A scale for measuring home-based cardiac rehabilitation exercise adherence: a development and validation study.
The benefits of home-based cardiac rehabilitation exercise are well-established and depend on long-term adherence. However, there is no uniform and recognized cardiac rehabilitation criterion to assess home-based cardiac rehabilitation exercise adherence for patients with cardiovascular disease. This study aimed to develop a home-based cardiac rehabilitation exercise adherence scale and to validate its psychometric properties among patients with chronic heart failure. The dimensions and items of the scale were created based on grounded theory research, literature content analysis, and defined by a Delphi survey. Item analysis was completed to assess the discrimination and homogeneity of the scale. Factor analysis was adopted to explore and validate the underlying factor structure of the scale. Content validity and calibration validity were evaluated using the Delphi survey and correlation analysis, respectively. Reliability was evaluated by Cronbach's α coefficients, split-half reliability coefficients, and test-retest reliability coefficients. A scale covering four dimensions and 20 items was developed for evaluating home-based cardiac rehabilitation exercise adherence. The content validity index of the scale was 0.986. In exploratory factor analysis, a four-factor structure model was confirmed, explaining 75.1% of the total variation. In confirmatory factor analysis, the four-factor structure was supported by the appropriate fitting indexes. Calibration validity of the scale was 0.726. In terms of reliability, the Cronbach's α coefficient of the scale was 0.894, and the Cronbach's α coefficients of dimensions ranged from 0.848 to 0.914. The split-half reliability coefficient of the scale was 0.695. The test-retest reliability coefficient of the scale was 0.745. In this study, a home-based cardiac rehabilitation exercise adherence scale was developed and its appropriate psychometric properties were confirmed.


Simultaneous early surgical repair of post-cholecystectomy major bile duct injury and complex abdominal evisceration: A case report.
Major bile duct injuries (BDIs) are hazardous complications during 0.4%-0.6% of laparoscopic cholecystectomies. Major BDIs usually require surgical repair, ideally either immediately or at least six weeks after the damage. The complexity of our case lies in the coexistence of early BDI followed by 2-week biliary peritonitis with massive midline evisceration which, in combination, has over 40% mortality risk. We describe the case of a 65-year-old male, transferred to our tertiary HPB service on day 14 after common bile duct complete transection during cholecystectomy and postoperative laparotomy. The patient presented with biliary peritonitis along with full wound dehiscence and extensive evisceration. During emergency peritoneal wash-out surgery we deemed immediate BDI repair feasible by primary Roux-en-Y hepaticojejunostomy (HJ), with multi-stage abdominal closure. In the following days we performed progressive abdominal wall closure in multiple sessions under general anesthesia, aided by vacuum-assisted wound closure and intraperitoneal mesh-mediated fascial traction-approximation (VAWCM) with permeable mesh. An expected late incisional hernia was eventually repaired through component separation and biological mesh. The simultaneous use of Roux-en-Y HJ and VAWCM has proven safe and effective in the treatment of BDI and 2-week biliary peritonitis with massive midline evisceration.


Growth, Characterization, and Application of Vertically Aligned Carbon Nanotubes Using the RF-Magnetron Sputtering Method.
The aim of this work is to synthesize and characterize a nanostructured material with improved parameters suitable as a chemiresistive gas sensor sensitive to propylene glycol vapor (PGV). Thus, we demonstrate a simple and cost-effective technology to grow vertically aligned carbon nanotubes (CNTs) and fabricate a PGV sensor based on Fe2O3:ZnO/CNT material using the radio frequency magnetron sputtering method. The presence of vertically aligned carbon nanotubes on the Si(100) substrate was confirmed by scanning electron microscopy and Fourier transform infrared (FTIR), Raman, and energy-dispersive X-ray spectroscopies. The uniform distribution of elements in both CNTs and Fe2O3:ZnO materials was revealed by e-mapped images. The hexagonal shape of the ZnO material in the Fe2O3:ZnO structure and the interplanar spacing in the crystals were clearly visible by transmission electron microscopy images. The gas-sensing behavior of the Fe2O3:ZnO/CNT sensor toward PGV was investigated in the temperature range of 25-300 °C with and without ultraviolet (UV) irradiation. The sensor showed clear and repeatable response/recovery characteristics in the PGV range of 1.5-140 ppm, sufficient linearity of response/concentration dependence, and high selectivity both at 200 and 250 °C without UV radiation. This is a basis for concluding that the synthesized Fe2O3:ZnO/CNT structure is the best candidate for use in PGV sensors, which will allow its further successful application in real-life sensor systems.


Fabrication and characterization of lipopeptide biosurfactant-based electrospun nanofibers for use in tissue engineering.
Nanofibers are a class of nanomaterial with specific physicochemical properties and characteristics making them quite sought after and investigated by researchers. Lipopeptide biosurfactant (LPB) formulation properties were previously established in wound healing. LPB were isolated from in vitro culture of Acinetobacter junii B6 and loaded on nanofibers formulation produced by electrospinning method with different ratios of carboxymethylcellulose (CMC), polyvinyl alcohol (PVA), and Poloxamer. Numerous experimental control tests were carried out on formulations, including physicochemical properties which were evaluated by using dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FT-IR), morphology study by scanning electron microscopy (SEM), and thermal stability. The best nanofibers formulation was obtained by the electrospinning method, with a voltage of 19.8 volts, a discharge capacity of 1cm/h, a cylindrical rotating velocity of 100rpm, and a needle interval of 7cm from the cylinder, which continued for 7hours. The formulation contained 2% (w/v) CMC, 10% (w/v) poloxamer, 9% (w/v) PVA, and 5% (w/v) LPB. This formula had desirable physicochemical properties including spreadability, stability, and uniformity with the particle size of about 590nm.


A controlled prospective study of neuropsychological dysfunction following carotid endarterectomy.
Although subtle cognitive injury as revealed by neuropsychological testing occurs in a substantial number of patients following carotid endarterectomy (CEA), there is controversy about whether this finding is a result of the surgery or the anesthesia. To examine the changes in neuropsychological test performance in patients following CEA vs a control group of patients older than 60 years following spine surgery, so as to determine whether neuropsychological dysfunction after CEA is a result of surgery or anesthesia. Patients undergoing CEA (n = 80) and lumbar spine surgery (n = 25) were assessed with a battery of neuropsychological tests preoperatively and on postoperative days 1 and 30. The neuropsychological performance of patients in the control group was used to normalize performance for patients in the CEA group, by calculating z scores using the mean and SD of the change scores in the control group. Significant cognitive dysfunction was defined as performance that exceeded 2 SDs above the mean performance of patients in the control group. Postoperative days 1 and 30 total deficit scores were significantly worse in the CEA group compared with the controls. When individual test results were examined, the CEA group performed significantly worse than the controls on the Rey Complex Figure test and Halstead-Reitan Trails B on day 1, and on the Rey Complex Figure on day 30. Overall, cognitive dysfunction was seen in 22 patients (28%) in the CEA group on day 1 and in 11 (23%) of 48 patients on day 30. Subtle cognitive decline following CEA occurs and persists for at least several weeks after surgery. This decline was absent in a control group.


Alkaloid and flavonoid rich fractions of fenugreek seeds (Trigonella foenum-graecum L.) with antinociceptive and anti-inflammatory effects.
The seeds of fenugreek (Trigonella foenum-graecum L.) have medicinal uses as hypoglycemic, antinociceptive and anti-inflammatory agents. We aimed to evaluate the antinociceptive and anti-inflammatory effects of the major fractions of fenugreek seeds. The methanolic extract of the plant seeds was partitioned using a liquid-liquid extraction procedure to give six major fractions. Following phytochemical screening of isolated fractions, the total extract and each fraction were evaluated for their antinociception and anti-inflammatory effects using formalin and carrageenan-induced paw edema tests respectively. The methanolic extract exhibited both antinociceptive and anti-inflammatory effects at a dose of 100mg/kg. Among the tested fractions, alkaline chloroform fraction (AKC), which was alkaloid positive in screening tests, showed the most anti-nociceptive effect in a dose-dependent manner. AKC fraction was as effective as morphine (5mg/kg) in this regard. Both aqueous and acidified chloroform fractions (ACC) could significantly inhibit paw edema at a different dose. The latter fraction dose-dependently inhibited carrageenan-induced paw edema. The results of phytochemical screening tests confirmed the presence of flavonoids in both ACC and aqueous fractions. It can be concluded that the alkaloid and flavonoid content of fenugreek seeds can be responsible for antinociception and anti-inflammatory effects of the plant respectively.


Taking microRNAs to heart.
MicroRNAs (miRNAs) are a class of highly conserved, small non-coding RNAs that regulate gene expression post-transcriptionally. The emerging field of miRNA biology has begun to reveal roles for these regulatory molecules in a wide range of biological processes. Dysregulated miRNA expression has been correlated to diseased hearts in human patients, whereas inhibiting the maturation of miRNAs conditionally in murine hearts has revealed that miRNAs are essential for cardiac development and function. Moreover, genetic studies have identified distinct roles for specific miRNAs during cardiogenesis, cardiac hypertrophy and electrical conduction. These previously unrecognized relationships shed new light on the regulatory mechanisms underlying heart development and pathology and suggest the potential importance of miRNAs as diagnostic markers and therapeutic targets for cardiovascular disease.


A rare case of acute myocardial infarction related to mobile papillary fibroelastoma of the aortic valve.
We present the case of a 75-year-old woman with typical myocardial infarction but a negative coronary angiogram. Echocardiography identified the rare cause of her chest pain: a mobile mass on the aortic valve that obstructed the coronary ostium. The histopathology revealed a papillary fibroelastoma (PFE), and her chest pain was relieved after surgical resection of the mass.


