Self-management practice, associated factors and its relationship with health literacy and patient activation among multi-morbid COPD patients from rural Nepal.
Chronic Obstructive Pulmonary Disease (COPD) is a progressive and debilitating condition that affects individuals' quality of life. COPD self-management and supports provided by carers is key to the quality of life people living with COPD. Health literacy (HL) and Patient Activation (PA) are main drivers of self-management practices (SMPs). However, their contribution remains to be fully explored. This study aimed to examine the level of self-management practices, and the relationship with socio-demographic factors, HL and PA among multi-morbid COPD patients from rural Nepal. This is a cross-sectional study conducted between July 2018 and January 2019. Patients completed a survey, including Self-management Practices questionnaire (SMPQ), five domains of the Health Literacy Questionnaire (HLQ), and Patient Activation Measure (PAM). The relationship between HL, PAM, and SMPs was examined using univariate statistics. Multivariable analysis was conducted to identify the factors associated with SMPs. A total of 238 patients responded to the study. The mean score of SMPQ was 45.31(SD = 9.00). The HLQ and PAM scores were positively correlated with the total score of SMPQ. Low level of SMPs were found to be positively associated with being uneducated (β = - 0.43, p = .001), having a low family income (β = - 5.22, p = .002), and, negatively associated with the presence of more than one co-morbidity (β = 3.58, p = 0.007) after controlling for other socio-demographic variables in the multivariable analysis. The overall SMPs among this sample of Nepalese with COPD were low. Our findings highlight the need to implement a self-management intervention program involving patient activation and health literacy-focused activities for COPD, creating a support system for patients from low-income families and low education.


Who regenerates the kidney tubule?
The kidney possesses profound regenerative potential and in some cases can recover completely 'restitutio at integrum' following an acute kidney injury (AKI). Emerging evidence strongly suggests that sometimes repair is incomplete, however, and, in this situation, an episode of AKI leads to future chronic kidney disease (CKD). Understanding the tubular response after AKI will shed light on the relationship between incomplete repair and future risk of CKD. The first repair phase after AKI is characterized by robust proliferation of epithelial cells in the proximal tubule. The exact source of these proliferating cells has been a source of controversy for the last decade. While nearly everyone now agrees that reparative cells arise within the proximal tubule, there is disagreement about whether all surviving cells possess an equivalent repair capacity through dedifferentiation, or alternatively whether a pre-existing intratubular stem cell population [so-called scattered tubular cells (STC)] is responsible for repair. This review will summarize the evidence on both sides of this issue and will discuss very recent genetic fate-tracing data that strongly points against the existence of intratubular stem cells but rather indicates that terminally differentiated proximal tubule epithelial cells undergo dedifferentiation upon injury to replace lost neighboring tubular epithelial cells through proliferative self-duplication. This new evidence includes data clearly indicating that STC are not committed tubular stem cells but instead represent individual dedifferentiated tubular epithelial cells that transiently express putative stem cell markers.


A novel system for rapid and cost-effective production of detection and diagnostic reagents of West Nile virus in plants.
The threat of West Nile virus (WNV) epidemics necessitates the development of a technology platform that can produce reagents to support detection and diagnosis rapidly and inexpensively. A plant expression system is attractive for protein production due to its low-cost and high-scalability nature and its ability to make appropriate posttranslational modifications. Here, we investigated the feasibility of using plants to produce two WNV detection and diagnostic reagents to address the current cost and scalability issues. We demonstrated that WNV DIII antigen and E16 monoclonal antibody are rapidly produced at high levels in two plant species and are easily purified. Furthermore, they are effective in identifying WNV and in detecting human IgM response to WNV infection. E16 mAb does not cross-react with other flaviviruses, therefore, is valuable for improving diagnostic accuracy. This study provides a proof of principle for using plants as a robust and economical system to produce diagnostic reagents for arboviruses.


Duplication of accessory phallic urethra (urethra triplication) in the female, signaling mesenchymal interruptions of the cloacal membrane as a cause for sagittal urethral duplications.
A specimen of accessory phallic urethra duplication (triplication) in a 32.5-week gestation female was studied histologically. The specimen demonstrated an anterior "phallic urethra" ending inside a penoclitoral organ in a megalourethra-like dilatation with a narrow epispadiac meatus and "anterior urethrocutaneous fistula" and a posterior canal opening with the anal canal. With histology suggestive of a split persistent urogenital sinus, correlation to normal development strongly suggests an error in the formation of the cloacal membrane and developing superficial cloaca at 26 to 29 days' ovulation age (2 to 4 mm), causing an isolated interruption of the membrane by mesenchyme, which by participating in the growth of the early cloaca may extend as far as the vaginal orifice later. Differences in number, position, and size of such mesenchymal interruptions can explain other duplications and triplications and offer a single alternative for the many current theories of pathogenesis, none of which are compatible with new insights in normal development.


Impact and applicability of pharmacogenomics in rheumatology: an integrated analysis.
Rheumatology medications are often associated with adverse drug reactions (ADRs) or inadequate response (IR). Pharmacogenomics may be a solution, but there is limited knowledge of its potential utility within rheumatology. We analysed medication changes and pharmacogenomically actionable prescriptions for all adult rheumatology outpatient encounters at our medical centre between 10/2012-12/2018. Three sources defined pharmacogenomic actionability: FDA labels, Clinical Pharmacogenetics Implementation Consortium guidelines, and our institutionally-deliverable pharmacogenomic clinical decision support (CDS) summaries. A subset of patients (validation cohort) had previously undergone broad, preemptive pharmacogenomic testing within other clinics but results were unavailable within rheumatology. We assessed the occurrence of specific pharmacogenomic ADRs/IRs in this group. From 174,834 prescribing events, 6300/7761 patients (81%) had clinically actionable pharmacogenomic drug prescriptions (i.e. institutional CDS summaries would have been deployable if testing had been done). Using more conservative standards (pharmacogenomically actionable by ≥2 guidance bodies), 4158/7761 (54%) patient prescriptions could have been impacted. The greatest proportions of potentially impacted rheumatologic prescriptions were for tramadol (47%), allopurinol (21%), azathioprine (17%) and celecoxib (8%). Among our validation cohort (94 previously-genotyped patients), 29 (31%) patients had a pharmacogenomic genotype that would have cautioned possible ADRs/IRs for ≥1 medication. Four patients actually suffered ADRs/IRs that would have been predicted by preemptive genotyping. Pharmacogenomic genotyping could inform prescribing for the majority of rheumatology patients and may prevent a subset of ADRs/IRs. These findings justify prospective evaluation of pharmacogenomic testing including assessment of cost-effectiveness in selected rheumatology populations to further understand impact on therapy-related toxicities and treatment outcomes.


Spatio-temporal variation in malaria transmission intensity in five agro-ecosystems in Mvomero district, Tanzania.
In Africa, malaria is predominantly a rural disease where agriculture forms the backbone of the economy. Various agro-ecosystems and crop production systems have an impact on mosquito productivity, and hence malaria transmission intensity. This study was carried out to determine spatial and temporal variations in anopheline mosquito population and malaria transmission intensity in five villages, representing different agro-ecosystems in Mvomero district, Tanzania, so as to provide baseline information for malaria interventions. The agro-ecosystems consisted of irrigated sugarcane, flooding rice irrigation, non-flooding rice irrigation, wet savannah and dry savannah. In each setting, adult mosquitoes were sampled monthly using light traps recommended by the Centers for Disease Control and Prevention (CDC) from August 2004 to July 2005. A total of 35,702 female mosquitoes were collected. Anopheles gambiae sensu lato was the most abundant (58.9%) mosquito species. An. funestus accounted for 12.0% of the mosquitoes collected. There was a substantial village to village variation and seasonality in the density of Anopheles mosquito population, with peaks in May towards the end of the warm and rainy season. Significantly larger numbers of anophelines were collected from traditional flooding rice irrigation ecosystem (70.7%) than in non-flooding rice irrigation (8.6%), sugarcane (7.0%), wet savannah (7.3%) and dry savannah (6.4%). The overall sporozoite rates for An. gambiae and An. funestus were 3.4% and 2.3%, respectively. The combined overall sporozoite rate (An. gambiae+An. funestus) was 3.2%. The mean annual entomological inoculation rate (EIR) for An. gambiae s.l. was 728 infective bites per person per year and this was significantly higher in traditional flooding rice irrigation (1351) than in other agro-ecosystems. The highest EIRs for An. gambiae s.l. and An. funestus were observed during May 2005 (long rainy season) and December 2004 (short rainy season), respectively. The findings support the evidence that malaria transmission risk varies even between neighbouring villages and is influenced by agro-ecosystems. This study therefore, demonstrates the need to generate spatial and temporal data on transmission intensity on smaller scales taking into consideration agro-ecosystems that will identify area-specific transmission intensity to guide targeted control of malaria operations.


[Perioperative prevalence of epiretinal membranes in eyes with senile cataract].
Results from epidemiologic studies suggest that cataract extraction is a risk-factor for the formation of epiretinal membranes (EM). 250 consecutive eyes which underwent uneventful phakoemulsification with implantation of a posterior chamber intraocular lens were examined within two weeks prior and an two weeks after surgery for the presence of epiretinal membranes. Cellophane macular reflex (CMR) was distinguished from macular pucker (MP). We found an increase in the prevalence of epiretinal membranes from preoperatively 12/250 (4.8%) to post-operatively 33/250 (13.2%). The prevalence of CMR increased from 8/250 (3.2%) to 27/250 (10.8%). The prevalence of MP remained almost the same 4/250 (1.6%) prior and 6/250 (2.4%) after surgery. Increased prevalence of epiretinal membranes following cataract extraction observed in epidemiological studies can be explained by easier detection of such membranes in pseudophakic eyes where the observer gets a clear view of the fundus. Therefore it is questionable whether uneventful extracapsular cataract extraction can induce the formation of epiretinal membranes.


