Initial experience from a combination of systemic and regional chemotherapy in the treatment of patients with nonresectable cholangiocellular carcinoma in the liver.
In nonresectable cholangiocellular carcinoma (CCC) therapeutic options are limited. Recently, systemic chemotherapy has shown response rates of up to 30%. Additional regional therapy of the arterially hyper vascularized hepatic tumors might represent a rational approach in an attempt to further improve response and palliation. Hence, a protocol combining transarterial chemoembolization and systemic chemotherapy was applied in patients with CCC limited to the liver. Eight patients (6 women, 2 men, mean age 62 years) with nonresectable CCC received systemic chemotherapy (gemcitabine 1 000 mg/m(2)) and additional transarterial chemoembolization procedures (50 mg/m(2) cisplatin, 50 mg/m(2) doxorubicin, up to 600 mg degradable starch microspheres). Clinical follow-up of patients, tumor markers, CT and ultrasound were performed to evaluate maximum response and toxicity. Both systemic and regional therapies were tolerated well; no severe toxicity (WHO III/IV) was encountered. Nausea and fever were the most commonly observed side effects. A progressive rarefication of the intrahepatic arteries limited the maximum number of chemoembolization procedures in 4 patients. A median of 2 chemoembolization cycles (range, 1-3) and a median of 6.5 gemcitabine cycles (range, 4-11) were administered. Complete responses were not achieved. As maximum response, partial responses were achieved in 3 cases, stable diseases in 5 cases. Two patients died from progressive disease after 9 and 10 mo. Six patients are still alive. The current median survival is 12 mo (range, 9-18); the median time to tumor progression is 7 mo (range, 3-18). Seven patients suffered from tumor-related symptoms prior to therapy, 3 of these experienced a treatment-related clinical relief. In one patient the tumor became resectable under therapy and was successfully removed after 10 mo. The present results indicate that a combination of systemic gemcitabine therapy and repeated regional chemoembolizations is well tolerated and may enhance the effect of palliation in a selected group of patients with intrahepatic nonresectable CCC.


Evaluating the impact of climate change on groundwater resources in a small Mediterranean watershed.
Western Mediterranean Region of Turkey is subject to considerable impacts of climate change that may adversely affect the water resources. Decrease in annual precipitation and winter precipitation as well as increase in temperatures are observed since 1960s. In this study, the impact of climate change on groundwater resources in part of Köyceğiz-Dalyan Watershed was evaluated. Evaluation was done by quantifying the impacts of climate change on the water budget components. Hydrological modeling was conducted with SWAT model which was calibrated and validated successfully. Climate change and land use scenarios were used to calculate the present and future climate change impacts on water budgets. According to the simulation results, almost all water budget components have decreased. SWAT was able to allocate less irrigation water because of the decrease of overall water due to the climate change. This resulted in an increase of water stressed days and temperature stressed days whereas crop yields have decreased according to the simulation results. The results indicated that lack of water is expected to be a problem in the future. In this manner, investigations on switching to more efficient irrigation methods and to crops with less water consumption are recommended as adaptation measures to climate change impacts.


[Diagnosis of vulvar diseases. 2. Discussion and conclusions for practice].
Dystrophic vulvar conditions are found to increase with age and to predominate in postmenopausal women. The differentiation of this entity from infectious lesions and from precancerous conditions by clinical examination is extremely difficult. Therefore, diagnostic procedures are necessary which supplement local inspection and palpation. Photography is useful for documentation and follow-up control and colposcopy is suited for examination of lesions exhibiting erythroplakia, but not for leukoplakia which is much more frequent. Exfoliative cytology occupies a key position in vulvar diagnosis, since negative findings almost rule out a precancerous process, so long as the criteria of malignancy are sufficiently extended to include all abnormalities of the horny cells. Infections frequently cause equivocal cytological findings which disappear after appropriate treatment. Such infections can be diagnosed by phase contrast cytology, cultures, or serological tests. In many cases, further investigation will reveal diabetes mellitus or other metabolic disorders (internal consultant), urinary incontinence (urological consultant), allergic dermatoses (dermatological consultant) or psychoneurotic disease (neurologic consultant). Positive cytological findings always prompt biopsy; but equivocal and negative findings will also lead to histologic examination, if repeated control reveals constancy or exacerbation of a lesion in spite of the use of different diagnostic and therapeutic procedures. Vital staining with the toluidine blue method (so-called Collins test) is well suited for marking para- or dyskeratotic skin areas which then can be removed by surgery.


Pediatric AIDS epidemic reflects the first half million AIDS cases in the U.S.
Almost seven thousand pediatric AIDS cases with a death rate of 55 percent have been reported. The continuing increase and spread of this epidemic to different child populations and areas in the country is reviewed. Because the progress of this epidemic, pediatric practitioners require an awareness of the evolving epidemiologic patterns require an awareness of the evolving epidemiologic patterns in both the pediatric and adult populations.


Anisotropy and coherent vortex structures in planetary turbulence.
High-resolution numerical simulations were made of unforced, planetary-scale fluid dynamics. In particular, the simulation was based on the quasi-geostrophic equations for a Boussinesq fluid in a uniformly rotating and stably stratified environment, which is an idealization for large regions of either the atmosphere or ocean. The solutions show significant discrepancies from the long-standing theoretical prediction of isotropy. The discrepancies are associated with the self-organization of the flow into a large population of coherent vortices. Their chaotic interactions govern the subsequent evolution of the flow toward a final configuration that is nonturbulent.


Maximizing outcomes in genitourinary cancers across the treatment continuum.
Key controversies concerning the management of genitourinary cancers across the treatment continua were discussed at the second annual Interactive Genitourinary Cancer Conference (IGUCC) held in February 2010 in Athens, Greece. Prostate cancer is the most common form of cancer among western men and prevention strategies are needed. Trials evaluating 5α-reductase inhibitors have reported beneficial and clinically meaningful results, but uptake remains low for primary prostate cancer prevention. Prostate cancer detection programmes are also important as curative treatments for advanced disease are unavailable. Two large landmark randomized controlled trials reported conflicting results concerning screening efficacy and uncovered high levels of over-diagnosis and potential over-treatment. Tailored management strategies after diagnosis are important and predictive markers that distinguish between aggressive and indolent tumours are needed. The majority of newly diagnosed cases of prostate cancer are clinically localized. Active surveillance of favourable risk patients may be beneficial in the intermediate term, while an integrated approach of multi-modality therapy in patients with adverse features is recommended. The benefits of new technologies such as high-intensity focused ultrasound (HIFU) and robotic prostatectomy have not been established in prospective randomized trials vs current standards of care. A multidisciplinary approach is essential to evolving the management of advanced prostate cancer into a chronic disease paradigm. Docetaxel plus prednisone is the standard first-line chemotherapy for patients with metastatic castration-resistant prostate cancer (mCRPC), but the optimal timing of chemotherapy initiation has not been addressed in randomized clinical trials. Retrospective analyses suggest that asymptomatic patients with adverse prognostic factors for survival may also benefit from receiving chemotherapy. Bladder cancer is a common malignancy and the most expensive cancer per patient. Non-muscle-invasive bladder cancer is a heterogenous disease that requires dynamic multidisciplinary management. Aggressive early intervention may be beneficial in some cases. Platinum-based therapies represent the first-line standard of care for advanced bladder cancer, but the maximum benefit may have been reached for conventional chemotherapies and new strategies are needed. Several ongoing clinical trials are assessing combination chemotherapy and targeted therapy.


A scoping review shows that several nonvalidated budget planning tools for randomized trials are available.
We aimed to provide a systematic overview of freely available tools which may help plan or monitor costs for randomized clinical trials (RCTs). We systematically searched MEDLINE, EMBASE, and EconLit and conducted internet searches via Google (last search, October 2018). We included all freely available tools and determined their specific purpose, which parts of clinical trial projects and which types of costs they covered, and if they were user-tested or validated in any form. We identified 25 available tools. Most tools were downloadable on websites from institutions related to clinical research. Seven tools were developed to plan the budget for an entire RCT, 17 tools for calculating budgets of an individual trial center, and one tool for monitoring costs of ongoing RCTs. Eighteen tools considered fixed, variable, and indirect costs. Only two tools were clearly user-tested or validated. Several freely available tools aim to support investigators in planning costs of an entire trial or in planning the budget for a clinical trial site. How valid and useful they are remains to be shown for most of them. Future tools should be openly shared, user-tested, and validated.


Polyphenols from the mangosteen (Garcinia mangostana) fruit for breast and prostate cancer.
The mangosteen (Garcinia mangostana) is a tropical fruit native to Southeast Asia and has long been reported to contain multiple health promoting properties. This fruit is an abundant source of xanthones, a class of polyphenolic compounds with a distinctive tricyclic aromatic ring system and is largely responsible for its biological activities including anti-cancer activity. Herein we describe the anti-cancer activity and mechanisms of mangosteen polyphenolic xanthones including α-Mangostin against breast cancer and prostate cancer. So far, extracts and individual xanthones have been found to induce apoptosis and inhibit proliferation on cancer cells in vitro and in vivo. Based on the reported findings there is clear evidence that these polyphenols target multiple signaling pathways involved in cell cycle modulation and apoptosis. Further work is required to understand its potential for health promotion and potential drug discovery for prostate and breast cancer chemoprevention.


Inhalation of mainstream and sidestream cigarette smoke retards embryo transport and slows muscle contraction in oviducts of hamsters (Mesocricetus auratus).
Prior experiments have shown that the functioning of hamster oviducts is impaired by in vitro exposure to cigarette smoke. To determine if cigarette smoke affects oviductal functioning in vivo, an inhalation experiment was done in which hamsters were exposed to doses of smoke similar to those received by human smokers. The effects of mainstream smoke (the bolus of smoke inhaled by active smokers) and sidestream smoke (the main component in environmental tobacco smoke) were compared. Transport of preimplantation embryos through the hamster oviduct was retarded in females inhaling doses of mainstream or sidestream smoke that produced serum cotinine levels within the range reported for women who actively or passively smoke during pregnancy. In addition, hamster oviductal muscle contraction rate decreased significantly during a single exposure of animals to either mainstream or sidestream smoke, and contraction rate failed to return to initial control values during a 25-min recovery period. Both preimplantation embryo transport and muscle contraction were more sensitive to sidestream than mainstream smoke. These data demonstrate that inhalation of doses of mainstream and sidestream cigarette similar to those received by active and passive human smokers adversely affects functioning of the oviduct and may explain the increased incidence of ectopic pregnancies reported in women who smoke.