Long-term cardiovascular outcomes of biodegradable polymer drug eluting stents in patients with diabetes versus non-diabetes mellitus: a meta-analysis.
Today, diabetes mellitus (DM) has become a worldwide concern. DM is a major risk factor for the development of cardiovascular diseases (CVD). Eligible patients with CVD are treated invasively by percutaneous coronary intervention (PCI) whereby a stent is implanted inside the coronary vessel with the particular lesion to allow sufficient blood flow. Newer scientific research have shown that even though associated with a lower rate of re-stenosis, first-generation drug eluting stents (DES) were associated with a higher rate of late stent thrombosis. Recently, newer stents, namely biodegradable polymer DES (BP-DES) have been developed to overcome the safety issues of earlier generation DES. In this analysis we aimed to systematically compare the long term (≥ 12 months) adverse cardiovascular outcomes observed in DM versus non-DM patients who were implanted with BP-DES. Cochrane central, MEDLINE (Subset PubMed), EMBASE, Web of Science, http://www. gov and Google scholar were searched for relevant publications involving BP-DES in patients with DM versus non-DM and their associated adverse cardiovascular outcomes. The mean follow-up time period ranged from 12 to 120 months. Data analysis was carried out with the latest version of the RevMan software (version 5.4). Based on the Mantel-Haenszel test, risk ratios (RR) with 95% confidence intervals (CI) were calculated and used to represent the results following analysis. Seven (7) studies with a total number of 10,246 participants were included in this analysis. Stents which were implanted during PCI were BP-DES. Participants were enrolled from the year 2006 to 2013. Our current results showed that in patients who were implanted with BP-DES, the risks of major adverse cardiac events (RR: 1.30, 95% CI: 1.18-1.43; P = 0.00001), myocardial infarction (RR: 1.48, 95% CI: 1.14-1.93; P = 0.003), all-cause mortality (RR: 1.70, 95% CI: 1.29-2.23; P = 0.0002), cardiac death (RR: 1.93, 95% CI: 1.28-2.93; P = 0.002), target vessel revascularization (RR: 1.35, 95% CI: 1.03-1.77; P = 0.03), target lesion revascularization (RR: 1.28, 95% CI: 1.07-1.54; P = 0.007) and target lesion failure (RR: 1.79, 95% CI: 1.52-2.12; P = 0.00001) were significantly higher in the DM group. Definite and probable stent thrombosis (RR: 1.80, 95% CI: 1.28-2.55; P = 0.0009) were also significantly higher in the DM group. Diabetes mellitus was an independent risk factor associated with long term adverse cardiovascular outcomes following PCI with BP-DES.


Enhancement of alcohol withdrawal seizures with 6-hydroxydopamine.
The relationship between central catecholamine neurons and alcohol withdrawal seizures was studied in rats pretreated with 6-hydroxydopamine to selectively destroy the central catecholamine nerve terminals. The alteration of alcohol withdrawal seizures was manifested by (1) a higher percentage of the rats developing the seizures, (2) an earlier onset of seizures, and (3) a greater severity of seizure activity. Seizure status was exhibited in 25% of the 6-hydroxydopamine-treated rats.


Development and validation of a new approach for computer-aided long bone fracture reduction using unilateral external fixator.
An innovative computer-aided method to plan and execute long bone fracture reduction using Dynafix unilateral external fixator (EF) is presented and validated. A matrix equation, which represents a sequential transformation from proximal to distal ends, was derived and solved for the amount of rotation and translation required at each EF joint to correct for a displaced fracture using a non-linear least square optimization method. Six polyurethane-foam models of displaced fracture tibiae were used to validate the method. The reduction accuracy was quantified by calculating the residual translations (xr, yr, zr), the residual displacement (dr), and the residual angulations (alphar, betar, gammar) based on the X-Y-Z Euler angle convention. The experiment showed that the mean+/-S.D. of alphar, betar, gammar, xr, yr, zr and dr were 1.57+/-1.14 degrees, 1.33+/-0.90 degrees, 0.71+/-0.70 degrees, 0.98+/-1.85, 0.80+/-0.67, 0.30+/-0.27, and 0.50+/-0.77 mm, respectively, which demonstrated the accuracy and reliability of the method. Instead of adjusting the fixator joints in-situ, our method allows for off-site adjustment of the fixator joints and employs the adjusted EF as a template to guide the surgeons to manipulate the fracture fragments to complete the reduction process. Success of this method would allow surgeons to perform fracture reduction more objectively, efficiently and accurately yet reduce the radiation exposure to both the involved clinicians and patients and lessen the extent of periosteum and soft tissue disruption around the fracture site.


A systematic review demonstrating correlation of MRI compositional parameters with clinical outcomes following articular cartilage repair interventions in the knee.
Compositional-MRI parameters enable the assessment of cartilage ultrastructure. Correlation of these parameters with clinical outcomes is unclear. This systematic review investigated the correlation of various compositional- MRI parameters with clinical outcome measures following cartilage repair or regeneration interventions in the knee. This study was registered with PROSPERO and reported in accordance with PRISMA. PubMed, Institute of Science Index, Scopus, Cochrane Central Register of Controlled Trials, and Embase databases were searched. All studies, regardless of type, that presented correlation of compositional- MRI parameters with clinical outcome measures were included. Two researchers independently performed data extraction and QUADAS-2 analysis. Compositional-MRI parameter change following intervention and correlation with clinical outcome measures were evaluated. 19 studies were included. Risk of bias was generally low. 5 different compositional parameters were observed from the included studies. However, due to the significant variability in the reporting of compositional-MRI parameters across studies, meta-analyses were possible only for T2 values and T2 index values (T2 value of repair cartilage relative to normal cartilage). Correlation of T2 values of repair cartilage with clinical outcome score was r = 0.33 [0.15, 0.52]. Correlation of T2 index with clinical outcome score was r = 0.52 [0.32, 0.77]. Correlation between T2 values and clinical outcome scores following knee cartilage repair were found. The heterogeneity of the correlations extracted from the included studies limited the scope for the meta-analysis. Thus, standardised, high-quality studies are required for better assessment of correlation between compositional MRI parameters and clinical outcome measures after cartilage repair. PROSPERO CRD42021287364.Study protocol available on PROSPERO website.


Efficacy of Montanide™ ISA 763 A VG as aquatic adjuvant administrated with an inactivated Vibrio harveyi vaccine in turbot (Scophthalmus maximus L.).
Turbot (Scophthalmus maximus L.) is a commercially important fish species in China. Despite of its great economic potential, fish farms often suffer severe economic losses due to certain fish diseases. Vaccination has become a common strategy to prevent diseases caused by pathogens in aquaculture industry. However, no inactivated vaccine against Vibrio harveyi of turbot has been reported so far. In this study, we developed an inactivated vaccine using formalin-killed cells of V. harveyi and the efficacy of a commercial adjuvant Montanide™ ISA 763 A VG on the inactivated vaccine was evaluated. We found that with an optimum vaccine dosage at 1.0 × 108 CFU/fish, a high relative percent survival (RPS) more than 75% was observed at 4 weeks post vaccination (w.p.v.). Moreover, enhanced antibody titer, lysozyme activity, total serum protein and antibacterial property in sera of vaccinated fish were observed at 4, 8, 12 and 16 w.p.v. In conclusion, we developed an efficient inactivated vaccine against V. harveyi in turbot, which not only induced humoral immunity, but also enhanced initial innate immune response for long-term protection.


An event-related fMRI study on risk taking by healthy individuals of high or low impulsiveness.
This event-related functional Magnetic Resonance Imaging study examined the differential neural activities associated with a Risky-Gains task in 18 healthy individuals of high (n=9) or low (n=9) impulsiveness, according to their scores on the Barratt Impulsiveness Scale (BIS). The neural activities of people belonging to the high and low impulsiveness groups were monitored by a 3T MRI scanner while they were performing the Risky-Gains task. We demonstrated that a stronger activation in the insula-orbitofrontal-parietal regions was found in the high impulsiveness group compared to the low impulsiveness group. However, the levels of activation in the lateral prefrontal and anterior cingulate regions did not differ between the two groups. The findings suggest that the neural substrates of comprehension of cognitive and affective information associated with risk-taking decision making may vary according to the impulsiveness among healthy individuals.


Recommendations of the Spanish Society of Neurology for the prevention of stroke. Interventions on lifestyle and air pollution.
To update the recommendations of the Spanish Society of Neurology regarding lifestyle interventions for stroke prevention. We reviewed the most recent studies related to lifestyle and stroke risk, including randomised clinical trials, population studies, and meta-analyses. The risk of stroke associated with such lifestyle habits as smoking, alcohol consumption, stress, diet, obesity, and sedentary lifestyles was analysed, and the potential benefits for stroke prevention of modifying these habits were reviewed. We also reviewed stroke risk associated with exposure to air pollution. Based on the results obtained, we drafted recommendations addressing each of the lifestyle habits analysed. Lifestyle modification constitutes a cornerstone in the primary and secondary prevention of stroke. Abstinence or cessation of smoking, cessation of excessive alcohol consumption, avoidance of exposure to chronic stress, avoidance of overweight or obesity, a Mediterranean diet supplemented with olive oil and nuts, and regular exercise are essential measures in reducing the risk of stroke. We also recommend implementing policies to reduce air pollution.


Social support and self-esteem as intervening variables in the relationship between social roles and women's well-being.
The effects of social roles on women's well-being are explored in an analysis which incorporates social support and self-esteem as intervening variables. The impact of roles on well-being is expected to occur primarily through these intervening variables. An analysis of a national sample of adult women reveals that the only social roles to impact well-being through effects on social support or self-esteem are employment and parenthood. Results indicate that parenthood has a weak positive effect on support and marriage reduces levels of distress. Employment does not enhance well-being via social support but does have a positive effect on self-esteem. Community programs which encourage social participation and which involve esteem enhancing activities are recommended.


Vitamin and mineral provision during enteral nutrition.
The adequacy of vitamin and mineral provision during enteral nutrition for a period of at least two weeks was studied in 20 patients. Significant increases were observed in plasma levels of vitamins C and E, and in B2, B6 and folate status. No significant changes were observed in vitamins A, B1, B12 or in plasma magnesium, zinc or copper. The requirements for vitamins and minerals during enteral nutrition are discussed.


First Strike personalized predictive radioiodine prescription for inoperable metastatic differentiated thyroid cancer.
The traditional practice of empiric radioiodine (I-131) prescription is scientifically obsolete and inappropriate for inoperable metastatic differentiated thyroid cancer. However, theranostically guided prescription is still years away for many institutions. A personalized predictive method of radioiodine prescription that bridges the gap between empiric and theranostic methods is presented. It is an adaptation of the "maximum tolerated activity" method, where serial blood sampling is replaced by population kinetics carefully chosen by the user. It aims to maximize crossfire benefits within safety constraints to overcome tumour absorbed dose heterogeneity for a safe and effective first radioiodine fraction i.e., the First Strike. The EANM method of blood dosimetry was incorporated with population kinetics, marrow and lung safety constraints, body habitus and clinical assessment of metastatic extent. Population data of whole body and blood kinetics in patients with and without metastases, prepared by recombinant human thyroid stimulating hormone or thyroid hormone withdrawal, and the maximum safe marrow dose rate were deduced from published data. For diffuse lung metastases, the lung safety limit was linearly scaled by height and separated into lung and remainder-of-body components. The slowest whole body Time Integrated Activity Coefficient (TIAC) amongst patients with any metastases was 33.5±17.0 h and the highest percentage of whole body TIAC attributed to blood was 16.6±7.9%, prepared by thyroid hormone withdrawal. A variety of other average radioiodine kinetics is tabulated. Maximum safe marrow dose rate was deduced to be 0.265 Gy/h per fraction, where blood TIAC is normalised to administered activity. An easy-to-use calculator was developed which only requires height, weight and gender to populate recommendations for personalized First Strike prescription. The user decides by clinical gestalt whether the prescription is to be constrained by marrow or lung, then selects an activity depending on how extensive the metastases are likely to be. A Standard Female with oligometastasis and good urine output without diffuse lung metastasis is expected to safely tolerate 8.03 GBq of radioiodine as the First Strike. This predictive method will help institutions rationalise the First Strike prescription based on radiobiologically sound principles, personalised to individual circumstances.


