Helicobacter pylori infection contributes to placental impairment in preeclampsia: basic and clinical evidences.
Preeclampsia (PE) is a major cause of maternal and neonatal morbidity and mortality. Epidemiological association between Helicobacter pylori (Hp) infection and PE onset has been widely shown. The aim of this study was to analyze a possible correlation between Hp infection and the severity of clinical presentation of PE and to identify an immunologic mechanism triggered by Hp infection potentially contributing to the pathogenesis of PE. Sera from 93 preeclamptic women and 87 healthy pregnant women were tested for Hp infection by immunoassay and for anti-CagA antibodies by Western blot assay. The serologic results were correlated with the clinical features of PE. The functional effect of serum IgG fractions, positive or negative for Hp, from preeclamptic women or controls were tested on trophoblast and endothelial cell cultures and in a murine model of angiogenesis. Preeclamptic women showed higher seroprevalence of Hp infection (57.0%) compared to controls (33.3%) (P<.001). The seropositivity for CagA-positive strains of Hp was 45.2% in preeclamptic women vs 13.7% in controls (P<.001). In PE women, Hp infection was associated with abnormality of uterine arteries Doppler (P<.001). Hp+ IgG fractions from preeclamptic women bound to trophoblast and endometrial endothelial cell cultures, reducing in vitro invasiveness and angiogenesis, respectively, and inhibited angiogenesis in mice. Our data show, for the first time, an association between Hp infection and PE with abnormal uterine arteries Doppler velocimetry, suggesting a role for Hp infection in impairing placental development and increasing the risk to develop PE. This study opens the new perspective of a potential screening and treatment for Hp infection in pregnancy.


Calcium and magnesium in essential hypertension.
1. Because disturbances of calcium metabolism have been described in hypertension, measurements of plasma and serum concentrations of ionized calcium, total calcium, magnesium and renin were made in 38 patients with essential hypertension and age- and sex-matched control subjects. Urinary excretion of calcium, magnesium and sodium was also determined. 2. The mean serum concentration of ionized calcium was 1.23 +/- 0.04 (SD) mmol/l in the hypertensive group and 1.21 +/- 0.03 mmol/l in controls, and results were similar after correction for pH. There was a weak positive correlation between serum ionized calcium (pH 7.4) and systolic pressure (r = 0.26, P less than 0.02), but no correlation with plasma renin concentration. 3. Although the difference between serum total calcium concentration in the hypertensive (2.29 +/- 0.09 mmol/l) and control (2.26 +/- 0.07 mmol/l) subjects was not significant, there was a significant correlation between total calcium and systolic pressure (r = 0.23, P less than 0.05) which was maintained after correction for other variables. 4. There were no differences in plasma concentrations of parathyroid hormone or 1,25-dihydroxycholecalciferol between hypertensive and control subjects. 5. The hypertensive group showed higher urinary excretion of calcium (5.9 +/- 3.0 mmol/24 h) than controls (4.6 +/- 1.7 mmol/24 h), but the difference was not maintained after correction for sodium excretion. 6. Serum concentrations of magnesium were similar in the two groups, but urinary excretion of magnesium was significantly lower in hypertensive (3.7 +/- 1.3 mmol/24 h) than control (4.5 +/- 1.6 mmol/24 h) subjects and there was an inverse correlation between magnesium excretion and blood pressure (r = 0.3-0.35, P less than 0.01).


Quinidine sulfate therapy for the slow-channel congenital myasthenic syndrome.
The slow-channel congenital myasthenic syndrome (SCCMS) is caused by gain of function mutations in subunits of the end-plate acetylcholine receptor (AChR). The mutations prolong the opening episodes of the AChR channel, leading to a depolarization block and an end-plate myopathy. Because levels of quinidine sulfate attainable in clinical practice shorten the opening episodes of genetically engineered mutant SCCMS receptors in vitro, we tested the notion that the drug can be of benefit in SCCMS. We treated 6 SCCMS patients with quinidine sulfate in an open-label trial, using objective clinical measures of muscle strength and repetitive stimulation studies as end points. One patient became allergic to quinidine after 7 days. The remaining patients tolerated the drug well and after 30 days of continuous therapy showed statistically significant improvement in muscle strength and in decrement of the compound muscle action potential elicited by rapid rates of stimulation.


A completely thrombosed, nongiant middle cerebral artery aneurysm mimicking an intra-axial neoplasm.
Few reports exist regarding thrombosed aneurysms where the initial work up was concerning for a neoplasm. To date, no published reports exist regarding a nongiant thrombosed middle cerebral artery aneurysm, where the primary workup and treatment plan was directed toward a preliminary diagnosis of intra-axial neoplasm. We report a 43-year-old female who presented with a generalized tonic-clonic seizure attributed to a lesion along the right superior temporal gyrus. The lesion enhanced on initial magnetic resonance imaging (MRI) of the brain, as well as on follow-up MRI. Subsequent vascular studies and metastatic work up were negative. A craniotomy with image guidance was performed and an intraoperative diagnosis was made of a thrombosed aneurysm along a branch of the middle cerebral artery. The aneurysm was trapped and resected as there was no significant flow from the branch as seen on the prior cerebral angiogram. The patient had an uneventful postoperative course. Completely thrombosed, nongiant aneurysms can mimic an intra-axial neoplasm. Typical imaging features for thrombosed aneurysms may be missed, especially if the aneurysms are small, where imaging characteristics of the intraluminal contents is more difficult to appreciate. Although imaging may be consistent with a neoplastic lesion, there should be suspicion for a potential underlying aneurysm.


Eye Care Quality and Accessibility Improvement in the Community (EQUALITY): impact of an eye health education program on patient knowledge about glaucoma and attitudes about eye care.
To assess the impact of the education program of the Eye Care Quality and Accessibility Improvement in the Community (EQUALITY) telemedicine program on at-risk patients' knowledge about glaucoma and attitudes about eye care as well as to assess patient satisfaction with EQUALITY. New or existing patients presenting for a comprehensive eye exam (CEE) at one of two retail-based primary eye clinics were enrolled based on ≥1 of the following at-risk criteria for glaucoma: African Americans ≥40 years of age, Whites ≥50 years of age, diabetes, family history of glaucoma, and/or preexisting diagnosis of glaucoma. A total of 651 patients were enrolled. A questionnaire was administered prior to the patients' CEE and prior to the patients receiving any of the evidence-based eye health education program; a follow-up questionnaire was administered 2-4 weeks later by phone. Baseline and follow-up patient responses regarding knowledge about glaucoma and attitudes about eye care were compared using McNemar's test. Logistic regression models were used to assess the association of patient-level characteristics with improvement in knowledge and attitudes. Overall patient satisfaction was summarized. At follow-up, all patient responses in the knowledge and attitude domains significantly improved from baseline (P≤0.01 for all questions). Those who were unemployed (odds ratio =0.63, 95% confidence interval =0.42-0.95, P=0.026) or had lower education (odds ratio =0.55, 95% confidence interval =0.29-1.02, P=0.058) were less likely to improve their knowledge after adjusting for age, sex, race, and prior glaucoma diagnosis. This association was attenuated after further adjustment for other patient-level characteristics. Ninety-eight percent (n=501) of patients reported being likely to have a CEE within the next 2 years, whereas 63% (n=326) had a CEE in the previous 2 years. Patient satisfaction with EQUALITY was high (99%). Improved knowledge about glaucoma and a high intent to pursue eye care may lead to improved detection of early disease, thus lowering the risk of blindness.


Increased transient receptor potential canonical type 3 channels in vasculature from hypertensive rats.
We tested the hypothesis that transient receptor potential canonical type 3 (TRPC3) channels are increased in vascular smooth muscle cells and aortic tissue from spontaneously hypertensive rats (SHR) compared with normotensive Wistar Kyoto rats. Expression of TRPC3 was analyzed by immunohistochemistry and Western blotting. TRPC3 gene knockdown was performed by specific small interfering RNA and TRPC3 overexpression using the pAdEasy-1 system. Cytosolic calcium was measured using fluorescence spectrophotometry and vasoconstriction of aortic rings using a force transducer. In SHR, the expression of TRPC3 channel protein was significantly higher in aortic rings (1.48+/-0.05 versus 1.00+/-0.06; each n=6; P<0.01) and vascular smooth muscle cells (1.28+/-0.08 versus 1.00+/-0.03; each n=6; P<0.05) compared with Wistar Kyoto rats. Knockdown of TRPC3 gene expression by specific small interfering RNA significantly reduced the angiotensin II-induced calcium influx by 30+/-3% (n=6; P<0.01), whereas TRPC3 overexpression significantly increased it by 55+/-3% (n=6; P<0.01). The angiotensin II-induced calcium increase was significantly enhanced in vascular smooth muscle cells from SHR compared with Wistar Kyoto rats, even in the presence of the calcium channel blocker amlodipine. Angiotensin II significantly elevated the TRPC3 channel protein expression in vascular smooth muscle cells from SHR from 1.28+/-0.08 to 1.61+/-0.08 (each n=6; P<0.01). Angiotensin II-induced TRPC3 expression was prevented by telmisartan. Administration of telmisartan to SHR for 4 weeks significantly reduced blood pressure, angiotensin II-induced vasoconstriction, and TRPC3 channel protein expression in aortic tissue. TRPC3 expression was not significantly reduced after reduction of blood pressure in SHR using amlodipine. In conclusion, we give experimental evidence that increased TRPC3 channel protein expression in the vasculature is important for elevated blood pressure.


Latissimus dorsi breast reconstruction. Long term results and return of sensibility.
The long-term results of 44 patients who underwent breast reconstruction after mastectomy with latissimus dorsi musculocutaneous flaps with endoprostheses were studied. Good symmetry without a brassiere was achieved in 15 patients, slight asymmetry in 24 and poor symmetry in five (11%). Symmetry when a brassiere was worn was acceptable in all but one of the patients (43/44). A third of the patients (n = 13) had developed unacceptable (grade III or IV) capsular contraction, but 39 (89%) of the patients studied were satisfied with the long-term reconstruction. Cutaneous sensibility, measured by von Frey's test, had returned to 28 (64%) of the cutaneous skin islands, to their medial parts in particular. The flaps in patients who had received concentrated radiation or who had large prostheses remained numb. Sensation was normal in the scars of the donor areas in all but three patients. Latissimus dorsi breast reconstruction with an endoprosthesis is safe and simple. It gives a subjectively satisfactory result in nine out of 10 patients and is therefore a valuable method of reconstruction after mastectomy.


