QSAR model to predict Kp,uu,brain with a small dataset, incorporating predicted values of related parameter.

The unbound brain-to-plasma concentration ratio (Kp,uu,brain) is a parameter that indicates the extent of central nervous system penetration. Pharmaceutical companies build prediction models because many experiments are required to obtain Kp,uu,brain. However, the lack of data hinders the design of an accurate prediction model. To construct a quantitative structure-activity relationship (QSAR) model with a small dataset of Kp,uu,brain, we investigated whether the prediction accuracy could be improved by incorporating software-predicted brain penetration-related parameters (BPrPs) as explanatory variables for pharmacokinetic parameter prediction. We collected 88 compounds with experimental Kp,uu,brain from various official publications. Random forest was used as the machine learning model. First, we developed prediction models using only structural descriptors. Second, we verified the predictive accuracy of each model with the predicted values of BPrPs incorporated in various combinations. Third, the Kp,uu,brain of the in-house compounds was predicted and compared with the experimental values. The prediction accuracy was improved using five-fold cross-validation (RMSE = 0.455, r2 = 0.726) by incorporating BPrPs. Additionally, this model was verified using an external in-house dataset. The result suggested that using BPrPs as explanatory variables improve the prediction accuracy of the Kp,uu,brain QSAR model when the available number of datasets is small.

Evaluation of sensitization to the crude extract of Dermatophagoides farinae and its derived allergens, Der f 2 and Zen 1, in dogs with atopic dermatitis in Southern Brazil.

BACKGROUND: Atopic dermatitis is associated with the production of IgE antibodies against environmental allergens and allergens of the house dust miteDermatophagoides farinae are frequently implicated in the disease. OBJECTIVES: We aimed to observe the allergen-specific IgE against crudeD. farinae, Der f 2 and Zen 1 in dogs with atopic dermatitis and report if these dogs are in contact with material that could shelter mite allergens. METHODS: 100 dogs with clinical diagnosis of atopic dermatitis were included after exclusion of other forms of pruritic skin disease and dogs that already received specific or non-specific immunotherapy. These dogs were of different breeds and ages and they were presented at a veterinary teaching hospital and a private service of veterinary dermatology, both located in Curitiba, Southern Brazil. At the time of anamnesis, some questions were applied to know the possibility of these dogs having had contact with furniture and textile material which could shelter house dust mites. Sera samples were obtained and further analyzed by ELISA assay to measure serum IgE levels against these allergens with an established cut-off of 0.200 IgE optical density. RESULTS: The allergen-specific IgE positivity against crudeD. farinae (92 %) and Zen 1 (77 %) was higher than Der f 2 (56 %). There was a correlation in sensitization to crude D. farinae and Zen 1 that was not observed between crude D. farinae and Der f 2 and Der f 2 and Zen 1. The sensitization to D. farinae and its allergens was associated with an unrestricted exposition to furniture and textile material. CONCLUSION & CLINICAL RELEVANCE: dogs with atopic dermatitis are frequently sensitized to D. farinae and its allergens, Der f 2 and Zen 1, may be considered major allergens in these dogs. Zen 1 may be the main allergen responsible for the sensitization to crude D. farinae.

Ocean (de)oxygenation from the Last Glacial Maximum to the twenty-first century: insights from Earth System models.

All Earth System models project a consistent decrease in the oxygen content of oceans for the coming decades because of ocean warming, reduced ventilation and increased stratification. But large uncertainties for these future projections of ocean deoxygenation remain for the subsurface tropical oceans where the major oxygen minimum zones are located. Here, we combine global warming projections, model-based estimates of natural short-term variability, as well as data and model estimates of the Last Glacial Maximum (LGM) ocean oxygenation to gain some insights into the major mechanisms of oxygenation changes across these different time scales. We show that the primary uncertainty on future ocean deoxygenation in the subsurface tropical oceans is in fact controlled by a robust compensation between decreasing oxygen saturation (O2sat) due to warming and decreasing apparent oxygen utilization (AOU) due to increased ventilation of the corresponding water masses. Modelled short-term natural variability in subsurface oxygen levels also reveals a compensation between O2sat and AOU, controlled by the latter. Finally, using a model simulation of the LGM, reproducing data-based reconstructions of past ocean (de)oxygenation, we show that the deoxygenation trend of the subsurface ocean during deglaciation was controlled by a combination of warming-induced decreasing O2sat and increasing AOU driven by a reduced ventilation of tropical subsurface waters.This article is part of the themed issue 'Ocean ventilation and deoxygenation in a warming world'.

