Concentrations of Staphylococcus species in indoor air as associated with other bacteria, season, relative humidity, air change rate, and S. aureus-positive occupants.
The aim of this study was to obtain knowledge about concentrations of Staphylococcus aureus, MRSA (methicillin-resistant S. aureus), and other Staphylococcus species in indoor air in Greater Copenhagen and about factors affecting the concentrations. The effects of season, temperature, relative humidity, air change rate (ACR), other bacterial genera, area per occupant, and presence of S. aureus-positive occupants were studied. In samples from 67 living rooms, S. hominis, S. warneri, S. epidermidis, and S. capitis were found in 13-25%; S. saprophyticus, S. cohnii, and S. pasteuri in 5-10%; and S. lugdunensis, S. haemolyticus, S. caprae, S. equorum, S. kloosii, S. pettenkoferi, S. simulans, and S. xylosus in less than 3%. Staphylococcus aureus were found in two of 67 living rooms: spa type t034 (an MRSA) was recovered from a farmhouse, while spa type t509 was found in an urban home. Two species, S. equorum and S. kloosii, were found only in the farmhouse. Staphylococcus was significantly associated with season with lowest concentration and richness in winter. Genera composition was associated with ACR with smaller fractions of Staphylococcus at higher ACR, while richness was significantly and negatively associated with area per occupant. Concentration of Staphylococcus correlated positively with the total concentration of bacteria, but negatively with the total concentration of other bacteria. The concentration of Staphylococcus was not significantly associated with concentrations of the other abundant genera Bacillus, Kocuria, and Micrococcus. In offices with S. aureus-positive occupants, airborne S. aureus was not found. In conclusion, Staphylococcus species constitute a considerable proportion of the airborne bacteria in the studied homes and offices. However, both S. aureus and MRSA had very low prevalence during all seasons. Thus, transmission of S. aureus and MRSA through the air in living rooms in Copenhagen is expected to be limited. The negative associations between ACR and the fraction Staphylococcus constituted out of total bacteria, and between area per occupant and Staphylococcus richness indicate that it might be possible to affect the presence of airborne Staphylococcus in homes.


Enhanced prediction of porcine islet yield and posttransplant outcome using a combination of quantitative histomorphometric parameters and flow cytometry.
Prediction of islet yield and posttransplant outcome is essential for clinical porcine islet xenotransplantation. Although several histomorphometric parameters of biopsied porcine pancreases are predictive of islet yield, their role in the prediction of in vivo islet potency is unknown. We investigated which histomorphometrical parameter best predicts islet yield and function, and determined whether it enhanced the predictive value of in vitro islet function tests for the prediction of posttransplant outcome. We analyzed the histomorphometry of pancreases from which 60 adult pig islet isolations were obtained. Islet function was assessed using the beta-cell viability index based on flow cytometry analysis, oxygen consumption rate, ADP/ATP ratio, and/or concurrent transplantation into NOD/SCID mice. Receiver operating characteristic (ROC) analysis revealed that only islet equivalent (IEQ)/cm(2) and the number of islets >200 microm in diameter significantly predicted an islet yield of >2000 IEQ/g (p < 0.001 for both) and in vivo islet potency (p = 0.024 and p = 0.019, respectively). Although not predictive of islet yield, a high proportion of large islets (>100 microm in diameter) best predicted diabetes reversal (p = 0.001). Multiple regression analysis revealed that the beta-cell viability index (p = 0.003) and the proportion of islets >100 microm in diameter (p = 0.048) independently predicted mean posttransplant blood glucose level (BGL). When BGL was estimated using both these parameters [area under the ROC curve (AUC), 0.868; 95% confidence interval (CI), 0.730-1.006], it predicted posttransplant outcome more accurately than the beta-cell viability index alone (AUC, 0.742; 95% CI, 0.544-0.939). In conclusion, we identified the best histomorphometric predictors of islet yield and posttransplant outcome. This further enhanced the predictive value of the flow cytometry analysis. These parameters should be useful for predicting islet yield and in vivo potency before clinical adult porcine islet xenotransplantation.


Human platelets possess receptors for a lymphokine: demonstration of high specific receptors for HuIFN-gamma.
This report demonstrates that 125I-recombinant human interferon-gamma (125I-rHuIFN-gamma) binds to high-affinity specific receptors on human platelets. Scatchard analysis of binding data indicates the presence of homogeneous sites estimated in the order of 150 to 200, with an apparent equilibrium dissociation constant, Kd, of 2 X 10(-10) M. The binding of 125I-rHuIFN-gamma to platelet membrane was inhibited by unlabeled rHuIFN-gamma but not by unlabeled rHuIFN-alpha or unlabeled rHuIFN-beta. High affinity binding sites for HuIFN-alpha were not detectable. Cross-linking of 125I-rHuIFN-gamma to platelet membrane proteins with the use of a bifunctional agent (DSS) yielded a predominant complex of 100,000 +/- 5,000 daltons on SDS-PAGE autoradiography, which confirms the presence of specific receptors for IFN-gamma. Two faint bands of lower m.w., 70,000 and 90,000, could also be visualized. Cross-linking of 125I-rHuIFN-alpha to platelet surface could not be demonstrated by using the same procedures. This is the first time that a receptor for a lymphokine (IFN-gamma) has been demonstrated on human platelets. These findings are consistent with data already published, suggesting an interrelationship between IFN and platelet function.


[Will the effectiveness of the immunization of chicks with live Salmonella vaccines be affected by maternal antibodies?].
In the progeny of breeder birds which had been vaccinated with live Salmonella Typhimurium and inactivated Salmonella Enteritidis vaccines, the caecal and systemic colonisation by a live Salmonella Enteritidis and a live Salmonella Typhimurium vaccine was studied. The efficacy of the oral immunisation of chicks from vaccinated and non-vaccinated breeders with a live Salmonella Enteritidis vaccine on day 1 of age was studied by an experimental challenge with Salmonella Enteritidis on day 30 of age. Antibody production of isotypes IgG, IgA and IgM was determined in sera and jejunum of the birds. Vaccination of parent birds resulted in an increase of the antibody concentration in sera and jejunum of the chicks. Own antibody production after administration of the live Salmonella vaccine to the day-old chicks was not detected until day 21 of life. Compared to controls, the number of vaccine organisms in the caeca of the progeny of vaccinated breeder birds was reduced by 0.5-1.5 log10 units. The reduction of the Salmonella Enteritidis vaccine was more pronounced than that of the Salmonella Typhimurium vaccine. However, the reduced colonisation by the live Salmonella vaccine strain did not impair the efficacy of the immunisation of the chicks. To ensure efficacy of the active oral immunisation of chicks from vaccinated parent birds with attenuated live Salmonella vaccines also in case where amounts of maternally transferred antibodies are even higher, it should be guaranteed that chicks take in via drinking water the recommended dose of the vaccine strain. In this connection, factors like the low intake of drinking water by very young chicks, the concentration of the vaccine organisms in the water and the survival of the vaccine should also be considered.


[Evaluation of costs in surgery of inguinal hernia. Day surgery and one day surgery versus ordinary admission].
The authors have completed an analytic research about costs of hospitalization and treatment for inguinal hernioplasty and costs of anesthesiologic and surgical techniques and hospitalization regimen. The authors consider possible in about 50% of cases the tension-free hernioplasty carried out with local anesthesia and day or one day surgery regimen and they have estimated that it is very less costly then traditional herniorraphy carried out with general anesthesia and hospitalization: L. 1.056.075 versus L. 2.252.650. In Emilia-Romagna we could have a considerable cost-saving, even if only the 50% of patients treated for uncomplicated inguinal hernia every year (7.133 patients with mean hospital stay = 5,8 days and total hospitalization = 41.731 days during 1993) could benefit by treatment in one day surgery regimen. In fact, leaving out of account the advantage of the rapid return the patient to work, the costs of hospital stay, esteemed in L. 25.038.600.000, would be L. 8.558.700.000. A considerable increase of one day surgery hernioplasties should be expected by the hospital administration in budget planning.


Secretory activity of Poecilia latipinna (Teleostei) pituitary in vitro: rostral pars distalis and proximal pars distalis.
The ultrastructure of each adenohypophysial secretory cell type was examined in pituitaries of adult female mollies (Poecilia latipinna) after various periods in vitro, and with varied medium osmotic pressure (OP), Na+, and Ca2+ concentrations. Prolactin (PRL) cells were markedly activated by 18 hr, and after 7 or 14 days were almost totally degranulated, with massive arrays of Golgi and RER. Reduction in OP, but not Na+ or Ca2+, caused an additional activation of PRL cells after periods of 18 hr or longer. Corticotroph (ACTH) cells became noticeably activated by 4 hr, and were possibly affected by OP, but not Na+ or Ca2+. Growth hormone (GH) cells were activated by 6 hr, and after 18 hr were quite degranulated with extensive arrays of RER. OP had no effect on GH cells before 3 days, when reduced OP appeared to cause an additional activation, with the appearance of large irregular secretory granule (SG)-like inclusions. Na+ and Ca2+ again had no effect. Gonadotrophic (GtH) cells appeared to be little affected by in vitro incubation; however, the very active cells from vitellogenic fish underwent a reduction in dilated RER after prolonged culture. Thyrotrophic (TSH) cells gradually became activated in vitro, but the response again varied with the sexual condition of the fish. Neither GtH nor TSH cells were affected by OP, Na+, or Ca2+. The findings are discussed in relation to hypothalamic control, via releasing/inhibiting factors, of adenohypophysial cell activity.


