative results were satisfactory with full recovery in nine out of fifteen cases treated by neurolysis, depending on the duration of the paralysis. In the literature, we found 264 cases over 50 years through a variety of clinical cases and five case series. A predominance of tumor etiology was found. Ignorance of the clinical presentation of a posterior interosseous nerve palsy frequently leads to misdiagnosis. Early complete neurolysis enables a satisfactory functional recovery.


Spontaneous lateral abdominal wall hematoma complicating chronic obstructive pulmonary disease exacerbation.
Lateral abdominal wall hematoma is a rare and potentially life-threatening condition. We report a case of a spontaneous lateral abdominal wall hematoma that developed in a patient with severe cough caused by chronic obstructive pulmonary disease (COPD) exacerbation. The hematoma resolved with conservative management.


Pediatric diffusion tensor imaging: normal database and observation of the white matter maturation in early childhood.
Recent advances in diffusion tensor imaging (DTI) have made it possible to reveal white matter anatomy and to detect neurological abnormalities in children. However, the clinical use of this technique is hampered by the lack of a normal standard of reference. The goal of this study was to initiate the establishment of a database of DTI images in children, which can be used as a normal standard of reference for diagnosis of pediatric neurological abnormalities. Seven pediatric volunteers and 23 pediatric patients (age range: 0-54 months) referred for clinical MR examinations, but whose brains were shown to be normal, underwent anatomical and DTI acquisitions on a 1.5 T MR scanner. The white matter maturation, as observed on DTI color maps, was described and illustrated. Changes in diffusion fractional anisotropy (FA), average apparent diffusion constant (ADC(ave)), and T2-weighted (T2W) signal intensity were quantified in 12 locations to characterize the anatomical variability of the maturation process. Almost all prominent white matter tracts could be identified from birth, although their anisotropy was often low. The evolution of FA, shape, and size of the white matter tracts comprised generally three phases: rapid changes during the first 12 months; slow modifications during the second year; and relative stability after 24 months. The time courses of FA, ADC(ave), and T2W signal intensity confirmed our visual observations that maturation of the white matter and the normality of its architecture can be assessed with DTI in young children. The database is available online and is expected to foster the use of this promising technique in the diagnosis of pediatric pathologies.


Influence of macular pigment optical density spatial distribution on intraocular scatter.
This study evaluated the summed measures of macular pigment optical density (MPOD) spatial distribution and their effects on intraocular scatter using a commercially available device (C-Quant, Oculus, USA). A customized heterochromatic flicker photometer (cHFP) device was used to measure MPOD spatial distribution across the central 16° using a 1° stimulus. MPOD was calculated as a discrete measure and summed measures across the central 1°, 3.3°, 10° and 16° diameters. Intraocular scatter was determined as a mean of 5 trials in which reliability and repeatability measures were met using the C-Quant. MPOD spatial distribution maps were constructed and the effects of both discrete and summed values on intraocular scatter were examined. Spatial mapping identified mean values for discrete MPOD [0.32 (s.d.=0.08)], MPOD summed across central 1° [0.37 (s.d.=0.11)], MPOD summed across central 3.3° [0.85 (s.d.=0.20)], MPOD summed across central 10° [1.60 (s.d.=0.35)] and MPOD summed across central 16° [1.78 (s.d.=0.39)]. Mean intraocular scatter was 0.83 (s.d.=0.16) log units. While there were consistent trends for an inverse relationship between MPOD and scatter, these relationships were not statistically significant. Correlations between the highest and lowest quartiles of MPOD within the central 1° were near significance. While there was an overall trend of decreased intraocular forward scatter with increased MPOD consistent with selective short wavelength visible light attenuation, neither discrete nor summed values of MPOD significantly influence intraocular scatter as measured by the C-Quant device.


Hepatic veno-occlusive disease due to pyrrolizidine (Senecio) poisoning in Arizona.
An infant with documented hepatic veno-occlusive disease due to ingestion of pyrrolizidine alkaloids is presented. The alkaloids were ingested in the form of an herbal tea commonly used as a folk remedy among the Mexican-American population. Among these people, this herb is known as gordolobo yerba. The patient presented with acute hepatocellular disease and portal hypertension which progressed over 2 months to extensive hepatic fibrosis. Other potential causes of hepatic venous occlusion were absent.


The effect of soil nutrient status on prey utilization in four carnivorous plants.
The hypothesis that carnivorous plants are less responsive to prey at high soil nutrient levels than at lower levels (Givnish et al. 1984) is tested on four plant species (Drosera rotundifolia, Pinguicula alpina, P. villosa and P. vulgaris) from a subarctic environment. The response, measured in terms of seven characteristics (winter bud weight, winter bud nitrogen and phosphorus content, flowering frequency, total seed weight, seed number and weight per seed), was analysed. Although all species responded to prey supply the response varied depending on the characteristic and species concerned. In 5 cases (out of 28 tests) the hypothesis was supported, whereas in 1 case it was refuted, i.e. the response to prey was higher for plants supplied with soil nutrients. In the remaining three-quarters of the tests, responses to prey were not significantly different between the two nutrient levels. Thus, the hypothesis that the response to prey diminishes as soil nutrient availability increases was not supported by our findings. A modification of the model presented by Givnish et al. (1984) is therefore suggested. This modified model measures the cost of carnivory as loss in growth rate and assumes that responses to prey remain unchanged as the soil nutrient content increases. Although the distribution of carnivorous plants is still predicted to be limited mainly to wet and sunny but nutrient-poor sites, the modified model also allows for their occurrence in richer habitats, provided competition is low.


Temporal instability and differences in injury severity between restrained and unrestrained drivers in speeding-related crashes.
Upon detecting a crash impact, the vehicle restraint system locks the driver in place. However, external factors such as speeding, crash mechanisms, roadway attributes, vehicle type, and the surrounding environment typically contribute to the driver being jostled within the vehicle. As a result, it is crucial to model unrestrained and restrained drivers separately to reveal the true impact of the restraint system and other factors on driver injury severities. This paper aims to explore the differences in factors affecting injury severity for seatbelt-restrained and unrestrained drivers involved in speeding-related crashes while accounting for temporal instability in the investigation. Utilizing crash data from Thailand between 2012 and 2017, mixed logit models with heterogeneity in means and variances were employed to account for multi-layered unobserved heterogeneity. For restrained drivers, the risk of fatal or severe crashes was positively associated with factors such as male drivers, alcohol influence, flush/barrier median roadways, sloped roadways, vans, running off the roadway without roadside guardrails, and nighttime on unlit or lit roads. For unrestrained drivers, the likelihood of fatal or severe injuries increased in crashes involving older drivers, alcohol influence, raised or depressed median roadways, four-lane roadways, passenger cars, running off the roadway without roadside guardrails, and crashes occurring in rainy conditions. The out-of-sample prediction simulation results are particularly significant, as they show the maximum safety benefits achievable solely by using a vehicle's seatbelt system. Likelihood ratio test and predictive comparison findings highlight the considerable combined impact of temporal instability and the non-transferability of restrained and unrestrained driver injury severities across the periods studied. This finding also demonstrates a potential reduction in severe and fatal injury rates by simply replicating restrained driver conditions. The findings should be of value to policymakers, decision-makers, and highway engineers when developing potential countermeasures to improve driver safety and reduce the frequency of severe and fatal speeding-related single-vehicle crashes.


