Synthesis of molecularly imprinted carbon dot grafted YVO4:Eu(3+) for the ratiometric fluorescent determination of paranitrophenol.
A facilely prepared ratiometric fluorescent molecularly imprinted sensor has been constructed for highly sensitive and selective detection of 4-nitrophenol (4-NP) using carbon dots (CDs) as the target sensitive fluorophore and YVO4: Eu(3+) nanoparticles (NPs) as the reference fluorophore. Through the hydrolysis and condensation reactions of the silica precursor, CDs and YVO4 Eu(3+) NPs can be incorporated into silica networks through silylation reaction by one pot synthesis procedure. The as-prepared fluorescent molecularly imprinted sensor shows characteristic fluorescence emissions of CDs (blue) and YVO4:Eu(3+) (red) under a single excitation wavelength. With the addition of 4-NP, the fluorescence of CDs is selectively quenched, resulting in the ratiometric fluorescence response. Under optimum conditions, the proposed sensor exhibits a high sensitivity with a linear range from 0 to 12.0μM and shows the limit of detection as low as 0.15μM in the determination of 4-NP, which is probably benefits from the tailor-made imprinted cavities for binding 4-NP. Furthermore, the proposed method was successfully applied for the determination of 4-NP in real water samples and human urine samples with great potentials for monitoring of 4-NP in environmental application.


Posttransfusion purpura: conversion of PLA1-negative platelets to the PLA1-positive phenotype by stored plasma is not due to the presence of soluble PLA1 antigen.
Three previous articles have reported a PLA1 antigen in the plasma of stored blood which is capable of binding to PLA1-negative platelets in the presence of divalent cations, rendering them PLA1 positive. Such a mechanism could explain the enigma of posttransfusion purpura (PTP), i.e., severe thrombocytopenia in a healthy subject with PLA1-negative platelets secondary to the infusion of blood containing PLA1-positive platelets. We find that the PLA1 antigen of stored blood is due to the presence of platelet fragments which can be removed by centrifugation and that divalent cation-chelating agents play no role in the apparent binding of these fragments to platelets. The apparent conversion of PLA1-negative platelets to the PLA1-positive phenotype by incubation with stored plasma from a PLA1-positive subject is due to the cosedimentation of platelet fragments with the platelets. No soluble PLA1 antigen was found in the plasma of five patients with acute posttransfusion purpura.


Piper sarmentosum is comparable to glycyrrhizic acid in reducing visceral fat deposition in adrenalectomised rats given dexamethasone.
Visceral obesity may be due to the dysregulation of cortisol production or metabolism that lead to metabolic disease. In adipose tissue, the enzyme 11beta-hydroxysteroid dehydrogenase type 1 regulates cortisol metabolism (11beta-HSD1). A previous study showed an increase in the visceral fat deposition in adrenalectomised rats given intramuscular dexamethasone. Glycyrrhizic acid (GCA) has been shown to reduce fat deposition because it is a known potent inhibitor of the 11beta-HSD1 enzyme. Piper sarmentosum (PS) is an edible medicinal plant commonly used in Asia as traditional medicine for treating diabetes, hypertension and joint pains. In this study, we determined the effects of PS extract on the disposition and morphology of perirenal adipocytes of adrenalectomised rats given intramuscular dexamethasone. A total of 21 male Spraque Dawley rats were adrenalectomised and given intramuscular dexamethasone, 120 μg/kg/day. These rats were further divided into three groups: adrenalectomised control (ADR+Dexa; n=7), GCA-treated (ADR+Dexa+GCA; dose=240 mg/kg/day; n=7) and PS-treated (ADR+Dexa+PS; dose=125 mg/kg/day; n=7) groups. The various treatments were given via gastric gavage following 2 weeks of adrenalectomy. Treatment with PS extract for 8 weeks showed decreased deposition of perirenal adipocytes which was similar to the GCA-treated group. However, PS-treated rats had thinner adipocyte membrane compared with that of the GCA-treated group. In conclusion, PS extract decreased perirenal fat deposition and reduced the diameter of the adipocyte membrane. However, the mechanisms of action needed further study.


Optimizing ovulation induction in women with polycystic ovary syndrome.
Recent developments in our understanding of the pathophysiology of polycystic ovary syndrome led to the introduction of new therapeutic approaches. It is apparent that a significant proportion of women with polycystic ovary syndrome have insulin resistance and compensatory hyperinsulinemia. Growing evidence indicates that elevated serum insulin induces hyperandrogenism, which in turn leads to anovulation and infertility. Hyperinsulinemia also contributes to the increased risk for cardiovascular disorders and type 2 diabetes mellitus. These concepts provide rationale for therapies focused on treatments of insulin resistance. In particular, weight loss and exercise have been shown to increase insulin sensitivity and improve ovulatory function. Metformin, an insulin-sensitizing agent, is particularly effective in women with polycystic ovary syndrome who have significant insulin resistance. Metformin use leads to a decrease in serum insulin and androgen levels as well as an improvement in ovulatory function. Moreover, it appears to ameliorate cardiovascular risk factors. Other approaches to ovulation induction in women with polycystic ovary syndrome include traditional therapies using clomiphene citrate or gonadotropins. In clomiphene-resistant subjects, one can consider laparoscopic ovarian drilling and other forms of partial ovarian resection or destruction.


Preliminary experiment with a newly developed double balloon, double lumen catheter for extracorporeal life support vascular access.
Recently, venovenous extracorporeal life support (VVECLS) using a double lumen catheter has been clinically used to avoid neurologic complications in the treatment of respiratory failure for neonates. However, recirculation, which is a limiting factor for oxygen delivery, still exists, and thus it does not contribute to oxygenation of the patient. We developed a newly designed double lumen catheter with a double balloon (DBDL) catheter for ECLS vascular access and performed two animal preliminary experiments in normal and hypoxic dog models (normal ventilation and one lung ventilation experiments) to investigate whether the DBDL catheter could prevent recirculation and maintain oxygen delivery to systemic circulation. The DBDL catheter (JCT Co., Hiroshima, Japan) of 15 Fr was fabricated from silicone. It consists of two lumens for drainage and return of blood with two balloons (distal and proximal balloons) that prevent oxygenated blood mixing with unoxygenated blood. VVECLS using a DBDL catheter was performed in 13 mongrel dogs (8 dogs for normal ventilation experiment weighing 12.9 +/- 1.6 kg [mean +/- SD], 5 dogs for one lung ventilation experiment weighing 16.6 +/- 2.5 kg [mean +/- SD]) under anesthesia in the two experiments. The bypass flow ranged from 10-40 ml/kg per minute in the normal ventilation experiment. VVECLS in the one lung ventilation experiment was performed with maximal bypass flow for 6 hours (ranged from 25.2 +/- 8.0-28.3 +/- 8.7 ml/kg per minute at balloon inflation and deflation). Recirculation and oxygen transfer of artificial lung with or without balloon inflation during VVECLS were studied. Recirculation decreased with balloon inflation at varied bypass flows during VVECLS in the normal ventilation experiment (varied from 1.5 +/- 14.6-12.8 +/- 16.7%) and for 6 hours after VVECLS initiation in the one lung ventilation experiment (varied from 12.2 +/- 12.2-19.2 +/- 6.5%). In particular, the values at 3 and 6 hours were significantly lower than that of balloon deflation in the one lung ventilation experiment. The difference in O2 content between inlet and outlet in the artificial lung with balloon inflation was significantly higher than that of balloon deflation (varied from 3.7 +/- 1.8-4.8 +/- 1.9 ml/dl, p < 0.05) at the bypass flow of 10-30 ml/kg per minute in the normal ventilation experiment and at 5 hours after VVECLS initiation in the one lung ventilation experiment (varied from 10.6 +/- 1.6-11.7 +/- 1.8 ml/dl). The blood gas analysis of systemic circulation with balloon inflation revealed that the values of PaO2 (varied from 83.8 +/- 11.4-96.9 +/- 23.4 mm Hg) and PaCO2 (37.7 +/- 9.2-40.4 +/- 11.8 mm Hg) were higher and lower, respectively, compared with balloon deflation. In particular, PaO2 level was significantly higher than that of the preECLS value at the bypass flow of 20-40 ml/kg per minute (varied from 83.8 +/- 11.4-96.9 +/- 23.4 mm Hg, p < 0.05). In the one lung ventilation experiment, systemic PaO2 and PaCO2 levels at balloon inflation were higher and lower, respectively, compared with balloon deflation during VVECLS for 6 hours. At balloon inflation, the value of PaO2 at 6 hours after VVECLS initiation was significantly higher than that at balloon deflation. A newly designed DBDL catheter for ECLS vascular access successfully reduced recirculation and maintained oxygen delivery to systemic circulation during VVECLS. These results suggest that a high bypass flow may not be necessarily required in terms of oxygen delivery to systemic circulation when the DBDL catheter was used as an ECLS vascular access.


Modeling the encephalopathy of prematurity in animals: the important role of translational research.
Translational research in preterm brain injury depends upon the delineation of the human neuropathology in order that animal models faithfully reiterate it, thereby ensuring direct relevance to the human condition. The major substrate of human preterm brain injury is the encephalopathy of prematurity that is characterized by gray and white matter lesions reflecting combined acquired insults, altered developmental trajectories, and reparative phenomena. Here we highlight the key features of human preterm brain development and the encephalopathy of prematurity that are critical for modeling in animals. The complete mimicry of the complex human neuropathology is difficult in animal models. Many models focus upon mechanisms related to a specific feature, for example, loss of premyelinating oligodendrocytes in the cerebral white matter. Nevertheless, animal models that simultaneously address oligodendrocyte, neuronal, and axonal injury carry the potential to decipher shared mechanisms and synergistic treatments to ameliorate the global consequences of the encephalopathy of prematurity.