How will the 'cancer moonshot' impact health disparities?
In 1971, President Nixon signed into law the National Cancer Act (NCA), colloquially known as the "War on Cancer", which pushed cancer onto the national agenda and is credited for many subsequent increases in the knowledge of the molecular, cellular, and genetic causes and effects of cancer. But even though cancer mortality has declined overall in intervening years after the NCA, cancer health disparities persist in the form of higher cancer incidence and mortality rates among certain cancer types and certain populations. Breast and cervical cancers disproportionately affect African American, Hispanic, and American Indian Women. Colorectal cancer is the second leading cause of death for Latinos (with men and women combined). Forty-five years after the NCA, how will the next enormous cancer initiatives-President Barack Obama's Cancer Moonshot and the All of Us Research Program (formerly the Precision Medicine Initiative Cohort Program)-impact cancer health disparities? The emergence of precision medicine and the sharing of information across sectors are at the heart of these large national initiatives and hold vast potential to address complex health disparities that remain in incidence reporting, incidence, treatment, prognoses, and mortality among certain cancer types and racial/ethnic minorities, including African Americans and Hispanics/Latinos, compared to Whites. But clinical research efforts and data collection have historically lacked diverse representation for various reasons, posing a large risk to these national initiatives in their ability to develop diverse cohorts that adequately represent racial/ethnic minorities. Efforts to reduce disparities and increase diversity in study cohorts have emerged, from patient navigation, to use of mobile technology to collect data, to national consortiums dedicated to including diverse groups, to university training on health disparities. These efforts point to the need for the Cancer Moonshot and precision medicine leaders to develop a multifaceted approach to address disparities in health and healthcare to promote a diverse healthcare workforce, patient-centered care, maintenance of a database of information regarding the state of health disparities, and the institution of measurable goals for improving care across all ethnic groups. If these elements are included, it is possible that the Cancer Moonshot and precision medicine will benefit the entire population of our country.


The impact of artificial intelligence in medicine on the future role of the physician.
The practice of medicine is changing with the development of new Artificial Intelligence (AI) methods of machine learning. Coupled with rapid improvements in computer processing, these AI-based systems are already improving the accuracy and efficiency of diagnosis and treatment across various specializations. The increasing focus of AI in radiology has led to some experts suggesting that someday AI may even replace radiologists. These suggestions raise the question of whether AI-based systems will eventually replace physicians in some specializations or will augment the role of physicians without actually replacing them. To assess the impact on physicians this research seeks to better understand this technology and how it is transforming medicine. To that end this paper researches the role of AI-based systems in performing medical work in specializations including radiology, pathology, ophthalmology, and cardiology. It concludes that AI-based systems will augment physicians and are unlikely to replace the traditional physician-patient relationship.


Crosstalk Between Transforming Growth Factor Beta-2 and Toll-Like Receptor 4 in the Trabecular Meshwork.
The trabecular meshwork (TM) is involved in the outflow of aqueous humor and intraocular pressure (IOP) regulation. Regulation of the extracellular matrix (ECM) by TGFβ2 signaling pathways in the TM has been extensively studied. Recent evidence has implicated toll-like receptor 4 (TLR4) in the regulation of ECM and fibrogenesis in liver, kidney, lung, and skin. Here, we investigated the role of TGFβ2-TLR4 signaling crosstalk in the regulation of the ECM in the TM and ocular hypertension. Cross sections of human donor eyes, primary human TM cells in culture, and dissected mouse TM rings were used to determine Tlr4 expression in the TM. Trabecular meshwork cells in culture were treated with TGFβ2 (5 ng/mL), TLR4 inhibitor (TAK-242, 15 μM), and a TLR4 ligand (cellular fibronectin isoform [cFN]-EDA). A/J (n = 13), AKR/J (n = 7), BALBc/J (n = 8), C3H/HeJ (n = 20), and C3H/HeOuJ (n = 10) mice were injected intravitreally with adenovirus 5 (Ad5).hTGFβ2c226s/c228s in one eye, with the uninjected contralateral eye serving as a control. Conscious IOP measurements were taken using a TonoLab rebound tonometer. Toll-like receptor 4 is expressed in the human and mouse TM. Inhibition of TLR4 signaling in the presence of TGFβ2 decreases fibronectin expression. Activation of TLR4 by cFN-EDA in the presence of TGFβ2 further increases fibronectin, laminin, and collagen-1 expression, and TLR4 signaling inhibition blocks this effect. Ad5.hTGFβ2c226s/c228s induces ocular hypertension in wild-type mice but has no effect in Tlr4 mutant (C3H/HeJ) mice. These studies identify TGFβ2-TLR4 crosstalk as a novel pathway involved in ECM regulation in the TM and ocular hypertension. These data further explain the complex mechanisms involved in the development of glaucomatous TM damage.


3D Printing Drug-Free Scaffold with Triple-Effect Combination Induced by Copper-Doped Layered Double Hydroxides for the Treatment of Bone Defects.
Tissue-engineered poly(l-lactide) (PLLA) scaffolds have been widely used to treat bone defects; however, poor biological activities have always been key challenges for its further application. To address this issue, introducing bioactive drugs or factors is the most commonly used method, but there are often many problems such as high cost, uncontrollable and monotonous drug activity, and poor bioavailability. Here, a drug-free 3D printing PLLA scaffold with a triple-effect combination induced by surface-modified copper-doped layered double hydroxides (Cu-LDHs) is proposed. In the early stage of scaffold implantation, Cu-LDHs exert a photothermal therapy (PTT) effect to generate high temperature to effectively prevent bacterial infection. In the later stage, Cu-LDHs can further have a mild hyperthermia (MHT) effect to stimulate angiogenesis and osteogenic differentiation, demonstrating excellent vascularization and osteogenic activity. More importantly, with the degradation of Cu-LDHs, the released Cu2+ and Mg2+ provide an ion microenvironment effect and further synergize with the MHT effect to stimulate angiogenesis and osteogenic differentiation, thus more effectively promoting the healing of bone tissue. This triple-effect combined scaffold exhibits outstanding antibacterial, osteogenic, and angiogenic activities, as well as the advantages of low cost, convenient procedure, and long-term efficacy, and is expected to provide a promising strategy for clinical repair of bone defects.


[The surgical procedure in splenic injuries].
An analysis of the character of operations in 106 patients with traumas of the spleen has been made. Organ-preserving operations with a laser scalpel were fulfilled on 28 patients. Absolute indications for performing the organ-preserving operation were revealed in 28% of the patients. Relative indications were found in 53%. Methods of laser coagulation are proposed which helped to preserve the spleen in 46% of the patients during the last 4 years.


Selective sorting of microRNAs into exosomes by phase-separated YBX1 condensates.
Exosomes may mediate cell-to-cell communication by transporting various proteins and nucleic acids to neighboring cells. Some protein and RNA cargoes are significantly enriched in exosomes. How cells efficiently and selectively sort them into exosomes remains incompletely explored. Previously, we reported that YBX1 is required in sorting of miR-223 into exosomes. Here, we show that YBX1 undergoes liquid-liquid phase separation (LLPS) in vitro and in cells. YBX1 condensates selectively recruit miR-223 in vitro and into exosomes secreted by cultured cells. Point mutations that inhibit YBX1 phase separation impair the incorporation of YBX1 protein into biomolecular condensates formed in cells, and perturb miR-233 sorting into exosomes. We propose that phase separation-mediated local enrichment of cytosolic RNA-binding proteins and their cognate RNAs enables their targeting and packaging by vesicles that bud into multivesicular bodies. This provides a possible mechanism for efficient and selective engulfment of cytosolic proteins and RNAs into intraluminal vesicles which are then secreted as exosomes from cells.


Patient-Derived Cancer Organoid Cultures to Predict Sensitivity to Chemotherapy and Radiation.
Cancer treatment is limited by inaccurate predictors of patient-specific therapeutic response. Therefore, some patients are exposed to unnecessary side effects and delays in starting effective therapy. A clinical tool that predicts treatment sensitivity for individual patients is needed. Patient-derived cancer organoids were derived across multiple histologies. The histologic characteristics, mutation profile, clonal structure, and response to chemotherapy and radiation were assessed using bright-field and optical metabolic imaging on spheroid and single-cell levels, respectively. We demonstrate that patient-derived cancer organoids represent the cancers from which they were derived, including key histologic and molecular features. These cultures were generated from numerous cancers, various biopsy sample types, and in different clinical settings. Next-generation sequencing reveals the presence of subclonal populations within the organoid cultures. These cultures allow for the detection of clonal heterogeneity with a greater sensitivity than bulk tumor sequencing. Optical metabolic imaging of these organoids provides cell-level quantification of treatment response and tumor heterogeneity allowing for resolution of therapeutic differences between patient samples. Using this technology, we prospectively predict treatment response for a patient with metastatic colorectal cancer. These studies add to the literature demonstrating feasibility to grow clinical patient-derived organotypic cultures for treatment effectiveness testing. Together, these culture methods and response assessment techniques hold great promise to predict treatment sensitivity for patients with cancer undergoing chemotherapy and/or radiation.