A Monte Carlo based three-dimensional dose reconstruction method derived from portal dose images.
The verification of intensity-modulated radiation therapy (IMRT) is necessary for adequate quality control of the treatment. Pretreatment verification may trace the possible differences between the planned dose and the actual dose delivered to the patient. To estimate the impact of differences between planned and delivered photon beams, a three-dimensional (3-D) dose verification method has been developed that reconstructs the dose inside a phantom. The pretreatment procedure is based on portal dose images measured with an electronic portal imaging device (EPID) of the separate beams, without the phantom in the beam and a 3-D dose calculation engine based on the Monte Carlo calculation. Measured gray scale portal images are converted into portal dose images. From these images the lateral scattered dose in the EPID is subtracted and the image is converted into energy fluence. Subsequently, a phase-space distribution is sampled from the energy fluence and a 3-D dose calculation in a phantom is started based on a Monte Carlo dose engine. The reconstruction model is compared to film and ionization chamber measurements for various field sizes. The reconstruction algorithm is also tested for an IMRT plan using 10 MV photons delivered to a phantom and measured using films at several depths in the phantom. Depth dose curves for both 6 and 10 MV photons are reconstructed with a maximum error generally smaller than 1% at depths larger than the buildup region, and smaller than 2% for the off-axis profiles, excluding the penumbra region. The absolute dose values are reconstructed to within 1.5% for square field sizes ranging from 5 to 20 cm width. For the IMRT plan, the dose was reconstructed and compared to the dose distribution with film using the gamma evaluation, with a 3% and 3 mm criterion. 99% of the pixels inside the irradiated field had a gamma value smaller than one. The absolute dose at the isocenter agreed to within 1% with the dose measured with an ionization chamber. It can be concluded that our new dose reconstruction algorithm is able to reconstruct the 3-D dose distribution in phantoms with a high accuracy. This result is obtained by combining portal dose images measured prior to treatment with an accurate dose calculation engine.


Investigation of phase-contrast magnetic resonance imaging underestimation of turbulent flow through the aortic valve phantom: experimental and computational study using lattice Boltzmann method.
The accuracy of phase-contrast magnetic resonance imaging (PC-MRI) measurement is investigated using a computational fluid dynamics (CFD) model with the objective to determine the magnitude of the flow underestimation due to turbulence behind a narrowed valve in a phantom experiment. An acrylic stationary flow phantom is used with three insertable plates mimicking aortic valvular stenoses of varying degrees. Positive and negative horizontal fluxes are measured at equidistant slices using standard PC-MRI sequences by 1.5T and 3T systems. The CFD model is based on the 3D lattice Boltzmann method (LBM). The experimental and simulated data are compared using the Bland-Altman-derived limits of agreement. Based on the LBM results, the turbulence is quantified and confronted with the level of flow underestimation. LBM gives comparable results to PC-MRI for valves up to moderate stenosis on both field strengths. The flow magnitude through a severely stenotic valve was underestimated due to signal void in the regions of turbulent flow behind the valve, consistently with the level of quantified turbulence intensity. Flow measured by PC-MRI is affected by noise and turbulence. LBM can simulate turbulent flow efficiently and accurately, it has therefore the potential to improve clinical interpretation of PC-MRI.


Ultra pH-sensitive polymeric nanovesicles co-deliver doxorubicin and navitoclax for synergetic therapy of endometrial carcinoma.
Endometrial carcinoma is a kind of epithelial malignant tumor occurring in the endometrium with high incidence (nearly 200 000 people are diagnosed every year). At present, surgery is the main strategy for the treatment of endometrial carcinoma. However, in special cases such as serous, clear cell carcinoma and postoperative recurrences, chemotherapy is still essential and indispensable. The combined chemotherapy schemes of cisplatin, paclitaxel and doxorubicin (DOX) in clinical applications are unfortunately complicated and easily cause severe side effects. In recent years, with the development of nanotechnology, the targeted delivery of multi-chemotherapeutic drugs shows great advantages in reducing side effects and improving anticancer efficacy. Here, an ultra pH-sensitive nanovesicle based on polyethylene glycol-poly(diisopropylamino)ethyl methacrylate (PEG-PDPA) was fabricated. A chemotherapeutic drug (doxorubicin) and an anti-apoptotic Bcl-2 inhibitor (navitoclax) were co-encapsulated in the hydrophilic cavity and hydrophobic membrane of the vesicle, respectively. After accumulating in the tumor tissue via the enhanced permeability and retention (EPR) effect, the nanovesicles could be efficiently diffused in tumor cells by endocytosis and then rapidly release drugs in response to the lysosomal acidic environment, leading to an enhanced tumor-killing effect based on the combination therapy between DOX and the Bcl-2 inhibitor. The drug co-delivery system and microenvironment-triggered drug release may provide an efficient strategy for endometrial carcinoma therapy.


[Computed tomography and conventional x-ray diagnosis of interstitial lung diseases].
One hundred and sixty-four patients with pulmonary fibrosis were examined by CT and by conventional radiological methods. Sixty patients had asbestosis, thirty-nine silicosis, forty sarcoidosis and twenty-five had idiopathic pulmonary fibrosis. CT is superior to conventional radiography in evaluating interstitial pulmonary changes, particularly of the pleura and the lung parenchyma. Areas of fibrosis and of emphysema can be demonstrated without any overlap. In sixty-nine patients there were some findings which could only be demonstrated by CT. In asbestosis, silicosis and sarcoidosis the CT classification of the lung parenchyma which we have suggested produces significantly better correlation with vital capacity than can be achieved from conventional chest films, according to the guide-lines of the I.L.O.


Noncontact detection of ultrasonic waves using fiber optic Sagnac interferometer.
This paper describes a fiber optic sensor suitable for noncontact detection of ultrasonic waves. This sensor is based on the fiber optic Sagnac interferometer, which has a path-matched configuration and does not require active stabilization. Quadrature phase bias between two interfering laser beams in the Sagnac loop is applied by controlling the birefringence using a fiber polarization controller. A stable quadrature phase bias can be confirmed by observing the interferometer output according to the change of phase bias. Additional signal processing is not needed for the detection of ultrasonic waves using the Sagnac interferometer. Ultrasonic oscillations produced by conventional ultrasonic piezoelectric transducers were successfully detected, and the performance of this interferometer was investigated by a power spectrum analysis of the output signal. Based on the validation of the fiber optic Sagnac interferometer, noncontact detection of laser-generated surface waves was performed. The configured Sagnac interferometer is very effective for the detection of small displacement with high frequency, such as ultrasonic waves used in conventional nondestructive testing (NDT).


Molecular characterization of Mycobacterium bovis isolates from Ethiopian cattle.
Bovine Tuberculosis (BTB) is a widespread and endemic disease of cattle in Ethiopia. Information relating to genotypic characteristics of Mycobacterium bovis strains affecting the cattle population in Ethiopia is limited. We carried out molecular characterization of M. bovis strains isolated from BTB infected cattle using the spoligotyping technique. The relationship between distribution of spoligotypes and recorded variables was also investigated. A new approach that can numerically reflect the degree of genetic polymorphism in a M. bovis population was also developed. The study was conducted from July 2006 to January 2007 in cattle slaughtered at five representative abattoirs in Ethiopia. Forty-five M. bovis isolates were obtained from 406 pathologic tissue specimens collected from 337 carcasses with lesions compatible with BTB. Twelve spoligotypes were identified from 34 distinct strains; with SB1176 as a dominant spoligotype (41.2% of the isolates) followed by SB0133 (14.7%). Comparison of spoligotypes with an M. bovis global database http://www.mbovis.org revealed six new spoligotypes which were subsequently registered in the database with international identification codes of SB1517, SB1518, SB1519, SB1520, SB1521 and SB1522. The majority of strains were obtained from cattle slaughtered at Addis Ababa abattoir. On the basis of the Spoligotype Evolutionary Index, SEI (a numeric expression approach to make standardized comparison of spoligotype evolution), M. bovis isolates from Ethiopia were relatively more heterogeneous (SEI = 3.2) compared to isolates from other countries. This might be attributed to extensive livestock movement linked to trading or seasonal migration, high degree of livestock mingling, and also diversities of the country's agricultural and livestock ecosystems, in addition to lack of disease control measures that led to high infection prevalence. Multiple spoligotype infection was recorded in nine (50%) of infected carcasses and this may indicate the prevailing high degree of super infection. This study provided molecular evidence for the widespread distribution of M. bovis in the cattle population in Ethiopia. It also demonstrated a relatively high degree of genetic polymorphism of the isolates. Further molecular investigation of M. bovis strains in humans and other domestic animals is recommended in order to elucidate the zoonotic importance as well as reservoirs and pattern of transmission among various hosts.


Development and evaluation of a molecular viability assay for Pneumocystis carinii.
Despite recent declines in incidence, Pneumocystis carinii pneumonia (PCP) remains the most commonly occurring opportunistic illness among persons with AIDS in the United States. While P. carinii DNA has been detected in patient respiratory specimens and in air samples collected from various indoor environments housing PCP patients, the viability of these organisms is unknown. For this reason, we have developed and evaluated a molecular viability assay for P. carinii. This method is based upon the detection of P. carinii mRNA by a reverse transcription-PCR that employs specific primers from a member of the heat shock protein 70 family. Under optimal assay conditions, these primers were capable of detecting as few as 100 viable trophozoites as determined by ethidium bromide staining, while no signal was obtained from 10(6) trophozoites killed by heat, desiccation, or UV radiation. This assay was also capable of distinguishing P. carinii from other common fungi present in the air. Therefore, this molecular viability assay may be useful in conjunction with standard bioaerosol collection devices and procedures for the detection of viable P. carinii collected from various indoor environments. It may also be useful in confirming the presence of viable trophozoites in respiratory specimens collected by noninvasive techniques from putatively infected individuals.


Sensitivity of rat renal luminal and contraluminal sulfate transport systems to DIDS.
4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) was tested as an inhibitor of the sulfate transport systems in rat renal brush border and basolateral membrane vesicles. Na+-driven sulfate uptake into brush border membrane vesicles was half-maximally inhibited at 350 microM DIDS. Proton gradient-driven sulfate uptake into basolateral membrane vesicles was competitively inhibited by DIDS with a Ki of 2.4 microM. The Km for delta pH-driven sulfate uptake was 5.4 microM. The different affinities of the sulfate transport systems for DIDS correlated with different substrate specificities. The luminal transport system accepted a smaller range of anions than the contraluminal system and did not operate as a Na+-independent anion exchanger. After treatment of basolateral membrane vesicles with 50 microM DIDS at pH 8.4 for 30 min, an irreversible inhibition of sulfate uptake was observed. With brush border membranes, only a small irreversible inhibition was obtained. Lack of inhibition after treatment of basolateral membranes with DIDS at pH 6.4 indicated that DIDS reacted with deprotonated amino groups of the transport protein. Sulfate was protected from the irreversible inhibition by DIDS. Sodium-driven uptake of L-glutamate and methylsuccinate into basolateral membrane vesicles was not irreversibly inhibited by DIDS, indicating a specific action of DIDS on the contraluminal sulfate transport system. Irreversible and substrate-protectable inhibition of sulfate transport render DIDS suitable for future affinity labeling studies on the sulfate transport system in basolateral membranes.