Truncation of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) from Rhodospirillum rubrum affects the holoenzyme assembly and activity.
Truncations of the subunit of ribulose bisphosphate carboxylase/oxygenase (Rubisco) from Rhodospirillum rubrum were generated by site-directed mutagenesis to examine the role of the C-terminal tail section. Removal of the last and the penultimate alpha-helices in the tail section changes the quaternary structure of the protein. Electrophoretic and electron microscope analysis revealed that the truncated subunits assemble into an octamer, whereas the wild-type enzyme has a dimeric structure. The octomerization of the mutant protein is due to a hydrophobic patch exposed to the solvent by truncation of the subunit. The mutant protein thus consists of four dimers, bound end-to-end by hydrophobic interactions. Insertion of a polar amino acid in the hydrophobic patch by a L424 to N424 substitution restores the familiar dimeric structure. Truncation of the subunit is associated with a considerable decrease in catalytic activity. The mutants undergo carbamylation but bind the reaction intermediate analog, 2-carboxy arabinitol-1,5-bisphosphate, poorly. This indicates that loss of activity in the mutant is due to weakened substrate binding. These findings suggest that the mutations in the tail section of the subunit are transmitted to the active site, although the C-terminal region is far from the active site. On the basis of the crystal structure of Rubisco, we propose a model for how the truncations of the enzyme subunit induce conformational changes in one of the two phosphate binding sites.


The mediating effects of job satisfaction on turnover intention for long-term care nurses in Taiwan.
This study explores the mediating effects of job satisfaction on work stress and turnover intention among long-term care nurses in Taiwan. Healthcare institutions face a nursing shortage, and it is important to examine the factors that influence turnover intention among nurses. Excessive levels of work stress may lead to employee dissatisfaction and a significant inverse relationship between work stress and job satisfaction, including subsequent effects on turnover among nurses. However, little is known about the mediating role of job satisfaction on work stress and turnover intention among long-term care nurses. A cross-sectional survey and a correlation design were used. Multistage linear regression was used to test the mediation model. This study showed that job satisfaction significantly mediated the relationship between work stress and turnover intention. Thirty-eight percent of the variance in turnover intention explained by work stress was accounted for by the mediation pathway. The results of this study showed that higher job satisfaction significantly decreased work stress and turnover intention among long-term care nurses. This study provides nursing administrators with a resource to build a supportive environment to increase nurses' job satisfaction and to decrease their stress and turnover.


[Replacement therapy of acquired antithrombin III deficiency in experimental nephrotic syndrome].
The influence of antithrombin III on hemostasis and renal function was studied in experiments on rats with nephrotic syndrome. The development of nephrotic syndrome was accompanied by the activation of blood coagulation and appearance of acquired antithrombin III deficiency due to its loss with the urine. The replacement therapy by bovine antithrombin III at a dose of 25 U/kg a day for 10 days decreased the signs of excessive thrombinogenesis in experimental animals and increased the amount of thrombin-antithrombin III complexes in the blood flow. The activation of coagulation in rats with nephrotic syndrome predominantly induced the disturbances of the excretory renal function which could be efficiently corrected by antithrombin III.


Preparative isolation and purification of phillyrin from the medicinal plant Forsythia suspensa by high-speed counter-current chromatography.
Forsythia suspensa (Thunb.) Vahl. has been used widely in traditional medicines to treat gonorrhea, erysipelas, inflammation, pyrexia and ulcer. It has also shown antioxidant activity, as well as antibacterial, antiviral, choleretic and antiemetic effects. A high-speed counter-current chromatography (HSCCC) method was developed for the preparative separation and purification of the bioactive molecule phillyrin from F. suspensa (Thunb.) Vahl. The crude phillyrin was obtained by extraction with 50% ethanol from the dried fruits of F. suspensa (Thunb.) Vahl. under sonication. Preparative HSCCC with a two-phase solvent system composed of n-hexane-ethyl acetate-ethanol-water (1:9:1:9, v/v/v/v) was successfully performed, and the components purified and collected were analyzed by high-performance liquid chromatography. The method yielded 5.6 mg phillyrin at 98.6% purity from 500 mg of the crude extract (1.2% phillyrin) with the recovery of 92% in a one-step separation.


Interdisciplinary service learning and substance abuse screening in free clinic settings.
Interdisciplinary groups of students learned screening tools for substance use and practiced skills of brief intervention while serving needs of a local free clinic.


Towards an understanding of redox heterogeneity of the photosystem II cytochrome b559 in the native membrane.
A complex redox titration pattern of cytochrome (Cyt) b559 in preparations of thylakoid membranes and photosystem (PS) II membrane fragments is commonly attributed to the presence of three conformational forms differing by a structure of the heme microenvironment. However, despite decades of research, structural determinants underlying differences between the redox forms of Cyt b559 have not been defined. In this work, we propose a different interpretation of redox heterogeneity in the native population of Cyt b559 assuming redox interaction between the Cyt b559 heme group and a nearby bound quinone (Q). The interacting quinone is supposed to be plastoquinone QC present in the unusual singly protonated form (QCH). The model successfully explains the unique redox properties of Cyt b559 and may provide a simple and effective mechanism of redox regulation of secondary electron transport in PS II. At the present time, the model of heme-quinone redox interaction can be considered as an alternative to the idea of conformational differences between the native redox forms of Cyt b559.


Intensification of infliximab therapy in Crohn's disease: efficacy and safety.
The response of Crohn's disease (CD) to infliximab is initially good, although a loss of efficacy is observed over time. Dose escalation has been recommended in such cases. To study the response to an intensified infliximab regimen in patients with CD; and to evaluate the adverse effects associated with intensification of therapy and identify predictors of loss of response. We performed a retrospective multicenter survey of all patients with CD who had been treated with at least the 3 induction doses of standard infliximab therapy, and for whom treatment had to be intensified due to loss of response. We analyzed the efficacy of the intensified regimen. Thirty-three patients were included. After the first intensification dose, 79% of patients had a clinical response (33.5% complete response, 45.5% partial response). In the long term, 83%, 69%, 47%, and 29% of patients who had an initial response to the intensification maintained the response at 6, 12, 18, and 36 months, respectively. The loss of efficacy after escalation was 43% per patient-year of follow-up. One patient had an infusion reaction after 36 doses. One patient developed a herpes zoster infection. A high proportion of patients whose dose of infliximab is increased due to loss of efficacy respond initially. However, nearly half lose the response after one year. The safety profile of an intensified infliximab regimen is good.


Analysis of the uncharted, druglike property space by self-organizing maps.
Physicochemical properties are fundamental to predict the pharmacokinetic and pharmacodynamic behavior of drug candidates. Easily calculated descriptors such as molecular weight and logP have been found to correlate with the success rate of clinical trials. These properties have been previously shown to highlight a sweet-spot in the chemical space associated with favorable pharmacokinetics, which is superior against other regions during hit identification and optimization. In this study, we applied self-organizing maps (SOMs) trained on sixteen calculated properties of a subset of known drugs for the analysis of commercially available compound databases, as well as public biological and chemical databases frequently used for drug discovery. Interestingly, several regions of the property space have been identified that are highly overrepresented by commercially available chemical libraries, while we found almost completely unoccupied regions of the maps (commercially neglected chemical space resembling the properties of known drugs). Moreover, these underrepresented portions of the chemical space are compatible with most rigorous property filters applied by the pharma industry in medicinal chemistry optimization programs. Our results suggest that SOMs may be directly utilized in the strategy of library design for drug discovery to sample previously unexplored parts of the chemical space to aim at yet-undruggable targets.