Hospital-based surveillance to evaluate the impact of rotavirus vaccination in São Paulo, Brazil.
Brazil implemented routine immunization with the human rotavirus vaccine, Rotarix, in 2006 and vaccination coverage reached 81% in 2008 in São Paulo. Our aim was to assess the impact of immunization on the incidence of severe rotavirus acute gastroenteritis (AGE). We performed a 5-year (2004-2008) prospective surveillance at a sentinel hospital in São Paulo, with routine testing for rotavirus in all children less than 5 years of age hospitalized with AGE. Genotypes of positive samples were determined by reverse transcription polymerase chain reaction. During the study, 655 children hospitalized with AGE were enrolled; of whom 169 (25.8%) were positive for rotavirus. In the postvaccine period, a 59% reduction in the number of hospitalizations of rotavirus AGE and a 42.2% (95% confidence interval [CI], 18.6%-59.0%; P = 0.001) reduction in the proportion of rotavirus-positive results among children younger than 5 years were observed, with the greatest decline among infants (69.2%; 95% CI, 24.7%-87.4%; P = 0.004). Furthermore, the number of all-cause hospitalizations for AGE was reduced by 29% among children aged <5 years. The onset and peak incidences of rotavirus AGE occurred 3 months later in the 2007 and 2008 seasons compared with previous years. Genotype G2 accounted for 15%, 70%, and 100% of all cases identified, respectively, in 2006, 2007, and 2008. After vaccine implementation, a marked decline in rotavirus AGE hospitalizations was demonstrated among children younger than 5 years of age, with the greatest reduction in the age groups targeted for vaccination. The predominance of genotype G2P[4] highlights the need of continued postlicensure surveillance studies.


[Clinical experience with low- and minimal-flow isoflurane in extensive resections of the liver and liver transplantation].
A comparative study was performed of general balanced anesthesia on the basis of neuroleptic analgesia (NLA) and inhalation low- and minimal-flow anesthesia with isoflurane in anesthesiological management of extensive operations on the liver. A total of 75 anesthesias were conducted. Because of low hepatotoxicity, absence of its metabolites' pharmacological activity, fast elimination from the body unchanged, isoflurane is effective in long and traumatic operations on the liver. Low-flow isoflurane significantly lowers pharmacological load with opiates, myorelaxants which is essential in patients with hepatic diseases. This leads to more rapid recovery of adequate spontaneous respiration and activation of the patient in low risk of postoperative iatrogenic complications.


Lysophosphatic acid modulates prostaglandin secretion in the bovine uterus.
Lysophosphatidic acid (LPA) modulates prostaglandin (PG) synthesis via LPA receptor 3 (LPAR3) in the murine endometrium. The lack of functional LPAR3 in mice may lead to embryo mortality. In the present study, we examined the role of LPA in the bovine uterus. We confirmed that LPA is locally produced and released from the bovine endometrium. Moreover, there are enzymes involved in LPA synthesis (phospholipase (PL) D(2) and PLA2G1B) in the bovine endometrium during estrous cycle and early pregnancy. Expression of the receptor for LPA (LPAR1) was positively correlated with the expression of PGE(2) synthase (PGES) and negatively correlated with the expression of PGF(2alpha) synthase (aldose reductase with 20 alpha-hydroxysteroid dehydrogenase activity - PGFS) during early pregnancy. In vivo LPA induced P4 and PGE(2) secretion was inhibited by LPAR1 antagonist (Ki16425). The overall results indicate that LPA is locally produced and released from the bovine endometrium. Moreover, LPAR1 gene expression in the endometrium during the estrous cycle and early pregnancy indicates that LPA may play autocrine and/or paracrine roles in the bovine uterus. LPAR1 gene expression is positively correlated with the expression of the enzyme responsible for luteotropic PGE(2) production (PGES) in endometrium. In cow, LPA stimulates P4 and PGE(2) secretion. Thus, LPA in the bovine reproductive tract may indirectly (via endometrium) or directly support corpus luteum action via the increase of P4 synthesis and the increase of PGE(2)/PGF(2)(alpha) ratio. It suggests that LPA may serve as an important factor in the maintenance of early pregnancy in cow.


Recovery of Volatile Fatty Acids from Fermented Wastewater by Adsorption.
Separation of volatile fatty acids (VFAs) from fermented wastewater is challenging, due to low VFA concentrations in mineral-rich streams. As a result, separation capacity and selectivity with traditional solvents and adsorbents are both compromised. In this study, using a complex artificial model solution mimicking real fermented wastewaters, it is shown that a simple and robust adsorption-based separation technique can retain a remarkable capacity and selectivity for VFAs. Four types of polystyrene-divinylbenzene-based resins (primary, secondary, and tertiary amine-functionalized, and nonfunctionalized) were examined as the adsorbents. The presence of chloride, sulfate, and phosphate salts resulted in coadsorption of their acidic forms HCl, H2SO4, and H3PO4 on amine-functionalized adsorbents, and severely reduced the VFA capacity. With the nonfunctionalized adsorbent, almost no mineral acid coadsorption was observed. This together with a high total VFA capacity of up to 76 g/kg in equilibrium with the model solution containing a total VFA concentration of 1 wt % resulted in a very high selectivity for the VFAs. Nitrogen-stripping with various temperature profiles was applied to regenerate the adsorbent, and study the potential for fractionation of the VFAs during regeneration. Butyric acid (HBu) was obtained in mole fractions of up to 0.8 using a stepwise increase in the stripping temperature from 25 °C via 120 to 200 °C. During four successive adsorption-regeneration cycles, no reduction in the adsorption capacity was observed.


Variation in mortality burden of the COVID-19 pandemic across federal states in Germany.
Intra-annual excess mortality is the most reliable measure of losses of lives due to short-term risk factors. The objectives of our study are (i) to estimate excess mortality across German states in the course of the coronavirus disease 2019 (COVID-19) pandemic years 2020 and 2021 and (ii) to identify possible regional-level determinants of spatial inequality in pandemic-related excess mortality. We use weekly mortality data series for the calculation of weekly death rates, standardized by age for each federal state of Germany. We estimate the expected level of mortality as state-specific mortality trends and excess mortality in 2020 and 2021. We explore ecological statistical relationships between excess mortality, COVID-19 morbidity, and selected regional socioeconomic indicators using fixed-effects regression models. Our study shows that during the first pandemic year, there was South-to-North gradient in excess mortality in Germany, with excess mortality being higher in the South. Over the course of the second pandemic year 2021, this gradient changed to become an East-to-West gradient, with excess mortality being higher in the East. The results of the study show stronger effects of COVID-19 morbidity on excess mortality in East Germany. State-level indicators reflecting economic activity, employment, and capacity of intensive care units show significant correlations with excess mortality across the states. The results show pronounced state-level differences in the magnitude of excess mortality during the COVID-19 pandemic in Germany. Economic activity, employment and capacity of intensive care units were the most important state-level characteristics associated with the observed spatial variations in excess mortality.


A study of the candidate virulence factors of Bacteroides fragilis.
Bacteroides fragilis strains were classified as virulent or avirulent on the basis of their clearance from the subcutaneous tissues of mice. To determine the factors which may contribute to the virulence of B. fragilis strains, we studied encapsulation, hydrophobicity, growth rate, serum sensitivity, agglutination with erythrocytes of different origin, and neuraminidase production. The strains of the virulent group displayed a higher growth rate in broth and a lower sensitivity to the bactericidal activity of serum than the strains of the avirulent group. They also agglutinated different types of erythrocytes more strongly than did the avirulent strains. No significant differences were found between the two groups of strains as regards encapsulation, hydrophobicity and neuraminidase activity.


Single-level posterolateral arthrodesis, with or without posterior decompression, for the treatment of isthmic spondylolisthesis in adults. A prospective, randomized study.
Forty-two neurologically intact adults in whom non-operative treatment of grade-I or grade-II isthmic spondylolisthesis of the most caudad lumbar segment had failed were entered into a prospective study of the results of operative treatment. Twenty patients who smoked were managed with a posterolateral arthrodesis with instrumentation (transpedicular fixation), and twenty-two patients who did not smoke were managed with a posterolateral arthrodesis without instrumentation. Of the patients who were managed with instrumentation, eight were randomized to treatment with a decompressive laminectomy and twelve, to treatment without it; in the group that was managed without instrumentation, the distribution was ten and twelve patients, respectively. The patients were followed clinically for a mean of 4.5 years (range, 3.5 to six years). Of the eighteen patients who had been managed with decompression, four had a pseudarthrosis and six had an unsatisfactory result compared with none and one of the twenty-four who had been managed without decompression (p = 0.02 and p = 0.01, respectively). In the group of twenty patients (smokers) who had been managed with instrumentation, none of the twelve managed without decompression had a pseudarthrosis compared with one of the eight managed with decompression (p = 0.2). In the group of twenty-two patients (non-smokers) who had been managed without instrumentation, none of the twelve managed without decompression had a pseudarthrosis compared with three of the ten managed with decompression (p = 0.04). In the group managed with instrumentation, two of the eight who had had decompression had an unsatisfactory result compared with none of the twelve who had not had decompression. In the group managed without instrumentation, four of the ten who had had decompression had an unsatisfactory result compared with one of the twelve who had not had decompression. The addition of decompression to arthrodesis, performed with or without instrumentation, for the treatment of low-grade isthmic spondylolisthesis in patients who do not have a serious neurological deficit does not appear to improve the result and may significantly increase the rates of pseudarthrosis and unsatisfactory results.


