Suture bridge fixation of a femoral condyle traumatic osteochondral defect.
Internal fixation of a traumatic osteochondral defect presents a challenge in terms of obtaining anatomic reduction, fixation, and adequate compression for healing. Fixation with countersunk intraarticular screws, Herbert screws, bioabsorbable screws and pins, mini-cancellous screws, and glue tissue adhesive have been reported with varying results. We present an alternative fixation method used in two patients for femoral condylar defects that achieved anatomic reduction with compression via a cruciate-shaped suture bridge construct tied down over a bony bridge. This fixation method allowed early passive range of motion and permitted high-quality MRI for followup of fracture healing and articular cartilage integrity. Arthroscopic examination of one of two patients at 6 months followup showed the gross appearance of a healed, anatomically reduced fracture. With 1 year followup for one patient and 2 years for the other, the patients have resumed activity as tolerated with full, painless range of motion at the knee. Longer-term outcomes are unknown. However, the suture bridge is an alternative means of fixation with encouraging early results for treatment of traumatic osteochondral fragments in the knee. Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.


New histopathological evidence for the relationship between hydromyelia and hydrocephalus following subarachnoid hemorrhage: An experimental study.
Subarachnoid hemorrhage (SAH) is a serious pathology with a high death and morbidity rate. There can be a relationship between hydromyelia and hydrocephalus following SAH; however, this subject has not been well investigated. Twenty-four rabbits (3 ± 0.4 years old; 4.4 ± 0.5 kg) were used in this study. Five of them were used as the control, and five of them as the SHAM group. The remaining animals (n = 14) had been used as the study group. The central canal volume values at the C1-C2 levels, ependymal cells, numbers of central canal surfaces, and Evans index values of the lateral ventricles were assessed and compared. Choroid plexus edema and increased water vesicles were observed in animals with central canal dilatation. The Evans index of the brain ventricles was 0.33 ± 0.05, the mean volume of the central canal was 1.431 ± 0.043 mm3, and ependymal cells density was 5.420 ± 879/mm2 in the control group animals (n = 5); 0.35 ± 0.17, 1.190 ± 0.114 mm3, and 4.135 ± 612/mm2 in the SHAM group animals (n = 5); and 0.44 ± 0.68, 1.814 ± 0.139 mm3, and 2.512 ± 11/mm2 in the study group (n = 14). The relationship between the Evans index values, the central canal volumes, and degenerated ependymal cell densities was statistically significant (P < 0.05). This study showed that hydromyelia occurs following SAH-induced experimental hydrocephalus. Desquamation of ependymal cells and increased cerebrospinal fluid secretion may be responsible factors in the development of hydromyelia.


Dengue fever: a Wikipedia clinical review.
Dengue fever, also known as breakbone fever, is a mosquito-borne infectious tropical disease caused by the dengue virus. Symptoms include fever, headache, muscle and joint pains, and a characteristic skin rash that is similar to measles. In a small proportion of cases, the disease develops into life-threatening dengue hemorrhagic fever, which results in bleeding, thrombocytopenia, and leakage of blood plasma, or into dengue shock syndrome, in which dangerously low blood pressure occurs. Treatment of acute dengue fever is supportive, with either oral or intravenous rehydration for mild or moderate disease and use of intravenous fluids and blood transfusion for more severe cases. Along with attempts to eliminate the mosquito vector, work is ongoing to develop a vaccine and medications targeted directly at the virus.


Strength of hindsight bias as a consequence of meta-cognitions.
Hindsight bias is the tendency of people to falsely believe that they would have correctly predicted the outcome of an event once it is known. The present paper addresses the ongoing debate as to whether the hindsight bias is due to memory impairment or biased reconstruction. The memory impairment approach maintains that outcome information alters the memory trace of the initial judgement, whereas the biased reconstruction approach assumes that people who have forgotten their initial judgements are forced to guess and, in the presence of outcome information, are likely to use this information as an anchor. Whereas the latter approach emphasises the role of meta-cognitive considerations, meta-cognitions are not included in the memory impairment explanation. Two experiments show that the biased reconstruction approach provides a better explanation for empirical findings in hindsight bias research than does the memory impairment explanation.


Opinions of ageing workers on relative importance of health promotion.
This study describes individual, workplace and occupational health-promoting factors, and their impacts for worker's health from the perspective of ageing Finnish workers. The pretested questionnaire was sent to 150 ageing workers, of whom 93 returned the form. Statistical analyses were performed using frequencies, means, Mann-Whitney U-test and Krushkal-Wallis test. Over 90% of respondents stated that health habits, individual arrangements in the workplace, good workplace atmosphere, access to health checks, counselling and nursing care all represented important factors for health promotion. Better health, work satisfaction and motivation of employees were the main factors impacting on health promotion. Ageing workers stated that health and safety organization and rehabilitation institutes were the most important copartners. Management must take a positive attitude towards ageing workers and make the necessary arrangements to support their well-being and this should be done in collaboration with occupational health professionals.


[A novel myocardial motion estimation algorithm for ultrasonic image using optimal window size].
To establish a novel speckle tracking algorithm for estimating myocardial motion. A search method was proposed to find the optimal window size for image matching. Simulation and clinical experiment were conducted to demonstrate the validity of this algorithm. The optimal window size for image matching was determined using this algorithm. Correct speckle tracking could be fulfilled with the algorithm proposed. The method proposed in this paper is effective for speckle tracking.


Regulatory issues relating to therapies for periodontal regeneration.
The Food and Drug Administration (FDA) has regulated medical devices since May 1976, when the Medical Device Amendments were enacted. The clinical trial requirements for the marketing of periodontal regeneration devices have been dependent, in part, on the degree of their similarity to devices marketed prior to the legislative enactment date in terms of materials, indication statements, and labeling claims. Nonresorbable barriers were allowed to be marketed based on their equivalence to devices marketed prior to the enactment date based on biocompatability and clinical trial data under the premarket notification requirements section of the law. Bone filling materials such as hydroxyapatite were first marketed based on the finding of equivalence to predicate devices. Newer technologies such as bioabsorbable barriers have also been reviewed under the premarket notification provisions of the law, but manufacturers have been required to provide more extensive safety and effectiveness data to establish equivalence to pre-Amendments devices. Data to answer questions related to the potential toxicity of breakdown products, period of absorption, and ultimate clinical effectiveness needed to be answered prior to marketing. New devices that incorporate technologies that are not substantially equivalent to predicate devices must proceed through the premarket approval route to marketing. For new devices considered a potential significant risk to the patient population, clinical trials are conducted via the investigational device exemption (IDE) requirements that specify the means by which trials will proceed in order to protect the rights of patients. New devices of organic origin, such as bone morphogenic protein, have followed the premarket approval route with IDE requirements instituted as a condition for their path to the marketplace. Issues associated with immediate and long-term contact including potential toxicity, tumorigenicity, and sensitization need to be addressed with appropriate animal models.


Laser photocoagulation around the foci of toxoplasma retinochoroiditis: a descriptive statistical analysis of 35 patients with long-term follow-up.
Thirty-five patients with toxoplasma retinochoroiditis, receiving medical treatment and then treated with laser photocoagulation around the foci, were retrospectively evaluated for the risk of recurrence of the retinochoroiditis with a Kaplan-Meier representation. The recurrence rates with 95% symmetric confidence intervals were: at 1 year, 12.7 + or - 13%, at 2 years, 19.8 + or - 15%; at 3 years, 24.0 + or - 16%; at 4 years, 33.3 + or - 19%; at 5,6 and 7 years, 53.5 + or - 21%; at 8 and 9 years 66. 8 + or - 22%. With the data provided by our series, it is not possible to show the efficacy of laser photocoagulation as a prevention of recurrence in toxoplasma retinochoroiditis. Moreover, because of their heterogeneity, the recurrence rates from the literature cannot provide precise data for a comparison. Concerning the laser-induced thermal damage, the potential therapeutic mechanism of the laser procedure is discussed.


Boosting the Signal Intensity of Nanoelectrospray Ionization by Using a Polarity-Reversing High-Voltage Strategy.
Continuous efforts have been made to further improve the performance of nano-ESI. In this work, we made use of a polarity-reversing high-voltage strategy for the generation of nano-ESI (PR-nESI). Typically, a negative high voltage of -3.0 kV was first applied to the electrode and maintained for 6 s. Then the polarity was reversed, and a positive high voltage of +1.75 kV was applied for the generation of electrospray. Compared with conventional nano-ESI, PR-nESI significantly enhanced the signal intensity of protonated protein ions. The signal-to-noise ratio (S/N) of protonated protein ions was increased by 1-2 orders of magnitude. The increase of S/N was even more remarkable at lower concentrations. Furthermore, PR-nESI also had a desalting effect. Metal ion adducts of proteins were effectively removed. No metal ion adducts were identified from the spectra, even if the concentration of salt was increased to the millimolar level. The performance of PR-nESI was confirmed in the detection of different molecules including proteins, peptides, amino acids, and other small-molecule compounds. The intact folded structure of proteins was preserved during PR-nESI. No unfolding was observed in the spectra. PR-nESI was further applied to the analysis of noncovalent protein-ligand complexes and protein digest. At last, investigations into the mechanism of PR-nESI were carried out. The enhancement of signal intensity and desalting effect were related to the electromigration of the solutes in solution. With all the advantages above, PR-nESI would be a promising method in the future analytical and bioanalytical applications.


A new method for measuring urinary orotic acid.
A relatively simple and specific method for measuring urinary orotic acid is reported. With this method, orotic acid is enzymatically converted to uridine 5-phosphate. The difference in absorbance produced by a simple colorimetric procedure in the presence and absence of the enzymatic conversion allows specific measurement of orotic acid. Normal values for urine are less than 4 micrograms/mg creatinine in infants and less than 3 micrograms/mg creatinine in older children and adults.