[Postoperative iatrogenic coronary-ventricular fistula].
Acquired coronary cardiac fistulas are rare. To date, thirty cases have been published in the literature, all secondary to thoracic trauma. The right cardiac chambers were more frequently involved. A recent continuous cardiac murmur is the most constant finding. Nontreated, these lesions tend to induce coronary insufficiency and congestive heart failure. 22 of the 30 reported cases were managed surgically. We hereby report a case of postoperative coronary cardiac fistula secondary to left ventricular venting, in which the fistula involved the left ventricular cavity.


Effect of Rifampicin on the Pharmacokinetics of Evogliptin in Healthy Volunteers.
Evogliptin (DA-1229) is a novel, potent, and selective dipeptidyl peptidase 4 (DPP-4) inhibitor for treating type 2 diabetes mellitus. This study investigates the effect of rifampicin on evogliptin pharmacokinetics. An open-label, crossover, one-sequence study was conducted on 12 healthy subjects. Reference baseline pharmacokinetic samples were collected on day 1 after the subjects were administered a single dose of 5 mg evogliptin. After a washout period, the subjects were administered 600 mg rifampicin once daily for 10 days, from days 8 to 17, for full induction of hepatic enzyme activity. On day 17, single doses of evogliptin (5 mg) were administered along with rifampicin (600 mg). The test pharmacokinetic samples were collected with a sampling schedule identical to that used for the reference. Maximum concentration (Cmax) and area under the plasma drug concentration-time curve (AUC0-96h) of evogliptin with and without co-administration of rifampicin were compared. Reference and test Cmax and AUC0-96h values of evogliptin were 4.70 ng/mL vs 4.86 ng/mL and 153.97 ng∙h/mL vs 58.83 ng∙h/mL, respectively. All adverse events were mild in intensity and considered unrelated to evogliptin administration. Rifampicin decreased the AUC0-96h of evogliptin by 61.8% without significantly affecting Cmax. The mechanism underlying the decrease in AUC0-96h is thought to be the induction of cytochrome P450 (CYP), especially 3A, by rifampicin. The adverse events, none of which were serious, were not significantly altered by the concomitant administration of evogliptin and rifampicin. Nevertheless, it would be prudent that evogliptin dosing should be carefully considered when co-administered with CYP3A inducers.


Ethnicity, gender, and depressive symptoms in older workers.
We used data from a prospective investigation of full-time workers aged 58 to 64 years and residing in a North Carolina metropolitan area at baseline to examine a causal model for depressive symptomatology among White men, White women, African American men and African American women. We found significant group differences. (1) White men were more vulnerable to social network losses than White women; (2) Work stressors had long-term effects on African American men whose levels of depressive symptoms were also elevated by poor health and retirement; and (3) The influence of income was more dominant among African Americans and its effect was greater for African American women.


8 Å structure of the outer rings of the Xenopus laevis nuclear pore complex obtained by cryo-EM and AI.
The nuclear pore complex (NPC), one of the largest protein complexes in eukaryotes, serves as a physical gate to regulate nucleocytoplasmic transport. Here, we determined the 8 Å resolution cryo-electron microscopic (cryo-EM) structure of the outer rings containing nuclear ring (NR) and cytoplasmic ring (CR) from the Xenopus laevis NPC, with local resolutions reaching 4.9 Å. With the aid of AlphaFold2, we managed to build a pseudoatomic model of the outer rings, including the Y complexes and flanking components. In this most comprehensive and accurate model of outer rings to date, the almost complete Y complex structure exhibits much tighter interaction in the hub region. In addition to two copies of Y complexes, each asymmetric subunit in CR contains five copies of Nup358, two copies of the Nup214 complex, two copies of Nup205 and one copy of newly identified Nup93, while that in NR contains one copy of Nup205, one copy of ELYS and one copy of Nup93. These in-depth structural features represent a great advance in understanding the assembly of NPCs.


Multi-Atlas Spleen Segmentation on CT Using Adaptive Context Learning.
Automatic spleen segmentation on CT is challenging due to the complexity of abdominal structures. Multi-atlas segmentation (MAS) has shown to be a promising approach to conduct spleen segmentation. To deal with the substantial registration errors between the heterogeneous abdominal CT images, the context learning method for performance level estimation (CLSIMPLE) method was previously proposed. The context learning method generates a probability map for a target image using a Gaussian mixture model (GMM) as the prior in a Bayesian framework. However, the CLSSIMPLE typically trains a single GMM from the entire heterogeneous training atlas set. Therefore, the estimated spatial prior maps might not represent specific target images accurately. Rather than using all training atlases, we propose an adaptive GMM based context learning technique (AGMMCL) to train the GMM adaptively using subsets of the training data with the subsets tailored for different target images. Training sets are selected adaptively based on the similarity between atlases and the target images using cranio-caudal length, which is derived manually from the target image. To validate the proposed method, a heterogeneous dataset with a large variation of spleen sizes (100 cc to 9000 cc) is used. We designate a metric of size to differentiate each group of spleens, with 0 to 100 cc as small, 200 to 500cc as medium, 500 to 1000 cc as large, 1000 to 2000 cc as XL, and 2000 and above as XXL. From the results, AGMMCL leads to more accurate spleen segmentations by training GMMs adaptively for different target images.


Impact of Standardized Patients on First Semester Nursing Students Self-Confidence, Satisfaction, and Communication in a Simulated Clinical Case.
Utilizing standardized patients (SPs) as a strategy to potentially improve beginning level nursing students' confidence, satisfaction, and communication after simulated clinical cases is an innovative approach in nursing education. The aim of this study was to examine to what extent an SP affected first semester nursing students' self-confidence, satisfaction, and communication using a simulated clinical case. First semester undergraduate students in a bachelors of nursing program at a large university in the South-Central region of the United States (N = 100), were randomly assigned to one of the two groups. Each group was assigned the same case using either an SP or high-fidelity manikin. Students completed postsurveys immediately following completion of the simulation. Student's self-confidence, satisfaction, and communication were measured using the National League for Nursing Student Satisfaction and Self-Confidence in Learning for Nursing Education Research and an SP/Faculty Communication Checklist. An independent sample t test comparing the two student groups on each of the outcome variables was conducted for each of the research questions. Students who completed the simulation with an SP, reported greater satisfaction, and improved communication. Student reflective comments were significantly more positive in the SP group. There was no statistical difference between the two groups in self-confidence. Further research is needed to determine whether the use of SPs versus high-fidelity manikins in simulated cases results in increased self-confidence in beginning level nursing students. Student satisfaction and communication are key components for nursing student success. The impact of SPs and the effect on student outcomes could have long-term benefits for undergraduate nursing programs.


Mandibular Retromolar Foramen and Canal - A Systematic Review and Meta-Analysis.
The retromolar fossa is a small triangular area posterolateral to 3rd molar region in the mandible. The retromolar fossa often contains the retromolar foramen (RMF) as an anatomical variant. When the RMF is present, the foramen is connected with the mandibular canal (MC) through another canal known as the retromolar canal (RMC). RMC contains neurovascular bundle, which gives additional supply to the mandible. Although few studies have been conducted in past, a lacunae in comprehensive review is lacking. Although, these variations posed challenging situations for the practicing surgeons, they have been quite neglected and not well presented in textbooks. Hence, we made an attempt to provide a comprehensive and consolidated review regarding RMF and RMC. The relevant articles were selected by hand search and electronic media (Google scholar, PubMed, Science Direct, Medline, Embase and Cochrane) from 1987 to 2019. All the relevant articles were properly screened and findings were extracted from the articles. There seems to be wide variations in morphology and morphometry of RMF and RMC. Detailed knowledge of these anatomical variations is important in surgical procedure involving the retromolar area to protect the patient from complications such as unexpected bleeding, hematoma formation, and nerve damage. Furthermore, its knowledge makes us understand about the failed inferior alveolar nerve block, spread of infection, and metastasis in case of carcinoma. When there is any suspicious alteration in the MC, we suggest more accurate examination technique like CBCT.


[Unpaired bases in the B--Z junction of the supercoiled plasmid].
The restriction analysis has been used to establish that O-beta-diethylaminoethylhydroxylamine (OHA) produces modification of unpaired cytidines in the polylinker region adjacent to the Z-insert (dG-dC)10. (dG-dC)10 in the negatively supercoiled plasmid pGC20. The length of the transition region between B- and Z-portions of DNA is not less than 36 bps. The reaction of OHA with the unpaired cytidines in the B-Z junction is a fixing one and produces no secondary despiralling of the neighboring regions. The reaction with DNA proceeds much slower than the one with monomers and single-strand polynucleotides. The structural nonuniformity has been observed, which is manifested in the alternating B and "non-B" form DNA in the B-Z junction. It is suggested that these junctions may contain nucleotide sequences which are stable to violation of the B structure during the change in superhelical density of DNA.


Palladium-coated plasmonic optical fiber gratings for hydrogen detection.
Surface plasmon resonance excitation with tilted fiber Bragg gratings has been typically studied using gold films to target biochemical sensing applications. However, surface plasmons can be excited on other metal coatings as well. In this work, plasmonic optical fiber grating platforms are developed using palladium films. Since the optical properties of this metal differ from the ones of gold, simulations are carried out to define the optimal thickness. Due to the phase transition of palladium in the presence of hydrogen, intensity changes in the optical transmission of the devices are produced. It is demonstrated that these platforms can be used for hydrogen detection at concentrations way below the lower explosive limit.


Transfer functions of the Streptococcus faecalis plasmid pAD1: organization of plasmid DNA encoding response to sex pheromone.
The conjugative plasmid pAD1 (59.6 kilobases) of Streptococcus faecalis shows a 10,000-fold increase in transfer frequency following induction by the sex pheromone cAD1. Mutagenesis of the plasmid with transposon Tn917 was undertaken to determine the region(s) of pAD1 required for the mating response. The relevant genetic material was found to be distributed over a 31.2-kilobase contiguous region of the plasmid. Although insertions in two previously identified regions (traA and traB) exhibited increased transfer frequencies, insertions in five new regions (D, E, F, G, and H) decreased the ability of pAD1 to transfer. Insertions in region H allowed the cells to form visible mating aggregates, but the plasmid transfer frequency was decreased to levels below detection during a 1-h broth mating. Mutants with mutations in region G were able to form aggregates; however, insertions in regions D, E, and F prevented aggregate formation. Insertions in region C decreased the sensitivity of the cell to exogenous cAD1 and exhibited increased activity of the pheromone inhibitor iAD1. Surface protein profiles produced by a number of these mutants were examined, and in some cases were found to be different from those of the wild type. A map showing the various regions is presented, and related aspects of the regulation of the pAD1 mating response are discussed.