Validity and reliability of the Family Empowerment Scale for caregivers of adults with mental health issues.

WHAT IS KNOWN ON THE SUBJECT?: Empowerment of family caregivers of adults with mental health issues has received increasing attention among mental health nurses in Japan and has been recognized as a new goal of family interventions. The Family Empowerment Scale (FES) was originally developed to measure the empowerment status of parents of children with emotional disorders. However, it was later applied to broader health issues. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: We developed a Japanese version of the FES for family caregivers of adults with mental health issues (FES-AMJ) and examined the validity and reliability among parents. Results showed that the FES-AMJ had acceptable concurrent validity and reliability; however, insufficient construct validity was found, especially for the subscale regarding the service system. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Further studies need to modify the scale. Clarification of ideal family empowerment status in the service system through discussion with mental health nurses and family caregivers may be important. ABSTRACT: Introduction The Family Empowerment Scale (FES) was originally developed for parents of children with emotional disorders. In Japan, family empowerment is gaining increasing attention and may be one goal of nursing interventions. Aim To develop a Japanese version of the FES for family caregivers of adults with mental health issues and to study the validity and reliability of this scale among parents. Method We translated the FES into Japanese and administered this self-report questionnaire to 275 parents. Results The multitrait scaling analysis revealed acceptable convergent validity and insufficient discriminant validity among all subscales. In particular, all items of the Service system subscale had insufficient discriminant and/or convergent validity. Each subscale significantly correlated with the indicator of empowerment. The intraclass correlation coefficients of each subscale were .855-.917. Cronbach's alpha of each factor ranged from .867 to .895. Discussion The Service system subscale may not linearly reflect family empowerment, and instead may depend on unclear roles of family caregivers of adults, disorder severity or insufficient services. Implications for practice Further studies need to modify the scale. Clarification of ideal family empowerment status in the service system through discussion with mental health nurses and family caregivers may be important.

Evaluation of injection force of three insulin delivery pens.

OBJECTIVE: Reduced injection force is among the modifications to the Next Generation FlexPen (NGFP). This force was compared with two other prefilled pens: SoloStar (SS) and KwikPen (KP). RESEARCH DESIGN/METHODS: The injection force of the pens was measured, with either a BD Micro-Fine 31G thin-wall needle, or a NovoFine 32G Tip extra thin wall needle attached. Pens of each type were tested with both needles, during injection of 20 U insulin, at speeds 3.3, 5 and 8.3 mm/s. RESULTS: NGFP had a significantly (p < 0.05) lower mean injection force than SS or KP, at all injection speeds, with both needles. Injection forces (mean +/- s.d.) with NGFP and the BD Micro-Fine() 31G thin-wall needle were: 8.1 +/- 0.7, 10.7 +/- 1.4 and 15.6 +/- 0.9 N at the three speeds, respectively. For SS, the corresponding values were: 9.2 +/- 0.5, 13.3 +/- 0.8 and 20.7 +/- 2.4 N. For KP they were: 12.5 +/- 1.6, 16.9 +/- 1.2 and 24.5 +/- 2.6 N. Attached to the NovoFine 32G Tip extra thin wall needle, the NGFP injection forces were: 5.7 +/- 0.4, 8.2 +/- 0.7 and 12.7 +/- 0.5 N; with SS were: 6.7 +/- 0.3, 10.4 +/- 2.1 and 16.3 +/- 1.1 N; and with KP were: 9.1 +/- 1.3, 13.1 +/- 0.8 and 21.6 +/- 2.0 N. The injection force with NGFP was 12 - 25% lower compared with SS and 35 - 41% lower compared with KP. CONCLUSIONS: This study shows that NGFP has a significantly lower injection force than SS or KP.

The deep ocean during the last interglacial period.

Oxygen isotope analysis of benthic foraminifera in deep sea cores from the Atlantic and Southern Oceans shows that during the last interglacial period, North Atlantic Deep Water (NADW) was 0.4 degrees +/- 0.2 degrees C warmer than today, whereas Antarctic Bottom Water temperatures were unchanged. Model simulations show that this distribution of deep water temperatures can be explained as a response of the ocean to forcing by high-latitude insolation. The warming of NADW was transferred to the Circumpolar Deep Water, providing additional heat around Antarctica, which may have been responsible for partial melting of the West Antarctic Ice Sheet.