ECG-derived spatial QRS-T angle is associated with ICD implantation, mortality and heart failure admissions in patients with LV systolic dysfunction.
Increased spatial QRS-T angle has been shown to predict appropriate implantable cardioverter defibrilIator (ICD) therapy in patients with left ventricular systolic dysfunction (LVSD). We performed a retrospective cohort study in patients with left ventricular ejection fraction (LVEF) 31-40% to assess the relationship between the spatial QRS-T angle and other advanced ECG (A-ECG) as well as echocardiographic metadata, with all-cause mortality or ICD implantation for secondary prevention. 534 patients ≤75 years of age with LVEF 31-40% were identified through an echocardiography reporting database. Digital 12-lead ECGs were retrospectively matched to 295 of these patients, for whom echocardiographic and A-ECG metadata were then generated. Data mining was applied to discover novel ECG and echocardiographic markers of risk. Machine learning was used to develop a model to predict possible outcomes. 49 patients (17%) had events, defined as either mortality (n = 16) or ICD implantation for secondary prevention (n = 33). 72 parameters (58 A-ECG, 14 echocardiographic) were univariately different (p<0.05) in those with vs. without events. After adjustment for multiplicity, 24 A-ECG parameters and 3 echocardiographic parameters remained different (p<2x10-3). These included the posterior-to-leftward QRS loop ratio from the derived vectorcardiographic horizontal plane (previously associated with pulmonary artery pressure, p = 2x10-6); spatial mean QRS-T angle (134 vs. 112°, p = 1.6x10-4); various repolarisation vectors; and a previously described 5-parameter A-ECG score for LVSD (p = 4x10-6) that also correlated with echocardiographic global longitudinal strain (R2 = - 0.51, P < 0.0001). A spatial QRS-T angle >110° had an adjusted HR of 3.4 (95% CI 1.6 to 7.4) for secondary ICD implantation or all-cause death and adjusted HR of 4.1 (95% CI 1.2 to 13.9) for future heart failure admission. There was a loss of complexity between A-ECG and echocardiographic variables with an increasing degree of disease. Spatial QRS-T angle >110° was strongly associated with arrhythmic events and all-cause death. Deep analysis of global ECG and echocardiographic metadata revealed underlying relationships, which otherwise would not have been appreciated. Delivered at scale such techniques may prove useful in clinical decision making in the future.


New concepts of biomarkers and clinical outcomes for therapeutic cancer vaccines in clinical trials.
This study aimed to derive meaningful parameters for immune monitoring during cancer vaccine development by analysis of the literature. This retrospective study was based on analysis of clinical trials registered at ClinicalTrials.gov and published data available on PubMed. The most common sample evaluated in immune monitoring was peripheral blood. All trials employed ELISA for detecting a humoral immune response; however, cellular immune assays were not used across trials. Most cellular immune assays failed to correlate with clinical outcome, although results of other methods did. Standardization of the cellular immune assays across trials is important for predicting the effects of therapeutic cancer vaccines when considering the reliability and characteristics of the methods. Currently, assays mostly target detection of T-cell function, such as proliferation and cytokine release; however, T-cell phenotype analysis in peripheral blood and/or tumor sites may also be considered in the future.


Nanotube x-ray for cancer therapy: a compact microbeam radiation therapy system for brain tumor treatment.
Microbeam radiation therapy (MRT) is a promising preclinical modality for cancer treatment, with remarkable preferential tumoricidal effects, that is, tumor eradication without damaging normal tissue functions. Significant lifespan extension has been demonstrated in brain tumor-bearing small animals treated with MRT. So far, MRT experiments can only be performed in a few synchrotron facilities around the world. Limited access to MRT facilities prevents this enormously promising radiotherapy technology from reaching the broader biomedical research community and hinders its potential clinical translation. We recently demonstrated, for the first time, the feasibility of generating microbeam radiation in a laboratory environment using a carbon nanotube x-ray source array and performed initial small animal studies with various brain tumor models. This new nanotechnology-enabled microbeam delivery method, although still in its infancy, has shown promise for achieving comparable therapeutic effects to synchrotron MRT and has offered a potential pathway for clinical translation.


Pinosylvin exacerbates LPS-induced apoptosis via ALOX 15 upregulation in leukocytes.
Pinosylvin is known to have anti-inflammatory activity in endothelial cells. In this study, we found that pinosylvin had a pro-apoptotic activity in lipopolysaccharide (LPS)-preconditioned leukocytes. This finding suggests that pinosylvin has an effect on the resolution of inflammation. To understand the detailed mechanism, we examined if pinosylvin enhances cyclooxygenase (COX) or lipoxygenase (LOX) activity in THP-1 and U937 cells. LOX activity was found to be markedly increased by pinosylvin, whereas COX activity was not altered. Furthermore, we found that pinosylvin enhanced both levels of ALOX 15 mRNA and protein, implying that LOX activity, elevated by pinosylvin, is attributed to upregulation of ALOX 15 expression. From this cell signaling study, pinosylvin appeared to promote phosphorylations of ERK and JNK. ERK or JNK inhibitors were found to attenuate ALOX 15 expression and LPS-induced apoptosis promoted by pinosylvin. In conclusion, pinosylvin enhances the apoptosis of LPSpreconditioned leukocytes by up-regulating ALOX 15 expression through ERK and JNK. These findings suggest that pinosylvin may induce the resolution of inflammation. [BMB Reports 2018; 51(6): 302-307].


Down-regulation of cell surface cyclic AMP receptors and desensitization of cyclic AMP-stimulated adenylate cyclase by cyclic AMP in Dictyostelium discoideum. Kinetics and concentration dependence.
cAMP binds to Dictyostelium discoideum surface receptors and induces a transient activation of adenylatecyclase, which is followed by desensitization. cAMP also induces a loss of detectable surface receptors (down-regulation). Cells were incubated with constant cAMP concentrations, washed free of cAMP, and cAMP binding to surface receptors and cAMP-induced activation of adenylate cyclase were measured. cAMP could induce maximally 65% loss of binding activity and complete desensitization of cAMP-stimulated adenylate cyclase activity. Half-maximal effects for down-regulation were observed at 50 nM cAMP and for desensitization at 5 nM cAMP. Down-regulation was rapid with half-times of 4, 2.5, and 1 min at 0.1, 1, and 10 microM cAMP, respectively. Similar kinetic data have been reported for desensitization (Dinauer, M.C., Steck, T.L., and Devreotes, P.N. (1980) J. Cell Biol. 86, 554-561). Down-regulation and desensitization were not reversible at 0 degrees C. Down-regulation reversed slowly at 20 degrees C with a half-time of about 1 h. Resensitization of adenylate cyclase was biphasic showing half-times of 4 min and about 1 h, respectively; the contribution of the rapidly resensitizing component was diminished when down-regulation of receptors was enhanced. These results suggest that cAMP-induced down-regulation of receptors and desensitization of adenylate cyclase stimulation proceed by at least two steps. One step is rapidly reversible, occurs at low cAMP concentrations, and induces desensitization without down-regulation, while the second step is slowly reversible, requires higher cAMP concentrations, and also induces down-regulation.


The Pocket Smell Test: successfully discriminating probable Alzheimer's dementia from vascular dementia and major depression.
The present study extended previous work on olfactory dysfunction (odor identification deficits) by using the Pocket Smell Test (PST) to discriminate between groups of patients with Alzheimer's disease (AD), vascular dementia (VaD), and major depression (MD). Sixty patients meeting the DSM-IV criteria for either AD, VaD, or MD (20 per group) underwent assessment with the PST, a three-item screening measure of odor identification, and the Mini-Mental State Examination (MMSE). Patients with AD scored significantly lower than patients with either VaD or MD on the PST, even after controlling for MMSE scores. A PST score of > or =1 (i.e., 1 or 0 correct) discriminated between patients with and without AD with a classification accuracy of 95% (sensitivity 100%, specificity 92.5%). Olfactory assessment may be of diagnostic utility in the differential diagnosis of AD versus VaD versus MD in elderly patients.


Immunoglobulin- and hepatitis B surface antigen-specific circulating immune complexes in chronic hepatitis B virus infection.
For assessing the role of circulating immune complexes (CIC) in chronic hepatitis B virus (HBV) infection, CICs containing IgM, IgG, and HBsAg were determined by C1q and conglutinin (K) assays in 216 patients with chronic HBV infection and 54 healthy controls. The concentration of each type of CIC in patients is higher than in controls (P = 0.0001). CIC is a common feature of chronic HBV infection with 95.8% of cases having at least one abnormal test result. At least one type of HBsAg-CIC is positive in 54.2% of patients. HBsAg-CIC positivity is associated with HBeAg positivity (P = 0.0001), higher aminotransferase levels (P < 0.002), and younger age (P = 0.001). IgG-CIC or IgM-HBsAg-CIC correlates with higher aminotransferase activity (P = 0.001). In conclusion, HBsAg-CIC correlates with HBV replication. IgG-CIC and/or IgM-HBsAg-CIC correlate with disease activity. Immune-mediated injury may play a role in the pathogenesis of chronic HBV infection.


Dermatophyte Antigen Kit.
The dermatophyte antigen kit uses monoclonal antibodies that react with polysaccharides present in the dermatophyte cell wall to detect dermatophyte antigens in specimens based on the principle of immunochromatography. Clinical studies showed that the kit was very useful in the diagnosis of tinea unguium but not tinea pedis. The kit was therefore further developed as an in vitro diagnostic tool for tinea unguium and was approved by the Pharmaceuticals and Medical Devices Agency of Japan. The kit's extraction solution can extract antigens from nail specimens quickly and efficiently. When direct microscopy fails to detect fungal elements in a specimen of suspected tinea unguium, the kit can be used so that positive samples are re-examined by direct microscopy, in order to reduce the likelihood of false-negative detection. In addition, in settings where direct microscopy is unavailable, the kit can be used so that treatment for dermatophytes is withheld when results are negative. Such an approach can reduce both wasteful treatment and medical costs. It is important to note that the kit is used to complement conventional fungus testing methods and that direct microscopy must be used to confirm the final morphological diagnosis of the pathogenic fungal infection. Use of a combination of direct microscopy and this kit should improve the accuracy of diagnosis of tinea unguium.


Comparison of clinical, radiographic, and histometric measurements following treatment with guided tissue regeneration or enamel matrix proteins in human periodontal defects.
The purpose of this study was to compare the clinical and radiographic parameters with the histometric findings following 2 different regenerative procedures in humans. Fourteen advanced intrabony defects at teeth scheduled for extraction were randomly treated as follows: 8 with guided tissue regeneration (GTR) using bioabsorbable barriers and 6 with an enamel matrix protein derivative (EMD). Standardized radiographs, probing depths (PD), and attachment levels (CAL) at baseline and 6 months after therapy were evaluated and compared to the histometric measurements made following the removal of teeth and surrounding tissues 6 months after the surgery. Significant PD reductions (GTR: -5.62 mm; EMD: -5.00 mm) and CAL gains (GTR: 3.87 mm; EMD: 2.67 mm) were observed in both groups. Six months after surgery, minor resorptions of the alveolar crest (AC) (GTR: 0.40 mm; EMD: 0.33 mm) and bony gain at the bottom of the defects (GTR: 0.47 mm; EMD: 1.05 mm) were observed radiographically. No statistically significant differences in the change of clinical and radiographic parameters between the GTR and EMD groups were found. Histometrically, significant amounts of new connective tissue attachment (i.e., cementum with inserting collagen fibers) were observed in both groups (GTR: 2.29 mm; EMD: 1.81 mm). Bone regeneration was found to be significant only in the GTR group (GTR: 1.93 mm; EMD: 0.78 mm). However, the study lacked statistical power for determining equivalence between the groups. Within the limitations of the present study, it may be concluded that at 6 months after GTR or enamel matrix protein derivative therapy, formation of new cementum and bone may be histometrically demonstrated. Except for the formation of new bone, no statistically significant differences between both therapies could be seen for clinical, radiographic, and histometric results 6 months after surgery.