Pharmacologic stress perfusion imaging with adenosine: role of simultaneous low-level treadmill exercise.
Adenosine is commonly used for pharmacologic stress myocardial perfusion imaging (MPI). However, it frequently results in adverse effects, and the subdiaphragmatic tracer uptake may interfere with the image interpretation. Our aim was to determine the feasibility of combining low-level treadmill exercise with adenosine MPI and its impact on adverse effects, image quality, and myocardial ischemia. Forty-one patients underwent technetium 99m sestamibi single photon emission computed tomography following adenosine and adenosine with low-level exercise (adenosine-Ex) on separate occasions and rest MPI. A comparison was made of symptoms, hemodynamic response, electrocardiographic changes, image quality, and image interpretation between the 2 protocols. With adenosine-Ex, fewer patients had one or more adverse effects (61% vs 90%; P =.006), more patients had ischemic electrocardiographic changes (34% vs 15%; P =.03), a higher percentage had excellent- or fair-quality images (88% vs 61%; P =.003), and they had higher heart-liver ratios (1.0 +/- 0.37 vs 0.84 +/- 0.29; P =.002) compared with adenosine alone. Four adenosine MPI studies, but only 2 adenosine-Ex studies, were uninterpretable because of excessive subdiaphragmatic radiotracer activity. Of the 39 patients with at least 1 interpretable stress study, interpretation was discordant in 11 (28%): 7 showed greater ischemia with adenosine-Ex, 2 uninterpretable adenosine studies were interpretable with adenosine-Ex, and 2 studies interpreted as abnormal with adenosine were normal by adenosine-Ex (both had normal coronary angiograms). Simultaneous low-level treadmill exercise with adenosine Tc-99m sestamibi imaging is safe and feasible, significantly reduces unfavorable side effects, enhances image quality, and may result in greater ischemia detection compared with adenosine alone.


Substituent effects on exchange coupling: 5-Aryl-substituted semiquinones and their complexes with MnII and CuII.
A series of functionalized radical anion semiquinone (SQ-Ar) ligands and their MnII- and CuIIhydro-tris(3-cumenyl-5-methylpyrazolyl)borate (TpCum,MeMII) complexes were prepared and characterized. The semiquinone ligands have substituted phenyl rings (Ar = -C6H5NO2, -C6H5OMe, -C6H5-tert-Bu, etc.) attached to the SQ 5-position. Despite the "remoteness" of the phenyl ring substituents, the MII-SQ exchange parameters, J, were found to vary nearly 3-fold. Attempts to quantify the substituent effects on J are complicated by the fact that not all complexes could be structurally characterized. As such, substituent effects and phenyl-ring torsion angles could conspire to produce the observed variation in J values. Although there is no clear trend in the J values as a function of SQ substituent for the MnII complexes, for the CuII complexes, electron-withdrawing substituents on the phenyl ring have greater ferromagnetic J values than the CuII complexes of SQ ligands with electron-donating substituents. This trend suggests a FM contribution from MLCT excited states in the copper complexes.


Reliability and validity of proxy respondent information about childhood injury: an assessment of a Canadian surveillance system.
The reliability and validity of proxy respondent information in the Canadian Hospitals Injury Reporting and Prevention Program surveillance system was assessed. A standardized form was used to collect data on injury date, location, context (activity at the time), breakdown factor (what went wrong), mechanism, product involvement, safety precaution use, and motor vehicle involvement. The test-retest method determined reliability, with the kappa coefficient quantifying agreement between respondent information provided in the emergency department and later during a telephone interview. Of 421 eligible respondents, 325 (77%) completed the telephone interview, with a median time to interview of 33 hours (range 24-70 hours). Agreement was high for all items; kappa coefficients ranged from 0.79 (substantial agreement) to 1.00 (perfect agreement). Reliability was not significantly modified by respondent view of the injury event, age of the child, language of the form, or level of respondent education. Validity was determined by measuring the agreement between respondent information and that provided by an independent witness. Witness information was considered to represent the truth. Of the 140 injury events selected, 92 (66%) had the form completed by both the original respondent and an independent witness. Kappa coefficients were greater than 0.65 for all but one item (safety precaution use), and the positive predictive value of respondent information for item categories whose prevalence was > or = 0.25 ranged from 0.82 to 0.95. The authors conclude that proxy respondent data on childhood injury are both reliable and valid.


Effect of Adjuvant Chemotherapy on Left Ventricular Remodeling in Women with Newly Diagnosed Primary Breast Cancer: A Pilot Prospective Longitudinal Cardiac Magnetic Resonance Imaging Study.
The aim of this study was to assess the left ventricular (LV) remodeling response to chemotherapy in low-cardiac-risk women with newly diagnosed nonmetastatic breast cancer. Cardiotoxic effects of chemotherapy are an increasing concern. To effectively interpret cardiac imaging studies performed for screening purposes in patients undergoing cancer therapy it is necessary to understand the normal changes in structure and function that may occur. Twenty women without preexisting cardiovascular disease, of a mean age of 50 years, newly diagnosed with nonmetastatic breast cancer and treated with anthracycline or trastuzumab, were prospectively enrolled and evaluated at four time points (at baseline, during chemotherapy, 2 weeks after chemotherapy, and 6 months after chemotherapy) using cardiac magnetic resonance imaging, blood samples, and a clinical questionnaire. Over a 6-month period, the left ventricular ejection fraction (%) decreased (64.15±5.30 to 60.41±5.77, P<0.002) and the LV end-diastolic (mm) and end-systolic (mm) volumes increased (124.73±20.25 to 132.21±19.33, P<0.04 and 45.16±11.88 to 52.57±11.65, P<0.00, respectively). The LV mass (g) did not change (73.06±11.51 to 69.21±15.3, P=0.08), but the LV mass to LVEDV ratio (g/mm) decreased (0.594±0.098 to 0.530±0.124, P<0.04). In low-cardiac-risk women with nonmetastatic breast cancer, the increased LV volume and a mildly decreased left ventricular ejection fraction during and after chemotherapy do not seem to be associated with laboratory or clinical evidence of increased risk for heart failure.


Effects of hypovolemia on local metabolic changes in skeletal muscle following high velocity missile injury.
The effect of blood loss and reinfusion after 6 h on the tissue damage around a high-velocity missile tract in skeletal muscle has been studied in pigs (n = 13). Hemodynamic variables and blood chemistry were monitored and the levels of ATP, creatine phosphate (CP), glucose, glucose-6-phosphate ( G6 -P), and lactate were repeatedly analyzed in muscle samples from the wound area and from control tissue. In vitro amino acid incorporation into proteins by isolated ribosomes was also studied. The missile injury induced pronounced local metabolic disturbances in the muscle tissue surrounding the missile tract. After 6 h these disturbances were more pronounced and extended further out from the wound channel in bled than in unbled animals. One hour after reinfusion of the shed blood, no remaining difference in the size of the metabolically disturbed tissue area between the two groups of animals could be demonstrated. It is thus concluded that a moderate hypovolemia markedly increases the metabolic deterioration around a high-velocity missile tract in skeletal muscle but that volume restitution, even if given as late as 6 h after the missile injury and the blood loss, will almost completely within 1 h reverse the effects caused by the hypovolemia.


Attitudes, access and anguish: a qualitative interview study of staff and patients' experiences of diabetic retinopathy screening.
To examine the experiences of patients, health professionals and screeners; their interactions with and understandings of diabetic retinopathy screening (DRS); and how these influence uptake. Purposive, qualitative design using multiperspectival, semistructured interviews and thematic analysis. Three UK Screening Programme regions with different service-delivery modes, minority ethnic and deprivation levels across rural, urban and inner-city areas, in general practitioner practices and patients' homes. 62 including 38 patients (22 regular-screening attenders, 16 non-regular attenders) and 24 professionals (15 primary care professionals and 9 screeners). Antecedents to attendance included knowledge about diabetic retinopathy and screening; antecedents to non-attendance included psychological, pragmatic and social factors. Confusion between photographs taken at routine eye tests and DRS photographs was identified. The differing regional invitation methods and screening locations were discussed, with convenience and transport safety being over-riding considerations for patients. Some patients mentioned significant pain and visual disturbance from mydriasis drops as a deterrent to attendance. In this, the first study to consider multiperspectival experiential accounts, we identified that proactive coordination of care involving patients, primary care and screening programmes, prior to, during and after screening is required. Multiple factors, prior to, during and after screening, are involved in the attendance and non-attendance for DRS. Further research is needed to establish whether patient self-management educational interventions and the pharmacological reformulation of shorter acting mydriasis drops, may improve uptake of DRS. This might, in turn, reduce preventable vision loss and its associated costs to individuals and their families, and to health and social care providers, reducing current inequalities.


Clinico-laboratory profile of 45 filarial arthritis cases.
This prospective observational study was done during the period from January 2000 to December 2004 including 45 cases of lymphatic filariasis manifested with acute arthritis. Different investigations were carried out to exclude allergy, parasitic and infectious diseases, autoimmune disorder and malignancy. They were given standard treatment with oral non-steroidal anti-inflammatory drugs (NSAIDs). Articular symptoms were not relived satisfactorily. Later they were given oral corticosteroids. During treatment slight relief of symptoms were noted, but all sign-symptoms reappear after withdrawal of corticosteroid drugs. Treatment with oral diethylcarbamazine citrate (DEC) (150 mg/day) for 3 weeks showed complete resolution of arthritis. No side effects or relapse were encountered. The basic mechanism of relief of pain remains unknown. It was assumed that during benign course of lymphatic filariasis, development of arthritis result most likely due to reaction against some occult agents in the joints.


Optic neuritis as an early sign of multiple sclerosis.
Optic neuritis (ON) is an acute inflammatory demyelinating disorder of the optic nerve. The general characteristics of isolated ON include unilateral, subacute, and painful visual loss without systemic or other neurological symptoms. The etiology for ON varies including demyelinating disorders or infections, inflammation, toxic reasons, and genetic disorders. In most cases the responsible etiology may not be known for ON and in this case, it is termed idiopathic ON. When a patient presents with an initial episode of ON, patients should undergo further tests. Assessing the patient with routine blood work, magnetic resonance imaging, cerebrospinal fluid tests, and visual evoked potentials provide further insight. In this review, we aimed to provide a review of ON as an initial symptom of multiple sclerosis and present clinical characteristics, therapy options, and recent literature.


Cannabis 'dependence' and attentional bias for cannabis-related words.
Drug users have attentional biases for drug-related stimuli, and the frequency of drug use and craving are associated with attentional bias. However, research to date has not investigated the relationship between the severity of cannabis dependence, and attentional bias for cannabis-related stimuli. In the present study, 28 recreational cannabis users completed a modified Stroop task with cannabis-related and control words, plus questionnaire measures of cannabis dependence and craving. Participants were split into those who met diagnostic criteria for cannabis dependence based on scores on the Cannabis Severity of Dependence Scale (C-SDS), and those who did not. The cannabis-dependent group had a significant attentional bias for the cannabis-related words, but the non-dependent group did not. Correlations indicated that attentional bias was also associated with the frequency of cannabis use, and with subjective craving.