Spatial evaluation of prevalence, pattern and predictors of cervical cancer screening in India.
To investigate the social determinants of cervical cancer screening and report the locations vulnerable to poor utilization of cervical cancer screening services. An ecological study with the data derived from fourth round of the National Family Health Survey conducted in India in the period 2015-2016. The study focused on the percentage of women who have never undergone cervical cancer screening across 639 districts in India. Moran's I statistic was used to investigate the overall clustering of location. The Getis-Ord Gi* statistic was used for the detection of significant local clusters. Spatial error, spatial lag, spatial Durbin and spatial Durbin error models were compared, and the model with best fit was reported. ArcGIS, GeoDa and R software were used for the analysis. The existence of spatial autocorrelation (Moran's I = 0.61) necessitates the consideration of spatial component while studying the screening data. A significant clustering of districts with poor screening has been observed in the North-Central and North-Eastern regions of India. The geographic arrangement of the percentage of women who have undergone cervical cancer screening was associated with the percentage of women with poor wealth index (P < 0.001), not using a modern method of contraception (P < 0.001), residing in rural areas (P = 0.033) and never heard of sexually transmitted infection (P = 0.014). The range of percentage of women getting cervix screened for cancer was 0.5-68.4%, presenting the heterogeneity among the population elements. A higher risk of poor cervical cancer screening is observed in the districts where most of the women have poor wealth index, reside in urban area, have never heard of sexually transmitted infection and do not use a modern method of contraception.


Impact of external forces on cyanophage-host interactions in aquatic ecosystems.
Cyanobacterial (algal) blooms have by convention been attributed to the excessive level of nutrients from pollution and runoff, which promotes the rapid growth and multiplication of cyanobacteria or algae. The cyanophage (virus) is the natural predator of cyanobacteria (the host). The aim of this review is to unveil certain pressures that disrupt cyanophage-host interactions and the formation of cyanobacterial blooms. This review focuses principally on the impact of greenhouse gases, ozone depletion, solar ultraviolet radiation (SUR) and the role of recently discovered virophages, which coexist with and in turn are the natural predator of phages. The key findings are that the increase in SUR, the mutation of cyanophages and cyanobacteria, along with changing nutrient levels, have combined with virophages to impede cyanophage-host interactions and the resultant viral infection and killing of the cyanobacterial cell, which is a necessary step in controlling cyanobacterial blooms. Consider this a 'call to action' for researchers interested in corrective action aimed at evolving aquatic ecosystems.


Synthesis and crystal structure of a heterobimetallic nickel-manganese 12-metallacrown-4 methanol disolvate monohydrate compound.
The synthesis and crystal structure of the title compound [systematic name: di-μ-acetato-tetra-kis-(μ4-N,2-dioxido-benzene-1-carboximidato)hexa-methano-ltetra-manganese(III)nickel(II) methanol disolvate monohydrate], [Mn4Ni(C7H4NO3)4(C2H3O2)2(CH4O)6]·2CH4O·H2O or Ni(OAc)2[12-MCMn(III)N(shi)-4](CH3OH)6·2CH3OH·H2O, where MC is metallacrown, -OAc is acetate, and shi3- is salicyl-hydroximate, are reported. The macrocyclic metallacrown is positioned on an inversion center located on the NiII ion that resides in the central MC cavity. The macrocycle consists of an MnIII-N-O repeat unit that recurs four times to generate an overall square-shaped mol-ecule. Both the NiII and MnIII ions are six-coordinate with an octa-hedral geometry. In addition, the MnIII ions possess an elongated Jahn-Teller distortion along the z-axis of the coordination environment. The inter-stitial water mol-ecule is slightly offset from and disordered about an inversion center.


The Validity of Body Adiposity Indices in Predicting Metabolic Syndrome and Its Components among Egyptian Women.
To assess the associations between the body adiposity indices and risk of metabolic syndrome (MS) and its components in Egyptian women and to evaluate their predictive power. This was a cross-sectional analysis performed on 180 Egyptian women aged between 25-35 years. They were 90 women with MS diagnosed by International Diabetes Federation (IDF) and 90 healthy age matched controls. Body adiposity index (BAI), body mass index (BMI), waist to hip ratio (WHR) and waist to height ratio (WHtR) were calculated and serum samples were analyzed for metabolic parameters. Receiver operating characteristic curves (ROC) was used to determine the discriminatory capacity of BAI, WHR WHtR and BMI for MS. Area under the curve (AUC) was highest for BIA, followed by WHR, WHtR and then BMI. All adiposity indices were significantly correlated with metabolic components and BAI had the highest correlation coefficients compared to other indices. BAI is a practical predictor for MS and has satisfactory diagnostic accuracy for diagnosing MS among Egyptian women and can be used in addition to WHR, WHtR and BMI for identifying MS in the field studies.


miR-630 functions as a tumor oncogene in renal cell carcinoma.
MicroRNAs (miRNAs) are non-coding RNAs that regulate multiple cell processes during cancer progression. Renal cell carcinoma (RCC) is a malignancy with a poor prognosis. In this study, we aimed to investigate the roles of miR-630 in RCC progression. Expression of miR-630 was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) in four renal cancer cell lines (786-O, ACHN, Caki-1, and Caki-2) and one normal human proximal tubule epithelial cell line (HK-2). Next, miR-630 inhibitor was used to inhibit miR-630 expression in 786-O cells. Finally, its effects on cell proliferation, apoptosis, migration, and invasion were evaluated. The expression level of miR-630 was higher in renal cancer cell lines 786-O, ACHN, Caki-1, and Caki-2 than that in the normal renal cell line HK-2 (p < 0.05). Furthermore, a proliferation assay, apoptosis assay, migration assay and invasion assay were performed, and the results showed that down-regulation of miR-630 expression by miR-630 inhibitor significantly inhibited cell proliferation, migration, and invasion, which meanwhile induced cell apoptosis of the renal cancer cell line 786-O. This is the first time that miR-630 expression has been shown to be associated with renal cancer progression, and down-regulation of miR-630 can inhibit tumor progression, which provides a potential therapeutic target for renal cancer treatment.


Response to neoplastic antigens in human oncology: assessment and results of LIF (leucocyte inhibitory factor) test in breast cancer patients.
The leucocyte inhibition factor (LIF) test, revealing the inhibition of leucocyte migration from capillary tubes, was studied with leucocytes from 47 patients with breast cancer, from 14 patients with benign breast tumors, and from 56 normal subjects. As antigens we used formalin-fixed tumor cells. The LIF assay was positive in 38/47 (80.8%) breast cancer patients, in 10/14 (71.4%) benign breast tumor patients, and in 13/56 (23.2%) normal subjects. The negative LIF assays were higher with leucocytes from patients with metastases than with those from patients with no metastases. We found no correlation between the LIF-test response and the histopathologic pattern of the tumors, type of treatment (almost always surgical), and remission or relapse state of our patients at the time of testing.


Childhood Obesity Prevention in Childcare Settings: the Potential of Policy and Environmental Change Interventions.
Current obesity rates in young children are a serious public health concern; developing and implementing obesity prevention interventions in childcare settings is a promising avenue to address this issue. In recent years, there has been increasing focus on environmental and policy change interventions for this setting. Improving access to and quality of outdoor play spaces and implementing the Nutrition and Physical Activity Self-Assessment for Child Care (NAP SACC) are two promising environmental change strategies in this setting. Laws at the local, state, and federal level have also been implemented; New York City and Delaware are two jurisdictions that have passed policies and provided preliminary evidence of the potential of policy interventions to change child outcomes. A combination of programmatic, environmental, and policy change strategies will likely be most effective in maximizing the potential of childcare settings to promote healthy weight in children.


Isolation of subclones with different tumorigenicity and metastatic ability from rat nephroblastoma cell line, ENUT.
Seven subclones derived from a chemically induced rat nephroblastoma cell line, ENUT, were isolated and their cytological characteristics were examined in order to investigate the biological nature of the parent tumor. The subclones were divisible into two types based on morphological and biological features: polygonal cells with well developed junctional complexes and less developed cell surface microvilli, showing a doubling time of 13.0 to 14.0 h and tumorigenicity in nude mice of 42-100%, and spindle-shaped cells with poorly developed junctional complexes and well developed microvilli, showing a doubling time of 9.7 to 12.2 h and 100% tumorigenicity. Potential for both spontaneous and experimental metastasis to the lungs was apparently higher in the spindle-shaped clones than in the polygonal clones. In spite of their differing characteristics, the cytochemical phenotypes of the two clonal types were almost identical to those of immature renal tubules of the developing fetal kidney. The present findings suggest that these subclones possess characteristics of early nephrogenic epithelial cells, and we speculate that the biological differences observed among the subclones may be explained by differences in malignant progression. In addition, these clones appear to be a useful model for the study of tumorigenicity and metastasis.