Antenatal glucocorticoids counteract LPS changes in TGF-β pathway and caveolin-1 in ovine fetal lung.
Inflammation and antenatal glucocorticoids, the latter given to mothers at risk for preterm birth, affect lung development and may contribute to the development of bronchopulmonary dysplasia (BPD). The effects of the combined exposures on inflammation and antenatal glucocorticoids on transforming growth factor (TGF)-β signaling are unknown. TGF-β and its downstream mediators are implicated in the etiology of BPD. Therefore, we asked whether glucocorticoids altered intra-amniotic lipopolysaccharide (LPS) effects on TGF-β expression, its signaling molecule phosphorylated sma and mothers against decapentaplegic homolog 2 (pSmad2), and the downstream mediators connective tissue growth factor (CTGF) and caveolin-1 (Cav-1). Ovine singleton fetuses were randomized to receive either an intra-amniotic injection of LPS and/or maternal betamethasone (BTM) intramuscularly 7 and/or 14 days before delivery at 120 days gestational age (GA; term = 150 days GA). Saline was used for controls. Protein levels of TGF-β1 and -β2 were measured by ELISA. Smad2 phosphorylation was assessed by immunohistochemistry and Western blot. CTGF and Cav-1 mRNA and protein levels were determined by RT-PCR and Western blot. Free TGF-β1 and -β2 and total TGF-β1 levels were unchanged after LPS and/or BTM exposure, although total TGF-β2 increased in animals exposed to BTM 7 days before LPS. pSmad2 immunostaining increased 7 days after LPS exposure although pSmad2 protein expression did not increase. Similarly, CTGF mRNA and protein levels increased 7 days after LPS exposure as Cav-1 mRNA and protein levels decreased. BTM exposure before LPS prevented CTGF induction and Cav-1 downregulation. This study demonstrated that the intrauterine inflammation-induced TGF-β signaling can be inhibited by antenatal glucocorticoids in fetal lungs.


Food intakes and habits of rural elderly Malays.
A cross-sectional nutritional survey was carried out on 350 elderly Malays aged 60 and above from 11 randomly selected villages in a rural area on the east coast of Malaysia. The findings indicated that the mean intakes of energy and of all of the nutrients investigated were below the Malaysian Recommended Dietary Allowances, except for protein and vitamin C. With respect to dietary habits, almost all of the subjects reported that they had breakfast (99.3%), lunch (97.9%) and dinner (90.4%) daily or almost daily (5-6 times/week). However, approximately half of the subjects, especially women, had particular beliefs and prohibitions about specific foods. Most of the subjects usually ate their meals at home, particularly dinner, with 99.3% always having dinner in their own home. Thus, although the rural elderly Malays studied had regular meal intakes, the dietary intake was inadequate. There is a need to plan community-based intervention programmes in order to prevent the subsequent consequences of malnutrition that lead to increased morbidity and mortality.


Predicting the dimensions of life satisfaction.
Taking multidimensional life satisfaction as the basic premise of this study, a four-equation multiple regression model was constructed for its prediction. The set of regressors included some conventional biographical characteristics, a number of activity variables, and three indicators of retirement experience. A stepwise regression estimation method was adopted. Results indicated that the pattern of regressor influence varied greatly between equations, providing fairly specific evidence on a number of previously espoused hypotheses. In particular, the Activity perspective on aging was found to be important in the prediction of over-all affect or mood tone, but of little relevance for the other dimensions of life satisfaction, and a modicum of support for the Disengagement perspective was observed.


The toll-like receptor ligands Hiltonol® (polyICLC) and imiquimod effectively activate antigen-specific immune responses in Tasmanian devils (Sarcophilus harrisii).
Devil facial tumour disease (DFTD) describes two genetically distinct transmissible tumours that pose a significant threat to the survival of the Tasmanian devil. A prophylactic vaccine could protect devils from DFTD transmission. For this vaccine to be effective, potent immune adjuvants will be required. Toll-like receptors (TLRs) promote robust immune responses in human cancer studies and are highly conserved across mammalian species. In this study, we investigated the proficiency of TLR ligands for immune activation in the Tasmanian devil using in vitro mononuclear cell stimulations and in vivo immunisation trials with a model antigen. We identified two such TLR ligands, polyICLC (Hiltonol®) (TLR3) and imiquimod (TLR7), that in combination induced significant IFNγ production from Tasmanian devil lymphocytes in vitro. Immunisation with these ligands and the model antigen keyhole limpet haemocyanin activated robust antigen-specific primary, secondary and long-term memory IgG responses. Our results support the conserved nature of TLR signaling across mammalian species. PolyICLC and imiquimod will be trialed as immune adjuvants in future DFTD vaccine formulations.


Translational efficiency of EMCV IRES in bicistronic vectors is dependent upon IRES sequence and gene location.
The internal ribosomal entry site (IRES)from encephalomyocarditis virus (EMCV) is a popular RNA element used widely in experimental and pharmaceutical applications to express proteins in eukaryotic cells or cell-free extracts. Inclusion of the wild-type element in monocistronic or bicistronic messenger RNAs (mRNAs) confers a high level of cap-independent translation activity to appropriately configured cistrons. The history of this element and the experimental consequences of sequence derivations inherent to commercial IRES vectors are less well known. Compared head-to-head with dual-luciferase reporter constructs, a native EMCV IRES in a bicistronic configuration directed 8- to 10-fold more protein than a similarly configured pIRES vector. It also produced nearly twice as much protein as pCITE-1, an early monocistronic iteration, harboring a suboptimal A7 sequence in a crucial structural motif The results indicate that investigators should be aware of and carefully report the sequence of their IRES in any comparative study. The preferred IRES (viral bases 273-845) and the minimum IRES (viral bases 400-836) for optimum activity are illustrated.


Impact of a formal pharmacist-run oral antineoplastic monitoring program: A pilot study in an adult genitourinary oncology clinic.
In recent years, there has been a changing paradigm in the management of oncologic disease states from the use of intravenous therapies, requiring a visit to the infusion center or hospitalization, to new therapies that can be administered orally.1,2 Several publications have evaluated the role pharmacists may play in the initial prescribing of oral chemotherapy, however the impact of a formalized pharmacist follow-up program has not been well defined. This study evaluates the impact of a pilot pharmacist-run oral antineoplastic monitoring program. This retrospective cohort analysis evaluated patients prescribed an oral antineoplastic in the genitourinary oncology clinic at an academic medical center between 1 July 2014 and 15 March 2017. Patients enrolled in the program were compared to a historical control group. The primary objective was adherence to pre-defined standards for monitoring. Secondary objectives include persistence on therapy, need to seek medical care, analysis of pharmacist interventions, patient satisfaction, and financial impact for the on-site retail pharmacy. In total, 33 patients were evaluated (11 cases, 22 controls). Average adherence to monitoring recommendations was significantly higher in the case group compared to controls (89% vs. 61%; p = 0.008). In total, 67 interventions were made by the clinical pharmacist with an average of 6 per patient. This study shows that formalized pharmacist follow-up programs can improve patients' adherence with antineoplastic monitoring standards. Additionally, pharmacists made clinically significant interventions and had high patient satisfaction, providing justification for expansion into other disease states.


The Use of Pit and Fissure Sealants-A Literature Review.
This paper reviews the literature and discusses the latest updates on the use of pit and fissure sealants. It demonstrates the effectiveness of pit and fissure sealants in preventing caries and the management of early carious lesions. It compares the use of different sealant materials and their indications. It describes the application technique for sealants. It also reviews the cost-effectiveness of sealants as a preventive strategy. From this review and after the discussion of recently published studies on pit and fissure sealants, it is evident that sealants are effective in caries prevention and in preventing the progression of incipient lesions. It is therefore recommended that pit and fissure sealant be applied to high-caries-risk children for optimum cost-effectiveness. It is a highly sensitive technique that needs optimum isolation, cleaning of the tooth surface, etching, and the application of a thin bonding layer for maximum benefit. Recall and repair, when needed, are important to maximize the effectiveness of such sealant use.


SUMO-4: A novel functional candidate in the human placental protein SUMOylation machinery.
Small ubiquitin-like modifiers (SUMOs) conjugate to proteins post-translationally, thereby affecting target localization, activity and stability. Functional SUMO family members identified in the human placenta include SUMO-1 to SUMO-3, which are elevated in pre-eclampsia. Whether the fourth isoform, SUMO-4, plays a role in placental development and function remains unknown. We tested the hypothesis that SUMO-4 is expressed in the human placenta and demonstrates altered SUMOylation in pre-eclamptic pregnancies. SUMO-4 mRNA (qRT-PCR) and protein (Western blot and immunohistochemistry) were measured in Jar cells, BeWo cells, first trimester placental villous explants and placental tissues across normal gestation and in pre-eclampsia. SUMO-4 expression in response to oxidative stress (H2O2: 0, 0.1, 1 and 5mM), as well as, hypoxia-reperfusion (O2: 1%, 8% and 20%) was measured. Lastly, SUMO-4 binding (covalently vs. non-covalently) to target proteins was investigated. SUMO-4 mRNA and protein were unchanged across gestation. SUMO-4 was present in the villous trophoblast layer throughout gestation. SUMO-4 mRNA expression and protein levels were increased ~2.2-fold and ~1.8-fold in pre-eclamptic placentas compared to age-matched controls, respectively (p<0.01). SUMO-4 mRNA and protein expression increased in Jars, BeWos and first trimester placental explants with 5mM H2O2 treatment, as well as with exposure to hypoxia-reperfusion. SUMO-1 to SUMO-3 did not show consistent trends across models. SUMO-4 hyper-SUMOylation was predominantly covalent in nature. SUMO-4 is expressed in normal placental development. SUMO-4 expression was increased in pre-eclamptic placentas and in models of oxidative stress and hypoxic injury. These data suggests that SUMO-4 hyper-SUMOylation may be a potential post-translational mechanism in the stressed pre-eclamptic placenta.