Ancestry Prediction Comparisons of Different AISNPs for Five Continental Populations and Population Structure Dissection of the Xinjiang Hui Group via a Self-Developed Panel.
Ancestry informative markers are genetic markers that show distinct genetic divergences among different populations. These markers can be utilized to discern population substructures and estimate the ancestral origins of unknown individuals. Previously, we developed a multiplex system of 30 ancestry informative single nucleotide polymorphism (AISNP) loci to facilitate ancestral inferences in different continental populations. In the current study, we first compared the ancestry resolutions of the 30 AISNPs and the other previously reported AISNP panels for African, European, East Asian, South Asian and American populations. Next, the genetic components of the Xinjiang Hui group were further explored in comparison to these continental populations based on the 30 AISNPs. Genetic divergence analyses of the 30 AISNPs in these five continental populations revealed that most of the AISNPs showed high genetic differentiations between these populations. Ancestry analysis comparisons of the 30 AISNPs and other published AISNPs revealed that these 30 AISNPs had comparable efficiency to other AISNP panels. Genetic relationship analyses among the studied Hui group and other continental populations demonstrated that the Hui group had close genetic affinities with East Asian populations and might share the genetic ancestries with East Asian populations. Overall, the 30 AISNPs can be used to predict the bio-geographical origins of different continental populations. Moreover, the obtained genetic data of 30 AISNPs in the Hui group can further enrich the extant reference data, which can be used as reference data for ancestry analyses of the Hui group.


Magnetic resonance imaging findings in pulmonary Kaposi's sarcoma: a series of 10 cases.
Since chest X-ray and CT scan features of Kaposi's sarcoma (KS) are nonspecific, we wanted to test the hypothesis that the histological components of this tumour and/or the associated haemorrhagic component, may result in a characteristic signal pattern on magnetic resonance imaging (MRI). Thoracic MRI was performed in a prospective manner in ten patients with acquired immune deficiency syndrome (AIDS) and pulmonary KS. MRI examinations (1.5 Tesla) included Spin-echo T1 (SE-T1), before and after gadolinium injection, as well as T2-weighted sequences (SE-T2). For each sequence the signal intensity of lesions was measured and compared with each other as well as with the signal intensity of muscle. Results were compared to the hemosiderin content of macrophages in the bronchoalveolar lavage (BAL) in all patients and with histological findings in three. The results were compared to values obtained in a control group of seven patients with pneumocystis carinii pneumonia. SE-T1 showed focally increased signal intensity in the pulmonary parenchyma (n = 5). Signal enhancement in parenchymal lesions (n = 10) and along peribronchovascular trees (n = 5) was observed after gadolinium injection. The second echo of SE-T2 showed a markedly reduced signal intensity in pathologic areas (n = 10). This last finding was not observed in the control group. In conclusion, we have identified a pattern of MRI signal abnormalities suggestive of Kaposi's sarcoma. The MRI signal intensity of KS lesions may be related to the angiomatous and fibrous components of the tumour.(ABSTRACT TRUNCATED AT 250 WORDS)


Functional rs6265 polymorphism in the brain-derived neurotrophic factor gene confers protection against neurocognitive dysfunction in posttraumatic stress disorder among Chinese patients with hepatocellular carcinoma.
Posttraumatic stress disorder (PTSD) is a psychiatric disorder that plagues trauma survivors. Evidence shows that brain-derived neurotrophic factor (BDNF) may be involved in the occurrence and development of PTSD. Here we tried to demonstrate whether BDNF gene polymorphisms are correlated with neurocognitive function following PTSD in patients with hepatocellular carcinoma (HCC). This study included 102 patients with HCC complicated with PTSD, 146 HCC patients, and 152 healthy volunteers. Initially, we evaluated the neurocognitive function of the study subjects. Next, we measured BDNF G11757C and rs6265 polymorphisms by polymerase chain reaction-restriction fragment length polymorphism. The correlation of BDNF polymorphisms and BDNF level with HCC complicated with PTSD was evaluated. The results revealed that HCC complicated with PTSD showed decreased serum BDNF level and Mini-mental state examination (MMSE) score. Serum BDNF level of HCC and HCC complicated with PTSD was positively correlated with MMSE score. GA + AA allele and A allele of rs6265 increased the risk of PTSD among patients with HCC. GA and AA genotypes of rs6265 were correlated with the decreased MMSE score of HCC complicated with PTSD. Haplotype GA of rs6265 and G11757C increased the risk of PTSD for HCC, while haplotype CG decreased this risk. Lastly, the logistic regression analysis suggested that low BDNF level was a contributor to HCC complicated with PTSD, while GG genotype of rs6265 served as a protective factor. Collectively, this study defines the GG genotype of BDNF rs6265 polymorphism as a protector to HCC complicated with PTSD. In addition, these results provided a promising target for PTSD prevention in patients with HCC.


Enhanced mindfulness-based stress reduction in episodic migraine-effects on sleep quality, anxiety, stress, and depression: a secondary analysis of a randomized clinical trial.
Patients with migraine suffer from high morbidity related to the repeated headache attacks, characteristic of the disorder, poor sleep, and a high prevalence of comorbid psychosocial disorders. Current pharmacological therapies do not address these aspects of migraine, but nonpharmacological treatments such as mindfulness-based stress reduction (MBSR) have been shown to improve both pain and psychological well-being. In this secondary analysis, we examined the change over time in sleep quality and psychosocial outcomes from the magnetic resonance imaging outcomes for mindfulness meditation clinical trial and assessed how these mediated treatment response (50% reduction in headache frequency postintervention). We also examined the relationship between baseline values and treatment response. The trial (primary outcomes previously reported) included 98 patients with episodic migraine randomized to either enhanced MBSR (MBSR+) or stress management for headache. They completed psychosocial questionnaires and headache diaries at baseline (preintervention), midintervention (10 weeks after baseline), and postintervention (20 weeks after baseline). There was a significant improvement in sleep quality from baseline to postintervention (P = 0.0025) in both groups. There were no significant changes from baseline or between groups in anxiety, depression, and stress. There was also no significant association between baseline scores and treatment response. Mediation analysis showed a significant indirect effect of 6% for sleep: In other words, small improvements in sleep may have contributed to the efficacy of MBSR+.Trial registration: NCT02133209.


[Minocycline-induced hyperpigmentation].
A common adverse effect of minocycline therapy is cutaneous pigmentation. We describe two patients who presented with hyperpigmentation caused by minocycline. One patient, aged 54 years, had taken minocycline due to lung silicosis for 3 years before black pigmentation of the face occurred. The other 49 year-old patient developed grey-black hyperpigmentation on both lower legs after a 6-month therapy with minocycline for folliculitis. This patient was treated with the Q-switched ruby laser and the pigmentation resolved in the treated area. The different clinical and histological forms of minocycline-induced hyperpigmentation are discussed.


Estimating the conditional probability of developing human papilloma virus related oropharyngeal cancer by combining machine learning and inverse Bayesian modelling.
The epidemic increase in the incidence of Human Papilloma Virus (HPV) related Oropharyngeal Squamous Cell Carcinomas (OPSCCs) in several countries worldwide represents a significant public health concern. Although gender neutral HPV vaccination programmes are expected to cause a reduction in the incidence rates of OPSCCs, these effects will not be evident in the foreseeable future. Secondary prevention strategies are currently not feasible due to an incomplete understanding of the natural history of oral HPV infections in OPSCCs. The key parameters that govern natural history models remain largely ill-defined for HPV related OPSCCs and cannot be easily inferred from experimental data. Mathematical models have been used to estimate some of these ill-defined parameters in cervical cancer, another HPV related cancer leading to successful implementation of cancer prevention strategies. We outline a "double-Bayesian" mathematical modelling approach, whereby, a Bayesian machine learning model first estimates the probability of an individual having an oral HPV infection, given OPSCC and other covariate information. The model is then inverted using Bayes' theorem to reverse the probability relationship. We use data from the Surveillance, Epidemiology, and End Results (SEER) cancer registry, SEER Head and Neck with HPV Database and the National Health and Nutrition Examination Surveys (NHANES), representing the adult population in the United States to derive our model. The model contains 8,106 OPSCC patients of which 73.0% had an oral HPV infection. When stratified by age, sex, marital status and race/ethnicity, the model estimated a higher conditional probability for developing OPSCCs given an oral HPV infection in non-Hispanic White males and females compared to other races/ethnicities. The proposed Bayesian model represents a proof-of-concept of a natural history model of HPV driven OPSCCs and outlines a strategy for estimating the conditional probability of an individual's risk of developing OPSCC following an oral HPV infection.


Eligibility for treatment and angiographic features at the early stage of exudative age related macular degeneration.
To determine the eligibility for laser photocoagulation treatment or for photodynamic therapy (PDT) with verteporfin in eyes at the earliest stage (first month of symptoms) of exudative age related macular degeneration (AMD) based on fluorescein angiographic (FA) features; to evaluate the potential contribution of indocyanine green angiography (ICG-A) for occult choroidal neovascularisation (CNV) at this stage. Retrospective review of 252 consecutive patients (269 eyes) examined within the first month of symptoms of exudative AMD. On FA, 97 eyes (36%) had classic CNV alone. Occult CNV associated with fibrovascular retinal pigment epithelium detachments (PEDs) was observed in 71 eyes (26%) and without fibrovascular PED in 101 eyes (38%). 91 eyes (34%) met the Macular Photocoagulation Study criteria for laser photocoagulation. 53 eyes (20%) met the Verteporfin In PDT (VIP) or Treatment of AMD with PDT (TAP) studies criteria. By ICG-A, occult CNV was visualised as focal spots in 49% of eyes examined within 15 days v 32% of eyes examined between 16 and 30 days after the onset of symptoms (p=0.07). 8.5% of late staining plaques disclosed in eyes examined within 15 days were combined with focal spots v 36% in eyes examined between 16 and 30 days (p<0.01). Early examination of eyes with exudative AMD would allow the treatment of 47% of eyes. 60% of eyes with subfoveal CNV would be eligible for PDT with verteporfin. Up to half of eyes with occult CNV would be converted by ICG-A into well delineated focal spots.