Technical Note: ADAM PETer - An anthropomorphic, deformable and multimodality pelvis phantom with positron emission tomography extension for radiotherapy.
To develop an anthropomorphic, deformable and multimodal pelvis phantom with positron emission tomography extension for radiotherapy (ADAM PETer). The design of ADAM PETer was based on our previous pelvis phantom (ADAM) and extended for compatibility with PET and use in 3T magnetic resonance imaging (MRI). The formerly manually manufactured silicon organ surrogates were replaced by three-dimensional (3D) printed organ shells. Two intraprostatic lesions, four iliac lymph node metastases and two pelvic bone metastases were added to simulate prostate cancer as multifocal and metastatic disease. Radiological properties [computed tomography (CT) and 3T MRI] of cortical bone, bone marrow and adipose tissue were simulated by heavy gypsum, a mixture of Vaseline and K2 HPO4 and peanut oil, respectively. For soft tissues, agarose gels with varying concentrations of agarose, gadolinium (Gd) and sodium fluoride (NaF) were developed. The agarose gels were doped with patient-specific activity concentrations of a Fluorine-18 labelled compound and then filled into the 3D printed organ shells of prostate lesions, lymph node and bone metastases. The phantom was imaged at a dual energy CT and a 3T PET/MRI scanner. The compositions of the soft tissue surrogates are the following (given as mass fractions of agarose[w%]/NaF[w%]/Gd[w%]): Muscle (4/1/0.027), prostate (1.35/4.2/0.011), prostate lesions (2.25/4.2/0.0085), lymph node and bone metastases (1.4/4.2/0.025). In all imaging modalities, the phantom simulates human contrast. Intraprostatic lesions appear hypointense as compared to the surrounding normal prostate tissue in T2-weighted MRI. The PET signal of all tumors can be localized as focal spots at their respective site. Activity concentrations of 12.0 kBq/mL (prostate lesion), 12.4 kBq/mL (lymph nodes) and 39.5 kBq/mL (bone metastases) were measured. The ADAM PETer pelvis phantom can be used as multimodal, anthropomorphic model for CT, 3T-MRI and PET measurements. It will be central to simulate and optimize the technical workflow for the integration of PET/MRI-based radiation treatment planning of prostate cancer patients.


Better view on attitudes and perceived parental reactions behind waterpipe smoking among Iranian students.
Because of the increasing usage of waterpipe globally, we need to know more about the different factors related to waterpipe and cigarette smoking. Therefore, the present study aims at gaining more insight on waterpipe and cigarette smoking based on perceived parental reaction and appeal and repellent of smoking among adolescents. A cross-sectional survey entitled "Isfahan Tobacco Use Prevention Program" (ITUPP) was conducted among 5,500 adolescents in Isfahan Province, Iran in 2010 using a self-administered anonymous questionnaire. Demographic factors, cigarette and waterpipe smoking status, appeal and repellent of smoking, perceived parental reactions, and the main reasons behind the increase in waterpipe smoking were measured. Chi-square, univariate logistic regression, and multiple logistic regression were used. For all analyses, we defined statistical significance a priori with a two-tailed alpha of 0.05. Statistical analyses were conducted using the Statistical Package for the Social Sciences (SPSS) version 15. 50% of the sample was female and 89% lived in urban areas. The average age of the respondents was 14.37 ± 1. 70 years. While a majority of cigarette smokers (70.9%) were waterpipe smokers, only 35.7% of waterpipe smokers smoked cigarettes. The incidence of smoking was high in those who expected less extensive parental reaction with odds ratio (OR) = 1.89 [95% confidence interval (CI): 1.35-2.63] (P < 0.001) among cigarette smokers and OR = 2.75 (95% CI: 2.16-3.50) (P < 0.001) among waterpipe smokers. "Taste" was rated the most attractive feature by waterpipe and cigarette smokers 2.83-fold (95% CI: 2.06, 3.90) (P < 0.001). Most waterpipe smokers compared to nonsmokers believed that the main reason behind waterpipe popularity was habit. The factors related to waterpipe smoking were different from those in cigarette smoking; so we need to implement different interventions to overcome the surging usage of tobacco use.


Hoechst 33342: the dye that enabled differentiation of living X-and Y-chromosome bearing mammalian sperm.
Hoechst 33342 is the fluorophore used routinely to measure DNA in X- and Y-chromosome-bearing mammalian sperm so they can be separated by flow sorting. A difference of <3% in DNA mass can be detected. This synthetic dye consists of two adjacent benzimidazole rings with N-methyl-piperazine and phenolic groups at the ends. The molecule permeates the cell membrane of living cells and binds selectively to A-T base pairs exposed in the minor-groove of double stranded DNA. Capability to distinguish and separate X- and Y-chromosome-bearing sperm has led to artificial insemination of somewhere around a million female mammals. Offspring with obvious abnormalities are no more frequent than after insemination of unsorted sperm into cows, horses, humans, pigs, sheep, rabbits, dolphins and other mammals. There is no apparent genotoxic effect from exposure of sperm to Hoechst 33342, although information on cellular toxicity or development of embryos resulting from Hoechst 33342-stained sperm is less reassuring. Little is known about the fate of sperm-delivered Hoechst dye in the female reproductive tract or on progeny of resultant offspring.


Sensitivity of fructose-1,6-biphosphatase from yeast, liver and skeletal muscle to fructose-2,6-biphosphate and 5'-adenosine monophosphate.
As a prerequisite for future studies on the possible effect of sulphite, an anti-microbial agent, on gluconeogenesis in yeast, a comparative study of fructose-1,6-bisphosphatase (FBPase), a key enzyme of gluconeogenesis, from yeast, liver and skeletal muscle is reported. In contrast to FBPase from yeast or liver, FBPase from skeletal muscle is approximately 1000-fold more sensitive to inhibition by 5' adenosine monophosphate and 30 to 250-fold less sensitive to inhibition by fructose-2,6-bisphosphate. The kinetic properties of the FBPases, determined by the ratios R(Mg2+/Mn2+) and R (pH 7/9) of the enzyme activities, measured at 10 mM Mg2+ and 2 mM Mn2+ and at pH 7.0 and 9.0, respectively, show a drastic difference between the skeletal muscle and the yeast or liver enzymes. The data support the idea that the enzymes from yeast and liver function in gluconeogenesis, whereas the enzyme from skeletal muscle is involved in other biological functions.


Climate and the distribution of intestinal Trichostrongylus spp. of sheep.
The relative prevalences of Trichostrongylus vitrinus, T. colubriformis and T. rugatus in sheep in south-west Western Australia were examined for evidence of associations with climatic conditions in different localities. The region has a mediterranean-type climate with hot, dry summers and cool, wet winters. The intestinal Trichostrongylus spp. populations in sheep sampled comprised 50% T. vitrinus, 38% T. colubriformis and 12% T. rugatus. The prevalence of T. vitrinus was negatively correlated with mean autumn, winter and spring temperatures of a locality. The prevalence of T. colubriformis was positively correlated with mean autumn, winter and spring temperatures. The prevalence of T. rugatus was not correlated with temperature of any season, but was negatively correlated with mean annual rainfall and length of growing season of a locality. There were suggestions of association of amount of rainfall of a locality and prevalence of T. rugatus was not correlated with temperature of any season, but was negatively correlated with mean annual rainfall and length of growing season of a locality. There were suggestions of association of amount of rainfall of a locality and prevalence of T. colubriformis and of differences in seasonal prevalence of T. vitrinus, but the significance of these was obscured by confounding of some climatic factors. The differences in prevalence of the three Trichostrongylus spp. at different locations was attributed to differences in preferred ambient conditions for development and survival of the free-living stages.


Studies of zinc transport into brush-border membrane vesicles isolated from pig small intestine.
Zinc transport into brush-border membrane vesicles was investigated by measuring uptake rates at a very short incubation time (2 seconds), during the initial linear uptake. A divalent cation chelator (EGTA) was added to the stop and washout solutions in order to remove the zinc bound to the external surface of the vesicles. Under these conditions, we showed that zinc enters the vesicles by (1) a saturable carrier-mediated process, and (2) an unsaturable pathway. The kinetic parameters we calculated were an affinity of 0.215 +/- 0.039 mM, a Jmax of 17.2 +/- 1.7 nmol.min-1.(mg protein)-1 and an unsaturable constant of 0.025 +/- 0.006 (n = 6). The imposition of an outwardly directed K+ gradient (negative inside) did not affect the Jmax value of the zinc uptake but increased the Km value significantly. This suggests that, at least a portion of zinc which crosses the membrane does not do so in a cationic form. Zinc uptake was decreased or increased according to the nature of accompanying anions (Cl-, SO4(2)-, SCN-) in the absence of any membrane potential. With highly permeant anions such as thiocyanates, zinc uptake was considerably augmented, suggesting a movement of zinc in a complexed form involving the presence of negative species. We also showed that cadmium competitively inhibited the zinc uptake; we measured a Ki value of 0.21 mM, indicating a similar affinity of cadmium for the carrier as zinc itself. By contrast, the presence of calcium had little effect on zinc entry into vesicles. The calcium ionophore A23187 had only a slight stimulating effect on zinc uptake. These results indicate that zinc and calcium transports are probably independent of each other.


Efficacy and safety of tangshen formula on patients with type 2 diabetic kidney disease: a multicenter double-blinded randomized placebo-controlled trial.
Persons with diabetes are at high risk of developing diabetic kidney disease (DKD), which is associated with high morbidity and mortality. Current drug therapies for DKD, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), are not entirely satisfactory. This study aimed to evaluate the additional benefit and safety of the Chinese herbal granule Tangshen Formula (TSF) in treating DKD. The study was designed as a six-center randomized, double-blind, placebo-controlled trial. From April 2007 through December 2009, 180 patients with DKD were enrolled. In addition to conventional treatment with ACEIs or ARBs, 122 participants were randomly assigned to receive TSF and 58 participants to receive placebo for 24 weeks. Primary outcome was urinary protein level, measured by urinary albumin excretion rate (UAER) for participants with microalbuminuria, 24-hour urinary protein (24h UP) for participants with macroalbuminuria. Secondary outcomes included renal function, serum lipids, quality of life, symptoms, and adverse events. After 24 weeks of treatment, no statistically significant difference in UAER (TSF -19.53 μg/min compared with placebo -7.01 μg/min, with a mean difference of -12.52 μg/min; 95%CI, -68.67 to 43.63, P = 0.696) was found between TSF and placebo groups. However, TSF displayed a statistically significant decrease in 24h UP (TSF-0.21 g compared with placebo 0.36 g, with a mean difference of -0.57g; 95%CI, -1.05 to -0.09, P = 0.024). Estimated glomerular filtration rate (eGFR) was improved in both patients with microalbuminuria and macroalbuminuria, with a mean difference of 15.51 ml/min/1.73 m2 (95%CI, 3.71 to 27.31), 9.01 ml/min/1.73 m2 (95%CI, -0.10 to 18.13), respectively. Other secondary outcomes showed no statistically significant difference between groups or in the incidence of adverse events. Based on conventional treatments, TSF appears to provide additional benefits compared with placebo in decreasing proteinuria and improving eGFR in DKD patients with macroalbuminuria. Nevertheless, further study is needed to evaluate TSF treating patients with microalbuminuria. Chinese Clinical Trial Registry ChiCTR-TRC-10000843.