Partial purification and characterization of a colony-stimulating factor secreted by a T lymphocyte clone.
The mouse T lymphocyte clone L2 secretes a minimum of 10 lymphokine activities affecting at least 5 different target cells. Large amounts of colony-stimulating factor (CSF) (8.6 X 10(6) U/ml) can be obtained by stimulating L2 cells with concanavalin A. The major CSF activity secreted by L2 cells has been enriched to a specific activity of approximately 2-4 X 10(8) colonies/mg of protein using hydrophobic-interaction, gel-permeation, ion-exchange, and lectin-affinity chromatography. This preparation of CSF contains no detectable interleukin 2, interleukin 3, or interferon. The major L2-cell CSF induces granulocyte/macrophage colonies from bone marrow cells. This GM CSF has an apparent Mr of 22,000 as determined by gel-permeation chromatography. Treatment of L2-cell CSF with proteolytic enzymes abrogates biologic activity.


A preliminary investigation of the new and revised symptoms of posttraumatic stress disorder in DSM-5.
Research has shown that posttraumatic stress disorder (PTSD) is highly comorbid with other mental disorders. The DSM-5 marks an opportunity to increase the differential diagnosis of PTSD by emphasizing symptoms that are specific to PTSD and deemphasizing symptoms that are common to many mental disorders. This study analyzes the new and revised PTSD symptom criteria proposed for DSM-5 by examining their relations with diagnoses and measures of PTSD. In addition, we report the specificity of DSM-5 symptoms with PTSD compared to depressive disorders and substance use. This study utilized pre- and postdeployment data collected from a sample of 213 National Guard Brigade Combat Team soldiers who were deployed to Iraq. Questionnaire data were collected pre- and postdeployment and interview data were collected postdeployment. Scales to measure the DSM-5 symptoms were created using structural analyses and were correlated with interview and self-report measures of PTSD, depression, and substance use. The DSM-5 symptom of anger shows the most increase from pre- to postdeployment in participants diagnosed with PTSD. In addition, this scale showed the strongest relation to PTSD and showed some evidence of specificity. Other symptom scales, including those measuring negative expectations and aggressive behaviors, showed equivalent correlations with PTSD, depression, and substance use. It will be important to continue studying the specificity of anger with PTSD. Several of the other new and revised DSM-5 symptoms appear to be nonspecific, and it is unlikely that their inclusion in the diagnostic criteria for PTSD will improve differential diagnosis.


Violence against children and adolescents: the perspective of Primary Health Care.
To analyze the care provided by Basic Health Units (BHU) to families involved in domestic intrafamily violence against children and adolescents. Qualitative research, based on the Paradigm of Complexity. Data collection was performed with 41 professionals through focus groups and semi-structured interviews. The following categories emerged from data analysis: 'Everything comes here', which reflects the legitimate place of BHUs for the population and the actions taken to build care for families; and 'We only do what is really necessary', which brings the look to violence still based on the positivist and biomedical paradigm. The model of understanding and construction of work processes in the BHU is structured in the aforementioned paradigm. Nurses have the possibility to become agents of change, both in professionals' training and in the care thought and provided to communities.


A systematic review of the impact of chronic pain on adolescents' school functioning and school personnel responses to managing pain in the schools.
To critically synthesize empirical studies on the impact of chronic pain on adolescents' school functioning and school personnel responses to managing pain in schools. Mixed method systematic review. Medline, CINAHL, PsycINFO, ERIC, ScienLO, Cochrane Library, and EMBASE were searched for published articles from inception to December 2018. Fourteen studies met the inclusion criteria. Data from the qualitative and quantitative studies were synthesized using parallel-results convergent integrated design. The Critical Appraisal Skills Programme and Mixed Methods Appraisal Tool version 2018 were used for assessing the quality of included studies. Chronic pain appears to have a significant negative influence on adolescents' school attendance, academic performance/achievement, academic competence, physical activities, and social functioning. However, other studies indicated that adolescents with chronic pain had better academic performance and competence than healthy peers and that chronic pain did not affect older adolescents' social functioning. There is limited guidelines and resources for how school personnel can help adolescents to manage pain in schools. This review supports the need for future research on the impact of adolescents' chronic pain on the full dimensions of school functioning and to identify the effective responses of school personnel to managing adolescents' pain in schools. Although findings are somewhat conflicting, overall adolescent's chronic pain appears to have a negative influence on school functioning. Yet limited guidelines exist for how school personnel should respond effectively to manage adolescents' pain in schools. The review indicates the importance of written policies to guide teachers on how to facilitate optimal pain management in schools. It also highlights the significance of clear communication between healthcare professionals and school personnel, adolescents with chronic pain and their parents to support optimal school functioning.


A survey around the Italian pediatric units on current clinical practice for Sleep Disordered Breathing (SDB).
During recent years, interest on Sleep Disordered Breathing (SDB) in pediatric age has increased, due to the impact on quality of life, psycho-physical attitude and other serious morbidities if undiagnosed and untreated. Italian Pediatric Respiratory Diseases Society (SIMRI) SDB-Working Group carried out an exploratory survey in Italy, from January to December 2016, to assess the diagnostic and therapeutic pathways, perception and relevance of SDB in Italian Hospitals. A questionnaire was sent to 180 Pediatric Units (PUs) distributed throughout the Italy; 102 Pediatric Units (PUs; 56.6%) answered and among them 57% dealt with SDB, and 94% recognized SDB as a major problem. Instrumental tests performed by the PUs were saturimetry (66%), nocturnal polygraphy with complete cardio-respiratory monitoring (46%) and full polysomnography (23%). In addition, hospital pediatricians reported that 54% of parents were unaware of the SDB and 84% did not know their complications. In the Northern Italy, the diagnosis was frequently performed with instrumental tools and the treatment was often surgical. In the Southern Italy the diagnosis was clinical, and the treatment was usually with drugs. The results of our study showed a heterogeneity in the diagnosis and treatment of SDB throughout Italy. Parents know little about SDB and their complications. The operator satisfaction was associated with the availability of tools for diagnosing SDB.


Diagnostic performance of PET in thyroid cancer with elevated anti-Tg Ab.
We aimed to explore the role of the diagnostic accuracy of F-18 fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) for the detection of recurrent and/or metastatic diseases in differentiated thyroid cancer (DTC) patients with progressively and/or persistently elevated TgAb levels and negative radioactive iodine whole-body scan (RI-WBS) through a systematic review and meta-analysis. The MEDLINE, EMBASE and Cochrane Library database, from the earliest available date of indexing through June 30, 2017, were searched for studies evaluating the diagnostic performance of F-18 FDG PET/CT for the detection of recurrent and/or metastatic diseases in DTC patients with progressively and/or persistently elevated TgAb levels and negative RI-WBS. We determined the sensitivities and specificities across studies, calculated positive and negative likelihood ratios (LR+ and LR-). Across 9 studies (515 patients), the pooled sensitivity for F-18 FDG PET/CT was 0.84 (95% CI; 0.77-0.89) a pooled specificity of 0.78 (95% CI; 0.67-0.86). Likelihood ratio (LR) syntheses gave an overall positive likelihood ratio (LR+) of 3.8 (95% CI; 2.5-5.7) and negative likelihood ratio (LR-) of 0.21 (95% CI; 0.14-0.30). The pooled diagnostic odds ratio (DOR) was 18 (95% CI; 10-34). The area (AUC) under the hierarchical summary receiver-operating characteristic (HCROC) curve was 0.88 (95% CI: 0.85-0.90). F-18 FDG PET or PET/CT demonstrated moderate sensitivity and specificity for the detection of recurrent and/or metastatic diseases in DTC patients with progressively and/or persistently elevated TgAb levels and negative RI-WBS.


A method of precise mRNA/DNA homology-based gene structure prediction.
Accurate and automatic gene finding and structural prediction is a common problem in bioinformatics, and applications need to be capable of handling non-canonical splice sites, micro-exons and partial gene structure predictions that span across several genomic clones. We present a mRNA/DNA homology based gene structure prediction tool, GIGOgene. We use a new affine gap penalty splice-enhanced global alignment algorithm running in linear memory for a high quality annotation of splice sites. Our tool includes a novel algorithm to assemble partial gene structure predictions using interval graphs. GIGOgene exhibited a sensitivity of 99.08% and a specificity of 99.98% on the Genie learning set, and demonstrated a higher quality of gene structural prediction when compared to Sim4, est2genome, Spidey, Galahad and BLAT, including when genes contained micro-exons and non-canonical splice sites. GIGOgene showed an acceptable loss of prediction quality when confronted with a noisy Genie learning set simulating ESTs. GIGOgene shows a higher quality of gene structure prediction for mRNA/DNA spliced alignment when compared to other available tools.


Sinorhizobium meliloti Controls Nitric Oxide-Mediated Post-Translational Modification of a Medicago truncatula Nodule Protein.
Nitric oxide (NO) is involved in various plant-microbe interactions. In the symbiosis between soil bacterium Sinorhizobium meliloti and model legume Medicago truncatula, NO is required for an optimal establishment of the interaction but is also a signal for nodule senescence. Little is known about the molecular mechanisms responsible for NO effects in the legume-rhizobium interaction. Here, we investigate the contribution of the bacterial NO response to the modulation of a plant protein post-translational modification in nitrogen-fixing nodules. We made use of different bacterial mutants to finely modulate NO levels inside M. truncatula root nodules and to examine the consequence on tyrosine nitration of the plant glutamine synthetase, a protein responsible for assimilation of the ammonia released by nitrogen fixation. Our results reveal that S. meliloti possesses several proteins that limit inactivation of plant enzyme activity via NO-mediated post-translational modifications. This is the first demonstration that rhizobia can impact the course of nitrogen fixation by modulating the activity of a plant protein.


