Rotavirus infection in wild marsupials (Didelphis marsupialis) of the Amazon region.
Rotavirus was detected by enzyme-linked immunosorbent assay in faecal specimens collected from two (1.35%) of 148 marsupials trapped in the Amazon jungle environment. The positive samples were both from the "common opossum", Didelphis marsupialis. No infections were found in the stools of 198 animals belonging to other mammalian species: the latter included small rodents, chiropterans and primates. Electron microscopic examination of one (MA 5928) rotavirus-positive specimen showed a large number of empty particles. However, both rotavirus strains grew when inoculated in MA 104 cells (foetal Rhesus monkey kidney cells) producing clear cytopathogenic effect; indirect immunofluorescence technique of these cells showed a typical granular cytoplasmic fluorescence. The electrophoretic profile of strain MA 5928 showed a high grade of homology with that of SA 11, but also showed minor differences.


Rohypnol-induced sexual dysfunction is via suppression of hypothalamic-pituitary-testicular axis: An experimental study in rats.
Sexual activity is an essential part of reproductive functions and needed for the maintenance of fertility. Drugs, particularly substances of abuse, impair male reproductive function either by interrupting hormonal functions or through the nonhormonal pathways. This study evaluated the impact of Rohypnol use in sexual behaviour. Materials and methods: Thirty adult male Wistar rats of comparable weights (180-200 g) were randomly allocated into three groups, the control and low-dose and high-dose Rohypnol-treated groups. The control group received 0.5 ml of distilled water, while the low- and high-dose Rohypnol-treated groups received 2 mg/kg b.w and 4 mg/kg b.w of Rohypnol via oral lavage once daily for 28 days. Rohypnol significantly increased mount latency, intromission latency, ejaculation latency and post-ejaculatory interval, as well as lowered mount frequency, intromission frequency and ejaculation frequency. Rohypnol-induced sexual dysfunction was found to be associated with significant suppression of circulatory follicle-stimulating hormone, luteinising hormone, testosterone and oestrogen. The present study reveals that Rohypnol induces sexual dysfunction through suppression of hypothalamic-pituitary-testicular axis. It also implicates Rohypnol as a potential candidate for drug-induced infertility.


Structural analogue-based protein structure domain assembly assisted by deep learning.
With the breakthrough of AlphaFold2, the protein structure prediction problem has made remarkable progress through deep learning end-to-end techniques, in which correct folds could be built for nearly all single-domain proteins. However, the full-chain modelling appears to be lower on average accuracy than that for the constituent domains and requires higher demand on computing hardware, indicating the performance of full-chain modelling still needs to be improved. In this study, we investigate whether the predicted accuracy of the full-chain model can be further improved by domain assembly assisted by deep learning. In this article, we developed a structural analogue-based protein structure domain assembly method assisted by deep learning, named SADA. In SADA, a multi-domain protein structure database was constructed for the full-chain analogue detection using individual domain models. Starting from the initial model constructed from the analogue, the domain assembly simulation was performed to generate the full-chain model through a two-stage differential evolution algorithm guided by the energy function with an inter-residue distance potential predicted by deep learning. SADA was compared with the state-of-the-art domain assembly methods on 356 benchmark proteins, and the average TM-score of SADA models is 8.1% and 27.0% higher than that of DEMO and AIDA, respectively. We also assembled 293 human multi-domain proteins, where the average TM-score of the full-chain model after the assembly by SADA is 1.1% higher than that of the model by AlphaFold2. To conclude, we find that the domains often interact in the similar way in the quaternary orientations if the domains have similar tertiary structures. Furthermore, homologous templates and structural analogues are complementary for multi-domain protein full-chain modelling. http://zhanglab-bioinf.com/SADA. Supplementary data are available at Bioinformatics online.


Sodium nitroprusside induced hypotension and isovolemic hemodilution in dogs.
Hypotension at 70 mm Hg was induced with sodium nitroprusside in 6 hemodiluted and 6 control dogs. In contrast to the control dogs, the reduction in mean arterial pressure was not primarily due to the peripheral resistance reduction, but the result of a hazardous fall in cardiac output.


Circulating Proteins Associated with Response and Resistance to Neoadjuvant Chemotherapy in HER2-Positive Breast Cancer.
Despite the increasing use of neoadjuvant chemotherapy (NAC) in HER2-positive breast cancer (BC) patients, the clinical problem of predicting individual treatment response remains unanswered. Furthermore, the use of ineffective chemotherapeutic regimens should be avoided. Serum biomarker levels are being studied more and more for their ability to predict therapy response and aid in the development of personalized treatment regimens. This study aims to identify effective protein networks and biomarkers to predict response to NAC in HER2-positive BC patients through an exhaustive large-scale LC-MS/MS-based qualitative and quantitative proteomic profiling of serum samples from responders and non-responders. Serum samples from HER2-positive BC patients were collected before NAC and were processed by three methods (with and without nanoparticles). The qualitative analysis revealed differences in the proteomic profiles between responders and non-responders, mainly in proteins implicated in the complement and coagulation cascades and apolipoproteins. Qualitative analysis confirmed that three proteins (AFM, SERPINA1, APOD) were correlated with NAC resistance. In this study, we show that serum biomarker profiles can predict treatment response and outcome in the neoadjuvant setting. If these findings are further developed, they will be of significant clinical utility in the design of treatment regimens for individual BC patients.


Sheet conductor model of brain slices for stimulation and recording with planar electronic contacts.
Current and voltage in a brain slice are considered, taking into account the boundary conditions at the surface to an electrolyte bath and at the substrate of an electron conductor. A sheet conductor model is introduced with ohmic leak conductance to the bath and capacitive coupling to the substrate. It assigns a current-source density of neuronal activity to extracellular field potentials recorded by planar contacts, and it relates the current of planar capacitive contacts to the field potential that elicits neuronal activity. Two examples are analytically solved: the recording across a layered brain slice and the stimulation by a circular electrode. The study forms the basis for neurophysical experiments with brain slices or retinae on microelectronic chips.


Identification of Unequal Flow-Carrying Capabilities of Choke Vessels in Rat Abdominal Flaps.
Although the angiosome concept is a well-accepted theory, unexpected necrosis suggests that other factors can influence the flap survival. Our study uses the rat model to explore the flow capacity of the choke vessels across 2 angiosomes. The medioventral line of Sprague-Dawley rats' abdominal flap was equally divided into 4 sections, which were preserved in 7 different groups (n = 6/group): A, no dissection; B to D, preserve the inferior 1/4, 2/4, and 3/4 sections; E to G, preserve the superior 1/4, 2/4, and 3/4 sections. The ratio (%) of the survival area of the distal/proximal territory was calculated. Indocyanine green, lead-oxide gel imaging, hematoxylin and eosin, and CD31 histology tests were performed. Compared with 96.0 ± 1.4% flap survival in group A, groups B, C, and D had distal territory flap loss (34.8% ± 4.1%, 65.0% ± 3.7%, and 94.3% ± 3.1% respectively). Group E lost the majority of the distal territory (3.5% ± 2.4%), whereas groups F and G (15.5% ± 3.8% and 79.2% ± 3.3%, respectively) had larger flap survival. Except for groups A and D, each of the other 2 groups showed statistically significant results ( P < 0.001). Indocyanine green indicated no blood flow at the superior 1/4 part. Lead-oxide gel and histology showed that the choke vessels residing along the medioventral line had no significant difference. Choke vessels do not carry blood flow equally. Two categories of choke vessels-"resting" and "active"-are proposed. The "active" form has variable flow carrying capabilities when the flap is harvested in different designs.


Identification of novel microRNAs in the embryonic mouse brain using deep sequencing.
Many advances in small RNA-seq technology and bioinformatics pipelines have been made recently, permitting the discovery of novel miRNAs in the embryonic day 15.5 (E15.5) mouse brain. We aimed to improve miRNA discovery in this tissue to expand our knowledge of the regulatory networks that underpin normal neurodevelopment, find new candidates for neurodevelopmental disorder aetiology, and deepen our understanding of non-coding RNA evolution. A high-quality small RNA-seq dataset of 458 M reads was generated. An unbiased miRNA discovery pipeline identified fifty putative novel miRNAs, six of which were selected for further validation. A combination of conservation analysis and target functional prediction was used to determine the authenticity of novel miRNA candidates. These findings demonstrate that miRNAs remain to be discovered, particularly if they have the features of other small RNA species.


Predictive value of programmed ventricular stimulation in patients with ischaemic cardiomyopathy: implications for the selection of candidates for an implantable defibrillator.
The present study assessed the role of programmed ventricular stimulation (PVS) in risk stratification of patients with ischaemic cardiomyopathy (ICM), candidates for implantable cardioverter-defibrillator (ICD). Consecutive patients with ICM and LVEF < or = 40% (n = 106, age 61 +/- 7 years, LVEF 27 +/- 7%) underwent PVS. This was considered positive in case of inducibility of monomorphic ventricular tachycardia (VT) with < or =3 extrastimuli; polymorphic VT, ventricular fibrillation (VF), and fast monomorphic VT (CL < or = 230 ms) with < or =2 extrastimuli. Primary end-point was the combination of arrhythmic death and VF requiring ICD shock. Forty-nine patients (46%) were inducible at PVS; 74 (70%) were implanted with ICD. During a 24-month follow-up, the primary end-point occurred more frequently in positive PVS patients among the overall population, among patients with LVEF < or = 30% (n = 80) and among patients with an ICD. The negative predictive value of PVS was 96% in each group. In the overall population, both PVS (HR 7.32, 95% CI 1.6-32) and LVEF (HR 4.59, 95% CI 1.6-13) predicted the primary end-point. PVS may still have a role in predicting the arrhythmic risk in patients with ICM. A negative PVS identifies a subgroup with a very low risk of arrhythmic events even in patients with LVEF < or = 30%.


Mosaic organization of calcineurin immunoreactivity in the adult cat striatum.
Calcineurin is a Ca2+/calmodulin-regulated protein phosphatase which is thought to play an essential role in the intracellular Ca(2+)-signal transduction. The present study showed that calcineurin immunolabeling was differentially concentrated in the two distinct compartments showing a mosaic-like pattern in the adult cat striatum. The compartment of heightened calcineurin immunolabeling corresponded to the extrastriosomal matrix visualized by calbindin-D28K immunostaining. Under the light microscope, striatal neurons appeared to be less strongly immunoreactive for calcineurin in the striosomes than in the matrix compartment. These findings suggest that the novel striatal compartments may differ in the intracellular Ca(2+)-signaling cascade associated with protein dephosphorylation.