Climate change mitigation by coral reefs and seagrass beds at risk: How global change compromises coastal ecosystem services.
Seagrass meadows provide valuable ecosystem services of coastal protection and chemical habitat formation that could help mitigate the impact of sea level rise and ocean acidification. However, the intensification of hydrodynamic forces caused by sea level rise, in addition to habitat degradation threaten the provision of these ecosystem services. With quantitative field measurements of the coastal protection and chemical habitat formation services of seagrass meadows, we statistically model the relationships between hydrodynamic forces, vegetation density and the provision of these ecosystem services. Utilising a high-resolution hydrodynamic model that simulates end of the century hydrodynamic conditions and three scenarios of coral reef degradation (i.e., keep up, remain or loss) we quantify how the environmental conditions within a tropical bay will change given changes to the provision of ecosystem services. Our study shows that increasing hydrodynamic forces lead to a seafloor made up of a larger grain size that is increasingly unstable and more vulnerable to erosion. The loss of a fringing reef leads to larger hydrodynamic forces entering the bay, however, the 0.87 m increase in depth due to sea-level rise reduces the bed shear stress in shallower areas, which limits the change in the ecosystem services provided by the current benthic seagrass meadow. Loss of seagrass constitutes the greatest change in a bay ecosystem, resulting in the sediment surface where seagrass existed becoming unstable and the median sediment grain size increasing by 5-7 %. The loss of seagrass also leads to the disappearance of the unique fluctuating chemical habitat, which leaves the surrounding community vulnerable to ocean acidification. A reduction or complete loss of these ecosystem services would impact the entire community assemblage while also leaving the surrounding coastline vulnerable to erosion, thus exacerbating negative effects brought about by climate change.


Ultrasonography and Fine-Needle Aspiration in Indeterminate Thyroid Nodules: A Systematic Review of Diagnostic Test Accuracy.
Sonographic risk criteria may assist in further prognostication of indeterminate thyroid nodules (ITNs). Our aim was to determine whether sonographic criteria could further delineate the post-test probability of malignancy in ITNs. Meta-analysis of diagnostic test accuracy. A systematic review of Web of Science, MEDLINE, EMBASE, and CINAHL was performed from inception to April 15, 2021. Eligible studies included those which reported ultrasonographic evaluations with the American Thyroid Association (ATA) or the Thyroid Imaging Reporting and Data System (TIRADS) in adult patients with ITNs. ATA or TIRADS were scored as low (negative) or high (positive) malignancy risk using a previously validated binary classification. Primary outcomes included pooled sensitivity, specificity, likelihood ratios, and diagnostic odds ratio for all sonographic criteria. Studies were appraised using Quality Assessment of Diagnostic Accuracy Studies and the data were pooled using bivariate random-effects models. Seventeen studies were included in the analysis. For Bethesda III, ATA had a specificity (0.90, 95% confidence interval (CI): 0.74-0.94), but a sensitivity of 0.52 (95% CI: 0.25-0.77). Conversely, K-TIRADS had the highest sensitivity (0.78, 95% CI: 0.62-0.89) with a specificity of 0.53 (95% CI: 0.31-0.74). Furthermore, American College of Radiology and EU TIRADS had specificities of 0.60 (95% CI: 0.36-0.80) and 0.81 (95% CI: 0.73-0.87) with sensitivities of 0.70 (95% CI: 0.37-0.90) and 0.38 (95% CI: 0.20-0.60), respectively. There were few studies with Bethesda IV nodules. Though dependent on malignancy rates, Bethesda III nodules with low-suspicion TIRADS features may benefit from clinical observation, whereas nodules with high-suspicion ATA features may require molecular testing and/or surgery. NA Laryngoscope, 132:242-251, 2022.


Patient characteristics at hospital discharge and a comparison of home care referral decisions.
Describe the characteristics of hospitalized older adults who were not referred for home care, compare the referral decisions of hospital clinicians with those of nurses with expertise in discharge planning and transitional care, and compare the characteristics of hospitalized older adults who did not receive a home care referral with patients who did receive a home care referral. Secondary analysis, descriptive, case series. Subjects were discharged to home from one of two urban hospitals in Philadelphia, Pennsylvania. Ninety-nine patients for this study were drawn from the control group (n = 186) of a prior randomized clinical trial of advanced practice nurse hospital discharge planning and home follow-up. These 99 patients, or 56 of the control group, did not receive a home care referral even though they were screened into the original study as meeting at least one of the risk criteria associated with poor postdischarge outcomes. Case studies were generated from research records of the control group patients who did not receive a home care referral. They included patient sociodemographic and health characteristics. Nurses with expertise in discharge planning and transitional care, blinded to the actual decision, reviewed each case study and made a referral decision. Case studies revealed that control group patients, discharged without home follow-up, had many characteristics associated with the need for a home care referral, with the likelihood of receiving a referral, or with developing poor postdischarge outcomes. Overall, compared with control group patients who did not receive home care, those who did were older, had a longer hospital stay, more often rated their health as fair or poor, and had worse functional status. However, transitional care nurses judged that 96 of 99 of the control group patients discharged without home care had unmet discharge needs that may have benefited from a postdischarge referral. In addition, the transitional care nurses identified 49 of these 99 patients as having a high-priority need for home care. These patients had at least three of the characteristics associated with the need for a home care referral, the likelihood of receiving a referral, or of developing poor postdischarge outcomes. High-priority patients were significantly different in many sociodemographic and health characteristics and were rehospitalized significantly more often than other control group patients who were discharged without home care (P = .032). Study findings have demonstrated that the majority of older adults in this sample were discharged without postdischarge referrals despite the presence of several characteristics associated with the need for home care and risk of poor discharge outcomes. Findings suggest the need for improved methods to identify and synthesize patient characteristics associated with the need for postdischarge referral and to support clinical decision-making. Insurance or homebound status should also be explored as barriers to patients receiving the postdischarge care that they need.


Nitrogen and phosphate removal from wastewater with a mixed microalgae and bacteria culture.
Microalgae are able to convert nutrients (nitrogen and phosphorus) from wastewater into biomass and bio-products, thus improving the sustainability of wastewater treatment. In High Rate Algal Ponds (HRAP), biomass productivity and water treatment efficiency are highly dependent on environmental parameters such as temperature, light intensity and photoperiod. The influence of temperature and photoperiod on biomass productivity and the removal of dissolved nitrogen and phosphorus from municipal wastewater by a native microalgae-bacteria consortium was assessed in batch cultures in view of the development of an HRAP at a larger scale. Temperature affected the growth rate and microalgae biomass production as well as ammonium and phosphate removal rates. At the temperatures 15 and 25 °C, the average total nitrogen and phosphorus removal extents ranged from 72 to 83% and 100% respectively. Additionally 33.0 ± 0.1% of the total nitrogen was eliminated by stripping at 25 °C, and 50 ± 2% was assimilated by the microorganisms under all conditions tested.


[Measurement of skin temperature by means of crystalline fluids].
The use of cristalline fluids allows to gauge the changes of the superficial temperature by changing of the colour and to make them reproducible and visible. In a survey it is described as a new method of the measurement of the temperature of the skin.


Association Between Power Doppler Ultrasound Signals and Chronic Pain After Total Knee Arthroplasty: A Cross-Sectional Explorative Study.
Some patients experience chronic postsurgical pain (CPSP) after total knee arthroplasty (TKA) despite the absence of clinical or radiographic abnormalities. Postoperative synovitis as a cause of CPSP after TKA has received limited research attention. This study aimed to investigate the relationship between synovitis after TKA and CPSP. A total of 111 knees of 85 patients, with at least 1-year post-TKA follow-up, were assessed retrospectively and cross-sectionally. Power Doppler (PD) ultrasonography was used to detect the synovial hypervascularity associated with synovitis. The knee joint was divided into 15 areas, and PD signals were graded semi-quantitatively (0-3) in each area, the sum of which was defined as the total PD score. Clinical information regarding CPSP, including the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscales, was recorded. The relationship between pain and PD ultrasonography findings was accessed. Patients were divided into two groups (CPSP+ and CPSP- groups) based on pain severity. Clinical information, including PD ultrasonography findings and other possible causes, was compared between the groups. The WOMAC pain subscale was significantly correlated with the total PD score and maximum PD grade (r=0.3977, p<0.0001; r=0.2797, p=0.0029; respectively). The CPSP+ group had a significantly higher maximum PD grade and total PD score than the CPSP- group (median [interquartile range]: 2 [1, 2] vs 1 [1, 2], p=0.0001; 6 [2, 11] vs 2 [1, 4], p=0.0002; respectively). Multiple and logistic regression analyses showed that the total PD score was an independent factor for the WOMAC pain subscale (β=0.3822, 95% confidence interval [CI]=0.1460, 0.6184, p=0.00176) and CPSP (odds ratio=1.19, 95% CI=1.01, 1.41, p=0.0424). This study indicated a possible association between the total PD score and chronic pain after TKA; however, further studies are needed to corroborate these findings.


Ex vivo coronary angiography of a donor heart in the organ care system.
The international demand for donor hearts for transplantation is steadily increasing. Thus, longer transportation distances and explantation from sites with limited abilities for preexplantation diagnostics have to be considered. The development of the Organ Care System® (OCS) (TransMedics, Andover, MA, USA) may extend the extracorporeal period, with the possibility to constantly evaluate and interact during organ transport. One of the potential advantages of the OCS® is the ability to even perform coronary angiography of the donor heart, if a preexplantation angiography evaluation is not possible at the donor hospital and if significant evidence for coronary artery disease in the donor heart becomes known, because of the donor's medical history or after palpation of sclerotic coronary ostia. In this report, we present the first ex vivo coronary angiography evaluation of a potential donor heart that was performed in the OCS®. Upon explantation of the donor heart, sclerosis of the left coronary artery was palpated. After reaching the implantation site, a coronary angiography was performed by placing the OCS® on a catheterization table and inserting a 6F sheath into the access site of the OCS®. A 6F guide catheter was used to intubate the left coronary ostium. Injection of contrast agent led to strong contrast for visualization of the left coronary system. This procedure allowed sufficient assessment of the coronary arteries, which showed a slight diffuse sclerosis without any significant stenosis. This report demonstrates the advantage of the OCS® in the complex assessment of donor hearts after explantation. While the donor heart is still in the OCS®, not only is it possible to measure metabolic parameters and pressures, but even coronary angiography is feasible. With the increasing international demand for donor organs, such ex vivo examinations might play a more important role, because longer transportation distances can be accepted and organs from suboptimal donors without preexplantation diagnostics may be considered at donor sites with limited diagnostic options.


Flying ticks: anciently evolved associations that constitute a risk of infectious disease spread.
Ticks are important vectors of emerging zoonotic diseases affecting human and animal health worldwide. Ticks are often found on wild birds, which have been long recognized as a potential risk factor for dissemination of ticks and tick-borne pathogens (TBP), thus raising societal concerns and prompting research into their biology and ecology. To fully understand the role of birds in disseminating some ticks species and TBP, it is important to consider the evolutionary relationships between birds, ticks and transmitted pathogens. In this paper we reviewed the possible role of birds in the dissemination of TBP as a result of the evolution of host-tick-pathogen associations. Birds are central elements in the ecological networks of ticks, hosts and TBP. The study of host-tick-pathogen associations reveals a prominent role for birds in the dissemination of Borrelia spp. and Anaplasma phagocytophilum, with little contribution to the possible dissemination of other TBP. Birds have played a major role during tick evolution, which explains why they are by far the most important hosts supporting the ecological networks of ticks and several TBP. The immune response of birds to ticks and TBP has been largely overlooked. To implement effective measures for the control of tick-borne diseases, it is necessary to study bird-tick and bird-pathogen molecular interactions including the immune response of birds to tick infestation and pathogen infection.