Cryptic Streptococcus mutans 5.6-kb plasmids encode a toxin-antitoxin system for plasmid stabilization.
In all Streptococcus mutans strains, 5-13% carry a 5.6-kb plasmid. Despite its frequency, little is known about its mediated functions with most of the information coming from a single study focussing on plasmid pUA140. Here, we describe the sequence and genetic organization of two S. mutans 5.6-kb plasmids, pDC09 and pNC101. Based on PicoGreen dsDNA quantification and Real-Time quantitative PCR (RTQ-PCR), the plasmid copy number was found to range between 10 and 74, depending on the strain tested. In contrast to literature, we identified six instead of five open reading frames (ORFs). While the putative gene products of ORF1 (as a Rep-protein) and ORF2 (as a Mob-protein) could be confirmed as being identical to those from pUA140, the functions of ORF3 (unknown) and ORF 4 (possibly AtpE homologue) could not be further revealed. However, the product of ORF5 showed a fairly high identity (38-50%) and structural similarity (58-74%) to RelE of Streptococcus pneumoniae, Streptococcus equi, and Streptococcus downei. In addition, we identified a functionally corresponding ORF6 encoding a protein with 61-68% identity (81-86% similarity) to the S. equi and S. downei antitoxin of the RelB family. RelE and RelB together form a plasmid-encoded toxin-antitoxin (TA) system, RelBE(plas). Despite its rather limited sequence similarity with chromosomal TA systems in S. mutans (RelBE(chro), MazEF, HicBA), we found similar tertiary structures applying I-Tasser protein prediction analysis. Type II-toxins, as the plasmid-encoded RelE, are RNA endonucleases. Depending on their mRNA cleavage activity, they might 1) kill every plasmid-free progeny, thereby stabilizing plasmid transfer at the expense of the host and/or 2) help S. mutans enter a dormant state and survive unfavourable environmental conditions. Whilst a function in plasmid stabilization has been confirmed, a function in persistence under nutritional stress, tested here by inducing amino acid starvation, could not be demonstrated so far.


Serum albumin is a useful prognostic indicator and adds important information to NT-proBNP in a Chinese cohort of heart failure.
To evaluate the effect of serum albumin on prognosis and the power of albumin adding information to NT-proBNP in a Chinese cohort of heart failure. 385 consecutive patients (male vs. female: 292 vs. 93; mean age: 54.89±14.41years; NYHA classes II-V) admitted for heart failure exacerbation with LVEF≤45% were enrolled, and biochemical data was measured at baseline. The endpoint was defined as cardiac death or rehospitalization for aggravated heart failure. Follow-up period was 25±7months. Multivariate analysis in a Cox proportional hazard model revealed serum albumin was an independent predictor for adverse prognosis (HR 0.96,CI 0.94-0.99, P=0.02), and the patients with higher NT-proBNP and lower albumin than median had the highest risk for cardiac events (HR 2.89, CI 1.90-4.40, P<0.01). Serum albumin is a significant prognosis indicator for heart failure and it adds important information to NT-proBNP.


Meatoplasty keloid: a rare lesion treated with an unusual surgical approach.
Keloid scarring is a benign hyperproliferation of fibrous tissue occurring at a wound healing site. Keloid formation related to the ear is generally the result of ear-piercing, mainly causing cosmetic disfigurement. We present an unusual case of keloid formation at a previous meatoplasty incision scar in a 10-year-old Caucasian with a modified radical mastoid cavity. This lesion prevented the cavity from self-cleaning and obstructed microscopic evaluation of the cavity. Treatment was successfully performed by surgical excision, with closure of the defect using supra-keloid skin flaps, followed by serial steroid injection therapy.


The use of embryonic stem cells to study hedgehog signaling.
Because they are capable of differentiating into cell types of all three primary germ layers, embryonic stem cells provide an ideal in vitro system in which to study the signals that regulate differentiation toward a specific cell type. Here, we describe methods for using embryonic stem cells to study the signals that control differentiation into neurectoderm and into vascular cell types, focusing on the Hedgehog signaling pathway.


Indentation instrument for the measurement of cartilage stiffness under arthroscopic control.
Changes in the biomechanical properties of articular cartilage are one of the first signs of the tissue degeneration. We have developed a small size indentation instrument for the quantification of cartilage stiffness under arthroscopic control. During measurement, the indenter imposes a constant deformation on the cartilage and the maximal indenter force, by which the cartilage resists the deformation, is used as a measure for cartilage stiffness. The instrument has been tested in laboratory conditions with elastomer and cadaver knee joint cartilage samples. A linear relationship was found between indenter force and elastomer stiffness (r = 0.990, n = 14) as well as between indenter force and cartilage shear modulus obtained by a reference device (r = 0.879, n = 22). Also, the correlation between two repeated measurements at the measurement sites, used to evaluate the reproducibility, was linear (r = 0.953, n = 16). Quantitative detection of cartilage stiffness is possible with the instrument.


Non-syndromic hemihyperplasia in a male and his mother.
We present two family members with non-syndromic hemihyperplasia (HHP), which developed in adolescence. We have reviewed reported familial cases of HHP and conclude that presentation is similar to sporadi cases and that all affected family members have been related through a maternal relative.


[Serum 1, 5-anhydroglucose alcohol: a serum indicator for estimating acute blood sugar fluctuation in patients with fulminant type 1 diabetes].
To test the feasibility of using 1,5-anhydroglucose alcohol (1,5-AG) as a diagnostic indicator of fulminant type 1 diabetes (FT1DM). Fifteen patients with newly diagnosed FT1DM and 52 with type 2 diabetes (T2DM) were examined for serum biochemistry, glycosylated hemoglobin (HbAlc), and serum 1, 5-AG level. The patients with FT1DM and T2DM showed significantly different fasting levels of blood glucose (FBG), fructosamine (FMN), creatinine (Cr), urea, HbAlc and serum 1,5-AG (P<0.05). In FT1DM patients, serum 1,5-AG was found to inversely correlate with FBG (r=-0.646, P=0.032) and FMN (r=-0.680, P=0.021), and in T2DM patients, serum 1,5-AG was inversely correlated with FBG (r=-0.407, P=0.001), FMN (r=-0.314, P=0.01) and HbAlc (r=-0.576, P<0.01). Receiver-operating characteristic (ROC) curve analysis showed an area under the curve of serum 1,5-AG of 0.804 with a cutoff value of 67.95, a sensitivity of 82.9% and a specificity of 60% for FT1DM diagnosis. Serum 1, 5-AG can reflect acute blood glucose fluctuation in FT1DM patients and is useful for differential diagnosis of FT1DM when combined with evaluations of the clinical characteristics of the patients and other related indicators.