The contribution of chromatic and achromatic valence to spectral saturation.
The spectral efficiency of the achromatic and opponent chromatic channels was measured in three subjects by use of heterochromatic flicker photometry and hue cancellation, respectively. Heterochromatic brightness matching was also used for measuring achromatic spectral efficiency. These data were then used to predict spectral saturation based on Hurvich and Jameson's (1957; Psychological Review, 64, 384-404) opponent colors model. A standard color-naming procedure and a saturation matching technique were used for measures of spectral saturation. The ratio of saturation of short-wave to long-wave lights was found to be less than that predicted by the linear valence model. Allowing for nonlinearity at the opponent site of the yellow-blue channel plus a desaturating signal from the rods provided a good fit between data and theory.


Tenidap, but not nonsteroidal anti-inflammatory drugs, inhibits T-cell proliferation and cytokine induction.
T-lymphocytes are involved in the inflammatory response that occurs in affected joints of patients with rheumatoid arthritis (RA). Some second-line disease modifying anti-rheumatic drugs used in the treatment of patients with RA are known to block T-cell activation. The present study assessed whether tenidap, an investigational anti-rheumatic drug, affects in vitro T-cell responses such as proliferation and cytokine production. It was found that tenidap, in contrast to several nonsteroidal anti-inflammatory drugs, inhibits anti-CD3 or IL-2 driven proliferative responses of cloned human T-cells. Furthermore, tenidap was found to inhibit IFN-gamma production as well as the induction of mRNA encoding IFN-gamma or TNF-alpha. The results indicate that tenidap may exert at least part of its anti-inflammatory activity via inhibition of T-cell function and cytokine production.


High denitrification potential but low nitrous oxide emission in a constructed wetland treating nitrate-polluted agricultural run-off.
Constructed wetlands (CW) can efficiently remove nitrogen from polluted agricultural run-off, however, a potential caveat is nitrous oxide (N2O), a harmful greenhouse gas and stratospheric ozone depleter. During five sampling campaigns, we measured N2O fluxes from a 0.53 ha off-stream CW treating nitrate-rich water from the intensively fertilized watershed in Rampillon, France, using automated chambers with a quantum cascade laser system, and manual chambers. Sediment samples were analysed for potential N2 flux using the HeO2 incubation method. Both inlet nitrate (NO3-) concentrations and N2O emission varied significantly between the seasons. In the Autumn and Winter inlet concentrations were about 11 mg NO3--N L-1, and < 6.5 mg NO3--N L-1 in the Spring and Summer. N2O emission was highest in the Autumn (mean ± standard error: 9.7 ± 0.2 μg N m-2 h-1) and lowest in the Summer (wet period: 0.2 ± 0.3 μg N m-2 h-1). The CW was a very weak source of N2O emitting 0.32 kg N2O-N ha-1 yr-1 and removing around 938 kg NO3--N ha-1 yr-1, the ratio of N2O-N emitted to NO3--N removed was 0.033%. The automated and manual chambers gave similar results. From the potential N2O formation in the sediment, only 9% was emitted to the atmosphere, the average N2 N 2O ratio was high: 89:1 for N2-Npotential: N2O-Npotential and 1353:1 for N2-Npotential: N2O-Nemitted. These results indicate complete denitrification. The focused principal component analysis showed strong positive correlation between the gaseous N2O fluxes and the following environmental factors: NO3--N concentrations in inlet water, streamflow, and nitrate reduction rate. Water temperature, TOC and DOC in the water and hydraulic residence time showed negative correlations with N2O emissions. Shallow off-stream CWs such as Rampillon may have good nitrate removal capacity with low N2O emissions.


Associations of air pollution concentrations and energy production dynamics in Pakistan during lockdown.
This study investigated atmospheric changes that occurred due to changes in energy production and consumption before and during the COVID-19 pandemic. We analyzed nitrogen dioxide (NO2), aerosol optical depth (AOD), and rainfall patterns to understand the associated changes in emissions, especially from the power generation sector, before (2018 and 2019) and during the lockdown of 2020 across Pakistan. Regression analysis indicated a strong association between energy production by thermal power plants and tropospheric NO2 concentrations. Notably, a comparison between emission sources showed that the NO2 emissions from a single thermal power plant were equivalent to the emissions from a major city. During the lockdown, we observed a 40% reduction in NO2 emissions from coal-based power plants and a 30% reduction in mega- and major cities compared to the same retro in 2019. We also observed an approximate 25% decrease in AOD in the industrial and energy sectors, although no major decrease was obvious in the cities. Rainfall contributed to reducing the NO2 concentrations during monsoon season across all power plants in Pakistan, whereas it did not significantly correlate with AOD. The findings highlight the need for appropriate management and use of renewable energy in the industrial sector and transportation systems. Future research could estimate the environmental and public health costs linked to pollution originating from thermal energy production and poor transportation infrastructure.


Identification and Pyramiding of QTLs for Rice Grain Size Based on Short-Wide Grain CSSL-Z563 and Fine-Mapping of qGL3-2.
Chromosome segment substitution lines (CSSLs) can be used to dissect complex traits, from which single-segment substitution lines (SSSLs) containing a target quantitative trait loci (QTL) can be developed, and they are thus important for functional analysis and molecular breeding. A rice line with short wide grains, CSSL-Z563, was isolated from advanced-generation backcross population (BC3F6) derived from 'Xihui 18' (the recipient parent) and 'Huhan 3' (the donor parent). Z563 carried seven segments from 'Huhan 3', distributed on chromosomes 3, 7, and 8, with average substitution length of 5.52 Mb. Eleven QTLs for grain size were identified using secondary F2 population of 'Xihui 18'/Z563. The QTLs qGL3-1, qGL3-2, and qGL7 control grain length in Z563 and have additive effects to reduce grain length; qGW3-1 and qGW3-2 control grain width in Z563 and have additive effects to increase grain width. Four SSSLs, three double-segment substitution lines (D1-D3), and two triple-segment substitution lines (T1 and T2) were developed containing the target QTLs. The genetic stability of eight QTLs, including qGL3-2, qGL3-1, and qGL7, was verified by the SSSLs. D1 (containing qGL3-2 and qGL3-1), D2 (qGL3-1 and qGL7), and T1 (qGL3-2, qGL3-1, and qGL7) had positive epistatic effects on grain length, and their grain length was shorter than that of the corresponding SSSLs. The QTL qGL3-2 was fine-mapped to a 696 Kb region of chromosome 3 containing five candidate genes that differed between 'Xihui 18' and Z563. These results are important for functional research on qGL3-2 and molecular breeding of hybrid rice cultivars. The short and wide grain of Z563 was mainly controlled by qGL3-1, qGL3-2, qGL7, qGW3-1 and qGW3-2. The major QTL qGL3-2 was fine-mapped to a 696 Kb region of chromosome 3 containing five candidate genes. Different QTLs pyramiding displayed various phenotypes. In essence, the performance after pyramiding of genes depended on the comparison between the algebraic sum of the additive and epistatic effects of QTLs in the pyramidal line and the additive effect value of the single QTL. The results lay good foundation in the functional analysis of qGL3-2 and molecular design breeding of novel hybrid rice cultivars.


Dynamic Antibody Responses in Patients with Different Severity of COVID-19: A Retrospective Study.
The coronavirus disease 2019 (COVID-19) pandemic is a serious public health event and poses a global health threat. To study the specific antibody responses would contribute to a better understanding of COVID-19. We collected complete follow-up data from 777 patients with pathogen-confirmed COVID-19 with corresponding immunoglobulin G and M (IgG/IgM) testing results. Overall, the positive rates of IgG and IgM in severe patients were slightly higher than those in non-severe patients. In addition, higher IgG levels were detected in severe patients compared to non-severe patients (P = 0.026). Through further analysis, differences in IgG were only significant in serum samples taken in the first 14 days of disease onset (P < 0.001). On the basis of analysis of antibody expression levels at different time points in 74 patients who had undergone more than three detection tests, we found that the differences in IgG levels between the severe/non-severe patients were more pronounced than those of IgM. On multivariate logistic regression, after adjusting for cofactors, the higher anti-SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) IgG levels observed in the first 14 days of disease onset were independently associated with severe COVID-19 disease (odds ratio (OR) = 1.368, 95% confidence interval (CI) 1.138-1.645). We observed differences in antibody responses among patients with different severity of COVID-19. A high IgG level in the first 14 days of disease may be positively associated with disease severity.


Cross-Cultural Differences in Memory Specificity: Investigation of Candidate Mechanisms.
Previous research has revealed that people from Western cultures tend to remember more details of objects and events in autobiographical memory compared to people from Eastern cultures. The present experiments tested whether differences in pattern separation - the process by which new, but potentially similar, exemplars are discriminated from previously-encountered exemplars - account for these cultural difference in object memory. In two experiments, we investigated the extent to which North Americans and East Asians differ in pattern separation and whether these effects are related to cultural values. We also examined the role of response bias. These results revealed it is unlikely that pattern separation is the sole mechanism underlying cross-cultural memory specificity differences, as broader memory mechanisms, such as differences in memory resolution for previously-encoded items, could account for the differences observed between groups.


Midterm results of uncemented acetabular reconstruction for posttraumatic arthritis secondary to acetabular fracture.
At an average of 6.3 years after surgery, we evaluated midterm results of uncemented acetabular reconstruction in 31 hips with posttraumatic arthritis that developed after acetabular fracture. Patients were categorized by previous fracture treatments (open-reduction group and conservative-treatment group) and fracture patterns (simple group and complex group). Surgery duration and blood loss were greater in the open-reduction and complex groups than in the conservative-treatment and simple groups (P < .05). The mean Harris Hip Score increased from 49 before surgery to 89 after surgery. Survival with revision or radiographic acetabular loosening as an end point was 100%. Fracture treatments and patterns were associated with increased surgery duration and increased blood loss. Open reduction and internal fixation of a fracture favor anatomical restoration of the hip's rotational center.


Differences in mortality among patients with community-acquired pneumonia in California by ethnicity and hospital characteristics.
To determine ethnic disparities in mortality for patients with community-acquired pneumonia, and the potential effects of hospital characteristics on disparities, we compared the risk-adjusted mortality of white, African American, Hispanic, and Asian American patients hospitalized for community-acquired pneumonia. We studied patients discharged with community-acquired pneumonia in 1996 from an acute care hospital in California (n = 54,874). Logistic regression models were used to examine the association between ethnicity and hospital characteristics and 30-day mortality after adjusting for clinical characteristics. The overall 30-day mortality was 12.2%. After adjustment for demographic, clinical, and hospital characteristics, Hispanic (odds ratio [OR] = 0.81; 95% confidence interval [CI]: 0.73 to 0.90) and Asian American patients (OR = 0.88; 95% CI: 0.77 to 1.00) had lower mortality than did white patients, whereas African Americans had a similar mortality to whites (OR = 0.93; 95% CI: 0.83 to 1.06). There were no overall differences in mortality by hospital characteristics (i.e., teaching status, rural location, and public or district hospital). Hispanics and Asian Americans have a lower risk of death from community-acquired pneumonia than whites in California. No overall differences in mortality were observed by hospital characteristics.