A Lyapunov-Schmidt method for detecting backward bifurcation in age-structured population models.
Backward bifurcation is an important property of infectious disease models. A centre manifold method has been developed by Castillo-Chavez and Song for detecting the presence of backward bifurcation and deriving a necessary and sufficient condition for its occurrence in Ordinary Differential Equations (ODE) models. In this paper, we extend this method to partial differential equation systems. First, we state a main theorem. Next we illustrate the application of the new method on a chronological age-structured Susceptible-Infected-Susceptible (SIS) model with density-dependent recovery rate, an age-since-infection structured HIV/AIDS model with standard incidence and an age-since-infection structured cholera model with vaccination.


Effectiveness of Telemetry Guidelines in Predicting Clinically Significant Arrhythmias in Hospitalized Patients.
Cardiac rhythm monitoring is widely applied on hospitalized patients. However, its value has not been evaluated systematically. This study considered the utility of our institutional telemetry guidelines in predicting clinically significant arrhythmias. A retrospective analysis was performed of 562 patients admitted to the telemetry unit. A total of 1932 monitoring days were evaluated. Patients were divided into 2 groups based on telemetry guidelines: "telemetry indicated" and "telemetry not indicated". Differences in arrhythmia event rates and pre-defined clinical significance were determined. One hundred and forty-four (34%) vs. 16 (11%) patients had at least one arrhythmic event in the "telemetry indicated" group compared with the "telemetry not indicated" group, respectively (P = 0.001). No patient in the "telemetry not indicated" group had a clinically significant arrhythmia. In contrast, of patients in the "telemetry indicated" group who had at least one arrhythmic event, 36% were considered clinically significant (P < 0.05). In conclusion, this study validates and supports the use of our institutional telemetry guidelines to allocate this resource appropriately and predict clinically significant arrhythmias.


Systemic T Cell Subsets and Cytokines in Patients With Homozygous Sickle Cell Disease and Asymptomatic Urinary Tract Infections in Togo.
Background: In sickle cell disease (SCD), cytokine expression influences the pivotal pathways that contribute to disease pathogenesis. Additional infection could affect the immune profile of patients with SCD and increase disease mortality. The aim of this study was to investigate the cytokines and T helper cells profile in patients with asymptomatic urinary tract infection and homozygous SCD (HbSS). Methods: From July to September 2018, 22 HbSS subjects were recruited at Centre Hospitalier Universitaire Campus in Lomé, Togo, 12 of whom had urinary tract bacterial infections and 10 of whom were uninfected. Cytokines from plasma were measured by the enzyme-linked immunosorbent assay (ELISA) sandwich method, and immune cell profiles were performed by flow cytometry. The immunogenicity of bacteria-derived antigens isolated from the urine of HbSS subjects with asymptomatic urinary tract infections was studied in a cell culture system, and the induction of the cytokines was measured. Results: The mean age of HbSS subjects with urinary tract infections was 20.33 ± 3.58 years, and the male/female ratio was 0.09 (1:11). HbSS subjects with asymptomatic urinary tract infections had elevated plasma levels of interferon gamma (IFN-γ) and interleukin (IL)-10. CD4+Tbet+IFN-γ+ and CD4+FoxP3+IL-10+ T cell populations were decreased in HbSS subjects with asymptomatic urinary tract infections. Bacterial antigens from HbSS subjects induced the production of IL-10 but not IFN-γ in uninfected volunteer donors (HbAA). Conclusion: Our study demonstrated that patients with SCD and asymptomatic urinary tract infections had elevated IFN-γ and IL-10 levels. This chronic inflammatory condition could be a risk for this group of patients in terms of vaso-occlusive crisis. Systematic cytobacteriologic examination of the urine of HbSS subjects would be of interest.


Epigenetic regulation of neuronal cell specification inferred with single cell "Omics" data.
The brain is a highly complex organ consisting of numerous types of cells with ample diversity at the epigenetic level to achieve distinct gene expression profiles. During neuronal cell specification, transcription factors (TFs) form regulatory modules with chromatin remodeling proteins to initiate the cascade of epigenetic changes. Currently, little is known about brain epigenetic regulatory modules and how they regulate gene expression in a cell-type specific manner. To infer TFs involved in neuronal specification, we applied a recursive motif search approach on the differentially methylated regions identified from single-cell methylomes. The epigenetic transcription regulatory modules (ETRM), including EGR1 and MEF2C, were predicted and the co-expression of TFs in ETRMs were examined with RNA-seq data from single or sorted brain cells using a conditional probability matrix. Lastly, computational predications were validated with EGR1 ChIP-seq data. In addition, methylome and RNA-seq data generated from Egr1 knockout mice supported the essential role of EGR1 in brain epigenome programming, in particular for excitatory neurons. In summary, we demonstrated that brain single cell methylome and RNA-seq data can be integrated to gain a better understanding of how ETRMs control cell specification. The analytical pipeline implemented in this study is freely accessible in the Github repository (https://github.com/Gavin-Yinld/brain_TF).


Studies on the non-activated and activated forms of the estrogen receptor.
The activation of the steroid receptor is a necessary process for the biological role of the receptor. Many factors are involved in this mechanism; in addition to time, temperature, and salt concentration, RNA and RNAase can also affect the transformation of the non-activated to the activated form of the receptor. Using as a model the estrogen receptor of fetal uterus of guinea-pig, the studies of the interaction with three different monoclonal antibodies (D547, H222 and H226) reveal structural transformation during the process of the receptor activation. These conformational transformations suggest that a change in the exposure of the functional domains of the estrogen receptor occurs during activation.


Adiponectin and risk of coronary heart disease in older men and women.
Despite established insulin-sensitizing and antiatherogenic preclinical effects, epidemiological investigations of adiponectin have yielded conflicting findings, and its relationship with coronary heart disease (CHD) remains uncertain. Our objective was to investigate the relationship between adiponectin and CHD in older adults. This was a case-control study (n = 1386) nested within the population-based Cardiovascular Health Study from 1992--2001. Controls were frequency-matched to cases by age, sex, race, subclinical cardiovascular disease, and center. Incident CHD was defined as angina pectoris, percutaneous or surgical revascularization, nonfatal myocardial infarction (MI), or CHD death. A more restrictive CHD endpoint was limited to nonfatal MI and CHD death. Adiponectin exhibited significant negative correlations with baseline adiposity, insulin resistance, dyslipidemia, inflammatory markers, and leptin. After controlling for matching factors, adjustment for waist to hip ratio, hypertension, smoking, alcohol, low-density lipoprotein cholesterol, creatinine, and leptin revealed a modestly increased risk of incident CHD with adiponectin concentrations at the upper end [odds ratio = 1.37 (quintile 5 vs. 1-4), 95% confidence interval 1.02-1.84]. This association was stronger when the outcome was limited to nonfatal MI and fatal CHD (odds ratio = 1.69, 95% confidence interval 1.23-2.32). The findings were not influenced by additional adjustment for weight change, health status, or cystatin C, nor were they abolished by adjustment for potential mediators. This study shows an association between adiponectin and increased risk of first-ever CHD in older adults. Further research is needed to elucidate the basis for the concurrent beneficial and detrimental aspects of this relationship, and under what circumstances one or the other may predominate.


Diagrams benefit symbolic problem-solving.
The format of a mathematics problem often influences students' problem-solving performance. For example, providing diagrams in conjunction with story problems can benefit students' understanding, choice of strategy, and accuracy on story problems. However, it remains unclear whether providing diagrams in conjunction with symbolic equations can benefit problem-solving performance as well. We tested the impact of diagram presence on students' performance on algebra equation problems to determine whether diagrams increase problem-solving success. We also examined the influence of item- and student-level factors to test the robustness of the diagram effect. We worked with 61 seventh-grade students who had received 2 months of pre-algebra instruction. Students participated in an experimenter-led classroom session. Using a within-subjects design, students solved algebra problems in two matched formats (equation and equation-with-diagram). The presence of diagrams increased equation-solving accuracy and the use of informal strategies. This diagram benefit was independent of student ability and item complexity. The benefits of diagrams found previously for story problems generalized to symbolic problems. The findings are consistent with cognitive models of problem-solving and suggest that diagrams may be a useful additional representation of symbolic problems.


A Retrospective Study of Risk Factors for Symptomatic Anastomotic Leakage after Laparoscopic Anterior Resection of the Rectal Cancer without a Diverting Stoma.
Anastomotic leakage (AL) is a common and devastating postoperative issue for patients who have undergone anterior resection of rectal carcinoma and can lead to increased short-term morbidity and mortality. Moreover, it might be associated with a worse oncological prognosis of tumors. This study is aimed at exploring the risk factors for symptomatic AL after laparoscopic anterior resection (LAR) for rectal tumors without a preventive diverting stoma. This case control study retrospectively reviewed the data of 496 consecutive patients who underwent LAR of the rectum without a preventive diverting stoma at the Cancer Hospital, Chinese Academy of Medical Sciences between September 2016 and September 2017. All patients were divided into an AL group and a control group based on the occurrence of postoperative symptomatic AL. Factors regarding patient-related variables, operation-related variables, and tumor-related variables were collected and assessed between the two groups through univariate and multivariate logistic regression analyses to identify independent risk factors for AL. In total, 18 (3.6%) patients developed postoperative symptomatic AL. Univariate analysis showed that a synchronous primary malignancy of the left hemicolon (P = 0.047), intraoperative chemotherapy (P = 0.003), and level of anastomosis (P = 0.033) were significantly related with AL. Multivariate analysis was subsequently performed to adjust for confounding biases and confirmed that a synchronous primary malignancy of the left hemicolon (odds ratio (OR), 12.225; 95% confidence interval (CI), 1.764-84.702; P = 0.011), intraoperative chemotherapy (OR, 3.931; 95% CI, 1.334-11.583; P = 0.013), and level of anastomosis (OR, 3.224; 95% CI, 1.124-9.249; P = 0.030) were independent risk factors for symptomatic AL for patients who received LAR for rectal neoplasms without a preventive diverting stoma. Synchronous primary malignancy of the left hemicolon, intraoperative chemotherapy, and a low anastomotic level can increase the risks of postoperative symptomatic AL after LAR of the rectum without a protective diverting stoma.