Educational Outcomes Associated With School Behavioral Health Interventions: A Review of the Literature.
There is an unmet need for behavioral health support and services among children and adolescents, which school behavioral health has the potential to address. Existing reviews and meta-analyses document the behavioral health benefits of school behavioral health programs and frameworks, but few summaries of the academic benefits of such programs exist. We provide exemplars of the academic benefits of school behavioral health programs and frameworks. A literature review identified school behavioral health-related articles and reports. Articles for inclusion were restricted to those that were school-based programs and frameworks in the United States that included an empirical evaluation of intervention academic-related outcomes. Findings from 36 primary research, review, and meta-analysis articles from the past 17 years show the benefits of school behavioral health clinical interventions and targeted interventions on a range of academic outcomes for adolescents. Our findings are consistent with reports documenting health benefits of school behavioral health frameworks and programs and can facilitate further efforts to support school behavioral health for a range of stakeholders interested in the benefits of school behavioral health programs and frameworks on academic outcomes.


Theoretical Study of Addition Reactions of L4M(M = Rh, Ir) and L2M(M = Pd, Pt) to Li+@C60.
The addition reaction of M(Cl)(CO)(PPh3)2 (M = Rh, Ir) and M(PPh3)2 (M = Pd, Pt) fragments with X@C60 (X = 0, Li+) were characterized by density functional theory (DFT) and the artificial force-induced reaction (AFIR) method. The calculated free energy profiles suggested that the η2[6:6]-addition is the most favorable reaction, which is consistent with the experimental observations. In the presence of Li+ ion, the reaction is highly exothermic, leading to η2[6:6] product of L4IrLi+@C60. In contrast, an endothermic reaction was observed in the absence of a Li+ ion. The encapsulated Li+ ion can enhance the thermodynamic stability of the η2[6:6] product. The energy decomposition analysis showed that the interaction between metal fragment and X@C60 fragment is the key for the thermodynamic stability. Among the group IA and IIA metal cations, Be2+ encapsulation is the best candidate for the development of new fullerene-transition metal complexes, which will be useful for future potential applications such as solar cells, catalysts, and electronic devices.


Openness and topic avoidance in interpersonal communication about ovarian cancer: An uncertainty management perspective.
This study examined openness and topic avoidance in interpersonal communication about ovarian cancer. Guided by the uncertainty management theory, the researchers analyzed qualitative data from 28 ovarian cancer patients/survivors and found openness and topic avoidance to be complex communication behaviors which are connected to patients/survivors' uncertainty. Participants appraised uncertainty about disease prognosis and effectiveness of treatments as a threat; thus, they avoided topics such as treatment side effects and fears about death and disease recurrence to manage such uncertainty. Furthermore, findings showed that communication about ovarian cancer is layered with degrees of openness and avoidance relative to respective audiences and changing illness trajectories. Overall, the findings indicate connections between interpersonal communication about ovarian cancer and uncertainty management practices, suggesting that intervention efforts should help cancer patients/survivors and relational others practice sensitivity when discussing topics such as death and dying.


The effects of parental's cultural and economic capital and parental support on being an elite scientists.
Despite the rapid increase in the number of scientists all over the world in recent years, very few scientists can achieve to be part of elite scientist's category. Although there are many studies focusing on elite scientists, these studies generally do not focus on their childhood and parental background. In this study, which attempts to fill this gap, we focus on the cultural and economic capital of the families of elite scientists in Turkey and their parental support in childhood to analyze the roles of these variables in their being elite scientists. First, we assess the impact of cultural capital (institutional, objectified, and embodied), economic capital, parental support, and perceived academic success in basic education on the probability of becoming an elite scientist. Second, we analyze the differences among elite scientists to shed light on the gender gap in academia. We collected the data from 1,966 scientists working at 87 universities in Turkey through an online survey. Some of our main findings are as follows: (a) cultural capital, parental support, and academic success in basic education all have a strong positive effect on becoming an elite scientist; (b) objectified cultural capital has the highest impact in that an increase in this capital increases the probability of becoming elite scientists by 19%; (c) economic capital has no significant effect on elite scientists. Elite scholars have certain common characteristics, but significantly they are different from their average peers in terms of cultural capital and parental support and (d) elite female scientists have higher of cultural capital, economic capital, parental support, and academic success than elite male scientists. This finding supports the existence of the academic inequality and suggests that female scientists need higher cultural capital, economic capital, parental support, and perceived academic success to become elite scientists than their male counterparts.


FACTORS ASSOCIATED WITH POST-STROKE FATIGUE WITHIN THE FIRST 3 MONTH AFTER STROKE.
Aim - identify socio-demographic, personal and psychological factors associated with certain post-stroke fatigue (PSF) domains within first 3 months after stroke. There were examined patients consequently in definite time points after ischemic or hemorrhagic strokes: at hospital stay (234 patients), in 1 month (203 patients) and in 3 months (176 patients). Global PSF and certain PSF domains were measured by multidimensional fatigue inventory-20 (MFI-20) scale. In multivariate logistic regression analysis the majority of variables (gender, marital status, education level, smoking status, level of alcohol consumption, apathetic impairments, arterial hypertension, atrial fibrillation, ischemic heart disease, diabetes mellitus, body mass index, waist circumference) were not significantly associated with any PSF domain risk at any time point after stroke. On the other hand, it had been found reliable associations between risk of global PSF and employing status before stroke, pre-stroke fatigue, anxiety symptoms, excessive daytime sleepiness, pain. Majority of risk factors for specific PSF domains (physical, mental, activity-related, motivational) are the same as for global PSF. The exception is mild cognitive impairments for mental PSF and depression signs for motivational PSF. Management of modifiable risk factors (anxiety and depression signs, excessive daytime sleepiness, chronic pain) probably may be helpful for PSF prevention within first 3 months after stroke.


Genetic overlap between Alzheimer's disease and immune-mediated diseases: An atlas of shared genetic determinants and biological convergence.
The occurrence of immune disease comorbidities in Alzheimer's disease (AD) has been observed in both epidemiological and molecular studies, suggesting a neuroinflammatory basis in AD. However, their shared genetic components have not been systematically studied. Here, we composed an atlas of the shared genetic associations between 11 immune-mediated diseases and AD by analyzing genome-wide association studies (GWAS) summary statistics. Our results unveiled a significant genetic overlap between AD and 11 individual immune-mediated diseases despite negligible genetic correlations, suggesting a complex shared genetic architecture distributed across the genome. The shared loci between AD and immune-mediated diseases implicated several genes, including GRAMD1B, FUT2, ADAMTS4, HBEGF, WNT3, TSPAN14, DHODH, ABCB9 and TNIP1, all of which are protein-coding genes and thus potential drug targets. Top biological pathways enriched with these identified shared genes were related to the immune system and cell adhesion. In addition, in silico single-cell analyses showed enrichment of immune and brain cells, including neurons and microglia. In summary, our results suggest a genetic relationship between AD and the 11 immune-mediated diseases, pinpointing the existence of a shared however non-causal genetic basis. These identified protein-coding genes have the potential to serve as a novel path to therapeutic interventions for both AD and immune-mediated diseases and their comorbidities.


Factors involved in regulating primary and secondary immunity to infection with Histoplasma capsulatum: TNF-alpha plays a critical role in maintaining secondary immunity in the absence of IFN-gamma.
Primary infection to Histoplasma capsulatum often results in a self-limited upper respiratory infection in humans; however, in immunocompromised hosts, disseminated infection can occur through reactivation of a previous infection. Since disseminated histoplasmosis has emerged as a difficult clinical entity to treat in individuals infected with HIV, it was of interest to study the mechanisms involved in maintaining an effective memory immune response. It has been previously shown in a murine model of disseminated histoplasmosis that IL-12, IFN-gamma, and TNF-alpha were important factors in mediating primary protection. To study whether these and other factors were involved in maintaining a protective immune response following secondary infection, normal C57BL/6 mice were first infected with a sublethal dose of H. capsulatum (1 x 10(5)) and then reinfected 3 wk later with a lethal dose of H. capsulatum (6 x 10(5)). Under these conditions, all mice developed an effective immune response with sterilizing immunity. Moreover, normal C57BL/6 mice treated with neutralizing Abs against either IL-12, TNF-alpha, or IFN-gamma, depleted of neutrophils or treated with aminoguanidine at the time of reinfection, maintained an effective immune response. The ability of animals to survive a secondary infection in the absence of IFN-gamma was verified by showing that IFN-gamma(-/-) mice previously immunized with H. capsulatum and treated with amphotericin B at the time of primary infection had prolonged survival following reinfection with a normally lethal dose. It was further shown that enhancement of TNF-alpha production in IFN-gamma(-/-) mice was the major mechanism by which these mice were effective in controlling secondary infection.


Spatial facilitation and depression within one motor nerve terminal of frogs.
1. Perfused macropatch electrodes were used to stimulate and simultaneously measure release from two sites on the same terminal of the frog cutaneous pectoris muscle. 2. It was found that release occurring at one site often affected release at an adjacent site 50 microns away, either enhancing it ('spatial facilitation') or depressing it ('spatial depression'). Spatial facilitation (or depression) was defined as the release produced by a test pulse at the second site (test electrode) when preceded by a pulse at the first site (prepulse electrode) divided by the release produced by the test pulse alone. 3. Spatial facilitation varied with the time interval between the prepulse and the test pulse. Peak spatial facilitation, which on the average was 2.14, occurred with an interval of 1-3 ms. With longer intervals spatial facilitation decayed with a time constant between 3-6 ms. When the time interval between the prepulse and the test pulse was zero (no delay), the release after the test pulse was always depressed. 4. When Ca2+ was omitted from the perfusate of the prepulse electrode, spatial facilitation was abolished. When a brief hyperpolarizing pulse followed the depolarizing prepulse with zero delay spatial facilitation was also abolished. 5. Electrotonic spread or Ca2+ diffusion within the axon terminal are excluded as coupling agents for spatial facilitation. It is suggested that the coupling agent may possibly be related to a hypothetical release-promoting factor.


Have maternal or paternal ages any impact on the prenatal incidence of genomic copy number variants associated with fetal structural anomalies?
The objective of this study was to determine whether maternal or paternal ages have any impact on the prenatal incidence of genomic copy number variants (CNV) in fetuses with structural anomalies. We conducted a non-paired case-control study (1:2 ratio) among pregnancies undergoing chromosomal microarray analysis (CMA) because of fetal ultrasound anomalies, from December 2012 to May 2020. Pregnancies with any pathogenic copy number variant (CNV), either microdeletion or microduplication, were defined as cases. Controls were selected as the next two pregnancies with the same indication for CMA but with a normal result. Logistic regression was used, adjusting by use of assisted reproductive technology (ART) and parental smoking. Stratified analysis was performed according to CNV type (de novo/inherited and recurrent/non-recurrent). The study included 189 pregnancies: 63 cases and 126 controls. Mean maternal age in cases was 33.1 (SD 4.6) years and 33.9 (SD 6.0) years in controls. Mean paternal mean age was 34.5 (SD 4.8) years in cases and 35.8 (SD 5.8) years in controls. No significant differences in maternal or paternal age were observed, neither in stratified analysis according to the CNV type. Moreover, the proportion of cases were not significantly different between non-advanced and advanced ages, either considering paternal or maternal ages. The presence of pathogenic CNV at CMA in fetuses with structural anomalies was not found to be associated with advanced paternal or maternal age.