Different herd level factors associated with H1N1 or H1N2 influenza virus infections in fattening pigs.
Herd-level factors associated with European H1N1 or H1N2 swine influenza virus (SIV) infections were assessed by mean of a cross-sectional study carried out in 125 herds in France. Serum samples from 15 fattening pigs in each herd were tested by haemagglutination inhibition. Data related to herd characteristics, biosecurity, management and housing conditions were collected by questionnaire during the farm visit. Climatic conditions in the post-weaning and fattening rooms, where the sampled pigs were housed, were measured over 20 h. Factors associated with H1N1 or H1N2 sero-positive status of the herd were identified by logistic regressions for binary outcome. For both subtypes, the odds for a herd to be SIV sero-positive increased if there were more than two pig herds in the vicinity (OR=3.2, 95% confidence interval (95% CI): 1.4-7.6, p<0.01 and OR=3.5, 95% CI: 1.5-8.1 p<0.01 for H1N1 and H1N2 respectively). Different factors were specifically associated with either H1N1 or H1N2 SIV infections. The odds for a herd to be H1N1 sero-positive were significantly increased by having a large number of pigs per pen in the post-weaning room (OR=3.2, 95% CI: 1.2-8.6, p=0.02), temperature setpoints below 25 °C (OR=2.6, 95% CI: 1.1-6.4, p=0.03) and below 24 °C (OR=2.6, 95% CI: 1.1-6.1, p=0.03) for the heating device in the farrowing room and the ventilation controller, respectively, and moving the pigs to the fattening facility via a room housing older pigs (OR=3.3, 95% CI: 1.1-9.6, p=0.03). A H1N2 sero-positive status was associated with a brief down period in the farrowing room (OR=2.6, 95% CI: 1.1-6.3, p=0.03), small floor area per pig in the post-weaning pen (OR=2.9, 95% CI: 1.2-7.0, p=0.02), large-sized fattening room (OR=2.5, 95% CI: 1.1-5.9, p=0.03), lack of all-in all-out management in the fattening room (OR=2.4, 95% CI: 1.0-5.8, p=0.04) and a temperature range of less than 5 °C controlling ventilation in the fattening facilities (OR=3.2, 95% CI: 1.4-7.4, p<0.01). Factors related to external and internal biosecurity and to the control of inside climatic conditions should be considered together when implementing programmes to better control SIV infections.


Correction: Validation of an automated shape-matching algorithm for biplane radiographic spine osteokinematics and radiostereometric analysis error quantification.
[This corrects the article DOI: 10.1371/journal.pone.0228594.].


The application of intraoperative frozen section examination in multiparametric magnetic resonance imaging/transrectal ultrasound fusion prostate biopsy during a major pandemic.
To investigate the value of intraoperative frozen section examination (IFSE) in multiparametric magnetic resonance imaging/transrectal ultrasound (mpMRI/TRUS) fusion prostate biopsy in a major pandemic. A total of 35 patients were prospectively enrolled in our hospital from March 2020 to January 2021. The mpMRI/TRUS fusion system was used to perform a targeted biopsy, and the collected specimens were examined by IFSE (Observation Group 1). Then, a targeted biopsy was performed again for routine pathological examination (Observation Group 2). Finally, a systemic biopsy was performed, and the obtained specimens were routinely examined (Control Group). The positive rate, single core positive rate, Gleason score, and time to obtain pathological reports were compared between the groups. The positive rate was 48.6% (17/35) in the control group, 48.6% (17/35) in Observation Group 1, and 51.4% (18/35) in Observation Group 2, showing no significant difference (P>0.05). The single core positive rates were 17.8%, 44.6%, and 47.1% in the Control Group, Observation Group 1, and Observation Group 2, respectively. Observation Group 1 and Observation Group 2 were significantly different from the Control Group (P<0.001). No participants in Observation Group 1 had increased or decreased Gleason scores compared with those in Observation Group 2. The time to obtain the pathological report was 0.025±0.014 days and 4.216±1.073 days for Observation Group 1 and Observation Group 2, respectively, showing a significant difference (P<0.001). This study showed that IFSE can not only rapidly obtain the pathological report of an mpMRI/TRUS biopsy, but can also ensure the accuracy of the pathological diagnosis. CHICTR, Identifier: ChiCTR2000040789. Registered 10 December 2020 - Retrospectively registered, http://www.chictr.org.cn/edit.aspx?pid=63252&htm=4.


Effect of empiric dosing on blood levels of theophylline and phenytoin.
To evaluate empiric dosing guidelines for aminophylline and phenytoin in the management of acute exacerbations of obstructive lung disease and seizure disorders, we utilized an emergency department (ED)-based EMIT system to measure stat plasma theophylline and phenytoin levels in patients intended to receive these drugs. Plasma drug level results were available prior to initiation of therapy. Of the patients evaluated, 45 of 163 (27.6%) aminophylline patients and 21 of 73 (28.7%) phenytoin patients were projected to have plasma concentrations below the recommended therapeutic range if empiric dosing schedules were employed. In addition, 39 of 163 (23.9%) aminophylline and 10 of 73 (13.7%) phenytoin patients, had they received these drugs empirically, would have had plasma theophylline and phenytoin levels in excess of the recommended therapeutic range using empiric dosing. We conclude that the use of empiric dosing guidelines for aminophylline and phenytoin in the ED do not reliably produce therapeutic plasma concentrations. The development of a stat drug analysis laboratory in the hospital or within the ED would improve the effectiveness and safety of these acutely used drugs with narrow therapeutic ranges.


Septic arthritis in a patient after tonsillectomy.
Tonsillectomy is a common and relatively safe pediatric surgery. However, common and emergent complications from this procedure include hemorrhage, airway obstruction, and local infection. A rare but equally emergent complication is infection from hematogenous spread. We present a rare case of septic arthritis in a 6-year-old female of the ankle 3 days following tonsillectomy.


Global Analysis of Cellular Protein Flux Quantifies the Selectivity of Basal Autophagy.
In eukaryotic cells, macroautophagy is a catabolic pathway implicated in the degradation of long-lived proteins and damaged organelles. Although it has been demonstrated that macroautophagy can selectively degrade specific targets, its contribution to the basal turnover of cellular proteins has not been quantified on proteome-wide scales. In this study, we created autophagy-deficient primary human fibroblasts and quantified the resulting changes in basal degradative flux by dynamic proteomics. Our results provide a global comparison of protein half-lives between wild-type and autophagy-deficient cells. The data indicate that in quiescent fibroblasts, macroautophagy contributes to the basal turnover of a substantial fraction of the proteome at varying levels. As contrasting examples, we demonstrate that the proteasome and CCT/TRiC chaperonin are robust substrates of basal autophagy, whereas the ribosome is largely protected under basal conditions. This selectivity may establish a proteostatic feedback mechanism that stabilizes the proteasome and CCT/TRiC when autophagy is inhibited.


Simultaneous adsorption of aflatoxin B1 and zearalenone by mono- and di-alkyl cationic surfactants modified montmorillonites.
Organo-montmorillonites (OMts) modified with mono- and di-alkyl cationic surfactants were prepared to remove polar mycotoxin aflatoxin B1 (AFB1) and weak polar, hydrophobic mycotoxin zearalenone (ZER) simultaneously. The structural and surface properties of the prepared OMts were investigated. In vitro adsorption experiments were carried out to simulate the in vivo conditions of gastrointestinal tract of animals by a batch mode. The adsorption of AFB1 and ZER in both single and binary-contaminate systems were investigated systematically. Both OMts showed super enhanced adsorption capacities towards AFB1 and ZER whenever in single and binary-contaminate systems compared with raw Mt, indicating the effectiveness of the prepared OMts acted as mycotoxins adsorbents. DODAC-Mt showed a higher adsorption capacity towards AFB1 and ZER than OTAB-Mt. The equilibrium data of AFB1 on OMts were fitted satisfactorily with Freundlich and Linear models, suggesting the co-existence of different adsorption mechanism which were proposed to be ion-dipole interactions (between surfactant cations and carbonyl groups of AFB1) and adsorption/partition mechanisms. The adsorption isotherms of OMts to ZER matched best with Linear models, implying the adsorption/partition mechanism. For simultaneous adsorption, the adsorption process of one mycotoxin was slightly affected by the presence of the other mycotoxin due to the requirement of partial same sorption sites. In addition, the solution pH had negligible influence on the adsorption process of OMts, meaning no desorption occurred when the adsorbents pass through from stomach to intestine as animal feed.