Expression of beta 1, beta 3, beta 4, and beta 5 integrins by human epidermal keratinocytes and non-differentiating keratinocytes.
We have compared the adhesive properties and integrin expression profiles of cultured human epidermal keratinocytes and a strain of nondifferentiating keratinocytes (ndk). Both cell types adhered to fibronectin, laminin, and collagen types I and IV, but ndk adhered more rapidly and at lower coating concentrations of the proteins. Antibody blocking experiments showed that adhesion of both cell types to fibronectin was mediated by the alpha 5 beta 1 integrin and to laminin by alpha 3 beta 1 in synergy with alpha 2 beta 1. Keratinocytes adhered to collagen with alpha 2 beta 1, but an antibody to alpha 2 did not inhibit adhesion of ndk to collagen. Both cell types adhered to vitronectin by alpha v-containing integrins. Immunoprecipitation of surface-iodinated and metabolically labeled cells showed that in addition to alpha 2 beta 1, alpha 3 beta 1, and alpha 5 beta 1, both keratinocytes and ndk expressed alpha 6 beta 4 and alpha v beta 5. ndk expressed all these integrins at higher levels than normal keratinocytes. ndk, but not normal keratinocytes, expressed alpha v beta 1 and alpha v beta 3; they also expressed alpha 1 beta 1, an integrin that was not consistently detected on normal keratinocytes. Immunofluorescence experiments showed that in stratified cultures of normal keratinocytes integrin expression was confined to cells in the basal layer; terminally differentiating cells were unstained. In contrast, all cells in the ndk population were integrin positive. Our observations showed that the adhesive properties of ndk differ from normal keratinocytes and reflect differences in the type of integrins expressed, the level of expression and the distribution of integrins on the cell surface. ndk thus have a number of characteristics that distinguish them from normal basal keratinocytes.


Stereotactic Body Radiation Therapy With or Without Transarterial Chemoembolization Versus Transarterial Chemoembolization Alone in Early-Stage Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.
This study aims to review the current evidence on the utility of stereotactic body radiation therapy (SBRT), with or without transarterial chemoembolization (TACE), for early-stage hepatocellular carcinoma (ESHCC) patients not amenable to standard curative treatment options. Literature search was conducted using PubMed, ScienceDirect, and Google Scholar. Comparative studies reporting oncologic outcomes were included in the review. Five studies (one phase II randomized controlled trial, one prospective cohort, three retrospective studies) compared SBRT versus TACE. Pooled analysis showed an overall survival (OS) benefit after 3 years (OR 1.65, 95% CI 1.17-2.34, p = 0.005) which persisted in the 5-year data (OR 1.53, 95% CI 1.06-2.22, p = 0.02) in favor of SBRT. RFS benefit with SBRT was also seen at 3 years (OR 2.06, 95% CI 1.03-4.11, p = 0.04) which continued after 5 years (OR 2.35, 95% CI 1.47-3.75, p = 0.0004). Pooled 2-year local control (LC) favored SBRT over TACE (OR 2.96, 95% CI 1.89-4.63, p < 0.00001). Two retrospective studies compared TACE + SBRT versus TACE alone. Pooled analysis showed significantly improved 3-year OS (OR 5.47; 95% CI 2.47-12.11, p < 0.0001) and LC (OR: 21.05; 95% CI 5.01-88.39, p ≤ 0.0001) in favor of the TACE + SBRT group. A phase III study showed significantly improved LC and PFS with SBRT after failed TACE/TAE versus further TACE/TAE. Taking into account the limitations of the included studies, our review suggests significantly improved clinical outcomes in all groups having SBRT as a component of treatment versus TACE alone or further TACE. Larger prospective studies are warranted to further define the role of SBRT and TACE for ESHCC.


The time course of abstract visual representation.
Studies in change blindness re-enforce the suggestion that veridical, pictorial representations that survive multiple relocations of gaze are unlikely to be generated in the visual system. However, more abstract information may well be extracted and represented by the visual system. In this paper we study the types of information that are retained and the time courses over which these representations are constructed when participants view complex natural scenes. We find that such information is retained and that the resultant abstract representations encode a range of information. Different types of information are extracted and represented over different time courses. After several seconds of viewing natural scenes, our visual system is able to construct a complex information-rich representation.


NATIONAL SECURITY: Relief, Rebukes Follow Agreement on Lee.
What began as an explosive case of alleged nuclear espionage is expected to end quietly soon when physicist Wen Ho Lee walks free from an Albuquerque, New Mexico, courtroom after 9 months in jail. The ignominious collapse of the government's case and Lee's release have embarrassed federal prosecutors. However, the news was a relief to Asian-American researchers and others who say Lee's status as a suspect had heightened racial tensions at the national labs.


[Vaccination with Mycobacterium: can it cure allergies?].
In developed countries, the prevalence of tuberculosis has evolved in an opposite direction as to the one of allergy over the last century. The immunological response is mainly Th1 in tuberculosis while it features a Th2 pattern in allergy. Vaccination with BCG in early life is associated with a reduction in the prevalence of allergy later in childhood. In an experimental mouse model of asthma, administration of BCG or killed Mycobacterium vaccae inhibits the sensitisation process as well as the bronchial inflammation and hyperresponsiveness that follows allergen exposure. In children and adolescents suffering from atopic dermatitis, subcutaneous injection of killed Mycobacterium vaccae attenuates the severity of skin lesions.


Phylogenetic conservation of the regulatory and functional properties of the Vav oncoprotein family.
Vav proteins are phosphorylation-dependent GDP/GTP exchange factors for Rho/Rac GTPases. Despite intense characterization of mammalian Vav proteins both biochemically and genetically, there is little information regarding the conservation of their biological properties in lower organisms. To approach this issue, we have performed a characterization of the regulatory, catalytic, and functional properties of the single Vav family member of Drosophila melanogaster. These analyses have shown that the intramolecular mechanisms controlling the enzyme activity of mammalian Vav proteins are already present in Drosophila, suggesting that such properties have been set up before the divergence between protostomes and deuterostomes during evolution. We also show that Drosophila and mammalian Vav proteins have similar catalytic specificities. As a consequence, Drosophila Vav can trigger oncogenic transformation, morphological change, and enhanced cell motility in mammalian cells. Gain-of-function studies using transgenic flies support the implication of this protein in cytoskeletal-dependent processes such as embryonic dorsal closure, myoblast fusion, tracheal development, and the migration/guidance of different cell types. These results highlight the important roles of Vav proteins in the signal transduction pathways regulating cytoskeletal dynamics. Moreover, they indicate that the foundations for the regulatory and enzymatic activities of this protein family have been set up very early during evolution.


Induction of a host-specific chromatin-associated glycopolypeptide by human cytomegalovirus.
Analysis of chromatin preparations from [3H]glucosamine-labelled human foreskin fibroblasts revealed that a chromatin-associated glycopolypeptide with the approximate mol. wt. 130 000 (130K) is induced in response to either infection with human cytomegalovirus (HCMV) or serum treatment. Comparative limited proteolysis suggested that the [3H]glucosamine-labelled 130K polypeptides induced by these different stimuli were not identical. This observation was in contrast to results obtained by immunoprecipitation with antisera raised against the 130K glycopolypeptide from serum-induced cells which favoured a relatedness to the 130K polypeptide from virus-infected cultures. Two-dimensional separation by isoelectric focusing and SDS-polyacrylamide gel electrophoresis subsequently showed that the 130K glycopolypeptide from serum-induced cells consists of two components, one of which is identical to the single component observed in samples from HCMV-infected cultures. Experiments on the effect of glycosylation inhibitors on DNA replication in HCMV-infected as well as in serum-induced cells support the view that the host-specific chromatin-associated glycopolypeptide may be involved in DNA replication in infected cells.


Efficacy and safety of apatinib monotherapy in elderly patients with advanced metastatic non-small cell lung cancer.
No effective and definitive chemotherapeutic regimen has been established in patients with non-small cell lung cancer (NSCLC) who failed second-line treatment. The aim of this study was to evaluate apatinib, a VEGFR-2 inhibitor, as monotherapy in elderly patients with advanced metastatic NSCLC. We evaluated the efficacy and safety of apatinib in elderly patients (≥65 years old) with advanced metastatic NSCLC who failed second-line treatment from 2015 to 2016 in Huanggang Central Hospital. Survival analysis was performed by the Kaplan-Meier method. Toxicities were evaluated according to the National Cancer Institute Common Toxicity Criteria version 4.0. Twenty patients were included in the present study. Two patients achieved partial response, and 9 achieved stable disease, representing a response rate of 10% and a disease control rate of 55%. Median progression-free survival and overall survival were 2.8 and 6.0 months, respectively. The toxicities associated with apatinib were generally acceptable with a total grade 3/4 toxicity of 50%. Apatinib is an optional choice as salvage treatment in elderly patients with advanced metastatic NSCLC, with modest efficacy and acceptable toxicities.