Early and late outcomes with prolonged open chest management after cardiac surgery.
Open chest management (OCM) is an important intervention for patients who are unable to undergo sternal closure after cardiac surgery. This study reviews the factors associated with a prolonged need for this intervention and investigates its association with early and late mortality. Patients undergoing OCM from January 2009 to December 2014 were reviewed. Differences in the median duration of OCM when a perioperative variable was present versus its absence were determined and variables significant at P ≤ .1 were analyzed using Poisson regression for factors associated with prolonged OCM. Multivariable logistic regression and Cox proportional hazards models were developed to investigate perioperative factors that were associated with early and late mortality. A total of 201 patients (5%) required OCM and the overall median duration of this intervention was 3 days. The use a temporary assist device (median, 7 vs 2 days; P < .001), pneumonias (median, 11 vs 3 days; P < .001), sternal re-explorations (median, 6 vs 2 days; P < .001), and renal failure (median, 6 vs 3 days; P = .02) were among the factors that were highly associated with prolonged OCM using Poisson regression. Thirty-day mortalities occurred in 32 patients (16%) and were significantly associated with emergency surgery (P = .03), sternal re-explorations (P = .001), and OCM duration (median, 6 vs 3 days; P = .02). On multivariable logistic regression and Cox analysis, delaying sternal closure by 1-day increments increased the risk of early and late mortality by 11% (P = .01), and 9% (P < .001), respectively. Prolonged OCM was associated with increasing perioperative morbidity and a higher risk of early and late mortality.


[Management and prognosis in stage IV gestational trophoblastic neoplasia patients].
To analyze the management and prognosis in stage IV gestational trophoblastic neoplasia (GTN) patients. One thousand one hundred and thirty GTN patients were hospitalized and treated at Peking Union Medical College Hospital from year 1985 to 2004. Ninety-two of them were diagnosed as stage IV of GTN. Retrospective analyses were carried out on these patients in terms of management and prognosis. Of the 92 patients who had undergone treatment, complete remission (CR) was achieved in 33, partial remission in 37, and progress of the disease was seen in 22. Among all the CR patients, three had recurrence later. Thirty-three out of all the patients died during or after treatment. Among the 92 cases, 70 had one or two metastases, of whom 27 had CR, and 20 died. Of the 17 cases who had three metastases, 5 achieved CR, and 10 died. Of the five cases with >or= 4 metastases, one had CR, and three died. The number of metastatic organs was correlated with prognosis (P = 0.034) and death (P = 0.018). Multi-drug and multi-route chemotherapy and (or) combined surgical intervention may improve the survival rate of the stage IV GTN patients. The management should be individualized for different patients with metastases. With the increase in the number of metastatic organs, the remission rate decreases.


Effect of antithrombotic stewardship on the efficacy and safety of antithrombotic therapy during and after hospitalization.
Although the benefits of antithrombotic drugs are indisputable to reduce thrombotic events, they carry a high risk of compromising patient safety. No previous studies investigated the implementation and (cost-) effectiveness of a hospital-based multidisciplinary antithrombotic team on bleeding and thrombotic outcomes. The primary aim of this study was to compare the proportion of patients with a composite end point consisting of one or more bleeding episodes or one or more thrombotic event from hospitalization until three months after hospitalization. A prospective, multicenter before-after intervention study was conducted in two Dutch hospitals. Adult patients hospitalized between October 2015 and December 2017 treated with anticoagulant therapy were included. The primary aim was to estimate the proportion of patients with a composite end point consisting of one or more bleeding episodes or one or more thrombotic event from hospitalization until three months after hospitalization. The intervention was the implementation of a multidisciplinary antithrombotic team focusing on education, medication reviews by pharmacists, implementing of local anticoagulant therapy guidelines based on national guidelines, patient counselling and medication reconciliation at admission and discharge. The primary endpoint was analysed using segmented linear regression. We obtained data for 1,886 patients: 941 patients were included in the usual care period and 945 patients in the intervention period. The S-team study showed that implementation of a multidisciplinary antithrombotic team over time significantly reduced the composite end point consisting of one or more bleeding episodes or one or more thrombotic event from hospitalization until three months after hospitalization in patients using anticoagulant drugs (-1.83% (-2.58% to -1.08%) per 2 month period). This study shows that implementation of a multidisciplinary antithrombotic team over time significantly reduces the composite end point consisting of one or more bleeding episodes or one or more thrombotic event from hospitalization until three months after hospitalization in patients using anticoagulant drugs. Trialregister.nl NTR4887.


Automated multiple-layer spotting for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of synthetic polymers utilizing ink-jet printing technology.
Recently, a new multiple-layer matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) sample spotting technique for poly(ethylene glycol), offering improved analysis possibilities, was described. In this contribution the application of ink-jet printing to automated, multiple-layer MALDI-TOFMS sample preparation of synthetic polymers is presented, allowing accurate deposition of matrix, additive and analyte solutions. The new sample preparation technique was evaluated for poly(ethylene glycol) as well as poly(methyl methacrylate) standards, and optimized settings for both synthetic polymers have been obtained.


Comparing overall survival between first generation EGFR-TKIs and chemotherapy in lung cancer patients with Del19/L858R.
Combined overall survival (OS) analysis of Lux-Lung 3 and Lux-Lung 6 demonstrated that patients with epidermal growth factor receptor (EGFR) exon 19 deletions (Del19) would benefit from first-line second generation EGFR tyrosine kinase inhibitors (TKIs) afatinib but not for those with L858R. This study was to investigate the survival difference between first-line first generation EGFR-TKIs and chemotherapy in patients with either Del19 or L858R, and to directly compare OS in these two mutation groups. Eligibles were all prospective and retrospective studies comparing EGFR-TKIs with conventional chemotherapy or receiving single agent EGFR-TKIs and demonstrating survival analysis based on mutation types. The primary outcome was OS measured as pooled hazard ratios (HRs). All measures were pooled using randomeffects models and 95% confidential interval (95% CI) was calculated. A total of 14 studies incorporating 1,706 patients with either Del19 or L858R were included. Enrolling patients with Del19 or L858R in randomized controlled trials (RCTs), first-line first generation EGFR-TKIs were associated with no OS benefit, compared with chemotherapy (pooled HRTKI/Chemo for Del19: 0.82, 95% CI: 0.64-1.06, P = 0.14; pooled HRTKI/Chemo for L858R: 1.15, 95% CI: 0.85-1.56, P = 0.38). Direct comparison of Del19 with L858R receiving with first-line first generation EGFR-TKIs demonstrated no significant survival difference (pooled HR19/21: 0.88, 95% CI: 0.67-1.16, P = 0.37). Among patients with advanced non-small cell lung cancer (NSCLC) harboring Del19 and L858R, first-line first generation EGFR-TKIs demonstrated no survival benefit comparing with chemotherapy. Direct comparison between Del19 and L858R revealed no significant survival difference after first-line first generation EGFR-TKIs.


Subsarcolemmal lipid droplet responses to a combined endurance and strength exercise intervention.
Muscle lipid stores and insulin sensitivity have a recognized association although the mechanism remains unclear. We investigated how a 12-week supervised combined endurance and strength exercise intervention influenced muscle lipid stores in sedentary overweight dysglycemic subjects and normal weight control subjects (n = 18). Muscle lipid stores were measured by magnetic resonance spectroscopy (MRS), electron microscopy (EM) point counting, and direct EM lipid droplet measurements of subsarcolemmal (SS) and intramyofibrillar (IMF) regions, and indirectly, by deep sequencing and real-time PCR of mRNA of lipid droplet-associated proteins. Insulin sensitivity and VO2max increased significantly in both groups after 12 weeks of training. Muscle lipid stores were reduced according to MRS at baseline before and after the intervention, whereas EM point counting showed no change in LD stores post exercise, indicating a reduction in muscle adipocytes. Large-scale EM quantification of LD parameters of the subsarcolemmal LD population demonstrated reductions in LD density and LD diameters. Lipid droplet volume in the subsarcolemmal LD population was reduced by ~80%, in both groups, while IMF LD volume was unchanged. Interestingly, the lipid droplet diameter (n = 10 958) distribution was skewed, with a lack of small diameter lipid droplets (smaller than ~200 nm), both in the SS and IMF regions. Our results show that the SS LD lipid store was sensitive to training, whereas the dominant IMF LD lipid store was not. Thus, net muscle lipid stores can be an insufficient measure for the effects of training.


Dose escalating study of biweekly gemcitabine and carboplatin in patients with advanced cancer.
Combination chemotherapy with gemcitabine and carboplatin administered on a 3-week cycle is used commonly in the treatment of cancer. The purpose of our study was to establish a safe dose of combined gemcitabine and carboplatin when administered on a biweekly schedule to patients with advanced solid tumors. Gemcitabine was given intravenously over 30 minutes followed by carboplatin also given intravenously over 30 minutes once every 2 weeks (one cycle). Five dose levels were examined, ranging from gemcitabine at 1250 mg/m2 to 2000 mg/m2 and carboplatin at an area under the curve of 2.5 to 3.0. Twenty-six patients were studied (18 male and 8 female) with a median age of 57 years (range, 41-83 years); ECOG performance status was 0 or 1 in 22 patients (85%); median number of prior chemotherapy regimens was 2 (range, 0-4); median number of cycles administered per patient was 3 (range, 1-9) with a total of 89 cycles. Two dose-limiting toxicities were observed. Delay in treatment was seen in a total of 8 cycles with 6 of the delays due to myelosuppression. Grade 3 or 4 hematologic toxicity rates were as follows: anemia in one cycle (1%), neutropenia in 13 cycles (15%), and thrombocytopenia in one cycle of chemotherapy (1%). There were no hospitalizations for neutropenic fever. Mild fatigue was the most common nonhematologic toxicity. The median time to progression was 40 days (mean, 49 days; range, 4-133 days). Of the 21 evaluable patients, partial response or stable disease was observed in 11 (42%). The maximum tested dose of gemcitabine at 2000 mg/m2 and carboplatin at area under the curve of 3.0 was well tolerated on a biweekly schedule. Our findings indicate that further investigation of this biweekly regimen is warranted in patients with advanced cancer.