A new hotspot of macro-litter in the Rutland Island, South Andaman, India: menace from IORC.
Supralittoral zones of 13 sandy beaches of remote Rutland Island were divided into three zones to identify the litter contamination, its source, pathway of plastic transport to determine the level of macro-litter contamination, and its impact on coastal biota. Owing to the floral and faunal diversity, apart of the study area is protected under Mahatma Gandhi Marine National Park (MGMNP). The supralittoral zones of each sandy beach (between low-tide and high-tide line) were individually calculated from 2021 Landsat-8 satellite imagery before conducting the field survey. The total area of the surveyed beaches was 0.52 km2 (5,20,020.79 m2), and 317,565 litters representing 27 distinct litter types were enumerated. Two beaches in Zone-II and six in Zone-III were clean; however, all five in Zone-I were very dirty. The highest litter density (1.03 items/m2) was observed in Photo Nallah 1 and Photo Nallah 2, whereas the lowest (0.09 items/m2) was observed in Jahaji Beach. According to the Clean Coast Index (CCI), Jahaji Beach (Zone-III) is the very cleanest beach (1.74) while other beaches of Zone-II and Zone-III are clean. The findings of the Plastic Abundance Index (PAI) indicate that Zone-II and Zone-III beaches have a low abundance of plastics (< 1), while two beaches of Zone-I, viz., Katla Dera and Dhani Nallah, exhibited a moderate abundance of plastics (< 4) while a high abundance of plastics (< 8) was observed in the rest of three beaches of the same zone. The primary contributor of litter on Rutland's beaches was plastic polymers (60-99%), which were presumed to originate from the Indian Ocean Rim Countries (IORC). A collective litter management initiative by the IORC is essential in preventing littering on remote islands.


The Money Side: Billing, Coding, Reimbursement, Costs, and Marketing.
Billing, coding, reimbursement, costs, and marketing for a vascular lab (VL) may seem daunting. This article simplifies monetary aspects of setting up and running a successful VL so that they are less complex. In setting up the vascular lab (VL), there is a lot to consider regarding money. Many are not savvy in this respect; however key knowledge is needed to start up a successful VL. This article aims to simply describe some factors and ideas regarding money and the promotion to increase financial return.


Chromosome 1q21.3 amplification is a trackable biomarker and actionable target for breast cancer recurrence.
Tumor recurrence remains the main reason for breast cancer-associated mortality, and there are unmet clinical demands for the discovery of new biomarkers and development of treatment solutions to benefit patients with breast cancer at high risk of recurrence. Here we report the identification of chromosomal copy-number amplification at 1q21.3 that is enriched in subpopulations of breast cancer cells bearing characteristics of tumor-initiating cells (TICs) and that strongly associates with breast cancer recurrence. Amplification is present in ∼10-30% of primary tumors but in more than 70% of recurrent tumors, regardless of breast cancer subtype. Detection of amplification in cell-free DNA (cfDNA) from blood is strongly associated with early relapse in patients with breast cancer and could also be used to track the emergence of tumor resistance to chemotherapy. We further show that 1q21.3-encoded S100 calcium-binding protein (S100A) family members, mainly S100A7, S100A8, and S100A9 (S100A7/8/9), and IL-1 receptor-associated kinase 1 (IRAK1) establish a reciprocal feedback loop driving tumorsphere growth. Notably, this functional circuitry can be disrupted by the small-molecule kinase inhibitor pacritinib, leading to preferential impairment of the growth of 1q21.3-amplified breast tumors. Our study uncovers the 1q21.3-directed S100A7/8/9-IRAK1 feedback loop as a crucial component of breast cancer recurrence, serving as both a trackable biomarker and an actionable therapeutic target for breast cancer.


Intracranial magnetic resonance imaging findings in the surviving fetus after spontaneous monochorionic cotwin demise.
This study was undertaken to evaluate intracranial magnetic resonance imaging abnormalities in the surviving fetus after a cotwin demise. This is a retrospective observational study evaluating the intracranial findings of surviving twins after demise of a monochorionic cotwin. A total of 47 cases of cotwin demise were identified from an magnetic resonance imaging database consisting of all fetal magnetic resonance imagings performed at the University of California San Francisco. Twenty-one of these cases were monochorionic twins who had not undergone an intervention (fetal radiofrequency ablation and placental laser ablation) and these comprised the study group. The magnetic resonance imagings were reviewed by a pediatric neuroradiologist who was blinded to the ultrasound and clinical findings. The mean gestational age at the time of cotwin demise was 19(6/7) weeks (range 12(4/7) weeks-26(5/7) weeks) with an average interval of 4(3/7) weeks between the time of cotwin demise and fetal magnetic resonance imaging (range 0-12(1/7) weeks). Nine cases (41%) were associated with diagnosed twin-twin transfusion syndrome. Abnormal findings, including polymicrogyria, germinolytic cysts, intracranial hemorrhage, ventriculomegaly, and delayed sulcation were identified by fetal magnetic resonance imaging in 7 (33%) cases, the majority of which had a normal ultrasound. Prenatal magnetic resonance imaging is a valuable tool in evaluating the fetal brain after a cotwin demise.


Immunohistochemical demonstration of glial fibrillary acidic protein in normal rat Müller glia and retinal astrocytes.
The presence of glial fibrillary acidic protein (GFA)-positive Müller glia and retinal astrocytes were studied immunohistochemically in normal rat retina. Using GFA antiserum both Müller glia and separate star-shaped cells were observed in spread-preparations as well as cryostat sections. The retinal astrocytes were also visualized using two different monoclonal GFA antibodies. These cells were found to be located in the nerve fiber and ganglion cell layers. In contrast, Müller glia were not normally visualized with any of the monoclonal GFA antibodies but could be stained 4 days after an optic nerve crush. Our results demonstrate that normal rat Müller glia expresses GFA-like immunoreactivity.


pUC12-W1: a plasmid vector for the study of cloned DNA conformation.
pUC12-W1 is a new cloning vector for the study of torsion-induced structural transitions of insert DNA. It was derived from pUC12 by deleting three A + T-rich sequences which can undergo structural transitions when torsionally stressed. Transitions at these sites have low energy of activation and undefined structures. They complicate studies on transitions of DNA inserts by diverting torsional force and causing the vector to be undefined in helical and energetic terms. The new vector pUC12-W1, from which these segments have been deleted, will facilitate studies of torsion-induced structural transitions of insert DNA.


Can we prevent food allergy by manipulating the timing of food exposure?
Prevention of food allergies by maternal and infant feeding practices serves as a simple, inexpensive approach to address the growing number of subjects with food allergies in comparison with any emerging interventional therapies for existing food allergies, such as oral immunotherapy. This article provides a careful evaluation of the rationale and existing data on the effect of timing of the introduction of food allergens (during pregnancy, lactation, and early childhood) on the development of specific food allergies.


Magnetic mini-mover procedure for pectus excavatum III: safety and efficacy in a Food and Drug Administration-sponsored clinical trial.
The magnetic mini-mover procedure (3MP) uses magnetic force to gradually remodel pectus excavatum deformity. A magnet is implanted on the sternum and coupled with an external magnetic brace. Under Investigational Device Exemption and Institutional Review Board approval, we performed a pilot study of safety, probable efficacy, and cost-effectiveness of this new treatment of an orphan disease using an implantable pediatric device. Ten otherwise healthy patients, ages 8 to 14 years, with severe pectus excavatum (pectus severity index [PSI] > 3.5) underwent 3MP treatment (mean, 18.8 ± 2.5 months). Safety was assessed by postimplant and postexplant electrocardiograms and monthly chest x-rays. Efficacy was assessed by change in pectus severity index as measured using pretreatment and posttreatment computed tomographic scan. Cost of 3MP was compared with that of standard procedures. The 3MP device had no detectable ill effect. Device weld failure or malpositioning required revision in 5 patients. Average wear time was 16 h/d. Pectus severity index improved in patients in the early or mid puberty but not in patients with noncompliant chest walls. Average cost for 3MP was $46,859, compared with $81,206 and $81,022 for Nuss and Ravitch, respectively. The 3MP is a safe, cost-effective, outpatient alternative treatment for pectus excavatum that achieves good results for patients in early and midpuberty stages.