[A phenomenological approach of treatment-resistant depressions].
Hospital practitioners are regularly facing treatment-resistant depression, which may be defined according to the clinical picture or according to the therapeutic strategy. There are different levels of resistance and different levels of evidence for this resistance. Indeed, the notions of relative and absolute resistance describe the adequacy of assigned treatment. It thus seems necessary to specify the psychopathology of treatment-resistant depression and to highlight the endogeneity phenomenon in order to solve this problem. Our work addresses the concept of endogeneity (previously clarified by Hubertus Tellenbach) and will consider its implications in the management of treatment-resistant depression. We attempt to demonstrate that the phenomenological approach is an interesting tool in clinical practice through the highlight of endogenous characteristics. The first step consists in specifying the endogenous phenomena: abolition of rhythms, loss of the forward-looking deployment, overall impression, and reversibility, spatial and temporal characteristics from the phenotype. Our phenomenological approach continues by exploring the false resistances. Hence, we take into account anxious comorbidity, medical comorbidity, addictions, personality disorders and the hypothesis of a bipolar diathesis. First of all, it is difficult to show the patient in which way their behaviour results in stagnation. Indeed, it could strengthen the internal move that leads to an imperious necessity to cope with the surroundings. The psychotherapeutic help is elaborated by specifically highlighting the pathogenic situations whilst also taking into account the difficulties of an authentic therapeutic alliance. Our approach emphasizes the endogeneity phenomenon in depression, permitting the search for an optimal therapeutic strategy. It also provides assistance in resolving false resistance or what is apparent. In cases of endogenous depression, therapeutic orientation favours pharmacological and instrumental strategies (brain stimulation). If elements of self-understanding can be given to the patient, they must show that the rigid way in which the patient appropriates the daily reports is more stressful than the choice. Therefore, the psychotherapeutic help must take into account the situation and the individual vulnerability so as to develop a suitable care.


A valuable adjunct to FNA diagnosis of papillary thyroid carcinoma: in-house PCR assay for BRAF T1799A (V600E).
The diagnostic approach to thyroid nodules generally starts with FNA cytology. However, approximately one-fifth of cytologic evaluations yield indeterminate cytological findings but only 20% of cases with indeterminate thyroid nodule cytology have a cancer diagnosis, emphasizing the need for an effective ancillary test based on FNA material to help prevent unnecessary surgery. Detection of BRAFV600E mutation, the genetic signature of papillary thyroid carcinoma (PTC) in FNA material provides an invaluable diagnostic adjunct to overcome the limitations of FNA cytology. There are many ways to detect V600E, such as direct DNA sequencing, allele-specific PCR and hybridization-based colorimetric methods. In this study, a newer simple PCR method is presented that removes requirements for sequencing special equipment and commercial kits. Two forward primers including the mutant sequence specific (F2), and one common reverse (R) primer were optimized to generate a 241 bp fragment (F1R), an internal PCR control, and a 141 bp fragment (F2R) denoting the presence of V600E. Sensitivity studies revealed that the assay is capable of detecting V600E even in 1 ng of DNA. Direct sequencing data of 241 bp F1R fragment proved the specificity of the assay. For validation studies of the sequence specific multiplex PCR assay, archival FNA slides were used in a group of thyroid lesions including PTC, follicular carcinoma, follicular adenoma, Hashimoto thyroiditis, and benign thyroid nodules. The newer PCR-based method presented in this study is a practical, inexpensive one-step assay to detect the BRAF T1796A mutation on FNA samples.


The Appalachia Cancer Network: cancer control research among a rural, medically underserved population.
Residents of Appalachia, especially those in rural Appalachia, are generally considered to be medically underserved. In fact, cancer mortality in Appalachia, especially in rural Appalachia, is higher than it is in the remainder of the United States. Developing from the Appalachia Leadership Initiative on Cancer, the Appalachia Cancer Network (ACN) is a network of academic and community organizations that seek to conduct surveillance, intervention, and dissemination research to reduce this excess cancer burden in Appalachia. The purpose of this report is to (1) describe the approach to cancer control research in ACN, a Special Population Network, among the medically underserved of Appalachia, and (2) to put forward observations from this experience to enhance the research of other academic and community networks among underserved populations. ACN has instituted a conceptual model, organizational structure, and other methods to foster this research and to develop junior and community-based investigators. Important issues and questions related to the effectiveness of such research networks have also been articulated.


Profiling the unique protective properties of intracranial arterial endothelial cells.
Cardiovascular disorders, like atherosclerosis and hypertension, are increasingly known to be associated with vascular cognitive impairment (VCI). In particular, intracranial atherosclerosis is one of the main causes of VCI, although plaque development occurs later in time and is structurally different compared to atherosclerosis in extracranial arteries. Recent data suggest that endothelial cells (ECs) that line the intracranial arteries may exert anti-atherosclerotic effects due to yet unidentified pathways. To gain insights into underlying mechanisms, we isolated post-mortem endothelial cells from both the intracranial basilar artery (BA) and the extracranial common carotid artery (CCA) from the same individual (total of 15 individuals) with laser capture microdissection. RNA sequencing revealed a distinct molecular signature of the two endothelial cell populations of which the most prominent ones were validated by means of qPCR. Our data reveal for the first time that intracranial artery ECs exert an immune quiescent phenotype. Secondly, genes known to be involved in the response of ECs to damage (inflammation, differentiation, adhesion, proliferation, permeability and oxidative stress) are differentially expressed in intracranial ECs compared to extracranial ECs. Finally, Desmoplakin (DSP) and Hop Homeobox (HOPX), two genes expressed at a higher level in intracranial ECs, and Sodium Voltage-Gated Channel Beta Subunit 3 (SCN3B), a gene expressed at a lower level in intracranial ECs compared to extracranial ECs, were shown to be responsive to shear stress and/or hypoxia. With our data we present a set of intracranial-specific endothelial genes that may contribute to its protective phenotype, thereby supporting proper perfusion and consequently may preserve cognitive function. Deciphering the molecular regulation of the vascular bed in the brain may lead to the identification of novel potential intervention strategies to halt vascular associated disorders, such as atherosclerosis and vascular cognitive dysfunction.


Pregnancy in Women with Complex Congenital Heart Disease. A Constant Challenge.
The improvement in surgical techniques has contributed to an increasing number of childbearing women with complex congenital heart disease (CCC). However, adequate counseling about pregnancy in this situation is uncertain, due to a wide variety of residual cardiac lesions. To evaluate fetal and maternal outcomes in pregnant women with CCC and to analyze the predictive variables of prognosis. During 10 years we followed 435 consecutive pregnancies in patients (pts) with congenital heart disease. Among of them, we selected 42 pregnancies in 40 (mean age of 25.5 ± 4.5 years) pts with CCC, who had been advised against pregnancy. The distribution of underlying cardiac lesions were: D-Transposition of the great arteries, pulmonary atresia, tricuspid atresia, single ventricle, double-outlet ventricle and truncus arteriosus. The surgical procedures performed before gestation were: Fontan, Jatene, Rastelli, Senning, Mustard and other surgical techniques, including Blalock, Taussing, and Glenn. Eight (20,0%) pts did not have previous surgery. Nineteen 19 (47.5%) pts had hypoxemia. The clinical follow-up protocol included oxygen saturation recording, hemoglobin and hematocrit values; medication adjustment to pregnancy, anticoagulation use, when necessary, and hospitalization from 28 weeks, in severe cases. The statistical significance level considered was p < 0.05. Only seventeen (40.5%) pregnancies had maternal and fetal uneventful courses. There were 13 (30.9%) maternal complications, two (4.7%) maternal deaths due to hemorrhage pos-partum and severe pre-eclampsia, both of them in women with hypoxemia. There were 7 (16.6%) stillbirths and 17 (40.5%) premature babies. Congenital heart disease was identified in two (4.1%) infants. Maternal and fetal complications were higher (p < 0.05) in women with hypoxemia. Pregnancy in women with CCC was associated to high maternal and offspring risks. Hypoxemia was a predictive variable of poor maternal and fetal outcomes. Women with CCC should be advised against pregnancy, even when treated in specialized care centers.


Convergence model for effectual prevention and control of zoonotic diseases: a health system study on 'One Health' approach in Ahmedabad, India.
The complexity and increasing burden of zoonotic diseases create challenges for the health systems of developing nations. Public health systems must therefore be prepared to face existing and future disease threats at the human-animal interface. The key for this is coordinated action between the human and the animal health systems. Although some studies deal with the question of how these two systems interact during unforeseen circumstances such as outbreaks, a dearth of literature exists on how these systems interact on early detection, prevention and control of zoonotic diseases; assessing this problem from the health system perspective in a developing nation adds further complexity. Systems thinking is one of the promising approaches in understanding the factors that influence the system's complexity and dynamics of health maintenance. Therefore, this study aims to understand the generic structure and complexity of interaction between these actors within the domain of One Health for the effectual prevention and control of zoonotic diseases in India.The present study will be executed in Ahmedabad, located on the Western part of India, in Gujarat state, using a mixed methods approach. For the first step, zoonotic diseases will be prioritised for the local context through semi-quantitative tools. Secondly, utilising semi-structured interviews, stakeholders from the human and animal health systems will be identified and ranked. Thirdly, the identified stakeholders will be questioned regarding the current strength of interactions at various levels of the health system (i.e. managerial, provider and community level) through a quantitative network survey. Fourthly, utilising a vignette method, the ideal convergence strategies will be documented and validated through policy Delphi techniques. Finally, through a participatory workshop, the factors that influence convergence for the control and prevention of zoonotic diseases will be captured.This study will provide a comprehensive picture of the current strength of collaboration and network depth at various levels of the health system. Further, it will assist different actors in identifying the relevance of possible One Health entry points for participation, i.e. it will not only contribute but will also develop a system convergence model for the effectual prevention and control of zoonotic diseases.