[Lower limb discrepancy after total knee arthroplasty. Is it really an issue?]
Lower limb discrepancy after total knee arthroplasty (TKA) is common. The main objective of this study is to evaluate the incidence of lower limb discrepancy after TKA. this is an observational analytical retrospective cohort study. We have included all the patients who underwent unilateral TKA with the same type of implant. The limb length was measured with a panoramic lower limb x-ray. The cut-off point to consider the discrepancy was > 10 mm. The type of deformity and the functional outcomes were evaluated. In a total of 60 patients, 18 (30%) showed a lower limb discrepancy. Out of the patients who presented discrepancy, the most frequent deformity was valgus deformity with a 55,6% followed by varus deformity with 38.89% and 5.56% with neutral axis. The functional outcomes according to the KSS score and the postoperative knee KSS score demonstrated no difference in long term follow up between both groups. the incidence of lower limb discrepancy after TKA was 30%. None of the patients required surgery as a consequence of the discrepancy. The functional outcomes and pain in a long term follow up did not demonstrate differences between both groups.


Hybrid fitness, adaptation and evolutionary diversification: lessons learned from Louisiana Irises.
Estimates of hybrid fitness have been used as either a platform for testing the potential role of natural hybridization in the evolution of species and species complexes or, alternatively, as a rationale for dismissing hybridization events as being of any evolutionary significance. From the time of Darwin's publication of The Origin, through the neo-Darwinian synthesis, to the present day, the observation of variability in hybrid fitness has remained a challenge for some models of speciation. Yet, Darwin and others have reported the elevated fitness of hybrid genotypes under certain environmental conditions. In modern scientific terminology, this observation reflects the fact that hybrid genotypes can demonstrate genotype × environment interactions. In the current review, we illustrate the development of one plant species complex, namely the Louisiana Irises, into a 'model system' for investigating hybrid fitness and the role of genetic exchange in adaptive evolution and diversification. In particular, we will argue that a multitude of approaches, involving both experimental and natural environments, and incorporating both manipulative analyses and surveys of natural populations, are necessary to adequately test for the evolutionary significance of introgressive hybridization. An appreciation of the variability of hybrid fitness leads to the conclusion that certain genetic signatures reflect adaptive evolution. Furthermore, tests of the frequency of allopatric versus sympatric/parapatric divergence (that is, divergence with ongoing gene flow) support hybrid genotypes as a mechanism of evolutionary diversification in numerous species complexes.


Secondary Hyperparathyroidism Among Bariatric Patients: Unraveling the Prevalence of an Overlooked Foe.
Bariatric surgery (BS) is the most effective therapeutic approach to obesity. It is associated with great gastrointestinal anatomic changes, predisposing the patients to altered nutrient absorption that impacts phosphocalcium metabolism. This study aimed to clarify the prevalence of secondary hyperparathyroidism (SHPT) and its predictors in patients submitted to BS. Retrospective study of 1431 patients who underwent metabolic surgery between January 2010 and June 2017 and who were followed for at least 1 year. We compared the clinical and biochemical characteristics of patients with and without secondary hyperparathyroidism (considering SHPT a PTH ˃ 69 pg/mL). Two different analyses were performed: (1) paired analysis of participants before and 1 year after surgery (N = 441); (2) Cross sectional analysis of participants submitted to bariatric surgery before (N = 441), 1 year after (N = 1431) and 4 years after surgery (N = 333). Multiple logistic regression models were used to evaluate possible predictors of SHPT after BS. The overall prevalence of SHPT was 24.9% before surgery, 11.2% 1 year after surgery and 21.3% 4 years after surgery. Patients submitted to LAGB had the highest prevalence of SHPT 1 year after surgery (19.4%; vs RYGB, 12.8%, vs SG, 5.3%). Four years after surgery, RYGB had the highest prevalence of SHPT (27.0%), followed by LAGB (13.2%) and SG (6.9%). Higher body mass index and age, decreased levels of vitamin D and RYGB seem to be independent predictors of SHPT 1 year after surgery. The only independent predictor of SHPT 4 years after surgery was RYGB. The prevalence of SHPT is higher before and 4 years after BS than 1 year after surgery. This fact raises some questions about the efficacy of the implemented follow-up plans of vitamin D supplementation on the long term, mainly among patients submitted to RYGB.


Third annual William L. McGuire Memorial Lecture. "Studies on the estrogen receptor in breast cancer"--20 years as a target for the treatment and prevention of cancer.
In 1973, McGuire and Chamness (In: O'Malley BW and Means AR (ed) Receptors for Reproductive Hormones, Plenum Press) summarized their work on the estrogen receptor in animal and human breast tumors, and in so doing described a target for therapeutic intervention. At that time there were no clinically useful antiestrogens, but the subsequent development of tamoxifen for breast cancer therapy has revolutionized the approach to treatment. Long-term adjuvant tamoxifen adjuvant therapy (i.e., greater than one year) has proven efficacy to enhance the survival of breast cancer patients. In addition, because there is an associated 40% decrease in contralateral breast cancer during adjuvant tamoxifen therapy and tamoxifen maintains bone density and reduces fatal myocardial infarction, clinical trials to test the worth of tamoxifen as a preventive for breast cancer in high risk women have started in the United States, United Kingdom, and Italy. Initial concerns that long-term tamoxifen causes endometrial cancer have been placed in perspective and analyzed by a review of the literature. Tamoxifen only doubles the normal risk of detecting endometrial cancer (i.e., to 2 per 1,000 tamoxifen-treated women per year), and 80% of these cases are early stage, good prognosis disease. Annual gynecological examinations and education are essential to provide reassurance for patients. The success of tamoxifen has encouraged the development of new antiestrogens to exploit the estrogen receptor as a therapeutic target. Droloxifene and TAT-59 mimic the metabolite 4-hydroxytamoxifen in having a high affinity for the estrogen receptor (Jordan et al, J Endocrinol 75:305, 1977). These drugs appear to have a pharmacological profile similar to tamoxifen. In contrast, the new pure antiestrogens have a distinct mechanism of action and will be valuable either as a first line therapy for advanced breast cancer or as a second line endocrine therapy after the failure of long-term adjuvant tamoxifen therapy. Finally, a new strategy is being developed to exploit the target site specific action of antiestrogens. Raloxifene, an antiestrogen with high affinity for the estrogen receptor but only weak estrogenicity for the uterus, prevents rat mammary tumorigenesis and maintains bone density. The drug is to be evaluated as a treatment for osteoporosis, but may also prevent the development of breast and endometrial cancer in a broad group of treated subjects. The identification of the estrogen receptor as a target for therapeutic opportunities has proved to be extremely beneficial for the control of breast cancer and has the added potential to control osteoporosis and coronary heart disease in women.


Diffusion-weighted imaging properties of uterine fibroids pre- and post-uterine fibroid embolisation.
To determine the change in apparent diffusion coefficient (ADC) of uterine fibroids following uterine fibroid embolisation (UFE), and if the ADC change correlates with either volume loss or degree of contrast enhancement post-UFE. This study was approved by our institutional review board with waiver of consent. The pelvic MRI examinations, including diffusion-weighted MRI (DWI) using 4 b-values, of 50 consecutive patients prior to and 6 months post-UFE were analyzed. The volume, ADC and amount of enhancement were calculated for each fibroid both pre- and post-UFE. The percent residual enhancement for each fibroid was categorized as either: no (0-1%) residual enhancement or residual (>1%) enhancement. Statistical analysis compared ADC, enhancement and volume for each fibroid pre- and post-UFE using paired t-tests and Pearson correlation coefficients. The mean ADC of all (n=88) fibroids pre-UFE was 1.30±0.20×10(-3)mm(2)/s, and increased to 1.68±0.24×10(-3)mm(2)/s post-UFE (p<0.0001). Lower pre-UFE ADC correlated with greater ADC change post-UFE (r=-0.50; p<0.0001). There was no correlation between ADC change and volume change post-UFE (r=0.07; p=0.59). However, fibroids with no residual enhancement post-UFE had larger ADC change than those with residual enhancement (p=0.003). The ADC of fibroids rises post-UFE. ADC change post-UFE is associated with the degree of loss of enhancement and may therefore be valuable in predicting response to treatment in pre-procedural counseling.


Long-term follow-up after stereotactic radiosurgery of intracanalicular acoustic neurinoma.
The management of solely intracanalicular acoustic neurinoma (iAN) includes observation, microsurgical resection and radiation therapy. Treatment goals are long-term tumor control, hearing preservation and concurrently low side-effects. Stereotactic radiosurgery (SRS) has evolved as an alternative first-line treatment for small AN. Here we report about the long-term follow-up of a unique cohort of patients with iAN after LINAC or Cyberknife® based SRS. In this single center retrospective analysis, we included all patients with iAN who underwent single session LINAC or Cyberknife® based SRS between 1993 and 2015, and who had a minimum follow-up period of six weeks. Patient data were analyzed in terms of radiological and clinical tumor control (no further treatment necessary), subjective preservation of serviceable hearing, objective change in pure tone averages (PTA), and adverse events rated by the Common Terminology Criteria for Adverse Events (CTCAE; v4.03). Forty-nine patients (f/m = 21/28, median age 54 ± 12, range 20-77 years) were identified. Mean tumor volumes were 0.24 ± 0.12 cm3 (range, 0.1-0.68 cm3), the mean marginal dose was 12.6 ± 0.6 Gy (range, 11.0-14.0 Gy) and the prescription isodose was 75 ± 7.4% (range, 47-86%). Mean follow-up time was 65 months (range, 4-239 months). Radiological tumor control was 100% during further follow-up. 17 (35%) out of 49 patients had lost serviceable hearing prior to SRS. Those with preserved serviceable hearing remained stable in 78% (n = 25/32) at the last follow-up (LFU). The median PTA (n = 16) increased from 25.6 dB prior to SRS to 43.8 dB at LFU. Mild adverse events were observed temporarily in two patients (4%): one with CTCAE grade 1 facial nerve disorder after 3 months, resolving three months later, and one with CTCAE grade 2 facial muscle weakness resolving after 12 months. Three patients described permanent mild symptoms CTCAE grade 1 without limiting daily life (facial weakness n = 1, vertigo n = 2). SRS for iAN shows long-term reliable tumor control with a high rate of hearing preservation without considerable permanent side effects, and can be proposed as a safe and effective treatment alternative to microsurgical resection.