Involvement of transient receptor potential vanilloid 1 in ectopic pain following inferior alveolar nerve transection in rats.
Chronic pain often develops in the orofacial region after inferior alveolar nerve (IAN) injury. In animal models IAN injury often causes severe neuropathic pain-like behavior in the IAN-innervated region as well as the adjacent region that includes the whisker pad skin. However, the basis for the spreading of pain to adjacent facial areas after IAN injury is still unknown. In this study we determined if the transient receptor potential vanilloid 1 (TRPV1) was associated with altered nocifensive behavior evoked by stimulation of the whisker pad skin following IAN transection. Grooming behavior after capsaicin injection into the whisker pad region was significantly increased after IAN transection and the increase in the behavior was reversed by systemic administration of a TRPV1 antagonist. The number of phosphorylated extracellular signal-regulated kinase immunoreactive (IR) neurons in trigeminal spinal subnucleus caudalis and upper cervical spinal cord following capsaicin injection into the whisker pad region was significantly greater in IAN-transected rats than sham-operated rats. The number of TRPV1-IR trigeminal ganglion (TG) neurons innervating the whisker pad skin was also increased significantly after IAN transection. The present findings suggest that an increase in TRPV1 expression in TG neurons innervating the whisker pad skin after IAN transection may underlie the spreading of pain to the adjacent whisker pad skin.


Examining arts-based practice in midwifery education: An integrative review.
The aim of this integrative review is to synthesise the literature on creative teaching methods in midwifery education. The review question seeks to investigate the experiences of student midwives and midwifery educators of using creative methods as a learning approach. The benefits of creative teaching methods are widely acknowledged but the ways in which this may impact midwifery students' learning processes, or how this relates to their developing professional development, is not well understood. Research focused specifically on student midwives is yet to be synthesised. An integrative review was undertaken using data comparison with reflexive thematic analysis to identify common themes. Eight electronic databases were searched with key terms in June 2022. English language studies from qualitative, quantitative, mixed-methods and wider literature were included. Twenty-two texts were included in the synthesis. Four themes were generated from the data; 1) What is the offering - More than a lecture; exploring the educator and student exchange and environment for learning; 2) Working in parallel - examining the change in teaching dynamic and collaborative partnerships; 3) Journeying towards holism - focused on student's integration of learning processes; and 4) Stepping into the professional - engaging with how using creativity can aid students' growing sense of themselves as professionals. This highlights improvements in levels of confidence, professional development and emotional intelligence in midwifery students. Creative teaching and learning methods enable student midwives to make meaningful connections between theoretical and practice learning environments, assisting knowledge and skills acquisition.


National COVID-19 lockdown and trends in help-seeking for violence against children in Zimbabwe: an interrupted time-series analysis.
An estimated 1.8 billion children live in countries where COVID-19 disrupted violence prevention and response. It is important to understand how government policies to contain COVID-19 impacted children's ability to seek help, especially in contexts where there was limited formal help-seeking prior to the pandemic. We aimed to quantify how the national lockdown in Zimbabwe affected helpline calls for violence against children, estimated the number of calls that would have been received had the lockdown not occurred and described characteristics of types of calls and callers before and after the national lockdown. We used an interrupted time series design to analyse the proportion of violence related calls (17,913 calls out of 57,050) to Childline Zimbabwe's national child helpline between 2017 to 2021. We applied autoregressive integrated moving average regression (ARIMA) models to test possible changes in call trends before and after the March 2020 lockdown and forecasted how many calls would have been received in the absence of lockdown. In addition, we examined call characteristics before and after lockdown descriptively. The proportion of violence related calls decreased in the 90 days after the lockdown and subsequently returned to pre-COVID-19 levels. We estimate that 10.3% (95% confidence interval [CI] 6.0-14.6%) more violence related calls would have occurred in this period had there not been a lockdown. Violence was increasingly reported as occurring in children's households, with fewer reports from children and formal child protection actors. Lockdowns dramatically change everyday life and strain populations, which is unlikely to reduce violence prevalence but may reduce help-seeking. The three months after COVID-19 lockdowns may be key time periods when help-seeking for violence decreases drastically. Policy makers should ensure that in-person and remote services support help-seeking. Interventions and campaigns may additionally want to target adult female family members in encouraging reporting of suspected violence cases when they occur within households and are perpetuated by other family members. We suggest a composite approach of scaling-up remote reporting mechanisms that are accessible and geographically well-distributed, establishing non-traditional sites for help seeking within communities and continuing limited in-person home visitation for known cases of violence.


Colloidal gold based immunochromatographic detection of Mycoplasmopsis synoviae infection and its prevalence in avian species of Karachi, Pakistan.
Avian mycoplasmosis is an infection that commonly prevails in birds, particularly in poultry chickens. Among mycoplasmosis causing organisms, Mycoplasmopsis synoviae is a predominant and lethal pathogen to the aves. Considering the increased incidence of infections by M. synoviae, the prevalence of M. synoviae was deduced in poultry chickens and fancy birds of Karachi region. The lungs and tracheal samples from chicken and dead fancy birds and swab samples from live fancy birds were collected and investigated by amplifying 16 s rRNA gene of M. synoviae. Biochemical characteristics of M. synoviae was also evaluated. Furthermore, surface-associated membrane proteins, that represent key antigens for diagnosis of M. synoviae infection was extracted by Triton X- 114 method. Results showed that M. synoviae was detected more frequently in lungs than in trachea, that could be due to its invasion capacity and tissue affinity. SDS PAGE analysis of extracted membrane proteins showed two prominent hydrophobic proteins of different molecular mass including proteins of 150 and 50 kDa. Protein of 150 kDa was purified by size exclusion chromatography and it exhibited agglutinogen activity. Purified protein was used in the development of one-step immunochromatographic (ICT) assay for the detection of antibodies against M. synoviae using gold nanoparticles coated with polyclonal antibodies. Low levels of antibodies were detected by the developed ICT kit, which has 88% sensitivity with 92% specificity.


Alternating Stacking of Nanocrystals and Nanofibers into Ultrastrong Chiral Biocomposite Laminates.
Attaining high mechanical strength and flexibility for chiral nematic biopolymer composites without compromising their vivid optical iridescence is an intriguing but challenging task. Traditional cellulose nanocrystal (CNC) blend nanocomposite films typically lose their coloration and display weak mechanical performance due to poor load transfer between needle-like nanocrystals and the collapse of a twisted organization. Herein, we report a design of robust laminated biocomposites with an alternatively stacked chiral nematic CNC phase and a random cellulose nanofiber (CNF) phase via a hydrogen-bonding-assisted layer-by-layer method. In contrast to the traditional biopolymer blends, the alternating CNC-CNF stacked films possess many-fold enhancement in both mechanical strength and toughness with their vivid structural colors highly preserved. We suggest that the enriched hydrogen bonding and partial limited entanglements at the interfaces between the helicoidal and random phases are responsible for enhancing the mechanical performance of robust biocomposites with brilliant iridescent colors. Such organized cellulose-cellulose biocomposites with alternating helicoidal-random phases fabricated by a facile sequential strategy may facilitate the development of sustainably sourced, damage-tolerant, and photonic films for bioenabled display technologies, security indicators, soft robotics, camouflages, and pressure sensors.