Comprehensive analysis of the endoplasmic reticulum stress response in the soybean genome: conserved and plant-specific features.
Despite the relevance of the eukaryotic endoplasmic reticulum (ER)-stress response as an integrator of multiple stress signals into an adaptive response, knowledge about these ER-mediated cytoprotective pathways in soybean (Glycine max) is lacking. Here, we searched for genes involved in the highly conserved unfolded protein response (UPR) and ER stress-induced plant-specific cell death signaling pathways in the soybean genome. Previously characterized Arabidopsis UPR genes were used as prototypes for the identification of the soybean orthologs and the in silico assembly of the UPR in soybean, using eggNOG v4.0 software. Functional studies were also conducted by analyzing the transcriptional activity of soybean UPR transducers. As a result of this search, we have provided a complete profile of soybean UPR genes with significant predicted protein similarities to A. thaliana UPR-associated proteins. Both arms of the plant UPR were further examined functionally, and evidence is presented that the soybean counterparts are true orthologs of previously characterized UPR transducers in Arabidopsis. The bZIP17/bZI28 orthologs (GmbZIP37 and GmbZIP38) and ZIP60 ortholog (GmbZIP68) from soybean have similar structural organizations as their Arabidopsis counterparts, were induced by ER stress and activated an ERSE- and UPRE-containing BiP promoter. Furthermore, the transcript of the putative substrate of GmIREs, GmbZIP68, harbors a canonical site for IRE1 endonuclease activity and was efficiently spliced under ER stress conditions. In a reverse approach, we also examined the Arabidopsis genome for components of a previously characterized ER stress-induced cell death signaling response in soybean. With the exception of GmERD15, which apparently does not possess an Arabidopsis ortholog, the Arabidopsis genome harbors conserved GmNRP, GmNAC81, GmNAC30 and GmVPE sequences that share significant structural and sequence similarities with their soybean counterparts. These results suggest that the NRP/GmNAC81 + GmNAC30/VPE regulatory circuit may transduce cell death signals in plant species other than soybean. Our in silico analyses, along with current and previous functional data, permitted generation of a comprehensive overview of the ER stress response in soybean as a framework for functional prediction of ER stress signaling components and their possible connections with multiple stress responses.


Spatial and temporal changes in leaf coloring date of Acer palmatum and Ginkgo biloba in response to temperature increases in South Korea.
Understanding shifts in autumn phenology associated with climate changes is critical for preserving forest ecosystems. This study examines the changes in the leaf coloring date (LCD) of two temperate deciduous tree species, Acer palmatum (Acer) and Ginkgo biloba (Ginkgo), in response to surface air temperature (Ts) changes at 54 stations of South Korea for the period 1989-2007. The variations of Acer and Ginkgo in South Korea are very similar: they show the same mean LCD of 295th day of the year and delays of about 0.45 days year-1 during the observation period. The delaying trend is closely correlated (correlation coefficient > 0.77) with increases in Ts in mid-autumn by 2.8 days °C-1. It is noted that the LCD delaying and temperature sensitivity (days °C-1) for both tree species show negligible dependences on latitudes and elevations. Given the significant LCD-Ts relation, we project LCD changes for 2016-35 and 2046-65 using a process-based model forced by temperature from climate model simulation. The projections indicate that the mean LCD would be further delayed by 3.2 (3.7) days in 2016-35 (2046-65) due to mid-autumn Ts increases. This study suggests that the mid-autumn warming is largely responsible for the observed LCD changes in South Korea and will intensify the delaying trends in the future.


A High-throughput Automated ELISA Assay for Detection of IgG Antibodies to the SARS-CoV-2 Spike Protein.
The SARS-CoV-2 pandemic and vaccination campaign has illustrated the need for high throughput serological assays to quantitatively measure antibody levels. Here, we present a protocol for a high-throughput colorimetric ELISA assay to detect IgG antibodies against the SARS-CoV-2 spike protein. The assay robustly distinguishes positive from negative samples, while controlling for potential non-specific binding from serum samples. To further eliminate background contributions, we demonstrate a computational pipeline for fitting ELISA titration curves, that produces an extremely sensitive antibody signal metric for quantitative comparisons across samples and time.


Bayesian geostatistical modeling of Malaria Indicator Survey data in Angola.
The 2006-2007 Angola Malaria Indicator Survey (AMIS) is the first nationally representative household survey in the country assessing coverage of the key malaria control interventions and measuring malaria-related burden among children under 5 years of age. In this paper, the Angolan MIS data were analyzed to produce the first smooth map of parasitaemia prevalence based on contemporary nationwide empirical data in the country. Bayesian geostatistical models were fitted to assess the effect of interventions after adjusting for environmental, climatic and socio-economic factors. Non-linear relationships between parasitaemia risk and environmental predictors were modeled by categorizing the covariates and by employing two non-parametric approaches, the B-splines and the P-splines. The results of the model validation showed that the categorical model was able to better capture the relationship between parasitaemia prevalence and the environmental factors. Model fit and prediction were handled within a Bayesian framework using Markov chain Monte Carlo (MCMC) simulations. Combining estimates of parasitaemia prevalence with the number of children under we obtained estimates of the number of infected children in the country. The population-adjusted prevalence ranges from in Namibe province to in Malanje province. The odds of parasitaemia in children living in a household with at least ITNs per person was by 41% lower (CI: 14%, 60%) than in those with fewer ITNs. The estimates of the number of parasitaemic children produced in this paper are important for planning and implementing malaria control interventions and for monitoring the impact of prevention and control activities.


ATTED-II v11: A Plant Gene Coexpression Database Using a Sample Balancing Technique by Subagging of Principal Components.
ATTED-II (https://atted.jp) is a gene coexpression database for nine plant species based on publicly available RNAseq and microarray data. One of the challenges in constructing condition-independent coexpression data based on publicly available gene expression data is managing the inherent sampling bias. Here, we report ATTED-II version 11, wherein we adopted a coexpression calculation methodology to balance the samples using principal component analysis and ensemble calculation. This approach has two advantages. First, omitting principal components with low contribution rates reduces the main contributors of noise. Second, balancing large differences in contribution rates enables considering various sample conditions entirely. In addition, based on RNAseq- and microarray-based coexpression data, we provide species-representative, integrated coexpression information to enhance the efficiency of interspecies comparison of the coexpression data. These coexpression data are provided as a standardized z-score to facilitate integrated analysis with different data sources. We believe that with these improvements, ATTED-II is more valuable and powerful for supporting interspecies comparative studies and integrated analyses using heterogeneous data.


Conditioned inhibition of cyclophosphamide-induced taste aversion.
Rats in an experimental group received trials during which 1 flavor (saccharin) was always followed by cyclophosphamide, an immunosuppressive drug, but another (vanilla) was not. An unconditioned stimulus-only group served as a control. Flavor-preference tests revealed that conditioned excitation and conditioned inhibition occurred in the conditioned group subjects but not in the control group subjects. This demonstration suggests that a conditioned inhibitor might be used to modify conditioned and unconditioned immune system functions, for example, natural killer-cell activity.


Efficacy of micafungin for the treatment of invasive candidiasis and candidaemia in patients with neutropenia.
Neutropenia is linked to the development of invasive candidiasis/candidaemia, for which micafungin has demonstrated efficacy, but evidence in patients with neutropenia is limited. The aim of this study was to evaluate the efficacy of micafungin for the treatment of invasive candidiasis/candidaemia in patients with neutropenia (<500 neutrophils/μL) and without neutropenia. This pooled, post hoc analysis of 2 Phase 3 trials compared micafungin 100 mg/d (adults) and 2 mg/kg/d (paediatrics) with L-AmB 3 mg/kg/d (NCT00106288) and micafungin 100 mg/d and 150 mg/d with caspofungin 70 mg/d followed by 50 mg/d (adults) (NCT00105144); treatment duration 2-4 weeks (≤8 weeks for chronic disseminated candidiasis). Effects of neutropenia duration and Candida spp. on efficacy outcomes (treatment success, clinical and mycological response) were examined. Of 685 patients, 77 had neutropenia. The most common infection in patients with/without neutropenia was due to C. tropicalis (31/77) and C. albicans (295/608) respectively. Overall success was numerically lower in patients with vs without neutropenia (63.6% vs 72.9%). Clinical and mycological response was similar between groups. Neutropenia duration or Candida spp. did not impact micafungin's overall success rate. This analysis supports evidence that micafungin is effective against invasive candidiasis/candidaemia in patients with neutropenia, irrespective of neutropenia duration or Candida spp., although overall success may be lower than in patients without neutropenia.


Characterization of an Iron-Copper Bimetallic Metal-Organic Framework for Adsorption of Methyl Orange in Aqueous Solution.
Iron-based organic frame material MIL-53 (Fe) was synthesized by the hydrothermal method with Cu2+ incorporated to obtain bimetallic composite MIL-53 (Fe, Cu). The structure and morphology of the material were characterized by SEM, XRD, BET, FTIR, XPS, and zeta potential. The adsorption performance of MIL-53 (Fe, Cu) on methyl orange was tested under a variety of conditions, including the effects of pH and material dosage, by the static adsorption test. The results show that under the condition of pH = 7, a temperature of 30°C, and an adsorbent dosage of 20 mg, the removal rate of MIL-53 (Fe, Cu) for methyl orange can reach more than 96% within 4 h, and the maximum adsorption capacity after fitting by the thermodynamic model can reach 294.43 mg/g, showing the excellent adsorption performance of MIL-53 (Fe, Cu) on methyl orange. In addition, by exploring the adsorption mechanism of MIL-53 (Fe, Cu) on methyl orange, it is found that the adsorption of MIL-53 (Fe, Cu) on methyl orange depends on chemical adsorption, as evidenced by combining Fe3+ and Cu2+ in the material with methyl orange molecules to form complexes to achieve adsorption. While the specific surface area of the material had no obvious effect on adsorption, the effects of pH, temperature, and concentration were explored. At a pH of 6.5, greater adsorption occurred at higher temperatures, as determined by thermodynamic model fitting, as well as with higher initial methyl orange molecule concentration.