A comparison of three allied health manpower projection methodologies.
Three manpower projection methodologies most often employed in the allied health sciences were compared: population ratio, occupational matrix, and regression analysis. Comparisons were made among the methodologies themselves, their strengths, and their weaknesses. These methodologies were then applied to the largest allied health discipline - clinical laboratory sciences - using Kentucky statewide data. The resultant projections were then compared with actual data (F.J. Morris, PhD, unpublished data, 1985). The most appropriate methodology to be used by the administrator should be determined by his/her specific needs and goals in relation to the specific strengths and weaknesses of the individual methodology.


Lactoferrin Prevents Hepatic Injury and Fibrosis via the Inhibition of NF-κB Signaling in a Rat Non-Alcoholic Steatohepatitis Model.
Non-alcoholic steatohepatitis (NASH) can cause liver cirrhosis and hepatocellular carcinoma (HCC), with cases increasing worldwide. To reduce the incidence of liver cirrhosis and HCC, NASH is targeted for the development of treatments, along with viral hepatitis and alcoholic hepatitis. Lactoferrin (LF) has antioxidant, anti-cancer, and anti-inflammatory activities. However, whether LF affects NASH and fibrosis remains unelucidated. We aimed to clarify the chemopreventive effect of LF on NASH progression. We used a NASH model with metabolic syndrome established using connexin 32 (Cx32) dominant negative transgenic (Cx32ΔTg) rats. Cx32ΔTg rats (7 weeks old) were fed a high-fat diet and intraperitoneally injected with dimethylnitrosamine (DMN). Rats were divided into three groups for LF treatment at 0, 100, or 500 mg/kg/day for 17 weeks. Lactoferrin significantly protected steatosis and lobular inflammation in Cx32ΔTg rat livers and attenuated bridging fibrosis or liver cirrhosis induced by DMN. By quantitative RT-PCR, LF significantly down-regulated inflammatory (Tnf-α, Il-6, Il-18, and Il-1β) and fibrosis-related (Tgf-β1, Timp2, and Col1a1) cytokine mRNAs. Phosphorylated nuclear factor (NF)-κB protein decreased in response to LF, while phosphorylated JNK protein was unaffected. These results indicate that LF might act as a chemopreventive agent to prevent hepatic injury, inflammation, and fibrosis in NASH via NF-κB inactivation.


Health status in patients with coexistent COPD and heart failure: a validation and comparison between the Clinical COPD Questionnaire and the Minnesota Living with Heart Failure Questionnaire.
Chronic obstructive pulmonary disease (COPD) and heart failure (HF) are both common diseases that coexist frequently. Patients with both diseases have worse stable state health status when compared with patients with one of these diseases. In many outpatient clinics, health status is monitored routinely in COPD patients using the Clinical COPD Questionnaire (CCQ) and in HF patients with the Minnesota Living with Heart Failure Questionnaire (MLHF-Q). This study validated and compared which questionnaire, ie, the CCQ or the MLHF-Q, is suited best for patients with coexistent COPD and HF. Patients with both COPD and HF and aged ≥40 years were included. Construct validity, internal consistency, test-retest reliability, and agreement were determined. The Short-Form 36 was used as the external criterion. All questionnaires were completed at baseline. The CCQ and MLHF-Q were repeated after 2 weeks, together with a global rating of change. Fifty-eight patients were included, of whom 50 completed the study. Construct validity was acceptable. Internal consistency was adequate for CCQ and MLHF-Q total and domain scores, with a Cronbach's alpha ≥0.70. Reliability was adequate for MLHF-Q and CCQ total and domain scores, and intraclass correlation coefficients were 0.70-0.90, except for the CCQ symptom score (intraclass correlation coefficient 0.42). The standard error of measurement on the group level was smaller than the minimal clinical important difference for both questionnaires. However, the standard error of measurement on the individual level was larger than the minimal clinical important difference. Agreement was acceptable on the group level and limited on the individual level. CCQ and MLHF-Q were both valid and reliable questionnaires for assessment of health status in patients with coexistent COPD and HF on the group level, and hence for research. However, in clinical practice, on the individual level, the characteristics of both questionnaires were not as good. There is room for a questionnaire with good evaluative properties on the individual level, preferably tested in a setting of patients with COPD or HF, or both.


Delphi consensus on add-ons and social midia in Assisted Reproductive Technology.
This article reports the annals of a national consensus meeting on add-ons and social networks in Assisted Reproduction Techniques (ART). The panel of experts has developed a set of consensus points and this document is intended to be referenced as a national consensus to allow social networks and add-ons to be used in ART, following the standards of the Code of Medical Ethics and the Federal Council of Medicine, in a safe ethical and responsible way.


The predictive ability of EQ-5D-3L compared to the LACE index and its association with 30-day post-hospitalization outcomes.
To examine whether the EQ-5D-3L at the time of discharge from hospital provides additional prognostic information above the LACE index for 30-day post-discharge hospital readmission and to explore the association of EQ-5D-3L with readmissions, emergency department (ED) visits, and death within the same period. Using data (n = 495; mean age 62.9 years (SD 18.6), 50.5% female) from a prospective cohort study of patients discharged from medical wards at two university hospitals, the prognostic ability of EQ-5D-3L was examined using C-statistic, Integrated Discrimination Improvement (IDI) Index, and Akaike's Information Criterion (AIC). The associations between EQ-5D-3L dimensions, total sum, index and VAS scores at the time of discharge and 30-day post-discharge ED visits, readmission, and readmission/death were examined using multivariate logistic regression. At the time of discharge, 58.6% of participants reported problems in mobility, 28.3% in self-care, 62.1% in usual activities, 62.7% in pain/discomfort, and 42.4% in anxiety/depression. Mean (SD) total sum score was 7.9 (2.0), index score was 0.69 (0.21), and VAS score was 63.7 (18.4). In adjusted analyses, mobility, self-care, usual activities, and the total sum score were significantly associated with 30-day readmission and readmission/death. Differences in C-statistic for LACE readmission prediction models with and without EQ-5D-3L were small. AIC analysis suggests that readmission prediction models containing EQ-5D-3L dimensions or scores were more often preferred to those with the LACE index only. IDI analysis indicates that the discrimination slope of readmission prediction models is significantly improved with the addition of mobility, self-care, or the total sum score of the EQ-5D-3L. The EQ-5D-3L, especially the mobility and self-care dimensions as well as the total sum score, improves 30-day readmission prediction of the LACE index and is associated with 30-day readmissions or readmissions/death.


Evaluation of a bladder tumor antigen test for the diagnosis of lower urinary tract malignancies in dogs.
To evaluate the use of a human bladder tumor antigen test for diagnosis of lower urinary tract malignancies in dogs. Urine samples from dogs without urinary tract abnormalities (n = 18) and from dogs with lower urinary tract neoplasia (20) or nonmalignant urinary tract disease (16). Test results were compared among groups and among 3 observers. The effects of urine pH and specific gravity, degree of hematuria, and storage temperature and time of urine samples on test results were also assessed. Test sensitivity and specificity were 90 and 94.4%, respectively, for differentiating dogs with lower urinary tract neoplasia from dogs without abnormalities. However, specificity decreased to 35% for differentiating dogs with neoplasia from dogs with nonmalignant urinary tract disease. In dogs with neoplasia, results were significantly affected by degree of hematuria. However, addition of blood to urine from dogs without hematuria had no significant effect on test results. Although intraobserver variation was significant, urine pH, specific gravity, or storage time or temperature had no significant effect on results. Although this bladder tumor antigen test was sensitive for differentiating dogs with malignancies of the lower urinary tract from dogs without urinary tract disease, it was not specific for differentiating dogs with neoplasia from dogs with other lower urinary tract abnormalities. It cannot, therefore, be recommended as a definitive diagnostic aid for the detection of lower urinary tract malignancies in dogs.


Residual Cdk1/2 activity after DNA damage promotes senescence.
In response to DNA damage, a cell can be forced to permanently exit the cell cycle and become senescent. Senescence provides an early barrier against tumor development by preventing proliferation of cells with damaged DNA. By studying single cells, we show that Cdk activity persists after DNA damage until terminal cell cycle exit. This low level of Cdk activity not only allows cell cycle progression, but also promotes cell cycle exit at a decision point in G2 phase. We find that residual Cdk1/2 activity is required for efficient p21 production, allowing for nuclear sequestration of Cyclin B1, subsequent APC/CCdh1 -dependent degradation of mitotic inducers and induction of senescence. We suggest that the same activity that triggers mitosis in an unperturbed cell cycle enforces senescence in the presence of DNA damage, ensuring a robust response when most needed.


Recombinant human thyrotropin (rhTSH) in the follow-up and treatment of patients with thyroid cancer.
The follow-up of thyroid cancer is based on the detection of residual and recurrent thyroid carcinoma. This is traditionally done by means of measurements of serum thyroglobulin (Tg) combined with various imaging techniques (131I-whole body scan, ultrasound and other modalities). Tg serum levels and the uptake of 131I on a whole body scan (WBS) depend on TSH stimulation, which in thyroidectomized patients can be obtained either by withdrawal of thyroid hormone treatment (thyroxine) or by administration of exogenous TSH. At present exogenous human TSH is obtained by means of recombinant DNA technology, (recombinant human TSH (rhTSH), Thyrogen). Even if the administration of rhTSH and withdrawal of thyroid hormone are not completely equivalent, the use of rhTSH has already entered the clinical routine (rhTSH Tg test and rhTSH WBS) because with rhTSH the morbidity and discomfort associated with the withdrawal of thyroid hormone can be avoided. At a recent International Consensus Conference on the follow-up of differentiated thyroid carcinoma it was proposed to carry out only Tg measurement after rhTSH stimulation; moreover, it was stated that 131I whole body scan has to be discouraged in patients submitted to radical surgery and radioiodine ablation with no clinical evidence of residual tumor and with undetectable levels of Tg during hormonal suppression of TSH. Similar strategies in this respect tend to eliminate the 131I WBS and propose only the rhTSH Tg test combined with head and neck ultrasound (US). This is still a matter of debate, also because it is not valid for all risk groups and not all patients undergo the same clinical management (radical surgery or not, thyroid ablation with 131I or not). However, the availability of rhTSH will definitely change the management of papillary and follicular thyroid carcinoma, also with regard to iodine treatment. In fact, rhTSH can be used during radioiodine treatment to enhance the 131I uptake by the cancer cells in particular groups of patients. Patients who could benefit from this approach can be divided into three subgroups: 1) patients in whom thyroxine withdrawal may be dangerous because of the effects of long-term TSH stimulation on the tumor mass (brain metastases, vertebral metastases, presence of neurological signs, heart diseases); 2) patients affected by tumors with marked biological aggressiveness and a low iodine uptake (variants of follicular carcinoma, insular carcinoma, tall and columnar cell variants of papillary thyroid carcinoma, Hürthle cell carcinoma); 3) patients with hypothalamic-pituitary alterations. The potential efficiency of rhTSH in radiometabolic treatment is an important issue that has been studied in a limited number of patients, but is worthy of further investigations in large perspective. A recent clinical prospective trial has been proposed by the Thyroid Cancer Study Group of the Istituto Nazionale Tumori and is now ongoing.