Transformer-based light-evoked retinal spiking activity prediction.
Retinal visual prosthetic devices aim to restore vision via electrical stimulation delivered on the retina. While a number of devices have been commercially available, the stimulation strategies applied have not met the expectations of end-users. These stimulation strategies involve the neurons being activated based on their spatial properties, regardless of their functions, which may lead to lower visual acuity. The ability to predict light-evoked neural activities thus becomes crucial for the development of a retinal prosthetic device with better visual acuity. In addition to temporal nonlinearity, the spatial relationship between the 2-dimensional light stimulus and the spiking activity of neuron populations is the main barrier to accurate predictions. Recent advances in deep learning offer a possible alternative for neural activity prediction tasks. With proven performance on nonlinear sequential data in fields such as natural language processing and computer vision, the emerging transformer model may be adapted to predict neural activities. In this study, we built and evaluated a deep learning model based on the transformer to explore its predictive capacity in light-evoked retinal spikes. Our preliminary results show that the model is possible to achieve good performance in this task. The high versatility of deep learning models may allow us to make retinal activity predictions in more complex physiological environments and potentially enhance the visual acuity of retinal prosthetic devices in the future by enabling us to anticipate the desired neural responses to electrical stimuli.


Gender differences in risk factors for violence: an examination of the predictive validity of the Structured Assessment of Violence Risk in Youth.
The research literature on predicting violence is particularly lacking in specifying risk factors for violence in adolescent girls. The recently developed Structured Assessment of Violence Risk in Youth [SAVRY; Borum et al., 2006] shows promise as it is empirically derived and incorporates dynamic factors in its assessment of risk. To date, there exists little information attesting to the reliability and validity of the SAVRY, and few investigations of the SAVRY's utility across gender. This study investigated the SAVRY in a sample of 144 high-risk adolescents (80 males and 64 females), focusing on gender discrepancies in the predictive utility of the measure. Results indicate that the SAVRY moderately predicts violent and non-violent reoffending in the entire sample, and also suggest that the SAVRY operates comparably across gender. Although not precluding the existence of gender-specific domains of risk, current results suggest that validated risk factors in boys hold relevance for the prediction of violence and delinquency in girls.


A fast and powerful W-test for pairwise epistasis testing.
Epistasis plays an essential role in the development of complex diseases. Interaction methods face common challenge of seeking a balance between persistent power, model complexity, computation efficiency, and validity of identified bio-markers. We introduce a novel W-test to identify pairwise epistasis effect, which measures the distributional difference between cases and controls through a combined log odds ratio. The test is model-free, fast, and inherits a Chi-squared distribution with data adaptive degrees of freedom. No permutation is needed to obtain the P-values. Simulation studies demonstrated that the W-test is more powerful in low frequency variants environment than alternative methods, which are the Chi-squared test, logistic regression and multifactor-dimensionality reduction (MDR). In two independent real bipolar disorder genome-wide associations (GWAS) datasets, the W-test identified significant interactions pairs that can be replicated, including SLIT3-CENPN, SLIT3-TMEM132D, CNTNAP2-NDST4 and CNTCAP2-RTN4R The genes in the pairs play central roles in neurotransmission and synapse formation. A majority of the identified loci are undiscoverable by main effect and are low frequency variants. The proposed method offers a powerful alternative tool for mapping the genetic puzzle underlying complex disorders.


Urethral inflammation in male chimpanzees caused by ureaplasmas and Chlamydia trachomatis.
Specimens from men with acute non-gonococcal urethritis were tested to determine their microbial content and then given intra-urethrally to male chimpanzees. Two animals received ureaplasmas only and one became infected. The second did so when given a different strain. Both developed a polymorphonuclear leukocyte (PMNL) response. Two chimpanzees received a mixture of ureaplasmas and Chlamydia trachomatis and there was a suggestion that the ureaplasmas delayed or suppressed the chlamydial response. The latter, that is urethral infection with a pronounced PMNL response, was most clearly seen in a chimpanzee given C. trachomatis only. No inflammation was detected in two chimpanzees acting as controls. Three of five chimpanzees given ureaplasmas genitally, and one that had them endogenously, had them transiently in the oropharynx about 2 weeks later. The occurrence of ureaplasmas in the conjunctiva of three chimpanzees inoculated at this site was also transient and without inflammation. The possibility that Mycoplasma genitalium might have been in the inocula and caused urethral inflammation was discounted largely because no animal had antibody to this mycoplasma.


Taxation of unprocessed sugar or sugar-added foods for reducing their consumption and preventing obesity or other adverse health outcomes.
Global prevalence of overweight and obesity are alarming. For tackling this public health problem, preventive public health and policy actions are urgently needed. Some countries implemented food taxes in the past and some were subsequently abolished. Some countries, such as Norway, Hungary, Denmark, Bermuda, Dominica, St. Vincent and the Grenadines, and the Navajo Nation (USA), specifically implemented taxes on unprocessed sugar and sugar-added foods. These taxes on unprocessed sugar and sugar-added foods are fiscal policy interventions, implemented to decrease their consumption and in turn reduce adverse health-related, economic and social effects associated with these food products. To assess the effects of taxation of unprocessed sugar or sugar-added foods in the general population on the consumption of unprocessed sugar or sugar-added foods, the prevalence and incidence of overweight and obesity, and the prevalence and incidence of other diet-related health outcomes. We searched CENTRAL, Cochrane Database of Systematic Reviews, MEDLINE, Embase and 15 other databases and trials registers on 12 September 2019. We handsearched the reference list of all records of included studies, searched websites of international organisations and institutions, and contacted review advisory group members to identify planned, ongoing or unpublished studies. We included studies with the following populations: children (0 to 17 years) and adults (18 years or older) from any country and setting. Exclusion applied to studies with specific subgroups, such as people with any disease who were overweight or obese as a side-effect of the disease. The review included studies with taxes on or artificial increases of selling prices for unprocessed sugar or food products that contain added sugar (e.g. sweets, ice cream, confectionery, and bakery products), or both, as intervention, regardless of the taxation level or price increase. In line with Cochrane Effective Practice and Organisation of Care (EPOC) criteria, we included randomised controlled trials (RCTs), cluster-randomised controlled trials (cRCTs), non-randomised controlled trials (nRCTs), controlled before-after (CBA) studies, and interrupted time series (ITS) studies. We included controlled studies with more than one intervention or control site and ITS studies with a clearly defined intervention time and at least three data points before and three after the intervention. Our primary outcomes were consumption of unprocessed sugar or sugar-added foods, energy intake, overweight, and obesity. Our secondary outcomes were substitution and diet, expenditure, demand, and other health outcomes. Two review authors independently screened all eligible records for inclusion, assessed the risk of bias, and performed data extraction.Two review authors independently assessed the certainty of the evidence using the GRADE approach. We retrieved a total of 24,454 records. After deduplicating records, 18,767 records remained for title and abstract screening. Of 11 potentially relevant studies, we included one ITS study with 40,210 household-level observations from the Hungarian Household Budget and Living Conditions Survey. The baseline ranged from January 2008 to August 2011, the intervention was implemented on September 2011, and follow-up was until December 2012 (16 months). The intervention was a tax - the so-called 'Hungarian public health product tax' - on sugar-added foods, including selected foods exceeding a specific sugar threshold value. The intervention includes co-interventions: the taxation of sugar-sweetened beverages (SSBs) and of foods high in salt or caffeine. The study provides evidence on the effect of taxing foods exceeding a specific sugar threshold value on the consumption of sugar-added foods. After implementation of the Hungarian public health product tax, the mean consumption of taxed sugar-added foods (measured in units of kg) decreased by 4.0% (standardised mean difference (SMD) -0.040, 95% confidence interval (CI) -0.07 to -0.01; very low-certainty evidence). The study was at low risk of bias in terms of performance bias, detection bias and reporting bias, with the shape of effect pre-specified and the intervention unlikely to have any effect on data collection. The study was at unclear risk of attrition bias and at high risk in terms of other bias and the independence of the intervention. We rated the certainty of the evidence as very low for the primary and secondary outcomes. The Hungarian public health product tax included a tax on sugar-added foods but did not include a tax on unprocessed sugar. We did not find eligible studies reporting on the taxation of unprocessed sugar. No studies reported on the primary outcomes of consumption of unprocessed sugar, energy intake, overweight, and obesity. No studies reported on the secondary outcomes of substitution and diet, demand, and other health outcomes. No studies reported on differential effects across population subgroups. We could not perform meta-analyses or pool study results. There was very limited evidence and the certainty of the evidence was very low. Despite the reported reduction in consumption of taxed sugar-added foods, we are uncertain whether taxing unprocessed sugar or sugar-added foods has an effect on reducing their consumption and preventing obesity or other adverse health outcomes. Further robustly conducted studies are required to draw concrete conclusions on the effectiveness of taxing unprocessed sugar or sugar-added foods for reducing their consumption and preventing obesity or other adverse health outcomes.


Physical activity for pediatric cancer survivors: a systematic review of randomized controlled trials.
To collate evidence and evaluate the effects of physical activity interventions on physical activity level among pediatric cancer survivors who had completed active cancer treatment. Relevant published studies were identified in May 2020 via five databases and reference checking. Searches were limited to randomized controlled trials or controlled clinical trials, published in English involving pediatric cancer survivors aged 18 years or below. Interventions were related to promote physical activity among the survivors. Included studies were assessed using the revised version of the Cochrane's Risk of Bias Tool. Eight randomized controlled trials (620 pediatric cancer survivors and 53 caregivers of pediatric cancer survivors) were included. All studies investigated interventions for pediatric cancer survivors to increase their physical activity level. The interventions used varied across the eight included studies: three mHealth-medical and public health practice supported by mobile devices; two eHealth-the use of information and communication technologies to improve health care; two adventure-based training; and one educational program. Measures of physical activity level also varied: five used various objective measurements (i.e., accelerometer, pedometer, multisensory activity monitor); three used different self-reported questionnaires. Owing to high variability of the interventions and measures, it was impossible to perform meta-analysis. Overall, eHealth and mHealth interventions showed effectiveness and feasibility to promote physical activity among pediatric cancer survivors. eHealth and mHealth interventions appear to be increasingly important strategies to promote physical activity among pediatric cancer survivors. Future larger-scale studies using a core-set of assessment tools are warranted to further promote regular physical activity in pediatric cancer survivors.