Combination of Nimbolide and TNF-α-Increases Human Colon Adenocarcinoma Cell Death through JNK-mediated DR5 Up- regulation.
Tumor necrosis factor (TNF-α), an inflammatory cytokine that plays an important role in the control of cell proliferation, differentiation, and apoptosis, has previously been used in anti-cancer therapy. However, the therapeutic applications of TNF-α are largely limited due to its general toxicity and anti-apoptotic influence. To overcome this problem, the present study focused on the effect of active constituents isolated from a medicinal plant on TNF-α-induced apoptosis in human colon adenocarcinoma (HT-29) cells. Nimbolide from Azadirachta indica was evaluated for cytotoxicity by methyl tetrazolium 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay and phase contrast microscopy. Effects on apoptotic signaling proteins were investigated using Western blot analysis. Nimbolide showed cytotoxicity against HT-29 cells that was significantly different from the control group (<0.01), a concentration of 10 μM significantly inducing cell death (<0.01). In combination with TNF-α, nimbolide significantly enhanced-induced cell death. In apoptotic pathway, nimbolide activated c-Jun N-terminal kinase (JNK) phosphorylation, BH3 interacting-domain death agonist (Bid) and up-regulated the death receptor 5 (DR5) level. In the combination group, nimbolide markedly sensitized TNF-α-induced JNK, Bid, caspase-3 activation and the up-regulation of DR5. Our findings overall indicate that nimbolide may enhance TNF-α-mediated cellular proliferation inhibition through increasing cell apoptosis of HT-29 cells by up-reglation of DR5 expression via the JNK pathway.


Cost-effectiveness of exercise as a therapy for behavioural and psychological symptoms of dementia within the EVIDEM-E randomised controlled trial.
Although available evidence is modest, exercise could be beneficial in reducing behavioural and psychological symptoms of dementia. We aim to evaluate the cost-effectiveness of a dyadic exercise regimen for individuals with dementia and their main carer as therapy for behavioural and psychological symptoms of dementia. Cost-effectiveness analysis within a two-arm, pragmatic, randomised, controlled, single-blind, parallel-group trial of a dyadic exercise regimen (individually tailored, for 20-30 min at least five times per week). The study randomised 131 community-dwelling individuals with dementia and clinically significant behavioural and psychological symptoms with a carer willing and able to participate in the exercise regimen; 52 dyads provided sufficient cost data for analyses. Mean intervention cost was £284 per dyad. For the subsample of 52 dyads, the intervention group had significantly higher mean cost from a societal perspective (mean difference £2728.60, p = 0.05), but costs were not significantly different from a health and social care perspective. The exercise intervention was more cost-effective than treatment as usual from both societal and health and social care perspectives for the measure of behavioural and psychological symptoms (Neuropsychiatric Inventory). It does not appear cost-effective in terms of cost per quality-adjusted life year gain. The exercise intervention has the potential to be seen as cost-effective when considering behavioural and psychological symptoms but did not appear cost-effective when considering quality-adjusted life year gains.


Probing the Interactions of Thiazole Abietane Inhibitors with the Human Serine Hydrolases ABHD16A and ABHD12.
12-Thiazole abietanes are highly selective reversible inhibitors of hABHD16A that could potentially alleviate neuroinflammation. In this study, we used synthetic chemistry, competitive activity-based protein profiling, and computational methodologies to try to establish relevant structural determinants of activity and selectivity of this class of compounds for inhibiting ABHD16A over ABHD12. Five compounds significantly inhibited hABHD16A but also very efficiently discriminated between inhibition of hABHD16A and hABHD12, with compound 35 being the most effective, at 100 μM (55.1 ± 8.7%; p < 0.0001). However, an outstanding switch in the selectivity toward ABHD12 was observed in the presence of a ring A ester, if the C2' position of the thiazole ring possessed a 1-hydroxyethyl group, as in compound 28. Although our data were inconclusive as to whether the observed enzyme inhibition is allosteric or not, we anticipate that the structure-activity relationships presented herein will inspire future drug discovery efforts in this field.


Missing data methods for the assessment of surrogate outcomes and treatment mechanisms in clinical trial substudies.
Hypotheses about the mechanisms of action by which a treatment affects a clinical outcome may prompt consideration of an alternative outcome as a potential surrogate. In many cases, due to costs or other factors, the candidate for surrogacy will only be measured for patients randomized to a substudy within the main trial. In this situation, the substudy patients provide information about links between the true and surrogate outcomes and the treatment, and these links can be exploited, using methods for handling missing covariates, to allow available information for patients not in the substudy to be incorporated into the analysis. The increased precision with which the treatment effect can be estimated using these methods, compared with using substudy data alone, in turn allows more precise estimates of measures of surrogacy. This paper reviews and compares some methods for handling missing covariate data and applies the methodology to a large heart attack trial, in order to investigate the properties of four measures for assessing the extent to which early response to thrombolytic therapy, as measured by an improvement in coronary blood flow, can be regarded as a surrogate for 30-day survival following heart attack. Design issues for substudies intended to assess treatment mechanisms are also considered. In particular, we consider how the precision of surrogate measures varies with the size of the substudy relative to the main trial. The results suggest that for reasonable surrogates, substudies substantially smaller than the main study can extract most of the available information regarding surrogacy.


Leukocyte degranulation and vacuole formation in patients with chronic granulomatous disease of childhood.
A cellular defect associated with decreased bactericidal activity of the polymorphonuclear leukocyte has been found in a 2(1/2) yr old Negro boy with the typical clinical and pathological findings of chronic granulomatous disease. Unlike previously described patients his polymorphonuclear leukocytes were shown to undergo apparently normal degranulation and vacuole formation after phagocytosis. Metabolic studies of the leukocytes indicated a failure to increase oxygen consumption with phagocytosis or to reduce Nitroblue tetrazolium dye. These metabolic abnormalities are identical with those previously reported in patients with chronic granulomatous disease. Two additional patients with chronic granulomatous disease have also been found to have apparently adequate degranulation of polymorphonuclear leukocytes after phagocytosis. Our studies suggest that failure of degranulation may not be a necessary part of this functional leukocyte abnormality.


Linking household income and work–family conflict: a moderated mediation study.
Research on the work-family interface has not often explored the role of structural characteristics such as income in the associations among work stressors, work-family conflict and family stressors. The goal of this study was to examine household income as a moderator of the relations among these variables. Results from a nationally (US) representative sample of 1472 employed individuals who were married with children indicate that the relations between work-to-family interference and family strain were stronger for individuals with lower household incomes than for those with higher household incomes. Furthermore, family strain was more strongly associated with family-to-work interference for individuals in low-income households. Household income did not moderate other relations examined in the study. Potential explanations for these moderating effects are discussed, along with their implications for the generalizability of findings in the work-family literature across contexts.


Personality and self-reported use of mobile phones for games.
Mobile phones are popular devices that may generate problems for a section of the community. A previous study using the Eysenck Personality Questionnaire found that extraverts with low self-esteem reported more problems with their mobile phone use. The present study used the NEO FI and Coopersmith Self-Esteem Inventory to predict the self reported mobile phone use of 112 participants. Multiple regression found that people low on agreeableness were more likely to use their mobile phones to play games. The findings imply an interplay between personality traits and excessive or problematic use on mobile phones that is relevant to proposed innovations such as gambling on mobile phones.


[Dissection of the heart: a useful guide to understanding the three-dimensional gross anatomy].
In order to understand the three-dimensional gross anatomy of the heart, it is important to observe the inner structures of the chambers and the spatial relation between the valves and the ventricles. In our dissecting laboratory, we designed a guide to dissection of the heart according to the following procedures. First, we observe the surface anatomy of the heart in the pericardial cavity, remove the heart and then identify the coronary vessels, open the four chambers and observe the intra-cardiac structures. Next, we remove the atria from the ventricles and examine the relation between the valves and the chambers. Our guide is useful for learning the three-dimensional gross anatomy which is fundamental to understanding the normal function and disease of the heart.


Modelling Gender Differences in the Economic and Social Influences of Obesity in Australian Young People.
In Australia, as in many other developed economies, the prevalence of obesity has risen significantly in all age groups and especially in young males and females over the past decade. Using data from the Household, Income and Labour Dynamics in Australia (HILDA) Survey, this paper investigates the influence of economic, personality and social factor demographics on the incidence of obesity in Australian youths. The study uses two random parameters logit models, including one that allows for gender-specific differences in the conditioning variables. The models reveal notable differences between the most important variables affecting the incidence of obesity amongst females compared to males. These differences are notable to consider for policy and intervention programs aimed at reducing the problem of obesity.


Osmotic Shock-Triggered Assembly of Highly Charged, Nanoparticle-Supported Membranes.
Spherical nanoparticle-supported lipid bilayers (SSLBs) combine precision nanoparticle engineering with biocompatible interfaces for various applications, ranging from drug delivery platforms to structural probes for membrane proteins. Although the bulk, spontaneous assembly of vesicles and larger silica nanoparticles (>100 nm) robustly yields SSLBs, it will only occur with low charge density vesicles for smaller nanoparticles (<100 nm), a fundamental barrier in increasing SSLB utility and efficacy. Here, through whole mount and cryogenic transmission electron microscopy, we demonstrate that mixing osmotically loaded vesicles with smaller nanoparticles robustly drives the formation of SSLBs with high membrane charge density (up to 60% anionic lipid or 50% cationic lipid). We show that the osmolyte load necessary for SSLB formation is primarily a function of absolute membrane charge density and is not lipid headgroup-dependent, providing a generalizable, tunable approach toward bulk production of highly curved and charged SSLBs with various membrane compositions.


Quantification and study of the L-DOPA decarboxylase expression in gastric adenocarcinoma cells treated with chemotherapeutic substances.
3,4-Dihydroxy-L-phenylalanine decarboxylase (DDC) is an enzyme implicated in the biosynthetic pathways of the neurotransmitters dopamine and probably serotonin. DDC gene expression has been studied in numerous malignancies and the corresponding data have shown remarkable alterations in the mRNA and/or protein levels encoded by the gene. The aim of this study was to examine any modulations in the DDC mRNA levels in gastric cancer cells after their treatment with the chemotherapeutic agents 5-fluorouracil, leucovorin, irinotecan, etoposide, cisplatin, and taxol. The sensitivity of the AGS gastric adenocarcinoma cells to the antineoplastic drugs was evaluated using the MTT assay. Total RNA was extracted and reverse transcribed into cDNA. A highly sensitive quantitative real-time PCR methodology was developed for the quantification of DDC mRNA. GAPDH was used as a housekeeping gene. Relative quantification analysis was carried out using the comparative C T method ((Equation is included in full-text article.)). The treatment of AGS cells with several concentrations of various broadly used anticancer drugs resulted in significant modulations of the DDC mRNA levels compared with those in the untreated cells in a time-specific and drug-specific manner. Generally, DDC expression levels appeared to decrease after three time periods of exposure to the selected chemotherapeutic agents, suggesting a characteristic DDC mRNA expression profile that is possibly related to the mechanism of each drug. Our experimental data show that the DDC gene might serve as a new potential molecular biomarker predicting treatment response in gastric cancer cells.