Upper airway changes in Pierre Robin sequence from childhood to adulthood.
To investigate pharyngeal airway changes in patients with Pierre Robin sequence (PRS) longitudinally from childhood to adulthood. Cleft Lip and Palate Unit, Clinic of Orthodontics, University of Zurich. Twenty-four patients born between 1970 and 1990 with non-syndromic PRS. Lateral cephalograms at age 5 (T1), 10 (T2), 15 (T3) and 20 (T4) years were available. Variables describing pharyngeal airway dimensions, soft palate morphology, tongue and hyoid position, skeletal morphology and head posture were assessed. A significant increase in nasopharyngeal depth was found over the entire observation period (T1 10.7 to T4 19.1 mm, p < 0.001), especially between T2 and T3 (change 3.8 mm, p < 0.001), and was mainly due to adenoid recession (r = -0.75, p < 0.001; variation explained by 56%). Increase in velopharyngeal depth mainly took place between T3 and T4 (change 2.3 mm, p < 0.01). It was due to more anterior tongue posture (r = 0.65, p < 0.001; 42.5% of variation explained), in turn allowing the soft palate to take a more vertical position (r = -0.52, p < 0.001). Increase in oropharyngeal depth was associated with head extension and anterior mandibular positioning (36% of variation explained). However, significance was not reached (T1 8.3 to T4 9.8 mm, p > 0.05). Upper airway dimensions in children with PRS improve with time, except for the oropharyngeal airway. Despite large interindividual variation, the mean remained in the lower reaches of normality described in other studies. Thus, further research should investigate the prevalence of obstructive sleep apnoea in adults with PRS.


Prolonged gene expression and cell survival after infection by a herpes simplex virus mutant defective in the immediate-early genes encoding ICP4, ICP27, and ICP22.
Very early in infection, herpes simplex virus (HSV) expresses four immediate-early (IE) regulatory proteins, ICP4, ICP0, ICP22, and ICP27. The systematic inactivation of sets of the IE proteins in cis, and the subsequent phenotypic analysis of the resulting mutants, should provide insights into how these proteins function in the HSV life cycle and also into the specific macromolecular events that are altered or perturbed in cells infected with virus strains blocked very early in infection. This approach may also provide a rational basis to assess the efficacy and safety of HSV mutants for use in gene transfer experiments. In this study, we generated and examined the phenotype of an HSV mutant simultaneously mutated in the ICP4, ICP27, and ICP22 genes of HSV. Unlike mutants deficient in ICP4 (d120), ICP4 and ICP27 (d92), and ICP4 and ICP22 (d96), mutants defective in ICP4, ICP27, and ICP22 (d95) were visually much less toxic to Vero and human embryonic lung cells. Cells infected with d95 at a multiplicity of infection of 10 PFU per cell retained a relatively normal morphology and expressed genes from the viral and cellular genomes for at least 3 days postinfection. The other mutant backgrounds were too toxic to allow examination of gene expression past 1 day postinfection. However, when cell survival was measured by the capacity of the infected cells to form colonies, d95 inhibited colony formation similarly to d92. This apparent paradox was reconciled by the observation that host cell DNA synthesis was inhibited in cells infected with d120, d92, d96, and d95. In addition, all of the mutants exhibited pronounced and distinctive alterations in nuclear morphology, as determined by electron microscopy. The appearance of d95-infected cells deviated from that of uninfected cells in that large circular structures formed in the nucleus. d95-infected cells abundantly expressed ICP0, which accumulated in fine punctate structures in the nucleus at early times postinfection and coalesced or grew to the large circular objects that were revealed by electron microscopy. Therefore, while the abundant accumulation of ICPO in the absence of ICP4, ICP22, and ICP27 may allow for prolonged gene expression, cell survival is impaired, in part, as a result of the inhibition of cellular DNA synthesis.


Understanding the Legal Essentials of a Bowel Injury Lawsuit in Minimally Invasive Gynecologic Surgery.
Bowel injury is a known inherent complication of minimally invasive gynecologic surgery; however, it does not automatically signify medical malpractice. Plaintiff attorneys representing patients seeking legal recourse from a bowel injury typically allege claims of intraoperative negligence, delay in diagnosis, or lack of informed consent in an effort to circumvent the assertion that it is a known inherent complication. In addition, damage awards in bowel injury lawsuits can easily exceed the amount covered by the policy limits of a medical malpractice insurance plan, leaving the gynecologist financially responsible for the difference. Therefore, it is crucial to understand when it may be appropriate to consent to a settlement offer, which can relieve the gynecologist from financial liability for amounts awarded above the medical malpractice policy limits. The purpose of this medical-legal review is to make minimally invasive gynecologic surgeons more aware of the legal strategies used by plaintiff attorneys representing patients who have incurred bowel injuries, and how to limit liability in lawsuits.


Does fish oil supplementation in pregnancy reduce the risk of allergic disease in infants?
Parallel increases in many inflammatory diseases over the last 40 years suggest that common environmental changes are promoting inflammatory immune responses and/or inhibiting the processes that normally keep these in check. One key change during this period has been declining intakes of anti-inflammatory dietary factors, including omega-3 polyunsaturated fatty acids (n-3 PUFA). As allergic diseases often first manifest in early infancy, prevention strategies need to be targeted early, even in utero. This review will examine recent evidence for the use of fish oil during this early period as a primary prevention strategy for allergic disease. N-3 PUFA have well documented anti-inflammatory effects in vitro and have also been demonstrated to have health benefits in a range of chronic inflammatory diseases, including cardiovascular disease, rheumatoid arthritis and diabetes, supporting their role in modulating inflammation in vivo. Although the effects of fish oil supplementation in established allergic disease are less convincing, there is accumulating evidence that dietary n-3 PUFA may have greater effects before allergic responses are established. Supplementation of the maternal diet in pregnancy with n-3 PUFA may provide a non-invasive intervention with significant potential to prevent the development of allergic and possibly other immune-mediated diseases.


Childhood lichen planus: a report of fifty cases.
Lichen planus is an uncommonly encountered dermatosis in children. In the present study of 50 children the limbs were the most common site of involvement (70.0%). A majority of the children (60.0%) presented with the classic form of the disease. Hypertrophic lesions were present in 26.0% of children while linear lesions were seen in 8.0%. There was no scalp, nail, or hair involvement in any child. The Koebner phenomenon was observed in 28.0%, and mucosal involvement, which is very uncommon in children affected by lichen planus, was seen in 30.0%. In this subset of children, hypertrophic lesions were seen in 53.4% while widespread disease was present in only 6.7%. The response to treatment and the course of the disease were similar to that seen in adults.


The bimodal effect of interleukin 1 on rat pancreatic beta-cells--stimulation followed by inhibition--depends upon dose, duration of exposure, and ambient glucose concentration.
To investigate the hypothesis that interleukin 1 initially stimulates and then suppresses beta-cell function and that this sequential effect is directly related to interleukin 1 dose, duration of exposure, and ambient glucose concentration, insulin release was measured from cultured newborn rat islets exposed for 6 h to 6 days to interleukin 1 at doses ranging from 20 to 2000 ng/l at glucose concentrations of 3.3, 5.5 and 11 mmol/l. After 6 h of exposure and at all three glucose levels, all doses of interleukin 1 stimulated insulin release, maximal stimulation (370% of control) being observed at 5.5 mmol/l glucose and 100 ng/l interleukin 1. In contrast, after 6 days, all doses of interleukin 1 were inhibitory irrespective of glucose level, maximal inhibition (90%) being observed at 11 mmol/l glucose and 2000 ng/l interleukin 1. At 24 and 48 h of exposure, the biphasic effect of interleukin 1 was observed: lower doses of interleukin 1 at lower glucose concentrations at 24 h being more stimulatory with transition to inhibition directly related to higher glucose levels, higher interleukin 1 doses, and longer exposure. After 48 h, 200 ng/l of interleukin 1 increased insulin release to 220% at 3.3 mmol/l glucose, but at 11 mmol/l glucose a 60% suppression was seen. On the basis of these data we suggest that interleukin 1's effect on beta-cells is bimodal: stimulation followed by inhibition. Increasing interleukin 1 dose and ambient glucose concentration shift this response to the left. Experimental results will, and in vivo effects may, depend upon these three variables.


Recent trends in teen births in the United States.
Teenage births and birth rates have dropped steadily during the 1990s. Overall, the teen birth rate declined 15 percent between 1991 and 1997. The trend in the 1990s reverses a period of steep increases from 1986 to 1991. Despite the recent declines, the teen birth rate in 1997 is still higher than rates in the mid 1980s when they were at an all-time low (50-51 per 1,000). In general, teen birth rates have declined more for younger teenagers (15-17 years) than for older teens (18-19 years). Among all race and ethnic groups, black teenagers have experienced the greatest declines in childbearing during the 1990s. From 1991 to 1997, the rate for black teens 15-19 years dropped 23 percent to the lowest level on record. A particularly noteworthy finding is that the birth rate for second births to all teenagers who have had a first birth (repeat childbearing) declined by 21 percent between 1991 and 1996. Despite the recent decline in teen births and birth rates, a growing number and proportion are to unmarried teens. Most teenagers giving birth in the 1990s are not married--78 percent overall in 1997. Teenage childbearing has important social and health consequences for the teenage mother herself and for her baby. Most teen births are unintended, the educational attainment of teen mothers is limited, teen mothers are less likely to receive timely prenatal care, and teens are more likely to smoke during pregnancy than are older women. As a consequence of these and other factors, babies born to teen mothers are at greater risk of preterm delivery and low birthweight. Teen pregnancy prevention has become a major focus of attention over the past several years, contributing to a wide variety of initiatives and strategies at the national, state and community level.