Cytotoxicity of KDEL-terminated ricin toxins correlates with distribution of the KDEL receptor in the Golgi.
DNAs encoding ricin toxin A chain (RTA), with or without a C-terminal endoplasmic reticulum retention signal KDEL, were subcloned into pGEX2T bacterial expression plasmid. After transformation of JM105 E. coli cells and induction with isopropylthio-beta-galactoside (IPTG), fusion proteins were bound to an immobilized glutathione matrix and recombinant ricin A chains released with thrombin. Both recombinant wild-type RTA and RTA with KDEL had immunological reactivity and catalytic activity indistinguishable from plant RTA. The bacterial RTA products reassociated with plant ricin B chain (RTB) similarly to plant RTA. Cell cytotoxicities were measured on seven cell lines for each A-chain and heterodimer. Although KDEL sequences enhanced cytotoxicity in most cases, significant variability was observed. In each case, addition of KDEL enhanced A-chain cytotoxicity more than holotoxin cytotoxicity. Three cell lines showed reduced KDEL enhancement of both RTA and ricin cytotoxicity. The concentration of KDEL receptor was examined on each cell line by immunofluorescence microscopy with an antireceptor monoclonal antibody. Differences in sensitivity to KDEL-containing toxins correlated with altered distribution of KDEL receptor between endoplasmic reticulum (ER) and Golgi compartments.


Expression of sphingosine 1-phosphate receptors in the rat dorsal root ganglia and defined single isolated sensory neurons.
Previously, we demonstrated that sphingosine 1-phosphate (S1P) increased the excitability of small-diameter sensory neurons, in part, through activation of S1P receptor 1 (S1PR(1)), suggesting that other S1PRs can modulate neuronal excitability. Therefore, studies were undertaken to establish the expression profiles of S1PRs in the intact dorsal root ganglion (DRG) and in defined single isolated sensory neurons. To determine mRNA expression of S1PRs in the DRG, SYBR green quantitative PCR (qPCR) was used. To determine the expression of S1PR mRNAs in single neurons of defined diameters, a preamplification protocol utilizing Taqman primer and probes was used to enhance the sensitivity of detection. The preamplification protocol also permitted detection of mRNA for two hallmark neuronal receptor/ion channels, TRPV1 and P(2)X(3). Expression profiles of S1PR mRNA isolated from lung and brain were used as positive control tissues. In the intact DRG, the order of expression of S1PRs was S1PR(3)>>R(1)≈R(2)>R(5)≈R(4). In the single neurons, the expression of S1PRs was quite variable with some neurons expressing all five subtypes, whereas some expressing only one subtype. In contrast to the DRG, S1PR(1) was the highest expressing subtype in 10 of the 18 small-, medium-, and large-diameter sensory neurons. S1PR(1) was the second highest expressor in -50% of those remaining neurons. Overall, in the single neurons, the order of expression was S1PR(1)>>R(3)≈R(5)>R(4)>R(2). The results obtained from the single defined neurons are consistent with our previous findings wherein S1PR(1) plays a prominent but not exclusive role in the enhancement of neuronal excitability.


[Evaluation of the stability of pertussis vaccine OCO-3 standard].
The evaluation of the immunogenic activity and residual toxicity of the National Standard of pertussis vaccine (OCO-3) was carried out. As shown by observations lasting for a period of 25 years, the preparation possesses stable immunogenicity and its toxicity remained unchanged, which makes it possible to use OCO-3 for the routine control of the pertussis component of commercial lots of adsorbed DPT vaccine.


Angiogenic phenotype induced by basic fibroblast growth factor transfection in brain microvascular endothelial cells.
Basic fibroblast growth factor (bFGF) is expressed in the vascular endothelium of human brain tumors. To investigate the biological consequences of a possible autocrine modality of microvascular endothelial cell activation by endogenous bFGF in these tumors, mouse brain microvascular endothelial cells were stably transfected with a retroviral expression vector harboring a human bFGF cDNA. When grown on tissue culture plastic, bFGF-transfected clones show a transformed morphology and increased saturation density. bFGF-transfectants have an invasive behavior when seeded on three-dimensional fibrin gel and originate endothelial cell sprouts when embedded within fibrin. Also, bFGF-transfected cells undergo morphogenetic organization and produce a complex network of branching cord-like structures connecting foci of infiltrating cells when seeded on Matrigel, a laminin-rich extracellular matrix material. In contrast, parental and mock-transfected cells do not invade fibrin gels nor organize on Matrigel. These findings demonstrate that bFGF overexpression induces an angiogenic phenotype in brain microvascular endothelial cells characterized by an invasive behavior and morphogenic potential. They support the notion that neovascularization of brain tumors can be triggered by stimuli that induce vascular endothelium to produce its own autocrine factor(s).


[Dana Point: what is new in the diagnosis of pulmonary hypertension?].
The hemodynamic definition of pulmonary hypertension (PH) has not been evidence-based. Normal individuals have a pulmonary pressure of about 14 mm Hg. The respective normal range is up to 20 mm Hg. It was decided in Dana Point 2008 to introduce new thresholds for mean pulmonary arterial pressure with < 21 mm Hg = normal, 21 - 25 mm Hg = borderline, and > 25 mm Hg = manifest PH. Correspondingly, echocardiographic systolic tricuspid regurgitant velocity thresholds will be < 2.5 m/s = normal, 2.5 - 2.8 = borderline, > 2.8 m/s = manifest PH. Confirmation by right heart catheterization is mandatory as many false positive readings and patients with undetected diastolic filling disturbance can be expected, based on current literature. During exercise, PA pressure is strongly age-dependent. Therefore exercise values were left out of the definition. Cardiac magnetic resonance imaging (MRI) is expected to gain importance for routine examinations in the next years, although currently right heart catheterization regains territory. Genetic analysis of BMPR2 gene represents an important option for patients with idiopathic PAH and their relatives. However, it is not suitable for screening in the general population. Follow-up examinations in patients with targeted therapy are very important for the definition of specific therapy goals in order to improve prognosis. Future IN VIVO tests of vessel properties and right heart function could improve our understanding and the development of new therapies.


Manual therapy provided by physical therapists in a hospital-based setting: a retrospective analysis.
The purpose of this study was to compare outcomes, complications, and hospital disposition in a cohort of patients hospitalized for low back pain who receive physical therapist (PT)-administered manual therapy (mobilization and manipulation) vs those who do not receive manual therapy. The study was a retrospective data collection that used the Nationwide Inpatient Sample. Seventy-five patients hospitalized with low back pain who receive PT-administered manual therapy were matched using specific covariates with patients with low back who did not receive manual therapy. Bivariate analyses and regression modeling were used to determine comparisons between the 2 groups. Findings indicated that patients who received PT manual therapy had significantly longer lengths of hospital stay (P < .01) and had significantly higher inflation-adjusted costs of care (P < .01). After regression modeling and adjustments for covariates, findings for length of stay were still higher in the PT manual therapy group (P < .01), but costs were significantly lower for this group (P < .01). There were minimal findings of complications. Of 106 340 patients admitted for low back pain originally queried, only 75 patients (0.07%) received manual therapy, a markedly small number of patients. Outcomes may be reflective of the low effect size of manual therapy in a hospital setting or the inability to control for referral and hospital care patterns, thus disallowing appropriate matching.


Germline mutations in pediatric cancer cohort with mixed-ancestry Mexicans.
Childhood cancer is one of the primary causes of disease-related death in 5- to 14-year-old children and currently no prevention strategies exist to reduce the incidence of this disease. Childhood cancer has a larger hereditary component compared with cancer in adults. Few genetic studies have been conducted on children with cancer. Additionally, Latin American populations are underrepresented in genomic studies compared with other populations. Therefore, the aim of this study is to analyze germline mutations in a group of mixed-ancestry Mexican pediatric patients with solid and hematological cancers. We analyzed genetic variants from 40 Mexican childhood cancer patients and their relatives. DNA from saliva or blood samples was used for whole-exome sequencing. All variants were identified following GATK best practices. We found that six patients (15%) were carriers of germline mutations in CDKN2A, CHEK2, DICER1, FANCA, MSH6, MUTYH, NF1, and SBDS cancer predisposition genes, and additional new variants predicted to be deleterious by in silico algorithms. A population genetics analysis detected five components consistent with the demographic models assumed for modern mixed-ancestry Mexicans. This report identifies potential genetic risk factors and provides a better understanding of the underlying mechanisms of childhood cancer in this population.


Malignant epignathus teratoma.
A baby boy who had a left facial mass detected on antenatal ultrasound was delivered by Caesarian section after foetal distress was detected. Imaging investigations by plain radiographs and MRI showed a large mass with calcifications, soft tissue, fat and fluid components. A total surgical excision was perfomed and histology examination showed teratoma with no malignant features. Two weeks postoperatively, there was rapid recurrence of the tumour with intracranial involvement and obstructive hydrocephalus shown on MRI. The tumour was inoperable at surgery and the baby subsequently died at 5 weeks of life. This case describes the clinical course and imaging features of a neonatal epignathus teratoma with malignant and aggressive features.