Effects of Age, Sex, and Comedication on the Plasma Concentrations of Olanzapine in Chinese Patients With Schizophrenia Based on Therapeutic Drug Monitoring Data.
Olanzapine (OLA) is an atypical second-generation antipsychotic that exhibits significant pharmacokinetic variability. We retrospectively investigated the effects of age, sex, and specific comedications on OLA pharmacokinetics in Chinese patients with schizophrenia. Data on sex, age, and OLA dosage and steady-state plasma concentrations of 386 patients with schizophrenia (who have received OLA or a comedication of OLA with a psychotherapeutic drug) were collected and analyzed. The combined effects of dosage, age, sex, and comedication on OLA plasma levels were assessed via multiple linear regression analyses. A daily dose of OLA was positively correlated with the drug's plasma concentrations. Overall, the OLA plasma concentrations and concentration-to-dose ratio (C/D) of the studied patients varied by 53.6- and 64.1-fold, achieving median values of 42.7 ng/mL and 2.73 (ng/mL)/(mg/d), respectively. Furthermore, a 1.27-fold higher estimated C/D in patients 60 years or older than in those younger than 60 years was identified. Female patients demonstrated a 33.6% higher C/D than in male patients. When coadministered with mood stabilizers (valproate or lithium), the median OLA C/D was 24.1% to 26.1% lower than that of OLA monotherapy. Interestingly, the OLA plasma concentration and C/D were not significantly affected by a comedication with aripiprazole, haloperidol, amisulpride, risperidone, clozapine, ziprasidone, citalopram, or buspirone. The administered drug's dose was identified as an important determinant of the achieved OLA plasma concentration, with a positive correlation. The patients' sex and valproate (or lithium) comedication can significantly affect the C/D of OLA. Therapeutic drug monitoring should be routinely applied in cases of OLA-receiving patients with schizophrenia.


Translating a multifactorial fall prevention intervention into practice: a controlled evaluation of a fall prevention clinic.
Although multifactorial fall prevention interventions have been shown to reduce falls and injurious falls, their translation into clinical settings has been limited. This article describes a hospital-based fall prevention clinic established to increase availability of preventive care for falls. Outcomes for 43 adults aged 65 and older seen during the clinic's first 6 months of operation were compared with outcomes for 86 age-, sex-, and race-matched controls; all persons included in analyses received primary care at the hospital's geriatrics clinic. Nonsignificant differences in falls, injurious falls, and fall-related healthcare use according to study group in multivariate adjusted models were observed, probably because of the small, fixed sample size. The percentage experiencing any injurious falls during the follow-up period was comparable for fall clinic visitors and controls (14% vs 13%), despite a dramatic difference at baseline (42% of clinic visitors vs 15% of controls). Fall-related healthcare use was higher for clinic visitors during the baseline period (21%, vs 12% for controls) and decreased slightly (to 19%) during follow-up; differences in fall-related healthcare use according to study group from baseline to follow-up were nonsignificant. These findings, although preliminary because of the small sample size and the baseline difference between the groups in fall rates, suggest that being seen in a fall prevention clinic may reduce injurious falls. Additional studies will be necessary to conclusively determine the effects of multifactorial fall risk assessment and management delivered by midlevel providers working in real-world clinical practice settings on key outcomes, including injurious falls, downstream fall-related healthcare use, and costs.


Tough doughnuts: affect and the modulation of attention.
Positive affect has been associated with improvement in performance in various attentional domains. Negative affect has been associated with narrowing of attention and lowering of performance in attentional tasks. Previous behavioral studies have put forth the diffuse mental state idea as the mechanism of these effects, where attentional resources are more evenly distributed during positive affect and more focused during negative affect. To explore neural correlates of this mechanism, a two-stream rapid serial visual presentation (RSVP) paradigm with centrally presented, overlapping streams was used. Participants attended one of the streams at a time and steady-state visual evoked potentials (ssVEP) in response to the attended and unattended streams were recorded in a positive, negative or neutral affect state. We predicted that in the positive affect condition, ssVEP responses to the attended and the unattended stream would be more alike than in a neutral condition. In the negative affect condition, as an expression of a less diffuse mental state, ssVEP responses were predicted to be more dissimilar. Self-assessments confirmed the effectiveness of the emotional manipulation. In the negative affect condition power was found to be higher than in the neutral condition. However, the modulations in the ssVEP did not reflect the predicted neural correlate of the diffuse mental state mechanism. Thus, the results provide evidence for negative affect modulating attention but suggest that the diffuse mental state is not a spatially oriented phenomenon.


Refractory Evans syndrome after autologous stem cell transplantation for multiple myeloma: management with a second transplantation.
The development of autoimmune disease after autologous stem cell transplantation (ASCT) is very rare in multiple myeloma (MM). We describe the first case of Evans syndrome after ASCT for MM. A 60-year-old man with MM received ASCT and subsequently developed Evans syndrome following two febrile episodes. The syndrome was refractory to conventional therapies but it was managed with a second ASCT. This unique complication was thought to have been triggered by an infection during the recovery of the immune system. We assumed that reconstructing the immune system via ASCT might eliminate infection-induced autoantibodies to platelets and erythrocytes.


Effects on MC3T3-E1 Cells and In silico Toxicological Study of Two 6-(Propan-2-yl)-4-methyl-morpholine-2,5-diones.
Recently, we found that two cyclodidepsipeptides, 3,6-di-(propan-2-yl)-4-methyl-morpholine-2,5-dione (1) and 3-(2-methylpropyl)-6-(propan-2-yl)-4-methyl- morpholine-2,5-dione (2), are excellent inhibitors of xanthine oxidase. In order to obtain more information about the toxicological potential of compounds 1 and 2 on bone cells, the current study was designed to evaluate the effect of these compounds on viability and proliferation of MC3T3-E1 cells. Compound 1 showed neither cytotoxic nor stimulatory effect on cell viability, while compound 2 showed a slight stimulatory effect on cell viability. Both studied compounds showed slight stimulatory effects on proliferation of MC3T3-E1 cells, in a dose dependent manner. Additionally, an in silico toxicological study of compounds 1 and 2 was performed, and the results indicate that they have a good probability of safe biological intake.


Probing charge transport in oxidatively damaged DNA sequences under the influence of structural fluctuations.
We present a detailed study of the charge transport characteristics of double-stranded DNA oligomers including the oxidative damage 7,8-dihydro-8-oxoguanine (8-oxoG). The problem is treated by a hybrid methodology combining classical molecular dynamics simulations and semiempirical electronic structure calculations to formulate a coarse-grained charge transport model. The influence of solvent- and DNA-mediated structural fluctuations is encoded in the obtained time series of the electronic charge transfer parameters. Within the Landauer approach to charge transport, we perform a detailed analysis of the conductance and current time series obtained by sampling the electronic structure along the molecular dynamics trajectory, and find that the inclusion of 8-oxoG damages into the DNA sequence can induce a change in the electrical response of the system. However, solvent-induced fluctuations tend to mask the effect, so that a detection of such sequence modifications via electrical transport measurements in a liquid environment seems to be difficult to achieve.


Reduced CO2-elimination during combined high-frequency ventilation compared to conventional pressure-controlled ventilation in surfactant-deficient piglets.
Combined high-frequency ventilation (CHFV) combines a conventional low-frequency component with super-imposed high-frequency jet pulses. The intention is to overcome the limited CO2-elimination of high-frequency ventilation, and to decrease airway pressures and enhance hemodynamic performance by reducing the conventional component. The present study was performed to compare the effects of conventional continuous positive-pressure ventilation (CPPV) on gas exchange, airway pressures and cardiac output to those of CHFV at matched minute volume (MV) and mean airway pressure (MPAW). Sixteen anaesthetised piglets with lavage-induced surfactant deficiency were ventilated with CPPV, with positive end-expiratory pressure (PEEP) set to obliterate the lower inflection point of the inspiratory pressure-volume loop. This setting was compared to CHFV during which 50% of the total MV was applied as superimposed jet pulses of 20 Hz at otherwise unchanged settings, and to CPPV at a PEEP level which was reduced (CPPVred) until MPAW matched MPAW during CHFV. Gas exchange, airway pressures and hemodynamics were measured after the ventilatory setting had been applied for 20 min. MPAW decreased from (median) 2.7 kPa with CPPV to 2.4 kPa with CHFV (P < or = 0.05). Peak inspiratory pressure was 3.6 kPa with CPPV, 3.2 kPa with CHFV, and 3.2 kPa with CPPVred (P < or = 0.05 for differences to CPPV), respectively. PaCO2 was comparable during CPPV (5.9 kPa), CPPVred and CHFVCO2, while it increased during CHFV (6.8 kPa, (P < or = 0.05)). Cardiac output did not differ significantly between the settings. In the porcine lavage model, CO2-elimination is reduced during CHFV compared to CPPV at matched minute volume. At matched mean airway pressure, CHFV fails to reduce peak inspiratory airway pressure and to improve hemodynamic performance compared to CPPV.


Wu-Tou Decoction Inhibits Angiogenesis in Experimental Arthritis by Targeting VEGFR2 Signaling Pathway.
Wu-tou decoction (WTD) is a classic traditional Chinese medicine formula and has been extensively used for the treatment of rheumatoid arthritis (RA). Previous reports indicate that WTD possesses anti-inflammatory and antinociceptive activities, and inhibits the development of arthritic joints and disease severity of collagen-induced arthritis (CIA) or adjuvant-induced rats; however, its action on angiogenesis of RA has not been clarified. This study aims to determine the anti-angiogenic activity of WTD in CIA rats and in various angiogenesis models. Our data showed that WTD (0.95, 1.9, and 3.8 g/kg) markedly reduced the immature blood vessels in synovial membrane tissues of inflamed joints from CIA rats. It also inhibited in vivo angiogenesis in chick embryo and VEGF165-induced microvessel sprout formation ex vivo. Meanwhile, WTD suppressed VEGF165-/MH7A-induced migration, invasion, adhesion, and tube formation of human umbilical vein endothelial cells (HUVECs). Moreover, WTD significantly reduced the expression of angiogenic activators, including vascular endothelial growth factor (VEGF), VEGFR2, interleukin (IL)-1β, IL-17, transforming growth factor-β, platelet-derived growth factor, placenta growth factor, angiopoietin (Ang) I and Ang II in synovium of CIA rats, and/or in HUVECs. More interestingly, WTD blocked the autophosphorylation of VEGF165-induced VEGFR2 and consequently downregulated the signaling pathways of activated AKT, ERK1/2, JNK, and p38 in VEGF165-induced HUVECs. These findings suggest for the first time that WTD possesses the anti-angiogenic effect in RA in vivo, ex vivo, and in vitro by interrupting the targeting of VEGFR2 activation.