Effects of sodium butyrate on growth and cell-cycle kinetics of cultured rabbit articular chondrocytes.
The sodium salt of n-butyric acid was found to inhibit the growth of asynchronous cultures of rabbit articular chondrocytes. This inhibitory effect was dose-dependent between 1 mM and 5 mM, reversible, and accompanied by volume enhancement and modification of cellular morphology. Flow-cytometric analysis showed that drug exposure led to a slowing-down of the cell-cycle progression; after 1 day's exposure, cells accumulated in G1, and after 2 or 3 days' treatment, in G2, without a blockage in M; the increase of cells in G2 was in fact due to an enhancement of binculeated cells. The treated cells had an increased RNA content. Articular chondrocytes seem to be target cells for sodium butyrate and therefore it represents a valuable biological tool for studying the mechanisms of their growth regulation.


Anesthesia for patients with cardiac disease.
The entire spectrum of cardiac disease may be seen in patients who are in need of plastic surgical procedures. To conduct the patient safely through the perioperative period, the anesthesiologist and surgeon must carefully evaluate each patient preoperatively and understand the pathophysiology of the cardiac disease. In this article the preoperative evaluation and anesthetic and postoperative considerations for plastic surgical patients with four types of cardiac disease (congenital heart disease, coronary artery disease, valvular cardiac disease, and congestive cardiomyopathy) are discussed.


Metabolomics and microarrays for improved understanding of phenotypic characteristics controlled by both genomics and environmental constraints.
Advances in our understanding of functional genomics are best addressed by integrative studies that include measurements of mRNA, proteins, and low molecular weight metabolites over time and varied conditions. Bioinformatics can then be used to relate this data to the genome. Current technology allows for comprehensive and rapid mRNA expression profiling and mass spectrophotometric measurement of low molecular weight intermediates and metabolic products. In prokaryotic organisms, this combination provides a potentially powerful tool for identifying gene function and regulatory networks even in the absence of a combined proteomic approach.


Suppression of autoimmune arthritis in interleukin-1-deficient mice in which T cell activation is impaired due to low levels of CD40 ligand and OX40 expression on T cells.
To elucidate the roles of interleukin-1 (IL-1) in the development of 2 etiologically different rheumatoid arthritis (RA) models: the type II collagen (CII)-induced arthritis (CIA) model and the human T cell leukemia virus type I transgenic (HTLV-I Tg) mouse model. For the CIA model, DBA/1J-background IL-1alpha-/-, IL-1beta-/-, IL-1alpha/beta-/-, and wild-type littermate mice were immunized with CII. For the HTLV-I Tg model, BALB/c IL-1beta-/- or IL-1alpha/beta-/- mice were crossed with HTLV-I Tg mice. The effects of IL-1 deficiency were assessed as follows: Development of arthritis was assessed both macroscopically and microscopically. Serum antibody titer was measured by enzyme-linked immunosorbent assay. Proliferative response of lymph node cells was assayed by measurement of (3)H-thymidine incorporation. Expression of T cell surface molecule CD40 ligand (CD40L) and OX40 was determined by multicolor flow cytometric analysis. The development of arthritis was markedly suppressed in IL-1alpha/beta-/- mice in both models, although the effect was less prominent in HTLV-I Tg mice. Deficiency of only IL-1alpha or only IL-1beta was also associated with disease suppression. Antibody production after immunization with CII was normal in IL-1alpha/beta-/- mice, while autoantibody production was suppressed in IL-1alpha/beta-/- HTLV-I Tg mice. In IL-1alpha/beta-/- mice, the T cell proliferative response against CII was greatly reduced in both the CIA and the HTLV-I Tg models, suggesting inefficiency of T cell activation. Furthermore, expression of CD40L and OX40 on T cells was greatly reduced in IL-1alpha/beta-/- mice. These observations suggest that T cell activation by IL-1 is important for the development of autoimmunity and arthritis in these mice.


Quality of life improvement after a three-year course of sublingual immunotherapy in patients with house dust mite and grass pollen induced allergic rhinitis: results from real-life.
Along with its high prevalence, the burden of allergic rhinitis rests upon the serious impact on quality of life of patients. Allergic rhinitis is associated with impairments in daily activities, work and school performance, and practical problems. Patients suffer from sleep disorders and emotional problems. Тhe advantages of sublingual immunotherapy on quality of life have only recently begun to emerge. The objective of this prospective real-life study was to evaluate the effect of a three-year course of sublingual immunotherapy with house dust mite (HDM) and grass pollen extracts on quality of life in adults with allergic rhinitis. A total number of 191 adult patients [105 (54,979%) men; mean age 27.3 years (SD-6.14)] with moderate to severe allergic rhinitis and clinically relevant sensitization to house dust mites or grass pollen were prospectively evaluated in the course of management of their disease. Health-related quality of life was assessed by Rhinoconjunctivitis Quality of Life Questionnaire at baseline and after three-year course of sublingual immunotherapy. The mean overall Qol score assessed at baseline and at the end of the third year of treatment decreased significantly in patients treated with HDM extract (from 2.95 to 0.76) as well as with Grass pollen extract (from 2.83 to 1.22) (р < 0.001). The improvements in treated with HDM extract were as followed: activities - 3.52 to 0.68; sleep- 2.48 to 0.31; general problems - 1.79 to 0.49; practical problems - 3.57 to 0.68; nasal symptoms - 3.91 to 0.74; eye symptoms - 2.92 to 0.39; emotions - 3.03 to 0.39. The improvements in grass pollen group were: activities - 3.68 to 1.69; sleep- 1.85 to 0.84; general problems - 1.74 to 0.97; practical problems - 3.52 to 1.37; nasal symptoms - 3.72 to 1.57; eye symptoms - 3.58 to 1.3; emotions - 2.48 to 1.19. Our study conducted in real life provided evidence that a three-year course of SLIT with HDM extract as well as with grass pollen extract significantly increased QoL in patients with allergic rhinitis.


Continuous infusion of recombinant factor VIIa in patients with haemophilia and inhibitors. Experience in The Netherlands and Belgium.
Initial clinical experience with recombinant factor VIIa (rVIIa) for treatment of haemophilia patients with inhibitors against factor VIII or IX has been obtained by administration of rVIIa by repeated intravenous bolus injections. However, continuous infusion of rVIIa may be a more appropriate administration method if prolonged treatment is indicated. We have surveyed and analysed the initial experience with continuous infusion of rVIIa in the Netherlands and Belgium. Five hospitals treated 7 haemophilia patients with inhibitors on 9 different occasions (4 bleedings, 5 surgical interventions) by continuous infusion of rVIIa over a total of 59 days. Haemostatic coverage was considered effective in 8 out of 9 cases and partially effective in 1 case. Continuous infusion of rVIIa was aimed at rVIIa target plasma levels of 10 U/ml and a decrease in prothrombin time (PT) of 3 s compared to control levels. This was obtained by an initial bolus injection of 90 micrograms/kg prior to continuous infusion of rVIIa at doses between 30-6 micrograms/kg/h (mean 17.5 micrograms/kg/h). A conventional one-stage factor VII coagulation assay, often used in combination with a PT, was satisfactory in monitoring rVIIa treatment. The additional clinical value of anti-fibrinolytic and anti-thrombophlebitic treatment was unclear. In our experience, rVIIa appeared to be efficacious and safe when administered by continuous infusion. Continuous infusion of rVIIa is more convenient than bolus injections or rVIIa, easy to monitor and provides a cost reduction of > 50%. These advantages make continuous infusion an attractive administration method for prolonged treatment with rVIIa.