Manipulating Eryptosis of Human Red Blood Cells: A Novel Antimalarial Strategy?
Malaria is a major global health burden, affecting over 200 million people worldwide. Resistance against all currently available antimalarial drugs is a growing threat, and represents a major and long-standing obstacle to malaria eradication. Like many intracellular pathogens, Plasmodium parasites manipulate host cell signaling pathways, in particular programmed cell death pathways. Interference with apoptotic pathways by malaria parasites is documented in the mosquito and human liver stages of infection, but little is known about this phenomenon in the erythrocytic stages. Although mature erythrocytes have lost all organelles, they display a form of programmed cell death termed eryptosis. Numerous features of eryptosis resemble those of nucleated cell apoptosis, including surface exposure of phosphatidylserine, cell shrinkage and membrane ruffling. Upon invasion, Plasmodium parasites induce significant stress to the host erythrocyte, while delaying the onset of eryptosis. Many eryptotic inducers appear to have a beneficial effect on the course of malaria infection in murine models, but major gaps remain in our understanding of the underlying molecular mechanisms. All currently available antimalarial drugs have parasite-encoded targets, which facilitates the emergence of resistance through selection of mutations that prevent drug-target binding. Identifying host cell factors that play a key role in parasite survival will provide new perspectives for host-directed anti-malarial chemotherapy. This review focuses on the interrelationship between Plasmodium falciparum and the eryptosis of its host erythrocyte. We summarize the current knowledge in this area, highlight the different schools of thoughts and existing gaps in knowledge, and discuss future perspectives for host-directed therapies in the context of antimalarial drug discovery.


An adverse event trigger tool in dentistry: a new methodology for measuring harm in the dental office.
There is a dearth of knowledge about the type and frequency of adverse events (AEs) in dentistry. Current approaches to obtaining information rely on reviews of randomly selected records, which may not be the most efficient or effective methodology. Inspired by the Institute for Healthcare Improvement's (IHI) global and outpatient trigger tools, which identifies records with characteristics ("triggers") that are associated with AEs, the authors created the dental clinic trigger tool. The triggers included procedures for incision and drainage, failed implants and selected treatment patterns. The authors ran the trigger tool against six months of electronic health records data and compared its performance with that of a review of 50 randomly selected patient records. In total, 315 records were triggered, 158 (50 percent) of which were positive for one or more AEs; 17 (34 percent) of the 50 randomly selected records were positive for at least one AE. The authors assigned each AE an IHI severity ranking. Most AEs caused temporary harm, but nine were considered to have caused permanent harm according to a modified IHI severity ranking. The study results demonstrate the promise of a directed records review approach, as the dental clinic trigger tool was more effective in identifying AEs than was a review of randomly selected records. All dental practices should proactively monitor the safety of the care they provide. Use of the trigger tool will help make this process more efficient and effective.


Childhood cancer survivors' knowledge about their past diagnosis and treatment: Childhood Cancer Survivor Study.
Adult survivors of childhood cancer are at risk for adverse effects later in life but may have limited access to information about their diagnosis and treatment. This knowledge is necessary to motivate them to seek medical follow-up and to report essential history to health care professionals. To assess knowledge of adult survivors of childhood cancer about their primary cancer diagnosis and associated therapies. Cross-sectional survey of 635 consecutive survivors (approximately 5%) drawn from 12 156 participants 18 years or older participating in the Childhood Cancer Survivor Study (a multiinstitutional cohort of individuals diagnosed between January 1, 1970, and December 31,1986, at an age <21 years, who had survived 5 years from diagnosis). The survey assessed knowledge of their cancer diagnosis and associated therapies in a 3- to 5-minute telephone questionnaire. Responses were compared with medical record data for accuracy, sensitivity, specificity, and positive and negative predictive value. Overall, 72% accurately reported their diagnosis with precision and 19% were accurate but not precise. Individuals with central nervous system (CNS) cancer (odds ratio, 5.1; 95% confidence interval, 2.6-9.9) and neuroblastoma (OR, 4.2; 95% CI, 1.8-9.6) were more likely not to know their cancer diagnosis. Participants' accuracy rates for reporting their treatment history was 94% for chemotherapy, 89% for radiation, and 93% for splenectomy. Among those who received anthracyclines, only 30% recalled receiving daunorubicin therapy and 52% recalled receiving doxorubicin therapy, even after prompting with the drugs' names. Among those who received radiotherapy, 70% recalled the site of radiotherapy. History of receiving a written medical summary, attending a long-term follow-up clinic, and anxiety about late effects were not associated with greater knowledge. Important knowledge deficits exist among adult survivors of childhood cancer regarding basic aspects of their diagnosis and treatment. Such deficits could impair survivors' ability to seek and receive appropriate long-term follow-up care.


High-temperature pyrolysis/gas chromatography/isotope ratio mass spectrometry: simultaneous measurement of the stable isotopes of oxygen and carbon in cellulose.
Stable isotope analysis of cellulose is an increasingly important aspect of ecological and palaeoenvironmental research. Since these techniques are very costly, any methodological development which can provide simultaneous measurement of stable carbon and oxygen isotope ratios in cellulose deserves further exploration. A large number (3074) of tree-ring α-cellulose samples are used to compare the stable carbon isotope ratios (δ(13)C) produced by high-temperature (1400°C) pyrolysis/gas chromatography (GC)/isotope ratio mass spectrometry (IRMS) with those produced by combustion GC/IRMS. Although the two data sets are very strongly correlated, the pyrolysis results display reduced variance and are strongly biased towards the mean. The low carbon isotope ratios of tree-ring cellulose during the last century, reflecting anthropogenic disturbance of atmospheric carbon dioxide, are thus overestimated. The likely explanation is that a proportion of the oxygen atoms are bonding with residual carbon in the reaction chamber to form carbon monoxide. The 'pyrolysis adjustment', proposed here, is based on combusting a stratified sub-sample of the pyrolysis results, across the full range of carbon isotope ratios, and using the paired results to define a regression equation that can be used to adjust all the pyrolysis measurements. In this study, subsamples of 30 combustion measurements produced adjusted chronologies statistically indistinguishable from those produced by combusting every sample. This methodology allows simultaneous measurement of the stable isotopes of carbon and oxygen using high-temperature pyrolysis, reducing the amount of sample required and the analytical costs of measuring them separately.


Ewing's sarcoma: evaluation of chemotherapy in 17 cases.
Seventeen patients with Ewing's sarcoma were divided into 3 groups according to treatment. Ten patients were treated with complete chemotherapy; 9 with VACA protocol, composed of vincristine, actinomycin-D, cyclophosphamide and doxorubicin, and the remaining 1 with T-11 protocol. Four were given incomplete VACA protocol, and another 3 received no chemotherapy. Clinical results were evaluated in the three treatment subgroups described above. All patients without systematic chemotherapy died from lung metastasis within 1 year of the initial treatment. Three of 4 patients who were given incomplete chemotherapy died after a mean survival period of 17.7 months, and one developed cancerous pleuritis after 38 months. In the group receiving complete systematic chemotherapy, 5 of 10 patients are alive, and 2 have been disease-free for more than 3 years. Distant metastasis is likely when viable cells persist at the site of the primary tumor, even if the tumor size has been considerably reduced by preoperative chemotherapy. Therefore, immediate initiation of intensive chemotherapy and maintenance for the full course of therapy can improve the prognosis of Ewing's sarcoma.


Essential hypertension: abnormal renal vascular and endocrine responses to a mild psychological stimulus.
We have assessed the influence of a mild emotional stimulus on arterial blood pressure, heart rate, renal blood flow, plasma renin activity (PRA), and plasma aldosterone concentration in 24 normal subjects, eight of who had a parent with hypertension, and in 15 patients with essential hypertension. A nonverbal IQ test, Raven's Progressive Matrices, was employed as the stimulus. In 11 of the 15 hypertensives, arterial blood pressure rose transiently by 7 mm Hg or more, but in only three of 16 normal subjects (x2 = 7.23, p less than 0.01). Transient moderate increases in heart rate were also more common in the hypertensives (p less than 0.01). Renal blood flow rose in 11 of 16 normal subjects and fell in each of the 15 patients with essential hypertension (x2 = 15.1; p less than 0.005). As opposed to the transient changes in arterial pressure and heart rate, the fall in renal perfusion was sustained. The PRA fell in 10 of the 16 normal subjects with a negative family history and rose in 14 of 15 patients with essential hypertension (p less than 0.005). Changes in plasma angiotensin II concentration and in plasma aldosterone were in accord with the changes in PRA, but plasma cortisol did not change. Both the renal vascular response and the change in PRA were intermediate in normal subjects in whom family history was positive for hypertension. For the entire group of 39 subjects there was statistically significant agreement between the direction of the renal vascular response and the directional change in PRA: renal blood flow rose when PRA fell and fell when PRA rose (p less than 0.005). We conclude that there is an abnormality in the control of both the renal circulation and of renin release in patients with essential hypertension in response to psychological provocation, and that a similar process is present in some normotensive subjects whose parents have hypertension.


Endovenous laser ablation of varicose veins: review of current technologies and clinical outcome.
Symptomatic lower extremity varicose veins represent one of the most common vascular conditions in the adult population. Associated symptoms ranged from mild conditions such as fatigue, heaviness, and itching to more serious conditions such as skin discoloration and leg ulceration. The predominant causative factor of this condition is reflux of the great saphenous vein (GSV), which is traditionally treated with surgical saphenofemoral ligation and stripping of the incompetent saphenous vein. In recent years, there have been significant advances in saphenous vein ablation using percutaneous techniques, including the endovenous laser therapy (EVLT). In this article, the authors discuss the therapeutic evolution of this technology, theoretical basis of laser energy in GSV ablation, and procedural techniques of EVLT using duplex ultrasonography. Additional discussion of procedural-related complications, such as deep vein thrombosis, skin burn, saphenous nerve injury, and phletibis, and ecchymosis, are provided. Lastly, clinical results of EVLT in GSV ablation are discussed. Current literatures support EVLT as a safe and effective treatment option for varicosities caused by GSV incompetence.