Video-assisted repair of an eventrated left hemidiaphragm.
Video-assisted thoracoscopic surgery is emerging as a viable approach to increasingly complex intrathoracic therapeutic procedures. Here, we present a case of eventrated left hemidiaphragm caused by a blunt trauma in an elderly man. The diaphragm was repaired successfully using a video-assisted procedure, thus giving the patient the advantages of a minimally invasive operation.


The latex agglutination test versus counterimmunoelectrophoresis for rapid diagnosis of bacterial meningitis.
A modified latex agglutination (LA) test was compared with Gram-staining and counterimmunoelectrophoresis (CIE) for the rapid detection in the cerebrospinal fluid (CSF) of antigen to Haemophilus influenzae type b, Neisseria meningitidis groups A, B and C, Escherichia coli K1, Streptococcus pneumoniae and group B streptococci, seven frequent causes of bacterial meningitis in children. Of 50 CSF samples from patients with culture-proven bacterial meningitis 90% were correctly shown by the LA test to contain antigen of the responsible organism. Gram-staining revealed organisms in 80% of 45 of these samples. In 75% of the 40 samples that were of sufficient volume for CIE, positive results for the appropriate antigen were obtained. The concentration of antigen detected in the CSF by the LA test varied from undetectable to 800 000 ng/ml. Patients with a high concentration (more than 2000 ng/ml or a positive result at dilutions of CSF over 1/8) were significantly more likely to have a poor response to therapy (two died and two had persistent pleocytosis or bacteria in the CSF) than patients with a lower concentration (4/16 v. 0/18, P < 0.05). After appropriate therapy was begun the concentration of antigen fell dramatically, but measurable amounts of antigen persisted in the CSF for up to 6 days. The LA test detected bacterial antigen at concentrations 2 to 70 times below the lower limit detected by CIE. In seven additional patients who had received antibiotics before lumbar puncture was performed the LA test detected antigen from meningitis-causing bacteria even though cultures of the CSF were sterile. In another 145 patients who did not have meningitis the results of the LA test were negative. The LA test, done as described in this article, is easier to perform than CIE and should be a useful addition to the diagnostic tests carried out on the CSF of any patient suspected of having meningitis.


15-Deoxy-Delta12,14-prostaglandin J2 inhibits IL-1beta-induced cyclooxygenase-2 expression in mesangial cells.
Cyclooxygenase-2 (COX-2), a key enzyme in the synthesis of prostaglandins, is induced in mesangial cells in response to proinflammatory cytokines. Recently, 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2), one of the natural ligands of peroxisome proliferator-activated receptor gamma (PPARgamma), has been reported to have an anti-inflammatory effect. Therefore, we examined the effect of 15d-PGJ2 on COX-2 expression in cultured rat mesangial cells. Mesangial cells were incubated with 15d-PGJ2 for 30 minutes and then exposed to interleukin-1beta (IL-1beta). The expression of COX-2 mRNA and proteins was determined by Northern blot and immunoblot analyses, respectively. Accumulation of prostaglandin E2 (PGE2) was measured by an enzyme-linked immunosorbent assay (ELISA). Activities of mitogen-activated protein kinases (MAPKs) were evaluated by an immunoblot analysis. DNA binding activities of activator protein-1 (AP-1) or nuclear factor-kappaB (NF-kappaB) were examined by an electrophoretic mobility shift assay (EMSA). The activities of PPAR responsive elements (PPRE) and COX-2 promoter were measured by a luciferase reporter assay. 15D-PGJ2 significantly suppressed IL-1beta-induced COX-2 expression and PGE2 production, but thiazolidinediones, synthetic PPARgamma ligands, did not affect COX-2 expression. Moreover, the cells transfected with a PPRE luciferase reporter did not respond to 15d-PGJ2. IL-1beta rapidly activated extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK), which were involved in the up-regulation of COX-2 induction, but 15d-PGJ2 inhibited the activation of these kinases. 15d-PGJ2 inhibited the IL-1beta-induced increase in binding activities of nuclear proteins to consensus AP-1 site and AP-1-like site of COX-2 promoter but not of NF-kappaB. IL-1beta was unable to activate the COX-2 promoter when the AP-1-like site was mutated. These data suggest that 15d-PGJ2 inhibits IL-1beta-induced COX-2 expression, independent of PPARgamma activation, by suppression of ERK and JNK pathways and AP-1 activation in mesangial cells. Thus, 15d-PGJ2 may play an important role in the negative feedback mechanism of COX-2 expression in renal inflammation and may be useful as an anti-inflammatory agent.


Nebivolol-induced vasodilation of renal afferent arterioles involves β3-adrenergic receptor and nitric oxide synthase activation.
Nebivolol is a β(1)-adrenergic blocker that also elicits renal vasodilation and increases the glomerular filtration rate (GFR). However, its direct actions on the renal microvasculature and vasodilator mechanism have not been established. We used the in vitro blood-perfused juxtamedullary nephron technique to determine the vasodilator effects of nebivolol and to test the hypothesis that nebivolol induces vasodilation of renal afferent arterioles via an nitric oxide synthase (NOS)/nitric oxide (NO)/soluble guanylate cyclase (sGC)/cGMP pathway and the afferent arteriolar vasodilation effect may be mediated through the release of NO by activation of NOS via a β(3)-adrenoceptor-dependent mechanism. Juxtamedullary nephrons were superfused with nebivolol either alone or combined with the sGC inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) or the NOS inhibitor N(ω)-nitro-l-arginine (l-NNA) or the β-blockers metoprolol (β(1)), butoxamine (β(2)), and SR59230A (β(3)). Nebivolol (100 μmol/l) markedly increased afferent and efferent arteriolar diameters by 18.9 ± 3.0 and 15.8 ± 1.8%. Pretreatment with l-NNA (1,000 μmol/l) or ODQ (10 μmol/l) decreased afferent vasodilator diameters and prevented the vasodilator effects of nebivolol (2.0 ± 0.2 and 2.4 ± 0.6%). Metoprolol did not elicit significant changes in afferent vasodilator diameters and did not prevent the effects of nebivolol to vasodilate afferent arterioles. However, treatment with SR59230A, but not butoxamine, markedly attenuated the vasodilation responses to nebivolol. Using a monoclonal antibody to β(3)-receptors revealed predominant immunostaining on vascular and glomerular endothelial cells. These data indicate that nebivolol vasodilates both afferent and efferent arterioles and that the afferent vasodilator effect is via a mechanism that is independent of β(1)-receptors but is predominantly mediated via a NOS/NO/sGC/cGMP-dependent mechanisms initiated by activation of endothelial β(3)-receptors.


Rapid method that aids in distinguishing Gram-positive from Gram-negative anaerobic bacteria.
Several species of anaerobic bacteria display variable Gram stain reactions which often make identification difficult. A simple, rapid method utilizing a 3% solution of potassium hydroxide to distinguish between gram-positive and gram-negative bacterial was tested on 213 strains of anaerobic bacteria representing 19 genera. The Gram stain reaction and KOH test results were compared with the antibiotic disk susceptibilities (vancomycin and colistin) the preliminary grouping of anaerobic bacteria. All three procedures were in agreement for the majority of strains examined. Some strains of clostridia, eubacteria, and bifidobacteria stained gram negative or gram variable; the KOH and antibiotic disk susceptibility tests correctly classified these strains as gram-positive. The KOH test incorrectly grouped some strains of Bacteroides sp., Fusobacterium sp., Leptotrichia buccalis, and Veillonella parvula, but all Gram stain results for these strains were consistent for gram-negative bacteria. The KOH test is a useful supplement to the Gram stain and antibiotic disk susceptibility testing for the initial classification of anaerobic bacteria.


Activated prothrombin complex concentrates for the reversal of anticoagulant-associated coagulopathy.
Prothrombin complex concentrate (PCC) products are emerging as alternative strategies for reversing anticoagulant pharmacotherapy. Factor eight inhibitor bypassing activity (FEIBA, or anti-inhibitor coagulant complex) is an activated PCC (aPCC). Although FEIBA is approved by the FDA to control spontaneous bleeding episodes and to prevent bleeding with surgical interventions in hemophilia A and hemophilia B patients with inhibitors to factor VIII, recent data have suggested that the product may be used off-label as an anticoagulant-reversal agent. To evaluate the safety and efficacy of aPCC products in reversing anticoagulant pharmacotherapy, we searched online databases for English-language publications that discussed this topic. The EMBASE, MEDLINE, and International Pharmaceutical Abstracts databases were used. We evaluated all articles published in the English language identified from the data sources. We included studies conducted in human subjects and in in vitro and in vivo models in our review. Current published evidence suggests that the use of an aPCC, compared with fresh-frozen plasma, is associated with a significantly faster correction of supratherapeutic International Normalized Ratios (INRs) secondary to warfarin therapy. Conflicting evidence exists regarding the ability of aPCCs to reverse the prolonged bleeding times caused by the anticoagulant agents dabigatran etexilate (Pradaxa), rivaroxaban (Xarelto), apixaban (Eliquis), and fondaparinux (Arixtra). The theoretical risks of thrombosis associated with PCC products must be carefully considered before they are administered to patients who require coagulation therapy. The use of aPCCs to reverse the anticoagulant effects of warfarin, dabigatran, or rivaroxaban should be limited because of the lack of efficacy and safety data in humans. Moreover, the safety of aPCCs in off-label indications has not been adequately assessed.


Downregulation of glutamic acid decarboxylase in Drosophila TDP-43-null brains provokes paralysis by affecting the organization of the neuromuscular synapses.
Amyotrophic lateral sclerosis is a progressive neurodegenerative disease that affects the motor system, comprised of motoneurons and associated glia. Accordingly, neuronal or glial defects in TDP-43 function provoke paralysis due to the degeneration of the neuromuscular synapses in Drosophila. To identify the responsible molecules and mechanisms, we performed a genome wide proteomic analysis to determine differences in protein expression between wild-type and TDP-43-minus fly heads. The data established that mutant insects presented reduced levels of the enzyme glutamic acid decarboxylase (Gad1) and increased concentrations of extracellular glutamate. Genetic rescue of Gad1 activity in neurons or glia was sufficient to recuperate flies locomotion, synaptic organization and glutamate levels. Analogous recovery was obtained by treating TDP-43-null flies with glutamate receptor antagonists demonstrating that Gad1 promotes synapses formation and prevents excitotoxicity. Similar suppression of TDP-43 provoked the downregulation of GAD67, the Gad1 homolog protein in human neuroblastoma cell lines and analogous modifications were observed in iPSC-derived motoneurons from patients carrying mutations in TDP-43, uncovering conserved pathological mechanisms behind the disease.