Synthesis and Characterization of Amphiphilic Diblock Polyphosphoesters Containing Lactic Acid Units for Potential Drug Delivery Applications.
Multistep one-pot polycondensation reactions synthesized amphiphilic diblock polyphosphoesters containing lactic acid units in the polymer backbone. At the first step was synthesized poly[poly(ethylene glycol) H-phosphonate-b-poly(ethylene glycol)lactate H-phosphonate] was converted through one pot oxidation into poly[alkylpoly(ethylene glycol) phosphate-b-alkylpoly(ethylene glycol)lactate phosphate]s. They were characterized by 1H, 13C {H},31P NMR, and size exclusion chromatography (SEC). The effects of the polymer composition on micelle formation and stability, and micelle size were studied via dynamic light scattering (DLS). The hydrophilic/hydrophobic balance of these polymers can be controlled by changing the chain lengths of hydrophobic alcohols. Drug loading and encapsulation efficiency tests using Sudan III and doxorubicin revealed that hydrophobic substances can be incorporated inside the hydrophobic core of polymer micelles. The micelle size was 72-108 nm when encapsulating Sudan III and 89-116 nm when encapsulating doxorubicin. Loading capacity and encapsulation efficiency depend on the length of alkyl side chains. Changing the alkyl side chain from 8 to 16 carbon atoms increased micelle-encapsulated Sudan III and doxorubicin by 1.6- and 1.1-fold, respectively. The results obtained indicate that these diblock copolymers have the potential as drug carriers.


Child physical abuse: prevalence, characteristics, predictors, and beliefs about parent-child violence in South Asian, Middle Eastern, East Asian, and Latina women in the United States.
The present study examined the prevalence, characteristics, beliefs, and demographic predictors of parent-child physical violence among South Asian, Middle Eastern, East Asian, and Latina women in the United States. Two hundred fifty-one college-educated women from a middle to high SES (South Asian/Middle Eastern, n = 93; East Asian,n = 72; Latina,n = 86) completed a self-report survey on childhood experiences and beliefs regarding physical abuse. Seventy-three percent of the South Asian and Middle Eastern sample, 65% of the East Asian sample, and 78% of the Latina sample reported experiencing at least one type of physical abuse. Significant differences in characteristics and perpetrators of abuse were found across groups. Demographic factors did not predict physical abuse. Experiencing physical abuse was the only predictor for acceptance of physical discipline and as a parental privilege or right across groups. Implications of alternate cultural models of family violence based on beliefs and exposure to violence are discussed.


A genetic rat model of cholinergic hypersensitivity: implications for chemical intolerance, chronic fatigue, and asthma.
The fact that only some individuals exposed to environmental chemicals develop chemical intolerance raises the possibility that genetic factors could be contributing factors. The present communication summarizes evidence from a genetic animal model of cholinergic supersensitivity that suggests that an abnormal cholinergic system could be one predisposing genetic factor. The Flinders Sensitive Line (FSL) rats were established by selective breeding for increased responses to an organophosphate. It was subsequently found that these FSL rats were also more sensitive to direct-acting muscarinic agonists and had elevated muscarinic receptors compared to the selectively bred parallel group, the Flinders Resistant Line (FRL) rats, or randomly bred control rats. Increased sensitivity to cholinergic agents has also been observed in several human populations, including individuals suffering from chemical intolerance. Indeed, the FSL rats exhibit certain behavioral characteristics such as abnormal sleep, activity, and appetite that are similar to those reported in these human populations. In addition, the FSL rats have been reported to exhibit increased sensitivity to a variety of other chemical agents. Peripheral tissues, such as intestinal and airway smooth muscle, appear to be more sensitive to both cholinergic agonists and an antigen, ovalbumin. Hypothermia, a centrally mediated response, is more pronounced in the FSL rats after nicotine and alcohol, as well as agents that are selective for the dopaminergic and serotonergic systems. In some cases, the increased sensitivity has been detected in the absence of any changes in the receptors with which the drugs interact (dopamine receptors), while receptor changes have been seen in other cases (nicotine receptors). Therefore, there may be multiple mechanisms underlying the multiple chemical sensitivity-chemical intolerance of the FSL rats. An elucidation of these mechanisms may provide useful clues to those involved in chemical intolerance in humans.


Escin enhanced the efficacy of sorafenib by autophagy-mediated apoptosis in lung cancer cells.
Combining anti-cancer drugs has been exploited as promising treatment strategy to target lung cancer. Synergistic chemotherapies increase anti-cancer effect and reduce effective drug doses and side effects. In this study, therapeutic potential of escin in combination with sorafenib has been explored. 3-(4,5-Dimethylthiazol-2-yl)-2 5-diphenyltetrazolium bromide assay was used to calculate IC50 values. The synergy was evaluated using Chou-Talaly algorithm. Cellular reactive oxygen species, mitochondrial membrane potential, annexin V, and cell-cycle studies were done by flow-cytometer, and autophagy biomarkers expression were determined using western blotting. Moreover, autophagy was knocked down using ATG5 siRNA to confirm its role, diethylnitrosamine-induced lung cancer model was used to check the synergy of sorafenib/escin. Escin significantly reduced the IC50 of sorafenib in A549 and NCIH460 cells. The combination of sorafenib/escin produced a 2.95 and 5.45 dose reduction index for sorafenib in A549 and NCI-H460 cells. The combination of over-expressed p62 and LC3-II reflects autophagy block-mediated late apoptosis. This phenomenon was reconfirmed by ATG5 knockdown. This combination also selectively targeted G0/G1 phase of cancer cells. In in vivo study, the combination reduced tumour load and lower elevated serum biochemical parameters. The combination of sorafenib/escin synergistically inhibits autophagy to induce late apoptosis in lung cancer cells' G0/G1 phase.


Evaluation of interthalamic adhesion size as an indicator of brain atrophy in dogs with and without cognitive dysfunction.
Interthalamic adhesion thickness has been previously described as a parameter for quantifying canine brain atrophy and hypothesized to correlate with brain height or ventricular size. However, studies testing this hypothesis are lacking. This retrospective cross-sectional study aimed to compare interthalamic adhesion thickness, interthalamic adhesion thickness/brain height ratio, and interthalamic adhesion thickness/brain height ratio/lateral ventricle to brain height ratio values in dogs with and without cognitive dysfunction. Medical records for dogs meeting the following inclusion criteria were retrieved from two hospitals: available brain magnetic resonance imaging (MRI) or computed tomography (CT) studies, no cerebral parenchymal lesions, and no prior neurological treatment. For each included dog, values of interthalamic adhesion thickness, interthalamic adhesion thickness/brain height ratio, and interthalamic adhesion thickness/brain height ratio/lateral ventricle to brain height ratio were measured by one observer from transverse CT or MRI images and a consensus was reached. A total of 113 dogs met inclusion criteria. Dogs were divided into three groups based on the following criteria: Young group (no cognitive dysfunction, <9-year-old, n = 43), Aging group (no cognitive dysfunction, ≥9-year-old, n = 61), and Dementia group (n = 9). All three parameters were significantly lower in the dementia group than in the Young and Aging groups. In the Young and Aging groups, there was significant negative correlation of all three parameters with age and positive correlation of interthalamic adhesion thickness and interthalamic adhesion thickness/brain height ratio/lateral ventricle to brain height ratio with body weight, while there was no correlation of interthalamic adhesion thickness/brain height ratio with body weight (P < 0.05). There were no differences in all three parameters according to skull type or gender. Findings from the current study supported the use of interthalamic adhesion thickness, interthalamic adhesion thickness/brain height ratio, and interthalamic adhesion thickness/brain height ratio/lateral ventricle to brain height ratio for quantifying brain atrophy in dogs with cognitive dysfunction.


Ethylisocyanide equilibria of hemoglobins M Iwate, M Boston, M Hyde Park, M Saskatoon, and M Milwaukee-I in half-ferric and fully reduced states.
The ethylisocyanide equilibria of all the five known hemoglobins M, namely Hb M Iwate (alpha287 Tyrbeta2), Hb M Boston (alpha258 Tyrbeta2), Hb M Hyde Park (alpha2beta292 Tyr), Hb M Saskatoon (alpha2beta263 tyr), and Hb M Milwaukee-I (alpha2beta267 Glu), were studied both in the half-ferric and fully reduced heme states. In the half-ferric state, no heme-heme interaction was observed for Hb M Iwate, Hb M Boston, and Hb M Hyde Park, but Hb M Saskatoon and Hb M Milwaukee-I show small but definite heme-heme interaction with Hill's n of 1.3. The beta chain mutants, Hb M Hyde Park and Hb M Saskatoon, have almost normal affinity for ethylisocyanide and a normal Bohr effect, whereas the alpha chain mutants, Hb M Iwate and Hb M Boston, have abnormally low affinity and almost no Bohr effect. Hb M Milwaukee-I showed a large Bohr effect and low affinity. These results are consistent qualitatively with those on oxygen equilibria reported previously. In the fully reduced state, in which all four hemes were in the ferrous state and capable of binding ethylisocyanide distinct differences were found in the extent of heme-heme interaction. Namely, the n values for proximal histidine mutants, Hb M Iwate and Hb M Hyde Park, were 1.1 and 1.0, respectively, whereas the distal histidine mutants, Hb M Boston and Hb M Saskatoon, showed high n values of 2.4 and 1.6, respectively. Hb M Milwaukee-I also exhibited a high n value of 2.0 The ethylisocyanide affinity of the four histidine mutants was high compared with that of Hb A, while that for Hb M Milwaukee-I was almost normal. All five Hbs M had approximately normal magnitudes of Bohr effect. In the half-ferric state, the proximal and distal histidine mutants of the same chain showed similar affinity for ethylisocyanide and Bohr effect, rather different from those of the mutants of the opposite chain. These differences seem to be derived from the difference of abnormal bonding of ferric iron to tyrosine or glutamic acid. On the other hand, the reduction of iron, which abolished the abnormal bonding and made all of the chains capable of binding ligand, extinguished the differences of alpha and beta chains, and the effect of amino acid side chains close to iron on ligand binding properties became clear. Proximal histidine, which is considered to trigger the transition between the T and R states, seems to be essential to the heme-heme interaction.