Differentiating dopamine D2 ligands by their sensitivities to modification of the cysteine exposed in the binding-site crevice.
Cys118, in the third membrane-spanning segment of the dopamine D2 receptor, is exposed in the binding-site crevice. Cys118 reacts with the highly polar, sulfhydryl-specific reagents methanethiosulfonate ethylammonium (MTSEA) and methanethiosulfonate ethyltrimethylammonium (MTSET), and this reaction is retarded by the presence of antagonists and agonists. The reaction of MTSEA covalently attaches-SCH2CH2NH3+ to the cysteine sulfhydryl, producing a lysine-like side chain. The reaction of MTSEA with Cys118 decreased the affinity of substituted-benzamide antagonists, such as YM-09151-2, by 50-2800-fold, whereas the affinities of other antagonists, such as N-methyl-spiperone, were decreased < / = 6-fold. Agonist affinities were decreased 3-12,000-fold. Mutation of Cys118 to Lys had effects similar to that of the reaction of Cys118 with MTSEA. In contrast, mutation to the uncharged Met, the side-chain volume of which is similar to that of Lys, had much lesser effects on binding. All of the agonists and antagonists contain a positively charged nitrogen that is thought to interact with the side chain of Asp114, located one alpha-helical turn above Cys118. If this nitrogen is close to Asp114, then in the substituted-benzamides, the group on the nitrogen or the pyrrolidine ring itself could extend toward Cys118. Modification of Cys118 would then interfere with binding. The reaction of MTSET with Cys118 covalently attaches-SCH2CH2N(CH3)3+, which is bulkier and approximately 2 angstroms longer than the -SCH2CH2NH3+ added by MTSEA. In contrast to MTSEA, MTSET had equally large effects on the binding of YM-09151-2 and N-methyl-spiperone. Therefore, the effect on binding depends on both the size and the charge of the side chain substituted for that of Cys118.


N-γ-(L-Glutamyl)-L-selenomethionine enhances stress resistance and ameliorates aging indicators via the selenoprotein TRXR-1 in Caenorhabditis elegans.
Selenium is an essential trace nutrient for human health. This study investigates the organic form of selenium, N-γ-(L-Glutamyl)-L-selenomethionine (Glu-SeMet), for its effects on aging indicators and stress resistance. The role of the selenoprotein TRXR-1 was also evaluated in Caenorhabditis elegans. Glu-SeMet-treated wild-type N2 worms showed increased survival upon oxidative and thermal stress challenges. However, Glu-SeMet treatment did not extend the lifespan of wild-type N2 C. elegans under normal conditions (p = 0.128 for 0.01 μM and p = 0.799 for 10 μM Glu-SeMet). Under stress conditions, Glu-SeMet significantly increased the survival of wild-type N2 C. elegans, but the phenomenon was absent from trxr-1 null mutant worms. Furthermore, Glu-SeMet treatments significantly ameliorated aging indicators, including body bends, pumping rate, defecation duration, and lipofuscin accumulation in wild-type N2 nematodes. Nevertheless, the ameliorative effects by Glu-SeMet were absent in the trxr-1 null mutant worms. The findings indicate that enhanced stress resistance and improved aging indicators by Glu-SeMet in C. elegans are mediated by the selenoprotein TRXR-1. Glu-SeMet has potential for improving health and also provides new insights into selenium's regulatory mechanisms in intact organisms.


Effect of caffeine on DNA polymerase I from Escherichia coli: studies in vitro and in vivo.
The influence of caffeine on the activity of DNA polymerase I from E. coli was investigated. Caffeine had no effect on the polymerizing activity but did inhibit both 5' leads to 3' and 3' leads to 5' nuclease activities. The highest inhibition was observed with d(A--T)n as substrate: at a concentration of caffeine of 10 mM, inhibition was about 50%. In studies in vivo with 3 isogenic strains of E. coli, carrying different mutations in the DNA polymerase I gene, the effect of caffeine on survival after ultraviolet irradiation was most marked for the wild-type, pol+, followed by those mutants defective in 3' leads to 5', polA1, and 5' leads to 3' nuclease activities, polA107. Caffeine had little influence on survival of the resA1 mutant which lacks both 5' leads to 3' and 3' leads to 5' nuclease activities. These results support the idea that the influence of caffeine on dark repair may be explained in part by its effect on the nuclease activities of DNA polymerase I.


Marital status and cancer incidence: differences in the black and white populations.
A study of 59,070 cancers newly diagnosed during the years 1978 through 1982 among black and white males and females was conducted to assess variations in age-adjusted incidence rates across four marital categories, single, married, divorced, and widowed. Population data were obtained from the 1980 Census. Distinct patterns of cancer incidence by marital status were observed for black and white males and females. Single black males had the highest age-adjusted incidence rates for all 15 of the 15 sites analyzed among men. Similarly single black females' rates were highest for 14 of the 18 sites analyzed among women. Among white females, age-adjusted incidence rates were highest or second highest in widows for 16 of 18 sites analyzed. The variation in cancer incidence by marital status was not statistically significant for white men. In addition, there is a statistically significant concordance of cancer incidence by marital status across the four race-gender groups for three digestive tract sites. Clues to cancer etiology are suggested by this study, as well as potential directions for preventive health programs.


How to write a psychiatric report for litigation following a personal injury.
Psychiatrists are frequently asked to assess the psychiatric complications of personal injury cases for individuals who are seeking damages from third parties as the result of an accident. A selective review of the literature concerning the etiology and diagnoses applicable to psychiatric morbidity following personal injury is summarized. The author presents one outline of the medical-legal consultation. The reasons for inclusion of each category of information are discussed, and practical suggestions are made on how the data can be interpreted and used to educate the judicial system about the emotional consequences of accidents.


A systematic review of protein and energy supplementation for hip fracture aftercare in older people.
To evaluate whether protein and energy supplementation influences recovery after hip fracture. Systematic review of randomised and quasi-randomised trials in people aged 65 y and over. We searched seven electronic databases from 1966 to April 2002, four journals and reference lists of relevant articles. We contacted trial investigators and experts for details of other trials. Mortality, complications and unfavourable outcome (mortality or survivors with complications) were the primary outcomes. We also sought data on length of hospital stay, functional status after hip fracture, quality of life and compliance with supplementation. In total, 12 randomised trials involving 898 participants were included. Nine trials evaluated protein and energy supplementation (five oral and four nasogastric feeding), and a further three trials tested oral protein supplementation. Potential biases resulting from inadequate allocation concealment and lack of assessor blinding and intention-to-treat analysis, as well as the limited outcome data, mean that the results must be interpreted with caution. Pooled data from eight of the nine trials evaluating protein and energy supplements showed no evidence for an effect on mortality (relative risk 0.92, 95% CI 0.56-1.50). Limited data from only three trials showed that oral protein and energy supplements may reduce unfavourable outcome (relative risk 0.52, 95% CI 0.32-0.84). Based on limited evidence, oral protein and energy supplementation after hip fracture may reduce unfavourable outcome. Further evidence from good-quality randomised trials is required to inform clinical practice.


Climate, fire size, and biophysical setting control fire severity and spatial pattern in the northern Cascade Range, USA.
Warmer and drier climate over the past few decades has brought larger fire sizes and increased annual area burned in forested ecosystems of western North America, and continued increases in annual area burned are expected due to climate change. As warming continues, fires may also increase in severity and produce larger contiguous patches of severely burned areas. We used remotely sensed burn-severity data from 125 fires in the northern Cascade Range of Washington, USA, to explore relationships between fire size, severity, and the spatial pattern of severity. We examined relationships between climate and the annual area burned and the size of wildfires over a 25-year period. We tested the hypothesis that increased fire size is commensurate with increased burn severity and increased spatial aggregation of severely burned areas. We also asked how local ecological controls might modulate these relationships by comparing results over the whole study area (the northern Cascade Range) to those from four ecological subsections within it. We found significant positive relationships between climate and fire size, and between fire size and the proportion of high severity and spatial-pattern metrics that quantify the spatial aggregation of high-severity areas within fires, but the strength and significance of these relationships varied among the four subsections. In areas with more contiguous subalpine forests and less complex topography, the proportion and spatial aggregation of severely burned areas were more strongly correlated with fire size. If fire sizes increase in a warming climate, changes in the extent, severity, and spatial pattern of fire regimes are likely to be more pronounced in higher-severity fire regimes with less complex topography and more continuous fuels.


Antigenic modulation in vitro. I. Fate of thymus-leukemia (TL) antigen-antibody complexes following modulation of TL antigenicity from the surfaces of mouse leukemia cells and thymocytes.
The modulation or loss of thymus-leukemia (TL) antigenicity from the surfaces of mouse RADA1 leukemia cells and normal thymocytes during incubation with TL antibody in vitro at 37 degrees C was investigated by cytotoxicity, immunofluorescence, and immunoelectron microscopy. The fate of bivalent and monovalent antibody during modulation was visualized by fluorescence microscopy. Considerable antibody remained bound to the cell surface after modulation, bivalent antibody being displaced topographically into "patches" and "caps" while monovalent antibody was only slightly aggregated on the cell surface. Some antibody was internalized, presumably by pinocytosis, and was sequestered into the Golgi region of the cell. Capping usually occurred over the pole of the cell opposite from the Golgi region, which may explain the lack of extensive pinocytosis of modulating bivalent antibody. Since modulation with monovalent antibody occurs without patch or cap formation, gross topographical redistribution of TL antigen-antibody complexes is not required for modulation, although more subtle displacement of these complexes may be involved. Modulation was demonstrable by cytotoxicity with guinea pig C' but not with absorbed rabbit C', indicating that modulated TL antigens remain bound to the cell surface. A heat-labile factor in TL antiserum and in mouse serum in general is responsible for "blocking" the cytolytic interaction of guinea pig C' with modulated TL antigen-antibody complexes.


Stress from infertility, marriage factors, and subjective well-being of wives and husbands.
Stress associated with the inability to have a child is linked to four aspects of marriage and to five dimensions of life quality. Data come from 157 couples who met a standard medical definition for infertility. Wives and husbands were interviewed independently, and most of the following findings apply to both. A causal model suggests that fertility problem stress has direct effects that increase marital conflict and decrease sexual self-esteem, satisfaction with own sexual performance, and frequency of sexual intercourse. Also, fertility problem stress has both direct and indirect effects (via the marriage factors) that decrease evaluations of life-as-a-whole, self-efficacy, marriage, intimacy, and health. The negative effects on life quality are stronger for wives than for husbands. The model suggests that the life quality of couples with fertility problems could be improved if health care providers and couples themselves took steps to reduce such stresses and/or reduce their impact on the marriage factors.