Linking process and measurement models of recognition-based decisions.
When making inferences about pairs of objects, one of which is recognized and the other is not, the recognition heuristic states that participants choose the recognized object in a noncompensatory way without considering any further knowledge. In contrast, information-integration theories such as parallel constraint satisfaction (PCS) assume that recognition is merely one of many cues that is integrated with further knowledge in a compensatory way. To test both process models against each other without manipulating recognition or further knowledge, we include response times into the r-model, a popular multinomial processing tree model for memory-based decisions. Essentially, this response-time-extended r-model allows to test a crucial prediction of PCS, namely, that the integration of recognition-congruent knowledge leads to faster decisions compared to the consideration of recognition only-even though more information is processed. In contrast, decisions due to recognition-heuristic use are predicted to be faster than decisions affected by any further knowledge. Using the classical German-cities example, simulations show that the novel measurement model discriminates between both process models based on choices, decision times, and recognition judgments only. In a reanalysis of 29 data sets including more than 400,000 individual trials, noncompensatory choices of the recognized option were estimated to be slower than choices due to recognition-congruent knowledge. This corroborates the parallel information-integration account of memory-based decisions, according to which decisions become faster when the coherence of the available information increases. (PsycINFO Database Record


Functional data analysis of prosodic effects on articulatory timing.
An application of functional data analysis (FDA) (Ramsay and Silverman, 2005, Functional Data Analysis, 2nd ed. (Springer-Verlag, New York)) for linguistic experimentation is explored. The functional time-registration method provided by FDA is shown to offer novel advantages in the investigation of articulatory timing. Traditionally, articulatory studies examining the effects of linguistic variables such as prosody on articulatory timing have relied on comparing the durations of speech intervals of interest defined by kinematic landmarks. Such measurements, however, do not preserve information on the detailed, continuous pattern of articulatory timing that unfolds during these intervals. We present an approach that allows the analysis of entire, continuous kinematic trajectories obtained in a movement tracking experiment examining the influence of a phrasal boundary on articulatory patterning. FDA time deformation functions, after alignment of test and reference (control) signals, reveal delaying of articulator movement (i.e., slowing of the internal clock rate) in the presence of a phrase boundary as the speech stream recedes from the boundary. This is a theoretically predicted pattern (Byrd and Saltzman, 2003, The elastic phrase: Modeling the dynamics of boundary-adjacent lengthening, Journal of Phonetics 31, 149-180.), which would be more difficult to validate with a traditional interval-based approach. It is concluded that the FDA time alignment method provides a useful tool for characterizing timing patterns in linguistic experimentation based on continuous kinematic trajectories.


Gardner's syndrome, a rare combination in surgical practice.
A 45-year-old man presented to the emergency ward with features of intestinal obstruction of 2 days duration. On admission, there was abdominal distension and multiple sessile polyps found on digital rectal examination. In addition, a soft tissue swelling near the elbow and a bony swelling over scalp were noted. Abdominal radiography revealed gaseous distension of the small and large bowel, and ultrasound revealed diffuse, gas-filled bowel with sluggish peristalsis. The obstruction failed to resolve with conservative measures and at emergency laparotomy an irregular hard recto-sigmoid junction mass was identified. A defunctioning transverse loop colostomy was undertaken and the abdomen closed. During recovery, a colonoscopy was performed and a malignant appearing lesion was identified 15 cm proximal to the anal verge. Further per-stomal colonoscopy revealed multiple sessile polyps from the ileo-caecal valve to the descending colon. The cutaneous and abdominal findings were consistent with a rare acute presentation of Gardner's syndrome.


Analysis of bovine herpesvirus 1 transcripts during a primary infection of trigeminal ganglia of cattle.
During an infection of nonneuronal cells, bovine herpesvirus 1 (BHV-1) gene expression proceeds in a well-defined cascade. Products of immediate-early (IE) genes are expressed first, and they activate expression of early (E) and late (L) genes. Although the same cascade is assumed to occur during an infection of neurons in trigeminal ganglia (TG) of cattle, no experimental data is available to support this hypothesis. Consequently, we analyzed BHV-1 gene expression in bovine TG at 1, 2, 4, 7, and 15 days postinfection (dpi). Infectious virus was detected in ocular swabs from 1 to 7 dpi but not 15 dpi. By reverse transcription (RT)-PCR, IE (bICP4), E (thymidine kinase, ribonucleotide reductase [RR]), L (glycoprotein C, and alpha trans-inducing factor), and dual-kinetic (bICP0 and bICP22) transcripts were analyzed. When cDNA synthesis was primed with random hexamers, IE and E transcripts were detected at the same time. However, full-length and poly(A)+ (FL&P) RR or bICP22 RNAs were detected before FL&P IE RNAs. Furthermore, FL&P IE transcripts were not detected until viral DNA increased in TG. IE transcripts were detected before E or L RNAs when rabbit kidney cells were infected with a low multiplicity of infection and the same RT-PCR detection method was used. These studies suggested that expression of full-length and polyadenylated IE transcripts in trigeminal ganglia was not efficient compared to that of RR and bICP22 transcripts.


Advances of Reverse Vaccinology for mRNA Vaccine Design against SARS-CoV-2: A Review of Methods and Tools.
mRNA vaccines are a new class of vaccine that can induce potent and specific immune responses against various pathogens. However, the design of mRNA vaccines requires the identification and optimization of suitable antigens, which can be challenging and time consuming. Reverse vaccinology is a computational approach that can accelerate the discovery and development of mRNA vaccines by using genomic and proteomic data of the target pathogen. In this article, we review the advances of reverse vaccinology for mRNA vaccine design against SARS-CoV-2, the causative agent of COVID-19. We describe the steps of reverse vaccinology and compare the in silico tools used by different studies to design mRNA vaccines against SARS-CoV-2. We also discuss the challenges and limitations of reverse vaccinology and suggest future directions for its improvement. We conclude that reverse vaccinology is a promising and powerful approach to designing mRNA vaccines against SARS-CoV-2 and other emerging pathogens.


Simultaneous determination of 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, and 1,25-dihydroxyvitamin D in plasma or serum.
We describe a simultaneous assay for the principal vitamin D metabolites: 25-hydroxyvitamin D, 24-25-dihydroxyvitamin D, and 1,25-dihydroxyvitamin D. Special attention has been paid to simplification of the extensive extraction and purification procedures used in previously described simultaneous assays. All three metabolites were isolated with a single extraction step, followed by only one gradient liquid-chromatographic procedure. For final quantitation we used competitive protein binding assays, involving readily available binding proteins and commercially purchased tritiated vitamin D metabolites. Concentrations in the plasma of healthy subjects (mean age, 27 years), sampled during December were 51 (SD 17) nmol/L, 4.1 (SD 1.3) nmol/L, and 124 (SD 26) pmol/L for 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D and 1,25-dihydroxyvitamin D, respectively. Intra- and interassay CVs for the three metabolites were 4.4 and 3.9%, 6.7 and 8.0%, and 7.0 and 4.8%, respectively.


Effect of working memory and spatial attention tasks on gait in healthy young and older adults.
Changes in gait parameters induced by the concomitant performance of one of two cognitive tasks activating working memory and spatial attention, was examined in healthy young adults (YA) and older adults (OA). There was a main effect of task condition on gait-speed (p = .02), stride-length (p < .001) and double-support time (p = .04) independent of the group. There were no significant differences between working memory and spatial attention associated gait changes. Working-memory and spatial-attention dual-tasking led to a decrease in gait-speed (p = .09 and 0.01) and stride-length (p = .04 and 0.01) and increase in double-support time (p = .01 and 0.03) in YA and decrease in stride-length (p = .04 and 0.01) alone in OA. Cognitive task associated changes in gait may be a function of limited attentional resources irrespective of the type of cognitive task.


Genotyping, identification and multifunctional features of yeasts associated to Bosana naturally black table olive fermentations.
Directly brined black table olives of Bosana variety are a traditional food product of Sardinia island (Italy), spontaneously fermented by yeasts among other microorganisms. However, as far as we know, the identification, biotechnological and probiotic potential of this yeast community has not been investigated yet. In this work, a total of 72 yeast isolates previously obtained from Bosana olive brines were first genotyped by Random Amplified Polymorphic DNA (RAPD-PCR) analysis with primer M13, and then identified by sequencing of D1/D2 domains of rDNA 26S gene. The dominant species were Wickerhamomyces anomalus and Nakazawaea molendini-olei, albeit Candida diddensiae, Candida boidinii, Zygotorulaspora mrakii, and Saccharomyces cerevisiae were also present in lower proportions. For the different biotypes of yeasts obtained, the multivariate analysis of their technological (esterase, lipase and β-glucosidase activities, growth in presence of oleuropein, resistance and susceptibility to NaCl) and probiotic (removal of cholesterol, gastric and pancreatic digestions, biofilms assays alone and in co-culture with Lactobacillus pentosus) features, showed that W. anomalus Wa1 exhibited the best technological characteristics, while S. cerevisiae Sc24 and C. boidinii Cb60 showed promising probiotic features. Therefore, they may have potential application as multifunctional starters, alone or in combination with lactic acid bacteria, during olive processing, albeit further studies are necessary to validate these results.


Childhood intracranial germinoma with granulomatous reaction.
Central nervous system tumors are the second most common type of childhood cancer in Turkey. Germinomas constitute two thirds of intracranial germ cell tumors. The granulomatous inflammation occurring around germinomas can cause histological diagnostic difficulty. We present a 12-year-old girl with a diagnosis of germinoma in the corpus callosum associated with granulomatous reaction to emphasize the diagnostic challenge which may occur during stereotactic biopsy interpretation or intraoperative consultation.