An animal model of co-existing sarcopenia and osteoporotic fracture in senescence accelerated mouse prone 8 (SAMP8).
Sarcopenia and osteoporotic fracture are common aging-related musculoskeletal problems. Recent evidences report that osteoporotic fracture patients showed high prevalence of sarcopenia; however, current clinical practice basically does not consider sarcopenia in the treatment or rehabilitation of osteoporotic fracture. There is almost no report studying the relationship of the co-existing of sarcopenia and osteoporotic fracture healing. In this study, we validated aged senescence accelerated mouse prone 8 (SAMP8) and senescence accelerated mouse resistant 1 (SAMR1) as animal models of senile osteoporosis with/without sarcopenia. Bone mineral density (BMD) at the 5th lumbar and muscle testing of the two animal strains were measured to confirm the status of osteoporosis and sarcopenia, respectively. Closed fracture was created on the right femur of 8-month-old animals. Radiographs were taken weekly post-fracture. MicroCT and histology of the fractured femur were performed at week 2, 4 and 6 post-fracture, while mechanical test of both femora at week 4 and 6 post-fracture. Results showed that the callus of SAMR1 was significantly larger at week 2 but smaller at week 6 post-fracture than SAMP8. Mechanical properties were significantly better at week 4 post-fracture in SAMR1 than SAMP8, indicating osteoporotic fracture healing was delayed in sarcopenic SAMP8. This study validated an animal model of co-existing sarcopenia and osteoporotic fracture, where a delayed fracture healing might be resulted in the presence of sarcopenia.


Epidermal cyst of the breast treated by vacuum-assisted biopsy.
A 38-year-old woman presented for evaluation of a firm mass (measuring 20 × 20 mm) in the upper outer quadrant of her left breast. On the basis of the clinical and radiologic findings, we diagnosed a benign breast tumor and scheduled removal by a hand-held vacuum-assisted biopsy device (VABD) under ultrasonographic guidance. Because the first specimen removed from the tumor was white, flaky, and waxy material, we strongly suspected that the lesion was an epidermal cyst. We continued VABD treatment until the tumor was invisible on real-time ultrasonography. Histologic examination demonstrated that the tumor was composed of mature stratified squamous epithelium and laminated layers of keratin, findings consistent with a diagnosis of epidermal cyst. These cysts rarely occur in the breast and are sometimes difficult to distinguish from breast cancer. To our knowledge, this is the first report of an epidermal cyst treated by VABD.


Lessons in translation: insights from a collaboration integrating community health workers into diabetes care.
Beginning in 2007, a community health center and a community health worker organization collaborated on a community health worker initiative to improve diabetes outcomes among underserved communities. Despite a shared vision, the initiative ended prematurely because of a number of unexpected collaborative challenges. This article describes the results of a qualitative investigation into these challenges. Through examples, we show how our collaborative difficulties were due to 3 interacting influences: logistics, participation, and institutional culture. We argue for the importance of institutional cultural competency in health care collaborations and provide recommendations for future collaborations that takes into account these 3 overarching influences.


β-CuN3: the overlooked ground-state polymorph of copper azide with heterographene-like layers.
An unexpected polymorph of the highly energetic phase CuN3 has been synthesized and crystallizes in the orthorhombic space group Cmcm with a=3.3635(7), b=10.669(2), c=5.5547(11) Å and V=199.34(7) Å(3). The layered structure resembles graphite with an interlayer distance of 2.777(1) Å (=1/2 c). Within a single layer, considering N3(-) as one structural unit, there are 10-membered almost hexagonal rings with a heterographene-like motif. Copper and nitrogen atoms are covalently bonded with Cu-N bonds lengths of 1.91 and 2.00 Å, and the N3(-) group is linear but with N-N 1.14 and 1.20 Å. Electronic-structure calculations and experimental thermochemistry show that the new polymorph termed β-CuN3 is more stable than the established α-CuN3 phase. Also, β-CuN3 is dynamically, and thus thermochemically, metastable according to the calculated phonon density of states. In addition, β-CuN3 exhibits negative thermal expansion within the graphene-like layer.


Patient satisfaction with a hospital-based neuropsychology service.
Objective The aim of the present study was to develop and pilot a measure of patient satisfaction that encompasses themes, activities, settings and interactions specific to the neuropsychological assessment process. Methods A focus group of out-patients (n=15) was surveyed to identify the factors commonly associated with a satisfactory neuropsychological experience. Responses informed a purposely designed 14-item patient satisfaction scale (α=0.88) that was completed by 66 hospital out-patients with mild to moderate cognitive impairment. Results Satisfaction with the neuropsychological assessment process was generally reported, with the testing phase (85%) rated significantly more favourably than the pre-assessment (79%) and feedback (70%) phases. Commentaries provided by 32 respondents identified interpersonal facilitators to a satisfactory neuropsychological assessment experience, but also dissatisfaction with physical aspects of the testing environment in addition to service availability. Conclusions The patient satisfaction scale can be used as a quality assurance tool to evaluate neuropsychological service delivery. Large-scale research is needed to confirm the scale's psychometric properties. Further research may also include a broader perspective on the consumers' experience of neuropsychological services.


Beneficial effects of metoprolol on myocardial sympathetic function: Evidence from a randomized, placebo-controlled study in patients with congestive heart failure.
We sought to investigate whether beta-blockers exert a presynaptic effect in the myocardium as measured by 123I-metaiodobenzylguanidine. The study comprised 59 patients with congestive heart failure, New York Heart Association class II or III, and left ventricular ejection fraction <35%. After an open label titration phase, patients were randomized to their maximal tolerable dose of metoprolol or placebo. Myocardial MIBG uptake was measured before the titration phase and after 6 months of treatment. Other parameters were maximal oxygen consumption, 6-minute walking test, plasma neurohormones, and echocardiographic parameters. We found a 21.9% increase in mean myocardial MIBG uptake after 6 months of treatment with metoprolol. In contrast, MIBG uptake decreased by 7.8% in the placebo group (P = 0.03 compared with metoprolol). Left ventricular end-diastolic diameter decreased from 74 +/- 11 mm to 67 +/- 10 mm (P <.05, within-group comparison) and LVEF increased from 25.3% +/- 7.4% to 32.6% +/- 9.6% (P <.05, within-group comparison) in the metoprolol group. Placebo-treated patients showed no significant changes. Comparison of changes in left ventricular end-diastolic diameter and LVEF between metoprolol and placebo did not reach statistical significance (P = 0.2). This randomized, placebo-controlled study demonstrates that metoprolol has a presynaptic effect as measured by myocardial MIBG scintigraphy in both ischemic and nonischemic cardiomyopathy.


Comparison between SI and SII responses as a function of stimulus intensity.
In this MEG study we investigated the differences in responses to somatosensory electrical stimuli between primary (SI) and secondary (SII) sensory cortices using 10 different levels of stimulus intensity, starting from below the sensory threshold up to a weak painful level. SI dipole source linearly increased in amplitude as the stimulus intensity raised up to a strong motor level and then saturated at higher stimulation levels. The contralateral and ipsilateral SII dipole source strengths followed the stimulus intensity growing up to the motor threshold, but showed a decrease at the strong motor level, followed by an increase as the stimulus intensity raised towards the weak painful threshold. These results suggest different responses of SI and SII cortices as the intensity of stimulation rises from non-painful to painful values.


Decreasing motor stereotypy with competing stimuli and tasks: Analysis of prompted engagement and response blocking.
Competing stimulus assessments (CSAs) are used to empirically identify stimuli associated with low levels of problem behavior. For some individuals with automatically maintained behavior, it can be difficult to identify effective competing stimuli. Recent research shows that prompting engagement and response blocking can be employed during the CSA to obtain significant reductions in problem behavior. The purpose of the present study was to replicate and extend prior research on the use of these tactics not only with competing stimuli, but also competing tasks, which require the active completion of a discrete response or response sequence. In addition, the current study validated the results of these pretreatment assessments in an extended treatment analysis, and examined the isolated and combined effects of prompting and response blocking within a component analysis. Future research directions and implications for clinical practice are discussed.


[Study on treatment of iron-deficiency anemia by shengxuening].
To observe the therapeutic effect of shengxuening (SXN) in treating iron-deficiency anemia (IDA) and to explore its molecular mechanism on iron metabolism balance regulation. Patients with IDA were randomly divided into the treated group and the control group, 50 in each group. They were treated with SXN (0.1 g, three times per day) and ferrous gluconate (0.1 g, three times per day) respectively, for 30 days. Levels of serum iron (Fe), total iron binding capacity (TIBC), transferrin saturation (TS), serum ferritin (SF), transferrin (Tf), soluble transferrin receptor (sTfR) and blood routine test, as well as scoring of TCM qi-blood deficiency Syndrome were conducted before and after treatment. The total effective rate in the treated group reached 92%, it was shown that SXN could improve the iron metabolism, increase levels of Fe, TS, SF and reduce levels of TIBC, Tf, sTfR, it has obvious effect in promoting erythrocyte generation and could promote formation of leucocytes and platelets. The total effective rate in the control group was 32%, which was significantly lower than that in the treated group (P < 0.01). The effect of SXN in treating IDA and qi-blood deficiency Syndrome is evident, it could improve the iron metabolism, increase levels of Fe, TS, SF and lower levels of TIBC, Tf, sTfR.


[Effect of sarcolysin and asalin on the incorporation of thymidine-H3 in the DNA of sarcoma 45 and tissues of tumor-bearing rats].
A comparison was made of the action of sarcolysin and asalin on the synthesis of DNA in sarcoma 45, the spleen, thymus, bone marrow and liver of tumour-bearing rats depending of the time of administration of the preparation. There was seen a direct relationship between the selectivity of sarcolysin and asalin action with a different bearer structure and the capacity of these perparations to depress DNA synthesis in the tumour and in normal tissues.


[Determination of boron content in natural mineral and spring waters by ICP-OES technique].
Maximum admissible level of boron concentration in water intended for human consumption and in natural mineral and spring waters is usually estimated taking into account actual WHO criteria and requirements listed in Directive No 98/83/EC - 1 mg/l. In majority countries of European Union maximum admissible level of boron in water intended for human consumption is 1 mg/l, however in Slovakia and in Netherlands maximum admissible levels of this element are 0.3 mg/l and 0.5 mg/l, respectively. In this work developed and validated method of determination of boron by inductively coupled plasma emission spectrometry technique was applied for determination of this element in 26 natural mineral and spring waters. Concentrations of boron determined in sixteen mineral and spring waters analyzed were in the range from 0.029 mg/l to 0.552 mg/l while in ten waters analyzed the contents of boron were below 0.026 mg/l. The contents of boron in analyzed waters were below maximum admissible level in Poland presented in the Decree of Minister of Health from 29 March 2007 on the quality of water intended for human consumption and were not dangerous for human health.