Role, implementation, and effectiveness of advanced allied health assistants: a systematic review.
The purpose of this systematic review was to determine the effectiveness and implementation of advanced allied health assistant roles. A systematic search of seven databases and Google Scholar was conducted to identify studies published in English peer-reviewed journals from 2003 to 2013 and reporting on the effectiveness and implementation of advanced allied health assistant (A/AHA) roles. Reference lists were also screened to identify additional studies, and the authors' personal collections of studies were searched. Studies were allocated to the National Health and Medical Research Council hierarchy of evidence, and appraisal of higher-level studies (III-1 and above) conducted using the Centre for Evidence Based Medicine Systematic Review Critical Appraisal Sheet for included systematic reviews or the PEDro scale for level II and III-1 studies. Data regarding country, A/AHA title, disciplines, competencies, tasks, level of autonomy, clients, training, and issues regarding the implementation of these roles were extracted, as were outcomes used and key findings for studies investigating their effectiveness. Fifty-three studies were included, and most because they reported background information rather than investigating A/AHA roles, this representing low-level information. A/AHAs work in a range of disciplines, with a variety of client groups, and in a number of different settings. Little was reported regarding the training available for A/AHAs. Four studies investigated the effectiveness of these roles, finding that they were generally well accepted by clients, and provided more therapy time. Issues in integrating these new roles into existing health systems were also reported. A/AHA roles are being implemented in a range of settings, and appear to be effective in terms of process measures and stakeholder perceptions. Few studies have investigated these roles, indicating a need for research to be conducted in this area to enable policy-makers to consider the value of these positions and how they can best be utilized.


Do people with Alzheimer's disease improve with repeated testing? Unpacking the role of content and context in retest effects.
retest effects may be attributed to 'repeated content' in neuropsychological tests such as words in word list-learning tests, or the 'testing context' which involves procedural memory and reduced test anxiety following repeated administration. Alzheimer's Disease (AD) severely impairs episodic memory, so longitudinal cognitive testing among people with dementia may reveal the relative contributions of content versus context to retest effects in neuropsychological testing. we used data from the Critical Path Institute's repository of placebo arm data from randomized controlled trials (RCTs) of dementia conducted by participating pharmaceutical companies (N = 990 people, 4,170 study visits, up to 2.4 years of follow-up). To estimate retest effects on the Mini-Mental State Examination (MMSE), we used linear regressions with random effects for people and time, adjusting for age, sex and race, and longitudinal quantile regressions. average MMSE score (16.6 points, SD = 5.5, range 1, 27) declined by 2.0 points/year (95% confidence interval, CI: -2.3, -1.8). Mean retest effect was 0.6 points (95% CI: 0.4, 0.8) at second assessment (average 4 months after baseline). Retest effects were similar among participants with and without any recall on the short-delay word recall subscale score at baseline, and at the 30th, 50th and 70th percentiles of the MMSE distribution, suggesting similar retest effects across the spectrum from mild to severe cases of dementia. retest effects are apparent in people with dementia despite reduced episodic memory, suggesting a prominent role of the testing context in RCTs and cohort studies.


Associations Between Life's Essential 8 and Chronic Kidney Disease.
Chronic kidney disease (CKD) is closely associated with cardiovascular disease. We aimed to examine the association of Life's Essential 8 (LE8), the recently updated measurement of cardiovascular health, with the prevalence of CKD among US adults. This population-based cross-sectional study used data from the National Health and Nutrition Examination Survey from 2007 to 2018 and included adults aged ≥20 years. Multivariable logistic and restricted cubic spline models were used to assess the associations between LE8 and CKD. Among 24 960 participants, 4437 were determined to have CKD (weighted percentage, 14.11%). After the adjustment of potential confounders, higher LE8 scores were associated with reduced odds of CKD (odds ratio for each 10-point increase, 0.79 [95% CI, 0.76-0.83]), and a nonlinear dose-response relationship was observed. Similar patterns were also identified in the associations of health behavior and health factor scores with CKD. Meanwhile, higher scores for blood glucose (odds ratio, for each 10-point increase, 0.88 [95% CI, 0.87-0.90]) and blood pressure (odds ratio, for each 10-point increase, 0.92 [95% CI, 0.91-0.94]) in the LE8 component are significantly associated with a lower prevalence of CKD. The inversed association of LE8 score and CKD was significantly stronger among middle-aged, male, and coupled participants. LE8 was negatively associated with the prevalence of CKD in a nonlinear fashion. Promoting adherence to optimal cardiovascular health levels may be beneficial to reduce the burden of CKD.


Apolipoprotein E epsilon4 allele and familial aggregation of Alzheimer disease.
To investigate the relationship among risk for Alzheimer disease (AD), familial aggregation of AD, and the apolipoprotein E (apoE) epsilon4 allele in first-degree relatives of probands with AD and known apoE genotype. Two hundred ninety subjects fulfilling the criteria of the National Institute of Neurological Communicative Disease and Stroke-Alzheimer's Disease and Related Disorders Association for probable AD were ascertained from March 1, 1992, to December 31, 1996, through consecutive admissions in several university hospitals. Family data were collected on 1176 first-degree relatives (parents and siblings), aged 40 to 90 years. Most living relatives underwent a clinical examination, whereas we relied on family history for clinical data for deceased or unavailable relatives. First, we conducted standard survival analyses to estimate cumulative lifetime risk (LTR) for AD among relatives and to investigate for sex and apoE genotype effects on LTR. Then, we assessed to what extent clustering of secondary AD could be explained by the apoE epsilon4 allele by deriving the expected proportions of relatives with 0, 1, or 2 apoE epsilon4 alleles conditionally on the proband's genotype. Cumulative LTR for AD among first-degree relatives increased significantly with the number of epsilon4 alleles present in the proband. By 90 years of age, LTRs in relatives of probands with epsilon3/epsilon3, epsilon3/epsilon4, and epsilon4/epsilon4 genotypes were 29.2%, 46.1%, and 61.4%, respectively. Significant sex-by-apoE genotype interaction effects on LTR were observed. Women had about a 2-fold higher risk for AD than men among relatives of epsilon4 carriers but not among relatives of non-epsilon4 carriers. The predicted proportion of epsilon4 carriers in relatives of probands with epsilon3/epsilon3 genotype remains about 50% lower than the corresponding LTR for AD, indicating that familial clustering of AD is largely due to other factors than the apoE epsilon4 allele. Although aggregation of AD in families of probands with the epsilon4 allele is more prominent, we estimated that AD would not develop in about 30% of female and up to 60% of male relatives carrying at least 1 epsilon4 allele, even by 90 years of age. Our results support the hypothesis that the apoE epsilon4 allele enhances AD susceptibility, but putative factors enhancing risk for AD remain to be found.


Effects of Space Flight on the Chemical Constituents and Anti-Inflammatory Activity of Licorice (Glycyrrhiza uralensis Fisch).
Licorice, the oldest Chinese traditional medicine, is widely used in the treatment of human diseases. Due to the deficiency of wild resource, selecting and breeding becomes a key issue to expanding the supply of licorice. Spaceflight technology will become a new method for medicinal plants. The aim of this study was to investigate the effect of spaceflight on the components and anti-inflammatory activity in licorice. After flowing on a recoverable satellite for 18 days, licorice seeds were germinated and grown to maturity and the parallel ground-based seeds were also planted under the same conditions. The main components in licorice root were analyzed through HPLC. The contents of two components in spaceflight groups were higher than that of the ground control ones. Three acute inflammatory models including xylene-induced auricular edema, carrageenan-induced paw edema and acetic acid-induced vascular permeability were utilized to compare the anti-inflammatory activity of licorice pre and post spaceflight. The licorice extract showed the significant anti-inflammation activity. After the spaceflight, the pharmacological activity of licorice got higher than that of the ground control one. All of the models gained the tendency that the spaceflight group of species Hangjinqi had the strongest activity than other groups. The research provided the scientific data for a new breeding of medicinal plant through the spaceflight and indicated that the technology of space flight may be a new effective method for the breeding and cultivation of licorice.


Recognition Using Specular Highlights.
We present a novel approach to pose estimation and model-based recognition of specular objects in difficult viewing conditions, such as low illumination, cluttered background, large highlights, and shadows that appear on the object of interest. In such challenging conditions, conventional features are unreliable. We show that under the assumption of a dominant light source, specular highlights produced by a known object can be used to establish correspondence between its image and the 3D model, and to verify the hypothesized pose and the identity of the object. Previous methods that use highlights for recognition make limiting assumptions such as known pose, scene-dependent calibration, simple shape, etc. The proposed method can efficiently recognize free-form specular objects in arbitrary pose and under unknown lighting direction. It uses only a single image of the object as its input and outputs object identity and the full pose. We have performed extensive experiments for both recognition and pose estimation accuracy on synthetic images and on real indoor and outdoor images.


Chilling-related cell damage of apple (Malus × domestica Borkh.) fruit cortical tissue impacts antioxidant, lipid and phenolic metabolism.
'Soggy breakdown' (SB) is an internal flesh disorder of 'Honeycrisp' apple (Malus × domestica Borkh.) fruit that occurs during low temperature storage. The disorder is a chilling injury (CI) in which visible symptoms typically appear after several weeks of storage, but information about the underlying metabolism associated with its induction and development is lacking. The metabolic profile of flesh tissue from wholly healthy fruit and brown and healthy tissues from fruit with SB was characterized using gas chromatography-mass spectrometry (GC-MS) and liquid chromatograph-mass spectrometry (LC-MS). Partial least squares discriminant analysis (PLS-DA) and correlation networks revealed correlation among ester volatile compounds by composition and differences in phytosterol, phenolic and putative triacylglycerides (TAGs) metabolism among the tissues. anova-simultaneous component analysis (ASCA) was used to test the significance of metabolic changes linked with tissue health status. ASCA-significant components included antioxidant compounds, TAGs, and phytosterol conjugates. Relative to entirely healthy tissues, elevated metabolite levels in symptomatic tissue included γ-amino butyric acid, glycerol, sitosteryl (6'-O-palmitoyl) β-d-glucoside and sitosteryl (6'-O-stearate) β-d-glucoside, and TAGs containing combinations of 16:0, 18:3, 18:2 and 18:1 fatty acids. Reduced metabolite levels in SB tissue included 5-caffeoyl quinate, β-carotene, catechin, epicatechin, α-tocopherol, violaxanthin and sitosteryl β-d glucoside. Pathway analysis indicated aspects of primary metabolism differed according to tissue condition, although differences in metabolites involved were more subtle than those of some secondary metabolites. The results implicate oxidative stress and membrane disruption processes in SB development and constitute a diagnostic metabolic profile for the disorder.