Incidental mood state before dissonance induction affects attitude change.
The way that incidental affect impacts attitude change brought about by controlled processes has so far been examined when the incidental affective state is generated after dissonance state induction. We therefore investigated attitude change when the incidental mood occurs prior to dissonance state induction. We expected a negative mood to induce systematic processing, and a positive mood to induce heuristic processing. Given that both systematic processing and attitude change are cognitively costly, we expected participants who experienced the dissonance state in a negative mood to have insufficient resources to allocate to attitude change. In our experiment, after mood induction (negative, neutral or positive), participants were divided into low-dissonance and high-dissonance groups. They then wrote a counterattitudinal essay. Analysis of their attitudes towards the essay topic indicated that attitude change did not occur in the negative incidental mood condition. Moreover, written productivity-one indicator of cognitive resource allocation-varied according to the type of incidental mood, and only predicted attitude change in the high-dissonance group. Our results suggest that incidental mood before dissonance induction influences the style of information processing and, by so doing, affects the extent of attitude change.


Calcium dependence of spontaneous neurotransmitter release.
Spontaneous release of neurotransmitters is regulated by extracellular [Ca2+ ] and intracellular [Ca2+ ]. Curiously, some of the mechanisms of Ca2+ signaling at central synapses are different at excitatory and inhibitory synapses. While the stochastic activity of voltage-activated Ca2+ channels triggers a majority of spontaneous release at inhibitory synapses, this is not the case at excitatory nerve terminals. Ca2+ release from intracellular stores regulates spontaneous release at excitatory and inhibitory terminals, as do agonists of the Ca2+ -sensing receptor. Molecular machinery triggering spontaneous vesicle fusion may differ from that underlying evoked release and may be one of the sources of heterogeneity in release mechanisms.


Non-invasive in vivo imaging for liver tumour progression using an orthotopic hepatocellular carcinoma model in immunocompetent mice.
Maintenance of complex transgenic colonies and labour-intensive techniques pose significant challenges in work involving mouse models for hepatocellular carcinoma (HCC). Other animal models of unusual species are generally impractical for research purposes. To develop a highly reproducible orthotopic mouse model for HCC based on the murine α-foetoprotein (AFP), producing cell line Hepa1-6 and to monitor liver tumour progression via in vivo imaging, and measurement of plasma AFP. Intrahepatic tumour was induced following subcapsular implantation of 10(+6) Hepa1-6 cells into C57L/J mice. AFP production was examined in vitro and in vivo using immunoblotting. Three confirmatory non-invasive imaging modalities were applied to follow tumour progression over time including ultrasound biomicroscopy (UBM), micromagnetic resonance imaging (microMRI), and bioluminescence. α-foetoprotein expression was confirmed both in vitro and in vivo, with increasing levels in the plasma as tumours progressed. UBM, microMRI and bioluminescence detected intrahepatic tumours to a 2 mm resolution by day 14. Sequential imaging studies demonstrated an intrahepatic pattern of disease progression with an observed median survival of 29 days. Immunosuppression of tumour-bearing mice led to a greater tumour size and decreased survival. Intrahepatic implantation of Hepa1-6 as a mouse model for HCC is a highly reproducible in vivo system with tumour biology analogous to human disease and is regulated by the presence of an intact host immune system. Tumour progression may be monitored in vivo by UBM, microMRI and bioluminescence. Plasma AFP increases over time, allowing redundancy in non-invasive means of following tumour progression.


Real-time monitoring for bioaerosols--flow cytometry.
Bioaerosol detection in real time is an urgent civilian and military requirement. In this article, bioaerosol mass spectrometry, an instrument for real-time detection of bioaerosols using simultaneous measurement of particle aerodynamic size and intrinsic fluorescence, real-time qPCR, and FCM/FL were discussed. Although, challenging work remains to determine the interfering substances (e.g. particulates) of different environments, distinguish the specific species with specific probe, and overcome the high detection limit of FCM (10(4)-10(8) cells ml(-1)), literature reports suggested that FCM/FL has a great potential for real-time monitoring of bioaerosols.


Instrumental variables in the evaluation of diagnostic test procedures when the true disease state is unknown.
We explore the estimation of sensitivity and specificity of diagnostic tests when the true disease state is unknown. Instrumental variables which subdivide the patient population are used. A logistic model, relating these instrumental variables to the (unknown) true disease state is proposed. It is shown that this procedure allows the goodness-of-fit to the resulting model to be tested.


[Association of vitamin D receptor Fok I and Bsm I polymorphisms with dyslipidemias in elderly male patients with type 2 diabetes].
To assess the association of vitamin D receptor (VDR) gene Fok I and Bsm I polymorphisms with dyslipidemia in elderly male patients with type 2 diabetes of Han nationality. A total of 328 elderly male residents of Han nationality in Beijing, including 237 type 2 diabetic patients and 91 healthy control subjects, were enrolled in this study. The diabetic patients were divided into non-dyslipidemia group (DO group, n=134) and dyslipidemia group (DH group, n=103). All the participants were genotyped for Fok I and Bsm I polymorphisms in VDR gene using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing technology, and the results were compared with their clinical characteristics. For Fok I, the frequency of F allele was significantly higher in the diabetic patients than in the control group (Χ(2)=3.873, P=0.049, OR=1.439, 95% CI: 1.001-2.071). In the dominant model, the frequency of FF genotype was significantly higher in the diabetic group (Χ(2)=5.057, P=0.025, OR=1.756, 95% CI: 1.072-2.875) as well as in DH group (Χ(2)=6.168, P=0.013, OR=2.06, 95% CI: 1.161-3.663) than in the control group. There was no significant differences in the genotype frequency or allele distribution in other paired groups (P>0.05). Compared with Ff + ff genotype, FF genotype was associated with a significantly decreased average diastolic blood pressure (P=0.039) but significantly increased postprandial blood glucose (P=0.035), triglycerides (P=0.049) and uric acid (P=0.031). No significant difference was detected in genotype frequency or allele distribution of Bsm I polymorphisms between the groups (P>0.05); serum creatinine levels were significantly higher in bb genotype than in BB + Bb genotype group (P=0.011). VDR gene Fok I polymorphisms may be a risk factor for dyslipidemia in elderly male patients with type 2 diabetes among Chinese Han population, where Bsm I polymorphisms are not associated with diabetic dyslipdiemia.


Prenatal detection of neural tube defects. VI. Experience with 20,000 pregnancies.
Neural tube defects (NTDs) are among the most common major congenital malformations in the United States. Prenatal detection is possible in about 95% of cases by assaying amniotic fluid for alpha-fetoprotein (AFP), which leaks from open lesions. In 20,000 pregnancies, 334 (1.7%) had a raised level of AFP. Of these, 136 (40.7%) had open NTDs, 90 (26.9%) had other fetal defects or conditions, and 108 (32.3%) almost invariably had admixed fetal blood. Pregnancy was electively terminated in 11 cases in which the AFP concentration was thought to be elevated but in which the fetus was apparently normal (0.06%), but in only two of these cases was there no explanation for the raised level of AFP. The practical false-positive rate was considerably below 0.06%. Patients at risk for bearing children with NTDs should be counseled and offered prenatal diagnosis.


Hypervigilance in patients with obsessive-compulsive disorder.
The hypothesis that patients with obsessive-compulsive disorder (OCD) suffer from hypervigilant attention was investigated via explicit memory (incidental recall and recognition) and priming (reading speed) measures. OCD patients did not differ from normal controls on explicit measures of memory; specifically, recognition of unusual words (experiment 1) and recall and recognition of words and feature-specific information (experiment 2). Although both normal controls and OCD patients showed priming, the pattern of priming differed for the two groups (experiment 2). Specifically, patients with OCD failed to show feature-specific priming, suggesting they may have attended more focally on the priming task than did normal controls. These findings support previous reports of normal performance in OCD on explicit memory tasks, but suggest more sensitive measures may reflect differences in processing information.


In-vitro and In-vivo Hypolipidemic Activity of Spinach Roots and Flowers.
This study was designed in order to correlate the flavonoid and lipoidal matters content of Spinach roots and flowers to their hypolipidemic potential. The total flavonoid content was measured via complexation with aluminum chloride while determination of fatty acids methyl esters and unsaponifiable matters in both organs was performed using GC/MS. In an in-vitro study, the crude ethanol extracts of both organs and their different fractions were separately examined for inhibition of β-hydroxy-β-methyl glutaryl coenzyme A reductase (HMG-CoA reductase); the rate limiting enzyme of cholesterol biosynthesis. The percentage inhibition of alcohol extracts of roots and flowers were 78.19% and 72.68% respectively when compared to the control. The crude alcohol extracts of both organs were further examined in-vivo. Results showed that both extracts improved the investigated parameters by variable degrees compared to fenofibrate reference drug. The root extract showed significant improvement of TC, HDL-C, LDL-C, TG and total lipids (52.75, 209.85, 21.84, 49.26 and 29.62% respectively) when compared to hypercholesterolemic rats. The histopathological picture of liver showed a noticeable amelioration after treatment with root extract. The flavonoid content was higher in flower than root (983.4 and 300.2 mg/kg respectively) while the percentage of sterols and triterpenes in roots was greater than flowers (22.47% and 17.02 % respectively). In conclusion, the root ethanolic extract recorded more potent activity than flower as hypolipidemic agent either in-vitro or in-vivo examination which was more correlated to the sterol content than to the flavonoid content.


Induction of ultra-morphological features of apoptosis in mature and immature sperm.
There is a fundamental body of evidence suggesting that activated apoptosis signaling in ejaculated human sperm negatively influences their fertilization potential. However, it is still controversial whether this apoptotic signaling is a relic of an abortive apoptosis related to spermatogenesis or if it should be regarded as a functional preformed pathway in mature sperm leading to stereotypical morphological changes reflecting nuclear disassembly. To address this question, apoptosis was induced using betulinic acid in mature and immature ejaculated human sperm enriched by density gradient centrifugation. Execution of apoptosis was monitored by observing ultra-morphological changes via transmission electron microscopy. Typical morphological signs of apoptosis in somatic cells include plasma membrane blebbing with the formation of apoptotic bodies, impaired mitochondrial integrity, defects of the nuclear envelope, and nuclear fragmentation; these morphologies have also been observed in human sperm. In addition, these apoptotic characteristics were more frequent in immature sperm compared to mature sperm. Following betulinic acid treatment, apoptosis-related morphological changes were induced in mature sperm from healthy donors. This effect was much less pronounced in immature sperm. Moreover, in both fractions, the betulinic acid treatment increased the percentage of acrosome-reacted sperm. The results of our ultra-morphological study prove the functional competence of apoptosis in mature ejaculated human sperm. The theory of a sole abortive process may be valid only for immature sperm. The induction of the acrosome reaction by stimulating apoptosis might shed light on the biological relevance of sperm apoptosis.