Eprinomectin pour-on (EPRINEX® Pour-on, Merial): efficacy against gastrointestinal and pulmonary nematodes and pharmacokinetics in sheep.
The anthelmintic efficacy of the 0.5% w/v topical formulation of eprinomectin (EPN), EPRINEX® Pour-on (Merial) when administered at 1 mg/kg body weight was evaluated in sheep in two dose confirmation laboratory studies and one multicenter field study. In addition, the pharmacokinetics of EPN when administered at that dosage to adult sheep was determined. In the two dose confirmation studies, which included 10 sheep each, sheep treated with topical EPN had significantly (p < 0.05) fewer of the following nematodes than the untreated sheep with overall reduction of nematode counts by >99%: adult Dictyocaulus filaria, Haemonchus contortus, Teladorsagia circumcincta(pinnata/trifurcata), Trichostrongylus axei, T. colubriformis, T. vitrinus, Cooperia curticei, Nematodirus battus, Strongyloides papillosus, Chabertia ovina and Oesophagostomum venulosum, and inhibited fourth-stage Teladorsagia larvae. A total of 196 sheep harboring naturally acquired gastrointestinal nematode infections were included in the field efficacy study at two sites each in Germany (48 Merino x Ile de France lambs, 52 adult Merino females) and in Italy (adult male and female Bagnolese, Lacaune, Lacaune x Bagnolese, Bagnolese x Sarda sheep; 48 animals per site). Animals were blocked on pre-treatment body weight and within each block, one animal was randomly assigned to the control (untreated) group and three animals were randomly assigned to be treated with topical EPN. Examination of feces 14 days after treatment demonstrated that, relative to the controls, topical EPN-treated sheep had significantly (p < 0.0001) lower strongylid egg counts. Reduction was ≥97% at each site and 98.6% across all sites. Pharmacokinetics of EPN following single treatment with topical EPN were determined in eight ~4.5 year old female Merino cross sheep based on the analysis of plasma samples which were collected from two hours to 21 days following treatment. The main pharmacokinetic parameters were: Cmax 6.20 ± 1.71 ng/mL, AUClast 48.8 ± 19.2 day*ng/mL, Tmax 3.13 ± 2.99 days and T1/2 6.40 ± 2.95 days. No treatment-related health problems or adverse drug events were observed in any study. These studies demonstrated 0.5% w/v EPN administered topically at 1 mg/kg body weight to be highly efficacious against a broad range of ovine gastrointestinal nematodes and D. filaria lungworms and well tolerated by sheep of different ages, breeds, gender and physiological status.


Short- and medium-chain chlorinated paraffins in air and soil of subtropical terrestrial environment in the pearl river delta, South China: distribution, composition, atmospheric deposition fluxes, and environmental fate.
Research on the environmental fate of short- and medium-chain chlorinated paraffins (SCCPs and MCCPs) in highly industrialized subtropical areas is still scarce. Air, soil, and atmospheric deposition process in the Pearl River Delta of South China were investigated, and the average SCCP and MCCP concentrations were 5.2 μg/sampler (17.69 ng/m(3)) and 4.1 μg/sampler for passive air samples, 18.3 and 59.3 ng/g for soil samples, and 5.0 and 5.3 μg/(m(2)d) for deposition samples, respectively. Influenced by primary sources and the properties of chlorinated paraffins (CPs), a gradient trend of concentrations and a fractionation of composition from more to less industrialized areas were discovered. Intense seasonal variations with high levels in summer air and winter deposition samples indicated that the air and deposition CP levels were controlled mainly by the vapor and particle phase, respectively. Complex environmental processes like volatilization and fractionation resulted in different CP profiles in different environment matrixes and sampling locations, with C(10-11) C(l6-7) and C(14) C(l6-7), C(10-12) C(l6-7) and C(14) C(l6-8), and C(11-12) C(l6-8) and C(14) C(l7-8) dominating in air, soil, and atmospheric deposition, respectively. Shorter-chain and less chlorinated congeners were enriched in air in the less industrialized areas, while longer-chain and higher chlorinated congeners were concentrated in soil in the more industrialized areas. This is suggesting that the gaseous transport of CPs is the dominant mechanism responsible for the higher concentrations of lighter and likely more mobile CPs in the rural areas.


Nuclear-organelle interactions: the immutans variegation mutant of Arabidopsis is plastid autonomous and impaired in carotenoid biosynthesis.
The immutans (im) variegation mutant of Arabidopsis thaliana contains green- and white-sectored leaves due to the action of a nuclear recessive gene. The mutation is somatically unstable, and the degree of sectoring is influenced by light and temperature. Whereas the cells in the green sectors contain normal chloroplasts, the cells in the white sectors are heteroplastidic and contain non-pigmented plastids that lack organized lamellar structures, as well as small pigmented plastids and/or rare normal chloroplasts. This indicates that the plastids in im white cells are not affected equally by the nuclear mutation and that the expression of immutans is 'plastid autonomous'. In contrast to other variegation mutants with heteroplastidic cells, the defect in im is not maternally inherited. immutans thus represents a novel type of nuclear gene-induced variegation mutant. It has also been found that the white tissues of immutans accumulate phytoene, a non-colored C40 carotenoid intermediate. This suggests that immutans controls, either directly or indirectly, the activity of phytoene desaturase (PDS), the enzyme that converts phytoene to zeta-carotene in higher plants. However, im is not the structural gene for PDS. A secondary effect of carotenoid deficiency, both in immutans and in wild-type plants treated with a herbicide that blocks carotenoid synthesis, is an increase in acid ribonuclease activity in white tissue. It is concluded that the novel variegation generated by the immutans mutation should offer great insight into the complex circuitry that regulates nuclear-organelle interactions.


A Chromium(III)-Superoxo Complex as a Three-Electron Oxidant with a Large Tunneling Effect in Multi-Electron Oxidation of NADH Analogues.
Metal-superoxo species are involved in a variety of enzymatic oxidation reactions, and multi-electron oxidation of substrates is frequently observed in those enzymatic reactions. A CrIII -superoxo complex, [CrIII (O2 )(TMC)(Cl)]+ (1; TMC=1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane), is described that acts as a novel three-electron oxidant in the oxidation of dihydronicotinamide adenine dinucleotide (NADH) analogues. In the reactions of 1 with NADH analogues, a CrIV -oxo complex, [CrIV (O)(TMC)(Cl)]+ (2), is formed by a heterolytic O-O bond cleavage of a putative CrII -hydroperoxo complex, [CrII (OOH)(TMC)(Cl)], which is generated by hydride transfer from NADH analogues to 1. The comparison of the reactivity of NADH analogues with 1 and p-chloranil (Cl4 Q) indicates that oxidation of NADH analogues by 1 proceeds by proton-coupled electron transfer with a very large tunneling effect (for example, with a kinetic isotope effect of 470 at 233 K), followed by rapid electron transfer.


The experiences of parents of children diagnosed with cerebral adrenoleukodystrophy.
Adrenoleukodystrophy (ALD) is a rare X-linked neurodegenerative disease, affecting the brain, spinal cord and adrenal cortex. Childhood cerebral ALD (CCALD) is the most severe form of disease, involving rapidly progressive neurological deterioration. The treatment option for CCALD is allogenic haemopoietic stem cell transplant, which is only successful for early-stage disease. Parents' experiences of CCALD can inform healthcare delivery. To detail the experiences of parents of children diagnosed with cerebral ALD. A descriptive qualitative study. Parents were recruited via a UK-based community support organisation. Data collection involved single semi-structured interviews structured around a topic guide and conducted remotely. Data were analysed using the thematic analysis approach. Twelve parents from 11 families with a total of 16 children with ALD contributed to the study. Their 16 children with ALD followed one of three disease pathways, determined by the extent of neurological damage at diagnosis. Three themes, and their respective sub themes, describe the pathways and what they meant for parents. 'No possibility of treatment' concerns situations when CCALD was diagnosed at an advanced stage, the landslide of deterioration parents witnessed and their efforts to maintain normality. 'Close to the treatment threshold' describes situations where a small treatment window required parents to make agonising treatment decisions. 'Watching and waiting' explains the challenges for parents when disease was detected early enabling children to benefit from timely treatment. Parents' experiences were largely defined by the extent of cerebral damage at diagnosis, which determined the availability and success of treatment. There were specific challenges related to the three situations, indicating areas where support from health and care services may help parents deal with this devastating diagnosis. This study indicates support needs of parents across the spectrum of CCALD diagnoses and highlights the critical importance of early diagnosis.


Differences in Self-Reported Physical Activity and Body Mass Index Among Older Hispanic and Non-Hispanic White Men and Women: Findings from the 2009 California Health Interview Survey.
Older Hispanic Americans are a rapidly growing minority group who are disproportionately affected by diabetes mellitus and obesity. Given the importance of physical activity, particularly leisure-time activity, in the management of diabetes mellitus and obesity, the current study examined ethnic and sex differences in walking for transportation, leisure-time walking, moderate activity (not including walking), and vigorous activity between Hispanic and non-Hispanic white (NHW) older adults (age 55 and older) using the 2009 California Health Interview Survey, a population-based survey representative of California's noninstitutionalized population. The total sample consisted of 21,702 participants (20,148 NHW (7,968 men, 12,180 women) and 1,554 Hispanic (609 men, 945 women)). Multivariable logistic and linear regression analyses were adjusted for sociodemographic characteristics. The findings revealed that Hispanic men and women were significantly less likely to engage in self-reported leisure-time walking and vigorous activity than NHW men (adjusted odds ratio (aOR) = 0.71, 95% confidence interval (CI) = 0.51-0.99) and women (aOR = 0.60, 95% CI = 0.42-0.87). Regardless of ethnic group, men were more likely than women to engage in self-reported walking for transportation (aOR = 0.71, 95% CI = 0.58-0.87), moderate activity (aOR = 0.68, 95% CI = 0.57-0.81), and vigorous activity (aOR = 0.58, 95% CI = 0.50-0.68). All types of self-reported physical activity were associated with lower body mass index (BMI; P < .001), although significant interactions between sex and leisure time walking (P < .001), moderate activity (P < .001), and vigorous activity (P < .001) indicated that women who engaged in these activities reported the lowest BMIs. The findings highlight the importance of emphasizing walking in efforts to increase moderate and vigorous activity, particularly for older women.