Hypermutation of immunoglobulin genes in memory B cells of DNA repair-deficient mice.
To investigate the possible involvement of DNA repair in the process of somatic hypermutation of rearranged immunoglobulin variable (V) region genes, we have analyzed the occurrence, frequency, distribution, and pattern of mutations in rearranged Vlambda1 light chain genes from naive and memory B cells in DNA repair-deficient mutant mouse strains. Hypermutation was found unaffected in mice carrying mutations in either of the following DNA repair genes: xeroderma pigmentosum complementation group (XP)A and XPD, Cockayne syndrome complementation group B (CSB), mutS homologue 2 (MSH2), radiation sensitivity 54 (RAD54), poly (ADP-ribose) polymerase (PARP), and 3-alkyladenine DNA-glycosylase (AAG). These results indicate that both subpathways of nucleotide excision repair, global genome repair, and transcription-coupled repair are not required for somatic hypermutation. This appears also to be true for mismatch repair, RAD54-dependent double-strand-break repair, and AAG-mediated base excision repair.


Life after prostate cancer: A systematic literature review and thematic synthesis of the post-treatment experiences of Black African and Black Caribbean men.
Evidence shows that there are significant ethnic variations in prostate cancer prevalence and outcomes. Specifically, Black African and Black Caribbean men may encounter different post-treatment experiences than Caucasian men due to their disproportionately higher risk of being diagnosed with advanced prostate cancer. But to date, no review of these experiences has been undertaken. This review synthesised findings from existing literature on the post-treatment experiences of Black African and Black Caribbean men with prostate cancer and identified pertinent issues which may be useful to inform practice and future research. Seven databases were systematically searched using developed search terms. Four qualitative studies were identified and critically appraised. Findings are summarised under four main themes: symptom experience, healthcare experience, marital and social relationships and coping strategies. Cultural definitions of masculinity influenced the meanings men gave to their post-treatment experiences. While men's experiences of healthcare varied, the provision of professional support to address their post-treatment distress was lacking. Men derived most support from wives, peers and church communities. A culturally sensitive approach which recognises diversity among Black African and Black Caribbean populations and treats individuals within their religious and socio-cultural contexts could potentially improve men's post-treatment experiences. Areas for further research were also identified.


[Comparative evaluation of the hormonal changes in alimentaro-constitutional and hypothalamic obesity].
A study was made of change in hormone secretion in 243 patients with alimentary-constitutional and hypothalamic obesity. Activation of the somatostatin mechanism, a decrease in somatotropic and thyrotropic function of the hypophysis, an increment of corticotropin, beta-lipotropin and vasopressin levels in the blood, disturbance of circadian fluctuations of hormone secretion, an increase in insulin and C-peptide secretion, a decrease in glucagon secretion and triiodothyronine and cortisol levels in the blood, activation of the renin-aldosterone system and cortisol secretion rate were equally expressed both in alimentary-constitutional and primary hypothalamic obesity. The central mechanisms of the regulation of endocrine functions were incorporated in a pathological process even in alimentary-constitutional obesity. Disorders of the hypothalamic regulation lay in the basis of both types of obesity.


Association of angiotensin II type 1 receptor polymorphism with resistant essential hypertension.
Angiotensin II type 1 receptor (AT1) mediates the vasoconstrictive and growth-promoting effect of angiotensin II in humans. It has been reported that a polymorphism of the AT1 gene (an A/C transversion at position 1166: A-C1166) occurs more frequently in resistant hypertensives taking two or more antihypertensive drugs. On the contrary, a recent study of the influence of the A-C1166 polymorphism on aortic stiffness demonstrated that the distribution of the genotypes did not differ between normotensive and hypertensive subjects. In addition, a recent population-based survey of Caucasian hypertensives reported lower blood pressure values in CC homozygotes than in heterozygotes and AA homozygotes. Because of these controversial results and the lack of a sufficient amount of data the present study was designed to assess the contribution of the AT, gene A-C1166 polymorphism to resistant essential hypertension. Forty-eight subjects with resistant essential hypertension (HT) and 48 normotensive (NT), age and sex-adjusted controls (from a population of 300 healthy blood donors) were selected. All subjects were genotyped for the A-C1166 polymorphism in the 3'-UTR of the AT1 gene using PCR-based techniques. The influence of genotype on blood pressure (BP) was investigated using ANOVA Randomized Complete Block (ANOVA RCB) design according to sex, age and BMI. There were no significant differences in allele or genotype frequencies between HT and NT subjects (X2 = 0.61; P = NS). In HT subjects higher values of systolic blood pressure were associated with the C allele of the AT1 gene only in older and overweight patients (P < 0.001 and P < 0.001, respectively). Also in HT patients an association between the presence of the C allele of the AT1 gene and higher values of diastolic blood pressure was present in overweight patients (P = 0.001). These results suggest that in resistant hypertensive subjects the AT1 A-C1166 polymorphism is potentially involved in the regulation of blood pressure. As the effects of genotypes on blood pressure are pronounced in older and overweight subjects this polymorphism may amplify the effects of age and BMI on resistant essential hypertension.


Regulation of insulin-like growth factor I (IGF-I) gene expression in brain of transgenic mice expressing an IGF-I-luciferase fusion gene.
Insulin-like growth factor I (IGF-I) plays an important role in the development and function of the central nervous system (CNS). Little is known, however, about the factors and mechanisms involved in regulation of CNS IGF-I gene expression. To facilitate our goal to define mechanisms of IGF-I gene regulation in the CNS, we generated several lines of transgenic (Tg) mice that express firefly luciferase (LUC) under control of a 11.3-kb fragment from the 5' region of the rat IGF-I gene. Consistent with expression of the native IGF-I gene in murine brain, expression of the transgene predominated in neurons and astrocytes and used promoter 1, the major IGF-I promoter in the CNS and in most tissues. Transgene messenger RNA and protein expression rapidly increased after birth and peaked at postnatal (P) day 4 in all brain regions studied. LUC activities in all regions then gradually decreased to 0.5-4% of their peak values at P31, except for the olfactory bulb, which maintained about one third of its maximal activity. Compared with littermate controls, administration of dexamethasone decreased LUC activity and transgenic IGF-I messenger RNA abundance, whereas GH significantly increased the expression of the transgene. Addition of GH to cultured fetal brain cells from Tg mice for 12 h also increased LUC activity in a dose-dependent manner (77-388%). These results show that this IGF-I promoter transgene is expressed in a fashion similar to the endogenous IGF-I gene, and thus indicates that the transgene contains cis-elements essential for developmental, GH, and glucocorticoid regulation of IGF-I gene expression in the CNS. These Tg mice should serve as an useful model to study mechanisms of IGF-I gene regulation in the brain.


Penetration of bevacizumab and ranibizumab through retinal pigment epithelial layer in vitro.
To determine the permeability of bevacizumab and ranibizumab through highly-polarized retinal pigment epithelial (RPE) cells in vitro. Highly-polarized RPE cells were cultured in the upper chamber of a Transwell culture system. Bevacizumab or ranibizumab was added to the upper chamber. After 3 hours, the concentrations of bevacizumab or ranibizumab were determined in the upper and lower chambers. The cytotoxicities of the two anti-vascular endothelial growth factor agents were determined histologically. The effects of inhibiting endocytosis by pharmacologic inhibitors were also evaluated. The concentration of ranibizumab was higher than that of bevacizumab in the lower chamber (P < 0.05). Vascular endothelial growth factor was found mainly in the lower chamber under normal conditions. However, the concentration of vascular endothelial growth factor in the lower chamber was significantly less when ranibizumab was added to the upper chamber than when bevacizumab was added. Histology showed no obvious changes in bevacizumab-exposed or ranibizumab-exposed RPE cells. Pretreatment with protein kinase C inhibitor staurosporine had significant negative effects on the permeability of bevacizumab and ranibizumab (P < 0.05). Ranibizumab is more permeable than bevacizumab through the highly-polarized RPE layer at clinically equivalent concentrations, and their permeability was partially protein kinase C-dependent. Ranibizumab might be more therapeutically effective than bevacizumab on choroidal neovascularization beneath the RPE layer.


Why do pregnant women prefer cesarean birth? A qualitative study in a tertiary care center in Southern Thailand.
Increasing worldwide rates of cesarean section are of global concern. In recent years, cesarean births upon maternal request have become a hotly debated issue. Hence, this study aimed to explore maternal reasons for cesarean preference without medical indications. A descriptive qualitative study was conducted, using in-depth interviews with 27 pregnant women who preferred cesarean birth, attending antenatal care in Songklanagarind Hospital from September 2018 to June 2019. Data were analyzed using content analysis. Maternal reasons for cesarean preference were classified into six main categories: fear of childbirth, safety concerns related to health risk perceptions, negative previous birth experiences, positive attitudes toward cesarean birth, access to biased information and superstitious beliefs in auspicious birth dates. Most women had more than one reason for opting cesarean birth. Several reasons for cesarean birth preference have been elucidated. One striking reason was superstitious beliefs in auspicious birth dates, which are challengable for obstetricians to deal with. Obstetricians should explore the exact reasons why women request cesarean birth in order to prevent or diminish unnecessary cesarean births.


Nanovector therapeutics.
An ideal injected therapeutic drug would travel through the vasculature, reach the intended target at full concentration, and there act selectively on diseased cells and tissues only, without creating undesired side effects. Unfortunately, even the best current therapies fail to attain this ideal behavior, by a wide margin. A primary reason is the fact that the target recognition abilities of the current therapeutics molecules are quite limited. Furthermore, the natural defenses of the body present a sequence of formidable obstacles on the drug's pathway to the intended lesion. Requiring any molecule to have sufficient therapeutic efficacy, target recognition specificity, as well as all of the tools required to bypass multiple biological barriers is probably unrealistic. A different approach is to decouple the problem (i.e. employ the drug molecules for their therapeutic action only, and deliver them to the intended site by vectors that can be preferentially concentrated at desired body locations through the concurrent action of multiple targeting mechanisms). These vectors must also be large enough to comprise all the requirements for the evasion of the body defenses, while still sufficiently small so as not to create undesired blockages of even the smallest of blood vessels - and thus, by definition, nanotechnological.