An outbreak in three-yellow chickens with clinical tumors of high mortality caused by the coinfection of reticuloendotheliosis virus and Marek's disease virus: a speculated reticuloendotheliosis virus contamination plays an important role in the case.
Both reticuloendotheliosis and Marek's disease are neoplastic diseases of chickens caused by reticuloendotheliosis virus (REV) and Marek's disease virus (MDV), respectively. The infection of REV or MDV may lead to clinical tumors and also result in immunosuppression and easily allow secondary infection by other pathogens. Here, we investigated a breeder flock of three-yellow chickens in southern China that had been vaccinated with CVI988/Rispens at hatching and had experienced depression, weakness, reduction in weight gain, and an increased death rate after 120 d of age. The morbidity and mortality were 20% and 10%, respectively, at 140 d of age when this infection was diagnosed. The necropsy of the birds revealed significant tumor-like lesions in the heart, liver, spleen, and ceca. Peripheral blood lymphocytes and tumor-like tissues were sampled for PCR detection and for histopathological observation, for virus isolation and the subsequent immunofluorescent assay on the cell cultures and for gene sequencing of the isolated viruses. A REV isolate GX18NNR1 and a MDV isolate GX18NNM5 were both recovered from the sampled bird. Further phylogenetic analysis based on the env gene of REV and the meq gene of MDV demonstrated that GX18NNR1 was closely related to the reference REV strain MD-2, which was isolated from a contaminated commercial turkey herpesvirus vaccine. In addition, the GX18NNM5 was found to belong to the Chinese very virulent MDV strains' cluster. The coinfection of REV and MDV may contribute to tumor outbreaks with high morbidity and mortality in three-yellow chicken flocks.


Presence of pregnant females of the Gorgona guitarfish, Pseudobatos prahli, in the Mexican tropical Pacific.
Five specimens (four females and one male) of the Gorgona guitarfish, Pseudobatos prahli, were sighted during two dives carried out off the western Gulf of Tehuantepec. This document describes the reproductive condition of three adult females captured, two of which had uterine eggs, whereas one had embryos. The sighting and capture of specimens occurred during two Tehuano wind events; the authors, therefore, believe that variations in temperature and dissolved oxygen could have affected P. prahli, leading it to carry out temporal migrations towards coastal shallow waters.


ELA-DRA polymorphisms are not associated with Equine Arteritis Virus infection in horses from Argentina.
Polymorphisms at Major Histocompatibility Complex (MHC) genes have been associated with resistance/susceptibility to infectious diseases in domestic animals. The aim of this investigation was to evaluate whether polymorphisms of the DRA gene the Equine Lymphocyte Antigen is associated with susceptibility to Equine Arteritis Virus (EAV) infection in horses in Argentina. The equine DRA gene was screened for polymorphisms using Pyrosequencing® Technology which allowed the detection of three ELA-DRA exon 2 alleles. Neither allele frequencies nor genotypic differentiation exhibited any statistically significant (P-values=0.788 and 0.745) differences between the EAV-infected and no-infected horses. Fisher's exact test and OR calculations did not show any significant association. As a consequence, no association could be established between the serological condition and ELA-DRA.


[Use of ultrasonography for measurement of femur anteversion and tibial torsion in children].
Sonography has been used to measure femoral and tibial torsion. Their normal values have been established in a series of 97 healthy children 6 and 15 years old. Tibial torsion has been found to be 18 degrees, femoral neck anteversion decreases 12 degrees between sixth and fifteenth year of age. Sonography proved to be a reproducible and precise method for torsional measurements of the tibia and femur.


Positive allosteric modulators to peptide GPCRs: a promising class of drugs.
The task of finding selective and stable peptide receptor agonists with low molecular weight, desirable pharmacokinetic properties and penetrable to the blood-brain barrier has proven too difficult for many highly coveted drug targets, including receptors for endothelin, vasoactive intestinal peptide and galanin. These receptors and ligand-gated ion channels activated by structurally simple agonists such as glutamate, glycine and GABA present such a narrow chemical space that the design of subtype-selective molecules capable of distinguishing a dozen of glutamate and GABA receptor subtypes and possessing desirable pharmacokinetic properties has also been problematic. In contrast, the pharmaceutical industry demonstrates a remarkable success in developing 1,4-benzodiazepines, positive allosteric modulators (PMAs) of the GABAA receptor. They were synthesized over 50 years ago and discovered to have anxiolytic potential through an in vivo assay. As exemplified by Librium, Valium and Dormicum, these allosteric ligands of the receptor became the world's first blockbuster drugs. Through molecular manipulation over the past 2 decades, including mutations and knockouts of the endogenous ligands or their receptors, and by in-depth physiological and pharmacological studies, more peptide and glutamate receptors have become well-validated drug targets for which an agonist is sought. In such cases, the pursuit for PAMs has also intensified, and a working paradigm to identify drug candidates that are designed as PAMs has emerged. This review, which focuses on the general principles of finding PAMs of peptide receptors in the 21st century, describes the workflow and some of its resulting compounds such as PAMs of galanin receptor 2 that act as potent anticonvulsant agents.


Reproducibility of classification in non-squamous cell carcinomas of the uterine cervix.
Reproducibility of histopathologic classification systems is of major importance for their utility in daily practice and in research. The reproducibility of histologic classification of non-squamous carcinomas (non-SCC) of the uterine cervix was evaluated, using population-based material from two 5-year periods in Norway. Histologic slides from 388 tumors were reviewed by three experienced pathologists and analyzed for inter- and intraobserver agreement on histological subtypes and grade. Kappa values of inter- and intraobserver agreement were moderate to substantial for all major adenocarcinoma subgroups (endocervical, endometrioid, clear cell, or serous carcinoma), and fair to poor for mixed carcinomas and adenocarcinomas not otherwise specified (NOS). Interobserver agreement on villoglandular and adenosquamous carcinomas was poor, and the distinction of adenocarcinoma in situ from well-differentiated carcinoma proved difficult. Reproducibility of the high-risk subgroups of small cell and undifferentiated carcinomas was acceptable from a statistical point of view (kappa values >0.50). However, the authors agreed upon the diagnosis of small cell carcinomas and undifferentiated carcinomas only in 2/3 of these high-risk diagnoses. Patients with high-risk diagnoses showed significantly lower overall survival than patients with non-high-risk diagnoses (P < 0.001). This inferior survival was independent of whether the reviewers had agreed on the high-risk diagnosis or not. Clinicians should be aware of the potential inconsistencies of histopathologic diagnoses. No histopathological classification system will ever be perfectly reproducible. Future histopathologic classification of the uterine cervix should emphasize the distinction between groups of particularly low or high prognostic risks.


Welcoming, supportive care in US birthing facilities and realization of breastfeeding goals.
Emotional and physical support for birthing parents is positively associated with realization of their breastfeeding goals. However, few studies have investigated maternal descriptions of their postnatal unit experience of these domains. The objective was to investigate maternal report of their birthing facility experiences and quantify the extent to which accounts of postpartum support were associated with meeting their breastfeeding goals. After IRB review, data were obtained through an online survey distributed from November 2016-May 2017. This analysis utilizes data from 2,771 birthing parents who were at least 18 years of age, experienced maternity care in the United States within five years, and reported that they had intended to breastfeed. Bivariate analysis was followed by logistic regression controlling for significant covariates. In this sample of primarily non-Hispanic white birthing parents with intent to exclusively breastfeed, the following postnatal unit variables were associated with higher odds of meeting their breastfeeding goals, birthing parents feeling: welcomed (adjusted OR=1.36), that health care promoted their physical health (adjusted OR=1.41), that care promoted their emotional health (adjusted OR=1.38), that they were supported (adjusted OR=1.56), and that they were recognized by their health care team (adjusted OR=1.30). All the measured postnatal unit support variables were significantly correlated with each other, with correlation coefficients ranging from 0.15 to 0.81. Before the COVID-19 pandemic, birthing parents' experiences on the postnatal unit were interrelated and associated with meeting their breastfeeding goals. As health care services are reviewed and prioritized during the COVID-19 pandemic and as part of ongoing strengthening of systems, qualitative and observational research can address the mechanisms underlying breastfeeding outcomes to inform the provision of more holistic and effective support.


Performance of an Automated Detection Algorithm to Assess Objective Pulsatile Tinnitus.
In this paper we describe an automated detection algorithm that objectively detects pulsatile tinnitus (PT) and investigate its performance. Sound measurements were made with a sensitive microphone placed in the outer ear canal in 36 PT-patients referred to our tertiary clinic, along with a registration of the heart rate. A novel algorithm expressed the coherence between the recorded sound and heart rate as a pulsatility index. This index was determined for 6 octave bands of the recorded sound. We assessed the performance of the detection algorithm by comparing it with the judgement of 3 blinded observers. The algorithm showed good agreement compared with the majority judgement of the blinded observers (ROC AUC 0.83). Interobserver reliability for detecting PT in sound recordings by the three blinded observers was substantial (Fleiss's κ=0.64). The algorithm may be a reliable alternative to subjective assessments of in-canal sound measurements in PT-patients, thus providing clinicians with an objective measure to differentiate between subjective and objective pulsatile tinnitus.


Targeting Immune Cell Wiring in Ulcerative Colitis.
The cytokine TNF is thought to play a major role in the immunopathogenesis of ulcerative colitis, and anti-TNF antibodies are considered as cornerstones of clinical therapy. Two clinical trials published in The New England Journal of Medicine now challenge this paradigm and suggest new avenues for research.


Fathers attending the birth of their baby: Views, intentions and needs.
There is limited information about fathers' views, intentions and needs leading up to childbirth. This study explores the factors influencing fathers' intention to attend the birth, and the needs and supports required leading up to childbirth. Cross-sectional survey of 203 prospective fathers attending antenatal appointments at an outer metropolitan public teaching hospital in Brisbane, Australia. A total of 201/203 (99.0%) participants intended to attend the birth. The reported reasons included: responsibility (99.5%), protectiveness (99.0%), love for their partner (99.0%), the right thing to do (98.0%), desire to see the birth (98.0%), the perception that partners should attend (97.4%), duty (96.4%) and partner preference (91.4%). Some felt pressured by their partner (12.8%), society (10.8%), cultural expectations (9.6%) and family (9.1%), and 10.6% perceived adverse consequences for not attending. Most participants (94.6%) felt well supported, experienced good communication (72.4%), had the opportunity to ask questions (69.8%) and received an explanation of events (66.3%). They were less often supported by antenatal visits (46.7%) and by a plan for future visits (32.2%). Ten per cent of all fathers and 13.8% of experienced fathers requested better mental health support, and 9.0% prefer better clinician communication. Most fathers intend to attend childbirth for personal and moral reasons; however, a small proportion feel pressured. Most fathers feel well supported, although potential improvements include planning for future visits, provision of information, mental health support, clinician communication, increased involvement in their partner's care, the opportunity to ask questions and more frequent clinic visits.