Eating epilepsy characterized by periodic spasms.

Seizures induced by eating are generally considered rare. Eating epilepsy is a kind of reflex epilepsy. We report two patients aged 11 and 16, with seizures provoked by eating. The eating-provoked seizures in both patients were a series of tonic spasms. Both ictal EEGs showed a periodic pattern characterized by diffuse high voltage slow wave. These findings were consistent with periodic spasms described by Gobbi et al. The ECD were widely distributed in both patients, although that of Patient 1 was partially clustered in the right frontal region. This is the first report of patients with periodic spasms induced by eating.

How people respond to illness in Mexico: self-care or medical care?

OBJECTIVE: To analyse illness factors associated to the form of attention (self-care or medical care) used to resolve health problems in Mexico. METHODS: A total of 5640 individuals who reported sickness within the 2 weeks before the application of the 1994 National Health Survey were analysed. A descriptive analysis was conducted to study demographic and socioeconomic characteristics, access to medical services, perception of seriousness of the illness, treatment received, and reasons why medical care was not sought. Factors associated with the form of attention (self-care or medical care) were identified through logistic regression. RESULTS: Sixty-one percent of the sample was self-attended. Of those who perceived their illness as serious, 52% did not use medical services because they considered them too expensive or did not have the money to pay. In the multivariate analysis, a greater frequency of self-care was observed among males over 5 years old who lacked access to Social Security medical services, or system of private insurance, suffered a mild illness, and lived in poor, rural areas. DISCUSSION: In Mexico, self-care represents the most important response to illness. Socioeconomic conditions, regardless of the perception of seriousness of the symptoms, determine the higher frequency of self-care mainly among those people living in poverty.

An experience of percutaneous embolization to post-traumatic arterial priapism in a child.

We report an experience of percutaneous transcatheter embolization to posttraumatic arterial priapism in a child. Priapism was successfully treated with this method. Angiography with subsequent selective embolization should be considered to be the treatment of choice for arterial priapism in children as well as in adults when less invasive treatments fail.

Postoperative delirium and melatonin levels in elderly patients.

BACKGROUND: Melatonin, a hormone produced in the pineal gland, is involved in circadian rhythms and the sleep-wake cycle. Postoperative delirium is encountered frequently in elderly patients after major surgery; whether changes in the pattern of melatonin secretion are associated is unclear. METHODS: Plasma samples were obtained every 2 hours from 19 patients without delirium and 10 with delirium after major abdominal surgery. Postoperative delirium was determined using the Confusion Assessment Method in the Practice Guideline of the American Psychiatric Association. RESULTS: All patients without delirium showed nearly identical preoperative and postoperative melatonin secretion for 24 hours, although peak values were significantly lower in patients more than 80 years old (7.2 +/- 2.3 pg/mL) than in patients younger than 80 years (24.4 +/- 4.1 pg/mL, P = 0.022). Patients with delirium showed two different abnormal postoperative patterns: in 5 patients without complications, melatonin levels were lower than preoperative values (11.0 +/- 5.8 versus 6.5 +/- 4.2 pg/mL, P = 0.079); and in 5 patients with complications, melatonin levels were markedly increased (21.1 +/- 4.5 versus 58.8 +/- 12.4 pg/mL, P = 0.043). CONCLUSIONS: Abnormal melatonin secretion may be involved in postoperative sleep disturbances, which triggered delirium in elderly patients.

The R-type pyocin of Pseudomonas aeruginosa is related to P2 phage, and the F-type is related to lambda phage.

Pseudomonas aeruginosa produces three types of bacteriocins: R-, F- and S-type pyocins. The S-type pyocin is a colicin-like protein, whereas the R-type pyocin resembles a contractile but non-flexible tail structure of bacteriophage, and the F-type a flexible but non-contractile one. As genetically related phages exist for each type, these pyocins have been thought to be variations of defective phage. In the present study, the nucleotide sequence of R2 pyocin genes, along with those for F2 pyocin, which are located downstream of the R2 gene cluster on the chromosome of P. aeruginosa PAO1, was analysed in order to elucidate the relationship between the pyocins and bacteriophages. The results clearly demonstrated that the R-type pyocin is derived from a common ancestral origin with P2 phage and the F-type from lambda phage. This notion was supported by identification of a lysis gene cassette similar to those for bacteriophages. The gene organization of the R2 and F2 pyocin gene cluster, however, suggested that both pyocins are not simple defective phages, but are phage tails that have been evolutionarily specialized as bacteriocins. A systematic polymerase chain reaction (PCR) analysis of P. aeruginosa strains that produce various subtypes of R and F pyocins revealed that the genes for every subtype are located between trpE and trpG in the same or very similar gene organization as for R2 and F2 pyocins, but with alterations in genes that determine the receptor specificity.