A simple classification of the resolution and depth of imaging systems for pigmented skin lesions.
The resolving power of imaging systems used in the diagnosis of cutaneous malignant melanoma is usually presented in the literature in terms of numerical values, yet it is often difficult for the reader to ascertain what tangible information these systems are extracting. This paper presents a classification system of two aspects of imaging systems that allows rapid appraisal of the resolution of the different imaging systems used in the diagnosis of melanoma and the additional clinical information they reveal.


Nonstenotic Carotid Plaques and Embolic Stroke of Undetermined Source: A Multimodality Review.
Symptomatic nonstenotic carotid artery disease has been increasingly recognized as a thromboembolic source in patients who would otherwise be classified as having embolic stroke of undetermined source. Evidence suggests that certain plaque features seen on sonography, CT, and MR imaging in nonstenotic carotid artery disease may predispose to recurrent stroke in patients with embolic stroke of undetermined source. We performed a focused literature review to further study plaque features in the context of embolic stroke of undetermined source and to determine which plaque features may be associated with ipsilateral ischemic events in such patients. Plaque thickness as seen on both ultrasound and CT appears to have a consistent association with ipsilateral stroke in patients with embolic stroke of undetermined source across multiple studies. Intraplaque hemorrhage as seen on MR imaging is now understood to have a strong association with ipsilateral stroke in patients with embolic stroke of undetermined source. Continued study of various plaque features as seen on different modalities is warranted to uncover other potential associations.


Evaluation and treatment of neonatal hyperbilirubinemia.
Although neonatal jaundice is common, acute bilirubin encephalopathy and kernicterus (i.e., chronic bilirubin encephalopathy) are rare. Universal screening for neonatal hyperbilirubinemia is controversial. The American Academy of Pediatrics recommends universal screening with bilirubin levels or targeted screening based on risk factors. However, the U.S. Preventive Services Task Force and the American Academy of Family Physicians found insufficient evidence that screening improves outcomes. Universal screening may also increase rates of phototherapy, sometimes inappropriately. Younger gestational age and exclusive breastfeeding are the strongest risk factors for the development of hyperbilirubinemia. Infants who appear jaundiced should be evaluated by a risk score or by measurement of total serum or transcutaneous bilirubin. Phototherapy is an effective treatment for hyperbilirubinemia, but the number needed to treat varies widely depending on sex, gestational age, and time since delivery. If indicated, phototherapy should be initiated based on gestational age and risk factors. Exchange transfusion leads to complications in about 5% of treated infants and has a mortality rate of three or four per 1,000 infants. Infants who breastfeed exclusively-particularly those who consume inadequate calories-are at increased risk of hyperbilirubinemia. However, interrupting breastfeeding for the treatment of jaundice increases the risk of early discontinuation of breastfeeding. Encouragement from health care professionals is important to promote breastfeeding in these situations.


[Quality of life, gender, complaints and humor among dialysis patients].
This study tested the correlation between quality of life and sense of humour as well as the sociodemographic and biomedical characteristics of patients in dialysis due to renal failure. Gender differences in all these variables were also tested. All patients in need of dialysis in Sør-Trøndelag county, Norway in February 1998 (N = 52) were recruited; 46 patients completed the survey (32 males and 14 females). Males were more likely to be married and have a house of their own than were women. Correlation analysis stated that high quality of life was significantly associated with low comorbidity and a good sense of humour. The most efficient model to explain quality of life in multiple regression included serum albumin (not significant) and confirmed the independent contributions from low comorbidity and a good sense of humour. Comorbidity and a sense of humour were factors of greater importance than serum albumin to differences in quality of life among patients on dialysis.


Yellow/orange emissive heavy-metal complexes as phosphors in monochromatic and white organic light-emitting devices.
Owing to the electron spin-orbit coupling (SOC) and fast intersystem crossing (ISC), heavy-metal complexes (such as iridium(III), platinum(II) and osmium(II) complexes, etc.) are phosphorescent emitters at room temperature. Since 1998, heavy-metal complexes as phosphors have received considerable academic and industrial attention in the field of organic light-emitting diodes (OLEDs), because they can harvest both the singlet (25%) and triplet (75%) excitons for emission during the electro-generated processes. Among all the visible colors (blue, green, yellow, orange and red), the yellow/orange heavy-metal complexes play an important role for realizing full-color OLEDs as well as high-efficiency white OLEDs, and thus the development of highly efficient yellow/orange heavy-metal complexes is a pressing concern. In this article, we will review the progress on yellow/orange heavy-metal complexes as phosphors in OLEDs. The general principles and useful tactics for designing the yellow/orange heavy-metal complexes will be systematically summarized. The structure-property relationship and electrophosphorescence performance of the yellow/orange heavy-metal complexes in monochromatic phosphorescent OLEDs (PhOLEDs) and white OLEDs (WOLEDs) will be comprehensively surveyed and discussed.


Sexual behavior changes and protease inhibitor therapy. SEROCO Study Group.
To examine changes in sexual activity and unprotected sexual intercourse among HIV-infected patients before and after the initiation of protease inhibitor therapy. An analysis of data from the SEROCO Study, a French prospective cohort. All 191 patients who initiated protease inhibitor therapy after 1 January 1996, who were interviewed within one year before the initiation of therapy (Time 1), and who had at least 6 months of follow-up after therapy initiation (Time 2) were included. Patients provided information about sex partner characteristics and unprotected sexual intercourse. Eighty-one (42%) were gay or bisexual men, 46 (24%) were heterosexual men, and 64 (34%) were women. No significant increases were found in either the number of patients reporting anal or vaginal sex or the number reporting unprotected sexual intercourse after protease inhibitor initiation. However, in matched pair analysis, gay or bisexual men were three times more likely to report having had unprotected sexual intercourse with partners who were of HIV-negative or unknown serostatus after protease inhibitor initiation [relative risk (RR) = 3.0, 95% confidence interval (CI) = 1.2-7.6]. Non-significant decreases in unprotected sexual intercourse among both heterosexual men and women were also observed. No relationship between plasma viral load after protease inhibitor initiation and unprotected sexual intercourse was found in these data. A relapse in sex risk practices among some HIV-infected gay or bisexual men cannot be ruled out and requires both continued monitoring and immediate secondary preventative intervention.


Olfaction in Parkinson's disease and related disorders.
Olfactory dysfunction is an early 'pre-clinical' sign of Parkinson's disease (PD). The present review is a comprehensive and up-to-date assessment of such dysfunction in PD and related disorders. The olfactory bulb is implicated in the dysfunction, since only those syndromes with olfactory bulb pathology exhibit significant smell loss. The role of dopamine in the production of olfactory system pathology is enigmatic, as overexpression of dopaminergic cells within the bulb's glomerular layer is a common feature of PD and most animal models of PD. Damage to cholinergic, serotonergic, and noradrenergic systems is likely involved, since such damage is most marked in those diseases with the most smell loss. When compromised, these systems, which regulate microglial activity, can influence the induction of localized brain inflammation, oxidative damage, and cytosolic disruption of cellular processes. In monogenetic forms of PD, olfactory dysfunction is rarely observed in asymptomatic gene carriers, but is present in many of those that exhibit the motor phenotype. This suggests that such gene-related influences on olfaction, when present, take time to develop and depend upon additional factors, such as those from aging, other genes, formation of α-synuclein- and tau-related pathology, or lowered thresholds to oxidative stress from toxic insults. The limited data available suggest that the physiological determinants of the early changes in PD-related olfactory function are likely multifactorial and may include the same determinants as those responsible for a number of other non-motor symptoms of PD, such as dysautonomia and sleep disturbances.


RADON AND THORON PROGENY IN DUTCH DWELLINGS.
Radon and thoron progenies in Dutch dwellings cause ~400 cases of lung cancer per year. Some 30% of the risk is due to thoron progeny, which demonstrates that the influence of thoron progeny is much larger than previously anticipated. This was concluded from a national survey in 2500 Dutch dwellings, built since 1930. Radon concentrations (15.6 ± 0.3 Bq m-3 on average) are correlated to type of dwelling, year of construction, ventilation system, location (soil type) and smoking behaviour of inhabitants. The survey data support the establishment of a comparatively low national reference level for radon in dwellings in the Netherlands of 100 Bq m-3, in line with recommendations by WHO and ICRP. Some 24 thousand of the 6.2 million dwellings in the Netherlands (built since 1930) are expected to exceed this level. Around 80% of these are located in the relatively small group of naturally ventilated single-family houses in two designated geographical areas. Radon concentrations above 200 Bq m-3 are rare in the Netherlands and simple and inexpensive measures will be sufficient to reduce enhanced radon concentrations to values below the national reference level. Thoron progeny concentrations (0.64 Bq m-3, on average) show correlations with year of construction and smoking behaviour. In 75 additional dwellings, a pilot study was conducted to determine the relationship between the exhalation of thoron from walls and the concentration of thoron progeny in the room. Thoron exhalation values exceeding the median value of 2.2 × 10-2 Bq m-2 s-1 by a factor 10 or more were found frequently, but enhanced concentrations of thoron progeny were measured only occasionally. Under very unfavourable conditions, however, for instance if phosphogypsum is applied as finishing material on all walls and ceilings in the house, strongly elevated thoron progeny concentrations may occur. This survey yielded a maximum recording of 13.3 Bq m-3. There is no reason to expect that such levels are specific to the Netherlands, indicating that in other regions with low radon levels, thoron may be a more important contributor to the population dose as well.