[Psychiatric morbidity among adults in The Netherlands: the NEMESIS-Study. II. Prevalence of psychiatric disorders. Netherlands Mental Health Survey and Incidence Study].
To determine the prevalence of psychiatric disorders in non-institutionalised Dutch adults. Cross-sectional. Trimbos Institute, Utrecht, the Netherlands. A representative sample of 7076 adults (18-64 years) in the Netherlands' population were interviewed in 1996 to determine the prevalence of mental disorders ever, in the previous 12 months and in the previous month. Objectives and study design are described in the previous article (1997: 2448-52). The 'Composite international diagnostic interview' (CIDI) was used to assess the following mental disorders according to Diagnostic and statistical manual of mental disorders, 3rd revised edition (DSM-III-R): affective disorders, anxiety disorders, eating disorders, schizophrenia and other non-affective psychoses, substance dependence and substance abuse. Mental disorders were common in the general population: the prevalence 'ever' of all disorders was 41.2%, the 12-month prevalence 23.5%, without sex differences. Depression, anxiety disorders and alcohol abuse and dependence showed high prevalence and comorbidity. The prevalence 'ever' of schizophrenia and other non-affective psychoses was low (0.4%).


Functional Properties and Morphological Characters of Soluble Dietary Fibers in Different Edible Parts of Angelica Keiskei.
This study comparatively investigated the functional properties, chemical compositions, and morphological characters of soluble dietary fibers (SDFs) from the root, stem, and leaf of Angelica keiskei. The SDFs showed relevant functional properties, with the root SDF (RSDF) exhibiting the highest water-holding capacity (22.6 g/g), oil-holding capacity (6.29 mL/g), swelling capacity (36.6 mL/g), emulsion stability, and fat adsorption (5.66 g/g). Stem SDF (SSDF) gave the highest foam stability, toxic ions adsorption (Pb: 1.12 mg/g; As: 3.22 mg/g), and bile acid salts adsorption (sodium cholate: 85.6 mg/g; sodium glycocholate: 93.1 mg/g; sodium taurocholate: 125.7 mg/g). RSDF and SSDF presented similar monosaccharide compositions, thermal property, chemical bonds and groups, and irregular, rough, and porous surfaces. It can be concluded that the obtained SDFs, especially for RSDF and SSDF, can be used in the food industry as fiber-rich functional ingredients.


Quantitation of tyrosine hydroxylase and neuropeptide Y immunoreactivity in single rat sympathetic neurons: effects of preganglionic nerve activity.
Using computerised densitometry to measure immunocytochemical reaction product in a model system, we established conditions that produced a linear relationship between the logarithm of antigen concentration and the measured intensity of staining. We then applied the densitometric technique to assess the changes in tyrosine hydroxylase (TH) and neuropeptide tyrosine (NPY) within sympathetic neurons of rat superior cervical ganglion following chronic decentralization and following reserpine treatment. One week after surgical or pharmacological decentralization, there was appreciable reduction of neuronal levels of both TH and NPY. However, there remained considerable variation in the immunoreactivities of individual cells. Three days of treatment with reserpine elevated TH levels but substantially reduced NPY. Both these effects were prevented by prior decentralization of the ganglia. No differences were seen between normotensive and the Otago strain of genetically hypertensive rats, either in basal TH or NPY immunoreactivities or in responses to the maneuvers performed. Comparison of our findings with previous biochemical data indicate that densitometric immunocytochemistry provides an accurate index of neuronally localised antigen concentrations but also allows analysis of interneuronal differences that are not otherwise apparent.


Subdural hematoma after a fall in an elderly patient taking high-dose omega-3 fatty acids with warfarin and aspirin: case report and review of the literature.
The elderly population is at an increased risk for major bleeding, possibly due to increased sensitivity to anticoagulation, multiple comorbidities, and polypharmacy. Elderly patients receiving antiplatelet and anticoagulant therapy have an additional risk for bleeding. Omega-3 fatty acids, also known as fish oil, have been used for hyperlipidemia, coronary heart disease, hypertension, and other conditions. Some studies have demonstrated that consumption of fish oil concentrate, n-3 polyunsaturated fatty acid (n-3 PUFA), results in cardiovascular benefits that include reductions in mortality, sudden death, nonfatal myocardial infarction, and thrombotic stoke, as well as improvement in graft patency. The mechanism of action of n-3 PUFA is not completely understood, but a dual antiplatelet and anticoagulant effect has been proposed. Few data exist on whether or not fish oil can be used safely with other antiplatelet or anticoagulant drugs. We report the case of a patient who after a minor fall developed a subdural hematoma requiring craniotomy that likely was precipitated by concomitant use of high-dose omega-3 fatty acids 6 g/day with both aspirin and warfarin. These findings are important because of the wide availability of omega-3 fatty acids and the propensity for use of complementary and alternative medicine in patients with cardiovascular disease who are already taking antiplatelet and/or anticoagulant agents. Judicious use of these combinations is advised, and pharmacists can play an important role in educating patients and other health care providers about the bleeding risks associated with combination therapy.


The Health Impacts, Prevalence, and Acceptance Level of Cosmetics Interventions Among Females in Saudi Arabia.
With the rising global desire for beauty, cosmetic interventions have increased. Saudi Arabia ranked 29 among the top 30 fastest growing countries for cosmetic procedures. This study aims to investigate the prevalence, acceptance level, and health impacts of cosmetic interventions among females in Saudi Arabia. This cross-sectional study was conducted from December 2022 to January 2023 among females living in Saudi Arabia. Participants' acceptance of cosmetic interventions was assessed using an Arabic version of the validated Acceptance of Cosmetic Surgery Scale. The data were collected using a self-administered questionnaire. The study included 3007 females living in Saudi Arabia. About 58% of the participants were aged 18 to 25, and 72.9% were single. The prevalence of cosmetic interventions among the participants was 10%. A higher prevalence was observed among participants over 25 years, married, high economic status, employed, postgraduate, and participants recognizing the necessity of cosmetic interventions (P < .001). High acceptance levels toward cosmetic interventions were observed among older, married, employed, and postgraduate respondents and those with high economic status (P < .001). Meanwhile, knowing the adverse events of cosmetic interventions was associated with a low level of acceptance with a P-value of <.001. The present study demonstrated a surprising prevalence of cosmetic interventions among females in Saudi Arabia. However, below-average acceptance of these interventions among the same population was reported. This could be a result of the surrounding culture that does not support or encourage undergoing cosmetic interventions. Further studies are recommended to assess the prevalence of those interventions using objective tools, such as medical records.


Economic well-being and children's social adjustment: the role of family process in an ethnically diverse low-income sample.
Using latent variable structural equation modeling, a family economic stress model that links economic well-being to child well-being in an ethnically diverse, low-income sample of 419 elementary school-age children was evaluated. The sample was 57% African American and 28% Hispanic, and most families were headed by single mothers. The results provided support for the position that family process is a critical mediator of the effects of economic hardship on children's social adjustment. Lower levels of economic well-being, and the corollary elevated perceptions of economic pressure indirectly affected parenting behavior through an adverse impact on parental psychological well-being. Distressed parents reported feeling less effective and capable in disciplinary interactions with their child and were observed to be less affectionate in parent-child interactions. In turn, less than optimal parenting predicted lower teacher ratings of children's positive social behavior and higher ratings of behavior problems. Multiple-group analyses revealed that the pathways by which economic hardship influences children's behavior appear to operate similarly for boys and girls, and for African American and Hispanic families.


Evaluating Girls on the Run in Promoting Positive Youth Development: Group Comparisons on Life Skills Transfer and Social Processes.
Girls on the Run (GOTR), a physical activity-based positive youth development program, uses running as a platform to teach life skills and promote healthy behaviors. In this companion paper of our comprehensive project, the authors evaluated program impact on positive youth development by comparing GOTR participants to youth in other organized activities (Sport and physical education [PE]) on life skills transfer and social processes. Qualitative methods complemented quantitative data through interviews with GOTR stakeholders. The participants included 215 girls in GOTR and 692 girls in the same grades and schools who did not participate in GOTR (Sport = 485; PE = 207). They completed self-report measures of life skills transfer, peer and coach relatedness, and coach autonomy support at the season's end. GOTR subsamples of girls, coaches, caregivers, and school personnel participated in focus groups. Girls in GOTR compared favorably to the Sport and PE girls on all life skills-managing emotions, resolving conflicts, helping others, and making intentional decisions-and to the PE girls for all 3 social processes. The GOTR and Sport girls did not differ on coach relatedness and autonomy support, but the Sport girls rated teammate relatedness higher. The GOTR girls' scores on life skills transfer remained stable at a 3-month follow-up assessment. Stakeholders in the focus groups shared corroborating evidence that, through participating in GOTR, girls learn skills that generalize to school and home contexts. Using comparison groups, a retention assessment, and mixed methods, the findings provide evidence that GOTR is effective in teaching skills and strategies that generalize to broader life domains. The processes that explain group differences on life skills transfer include GOTR's intentional curriculum of skill-building activities delivered by coaches within a caring and autonomy-supportive climate.


A Novel Bradykinin-Related Peptide, RVA-Thr6-BK, from the Skin Secretion of the Hejiang Frog; Ordorrana hejiangensis: Effects of Mammalian Isolated Smooth Muscle.
A novel naturally-occurring bradykinin-related peptide (BRP) with an N-terminal extension, named RVA-Thr6-Bradykinin (RVA-Thr6-BK), was here isolated and identified from the cutaneous secretion of Odorrana hejiangensis (O. hejiangensis). Thereafter, in order to evaluate the difference in myotropic actions, a leucine site-substitution variant from Amolops wuyiensis skin secretion, RVA-Leu1, Thr6-BK, was chemically synthesized. Myotropic studies indicated that single-site arginine (R) replacement by leucine (L) at position-4 from the N-terminus, altered the action of RVA-Thr6-BK from an agonist to an antagonist of BK actions on rat ileum smooth muscle. Additionally, both BK N-terminal extended derivatives (RVA-Thr6-BK and RVA-Leu1, Thr6-BK) exerted identical myotropic actions to BK, such as increasing the frequency of contraction, contracting and relaxing the rat uterus, bladder and artery preparations, respectively.