Determinants of bone and blood lead concentrations in the early postpartum period.

OBJECTIVE: This study investigated determinants of bone and blood lead concentrations in 430 lactating Mexican women during the early postpartum period and the contribution of bone lead to blood lead. METHODS: Maternal venous lead was measured at delivery and postpartum, and bone lead concentrations, measured with in vivo K-x ray fluorescence, were measured post partum. Data on environmental exposure, demographic characteristics, and maternal factors related to exposure to lead were collected by questionnaire. Linear regression was used to examine the relations between bone and blood lead, demographics, and environmental exposure variables. RESULTS: Mean (SD) blood, tibial, and patellar lead concentrations were 9.5 (4.5) microg/dl, 10.2 (10.1) microg Pb/g bone mineral, and 15.2 (15.1) microg Pb/g bone mineral respectively. These values are considerably higher than values for women in the United States. Older age, the cumulative use of lead glazed pottery, and higher proportion of life spent in Mexico City were powerful predictors of higher bone lead concentrations. Use of lead glazed ceramics to cook food in the past week and increased patellar lead concentrations were significant predictors of increased blood lead. Patellar lead concentrations explained one third of the variance accounted for by the final blood lead model. Women in the 90th percentile for patella lead had an untransformed predicted mean blood lead concentration 3.6 microg/dl higher than those in the 10th percentile. CONCLUSIONS: This study identified the use of lead glazed ceramics as a major source of cumulative exposure to lead, as reflected by bone lead concentrations, as well as current exposure, reflected by blood lead, in Mexico. A higher proportion of life spent in Mexico City, a proxy for exposure to leaded gasoline emissions, was identified as the other major source of cumulative lead exposure. The influence of bone lead on blood lead coupled with the long half life of lead in bone has implications for other populations and suggests that bone stores may pose a threat to women of reproductive age long after exposure has declined.

Multiple myeloma evaluated with 201Tl scintigraphy compared with bone scintigraphy.

UNLABELLED: The purpose of this study was to investigate the clinical usefulness of 201Tl chloride scintigraphy in the diagnostic evaluation of 20 patients with multiple myeloma (19/20 patients) or extramedullary plasmacytoma (1/20 patients) in comparison with bone scintigraphy. METHODS: Both 201Tl and bone scintigraphy were performed to obtain planar images on the same instrument. RESULTS: 201Tl scintigraphy showed increased uptake in 15 of 20 patients (75%) and was negative in 5 of 20 patients (25%). In addition, 201Tl scintigraphy of multiple myeloma was more useful in detecting the lesions in 11 of 17 patients and less useful in 6 of 17 patients than bone scintigraphy. CONCLUSION: The combination of 201Tl and bone scintigraphy, compared with bone scintigraphy alone, shows promise in more accurately diagnosing multiple myeloma.

Inverse association between plasma cholesterol and gallstone disease.

BACKGROUND: The association between gallstone disease (gallstones or cholecystectomy) and plasma lipids was evaluated in 2,089 subjects who attended a private health care facility in Mexico City from August 1991 to August 1992. METHODS: All participants provided data on their sociodemographic status, non-insulin-dependent diabetes mellitus diagnoses, alcohol consumption, and smoking habits; women also gave data regarding their obstetric-gynecologic histories. Ultrasounds of the liver and biliary tract were performed. Cholesterol levels, high-density lipoproteins cholesterol, and triglyceride plasma concentration were determined. RESULTS: This study shows a strong inverse association between gallstone disease and plasma cholesterol concentration, with OR = 0.61 (95% CI = 0.42-0.89) in the category of 181-239 mg/dL, and OR = 0.49 (95% CI = 0.32-0.77) in the group of 240 mg/dL or more, when compared to 180 mg/dL or less, after adjusting for the following risk factors: gender, age, and body mass index. CONCLUSIONS: These results suggest an increment in the catabolic pool of cholesterol, reflected in lower levels of plasma cholesterol in subjects with gallstone disease.

[Work conditions, labor fatigue and low birth weight among street vendors]. / Condiciones de trabajo, fatiga laboral y bajo peso al nacer en vendedoras ambulantes.