WDM up-conversion employing frequency quadrupling in optical modulator.
This work presents an optical up-conversion system with frequency quadrupling for wavelength-division-multiplexing (WDM) communication systems using a dual-parallel Mach-Zehnder modulator without optical filtering. Four-channel 1.25-Gb/s wired fiber-to-the-x (FTTx) and wireless radio-over-fiber (RoF) signals are generated and transmitted simultaneously. Moreover, the decline in receiver sensitivities due to Mach-Zehnder modulator bias drifts is also investigated. Receiver power penalties of the 20-GHz up-converted WDM signals and baseband (BB) FTTx signals are less than 1 dB when bias deviation voltage is less the 20% of the half-wave voltage. After transmission over a 50-km SSMF, the receiver power penalties of both the BB and 20-GHz RF OOK signals are less than 1 dB. Notably, 60-GHz optical up-conversion can be achieved using 15-GHz radio frequency (RF) components and equipment.


Repression of retrovirus-mediated transgene expression by interferons: implications for gene therapy.
Retrovirus-mediated gene transfer is commonly used in gene therapy protocols and has the potential to provide long-term expression of the transgene. Although expression of a retrovirus-delivered transgene is satisfactory in cultured cells, it has been difficult to achieve consistent and high-level expression in vivo. In this investigation, we explored the possibility of modulating transgene expression by host-derived cytokines. Normal human keratinocytes and dermal fibroblasts were transduced with recombinant retroviruses expressing a reporter gene (lacZ). Treatment of transduced cells with a proinflammatory cytokine, gamma interferon (IFN-gamma), significantly reduced lacZ expression to less than 25% of that of nontreated cells. The inhibition was concentration dependent (peak at 5 ng/ml) and time dependent (maximal at 16 h for transcript and 24 h for protein); expression remained repressed in the continued presence of IFN-gamma but returned to normal levels 24 h after IFN-gamma withdrawal. The decrease in beta-galactosidase activity appeared to result from decrease in steady-state lacZ mRNA levels. Inhibitors of transcription and translation blocked IFN-gamma-induced repression, suggesting involvement of newly synthesized protein intermediates. Similar results were obtained by treatment of transduced cells with IFN-alpha but not with other proinflammatory cytokines, including tumor necrosis factor alpha, interleukin-2 (IL-1), IL-4, and granulocyte colony-stimulating factor. Although the level of lacZ mRNA was reduced by >70% following IFN treatment, the rate of lacZ transcription was not significantly different from that for nontreated cells. These results suggest that IFN-mediated regulation of transgene expression is at a posttranscriptional level. Interestingly, IFN-gamma also suppressed transgene expression driven by a cellular promoter (involucrin) inserted in an internal position in the retroviral vector. The presence of the overlapping 3' untranslated regions in transcripts initiated from the internal promoter and the long terminal repeat is suggestive of a posttranscriptional regulation, likely at the level of RNA stabilization. These results provide direct evidence for modulatory effects of IFNs on retrovirus-mediated transgene expression and suggest that gene therapy results may be altered by host inflammatory responses.


Absent correlation between vaginal bleeding and oestradiol levels or endometrial morphology during tibolone use in early postmenopausal women.
To investigate a potential correlation between vaginal bleeding and oestradiol (E2) levels/endometrial morphology in early postmenopausal women using tibolone (Livial(R)). A 2-year randomised placebo-controlled study of 94 healthy women, 1-3 years after spontaneous menopause, receiving either placebo (n=23), 1.25 mg/day (n=36) or 2.5 mg/day (n=35) tibolone. Episodes of vaginal bleeding throughout the 2-year study period were recorded. Age, age of menopause, months since menopause and body mass index were recorded. Serum E2 levels were assessed at baseline and at 3-month intervals throughout the study period. In case of vaginal bleeding, endometrium morphology was assessed by Vabra Curettage. Fifty-one percent (n=18, P<0.05) of women in the 2.5 mg/day tibolone group and 44% (n=16, P=0.07) in the 1.25 mg/day tibolone group presented with at least one period of vaginal bleeding, compared with 22% (n=5) in the placebo group. The women who bled in the placebo group were younger (P<0.01), had menopause at an earlier age (P<0.05), had a shorter duration since menopause (P<0.05) and had a higher median E2 serum level prior to bleeding (P<0.05). In contrast, in both tibolone groups, no determinants could be found for the vaginal bleeding. Ninety percent of the first bleedings occurred within 9 months after starting the treatment. At Vabra endometrium sampling, there was no evidence of endometrial stimulation. In the present study, early postmenopausal women using 1.25 or 2.5 mg/day tibolone are 2-2.5 times more likely to present with vaginal bleeding compared with placebo (P<0.05) without evidence of higher serum E2 levels or endometrial stimulation.


Chemical bonding analysis of excited states using the adaptive natural density partitioning method.
A novel approach to chemical bond analysis for excited states has been developed. Using an extended adaptive natural density partitioning method (AdNDP) as implemented in AdNDP 2.0 code, we obtained chemically intuitive bonding patterns for the excited states of H2O, B5+, and C2H4+ molecules. The deformation pathway in the excited states could be easily predicted based on the analysis of the chemical bond pattern. We expect that this new method of chemical bonding analysis would be very helpful for photochemistry, photoelectron spectroscopy, electron spectroscopy and other chemical applications that involved excited states.


Genetic variability in plasma melatonin in sheep is due to pineal weight, not to variations in enzyme activities.
This study was conducted to determine the origin of the high variability in the mean nocturnal plasma melatonin concentration (MC) in sheep. Two extreme groups of 25 lambs each [low (L) and high (H)] were obtained by calculating their genetic value on the basis of the MC of their parents. The MC of lambs was significantly higher in the H group than in the L group (L: 189.7 +/- 24.4 vs. H: 344.1 +/- 33.0 pg/ml, P < 0.001). Within each group, 13 lambs were slaughtered during the day (D) and 12 lambs during the night (N). Pineal weight was significantly higher in the H group than in the L group (L: 83.5 +/- 6.7 vs. H: 119.1 +/- 9.2 mg, P < 0.01) but did not differ between D and N. The amount of melatonin released in vitro per milligram of pineal gland, the arylalkylamine N-acetyltransferase (AANAT) activity, the AANAT protein content, and the level of AANAT mRNA differed significantly between D and N but not with genetic group. Hydroxyindole O-methyltransferase activity did not differ significantly between D and N or between genetic groups. Therefore, the genetic difference in MC between the two groups of lambs was attributed to a difference in pineal size, not in enzymatic activity of the pinealocytes.


Laboratory strategic defense initiatives against transmission of human immune deficiency virus in blood and blood products.
Serological methods based on enzyme linked immunosorbent assay (ELISA) and Western blot tests for detecting the presence of antibodies against the human immune deficiency virus are the standard techniques for identifying infected blood donors. However, these tests could not detect infected seronegative donors who were in the window period at the time of donation. Such donors can be identified by more elaborate methods including antigen detecting ELISA and polymerase chain reaction, which can detect viral antigens and nucleic acids in infected donor blood even in window period. In addition, the process of donor selection whereby individuals who were at high risk for HIV infections were excluded from the donor panel had substantially reduced the risk of window period donation. Furthermore, in order to ensure greater safety, transfusion centers nowadays undertake additional measures in the form of virucidal techniques such as the use of heat, detergents and photochemical agents to treat blood and blood products. Despite all of these measures, a risk-free transfusion was not practically achievable. However, risk-free transfusion is now possible with the introduction of recombinant blood products, the use of which is severely limited by their cost. Nonetheless, a risk-free transfusion is still achievable at a relatively little cost by transfusing suitably eligible patients with their own blood through the autologous blood transfusion program. Antibody testing is virtually the only method currently available in Nigerian blood banks. There is the need to reactivate and expand the scope of our National Blood Transfusion Service in order to make our blood and products safer.


Anatomical contribution to the surgical construction of the sartorius muscle flap.
The sartorius muscle (SM) is frequently used as a surgical flap. This study intends to describe sartorius nerve and artery distribution in adult men. Fifty-three specimens obtained from fresh cadavers were prepared as described: 32 specimens were injected with a red-colored gelatin solution through the femoral artery so that intra-muscular arteries and nerves were dissected; six specimens were injected with barium sulfate solution through the femoral artery for radiography; seven specimens were injected with a Chinese ink solution, also through the femoral artery, for diaphanization; seven specimens were injected with a solution of vinyl acetate, through the femoral artery, to obtain an arterial cast and one specimen was cut and colored by Masson's Trichrome. Sartorius branching patterns of the nerve and artery were schematized. The following measurements were taken for each dissected muscle: total length, arterial pedicle length and distance between each arterial pedicle to the proximal muscle extremity. Five to nine arterial pedicles were found in the sample. In their trajectories, these arteries may give rise to many branches to form a dense and elongated net of anastomoses. Intra- and inter-pedicular anastomoses were observed in the inner part of the muscle. The nerve supply originated from one or two branches, which enter the muscle together with the first or second arterial pedicle. The nerve branches were divided into two or three territorial branches, and then into four or five segmental branches, running longitudinally inside the muscle. The muscles showed an average length of 44.81 cm. SM is a segmented structure and it can be divided into as many as five arterial and nervous segments. In the proximal and middle parts, the muscle has better arterial supply. The segments can be filled by adjacent pedicles, due to an elongated net of anastomoses, which allow a longer arc of rotation in the construction of pedicled flaps.


Use of diuretics in chronic renal failure.
Patients with chronic renal failure retain Na+ and H2O, and they retain K- and acid. This disordered homeostasis results in hypertension, edema, hyperkalemia and acidosis. Diuretics may be used to favorably modify these disturbances. However, because of the limited filtered load of water and electrolytes, and the low renal blood flow, measures need to be taken to maximize the response to diuretics. These measures include: (a) the use of the most bioavailable drug, torasemide, when using the oral route; (b) the use of the drug with the least hepatic elimination, furosemide, when using the intravenous route; (c) the use of combinations of loop- and distal tubule-acting diuretics; (d) the use of the maximum effective diuretic dose; and (e) the use of repeated doses or constant infusion. In benefiting hypertension, vascular congestion and hyperkalemia diuretics appear to exert their effects not only on the kidneys but also on extrarenal sites, such as the vascular tree and the gastrointestinal tract. The use of diuretics, however, is not without complications, which include: intravascular volume depletion and azotemia, ototoxicity (when using loop-acting diuretics), hyperlipidemia, acute pancreatitis, hyperkalemia (when using K(+)-sparing agents), and acidosis (when using carbonic anhydrase inhibitors).