Bandpass measurements in the electroretinographic electrode circuit.
In the experiments in this study band-pass measurements in electroretinographic electrode circuits were done for the first time, according to the information presently available to us. Our experiments show that in the much faster band-pass assessment by analysis of sawtooth and square waves no major error is involved. It may be concluded from our results that the recordings of ERG potentials are not changed by the characteristic properties of the electrode circuit in the frequency range of interest.


Effect of slow release IL-12 and IL-10 on inflammation, local macrophage function and the regional lymphoid response during mycobacterial (Th1) and schistosomal (Th2) antigen-elicited pulmonary granuloma formation.
This study examines the local and regional effects of exogenously administered interleukins 10 (IL-10) and 12 (IL-12) on pulmonary granulomas mediated by Th1/type 1-(IFN-gamma) and Th2/type 2-(IL-4, IL-5 cytokines. MATERIALS AND TREATMENTS: Granulomas (GR) were induced in presensitized CBA mice by embolization of beads coated with Mycobacteria tuberculosis or Schistosoma mansoni egg antigens. Before challenge, osmotic pumps distributing IL-10 or IL-12 (50 micrograms/kg/day) were implanted intraperitoneally, then GR and draining lymph nodes were examined 4 days. GR sizes and composition were determined by morphometry and differential analysis. Isolated GR macrophages and draining lymph nodes were assessed for cytokine production by ELISA. IL-10 did not effect GR sizes but reduced neutrophils in type 1 GR. IL-12 minimally reduced type 1 GR but decreased the type 2 lesion by up to 70%, primarily curtailing eosinophils. Type 2 GR macrophages were unaffected but type 1 were impaired by IL-10. Conversely, type GR macrophages were more resistant to IL-12 while type 2 showed enhanced IL-10, IL-12 and TNF, but reduced MCP-I production. In lymph nodes, IL-10 caused paradoxical effects, enhancing IFN-gamma in the type 1 and decreasing Th2 cytokines in the type 2 response. Exogenous IL-12 profoundly augmented IFN-gamma and abrogated type 2 cytokines while inhibiting intrinsic IL-12 production in lymph nodes. These findings provide novel information regarding cytokine regulation and the effects of systemic cytokine therapy.


Cortical serotonin receptor subtypes after lesion of ascending cholinergic neurones in rat.
Serotonin (5-HT) S1 and S2 receptors were studied in rat cortex after lesion of the ascending cholinergic systems by injection of ibotenic acid into the nucleus basalis. The lesions produced a large (56%) decrease in choline acetyltransferase activity with no change in markers of gamma-aminobutyric acid, dopamine and 5-HT containing neurones. Lesions of the ascending cholinergic neurones were accompanied by a loss of 5-HT S1 receptor binding sites with no change in S2 receptors. These results suggest that a proportion of S1 receptors may be associated with cholinergic terminals.


Process characteristics of cell lysis mutants of Saccharomyces cerevisiae.
Several temperature-sensitive lysis mutants of Saccharomyces cerevisiae were selected according to their ability to release alkaline phosphatase when incubated at a nonpermissive temperature. For two mutants, cell lysis and release of alkaline phosphatase reached a maximum when cells in the logarithmic growth phase were shifted to the nonpermissive temperature. Morphological changes, as well as changes in macromolecular composition of the cells, were observed. Growth is necessary and oxygen is important for the expression of cell lysis at the nonpermissive temperature.


Study on bisphenol F, a bisphenol A analogue, at a dairy company: Health hazard and risk assessment.
The occurrence of analogues of bisphenol A (BPA), including bisphenol F(BPF) in milk is still not well known. BPF may enter the milk chain at the farm and during milk processing at the dairy company. This study identified the main BPF contamination pathways using a monitoring model based on the identification of the hazard at three stages along the dairy chain: raw milk from the storage tank, pasteurized milk from the storage tank, and cardboard packaged milk. Quantitative analysis was performed by high-performance liquid chromatography with fluorometric detection (HPLC/FD) system. BPF was detected in all analysed stages (from <LOQ to 2.686 μg/L). The structural and toxicological similarity between BPF and BPA suggested considering both bisphenols for a more comprehensive risk evaluation. The daily intake of BPF and of the sum of BPF and BPA, and the worst-case scenario through the consumption of packaged milk were calculated. Exposure levels below the temporary daily intake, fixed for only BPA, were detected in all consumer age classes. Nevertheless, the use of BPA substitutes represents a risk to human health because of their potential synergic effects. The application of a monitoring program at each stage of milk processing at the dairy company may represent a useful strategy to ensure food safety in the milk chain.


The efficacy of the web-based childhood obesity prevention program in Chinese American adolescents (Web ABC study).
To examine the feasibility and efficacy of a theory-driven and family-based program delivered online to promote healthy lifestyles and weights in Chinese American adolescents. A randomized controlled study of a web-based intervention was developed and conducted in 54 Chinese American adolescents (ages, 12-15 years) and their families. Data on anthropometry, blood pressure, dietary intake, physical activity, and knowledge and self-efficacy regarding physical activity and nutrition were collected at baseline and 2, 6, and 8 months after the baseline assessment. Data were analyzed using linear mixed modeling. The intervention resulted in significant decreases in waist-to-hip ratio and diastolic blood pressure and increases in vegetable and fruit intake, level of physical activity, and knowledge about physical activity and nutrition. This web-based behavior program for Chinese American adolescents and their families seems feasible and effective in the short-term. Long-term effects remain to be determined. This type of program can be adapted for other minority ethnic groups who are at high-risk for overweight and obesity and have limited access to programs that promote healthy lifestyles.


Use of the Physiotherapy Evidence Database (PEDro) in Japan.
The Physiotherapy Evidence Database (PEDro) may help users to overcome some obstacles to evidence-based physiotherapy. Understanding the extent to which Japanese physiotherapists access research evidence via the PEDro website may suggest strategies to enhance evidence-based physiotherapy in Japan. To quantify usage of PEDro in Japan, to compare this to usage in other countries, and to examine variations in PEDro usage within Japan. An observational study of PEDro usage with geographic analysis. Data about visits to the home-page and searches of the database were recorded for 4 years. These data were analysed by each region of the World Confederation for Physical Therapy, each country in the Asia Western Pacific region, and each prefecture in Japan. From 2010 to 2013, users of PEDro made 2.27 million visits to the home-page and ran 6.28 million searches. Usage (ie, number of searches normalised by population) was highest in Europe, followed by North America Carribean, South America, Asia Western Pacific, and Africa. Within the Asia Western Pacific region, population-normalised usage was highest in Australia, then New Zealand and Singapore. Japan ranked 10 among the 26 countries in the region. Within Japan, the highest population-normalised usage was in the Nagano, Kumamoto and Aomori prefectures, which was ten-fold higher usage than in some other prefectures. Although Japan has higher PEDro usage than many other countries in the Asia Western Pacific region, some prefectures had very low usage, suggesting that evidence-based practice may not be being adopted uniformly across Japan.


Measurement of androstanediol in plasma in a radioimmunoassay using celite column chromatography.
A rapid and relatively simple, but specific, radioimmunoassay for the potent androgen, androstanediol (3 alpha-diol), is described. Despite the availability of a nonspecific C-19 androgen antibody requiring a 17 beta-hydroxy group, androstanediol can be measured in plasma by prior purification of a plasma solvent extract using a Celite microcolumn. Values obtained do not differ from those previously reported using more complicated chromatographic techniques.


Regulation of phospholipase D in HL-60 granulocytes. Activation by phorbol esters, diglyceride, and calcium ionophore via protein kinase- independent mechanisms.
It has recently been demonstrated that the chemotactic peptide N-formyl-Met-Leu-Phe activates phospholipase D (PLD) in dimethyl sulfoxide-differentiated HL-60 granulocytes to produce phosphatidic acid (PA) and, in the presence of ethanol, phosphatidylethanol (PEt) (Pai, J.-K., Siegel, M. I., Egan, R. W., and Billah, M. M. (1988) J. Biol. Chem. 263, 12472-12477). We now report that biologically active phorbol esters, a cell-permeable diacylglycerol, 1-oleoyl-2-acetylglycerol (OAG), and calcium ionophore A23187 are also potent inducers of PLD in these HL-60 granulocytes. HL-60 granulocytes have been selectively labeled in 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine (alkyl-PC) with 32P by incubating the cells with alkyl-[32P]lyso-phosphatidylcholine (PC). When these labeled cells are treated with phorbol 12-myristate 13-acetate (PMA), phorbol 12,13-dibutyrate, OAG, or A23187, alkyl-[32P]PA is formed. Because cellular ATP has not been labeled with 32P, the formation of alkyl-[32P]PA conclusively demonstrates PLD activation by these agents. In the presence of 0.5% ethanol, phorbol esters, OAG, and A23187 also induce formation of alkyl-[32P]PEt, demonstrating that the activated PLD catalyzes transphosphatidylation between the phosphatidyl moiety of the alkyl-[32P]PC and ethanol. Formation of alkyl-[32P]PA and alkyl-[32P]PEt in response to these various agents occurs in a time- and dose-dependent manner and exhibits differential Ca2+ requirements. Based on experiments with both [3H]alkyl-PC and alkyl-[32P]PC, it is concluded that alkyl-PA and alkyl-PEt formed in response to PMA, OAG, or A23187 are derived exclusively from PLD action on alkyl-PC. Furthermore, subthreshold concentrations of PMA (0.5-2.0 nM) or OAG (1.0-25 microM) combined with subthreshold levels of A23187 (15-60 nM) induce the formation of alkyl-[32P]PA and alkyl-[32P]PEt, suggesting that receptor-mediated activation of PLD might involve cooperative interactions between Ca2+ and diglyceride. Although PLD is activated by agents that also activate protein kinase C, the protein kinase C inhibitor, K252a, inhibits PMA-induced protein phosphorylation but causes only partial inhibition of PLD activation. We conclude that phorbol esters, OAG, and A23187 activate PLD in HL-60 granulocytes via protein kinase-independent as well as protein kinase-dependent mechanisms.


Perturbation of phospholipid bilayers by DDT.
The localization of the effects of DDT (5-50 mol%) addition on the acyl chain dynamics in unilamellar vesicles of two phosphatidylcholines (DPPC and egg PC) has been investigated by steady-state fluorescence polarization of a series of n-(9-anthroyloxy) fatty acids (n = 2, 6, 9, 12 and 16) whose fluorophore is located at a graded series of depths from the surface to the centre of the bilayer. The results show that DDT is a fluidizer of DPPC and egg PC bilayers. The increase in microviscosity of DPPC bilayers at 23 degrees C begins at the centre of the bilayer (5 mol% DDT) and proceeds outward to the surface with increasing concentration of DDT (17 mol%). This pattern of effects is not evident in fluid bilayers of DPPC at 54 degrees C or egg PC at 23 degrees C. DDT (33 mol%) also lowers the phase transition temperature of DPPC bilayers by approximately 2 Cdeg. DDT (17 mol%) had no effect on the mean excited fluorescence life-time of 2-AP and 12-AS in DPPC, DOPC and egg PC bilayers. No quenching of 2-AP fluorescence was evident.