Interferon-induced expression of If-1h and If-1l alleles in Newcastle disease virus-infected mouse macrophages is associated with specific differences in viral gene transcription.
We have studied the expression of cytokines and viral genes induced by Newcastle disease virus (NDV) and Sendai virus in bone marrow-derived macrophages (BMM) and lymphocytes from C57BL/6 mice and the congenic line B6.C-H-28c. These mice carry the loci If-1h (high) or If-1l (low), respectively, that are responsible for up to tenfold differences in the interferon (IFN)-alpha, IFN-beta, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) response to NDV but not to Sendai virus. Only BMM but not spleen lymphocytes showed allele-specific differences in NDV-induced cytokine levels, indicating cell-specific If-1 expression. The If-1 locus harbors IFN-inducible gene(s) whose expression is prevented in the presence of cycloheximide. Our data provide evidence that the If-1l allele acts by specifically suppressing the cytokine response to NDV. Cytokine production was dependent on infectious virions, and kinetic analyses revealed a close correlation between the amount of viral transcripts and individual cytokine mRNA. BMM from lf-1l mice strongly restricted transcription of the NDV nucleoprotein (NP) gene, whereas BMM from If-1h mice supported NP transcription. Following treatment with IL-4, which inhibited constitutive IFN-beta gene expression, however, If-1l BMM became highly permissive for transcription of the viral NP gene and released high amounts of cytokines. We conclude that If-1l gene products are responsible for the low producer phenotype by efficiently interfering with NDV transcription, leading to strongly reduced intracellular levels of cytokine inducing viral dsRNA intermediates.


Comparison of surgical variables and pain in cats undergoing ovariohysterectomy, laparoscopic-assisted ovariohysterectomy, and laparoscopic ovariectomy.
Laparoscopy is an established modality in veterinary medicine. To date, laparoscopy in feline surgery is rarely reported. The objectives of this study were to compare surgical time, complications, and postoperative pain in a group of cats undergoing laparoscopic ovariectomy (LOVE), laparoscopic-assisted ovariohysterectomy (LAOVH), and ovariohysterectomy via celiotomy (COVH). Eighteen healthy cats were randomly assigned to undergo LOVE, LAOVH, or COVH. Severity of pain was monitored 1, 2, 3, and 4 hr after surgery. Surgical time was significantly longer for LAOVH (mean ± standard deviation [SD], 51.6 ± 7.7 min) compared to COVH (mean ± SD, 21.0 ± 7.1 min) and LOVE (mean ± SD, 34.2 ± 11.2 min). There were no major intraoperative complications, although minor complications were more common in both laparoscopic groups. Cats sterilized via laparoscopy (LOVE and LAOVH) were statistically less painful than cats spayed via celiotomy (COVH) 4 hr following surgery. Results suggested that LOVE in cats is safe, can be performed in a comparable amount of time as COVH, and may result in less postoperative discomfort.


An innovative lipid-lowering approach to enhance attainment of low-density lipoprotein cholesterol goals.
To improve attainment of LDL-cholesterol (LDL-c) targets, an expert group proposed an algorithm for lipid-lowering therapy during hospitalization for acute coronary syndrome and during follow-up. We aimed to assess adherence to this algorithm, and evaluate its impact on LDL-c levels and on attainment of therapeutic LDL-c targets in a population of post-acute coronary syndrome patients. Prospective, observational study including patients admitted for acute coronary syndrome between February 2017 and September 2018. Patients admitted without statins or ezetimibe were considered 'naïve'. Baseline LDL-c was admission LDL-c in naïve patients, and for those taking lipid-lowering therapy at admission, baseline LDL-c was back-calculated. In line with the most recent guidelines, the target was a >50% reduction in naïve LDL-c and <55 mg/dL. In total, 270 patients were analysed, mean age 67 ± 12 years, 78% men, 26% diabetic. At admission, 175 (65%) were naïve, 95 (35%) had previous lipid-lowering therapy, of which 13 (5%) statin+ezetimibe. Average LDL-c at admission was 120 ± 47 mg/dL (136 ± 44 mg/dL in naïve, 91 ± 39 mg/dL in pretreated patients). Discharge prescription was in compliance with the algorithm in 204 (76%) patients. Average LDL-c at two months was 57 ± 28 mg/dL; it was <55 mg/dL in 135 (50%), and 178 (66%) achieved a >50% reduction. Overall, 125/270 (46%) achieved the LDL-c goal. The reduction in LDL-c observed at two months persisted at five months. Prescription of high-intensity statins, associated with ezetimibe where applicable, achieves LDL-c levels <55 mg/dL in 50% of patients at two months, and attains therapeutic goals defined by the European Society of Cardiology in 46% of cases.


Uterine leiomyoma with RAD51B::NUDT3 fusion: a report of 2 cases.
Three main uterine leiomyoma molecular subtypes include tumors with MED12 mutation, molecular aberrations leading to HMGA2 overexpression, and biallelic loss of FH. These aberrations are mutually exclusive and can be found in approximately 80-90% of uterine leiomyoma, in which they seem to be a driver event. Approximately 10% of uterine leiomyoma, however, does not belong to any of these categories. Uterine leiomyoma with HMGA2 overexpression is the most common subtype in cellular and second most common category of usual leiomyoma. In some of these tumors, rearrangement of HMGA2 gene is present. The most common fusion partner of HMGA2 gene is RAD51B. Limited data suggests that RAD51B fusions with other genes may be present in uterine leiomyoma. In our study, we described two cases of uterine leiomyoma with RAD51B::NUDT3 fusion, which occur in one case of usual and one case of highly cellular leiomyoma. In both cases, no other driver molecular aberrations were found. The results of our study showed that RAD51::NUDT3 fusion can occur in both usual and cellular leiomyoma. RAD51B may be a fusion partner of multiple genes other than HMGA2 and HMGA1. In these cases, RAD51B fusion seems to be mutually exclusive with other driver aberrations defining molecular leiomyoma subtypes. RAD51B::NUDT3 fusion should be added to the spectrum of fusions which may occur in uterine leiomyoma, which can be of value especially in cellular leiomyoma in the context of differential diagnosis against endometrial stromal tumors.


Substance abuse and the nurse manager: ethical and legal issues.
Nurse managers have a pivotal role in intervening in situations of substance abuse among employees. This article addresses ethical and legal dimensions of chemical impairment from the perspective of the nurse manager. The value of a rehabilitative rather than a punitive approach to the chemically impaired nurse is emphasized. Ethics of care and relevant legal considerations, including the Americans With Disabilities Act, are explored through case analysis. Covenantal relationships offer a framework for examining the responsibilities of the nurse manager with respect to the community, employer, the actual or allegedly chemically impaired nurse, and one's self.


Thrombotic thrombocytopaenic purpura and anuria: response to plasma exchange.
This report discusses the treatment and recovery of a 29-year-old woman with thrombotic thrombocytopaenic purpura complicated by servere renal failure. The case is reported because of the rarity of recovery from anuric renal failure in this disease and the probable contribution of plasma exchange to this recovery.


Resolution-enhanced integral imaging microscopy that uses lens array shifting.
A resolution-enhanced integral imaging microscope that uses lens array shifting is proposed in this study. The lens shift method maintains the same field of view of the reconstructed orthographic view images with increased spatial density. In this study, multiple sets of the elemental images were captured with horizontal and vertical shifts of the micro lens array and combined together to form a single set of the elemental images. From the combined elemental images, orthographic view images and depth slice images of the microscopic specimen were generated with enhanced resolution.


Integrin-mediated human glioblastoma cells adhesion, migration and invasion by native and recombinant phospholipases of Scorpio maurus venom glands.
Integrins are a large family of cell surface receptors mediating the interaction of cells with their microenvironment and they play an important role in glioma biology. In the present work, we reported the anti-tumor effect of Sm-PLGV a phospholipase A2 from Tunisian scorpion venom glands-as well as its recombinant forms expressed in Escherichia coli-through interference with integrin receptor function in malignant glioma cells U87. These phospholipases inhibited in a dose dependent manner the adhesion, migration and invasion onto fibrinogen and fibronectin without any cytotoxicity. We showed that Sm-PLGV and its recombinant constructs blocked U87 migration by reducing their velocity and directional persistence. The inhibitory effect was related to a blockage of the integrins αvβ3 and α5β1 function. Inactivation of the enzymatic activity of Sm-PLGV by chemical modification with p-bromophenacyl bromide did not affect its anti-tumor properties, suggesting the presence of 'pharmacological sites' distinct from the catalytic site in scorpion venom phospholipases A2.


Kinetics of monodisperse iron oxide nanocrystal formation by "heating-up" process.
We studied the kinetics of the formation of iron oxide nanocrystals obtained from the solution-phase thermal decomposition of iron-oleate complex via the "heating-up" process. To obtain detailed information on the thermal decomposition process and the formation of iron oxide nanocrystals in the solution, we performed a thermogravimetric-mass spectrometric analysis (TG-MS) and in-situ magnetic measurements using SQUID. The TG-MS results showed that iron-oleate complex was decomposed at around 320 degrees C. The in-situ SQUID data revealed that the thermal decomposition of iron-oleate complex generates intermediate species, which seem to act as monomers for the iron oxide nanocrystals. Extensive studies on the nucleation and growth process using size exclusion chromatography, the crystallization yield data, and TEM showed that the sudden increase in the number concentration of the nanocrystals (burst of nucleation) is followed by the rapid narrowing of the size distribution (size focusing). We constructed a theoretical model to describe the "heating-up" process and performed a numerical simulation. The simulation results matched well with the experimental data, and furthermore they are well fitted to the well-known LaMer model that is characterized by the burst of nucleation and the separation of nucleation and growth under continuous monomer supply condition. Through this theoretical work, we showed that the "heating-up" and "hot injection" processes could be understood within the same theoretical framework in which they share the characteristics of nucleation and growth stages.