Attenuation of glucose transport across Caco-2 cell monolayers by a polyphenol-rich herbal extract: interactions with SGLT1 and GLUT2 transporters.
Previous studies have indicated that secondary plant metabolites may modulate glucose absorption in the small intestine. We have characterized a polyphenol-rich herbal extract and its potential intestinal metabolites by LC-MS(2) and investigated the inhibition of glucose transporters SGLT1 and GLUT2 using the well-characterized Caco-2 intestinal model. Differentiated Caco-2 monolayers were incubated with an extract of a mixture of herbs and spices. Glucose transport under sodium-dependent and sodium-free conditions was determined by radiochemical detection of D-[U-(14) C]-glucose. A 54% decrease in transport was observed compared to control. Using sodium-dependent and sodium-free conditions, we demonstrate that the inhibition of GLUT2 was greater than SGLT1. Glycosidase and esterase enzymatic hydrolysis was used to assess the impact of metabolism on the efficacy of inhibition. Glucose transport across the membrane was reduced by 70% compared to the control and was associated with significant increases in flavonoid aglycones, caffeic acid, and p-coumaric acid. These results suggest that intact and hydrolyzed polyphenols, likely to be found in the lumen after ingestion of the supplement, play an important role in the attenuation of glucose absorption and may have potentially beneficial antiglycemic effects in the body.


Reactive nitrogen and oxygen species in anticoagulated blood of healthy sheep.
Little or no study has been done to compare the indices of 'nitrosative' and 'oxidative' stresses, especially in terms of correlation and the possible differential effects of the chelating agents. This preliminary study investigated possible correlations between the indices of reactive nitrogen species (RNS) and reactive oxygen species (ROS) in blood, effect of anticoagulated-blood tubes, and impact of blood-clotting pathways. Thirty blood samples from sheep were collected into ethylenediamine tetraacetic acid (EDTA) and citrate tubes at the Berrima Veterinary Laboratory using their standard protocol. Nitrosative and oxidative stress indices were then measured and correlation analyses performed. The ROS and RNS indices were weakly correlated (r > 0.2; p < 0.05) with each other from the EDTA sample, but not from citrated blood. None of the nitrosative or oxidative stress biomarkers was significantly associated with changes in the prothrombin time. The activated partial thromboplastin time showed statistically significant association with some oxidative stress indices (catalase and malondialdehyde), but with none of the nitrosative stress indices. Further, all measured parameters were higher in EDTA than in citrate blood (p < 0.0001). The choice of anticoagulated blood tube could affect the measures of nitrosative stress indices and may impact on the potential correlations between nitrosative versus oxidative stress biomarkers. Perhaps the suggestion that EDTA is better than citrate for hematological anticoagulant studies should be considered for nitrosative and oxidative stress studies.


On the character of the nuclear membrane-associated DNA of HeLa cells.
The nature of the nascent DNA-membrane complexes isolated from synchronized HeLa cells was examined. It was found that membrane-associated DNA is not the result of repair replication. A study of the stability of the complexes to various degradative agents and enzymes suggest that the DNA is associated with a structure which is composed of a lipoprotein. An examination of the physical structure of this DNA indicates that it might be a "nicked" duplex with a base content similar to that of the bulk DNA.


A hepcidin lowering agent mobilizes iron for incorporation into red blood cells in an adenine-induced kidney disease model of anemia in rats.
Anemia is a common complication of chronic kidney disease (CKD) that negatively impacts the quality of life and is associated with numerous adverse outcomes. Excess levels of the iron regulatory hormone hepcidin are thought to contribute to anemia in CKD patients by decreasing iron availability from the diet and from body stores. Adenine treatment in rats has been proposed as an animal model of anemia of CKD with high hepcidin levels that mirrors the condition in human patients. We developed a modified adenine-induced kidney disease model with a higher survival rate than previously reported models, while maintaining persistent kidney disease and anemia. We then tested whether the small molecule bone morphogenetic protein (BMP) inhibitor LDN-193189, which was previously shown to lower hepcidin levels in rodents, mobilized iron into the plasma and improved iron-restricted erythropoiesis in this model. Adenine-treated rats exhibited increased hepatic hepcidin mRNA, decreased serum iron, increased spleen iron content, low hemoglobin (Hb) and inappropriately low erythropoietin (EPO) levels relative to the degree of anemia. LDN-193189 administration to adenine-treated rats lowered hepatic hepcidin mRNA, mobilized stored iron into plasma and increased Hb content of reticulocytes. Our data suggest that hepcidin lowering agents may provide a new therapeutic strategy to improve iron availability for erythropoiesis in CKD.


Phenotypic constraints and community structure: linking trade-offs within and among species.
Trade-offs are central to many topics in biology, from the evolution of life histories to ecological mechanisms of species coexistence. Trade-offs observed among species may reflect pervasive constraints on phenotypes that are achievable given biophysical and resource limitations. If so, then among-species trade-offs should be consistent with trade-offs within species. Alternatively, trait variation among co-occurring species may reflect historical contingencies during community assembly rather than within-species constraints. Here, we test whether a key trade-off between relative growth rate (RGR) and water-use efficiency (WUE) among Sonoran Desert winter annual plants is apparent within four species representing different strategies in the system. We grew progeny of maternal families from multiple populations in a greenhouse common garden. One species, Pectocarya recurvata, displayed the expected RGR-WUE trade-off among families within populations. For other species, although RGR and WUE often varied clinally among populations, among-family variation within populations was lacking, implicating a role for past selection on these traits. Our results suggest that a combination of limited genetic variation in single traits and negative trait correlations could pose constraints on the evolution of a high-RGR and high-WUE phenotype within species, providing a microevolutionary explanation for phenotypes that influence community-level patterns of abundance and coexistence.


Prevalence and risk factors for refractive errors in adult Chinese in Singapore.
To determine the epidemiology of refractive errors in an adult Chinese population in Singapore. A disproportionate, stratified, clustered, random-sampling procedure was used to select names of 2000 Chinese people aged 40 to 79 years from the 1996 Singapore electoral register in the Tanjong Pagar district in Singapore. These people were invited to a centralized clinic for a comprehensive eye examination, including refraction. Refraction was also performed on nonrespondents in their homes. Myopia, high myopia, and hyperopia were defined as a spherical equivalent (SE) in the right eye of less than -0.5 D, less than -5.0 D, and more than +0.5 D, respectively. Astigmatism was defined as less than -0.5 D of cylinder. Anisometropia was defined as a difference in SE of more than 1.0 D between the two eyes. Only phakic eyes were analyzed. From 1717 eligible people, 1232 (71.8%) were examined. Adjusted to the 1997 Singapore population, the overall prevalence of myopia, hyperopia, astigmatism, and anisometropia was 38.7% (95% confidence interval [CI]: 35.5, 42.1), 28.4% (95% CI: 25.3, 31.3), 37.8% (95% CI: 34.6, 41.1), and 15.9% (95% CI: 13.5, 18.4), respectively. The prevalence of high myopia was 9.1% (95% CI: 7.2, 11.2), with women having significantly higher rates than men. The age pattern of myopia was bimodal, with higher prevalence in the 40 to 49 and 70 to 81 age groups and lower prevalence between those age ranges. Prevalence was reversed in hyperopia, with a higher prevalence in subjects aged 50 to 69. There was a monotonic increase in prevalence with age for both astigmatism and anisometropia. Increasing educational levels, higher individual income, professional or office-related occupations, better housing, and greater severity of nuclear opacity were all significantly associated with higher rates of myopia, after adjustment for age and sex. The results indicate that whereas myopia is 1.5 to 2.5 times more prevalent in adult Chinese residing in Singapore than in similarly aged European-derived populations in the United States and Australia, the sociodemographic associations are similar.


Silver Nanowire Network Hybridized with Silver Nanoparticle-Anchored Ruthenium Oxide Nanosheets for Foldable Transparent Conductive Electrodes.
Facile strategies in flexible transparent conductive electrode materials that can sustain their electrical conductivities under 1 mm-scale radius of curvature are required for wider applications such as foldable devices. We propose a rational design as well as a fabrication process for a silver nanowire-based transparent conductive electrode with low sheet resistance and high transmittance even after prolonged cyclic bending. The electrode is fabricated on a poly(ethylene terephthalate) film through the hybridization of silver nanowires with silver nanoparticles-anchored RuO2 nanosheets. This hybridization significantly improves the performance of the silver nanowire network under severe bending strain and creates an electrically percolative structure between silver nanowires and RuO2 nanosheets in the presence of anchored silver nanoparticles on the surface of RuO2 nanosheets. The resistance change of this hybrid transparent conductive electrode is 8.8% after 200,000 bending cycles at a curvature radius of 1 mm, making it feasible for use in foldable devices.


The Drivers of Discretionary Utilization: Clinical History Versus Physician Supply.
Because the effect of physician supply on utilization remains controversial, literature based on non-Medicare populations is sparse, and a physician supply expansion is under way, the potential for physician-induced demand across diverse populations is important to understand. A substantial proportion of gastrointestinal endoscopies may be inappropriate. The authors analyzed the impact of physician supply, practice patterns, and clinical history on esophagogastroduodenoscopy (EGD, defined as discretionary) among patients hospitalized with lower gastrointestinal bleeding (LGIB). Among 34,344 patients hospitalized for LGIB from 2004 to 2009, 43.1% and 21.3% had a colonoscopy or EGD, respectively, during the index hospitalization or within 6 months after. Linking to the Dartmouth Atlas via patients' hospital referral region, gastroenterologist density and hospital care intensity (HCI) index were ascertained. Adjusting for age, gender, comorbidities, and race/education indicators, the association of gastroenterologist density, HCI index, and history of upper gastrointestinal disease with EGD was estimated using logistic regression. EGD was not associated with gastroenterologist density or HCI index, but was associated with a history of upper gastrointestinal disease (OR 2.30; 95% CI 2.17-2.43), peptic ulcer disease (OR 4.82; 95% CI 4.26-5.45), and liver disease (OR 1.34; 95% CI 1.18-1.54). Among patients hospitalized with LGIB, large variation in gastroenterologist density did not predict EGD, but relevant clinical history did, with association strengths commensurate with risk for upper gastrointestinal bleeding. In the scenario studied, no evidence was found that specialty physician supply increases will result in more discretionary care within commercially insured populations.