Mental health of muslim nursing students in Thailand.
The purpose of this research was to explore the mental health and well-being of Muslim nursing students in Thailand. Specifically, the study investigated the factors that impact anxiety and depression among Muslim nursing students. This cross-sectional research was conducted with a half sampling method of Muslim undergraduate students who were studying at a public nursing college in Thailand. From the 220 self-identified Muslim nursing students, 110 were sampled for this study, representing 14% of the total nursing students at this college. Results indicated a moderate prevalence of anxiety and high prevalence of depression among Muslim nursing students. Stress (β = .42) was positively associated with anxiety, while self-esteem (β = -.42) was negatively associated with anxiety; together this model accounted for 46% of the variance in anxiety. Self-esteem (β = -.41) and social support (β = -.17) were negatively associated with depression, while stress (β = .37) was positively correlated with depression; together this model accounted for 57% of the variance in depression. Recommendations were given to help train Muslim nursing students to be competent nurses with good mental health and well-being who will succeed and contribute to the nursing profession.


The utilization of pneumococcal polysaccharide vaccine among elderly Medicare beneficiaries, 1985 through 1988.
Since July 1981, Medicare has paid for the administration of pneumococcal vaccine without regard to the deductible limit and without copayment. Claims submitted to Medicare for reimbursement for the 4-year period from 1985 through 1988 for a 5% sample of elderly Medicare beneficiaries enrolled in part B who were not members of health maintenance organizations were analyzed. Vaccine was administered to an estimated 1,392,840 beneficiaries (5.34%). The total estimated cost to Medicare was $14.3 million, or approximately $10.27 per dose. Crude 4-year rates indicated that white persons were much more likely to be immunized than black persons (5.60% vs 2.94%). Persons 70 through 84 years of age had higher immunization rates than either younger or older beneficiaries. The number of immunizations given peaked in 1986 and declined thereafter. A variety of vaccination strategies that may raise the immunization level in the elderly have been developed. The broad implementation of successful strategies will be important if the goal of a 60% immunization level in the elderly by the year 2000 is to be reached.


Arthrobacter flavus sp. nov., a psychrophilic bacterium isolated from a pond in McMurdo Dry Valley, Antarctica.
CMS 19YT, a psychrophilic bacterium, was isolated from a cyanobacterial mat sample from a pond in Antarctica and was characterized taxonomically. The bacterium was aerobic, gram-positive, non-spore-forming, non-motile, exhibited a rod-coccus growth cycle and produced a yellow pigment that was insoluble in water but soluble in methanol. No growth factors were required and it was able to grow between 5 and 30 degrees C, between pH 6 and pH 9 and tolerated up to 11.5% NaCl. The cell wall peptidoglycan was Lys-Thr-Ala3 (the A3alpha variant) and the major menaquinone was MK-9(H2). The G+C content of the DNA was 64+/-2 mol%. The 16S rDNA analysis indicated that CMS 19YT is closely related to group I Arthrobacter species and showed highest sequence similarity (97.91%) with Arthrobacter agilis. Furthermore, DNA-DNA. hybridization studies also indicated 77% homology between CMS 19YT and A. agilis. It differed from A. agilis, however, in that it was psychrophilic, non-motile, yellow in colour, exhibited a rod-coccus growth cycle, had a higher degree of tolerance to NaCl and was oxidase- and urease-negative and lipase-positive. In addition, it had a distinct fatty acid composition compared to that of A. agilis: the predominant fatty acids were C15:0, anteiso-C15:0, C16:0, iso-C16:0, C17:0, anteiso-C17:0 and C18:0. It is proposed, therefore, that CMS 19YT should be placed in the genus Arthrobacter as a new species, i.e. Arthrobacter flavus sp. nov. The type strain of A. flavus is CMS 19YT (= MTCC 3476T).


The impact of numeracy ability and technology skills on older adults' performance of health management tasks using a patient portal.
Patient portals, which allow patients to access their health record via the Internet, are becoming increasingly widespread and are expected to be used by diverse consumer populations. In addition to technology skills, numeracy skills are also likely to be critical to performing health management tasks, as much of the data contained in the portal are numeric. This study examined how factors such as Internet experience, numeracy, and education impacted the performance of common tasks using a simulated patient portal among a sample of older adults. In addition, information was gathered on the ability of older adults to estimate their numeracy skills. Results indicated that numeracy and Internet experience had a significant impact on their ability to perform the tasks and that older adults tended to overestimate their numeracy skills. Results from this study can help to identify interventions that may enhance the usability of patient portals for older adults.


Risk assessment and disease prevention in travelers visiting friends and relatives.
Although VFR travelers are at risk for acquiring infections and experiencing illness while traveling, many of these diseases are preventable. A comprehensive approach to decreasing their travel-related morbidity requires continued surveillance, data collection, systematic analysis, and action. A review of the literature provides few examples of interventions designed specifically to address VFR travel needs. Given the geographic and cultural diversity of these populations, models grounded in health behavior theory provide the best potential for clinically relevant replication. Outreach aimed at improving knowledge and care-seeking behaviors among VFR travelers may be facilitated through community-based campaigns in areas with large foreign-born populations. In developed countries, policies must be reviewed to ensure that travel-related services are accessible, affordable, and appropriate for these diverse populations. In the clinical setting, providers must develop culturally appropriate methods of communicating with traveling populations to influence behavior. In particular, primary care providers should take an active approach through screening for high-risk travel, and increasing their competency in travel medicine. Special attention should be given to illness that is prevented by routine childhood immunization (eg, varicella, measles, and hepatitis B); by disease prevented by travel vaccines (eg, typhoid fever and hepatitis A); and disease that can be prevented by careful avoidance measures or compliance with preventive medication (eg, malaria and tuberculosis). With increased immigration from developing to developed regions and widely affordable travel, the number of VFR travelers is expected to increase. As such, increased efforts to prevent VFR traveler morbidity serve the individual while also contributing to global public health.


[Surgical treatment of mycetoma located in the face].
The first case described in Mexico, was studied by Cícero in 1900 and 1911 Ocaranza, in Sonora, reports some cases, pointing out that the first known case dates back to 1874. In USA González Ochoa identifies the causative agent of the cases he studied, as the same identified in USA, but he calls attention to the fact that it has already been described under the name of Actinomyces brasiliensis, finally, taxonomically it is included among the nocardias. In Mexico the micetoma is caused in 90% of the cases by Nocardia brasiliensis, and 8% by Streptomysis and other actinomycetos and only in 1.5% it is determined by true fungi. Until the observation of the present case, mycetomas had been reported located or scattered in different places of the human body, except the face. This case is observed in a 24 years old woman patient, of peasant extraction, who presents tumoration of the left hemiface, irregularly oval, 18 x 25 cm. of anfractous surface, with nodes and fistulas that secrete suppuration. The evolution is of seven years duration, and begins after a trauma. The mycologic and histopathologic study, confirms N. brasiliensis as the causative agent. X rays prove that the skull bones are not affected, but the mycosis cause anemia. Specific treatment for anemia is installed with trimetropryn and sulphametoxazol plus sulphone, for a period of six months. A change is made to streptomycin to a total of 40 g. and then this is replaced by isonizasyn, adding to both these drugs alphamatoxipyridazine, for a period of six months and in last months, riprampycin plus sulphone are given; always with bad results.(ABSTRACT TRUNCATED AT 250 WORDS)


High expressions of caveolins on the proliferating bile ductules in primary biliary cirrhosis.
An increase in bile ductular structures is observed in diverse human liver diseases, especially in primary biliary cirrhosis (PBC). These structures harbor the progenitor cell component of the liver. Caveolins are cholesterol-binding proteins involved in the regulation of several intracellular processes including cholesterol transport. This study aims to examine the role of caveolin in PBC. Immunohistochemical and Western blotting studies were performed on human liver specimens obtained from patients with PBC and normal liver samples. The expression of caveolin (CAV)-1 and -2 was determined using specific antibodies. In normal liver, scanty immunostaining for CAV-1 and -2 was observed in bile ductules. In PBC liver samples, the expression levels of CAV-1 and -2 were increased on proliferating bile ductules especially in stage 3 cases, but was sparse on interlobular bile duct in stage 1 specimens. Especially, the regenerating bile ductules at the interface of portal tracts and necrotic areas were immunostained intensely for CAV-1 and -2. These phenomena were confirmed by Western blot. The present results demonstrate increased expression of caveolins in proliferating bile ductules in PBC, which may be related to the homeostasis of cholesterol transport in regenerating bile ductules in PBC liver.