Soluble gp130 promotes intestinal epithelial hyperplasia during reovirus infection.
Soluble gp130 (sgp130) has been shown to suppress the inflammatory response of autoimmune pathologies; however, its effects on virus infection are not known. Here, we report that intraperitoneal treatment of mice with sgp130-Fc fusion protein at the time of oral reovirus serotype 3 infection resulted in altered morphopathological changes that were evident by less shortening of intestinal villi length and crypt depth after infection. That the effect mediated by sgp130 treatment was due to an increase in intestinal crypt cell proliferation was demonstrated by an increase in the number of crypt mitotic figures. This was further confirmed by increased immunoreactivity to the Cdc47 proliferation-associated antigen in crypts of sgp130-treated virus-infected mice compared to infected non-treated mice. These findings suggest that sgp130 may have a beneficial effect during intestinal virus infection by disrupting interleukin-6 trans-signalling, thereby reducing the local inflammatory response.


Prediction of pre-eclampsia in early pregnancy by estimating the spot urinary albumin: creatinine ratio using high-performance liquid chromatography.
To establish whether a spot urinary albumin: creatinine ratio (ACR) measured before 20 weeks of gestation can predict subsequent pre-eclampsia when urinary albumin is measured by high-performance liquid chromatography (HPLC). Prospective exploratory study. Antenatal clinic in a tertiary teaching hospital, Victoria, Australia. A cohort of 265 women with a singleton pregnancy, normal renal function, and no evident proteinuria, attending antenatal clinics between 12 and 20 weeks of gestation. The ACR was determined from a mid-stream urine (MSU) sample taken between 17 and 20 weeks of gestation. Intact urinary albumin was determined by HPLC; creatinine was measured by modified Jaffe's method. Pre-eclampsia (primary); gestational hypertension, small for gestational age (SGA), gestational diabetes mellitus, gestational age at delivery, and prematurity (secondary). The median ACR was 28 mg/mmol (IQR 16-46 mg/mmol). Women who subsequently developed pre-eclampsia had a significantly higher ACR (median 50 mg/mmol; IQR 33-90 mg/mmol) compared with women suffering from gestational hypertension (median 27 mg/mmol; IQR 8-35 mg/mmol), and compared with unaffected women (median 28 mg/mmol; IQR 16-46 mg/mmol). Mothers of SGA infants also had a significantly higher median ACR. By ROC analysis, the optimum ACR to predict pre-eclampsia was 35.5 mg/mmol: the relative risk of developing pre-eclampsia in women with a urinary ACR ≥ 35.5 mg/mmol was 7.8 times more than in those with a urinary ACR < 35.5 mg/mmol. When urinary albumin is measured by HPLC, spot urinary ACR values are higher in early uncomplicated pregnancy compared with previously reported conventional methods. When measured early in the second trimester, an ACR ≥ 35.5 mg/mmol predicted pre-eclampsia well before the onset of clinical manifestations.


Biomarker discovery for ovine paratuberculosis (Johne's disease) by proteomic serum profiling.
Paratuberculosis (Johne's disease) is a chronic granulomatous enteritis affecting ruminants and other species. It is caused by Mycobacterium avium subsp. paratuberculosis (MAP). In this study, surface enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI TOF-MS) was used as a platform to identify candidate biomarkers from sheep serum. Multivariate biomarker models which aimed to differentiate sheep with paratuberculosis and vaccinated-exposed sheep from unexposed animals were proposed based on classification and regression tree (CART) and linear discriminant analysis (LDA) algorithms from two array types. The accuracy of classification of sheep into unexposed or exposed groups ranged from 75 to 100% among models. SELDI was used to monitor protein profile changes over time during an experimental infection trial by examining sera collected at 4-, 8- and 13-months post infection. Although three different SELDI instruments were used, nine consistent proteomic features were observed associated with exposure to MAP. Two of the putative serum biomarkers were purified from serum using chromatographic methods and were identified as transthyretin and alpha haemoglobin by tandem mass spectrometry. They belong to highly abundant, acute phase reactants in the serum proteome and have also been discovered as serum biomarkers in human inflammatory conditions and cancer. Their relationship to the pathogenesis of Johne's disease remains to be elucidated.


Alpha-1 adrenergic input to solitary nucleus neurones: calcium oscillations, excitation and gastric reflex control.
The nucleus of the solitary tract (NST) processes substantial visceral afferent input and sends divergent projections to a wide array of CNS targets. The NST is essential to the maintenance of behavioural and autonomic homeostasis and is the source, as well as the recipient, of considerable noradrenergic (NE) projections. The significance of NE projections from the NST to other CNS regions has long been appreciated, but the nature of NE action on NST neurones themselves, especially on the alpha-1 receptor subtype, is controversial. We used a combination of methodologies to establish, systematically, the effects and cellular basis of action of the alpha-1 agonist, phenylephrine (PHE), to control NST neurones responsible for vago-vagal reflex regulation of the stomach. Immunocytochemical and retrograde tracing studies verified that the area postrema, A2, A5, ventrolateral medulla and locus coeruleus regions are sources of catecholaminergic input to the NST. In vivo electrophysiological recordings showed that PHE activates physiologically identified, second-order gastric sensory NST neurones. In vivo microinjection of PHE onto NST neurones caused a significant reduction in gastric tone. Finally, in vitro calcium imaging studies revealed that PHE caused dramatic cytosolic calcium oscillations in NST neurones. These oscillations are probably the result of an interplay between agonist-induced and inositol 1,4,5-trisphosphate (IP(3))-mediated intracellular calcium release and Ca(2+)-ATPase control of intracellular calcium storage pumps. The oscillations persisted even in perfusions of zero calcium-EGTA Krebs solution suggesting that the calcium oscillation is mediated principally by intracellular calcium release-reuptake mechanisms. Cyclical activation of the NST may function to increase the responsiveness of these neurones to incoming afferent input (i.e., elevate the "gain"). An increase in gain of afferent input may cause an amplification of the response part of the reflex and help explain the powerful effects that alpha-1 agonists have in suppressing gastric motility and producing anorexia.


Task cues are quickly updated into working memory as part of their processing: The multiple-cue task-switching paradigm.
Goal-directed behavior requires maintaining the relevant goal in working memory (WM) and using it to guide behavior. The contents of WM should be regulated, so only relevant goals, but not irrelevant ones, are maintained. Computational models suggest that a gate, which is closed by default, separates WM from perceptual input. Transient opening of the gate enables WM updating. Indeed, previous studies show that updating WM with relevant information is controlled, effortful, and slow. In contrast to the above, here we show that WM updating with goal information is faster and more accurate than not updating. A multiple-cue task-switching paradigm is introduced. Participants were presented with a sequence of task cues, followed by a single probe. They needed to respond to each cue using its corresponding key. The cues were presented in red or blue. When the probe appeared, participants had to judge it using the task cued by the most recent red (but not blue) cue. Accordingly, they had to update their WM when the cue appeared in red, but not when it was blue (the color mapping was counterbalanced in Experiment 2). In two experiments, we show that performance in update trials was faster and more accurate than in no-update trials, suggesting that updating, rather than not-updating, is the default mode of operation.


Solution structure of isoform 1 of Roadblock/LC7, a light chain in the dynein complex.
Roadblock/LC7 is a member of a class of dynein light chains involved in regulating the function of the dynein complex. We have determined the three-dimensional structure of isoform 1 of the mouse Roadblock/LC7 cytoplasmic dynein light chain (robl1_mouse) by NMR spectroscopy. In contrast to a previously reported NMR structure of the human homolog with 96% sequence identity (PDB 1TGQ), which showed the protein as a monomer, our results indicate clearly that robl1 exists as a symmetric homodimer. The two beta3-strands pair with each other and form a continuous ten-stranded beta-sheet. The 25-residue alpha2-helix from one subunit packs antiparallel to that of the other subunit on the face of the beta-sheet. Zipper-like hydrophobic contacts between the two helices serve to stabilize the dimer. Through an NMR titration experiment, we localized the site on robl1_mouse that interacts with the 40 residue peptide spanning residues 243 through 282 of IC74-1_rat. These results provide physical evidence for a symmetrical interaction between dimeric robl1 and the two molecules of IC74-1 in the dynein complex.


Changes in taste substances during fermentation of fish sauce and the correlation with protease activity.
Anchovy sauce shows different taste profiles under different fermentation time. The change rules of free amino acids was measured by amino acid analyzer, and other taste substances, such as nucleotides and organic acids in anchovy sauce under different fermentation time were also investigated. Moreover, the correlation between protease activity and taste substances in anchovy sauce fermentation was analyzed by orthogonal partial least squares. Throughout the fermentation process, the taste substances in anchovy sauce increased during early months and then decreased as time increased. The content of amino acid nitrogen, TCA-soluble peptides, 5'-nucleotides (AMP, GMP, IMP) and organic acids (lactic acid, succinic acid) in anchovy sauce increased by 26%, 33%, (45%, 35%, 68%) and (27%, 2%) respectively in comparison with 6 months fermentation. Total amino acid content reached its maximum after 18 months fermentation. Results of electronic tongue demonstrated that the umami of anchovy sauce after 12 months fermentation increased by 17% in comparison with 6 months fermentation. A model correlating changes in protease activity with taste formation suggested that protease activity impacted the content of Ala, Glu, Lys, Asp, Leu, TCA-soluble peptides and succinic acid. This study can provide empirical evidence to guide the efficient processing of anchovy sauce.


Application of thin-layer stick chromatographic identification test methods to drugs contained in preparations in the pharmacopoeia of Japan.
A simple, precise technique was developed for identifying the drugs in preparations containing crude drugs listed in the Pharmacopoeia of Japan using thin-layer stick chromatography (TLSC), which is an advanced version of thin layer chromatography in a cylindrical form. The target component in preparations and crude drugs could be detected easily by dipping the developed chromatographic stick in specific colour reagents or by exposure to ultraviolet rays. This technique was applied to the identification of drugs such as salicylic acid, phenol, acrinol and alkaloids and also vitamins contained in the 36 kinds of preparation.