[Biomechanics of injury of the cervical spine].
Whiplash injuries of the cervical spine are of special medical and socio-economic importance. Biomechanical studies of the injury have proven, that a hypertranslation of the capito-cervical region takes place first, leading to ligamentous hyperdistension and ruptures, when exceeding elastic deformation, thus possibly resulting in mechanical disturbance and rotatory malpositioning. Diagnosis of so called "functional disorders" bears difficulties concerning objective tests for structural lesions. This demands the definition of diagnostic parameters and clinical signs, which also consider vegetative phenomena. This paper aims at a systematic clinical and radiological check. Adequate therapeutic means have to be concordant to prognosis. Therefore functional parameters should already determine differential diagnosis. This is based on technical feasibilities and needs future scientific efforts.


Rapid separation and sensitive detection method for beta-blockers by pressure-assisted capillary electrochromatography-electrospray ionization mass spectrometry.
A new method for rapid separation and sensitive detection of beta-blockers by pressure-assisted capillary electrochromatography (pCEC) with electrospray ionization mass spectrometry (ESI-MS) using silica-based monolithic column was studied in this paper. The proposed method has been confirmed to be very powerful since the fast mass transfer property and good permeability of silica monolithic column was used in this pCEC-ESI-MS system. In this work, a silica monolithic column was prepared with sol-gel method for simultaneous fast separation of beta-blockers. Furthermore, in order to obtain the highly selective and sensitive result of pCEC-ESI-MS, both the CEC separation and MS detection parameters were optimized in detail. Under the optimized conditions, namely 80% acetonitrile and 20% 20 mmol/L ammonium acetate (pH 6.0) as the mobile phase, 20 kV and 8 bar as the separation voltage and the assisted pressure, isopropanol/water (1:1, v/v) containing 7.5 mmol/L acetic acid as the sheath liquid, and 3 microL/min as the flow rate of sheath liquid, seven beta-blockers were well separated within 11 min with detection limits in the range of 0.15-0.80 ng/mL (defined as S/N=3). The recoveries of spiked urine samples of these beta-blockers were between 86.3 and 103% with the RSDs lower than 8.0%. The real samples from some male volunteers were successfully analyzed and confirmed with the proposed method. Comparing with GC-MS or LC-MS, the new method has some superiority (such as fast analysis capacity and simple pretreatment) in clinical practice and doping control.


ProfileChaser: searching microarray repositories based on genome-wide patterns of differential expression.
We introduce ProfileChaser, a web server that allows for querying the Gene Expression Omnibus based on genome-wide patterns of differential expression. Using a novel, content-based approach, ProfileChaser retrieves expression profiles that match the differentially regulated transcriptional programs in a user-supplied experiment. This analysis identifies statistical links to similar expression experiments from the vast array of publicly available data on diseases, drugs, phenotypes and other experimental conditions. http://profilechaser.stanford.edu firstname.lastname@example.com Supplementary data are available at Bioinformatics online.


Acute Rhinosinusitis: Prescription Patterns in a Real-World Setting.
Understand real-world prescription patterns for patients presenting with a first diagnosis of ARS and evaluate adherence to published medical guidelines. Retrospective administrative database analysis. US-based outpatient settings. From a US claims database (MarketScan), 99,033 patients were identified with acute rhinosinusitis (ARS) in 2012 ("index"), with a complete medical and prescription history for 12 months preindex and 18 months postindex and no diagnoses of asthma or chronic rhinosinusitis. Of these, a random 10,000-patient sample was generated matched for age and sex to the initial cohort. Prescriptions and procedures at index, as well as complications up to 12 months postindex, were analyzed. Nearly 90% of all patients received a prescription at index. Antibiotics were prescribed for 84.8% patients, followed by antitussives (16.2% for adults, 6.2% for pediatrics), nasal corticosteroids (15.5% adults, 7.5% for pediatrics), and systemic corticosteroids (10.3% for adults, 5.5% for pediatrics), with 49% adults and 29% children receiving >1 medication at first visit. Macrolides were the most frequently prescribed antibiotics (35.6% adults, 28.6% pediatrics), followed by amoxicillin/clavulanate and amoxicillin. Within 12 months of index, 3 patients presented with meningitis and 3 with orbital cellulitis. Significant variability in ARS treatment was observed, highlighting the need for heightened awareness of existing guidelines.


Tethered virions are intermediates in the assembly and release of HIV-1 particles.
Vpu enhances HIV-1 release by suppressing CD317-mediated tethering of virions to the cell surface. In HeLa H1 cells, Vpu(+) infection produces significant amounts of tethered virions, although efficient virus release requires Vpu. We have analyzed membrane targeting and assembly of newly synthesized Gag in infected HeLa H1 cells by quantitative pulse-chase assays in both Vpu(+) and ΔVpu virus backgrounds and in the presence and absence of CD317. Our results show that formation of tethered virions precedes release of viruses to the culture medium in the Vpu(+) infection, and CD317 knockdown reduces tethering in both Vpu(+) and ΔVpu virus backgrounds. Significantly, our results indicate that tethered Vpu(+) viruses represent precursors for extracellular viruses, and Vpu thus appears to reverse tethering in HeLa H1 cells after budding.


Safety of classical swine fever virus vaccine strain LOM in pregnant sows and their offspring.
The present study aimed to evaluate the safety of the classical swine fever virus (CSFV) vaccine strain LOM in pregnant sows. Pregnant sows with free CSFV antibody were inoculated with a commercial LOM vaccine during early pregnancy (day 38; n=3) or mid-pregnancy (days 49-59; n=11). In pregnant sows vaccinated during the early stages of gestation, abortion (day 109) was observed in one case, with two stillbirths and seven mummified fetuses. The viability of live-born piglets was 34.9% in sows vaccinated during mid-pregnancy compared with 81.8% in the control group. Post-mortem examination of the organs of the sows and piglets did not reveal any pathological lesions caused by CSFV; however, CSFV RNA was detected in the organs of several vaccinated sows and their litters. The LOM strain was transmitted from sows with free CSFV antibody to their fetus, but did not appear to induce immune tolerance in the offspring from vaccinated pregnant sows. Side effects were not observed in pregnant sows with antibody to the LOM strain: transmission from sow to their litters and stillbirth or mummified fetuses. The LOM strain may induce sterile immunity and provide rapid, long-lasting, and complete protection against CSFV; however, it should be contraindicated in pregnant sows due to potential adverse effects in pregnant sows with free CSFV antibody.


The concept of specificity in the procercoid-copepod system: Bothriocephalus claviceps (Cestoda) a parasite of the eel (Anguilla anguilla).
This paper describes experimental work on parasite specificity in the copepod-procercoid system of Bothriocephalus claviceps. Two criteria were used to characterize five potential host species Macrocyclops albidus, Macrocyclops fuscus, Eucyclops serrulatus, Acanthocyclops robustus and Macrocyclops viridis viridis. The first criterion involves susceptibility of the copepods to infection. The results show random or aggregative distributions and variable susceptibilities according to the species. We observed an ethological barrier to infection in M. viridis viridis and M. fuscus. The second criterion involves the growth and development of the procercoid. Three factors modify the profiles of the growth curves: host species, sex and intensity of infection. The growth of the procercoids is density-dependent, whereas their development is independent of density. This last characteristic is interpreted as a factor favouring the aggregation of procercoid populations. The two most susceptible hosts are M. albidus and A. robustus.


Comparison of the diagnostic performance of digital breast tomosynthesis and magnetic resonance imaging added to digital mammography in women with known breast cancers.
To compare the diagnostic performance of digital breast tomosynthesis (DBT) and magnetic resonance imaging (MRI) added to mammography in women with known breast cancers. Three radiologists independently reviewed image sets of 172 patients with 184 cancers; mammography alone, DBT plus mammography and MRI plus mammography, and scored for cancer probability using the Breast Imaging Reporting and Data System (BI-RADS). Jack-knife alternative free-response receiver-operating characteristic (JAFROC), which allows diagnostic performance estimation using single lesion as a statistical unit in a cancer-only population, was used. Sensitivity and positive predictive value (PPV) were compared using the McNemar and Fisher-exact tests. The JAFROC figures of merit (FOMs) was lower in DBT plus mammography (0.937) than MRI plus mammography (0.978, P = 0.0006) but higher than mammography alone (0.900, P = 0 .0013). The sensitivity was lower in DBT plus mammography (88.2 %) than MRI plus mammography (97.8 %) but higher than mammography alone (78.3 %, both P < 0 .0001). The PPV was significantly higher in DBT plus mammography (93.3 %) than MRI plus mammography (89.6 %, P = 0 .0282). DBT provided lower diagnostic performance than MRI as an adjunctive imaging to mammography. However, DBT had higher diagnostic performance than mammography and higher PPV than MRI. • Digital breast tomosynthesis (DBT) plus mammography was compared with MRI plus mammography. • DBT had lower sensitivity and higher PPV than MRI. • DBT had higher diagnostic performance than mammography.


Cervical esophagostomy using indwelling catheter for analysis of gastric physiology in dogs.
To describe the technique of cervical esophagostomy with indwelling catheter for the collection of secretions and study of gastric emptying. Esophagostomy was performed in 14 dogs, and a tube was introduced into the animals' stomachs and maintained previous for eight weeks. The technique consisted of opening the left lateral surface of the neck for insertion of the tube, with the aid of a Mixter forceps, and the subsequent subcutaneous tunneling and exteriorization of the catheter on the dorsum of the animals. Successful use of the tube and its total permeability were observed in 13 animals (92.8%). In one animal, the tube was obstructed by hair, and it was replaced. Formation of a small abscess occurred in 3 animals (21.4%), followed by spontaneous drainage. No accidents occurred, and the bleeding was minimal. No deaths were registered. The described technique can be used in similar researches, as well as for animal feeding in investigations of the upper digestive tract, after esophageal resection and in major neck surgeries.