Vasculitis and Pregnancy: Disease State and Management.
Family planning in women with vasculitis requires an interdisciplinary approach. This article summarizes recommendations and guidance for each phase of family planning in persons with vasculitis including preconception counseling, birth control, pregnancy, and breastfeeding. Pregnancy complications are presented by category of vasculitis with accompanying diagnostic and therapeutic recommendations. Birth control and assisted reproductive technology options are reviewed with special considerations for women who are high risk or have a history of blood clots. This article can be used as a clinical reference for reproductive discussions in all patients with vasculitis.


Novel insights into wound age estimation: combined with "up, no change, or down" system and cosine similarity in python environment.
Wound age estimation is a complex, multifactorial issue. It is considered to have great practical significance that combining multi-biomarkers and multi-methods for injury time estimation. We optimized our earlier "up, no change, or down" model by adding data on the expression levels of mRNAs encoding ABHD2, MAD2L2, and ARID5A, and we converted the relative quantitative expression levels of seven genes into a vector rather than a color model. We used Python to derive the cosine similarity (CS) between a test set and the vector matrix; the highest similarity most accurately reflected the injury time. For the optimized model, the internal and external verifications were approximately 0.71 and 0.66, respectively. The good double-blinded results indicated that the model was stable and reliable. In summary, we used a vector matrix and cosine similarities derived by Python to mine the levels of genes expressed in contused skeletal muscle. We are the first to combine several biomarkers and methods for wound age estimation.


PITMAN: a FORTRAN program for exact randomization tests.
PITMAN performs exact randomization tests. It also performs Wilcoxon signed-rank tests and Wilcoxon-Mann-Whitney U tests in the presence of an arbitrary number of ties in the data. PITMAN requires an IBM PC with 256K of memory. The source code is available for those who wish to compile smaller or larger versions or wish to move PITMAN to another computer.


5-Hydroxytryptamine uptake and imipramine binding sites in neurotumor NCB-20 cells.
NCB-20 cells (neuroblastoma X fetal Chinese hamster brain hybrids) are equipped with a [3H]5-hydroxytryptamine [( 3H]5-HT) uptake system and [3H]imipramine recognition sites. Approximately 80% of the radioactivity taken up by cells incubated with [3H]5-HT was identified with 5-HT. [3H]5-HT uptake was temperature-dependent, partially sodium-dependent, saturable (Km = 7.3 +/- 0.6 microM; Vmax = 2.0 +/- 0.6 pmol/min/mg), and inhibited by clomipramine, imipramine, fluoxetine, and desipramine, but not by iprindole, mianserin, or opipramol. Lineweaver-Burk plots showed a competitive type of inhibition by imipramine and fluoxetine. [3H]5-HT uptake was not inhibited by nisoxetine or benztropine. [3H]Imipramine binding sites had a KD of 12 +/- 2 nM and a Bmax of 22 +/- 7 pmol/mg protein. The binding was sodium-sensitive although to a lesser extent than that found with brain membranes. Imipramine binding was displaced by tricyclic antidepressants with the following order of potency: clomipramine greater than imipramine greater than fluoxetine greater than desipramine much greater than iprindole = mianserin greater than opipramol. These results suggest that imipramine binding sites are present together with the 5-HT uptake sites in NCB-20 cells and that these sites interact functionally but are different biochemically.


Illicit psychotropic substances in the air: The state-of-art.
The occurrence of psychotropic substances (PSs) in the air is known since long time. Recently, attention was paid to illicit PS, with most investigations undertaken in Italy and Spain. In general, collection of illicit substances was performed through aspirating airborne particulates onto filters; afterwards, gas chromatography or high-performance liquid chromatography coupled with mass spectrometry were applied for the PS evaluation. Over twenty substances could be characterized simultaneously. Cocaine concentrations up to 17ngm(-3) were observed in Latin America, while this substance was absent (<0.003ngm(-3)) in Algiers (Algeria) and Pančevo (Serbia). Cannabinoids (comprising the psycho-active principle Δ(9)-tetrahydrocannabinol [THC]) were high in the winter and very low in the summer (up to 6ngm(-3) and <0.1ngm(-3), respectively). Many other substances (e.g., heroin, ephedrine and drug by-products) occurred less frequently and at lesser extents (<20pgm(-3)). In Rome (Italy), investigations were carried out in interiors of dwellings, schools, an office and a coffee bar, all sites resulting affected by drugs. Besides, solid phase microextraction methods were applied to detect ketamine and methamphetamine in interiors. The PS concentrations depended on substance, physical-chemical contour, and internal or external type of locations. Air monitoring allows detecting the drug consumption or preparation, because illicit substances prevail in sites frequented by abusers.


The etiology and outcome of non-traumatic coma in critical care: a systematic review.
Non-traumatic coma (NTC) is a serious condition requiring swift medical or surgical decision making upon arrival at the emergency department. Knowledge of the most frequent etiologies of NTC and associated mortality might improve the management of these patients. Here, we present the results of a systematic literature search on the etiologies and prognosis of NTC. Two reviewers independently performed a systematic literature search in the Pubmed, Embase and Cochrane databases with subsequent reference and citation checking. Inclusion criteria were retrospective or prospective observational studies on NTC, which reported on etiologies and prognostic information of patients admitted to the emergency department or intensive care unit. Eventually, 14 studies with enough data on NTC, were selected for this systematic literature review. The most common causes of NTC were stroke (6-54%), post-anoxic coma (3-42%), poisoning (<1-39%) and metabolic causes (1-29%). NTC was also often caused by infections, especially in African studies affecting 10-51% of patients. The NTC mortality rate ranged from 25 to 87% and the mortality rate continued to increase long after the event had occurred. Also, 5-25% of patients remained moderately-severely disabled or in permanent vegetative state. The mortality was highest for stroke (60-95%) and post-anoxic coma (54-89%) and lowest for poisoning (0-39%) and epilepsy (0-10%). NTC represents a challenge to the emergency and the critical care physicians with an important mortality and moderate-severe disability rate. Even though, included studies were very heterogeneous, the most common causes of NTC are stroke, post anoxic, poisoning and various metabolic etiologies. The best outcome is achieved for patients with poisoning and epilepsy, while the worst outcome was seen in patients with stroke and post-anoxic coma. Adequate knowledge of the most common causes of NTC and prioritizing the causes by mortality ensures a swift and adequate work-up in diagnosis of NTC and may improve outcome.


Device to promote pelvic floor muscle training for stress incontinence.
Many patients with stress urinary incontinence do not have enough motivation to continue pelvic floor muscle training (PFMT) by themselves. Therefore, a device was created to support PFMT, and its effect was examined. Forty-six women with stress urinary incontinence were assigned to a control group or a device group in order of presentation. A pamphlet on PFMT was given to control patients, while the same pamphlet plus the device and instructions on its use were given to patients in the device group. The device had a chime that was set to sound three times a day when exercise sessions were scheduled. PFMT consisted of fast and slow pelvic floor muscle contraction exercises that were performed for 2 min and followed a rhythm set by the device. After 8 weeks, 20 patients from the control group and 21 patients from the device group could be evaluated. In the control group, only the quality of life (QOL) index improved significantly. In the device group, however, the daily number of incontinence episodes, the number of pads used daily, the QOL index, and the pad weight in the pad test improved significantly. Patients in the device group said that they felt obligated to perform PFMT when the chime sounded. Forty-eight percent of patients from the device group were satisfied with the outcome of PFMT, while only 15% were satisfied in the control group. This device may be useful to support the management of stress urinary incontinence.