Proteolytic activities in hypertensive cardiomyopathy of rats.
Two-kidney, one clip Goldblatt hypertension of 2, 4 and 8 weeks duration was induced in 100-g male Wistar-Kyoto rats. Nucleic acid content was determined in the isolated cardiac muscle cells from the left ventricle. The profile for several major proteolytic activities in either isolated cardiac muscle cells or left ventricle preparations was also studied, using [3H]acetyl-casein as substrate. From the soluble fraction of the tissue or cell preparation, a pH 6 proteolytic activity, two forms of calcium-activated protease as well as cathepsin D were identifiable by inhibitor assay or DEAE-cellulose chromatography. From the myofibrillar fraction of the same preparation, two kinds of proteolytic activity were detected at alkaline pH: a phenylmethylsulfonyl fluoride (PMSF) inhibitable activity that was serine protease-like and the other a N-ethylmaleimide (NEM) inhibitable activity that resembled Ca2+-activated protease. At 2 weeks of hypertension, there was a significant increase in the pH 6 proteolytic activity as well as the calcium-activated protease I and the NEM-inhibitable alkaline protease activities, while the other identifiable proteolytic activities remained unchanged. Lysosomal cathepsin D showed a rise in activity only after 8 weeks of hypertension. These results may be related to the development of myocyte necrosis and lysis that occur in this model of hypertensive cardiomyopathy.


Deciphering the role of epigenetic modifications in fatty liver disease: A systematic review.
Fatty liver disease (FLD), primarily nonalcoholic fatty liver disease (NAFLD), is the most common liver disorder that affects a quarter of the global population. NAFLD is a spectrum of disease ranging from simple steatosis to nonalcoholic steatohepatitis, which is associated with increased risk of developing liver cancer. Given that the pathogenic mechanisms of fatty liver remain largely elusive, it is important to further investigate potential underlying mechanisms including epigenetic modifications. Here, we performed a systematic review of human epigenetic studies on FLD presence. Five bibliographic databases were screened until 28 August 2020. We included cross-sectional, case-control and cohort studies in humans that examined the association of epigenetic modifications including global, candidate or epigenome-wide methylation of DNA, noncoding RNAs and histone modifications with FLD. In total 36 articles, based on 33 unique studies, consisting of 12 112 participants met the inclusion criteria. Among these, two recent epigenome-wide association studies conducted among large population-based cohorts have reported the association between cg06690548 (SLC7A11) and FLD. Moreover, several studies have demonstrated the association between microRNAs (miRNAs) and FLD, in which miR-122, miR-34a and miR-192 were recognized as the most relevant miRNAs as biomarkers for FLD. We did not find any studies examining histone modifications in relation to FLD. Cumulative evidence suggests a link between epigenetic mechanisms, specifically DNA methylation and miRNAs, and FLD. Further efforts should investigate the molecular pathways by which these epigenetic markers may regulate FLD and also the potential role of histone modifications in FLD.


Hyperphagia induced by GABAA receptor-mediated inhibition of the nucleus accumbens shell: dependence on intact neural output from the central amygdaloid region.
To investigate the role of corticolimbic input in modulating feeding-related nucleus accumbens (Acb) circuitry, researchers temporarily deactivated sites within the basolateral amygdaloid complex (BLA) or central amygdaloid region (CeA) via GABA(A) agonist (muscimol) infusions and measured feeding responses following muscimol infusions into the Acb shell. Hyperphagia elicited by intra-Acb shell muscimol was not altered by coinfusions of intra-BLA muscimol. In contrast, muscimol infusions into the CeA dose-dependently reduced feeding elicited either by intra-Acb shell GABA(A) receptor stimulation or by food deprivation and produced a syndrome of forepaw treading. Intra-CeA tetrodotoxin infusions also blocked intra-Acb shell muscimol-induced hyperphagia. Hence, feeding elicited by intra-Acb shell GABA(A) receptor stimulation requires intact neural output from the CeA but not the BLA.


The effects of aerosolized STAT1 antisense oligodeoxynucleotides on rat pulmonary fibrosis.
Previous study showed that aerosolized signal transducer and activator of transcription-1 (STAT1) antisense oligodeoxynucleotide (ASON) inhibited the expression of STAT1 and ICAM-1 mRNA and protein in alveolar macrophages (AMs) and decreased the concentrations of TGF-beta, PDGF and TNF-alpha in bronchioalveolar lavage fluid (BALF) in bleomycin (BLM)-induced rat pulmonary fibrosis. Administration of STAT1 ASON ameliorated alveolitis in rat pulmonary fibrosis. However, further investigations are needed to determine whether there is an effect from administration of STAT1 ASON on fibrosis. This study investigated the effect of aerosolized STAT1 ASON on the expressions of inflammatory mediators, hydroxyproline and type I and type III collagen mRNA in BLM-induced rat pulmonary fibrosis. The results showed that STAT1 ASON applied by aerosolization could ameliorate alveolitis and fibrosis, inhibit the expressions of inflammatory mediators, decrease the content of hydroxyproline, and suppress the expressions of type I and type III collagen mRNA in lung tissue in BLM-induced rat pulmonary fibrosis. These results suggest that aerosolized STAT1 ASON might be considered as a promising new strategy in the treatment of pulmonary fibrosis.


Association of eConsult Implementation With Access to Specialist Care in a Large Urban Safety-Net System.
Accessing specialty care continues to be a persistent problem for patients who use safety-net health systems. To address this access barrier, hospital systems have begun to implement electronic referral systems using eConsults, which allow clinicians to submit referral requests to specialty clinics electronically and enable specialty reviewers to resolve referrals, if appropriate, through electronic dialogue without an in-person visit. Measure the effect of implementing an eConsult program on access to specialty care. Using an interrupted time series design with data from 2016 to 2020, this study analyzed 50 260 referral requests submitted during the year before and the year after eConsult implementation at 19 New York City Health + Hospitals (NYC H+H) specialty clinics that spanned 7 NYC H+H hospital facilities and 6 unique specialties. Referral request was submitted to a specialty clinic in the year following eConsult implementation. Main outcomes included the fraction of referral requests resolved without an in-person visit following eConsult implementation; and, among requests triaged to have an in-person visit, the fraction of referrals with a successfully scheduled appointment, mean wait time to a specialty appointment, and the fraction of referral requests with a completed specialty visit. Changes associated with eConsult implementation were estimated using multivariate linear regression adjusting for patient age, gender, and specialty clinic fixed effects. Across 19 NYC H+H specialty clinics, 26 731 referral requests were submitted in the year before and 23 529 referrals were submitted in the year after eConsult implementation. Following eConsult implementation, 13% of all requests were resolved electronically. Among requests requiring a follow-up visit, the fraction with an appointment successfully scheduled increased by 15.8%, from 66.5% to 82.3% (P < .001). The mean time to an appointment decreased from 61.0 days pre-eConsult to 54.1 days post-eConsult, an adjusted 8.2-day shorter wait time (or 13.3% reduction) following eConsult adoption (P < .001). The percentage of referrals with a completed follow-up visit with a specialist within 90 days of the request did not change (38.4% vs 37.9%, P = .07). Changes in outcomes were mitigated during months when most clinics underwent an electronic health record transition after implementing eConsult. In this quality improvement study, implementation of eConsults at a large multi-specialty safety-net system was associated with improvements in appointment scheduling rates and wait times. Despite an additional electronic health record transition, eConsults are a promising health care delivery tool for increasing access to specialty care.


Changes in the postsynaptic density with long-term potentiation in the dentate gyrus.
The present study documents alterations in the size of the postsynaptic density (PSD) of synapses formed by entorhinal afferents with granule cell dendritic spines with long-term potentiation (LTP). These changes appear early and persist for at least 60 minutes after LTP-inducing conditioning stimulation. Each animal received test and conditioning stimulation typical of LTP paradigms. Electron microscopic preparation of the dentate gyri from each animal followed conventional procedures. PSD trace lengths of identified asymmetric synaptic profiles were measured. The total PSD length for four categories of synaptic profiles was determined for each third of the molecular layer. PSD surface area per unit volume of tissue (SV) was then computed from these data. Statistical analysis of the SV data used multivariate analysis of variance. PSD surface area per synapse was also estimated. Total PSD surface area per unit volume does not change significantly throughout the entire molecular layer with LTP-inducing conditioning stimulation. However, in the activated portion of the molecular layer, total PSD surface area per unit volume tends to increase with conditioning stimulation. In the middle third of the molecular layer, total PSD surface area per unit volume associated with the concave spine profiles increases significantly while there is a statistically significant decrease in total PSD SV associated with the nonconcave spine profiles. The PSD surface area per synapse also increases markedly. Since it seems that there is an interconversion of spine synapses from nonconcave to concave with LTP (Desmond and Levy: J. Comp. Neurol. In press, '86a), these data suggest that potentiated synapses have larger responses because, in part, they have larger neurotransmitter receptive regions.


Real-world effectiveness of fulvestrant monotherapy as first endocrine treatment in patients with metastatic breast cancer.
Fulvestrant monotherapy is approved for postmenopausal women with hormone receptor-positive, metastatic breast cancer (MBC) who progressed following antiendocrine therapy, or those with hormone receptor-positive, human epidermal receptor 2-negative advanced breast cancer (BC) not previously treated with endocrine therapy (ET). However, real-world data are lacking. Retrospective reviews of 10 United States community oncology practices identified patients diagnosed with MBC between 1 January 2011 and 31 December 2015 who received fulvestrant as the first ET, either as initial therapy for metastatic disease or after progression following one line of chemotherapy. Endpoints were progression-free survival (PFS) and overall survival (OS). Patients were classified as ET-naïve or by relapse status following adjuvant ET ("early" recurrence during or ≤12 months of completing adjuvant ET, or "late" >12 months after completing adjuvant ET). Outcomes were evaluated using Kaplan-Meier methods. Among 121 patients, median PFS (95% confidence interval) was 8.3 months (4.8-12.3) for early relapse, 15.4 months (10.2-21.2) for late relapse, and 18.7 months (10.1-20.8) among ET-naïve patients (P = .018). Median OS was 39.8 months (25.0-55.1) for early relapse and 61.4 months (47.1-61.4) for late relapse, but was not reached (NR; 55.6-NR) for ET-naïve patients (P = .002). Fulvestrant monotherapy as the first ET after MBC diagnosis demonstrates PFS comparable to clinical study results; outcomes appeared better in patients without prior ET exposure and in patients with disease recurrence >12 months following adjuvant ET. These findings support fulvestrant monotherapy in patients with hormone receptor-positive MBC.