Alterations in mesenteric lymph node T cell phenotype and cytokine secretion are associated with changes in thymocyte phenotype after LP-BM5 retrovirus infection.
In this study, mouse MLN cells and thymocytes from advanced stages of LP-BM5 retrovirus infection were studied. A decrease in the percentage of IL-7(+) cells and an increase in the percentage of IL-16(+) cells in the MLN indicated that secretion of these cytokines was also altered after LP-BM5 infection. The percentage of MLN T cells expressing IL-7 receptors was significantly reduced, while the percentage of MLN T cells expressing TNFR-p75 and of B cells expressing TNFR-p55 increased. Simultaneous analysis of surface markers and cytokine secretion was done in an attempt to understand whether the deregulation of IFN-gamma secretion could be ascribed to a defined cell phenotype, concluding that all T cell subsets studied increased IFN-gamma secretion after retrovirus infection. Finally, thymocyte phenotype was further analyzed trying to correlate changes in thymocyte phenotype with MLN cell phenotype. The results indicated that the increase in single positive either CD4(+)CD8(-) or CD4(-)CD8(+) cells was due to accumulation of both immature (CD3(-)) and mature (CD3(+)) single positive thymocytes. Moreover, single positive mature thymocytes presented a phenotype similar to the phenotype previously seen on MLN T cells. In summary, we can conclude that LP-BM5 uses the immune system to reach the thymus where it interferes with the generation of functionally mature T cells, favoring the development of T cells with an abnormal phenotype. These new T cells are activated to secrete several cytokines that in turn will favor retrovirus replication and inhibit any attempt of the immune system to control infection.


Hydration of bilayered graphene oxide.
The hydration of graphene oxide (GO) membranes is the key to understand their remarkable selectivity in permeation of water molecules and humidity-dependent gas separation. We investigated the hydration of single GO layers as a function of humidity using scanning force microscopy, and we determined the single interlayer distance from the step height of a single GO layer on top of one or two GO layers. This interlayer distance grows gradually by approximately 1 Å upon a relative humidity (RH) increase in the range of 2 to ∼80%, and the immersion into liquid water increases the interlayer distance further by another 3 Å. The gradual expansion of the single interlayer distance is in good agreement with the averaged distance measured by X-ray diffraction on multilayered graphite oxides, which is commonly explained with an interstratification model. However, our experimental design excludes effects connected to interstratification. Instead we determine directly if insertion of water into GO occurs strictly by monolayers or the thickness of GO layers changes gradually. We find that hydration with up to 80% RH is a continuous process of incorporation of water molecules into single GO layers, while liquid water inserts as monolayers. The similarity of hydration for our bilayer and previously reported multilayered materials implies GO few and even bilayers to be suitable for selective water transport.


The impact of commodity price volatility on fiscal balance and the role of real interest rate.
The objective of this study is to explore the impact of commodity price volatility on the governments' fiscal balance. Using a dynamic panel data model for 108 countries from 1993 to 2018, this study finds that governments' fiscal balance deteriorates with commodity price volatility, especially for commodity-exporting economies. A one standard deviation increase in commodity price volatility leads to a reduction of approximately 0.04 units in the fiscal balance as a percentage of gross domestic product. Further, we examine the role of real interest rates in influencing the relationship between commodity price volatility and fiscal balance. The empirical results suggest that the negative impact of commodity price volatility on fiscal balance can be mitigated with a lower real interest rate. This implies under the sticky price assumption, an accommodative monetary policy could be effective in moderating the negative effect of commodity price volatility on fiscal balance.


A multimedia program for caregivers of pediatric patients with chronic kidney disease in Guatemala.
A multimedia medication training program for parents and legal guardians of children with chronic kidney disease (CKD) aimed to improve comprehension CKD and general information about medications used in pediatric patients attending The Foundation for Children with Kidney Disease (FUNDANIER, Guatemala City). A quasi-experimental study was carried out to measure the impact of the educational intervention on medication knowledge, at FUNDANIER from September to October 2019. Means and standard deviations was used to described test results. A Wilcoxon test was performed, to compare scores of pre and post-tests. Odds Ratio (OR) was used to determine if there was an improvement in the knowledge score before and after the intervention. Results There was significant improvement in knowledge scores knowledge before and after the intervention(27/35 versus 33/35, P < 0.005). Mestizo participants had higher odds of improvement before and after the intervention (OR 7, CI: 0.6-78). Parent-guardians with prior education, and who spoke Spanish had higher odds of improved knowledge scores (OR 3.2, CI:0.3-35; OR 1.1 CI: 0.1-14 respectively). Caregivers who participated in the educational workshop improved and retained information related to CKD comprehension and medications used. This study provides a model for educational modules that can be used, tested, and applied in other chronic disease settings in low to middle income countries. A culturally relevant multimedia CKD educational platform was effective in improving medication knowledge among parent/guardians of children with CKD in a low literacy setting.


Evaluation of the revised algorithm of Autism Diagnostic Observation Schedule (ADOS) in the diagnostic investigation of high-functioning children and adolescents with autism spectrum disorders.
The Autism Diagnostic Observation Schedule (ADOS) is a semi-structured, standardized assessment designed for use in diagnostic evaluation of individuals with suspected autism spectrum disorder (ASD). The ADOS has been effective in categorizing children who definitely have autism or not, but has lower specificity and sometimes sensitivity for distinguishing children with milder ASDs. Revised ADOS algorithms have been recently developed. The goals of this study were to analyze the predictive validity of different ADOS algorithms for module 3, in particular for high-functioning autism spectrum disorder. The participants were 252 children and adolescents aged between four and 16 years, with a full-scale IQ above 70 (126 with a diagnosis of ASD, 126 with a heterogeneous non-spectrum diagnosis). As a main finding, sensitivity was substantially higher for the newly developed 'revised algorithm', both for autism versus non-spectrum, as well as for the broader ASD versus non-spectrum, using the higher cut-off. The strength of the original algorithm lies in its positive predictive power, while the revised algorithm shows weaknesses in specificity for non-autism ASD. As the ADOS is valid and reliable even for higher functioning ASD, the findings of the present study have been used to make recommendations regarding the best use of ADOS algorithms in a high-functioning sample.


Collaborative quality improvement.
Quality improvement collaboratives were developed in many medical and surgical disciplines with the goal of measuring and improving the quality of care provided to patients. The aim of this review is to provide an overview of surgical quality improvement collaboratives, and in particular those aimed at improving urological care. Quality improvement collaboratives collect high-quality data using standardized methodologies, and use the data to provide feedback to physicians and practices, and then implement processes to improve patient outcomes. The largest regional collaborative in urology is the Michigan Urological Surgery Improvement Collaborative (MUSIC). Recent efforts by this group have been focused at understanding variation in care, improving patient selection for treatment, reducing treatment morbidity and measuring and optimizing technical skill. The American Urological Association has also recently launched a national quality registry (AQUA), with an initial focus on prostate cancer care. By understanding factors that result in exemplary performance, quality improvement collaboratives are able to develop best practices around areas of care with high variation that have the potential to improve outcomes and reduce costs. These developments have been made possible by the unique model offered by the collaborative structure with the goal of improving patient care at a population level.


Bethesda criteria for microsatellite instability testing: impact on the detection of new cases of Lynch syndrome.
In 1997 Bethesda Guidelines (BG) were established and in 2004 those criteria were revised (RBG), with the main goal of selecting colorectal cancers (CRC) that should be subjected to microsatellite instability (MSI) testing. High microsatellite instability (MSI-H) is an intermediate marker for mutational analysis of the mismatch repair (MMR) genes involved in the genesis of Lynch Syndrome (LS). We aimed to evaluate and compare BG/RBG in the detection of MSI-H and subsequent identification of pathogenic MMR genes mutations. We included 174 patients with CRC and indication for MSI analysis according to BG or RBG. MSI testing was performed with the Bethesda markers and mutational analysis of MLH1, MSH2 and MSH6 genes undertaken with DGGE, MLPA and direct sequencing. One hundred fourteen of 174 patients (65.5 %) fulfilled BG and all of them RBG. With the BG, MSI-H was detected in 37/114 (32.5 %) CRCs and mutational analysis was positive in 14/37 (37.8 %) patients. The RBG led to detection of MSI-H in 49/174 (28.2 %) of the CRCs, having the mutational analysis been positive in 16/49 (32.7 %) patients. We could identify 14/114 (12.3 %) new cases of LS, through BG and 16/174 (9.2 %) via RBG. BG presented a similar overall percentage for the detection of MSI-H and mutations when compared with RBG. RBG implicated the analysis of more patients, though they gave rise to detection of two additional LS cases. This difference has a significant impact on the establishment of preventive measures, mainly for CRC, in all the mutation-carriers belonging to these families.


Treatment of autoimmune diseases in MRL/lpr mice by allogenic bone marrow transplantation plus adult thymus transplantation.
MRL/lpr mice (H-2(k)) with Fas gene mutation develop severe autoimmune diseases, and their haematolymphoid cells such as bone marrow and spleen cells showed a low apoptotic activity by irradiation. Therefore, conventional bone marrow transplantation (BMT) cannot be used to treat autoimmune diseases in these mice (chimeric resistance). In the present study, we examine the effects of additional adult thymus transplantation (TT) from the same donor on successful BMT. When the MRL/lpr mice were lethally irradiated (9 x 5Gy) and reconstituted with 3 x 10(7) of C57BL/6 mouse (H-2b) bone marrow cells (BMCs) in conjunction with TT, the mice significantly survived long term and showed a high donor-derived chimerism in comparison with those treated with BMT alone. Interestingly, the numbers of not only donor-derived T cells but also B cells increased significantly in the mice treated with BMT plus TT, even at the early phase of BMT. The number of aberrant CD3+B220+ cells decreased significantly, and the numbers of lymphocyte subsets were also normalized 4 weeks after the treatment. Finally, the autoimmune diseases in MRL/lpr mice could be cured by BMT with TT. These results indicate that the combination of BMT plus TT can overcome the chimeric resistance and treat the autoimmune diseases in MRL/lpr mice.


Electroconvulsive therapy in drug resistant neuroleptic malignant syndrome.
We report a case of a 20 years female referred to us with a history of a brief psychotic episode for which she was given inj. Haloperidol. The patient presented in an unconscious state with high grade fever. The diagnosis was kept as neuroleptic malignant syndrome after ruling out other possibilities. The patient did not respond to Bromocriptine and Dantrolene. With the recent evidence of electroconvulsive therapy being useful in these patients, we went ahead with the same. We present this case to share our experience of the excellent response of neuroleptic malignant syndrome to electroconvulsive therapy.