OBJECTIVE: This study presents the demographic, socioeconomic profile, working conditions and labor fatigue among fertile age street vendors in Mexico City. MATERIAL AND METHODS: 426 female street vendors were interviewed in Mexico City. This population was described and the association between the components labor fatigue and low birth weight (LBW) was analyzed by logistic regression in a subgroup of women who worked as street vendors during their last pregnancy. RESULTS: Of the interviewed group, 56% works more than 48 h per week, 87% had no social security, and 68% only had primary school level. The risk of LBW increased when workers had to cover selling quotes (OR 6.5, CI95% 1.3-31) when the merchandise were seasonal tools such as accessories or spare parts (OR 6.3, CI95% 1.5-26), when women had to exhibit their merchandise on the floor or carry it (OR 7.7 CI95% 1.8-32) and when financial support to initiate vending activities came from someone other than a close relative or friend (OR 7.4 CI95%, 1.2-44). CONCLUSIONS: These results contribute to identify the female vendors with higher risk of having child with LBW and suggest preventive actions.

Direct Observation of Foam Film Rupture by Several Types of Antifoams Using a Scanning Laser Microscope.

It is well known that the stability of a pseudoemulsion film, a thin liquid film formed between an antifoam particle and air, can be important during defoaming action. We have compared the bursting behavior of a two-dimensional thin liquid film from an aqueous surfactant solution on a glass plate, in which six types of antifoam particles have been dispersed, using laser microscopic techniques. The used antifoams were a silicone oil, a mixed-type antifoam (mixture of silicone oil and hydrophobic solid particles), a hydrophobic silica, and a silicone-based solid antifoam (prepared by interfacial polymerization with oil and water). The antifoaming performance of these six types of antifoams, measured by the glass cylinder shaking test, was in the order: the mixed-type antifoam >== the silicone-based solid antifoam > the hydrophobic silica >== the silicone oil. Pseudoemulsion film rupture was observed at the film thickness less than 0.1 µm for both the silocone oil and the hydrophobic silica. In the case of particles with rough edges (the silicone-based antifoam), pseudoemulsion film on the top of the particles can be easily ruptured at a convex part of the solid surface. Furthermore, solid particles existing on the surface of an oil droplet in the mixed-type antifoams form marked projections and these projections give rise to distortion of the thinning film. As soon as the distortion of the thinning film took place on the top of the antifoam droplet, the pseudoemulsion film can be instantaneously ruptured. Referring to the antifoaming mechanisms for mixed-type antifoams, both steps from the pseudoemulsion film formation to the lens formation and from the counter pseudoemulsion film formation to the bridge formation would be very fast and cause a very high antifoaming efficiency. Copyright 1999 Academic Press.

Different serum soluble Fas levels in patients with allergic rhinitis and bronchial asthma.

BACKGROUND: The pathogeneses of allergic rhinitis and bronchial asthma are believed to be closely mutually related because of the similar dynamics of allergy-inducing cells and molecules and clinical overlap. In this study, we compared these diseases in the dynamics of cell apoptosis-regulating molecules. METHODS: Allergic rhinitis patients (n=36), bronchial asthma patients (n=22), and healthy subjects (n=32) were subjected to measurement of serum (soluble Fas) (sFas) levels during the stable and attack disease phases by a sandwich enzyme-linked immunosorbent assay. RESULTS: Serum sFas levels in patients with allergic rhinitis during the attack phase were significantly lower (P<0.0001) than those in healthy individuals. There were no differences between them during the attack and stable disease phases. In contrast, serum sFas levels in patients with bronchial asthma during the attack phase were higher (P<0.0005) than those in healthy individuals. Interestingly, the levels during the attack phase were lower (P<0.002) than those during the stable phase. CONCLUSIONS: Our results suggest a different pathogenesis for allergic rhinitis and bronchial asthma at the cell apoptosis-linked step.

123I-MIBG SPECT of Merkel cell carcinoma.

131I-MIBG may be useful in the detection of neuroendocrine tumours. Merkel cell carcinoma is a neuroendocrine tumour of the skin. We evaluated a patient with Merkel cell carcinoma using 123I-MIBG single photon emission computed tomography (SPECT) which demonstrated tumour accumulation of the radiotracer in the right eyelid. This result suggests that 123I-MIBG SPECT may be useful in the evaluation of Merkel cell carcinoma.