The Impact of Type II Diabetes on Tongue Dysplasia and p16-Related Aging Process: An Experimental Study.
To evaluate the effect of streptozotocin-induced experimental diabetes mellitus on p16, p53, Ki67, and Bcl2 expressions and histopathological changes in the tongue of the rats. Twenty-two adult female Sprague-Dawley rats were used. The rats were randomly divided into 2 groups (n = 14) as control (C) (n = 8) and diabetic (DM) (n = 6). The rats in the DM group were given streptozotocin as a single intraperitoneal dose for induction of diabetes. Histopathological and immunohistochemical evaluations of formalin-fixed and paraffin-embedded tissue sections of the tongue were used. Significant differences were observed between the DM group and the control group in terms of epithelial thickness, length of filiform papillae, and width of filiform papillae (p = 0.005, p = 0.001, and p = 0.006, respectively). There was no significant difference between the groups in terms of mononuclear inflammatory cell infiltration, capillary proliferation, and dysplasia (p = 0.204, p = 0.244, and p = 0.204, respectively). As a result of immunohistochemical studies, no significant difference was found between the groups in terms of p53, Ki67, and Bcl-2 expressions (p = 0.588, p = 0.662, and p = 0.686, respectively). A significant difference was found between the groups when p16 expression was evaluated (p = 0.006). In our study, streptozotocin-induced experimental diabetes mellitus induced p16 expression but did not show any difference in p53, Bcl-2, and Ki67 levels. It should be considered in the studies that the pathological changes at the early stages of the relationship between DM and oral cancer may be related to p16 expression; however, it may also be linked with p16-related aging process.


Mixed-linkage cellooligosaccharides: a new class of glycoside hydrolase inhibitors.
A new class of inhibitors for beta-D-glycoside hydrolases, in which a single alpha-(1-->4)-glycosidic bond is incorporated into an otherwise all-beta-(1-->4)-linked oligosaccharide, is described. Such mixed beta/alpha-linkage cellooligosaccharides are not transition-state mimics, but instead are capable of utilising binding energy from numerous subsites, spanning either side of the catalytic centre, without the need for substrate distortion. This binding is significant; a mixed alpha/beta-D-tetrasaccharide acts competitively on a number of cellulases, displaying inhibition constants in the range of 40-300 microM. Using the Bacillus agaradhaerens enzyme Cel5A as a model system, one such mixed beta/alpha-cellooligosaccharide, methyl 4(II),4(III)-dithio-alpha-cellobiosyl-(1-->4)-beta-cellobioside, displays a K(i) value of 100 microM, an inhibition at least 150 times better than is observed with an equivalent all-beta-linked compound. The three-dimensional structure of B. agaradhaerens Cel5A in complex with methyl 4(II),4(III)-dithio-alpha-cellobiosyl-(1-->4)-beta-cellobioside has been determined at 1.8 A resolution. This confirms the expected mode of binding in which the ligand, with all four pyranosides in the (4)C(1) chair conformation, occupies the -3, -2 and +1 subsites whilst evading the catalytic (-1) subsite. Such "by-pass" compounds offer great scope for the development of a new class of beta-D-glycoside hydrolase inhibitors.


Acute myocardial ischaemia in anaesthetized cats: effects of papaverine.
1 The effects of papaverine on coronary blood flow, myocardial oxygen consumption, myocardial oxygen tension and the ischaemic ECG pattern were studied in anaesthetized open-chest cats representing three models of acute coronary insufficiency: ligation, spasm, and perfusion of the coronary artery at a stabilized insufficient level. 2 Despite the increase in myocardial oxygen consumption reflecting elevation of oxygen demand, papaverine improved the signs of myocardial ischaemia (the myocardial oxygen tension and ECG pattern), as long as there was a possibility of an increase in blood supply to the affected zone. Where this was exluded, the symptoms were actually aggravated. 3 The results suggest that there is no basis for dividing coronary dilators into 'benign' and 'malignant' according to their ability to increase myocardial oxygen requirements. A coronary dilator enhancing oxygen demand may prove beneficial even following complete coronary artery occlusion.


Clinical outcomes in transplant-eligible patients with relapsed or refractory diffuse large B-cell lymphoma after second-line salvage chemotherapy: A retrospective study.
The prognosis of patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) is poor. Although patients who fail first-line salvage chemotherapy are candidates for second-line salvage chemotherapy, the optimal treatment strategy for these patients has not yet been established. The present, single-center, retrospective study included transplant-eligible patients with R/R DLBCL who received second-line salvage chemotherapy with curative intent. Seventy-six patients with R/R DLBCL received second-line salvage chemotherapy. Eighteen (23.7%) patients were responders to the first-line salvage chemotherapy. The overall response rate was 39.5%, and overall survival (OS) was significantly longer in patients who responded to second-line salvage chemotherapy than those who did not. Forty-one patients who proceeded to potentially curative treatment (autologous hematopoietic stem cell transplantation [ASCT], chimeric antigen receptor [CAR] T-cell therapy, or allogeneic hematopoietic stem cell transplantation) had a better prognosis than those who did not. Among the 46 patients who failed to respond to the second-line salvage regimen, only 18 (39.1%) could proceed to the curative treatments. However, among the 30 patients who responded to the second-line salvage regimen, 23 (76.7%) received one of the potentially curative treatments. Among 34 patients who received CAR T-cell therapy, OS was significantly longer in those who responded to salvage chemotherapy immediately prior to CAR T-cell therapy than in those who did not respond. In contrast, the number of prior lines of chemotherapy was not identified as a statistically significant prognostic factor of survival. No significant difference was detected in OS between patients receiving ASCT and those receiving CAR T-cell therapy after the response to second-line salvage chemotherapy. In this study, we demonstrated that chemosensitivity remained a crucial factor in predicting survival outcomes following CAR T-cell therapy irrespective of the administration timing, and that both ASCT and CAR T-cell therapy were acceptable after the response to second-line salvage chemotherapy.


Impact of H-aggregation on activatable MMP-2-specific probes for optical imaging.
In order to target and image MMP-2 activity using optical imaging, we developed a panel of new MMP-2 probes based on Cy5 and QSY21 as fluorophore/quencher FRET partners, separated by various MMP-2 specific peptide substrates. We compared these probes for their specificity against other MMPs, their rate of activation by MMP-2 and their initial quenching.


Enantioselective epoxidation of linolenic acid catalysed by cytochrome P450(BM3) from Bacillus megaterium.
Cytochrome P450(BM3), from Bacillus megaterium, catalyses the epoxidation of linolenic acid yielding 15,16-epoxyoctadeca-9,12-dienoic acid with complete regio- and moderate enantio-selectivity (60% ee). The absolute configuration of the product is tentatively assigned as 15(R),16(S)-. The Michaelis-Menten parameters kcat and Km for the reaction were determined to be 3126 +/- 226 min(-1) and 24 +/- 6 microM respectively.


Hypoxia promotes Mycobacterium tuberculosis-specific up-regulation of granulysin in human T cells.
Oxygen tension affects local immune responses in inflammation and infection. In tuberculosis mycobacteria avoid hypoxic areas and preferentially persist and reactivate in the oxygen-rich apex of the lung. Oxygen restriction activates antimicrobial effector mechanisms in macrophages and restricts growth of intracellular Mycobacterium tuberculosis (M.Tb). The effect of oxygen restriction on T cell-mediated antimicrobial effector mechanisms is unknown. Therefore we determined the influence of hypoxia on the expression of granulysin, an antimicrobial peptide of lymphocytes. Hypoxia increased the antigen-specific up-regulation of granulysin mRNA and protein in human CD4(+) and CD8(+) T lymphocytes. This observation was functionally relevant, because oxygen restriction supported the growth-limiting effect of antigen-specific T cells against virulent M.Tb residing in primary human macrophages. Our results provide evidence that oxygen restriction promotes the expression of granulysin and suggest that this effect-in conjunction with additional T cell-mediated immune responses-supports protection against mycobacteria. The therapeutic modulation of oxygen availability may offer a new strategy for the host-directed therapy of infectious diseases with intracellular pathogens.


Structure-based design of novel dihydroisoquinoline BACE-1 inhibitors that do not engage the catalytic aspartates.
The structure-activity relationship of a series of dihydroisoquinoline BACE-1 inhibitors is described. Application of structure-based design to screening hit 1 yielded sub-micromolar inhibitors. Replacement of the carboxylic acid of 1 was guided by X-ray crystallography, which allowed the replacement of a key water-mediated hydrogen bond. This work culminated in compounds such as 31, which possess good BACE-1 potency, excellent permeability and a low P-gp efflux ratio.


Down-regulation of tryptamine receptors following chronic administration of clorgyline.
Chronic treatment with clorgyline, a type A monoamine oxidase (MAO) inhibitor (1 mg/kg/day for 11 days), reduced the number (Bmax) but not the affinity (Kd) of [3H]tryptamine binding sites in rat frontal/parietal cortical membranes. Binding was reduced for at least 36 days following the last injection. The reduction in [3H]tryptamine binding was dose-related and appeared to be maximal following a daily dose of 3 mg/kg. Chronic treatment with deprenyl, a type B MAO inhibitor (1 mg/kg/day for 11 days), did not affect [3H]tryptamine binding. Acute clorgyline administration (11 mg/kg) also had no effect. These data suggest that [3H]tryptamine binds to neurotransmitter receptors for tryptamine since mere chemical recognition sites would not be expected to be modulated by chronic drug treatment. Also, since [3H]tryptamine binding was down-regulated by a type A, but not a type B, MAO inhibitor, tryptamine may be selectively metabolized by type A MAO in vivo.


Defining what a 'carer' is and the role they play in in-patient mental healthcare: A focus group study with patients, carers and clinicians.
The value of carer involvement has been extensively researched and promoted. However, the field lacks exploration of conceptual issues, which might help to explain why there are widespread difficulties in putting policy into practice in this area, as implementation rates remain low internationally. This qualitative study explored patients', carers' and clinicians' perspectives on the role of carers in mental healthcare, particularly with regards to in-patient settings. Sixteen focus groups were conducted with patients, carers and clinicians who have current or previous experience of in-patient settings. A thematic analysis was conducted on the transcripts, exploring two key domains: (a) what a 'carer' is, and (b) how the 'carer' role is described within the context of the hospital environment. Participants diverged in their opinions of what the 'carer' role entails, and the perceived helpfulness of it. Issues unique to the in-patient setting were identified, such as the role of the hospital environment in enabling or being a barrier to carer involvement. These differing perspectives and contextual factors had an impact on the position of carers in the hospital setting, as they could be viewed as helpful, a hindrance or as passive visitors, depending on the perspectives of clinicians. More clarity and agreement is needed between patients, carers and clinicians in terms of how the 'carer' role is defined. This has the potential to improve carers' experience of involvement in hospital settings.