Restoring In Vivo-Like Membrane Lipidomics Promotes Exosome Trophic Behavior from Human Placental Mesenchymal Stromal/Stem Cells.
Human mesenchymal stem cells (hMSCs) are an effective tool in regenerative medicine notably for their intrinsic plentiful paracrine activity rather than differentiating properties. The hMSC secretome includes a wide spectrum of regulatory and trophic factors, encompassing several naked molecules as well as different kinds of extracellular vesicles (EVs). Among EVs, exosomes represent an intriguing population, able to shuttle proteins, transcription factors, and genetic materials, with a relevant role in cell-to-cell communication, modulating biological responses in recipient cells. In this context, the extracellular milieu can greatly impact the paracrine activity of stem cells, modifying their metabolism, and the dynamics of vesicle secretion. In the present study, we investigated the effects elicited on exosome patterning by tailored, ad hoc formulated lipid supplementation (Refeed®) in MSCs derived from human fetal membranes (hFM-MSCs). Wound healing experiments revealed that stem cell exposure to exosomes obtained from Refeed®-supplemented hFM-MSCs increased their migratory capability, although the amount of exosomes released after Refeed® supplementation was lower than that yielded from non-supplemented cells. We found that such a decrease was mainly due to a different rate of exosomal exocytosis rather than to an effect of the lipid supplement on the endocytic pathway. Endoplasmic reticulum homeostasis was modified by supplementation, through the upregulation of PKR-like ER kinase (PERK) and inositol-requiring enzyme 1α (IRE1α). Increased expression of these proteins did not lead to stress-induced, unfolded protein response (UPR)-mediated apoptosis, nor did it affect phosphorylation of p38 kinase, suggesting that PERK and IRE1α overexpression was due to augmented metabolic activities mediated by optimization of a cellular feeding network afforded through lipid supplementation. In summary, these results demonstrate how tailored lipid supplementation can successfully modify the paracrine features in hFM-MSCs, impacting both intracellular vesicle trafficking and secreted exosome number and function.


Characterization of immunodominant and potentially protective epitopes of Mannheimia haemolytica serotype 1 outer membrane lipoprotein PlpE.
Mannheimia haemolytica serotype 1 (S1) is the most common bacterial isolate found in shipping fever pneumonia in beef cattle. Currently used vaccines against M. haemolytica do not provide complete protection against the disease. Research with M. haemolytica outer membrane proteins (OMPs) has shown that antibodies to one particular OMP from S1, PlpE, may be important in immunity. In a recently published work, members of our laboratory showed that recombinant PlpE (rPlpE) is highly immunogenic when injected subcutaneously into cattle and that the acquired immunity markedly enhanced resistance to experimental challenge (A. W. Confer, S. Ayalew, R. J. Panciera, M. Montelongo, L. C. Whitworth, and J. D. Hammer, Vaccine 21:2821-2829, 2003). The objective of this work was to identify epitopes of PlpE that are responsible for inducing the immune response. Western blot analysis of a series of rPlpE with nested deletions on both termini with bovine anti-PlpE hyperimmune sera showed that the immunodominant region is located close to the N terminus of PlpE. Fine epitope mapping, in which an array of overlapping 13-mer synthetic peptides attached to a derivatized cellulose membrane was probed with various affinity-purified anti-PlpE antibodies, identified eight highly reactive regions, of which region 2 (R2) was identified as the specific epitope. The R2 region is comprised of eight imperfect repeats of a hexapeptide (QAQNAP) and is located between residues 26 and 76. Complement-mediated bactericidal activity of affinity-purified anti-PlpE bovine antibodies confirmed that antibodies directed against the R2 region are effective in killing M. haemolytica.


Awareness and Practice of Cervical Cancer Screening among Female Health Professionals in Murtala Mohammed Specialist Hospital, Kano.
Cervical cancer, although largely preventable, remains the most common cause of cancer mortality among women in the developing world. Other members of the community see health care workers as models, therefore their attitudes and actions are predictors of societal health behaviour. We assessed the knowledge, attitude and practice regarding prevention of cervical cancer among female health professionals in a secondary health facility in Kano, Nigeria. A structured questionnaire was administered on 230 female respondents in the various health professions including doctors, pharmacists, nurses and laboratory technologists in Murtala Mohammed Specialist hospital, Kano. Over 60% of the respondents were able to correctly identify all the important aetiological factors associated with cervical cancer, while a similar figure knew the important signs and symptoms of the disease. Up to 94.7% of the respondents had a positive attitude towards Pap smear while 8.2% disapproved of it. Only 20.8% of the respondents have had a Pap smear done previously. Married respondents were more than four times likely to have had a previous Pap smear compared to their single counterparts. (X(2) = 13.3 df=1 P = 0.0003)[O.R=4.8, 95% confidence interval= 1.9 -14.4]. In contrast, religion appeared to have no significant influence on the practice (X(2)= 0.87 df=1 P=0.35). Despite a moderately high level of knowledge of cervical cancer screening and positive attitude towards it, the uptake of Pap smear was low. There is a need for continuing education to improve uptake of these services by health professionals so as to serve as a motivating factor for the public. Key words: cervical cancer screening, pap smear, female health workers, knowledge, practices.


Involvement of the N/OFQ-NOP system in rat morphine antinociceptive tolerance: Are astrocytes the crossroad?
The development of tolerance to the antinociceptive effect is a main problem associated with the repeated administration of opioids. The progressively higher doses required to relieve pain reduce safety and exacerbate the side effects of classical opioid receptor agonists like morphine. Nociceptin/orphanin FQ (N/OFQ) and its NOP receptor constitute the fourth endogenous opioid system that is involved in the control of broad spectrum of biological functions, including pain transmission. Aim of this work was to evaluate the relevance of the N/OFQ-NOP system in morphine antinociceptive action and in the development of morphine tolerance in the rat. Continuous spinal intrathecal infusion of morphine (1-3 nmol/h) evoked analgesic effects for 5 days in wild type animals. The same doses infused in NOP(-/-) rats showed a lower analgesic efficacy, while the onset of tolerance was delayed to day 9. N/OFQ (1-3 nmol/h), continuously infused in NOP(+/+) animals, showed an analgesic profile similar to morphine. Immunohistochemical analysis of the dorsal horn of the spinal cord of morphine tolerant NOP(+/+) rats showed an increased number of Iba1- and GFAP-positive cells (microglia and astrocytes, respectively). Interestingly, microglia but not astrocyte activation was observed in NOP(-/-) morphine tolerant rat. A selective activation of astrocytes was observed in the dorsal horn of wild type N/OFQ tolerant rats. The antinociceptive effect of morphine partially depends by the N/OFQ-NOP system that participates in the development of morphine tolerance. In particular, NOP receptors are involved in morphine-induced astrocyte activation, and N/OFQ per se increases astrocyte density.


Clearance of 99mTc-DTPA in pigeon fancier's hypersensitivity pneumonitis.
The rate of clearance of inhaled 99mTc-DTPA was measured in 20 nonsmoking pigeon fanciers and 7 control subjects. The degree of their avian contact and pigeon-related symptoms were noted, humoral immune response in the form of IgG antibody to pigeon gamma globulin was quantified, and diffusing capacity and total lung capacity were measured. Thirteen fanciers who had a high level of antibody had increased rates of clearance of 99mTc-DTPA (mean half-time clearance of 16.8 [+/- SEM 2.02] min [p = 0.001]) even if they were asymptomatic and even if their diffusing capacity and total lung capacity were normal. Seven control subjects without exposure to pigeon-derived antigens had normal clearance (mean 72.6 [+/- 5.98] min), and seven fanciers with antigen exposure but without an antibody response had intermediate rates of clearance (mean 42.57 [+/- 5.11] min). Clearance was not directly related to the indices of intensity and duration of antigen exposure. The measurement of rate of clearance of 99mTc-DTPA in pigeon fanciers can identify an alteration in pulmonary integrity more subtle than found with conventional pulmonary function tests and may therefore be a useful test for studying the pulmonary response to inhaled antigen and for detecting the earliest stages in the evolution of hypersensitivity pneumonitis.


Ultrastructure of the developing fetal hepatocyte of Macaca arctoides: a proposed model for studies of fetal drug metabolism.
The ultrastructure of the hepatocyte of the fetal stumptail monkey was examined with the aim of defining a possible model for studies of fetal drug metabolism. Hepatocytes from fetuses of 80 and 160 days gestation, as well as from one animal one week of postnatal age, were examined and compared to human fetal hepatocytes at 12 and 16 weeks gestation. Marked variation was observed in the amount of lipid and the distribution of organelles within the cytoplasm of the hepatocyte in the monkey population. These differences were attributed to genetic variation. Two changes were seen which correlated with developmental age. The amount of hemopoietic tissue decreased and the amount of smooth endoplasmic reticulum increased as the animal matured. The problems of genetic variation and the relative number of hepatocytes at different stages of development were discussed relative to the use of this animal as a model for fetal drug metabolism studies. Attention to both of these problems is considered necessary for the interpretation of biochemical data in future studies.


Preventing teen pregnancy through persuasive communications: realities, myths, and the hard-fact truths.
Effective campaigns are desperately needed to combat the serious social problem of teen pregnancy. However, public health campaigns are most often noted for failures, rather than successes. One reason for a campaign failing to have the intended effect is lack of theoretical guidance at the formative evaluation stage. The study reported here is a theoretically-based formative evaluation with inner city teens. Six focus groups were conducted to determine knowledge, attitudes, beliefs, and recommendations for effective campaigns to deter teen pregnancy. The results indicate that campaign messages need to combat positive attitudes toward pregnancy, negative attitudes toward birth control, the perception of personal invulnerability, and emphasize the negative consequences of sexual intercourse. This study's findings also suggest that campaigns with these messages need to start at an early age in order to effectively prevent teen pregnancy.


Modeling mitral valve stenosis: A parametric study on the stenosis severity level.
New computational techniques providing more accurate representation of human heart pathologies could help uncovering relevant physical phenomena and improve the outcome of medical therapies. In this framework, the present work describes an efficient computational model for the evaluation of the ventricular flow alteration in presence of mitral valve stenosis. The model is based on the direct numerical simulation of the Navier-Stokes equations two-way coupled with a structural solver for the left ventricle and mitral valve dynamics. The presence of mitral valve stenosis is mimicked by a single-parameter constraint acting on the kinematics of the mitral leaflets. Four different degrees of mitral valve stenosis are considered focusing on the hemodynamic alterations occurring in pathologic conditions. The mitral jet, generated during diastole, is seen to shrink and strengthen when the stenosis gets more severe. As a consequence, the kinetic energy of the flow, the tissues shear stresses, the transvalvular pressure drop and mitral regurgitation increase. It results that, as the stenosis severity level increases, the geometric and effective orifice areas decrease up to 50% with respect the normal case due to the reduced leaflets mobility and stronger blood acceleration during the diastolic phase. The modified intraventricular hemodynamics is also related to a stronger pressure gradient that, for severe stenosis, can be more than ten times larger than the healthy valve case. These computational results are fully consistent with the available clinical literature and open the way to the virtual assessment of surgical procedures and to the evaluation of prosthetic devices.