Attachment representations in sexually abused preschoolers: a comparative study.
Attachment theory provides a relevant framework for understanding the psychosocial adjustment of victims of child sexual abuse (CSA). However, most studies have been conducted among adult populations and none have focused on the impact of both preschoolers' and mothers' experience of sexual abuse on attachment security. The aim of this study was to compare attachment representations in sexually abused (n = 258) and non-abused preschoolers (n = 133), and to explore the relation between maternal history of CSA and children's attachment representations. A story completion task assessing attachment representations was administered to children (Bretherton, Ridgeway, & Cassidy, 1990). The results revealed that CSA preschoolers presented significantly higher levels of attachment disorganization compared to non-abused children, and that abused boys were at particular risk for hyperactivation and disorganization. Associations between mothers' history of CSA and children's attachment representations were non-significant. These findings support the need to consider victims' attachment representations in the implementation of efficient treatment programs. Targeting parent-child relationships in interventions could help promote attachment security in a vulnerable population of preschool victims.


Prognosis for children with acute kidney injury in the intensive care unit.
To define factors of prognostic importance for critically ill infants and children with acute kidney injury (AKI), we have studied 110 children, ages from 1 month to 180 months, admitted between March 1, 2002 and September 30, 2004 to the intensive care unit of Joana de Gusmão Children's Hospital. These patients represent 8% of all intensive care unit admissions during the entire study period. The diagnosis at admission was primary renal parenchyma disease (eight patients, 7.2%) and secondary renal disease (102 patients, 92.8%). Thirty-seven patients (33.6%) died, all of whom had secondary renal insufficiency; six patients (5.4%) died as a result of septic shock, and 31 (28.2%) patients died from multiple organ failure (MOF). The variables were analyzed using Fisher's exact test for qualitative variables and Student's t-test for quantitative variables. Stratified analysis was performed to assess the relative importance of variables using the Mantel-Haenszel technique. Among the variables analyzed, the following were found to be significantly related to mortality: anuria, oliguria, arterial hypotension, need for pressor drugs, need for mechanical ventilation, need for dialysis, the association with MOF, and high values of lactic acid.


Prenatal induced chronic dietary hypothyroidism delays but does not block adult-type Leydig cell development.
Transient hypothyroidism induced by propyl-2-thiouracyl blocks postpartum Leydig cell development. In the present study, the effects of chronic hypothyroidism on the formation of this adult-type Leydig cell population were investigated, using a more physiological approach. Before mating, dams were put on a diet consisting of an iodide-poor feed supplemented with a low dose of perchlorate and, with their offspring, were kept on this diet until death. In the pups at day 12 postpartum, plasma thyroid-stimulating hormone levels were increased by 20-fold, whereas thyroxine and free tri-iodothyronine levels were severely depressed, confirming a hypothyroid condition. Adult-type progenitor Leydig cell formation and proliferation were reduced by 40-60% on days 16 and 28 postpartum. This was followed by increased Leydig cell proliferation at later ages, suggesting a possible slower developmental onset of the adult-type Leydig cell population under hypothyroid conditions. Testosterone levels were increased 2- to 10-fold in the hypothyroid animals between days 21 and 42 postpartum compared with the age-matched controls. Combined with the decreased presence of 5alpha-reductase, this implicates a lower production capacity of 5alpha-reduced androgens. In 84-day-old rats, after correction for body weight-to-testis weight ratio, plasma insulin-like factor-3 levels were 35% lower in the hypothyroid animals, suggestive of a reduced Leydig cell population. This is confirmed by a 37% reduction in the Sertoli cell-to-Leydig cell ratio in hypothyroid rats. In conclusion, we show that dietary-induced hypothyroidism delays but, unlike propyl-2-thiouracyl, does not block the development of the adult-type Leydig cell population.


Polyethylene glycated leukemia inhibitory factor antagonist inhibits human blastocyst implantation and triggers apoptosis by down-regulating embryonic AKT.
To study the effect of polyethylene glycated leukemia inhibitory factor (LIF) antagonist (PEGLA) in the human blastocyst viability and implantation process. In vitro study. University hospital and research laboratory. Endometrial biopsy samples from fertile donors (n = 20), and surplus, frozen, good-quality human embryos obtained from an in vitro fertilization (IVF) clinic that survived thawing (n = 51). Timed human endometrial biopsy on the day of luteinizing hormone peak + 4 days (LH + 4). Human embryo attachment rate, embryo quality, and expression of AKT and caspase-3. PEGLA significantly reduced the embryo attachment rate to the endometrial construct. It decreased both mRNA and protein for LIF in the endometrial construct. Inhibition of embryonic LIF triggered apoptosis. Analysis of these blastocysts by immunofluorescence and real-time polymerase chain reaction showed a down-regulation in AKT activation and an increase in caspase-3 activation compared with the control group of blastocysts. The LIF inhibitor PEGLA could be a potential nonsteroidal fertility-regulating agent in humans. It acts on endometrial epithelial cells by down-regulating endometrial epithelial LIF. Inhibition of blastocyst LIF decreased its cell survival factor p-AKT and increased apoptosis (cleaved caspase-3). This highlights that embryonic LIF is vital for human embryo implantation.


Multimodality treatment in a case of primary cardiac lymphoma.
Primary cardiac lymphoma(PCL) is an exceptionally rare entity associated with a poor progonosis. The patient in this report underwent successful surgical resection of a PCL. We now describe her multimodality treatment including autologous stem cell transplantation which resulted in a 22 month survival.


[Biosynthesis of gold nanoparticles by Azospirillum brasilense].
Plant-associated nitrogen-fixing soil bacteria Azospirillum brasilense were shown to reduce the gold of chloroauric acid to elemental gold, resulting in formation of gold nanoparicles. Extracellular phenoloxidizing enzymes (laccases and Mn peroxidases) were shown to participate in reduction of Au+3 (HAuCl4) to Au(0). Transmission electron microscopy revealed accumulation of colloidal gold nanoparticles of diverse shape in the culture liquid of A. brasilense strains Sp245 and Sp7. The size of the electron-dense nanospheres was 5 to 50 nm, and the size of nanoprisms varied from 5 to 300 nm. The tentative mechanism responsible for formation of gold nanoparticles is discussed.


Blood cultures taken from patients attending emergency departments in South Africa are an important antibiotic stewardship tool, which directly influences patient management.
Febrile illness with suspected blood stream infection (BSI) is a common reason for admission to hospital in Africa and blood cultures are therefore an important investigation. Data on the prevalence and causes of community acquired BSI in Africa are scarce and there are no studies from South Africa. There are no validated clinical prediction rules for use of blood cultures in Africa. A prospective observational cohort study of patients attending 2 urban emergency departments in Cape Town, South Africa. The decision to take a blood culture was made by the attending clinician and information available at the time of blood draw was collected. Bottles were weighed to measure volume of blood inoculated. 500 blood culture sets were obtained from 489 patients. 39 (7.8 %) were positive for pathogens and 13 (2.6 %) for contaminants. Significant independent predictors of positive cultures were diastolic blood pressure <60 mmHg, pulse >120 bpm, diabetes and a suspected biliary source of infection, but not HIV infection. Positive results influenced patient management in 36 of 38 (95 %) cases with the organism being resistant to the chosen empiric antibiotic in 9 of 38 (24 %). Taking <8 ml of blood was predictive of a negative culture. The best clinical prediction rule had a negative predictive value (NPV) of 92 % which is unlikely to be high enough to be clinically useful. Blood cultures taken from patients attending emergency departments in a high HIV prevalent city in South Africa are frequently positive and almost always influence patient management. At least 8 ml of blood should be inoculated into each bottle. Blood cultures should be taken from all patients attending EDs in South Africa suspected of having BSI particularly if diabetic, with hypotension, tachycardia or if biliary sepsis is suspected.


Effect of child marriage on girls' school dropout in Nepal: Analysis of data from the Multiple Indicator Cluster Survey 2014.
School dropout and child marriage are interrelated outcomes that have an enormous impact on adolescent girls. However, the literature reveals gaps in the empirical evidence on the link between child marriage and the dropout of girls from school. This study identifies the 'tipping point' school grades in Nepal when the risk of dropout due to marriage is highest, measures the effect of child marriage on girls' school dropout rates, and assesses associated risk factors. Weighted percentages were calculated to examine the grades at highest risk and the distribution of reasons for discontinuing school. Using the Nepal Multiple Indicator Cluster Survey (MICS) 2014 data, we estimated the effect of marriage on school attendance and dropout among girls aged 15-17 by constructing logistic regression models. A multivariate logistic regression model was used to assess risk factors of school dropout due to child marriage. It was found that early marriage is the most common reason given for leaving school. Overall, the risk of school dropout due to marriage heightens after girls complete the fifth or sixth grade. The risk of girls' dropping out peaks in the seventh and eighth grades and remains noteworthy in the ninth and tenth grades. Married girls in Nepal are 10 times more likely to drop out than their unmarried peers. Little or no education of the household head, belonging to the Kirat religion, and membership of a traditionally disadvantaged social class each elevate the risk of school dropout due to early marriage. The findings underscore the need to delay girl's marriage so as to reduce girls' school dropout in Nepal. School-based programmes aimed at preventing child marriage should target girls from the fifth grade because they are at increased risk of dropping out, as well as prioritizing girls from disadvantaged groups.


Effect of interaction between acute administration of morphine and cannabinoid compounds on spontaneous excitatory and inhibitory postsynaptic currents of magnocellular neurons of supraoptic nucleus.
Opioids and cannabinoids are two important compounds that have been shown to influence the activity of magnocellular neurons (MCNs) of supraoptic nucleus (SON). The interaction between opioidergic and cannabinoidergic systems in various structures of the brain and spinal cord is now well established, but not in the MCNs of SON. In this study, whole cell patch clamp recording of neurons in rat brain slice was used to investigate the effect of acute morphine and cannabinoid administration on spontaneous inhibitory and excitatory spostsynaptic currents (sIPSCs and sEPSCs) in MCNs. Bath application of morphine produced an increase in sEPSCs frequency and a decrease in sIPSCs frequency. In contrast, bath application of URB597 (fatty acid amide hydrolase (FAAH) inhibitor) produced a decrease in sEPSCs frequency but an increase in sIPSCs frequency. WIN55212-2 (cannabinoid receptor agonist) decreased both sIPSCs and sEPSCs frequencies of MCNs. Co-application of morphine and URB597 attenuated the effect of morphine on MCNs. Taken together, these data indicated that at the cellular level, pharmacological augmentation of endocannabinoids could attenuate morphine effects on MCNs.