HIV prescriptions on the frontlines: Primary care providers' use of antiretrovirals for prevention in the Southeast United States, 2017.
HIV disproportionately affects persons in Southeast United States. Primary care providers (PCPs) are vital for HIV prevention. Data are limited about their prescribing of antiretrovirals (ARVs) for prevention, including non-occupational post-exposure prophylaxis (nPEP), pre-exposure prophylaxis (PrEP), and antiretroviral therapy (ART). We examined these practices to assess gaps. During April-August 2017, we conducted an online survey of PCPs in Atlanta, Baltimore, Baton Rouge, Miami, New Orleans, and Washington, DC to assess HIV-related knowledge, attitudes and practices. Adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) were used to estimate correlates of nPEP, PrEP and ART prescribing practices. Adjusting for MSA and specialty, the weighted sample (n = 820, 29.6% adjusted response rate) comprised 60.2% white and 59.4% females. PCPs reported ever prescribing nPEP (31.0%), PrEP (18.1%), and ART (27.2%). Prescribing nPEP was associated with nPEP familiarity (aPR = 2.63, 95% CI 1.59, 4.35) and prescribing PrEP (aPR = 3.57, 95% CI 2.78, 4.55). Prescribing PrEP was associated with PrEP familiarity (aPR = 4.35, 95% CI 2.63, 7.14), prescribing nPEP (aPR = 5.00, 95% CI 2.00, 12.50), and providing care for persons with HIV (aPR = 1.56, 95% CI 1.06, 2.27). Prescribing ART was associated with nPEP familiarity (aPR = 1.89, 95% CI 1.27, 2.78) and practicing in outpatient public practice versus hospital-based facilities (aPR = 2.14 95% CI 1.51, 3.04), and inversely associated with collaborations involving specialists (aPR = 0.60, 95% CI 0.42, 0.86). A minority of PCPs surveyed from the Southeast report ever prescribing ARVs for prevention. Future efforts should include enhancing HIV care coordination and developing strategies to increase use of biomedical tools.


Studies on the mechanism of estradiol uptake by rat uterine cells and on estradiol binding to uterine plasma membranes.
A method for the preparation of viable uterine cell suspensions is described. Using this system the kinetics of estradiol uptake were studied in order to asses whether the steroid enters uterine cells by passive diffusion (1) or protein mediated diffusion (2). The data presented show that a) the rates of estradiol entry are nonsaturable; b) temperature dependence of uptake kinetics gives a linear Arrhenius plot; c) E2-6-CMO-BSA does not inhibit 3H-E2 uptake; d) uterine plasma membranes do not contain specific estrogen binding sites. Thus, estrogen uptake occures by passive diffusion.


Culture serum-induced conversion from agonist to antagonist of a Vitamin D analog, TEI-9647.
The nuclear receptor for Vitamin D (VDR) mediates many of the effects of Vitamin D in target tissues by regulating gene expression. The transactivation function of ligand-bound VDR in target tissues is thought to depend on the tissue-type and the cellular-environment, but the molecular basis for these differences has not been fully understood. In this study, during characterization of TEI-9647 as a synthetic ligand for the VDR, we found that depletion of serum from the culture medium converted TEI-9647 from an antagonist to an agonist of VDR-mediated transactivation, whereas it retained antagonistic activity in the presence of serum. Consistent with these results, using a mammalian two-hybrid system, we found that TEI-9647 recruited different coactivators to the VDR in the presence and absence of serum. These findings suggest that an unknown serum factor modulates the transactivation function of the VDR.


Knee dislocations-a retrospective study comparing operative versus closed immobilization treatment outcomes.
Controversies over operative versus closed immobilization of traumatic complex multiple ligamentous knee injury are still debated. The aim of our study is to evaluate the outcome of reconstructive vs non-reconstructive (closed immobilization) treatment outcomes. This is a retrospective review of cases seen at our institution. All cases admitted with a diagnosis of knee dislocation, defined as patients with multidirectional knee instability in the setting of trauma, were reviewed. Twenty-nine consecutive patients from January of 1996 to June of 2002 were reviewed. Twenty-six patients (89.7%) were successfully recalled and their functional outcome analyzed. Comparing the operated group (n=15, 57.7%) with closed immobilized patients (n=11, 42.3%), there was no statistical difference in the range of motion (mean difference 8.55 degrees , p=0.202). While the operated group had more flexion contracture (mean difference 3.9 degrees , p=0.002), they had better stability and better overall knee function as measured by the International Knee Documentation Committee (IKDC) score (the mean difference of IKDC score was 12.13, p=0.005). In the operated group of 15 patients, we compared partial repair (n=7) with complete repair of all torn ligaments (n=8). Superior results were noted in the group with complete repair of all structures, with comparable range of motion (mean difference 0.6 degrees , p=0.861) and flexion contractures (mean difference 1.0 degrees , p=0.795) but better stability and IKDC score (mean difference of IKDC score 13.6, p=0.003). Our conclusion is that operative treatment with complete repair of all torn structures produces the best overall knee function with better knee stability and patient satisfaction.


Screening, endpoint classification, and safety monitoring in the Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF).
The MERIT-HF study was designed to investigate the effect of once-daily dosing of metoprolol succinate CR/XL added to standard therapy in patients with chronic heart failure. A screening programme, aiming at identifying eligible patients for the study was used by 231 out of 313 sites, resulting in 8912 screened patients. These patients were older, more often women, had marginally higher ejection fraction and were more often in NYHA class IV compared to the finally randomised patients. There was a positive correlation between the number of screened and randomised patients and due to the high inclusion rate the number of randomised patients was increased from 3200 to 3991 patients. The clinical events were defined by a manual and were based on identical classifications made independently by two members of an Independent Endpoint Committee. Data from the case report form and the classifications made by the Endpoint Committee were in accordance for hospitalisation due to worsening heart failure on 722 occasions. On 207 occasions the data from the case report forms and the classification made by the committee differed regarding this clinical event. The Independent Safety Committee monitored safety aspects of the study by using asymmetric group sequential procedures. The study was stopped early on recommendation from the Independent Safety Committee, when the second pre-specified interim analysis (50% of total number of expected deaths) showed that the criterion for stopping due to benefit had been met and exceeded. In conclusion, a screening programme facilitated patient recruitment and showed the characteristics of the background population, the event classification was improved by using an independent endpoint committee, and the safety monitoring allowed an early closure of the study due to mortality benefit, without jeopardising the final analyses of the results.


Effect of arm orientation on bone mineral mass and bone width measured using the Cameron-Sorenson technique.
Bone mineral content and bone width were measured as the distal and midshaft locations in the right radius and ulna with the arm in different orientations. The values of mineral content, width, and the ratio of bone mineral content divided by width, determined at each bone site were compared to establish the effect of orientation. Seven orientations were studied, two of which involved rotations of the forearm and five of which involved rotations of the upper arm about the axis of the forearm. Rotation of the forearm was found to affect the values of one or more of the measured quantities at all of the sites. Orientation of the upper arm was found to affect the values of all quantities at the midshaft radius, but not to affect the values of any of the quantities at the other sites.


A comprehensive review of intake estimates of di-isononyl phthalate (DINP) based on indirect exposure models and urinary biomonitoring data.
Di-isononyl phthalate (DINP) is a high molecular weight general purpose plasticizer used principally in the manufacture of flexible polyvinyl chloride (PVC) articles. DINP metabolites can be measured in biological media such as blood and urine. However, measurement of a substance in the blood or urine does not by itself mean that the chemical causes or is associated with adverse health outcomes. This is particularly pertinent given the advances in modern analytical techniques whereby ever diminishing trace amounts of substances can be detected. Therefore, it is a scientific necessity that risk assessors understand the relationship of biomonitoring data to estimation of exposure so that appropriate comparisons can be made to the no observed adverse effects levels (NOAELs) or other points of departure from toxicological studies in animals. In this paper, estimates of daily DINP intake are calculated for various population segments based on urinary biomonitoring data and are compared to estimates of exposure based on indirect methods and to health-based exposure guidance values. In general, intake estimates converge on a mean of 1-2μg/kg/day regardless of source of exposure or population cluster; a value 2-orders of magnitude lower than health-based exposure guidance values, ranging from 120 to 290μg/kg/day, which have been established by regulatory authorities and other authoritative bodies as representing acceptable levels.


Reproducibility of pediatric whole body bone and body composition measures by dual-energy X-ray absorptiometry using the GE Lunar Prodigy.
The use of dual-energy X-ray absorptiometry (DXA) in pediatrics is increasing. It is safe, readily available, and easily performed, but there is little information on reproducibility. The aim of this study is to evaluate the reproducibility of whole body DXA scans in children. Total and regional bone mineral density, bone mineral content, nonbone, lean fat mass, and percent fat were measured twice by whole body DXA (GE Lunar Prodigy) in 49 subjects (5 to 17 yr). Within each subject, between subjects, and reading standard deviations for each body component were evaluated as well as intraclass correlations (IC) and coefficients of variation (CV). Total body measurements had better IC and CV than regional results from the whole body scan, with legs and arms better than trunk and spine. IC values were >or=0.989 for total body, >or=0.976 for legs and arms, and >or=0.875 for trunk and spine. CV values ranged 0.18 to 1.97% for total body, and 0.96 to 6.91% for regional measures. These values confirm that body composition and bone mass by DXA are highly reproducible among pediatric subjects. The results of this study can be used by clinicians and researchers for interpretation of longitudinal observations and for power calculations.


Bioanalytical methods encompassing label-free and labeled tuberculosis aptasensors: A review.
The high incidence of tuberculosis (TB) infection is of great concern world-wide. The traditional TB diagnostic techniques are not ideal for TB diagnosis in resource-poor countries. This is due to their high complexity, expensive nature, long time duration, poor sensitivity and specificity, as well as their requirement for sophisticated laboratories with special biosafety conditions. These limitations are major factors contributing to late diagnosis of TB and its continuous persistence. Biosensors offer several advantages as diagnostic tool due to their independence on Mycobacterium tuberculosis, simplicity, low-cost, high sensitivity and specificity. Likewise, the increasing interest on aptamers as biorecognition elements in biosensor application lies in their ease of synthesis and modification, chemical and thermal stability, low-cost, and high sensitivity and specificity towards their targets. Several research works have been done and many more are still on-going on fabrication and application of aptasensors for TB diagnosis. This review summarizes the label-free and label-based electrochemical, piezoelectric and optical aptasensors for TB diagnosis published in the last decade. It focuses on their various aptamer sequence modifications, assay formats, sensitivities, nanomaterial and enzyme-based signal amplification strategies, and the possibility of miniaturization and automation using microfluidic devices.