Auditory brainstem response test results in normal hearing adolescents with subjective tinnitus.
The objective of the study was to analyze the auditory brainstem response (ABR) test results of adolescents with normal hearing threshold who have subjective tinnitus in an effort to determine the probable site of origin of tinnitus. Among the patients who visited the outpatient clinic of the Department of Otolaryngology at our tertiary hospital from January 2016 to December 2019, adolescents aged 13-18 years with the chief complaint of unilateral subjective tinnitus and pure tone audiometry (PTA) within 25 dB HL were enrolled and retrospectively reviewed. The ABR test parameters (amplitudes and latencies of waves I, III, and V and interpeak latencies [IPLs] of waves I-III, III-V, and I-V) were analyzed and compared between tinnitus ears and contralateral ears without tinnitus. Study participants were divided into the chronic tinnitus (tinnitus duration ≥6 months) and non-chronic tinnitus (tinnitus duration <6 months) groups, and the difference between the two groups was analyzed. Ten adolescents were included in the study, and their ABR test results were reviewed. IPL III-V was significantly prolonged in tinnitus ears compared to non-tinnitus ears (p = 0.035). Although other parameters were found to be statistically non-significant, there was preponderance in ABR wave I amplitude; it was smaller in tinnitus ears of chronic tinnitus adolescents than in those of non-chronic tinnitus adolescents (p = 0.114). The probable site of origin of tinnitus in adolescents with normal hearing might be in the upper brainstem of the auditory pathway. Further analysis of ABR test results in adolescents with tinnitus and normal hearing can help clarify the pathophysiology of tinnitus in adolescents.


Dielectrophoretic spectra of single cells determined by feedback-controlled levitation.
In this paper we have utilized the principle of dielectrophoresis (DEP) to develop an apparatus to stably levitate single biological cells using a digital feedback control scheme. Using this apparatus, the positive DEP spectra of both Canola plant protoplast and ligament fibroblast cells have been measured over a wide range of frequencies (1 kHz to 50 MHz) and suspending medium conductivities (11-800 muS/cm). The experimental data thus obtained have been interpreted in terms of a simple spherical cell model. Furthermore, utilizing such a model, we have shown that various cellular parameters of interest can be readily obtained from the measured DEP levitation spectrum. Specifically, the effective membrane capacitance of single cells has been determined. Values of 0.47 +/- 0.03 muF/cm2 for Canola protoplasts and 1.52 +/- 0.26 muF/cm2 for ligament fibroblasts thus obtained are consistent with those determined by other existing electrical methods.


Simulated microgravity disrupts intestinal homeostasis and increases colitis susceptibility.
The immune systems can be altered by spaceflight in many aspects, but microgravity-related mucosal immune changes and its clinical significance have not been well studied. The purpose of this study was to investigate whether simulated microgravity influences the intestinal homeostasis and increases the susceptibility to colon inflammation. The hindlimb unloading (HU) mouse model was used to simulate the microgravity condition. Three percent dextran sulfate sodium (DSS) was given to mice to induce colitis. Compared to ground control (Ctrl) mice, the HU ones revealed an impaired intestinal homeostasis and increased susceptibility to DSS-induced colitis. This includes an early-onset, 4-fold expansion of segmented filamentous bacteria (SFB), more than 2-fold decrease in regulatory T (Treg) cell numbers and IL-10 production, ∼2-fold increase in colonic IL-1β expression, 2-fold increase in circulating neutrophils, and colonic neutrophil infiltration. The application of antibiotics ameliorated the Treg and IL-10 reductions but did not significantly dampen neutrophilia and elevated expression of colonic IL-1β. These results indicate that the intestinal microflora and innate immune system both respond to simulated microgravity and together, contribute to the proinflammatory shift in the gut microenvironment. The data also emphasize the necessity for evaluating the susceptibility to inflammatory bowel diseases (IBDs) in distant space travels.


Effects of lipopolysaccharide on the biliary excretion of bile acids and organic anions in rats.
Lipopolysaccharide is known to be a cause of cholestasis associated with sepsis. It has also recently been reported to down-regulate the basolateral and canalicular transporters. The aim of the present study was to examine simultaneously the effect of lipopolysaccharide on the biliary excretion of typical substrates of bile salt export pump and multidrug resistance protein 2 in vivo, and the effect of lipopolysaccharide on the amount of these transporters. After intravenous administration of O127:B8-derived lipopolysaccharide (2.5 mg/kg), the biliary excretion of taurocholate and various organic anions was studied, and the protein levels of bile salt export pump and multidrug resistance protein 2 in the crude liver membrane was determined by western blot analysis. Lipopolysaccharide decreased the biliary excretion of tracer amounts of taurocholate, leukotriene C4, taurolithocholate-3-sulfate and temocapril without affecting bile flow. The biliary excretion of high doses of taurocholate and sulfobromophthalein was markedly inhibited by lipopolysaccharide. Lipopolysaccharide decreased bile salt export pump levels in the liver plasma membrane fraction to 48% of control rats, and markedly decreased multidrug resistance protein 2 levels to 17% of control rats. These findings support the hypothesis that down-regulation of the canalicular transporters by lipopolysaccharide causes the impairment of the biliary excretion of bile acids and organic anions in cholestasis of sepsis prior to the decrease of bile flow.


Major depression and subclinical (grade 2) hypothyroidism.
Subclinical hypothyroidism (SCH) has been reported to occur in patients with a variety of affective syndromes. However, the clinical correlates of SCH in patients with major depression have received limited attention. We therefore examined demographic, clinical and treatment response variables in a cohort of patients with unipolar, nonpsychotic major depression with and without SCH. Of 139 subjects, 19 had SCH defined as an elevated basal TSH with normal circulating levels of T3 and T4. Major depression with SCH differed from that without SCH by the presence of a concurrent panic disorder and a poorer antidepressant response.


The Use of Infant Pulmonary Function Tests in the Diagnosis of Neuroendocrine Cell Hyperplasia of Infancy.
Infant pulmonary function tests (iPFTs) in subjects with neuroendocrine cell hyperplasia of infancy (NEHI) have demonstrated substantial expiratory airflow obstruction and air trapping. Can indices from iPFTs be used in the diagnosis of NEHI? This is an observational case-control study evaluating iPFT results from a registry of patients assessed at the Hadassah Hebrew University Medical Center between 2008 and 2018. iPFTs results in infants with NEHI were compared to two disease control infant groups (infants evaluated for recurrent wheezing and infants evaluated due to prematurity) and a spirometry control group of infants with normal expiratory airflow, using the Kruskal-Wallis test. Receiver operating characteristic (ROC) curves were used to assess the diagnostic accuracy of iPFT indices. We evaluated iPFT data in 481 infants (15, NEHI; 292, wheezing; 128, premature; and 46, spirometry control group). Infants with NEHI had significantly increased trapped air volumes (median functional residual capacity measured with infant whole-body plethysmography [FRCpleth] was 199% predicted; median ratio of residual volume to total lung capacity was 59% predicted) when compared with results in all evaluated groups of infants (P < .001), including multiple pairwise comparisons. Airflow limitation was demonstrated in infants with NEHI when compared with the infants in the spirometry control group but was similar to the two disease control groups. FRCpleth had the best discriminatory ability for NEHI diagnosis, with an FRCpleth ≥ 150% predicted demonstrating a ROC of 0.91 (95% CI, 0.82-1.00), sensitivity of 86.7% (95% CI, 59.5%-98.3%), and specificity of 95.5% (95% CI, 93.2%-97.3%). Findings on iPFTs of markedly increased air trapping, out of proportion to the degree of airflow limitation, are characteristic of infants with NEHI. iPFT results demonstrating an FRCpleth ≥ 150% predicted are highly specific for NEHI and may aid in early diagnosis. Further research is required to confirm these findings in a prospective cohort and to understand the pathophysiologic explanation for these findings.


Antileishmanial effect of free and encapsulated sinefungin against Leishmania donovani infections in BALB/c mice.
Sinefungin, a C-nucleoside antibiotic, displays a high antiparasitic action. The effect of free and microencapsulated sinefungin was compared on BALB/c mice infected with Leishmania donovani; the encapsulated form proved more effective by one order of magnitude.


An adaptive and altruistic PSO-based deep feature selection method for Pneumonia detection from Chest X-rays.
Pneumonia is one of the major reasons for child mortality especially in income-deprived regions of the world. Although it can be detected and treated with very less sophisticated instruments and medication, Pneumonia detection still remains a major concern in developing countries. Computer-aided based diagnosis (CAD) systems can be used in such countries due to their lower operating costs than professional medical experts. In this paper, we propose a CAD system for Pneumonia detection from Chest X-rays, using the concepts of deep learning and a meta-heuristic algorithm. We first extract deep features from the pre-trained ResNet50, fine-tuned on a target Pneumonia dataset. Then, we propose a feature selection technique based on particle swarm optimization (PSO), which is modified using a memory-based adaptation parameter, and enriched by incorporating an altruistic behavior into the agents. We name our feature selection method as adaptive and altruistic PSO (AAPSO). The proposed method successfully eliminates non-informative features obtained from the ResNet50 model, thereby improving the Pneumonia detection ability of the overall framework. Extensive experimentation and thorough analysis on a publicly available Pneumonia dataset establish the superiority of the proposed method over several other frameworks used for Pneumonia detection. Apart from Pneumonia detection, AAPSO is further evaluated on some standard UCI datasets, gene expression datasets for cancer prediction and a COVID-19 prediction dataset. The overall results are satisfactory, thereby confirming the usefulness of AAPSO in dealing with varied real-life problems. The supporting source codes of this work can be found at https://github.com/rishavpramanik/AAPSO.


Towards an understanding of corporate image in the hospitality industry East Java, Indonesia.
The purpose of this study is to determine how the perceptions and understandings of hotel managers in East Java to improve the corporate image as a hotel marketing strategy. Research respondents are managers who work in the hospitality industry. A total of ninety-six stars hotel in East Java were assessed. Each star hotel has nine managers so that the study population is 621 managers. The research sample of 232 managers. The sampling technique is simple random sampling. Statistical techniques used Confirmatory Factor Analysis (CFA) and descriptive analysis of mean and mode. This research is related to the success of the hospitality marketing strategy; therefore, it is urgent to conduct an in-depth investigation of the corporate image of the hotel. The results showed that managers who work in the hotel industry better understand the corporate image of the hotel at an psychological level to maintain trust in customers. Trust becomes part of the psychological managers in implementing corporate image practices in the hospitality industry.


Classification staging systems on clinical and radiographic features of inverted sinonasal papilloma: A case report.
Inverted sinonasal papilloma is an infrequent tumor that mostly affects the elder group of 40-50 yr. This tumor is distinguished from other sinonasal tumors by three characteristics: a high rate of recurrence, carcinomatous changes, and a high potential for local destruction. In 40% of cases of inverted sinonasal papilloma showed an association with the human papillomavirus and considered as the main etiological agent. Here, we present a case of a 36-year-old male presented with pus discharge from the right upper back teeth region in the past 1 year. Correlating with clinical, radiographical features, a diagnosis of the Inverted sinonasal papilloma.


Reinnervation of denervated Meissner corpuscles: a sequential histologic study in the monkey following fasicular nerve repair.
The mechanism by which an axon regenerating into a fingertip becomes a functioning sensory end organ was investigated with light and electron microscopic evaluation of Meissner corpuscle (MC) morphology following nerve division and fascicular repair in the monkey. Sequential histologic analysis of the fingertip biopsies demonstrated degeneration of the MC followed by reinnervation of the MC by the regenerating axons. There was subsequent reversal of the degeneration process. Electron microscopy confirmed the reinnervation of the degenrated MC. There was no evidence of MC regeneration de novo.


[Isolation of flagellin antigens of salmonellae by the method of ultracentrifugation and their use for preparation of erythrocytic H-diagnostic agents].
Flagellar preparations were obtained from 6 salmonellae strains by differential ultracentrifugation; they were characterized by morphological, immunochemical, and serological tests. The results of investigations showed that the preparations possessed high serological activity; somatic antigen admixture was insignificant. Flagellins extracted from the flagellae were used to prepare erythrocytic H-diagnostic agents. The results of their use in the examination of sera of healthy persons, and of those suffering from typhoid fever and salmonellosis indicated the expediency of using passive H-hemagglutination for diagnostic purposes.


Pathologic and Immunophenotypic Characterization of Syncytial Giant Cell Variant of Pediatric Hepatocellular Carcinoma. A Distinct Subtype.
Hepatocellular carcinoma (HCC) in pediatrics has a uniformly poor prognosis. Complete surgical resection or liver transplantation remain the only curative options. In contrast to adult HCC, literature on pediatric HCC is sparse and a majority of the distinct subtypes are undefined with regards to their histology, immunohistochemistry and prognosis. Two infants, one with biliary atresia and another with transaldolase deficiency, underwent living donor liver transplants. Explant-liver histopathology revealed tumor with diffuse neoplastic syncytial giant cell pattern. Immunophenotypic characterization highlighted expression of epithelial cell adhesion molecule, alpha fetoprotein and metallothionein. HCC with syncytial giant cells variant can occur in infants with underlying liver disease, specifically in our experience, with biliary atresia and another with transaldolase deficiency.


Specific reduction of plasma large, light low-density lipoprotein by a bile acid sequestering resin, cholebine (MCI-196) in type II hyperlipoproteinemia.
The effect of a bile acid sequestrant, cholebine (3 g/day), on plasma lipoprotein subfractions was investigated in 16 patients with type II hyperlipoproteinemia. Activities of low density lipoprotein (LDL)-receptor and activities of lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) were assayed to address the mechanism of cholebine-induced changes in plasma lipoprotein subfractions. Twelve weeks of treatment with cholebine reduced plasma levels of total cholesterol (TC) and LDL-cholesterol (C) by 8.3 +/- 8.1% (mean +/- S.D.) and 14.4 +/- 11.9%, respectively (P < 0.001), but did not affect plasma levels of high density lipoprotein (HDL)-C. Cholebine significantly reduced plasma levels of LDL1-C (1.019 < d < 1.045) by 22.9 +/- 18.9% (P < 0.001) but did not affect plasma levels of very low density lipoprotein (VLDL)-C, intermediate density lipoprotein (IDL)-C, LDL2-C (1.045 < d < 1.063), HDL2-C, and HDL3-C (d > 1.125). Gradient polyacrylamide gel electrophoresis (PAGE) revealed that cholebine reduced large LDL in plasma but had almost no effects on small LDL and HDL subfractions. Cholebine did not alter the activities of LCAT and CETP. LDL-receptor activities of cultured lymphocytes negatively correlated with the reduction in plasma levels of LDL-C (r = -0.500, P < 0.05), IDL-C (r = -0.581, P < 0.02), and LDL1-C (r = -0.610, P < 0.01), respectively. Thus, cholebine seems to reduce further the plasma levels of IDL and large, light LDL in patients with lower LDL-receptor activities. We conclude that cholebine only reduces plasma levels of large, light LDL. This may be due to the stimulation of hepatic LDL-receptor activity.


Gene regulation and evolution in the chorion locus of Bombyx mori. Structural and developmental characterization of four eggshell genes and their flanking DNA regions.
We report on the detailed structural and developmental characterization of four chorion genes and a truncated pseudogene located within a 9.5 X 10(3) base chromosomal segment. These genes belong to the A and B multigene families and, like previously characterized moth chorion genes, are arranged in tightly linked pairs, which are divergently transcribed (A/B.L11 and A/B.L12). On the basis of their high degree of sequence divergence, the A genes define two distinct subfamilies, while the more homologous B genes represent different copies of the same gene type. The A.L11 and B.L11 introns are much longer, in each case because of a single inserted DNA segment that is missing from A.L12 or B.L12. The 2.1 X 10(3) base insertion in A.L11 is the first retrovirus-like transposable element characterized in Bombyx mori. The very short 5' flanking sequences of A/B.L11 and A/B.L12 (277 and 276 base-pairs) are distinct as shown by hybridization but both recur in additional chorion gene pairs, forming two respective classes that are expressed during distinctly different developmental periods. The divergently transcribed genes of each pair, which border the same 5' flanking sequence, are expressed co-ordinately, during the same developmental period. Detailed comparisons of the 5' flanking regions, and of the corresponding region of the Drosophila s15-1 chorion gene, revealed numerous, very short sequence elements that are shared. One such element, T-C-A-C-G-T, is also associated with all five sequenced Drosophila chorion genes. Some elements are repeated in a dyad symmetrical pattern, i.e. are associated with each of the two genes in a pair, while others, including T-C-A-C-G-T, occur only once per 5' flanking region, and, if functionally important, would presumably act bi-directionally on both genes of the pair.


Effects of resistance added on aerobic training on autonomic function in cardiac patients.
Autonomic imbalance in patients with chronic heart failure (CHF) and cardiovascular diseases (CVD) is characterized by reduced parasympathetic and enhanced sympathetic activity. Aerobic exercise improves autonomic function in patients with CHF and CVD. However, little is known about the effects of resistance training (RT) on cardiac autonomic function. Therefore, we aimed to investigate the effects of RT added on aerobic training on autonomic function in patients with CHF and CVD. The relevant clinical trials were searched in PubMed, Physiotherapy evidence Database (PEDro, Science Direct and Google Scholar databases using the following keywords, "resistance or strength training", "chronic heart failure", "coronary artery disease", "myocardial infarction", "hypertension", "cardiovascular disease", "heart rate variability (HRV)", "heart rate recovery (HRR)", "muscle sympathetic nerve activity (MSNA)", and "autonomic function". Twelve articles with 323 subjects were eligible to be evaluated. The outcome measures included HRV, HRR, and MSNA. There were seven studies on CHF, two on CAD, and three studies on hypertension. Meta-analysis of all the studies showed that combined RT and aerobic training decreased MSNA significantly in patients with CHF and CAD (mean difference: -3.796; CI: -6.779 to 0.813; p=0.013; I2 =93.5%). No study evaluated the effects of RT or combined training on HRR. We could not find sufficient data about the effects of RT alone on HRV and HRR, but the results showed that combined RT and aerobic training improved MSNA in patients with CHF and CAD, significantly. Further studies with similar methodological principles on the same patient population are needed.


Twice-yearly exams unnecessary for patients taking quetiapine.
To determine the necessity for the heightened level of monitoring for cataract development in patients taking quetiapine (Seroquel, AstraZeneca Pharmaceuticals, Wilmington, Delaware) dictated by the Physicians' Desk Reference. Also, to explore the possibility of cataractogenesis because of quetiapine therapy. Observational case series. Data were garnered from a series of 80 case reports collected at the National Registry of Drug-Induced Ocular Side Effects (Portland, Oregon). The World Health Organization (WHO) causality assessment guidelines were used to assess the relationship between quetiapine and cataractogenesis. There were 34 reports of cataracts associated with quetiapine therapy. Average age was 44 years with 23 females and 11 males studied. Average duration of therapy was 29.3 weeks on standard doses. Cataractogenesis secondary to quetiapine is "unlikely" by WHO guidelines. This probably makes it unnecessary to require biannual ophthalmic examinations as routine eye examinations are sufficient to screen for this condition.


Sequences of avian reovirus M1, M2 and M3 genes and predicted structure/function of the encoded mu proteins.
We report the first sequence analysis of the entire complement of M-class genome segments of an avian reovirus (ARV). We analyzed the M1, M2 and M3 genome segment sequences, and sequences of the corresponding muA, muB and muNS proteins, of two virus strains, ARV138 and ARV176. The ARV M1 genes were 2,283 nucleotides in length and predicted to encode muA proteins of 732 residues. Alignment of the homologous mammalian reovirus (MRV) mu2 and ARV muA proteins revealed a relatively low overall amino acid identity ( approximately 30%), although several highly conserved regions were identified that may contribute to conserved structural and/or functional properties of this minor core protein (i.e. the MRV mu2 protein is an NTPase and a putative RNA-dependent RNA polymerase cofactor). The ARV M2 genes were 2158 nucleotides in length, encoding predicted muB major outer capsid proteins of 676 amino acids, more than 30 amino acids shorter than the homologous MRV mu1 proteins. In spite of the difference in size, the ARV/MRV muB/mu1 proteins were more conserved than any of the homologous proteins encoded by other M- or S-class genome segments, exhibiting percent amino acid identities of approximately 45%. The conserved regions included the residues involved in the maturation- and entry- specific proteolytic cleavages that occur in the MRV mu1 protein. Notably missing was a region recently implicated in MRV mu1 stabilization and in forming "hub and spokes" complexes in the MRV outer capsid. The ARV M3 genes were 1996 nucleotides in length and predicted to encode a muNS non-structural protein of 635 amino acids, significantly shorter than the homologous MRV muNS protein, which is attributed to several substantial deletions in the aligned ARV muNS proteins. Alignments of the ARV and MRV muNS proteins revealed a low overall amino acid identity ( approximately 25%), although several regions were relatively conserved.


Success of stapedectomy performed by residents.
A retrospective study of 240 stapedectomies for otosclerosis performed in a teaching department during the last 10 years was done. The results and complications in patients operated on by residents and faculty were compared. Strict criteria for evaluating the surgical outcome were used. "Satisfactory" results obtained by residents during their entire training (79 per cent) were significantly poorer (P greater than 0.05) than those achieved by the faculty (90 per cent). In the second period of residency, however, the residents' success rate (89 per cent) was equal to that of the faculty. There was no statistically significant difference in the complication rate between residents and faculty. Two essential conditions are responsible for good stapedectomy results by residents: experience with sufficient numbers of patients requiring middle-ear surgery (including otosclerosis and chronic middle-ear disease) and close supervision by the faculty in the operating room.