Let-7a inhibits migration, invasion and tumor growth by targeting AKT2 in papillary thyroid carcinoma.
Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. Increasing evidence showed that microRNAs (miRNAs) play an important role in the PTC progression. In our study, the result showed that let-7a is significantly downregulated in PTC tissues and thyroid cancer cell lines. Overexpression of let-7a suppressed PTC cell proliferation, migration and invasion. Interestingly, we found that AKT2 was a direct target of let-7a and the expression levels of AKT2 were also observed to inversely correlate with let-7a expression in PTC tissues. Furthermore, enhancing AKT2 expression partially reversed the inhibitory effects of let-7a in PTC. Taken together, these findings suggest that let-7a acts as a novel suppressor by targeting the AKT2 gene and might be a candidate target for the development of novel therapeutic strategies to treat papillary thyroid carcinoma.


Community-based organizational capacity building as a strategy to reduce racial health disparities.
One of the biggest challenges facing racial health disparities research is identifying how and where to implement effective, sustainable interventions. Community-based organizations (CBOs) and community-academic partnerships are frequently utilized as vehicles to conduct community health promotion interventions without attending to the viability and sustainability of CBOs or capacity inequities among partners. Utilizing organizational empowerment theory, this paper describes an intervention designed to increase the capacity of CBOs and community-academic partnerships to implement strategies to improve community health. The Capacity Building project illustrates how capacity building interventions can help to identify community health needs, promote community empowerment, and reduce health disparities.


[Surgical treatment of injuries of large blood vessels of the limbs].
In treatment of 50 patients with injuries of large vessels of limbs the authors have employed all kinds of vascular plasty, including lateral and circular sutures, putting of a patch on the vascular wall, replacement of an arterial defect with an autovenous graft. Autovenous plasty employed in various modifications in 21 cases is felt to be the method of choice in operations on injured arteries in cases of an extensive damage of soft tissues of limbs and open fractures. The results of the treatment are described.


Pim kinases promote cell cycle progression by phosphorylating and down-regulating p27Kip1 at the transcriptional and posttranscriptional levels.
The serine/threonine kinase Pim is known to promote cell cycle progression and to inhibit apoptosis leading to tumorigenesis. However, the precise mechanisms remain unclear. We show, herein, that all the Pim family members (Pim1, Pim2, and Pim3) bind to and directly phosphorylate the cyclin-dependent kinase inhibitor p27(Kip1) at threonine-157 and threonine-198 residues in cells and in vitro. The Pim-mediated phosphorylation induced p27(Kip1) binding to 14-3-3 protein, resulting in its nuclear export and proteasome-dependent degradation. Ectopic expression of Pim kinases overcome the G(1) arrest mediated by wild-type p27(Kip1) but not by phosphorylation-resistant T157A-p27(Kip1) or T198A-p27(Kip1). In addition to the posttranslational regulations, p27(Kip1) promoter assay revealed that Pim kinases also had the ability to suppress p27(Kip1) transcription. Pim-mediated phosphorylation and inactivation of forkhead transcription factors, FoxO1a and FoxO3a, was involved in the transcriptional repression of the p27(Kip1) gene. In contrast, inhibition of Pim signaling by expressing the dominant-negative form of Pim1 increased nuclear p27(Kip1) level and attenuated cell proliferation. Because the CDK inhibitor p27(Kip1) plays a crucial role in tumor suppression by inhibiting abnormal cell cycle progression, Pim kinases promote cell cycle progression and tumorigenesis by down-regulating p27(Kip1) expression at both transcriptional and posttranslational levels.


Clinimetric properties of the Perme Intensive Care Unit Mobility Score -a multicenter study for minimum important difference and responsiveness analysis.
The use of instruments in clinical practice with measurement properties tested is highly recommended, in order to provide adequate assessment and measurement of outcomes. To calculate the minimum clinically important difference (MCID) and responsiveness of the Perme Intensive Care Unit Mobility Score (Perme Score). This retrospective, multicentric study investigated the clinimetric properties of MCID, estimated by constructing the Receiver Operating Characteristic (ROC). Maximizing sensitivity and specificity by Youden's, the ROC curve calibration was performed by the Hosmer and Lemeshow goodness-of-fit test. Additionally, we established the responsiveness, floor and ceiling effects, internal consistency, and predictive validity of the Perme Score. A total of 1.200 adult patients records from four mixed general intensive care units (ICUs) were included. To analyze which difference clinically reflects a relevant evolution we calculated the area under the curve (AUC) of 0.96 (95% CI: 0.95-0.98), and the optimal cut-off value of 7.0 points was established. No substantial floor (8.8%) or ceiling effects (4.9%) were observed at ICU discharge. However, a moderate floor effect was observed at ICU admission (19.3%), in contrast to a very low incidence of ceiling effect (0.6%). The Perme Score at ICU admission was associated with hospital mortality, OR 0.86 (95% CI: 0.82-0.91), and the predictive validity for ICU stay presented a mean ratio of 0.97 (95% CI: 0.96-0.98). Our findings support the establishment of the minimum clinically important difference and responsiveness of the Perme Score as a measure of mobility status in the ICU.


Flexibility modulates the catalytic activity of a thermostable enzyme: key information from optical spectroscopy and molecular dynamics simulation.
Enzymes are dynamical macromolecules and their conformation can be altered via local fluctuations of side chains, large scale loop and even domain motions which are intimately linked to their function. Herein, we have addressed the role of dynamic flexibility in the catalytic activity of a thermostable enzyme almond beta-glucosidase (BGL). Optical spectroscopy and classical molecular dynamics (MD) simulation were employed to study the thermal stability, catalytic activity and dynamical flexibility of the enzyme. An enzyme assay reveals high thermal stability and optimum catalytic activity at 333 K. Polarization-gated fluorescence anisotropy measurements employing 8-anilino-1-napthelenesulfonic acid (ANS) have indicated increasing flexibility of the enzyme with an increase in temperature. A study of the atomic 3D structure of the enzyme shows the presence of four loop regions (LRs) strategically placed over the catalytic barrel as a lid. MD simulations have indicated that the flexibility of BGL increases concurrently with temperature through different fluctuating characteristics of the enzyme's LRs. Principal Component Analysis (PCA) and the Steered Molecular Dynamics (SMD) simulation manifest the gatekeeper role of the four LRs through their dynamic fluctuations surrounding the active site which controls the catalytic activity of BGL.


Influence of adiponectin gene polymorphism SNP276 (G/T) on adiponectin in response to exercise training.
Adiponectin is an adipocytokine that is involved in insulin sensitivity. The adiponectin gene contains a single nucleotide polymorphism (SNP) at position 276 (G/T). The GG genotype of SNP276 (G/T) is associated with lower plasma adiponectin levels and a higher insulin resistance index. Therefore, we examined the influence of SNP276 (G/T) on the plasma level of adiponectin in response to exercise training. Thirty healthy Japanese (M12/F18; 56 to 79 years old) performed both resistance and endurance training, 5 times a week for 6 months. The work rate per kg of weight at double-product break-point (DPBP) was measured. Blood samples were obtained before and after the experiment. Plasma concentrations of adiponectin, HbA1c, insulin, glucose, total, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol, and triglyceride were measured. Genotypes of SNP276 were specified. Student's t-test for paired values and unpaired values was used. After the 6-month training period, the work rate per kg of weight at DPBP and the plasma HDL-cholesterol level were significantly improved (P<0.05), while no change was observed in the total plasma adiponectin level. However, the plasma adiponectin level in those with the GT + TT genotype had significantly increased (P<0.05). Additionally, the degree of the decrease in the HOMA-R level was significantly greater in the subjects with the GT + TT genotype than those with the GG genotype (p<0.05). Our results suggest that subjects with the genotype GT + TT at SNP276 (G/T) have a greater adiponectin-related response to exercise training than those with the GG genotype.


A randomized, open-label study to evaluate the safety and pharmacokinetics of human hepatitis C immune globulin (Civacir) in liver transplant recipients.
Chronic hepatitis C is the most common indication for liver transplantation, but viral recurrence is universal and progressive graft injury occurs in most recipients. Our aim was to assess the safety, pharmacokinetics (PK), and antiviral effects of high doses of a human hepatitis C antibody enriched immune globulin product (HCIG) in patients undergoing liver transplantation for chronic hepatitis C. This was a multicenter, randomized, open-label, controlled trial conducted at 4 transplant centers in the United States. A total of 18 patients with chronic hepatitis C, who underwent liver transplantation, were randomized to receive low-dose HCIG (75 mg/kg) or high-dose HCIG (200 mg/kg), or no treatment. A total of 17 infusions of HCIG were administered in each treated patient over 14 weeks using a time-dependent dosing strategy based on the PK of anti-hepatitis B immune globulin in liver transplant recipients. Hepatitis C virus levels, liver enzymes, and liver biopsies were obtained serially throughout the study period. PK profiles of HCV antibodies were determined on days 4, 10, and 98. HCIG infusions were safe and tolerated. The infusion rate could not be maximized because of symptoms for 18% to 30% of the doses. The half-life of HCIG was extremely short immediately after transplantation but was gradually prolonged. In the high-dose group, serum alanine aminotransferase (ALT) levels normalized in most subjects and no patient developed hepatic fibrosis. However, serum HCV RNA levels were not suppressed at either dose. In conclusion, HCIG, an anti-HCV enriched immune globulin product, appears to be safe in patients with chronic hepatitis C undergoing liver transplantation. Further studies are required to determine whether the drug has beneficial effects in this group of patients.


ICIQ symptom and quality of life instruments measure clinically relevant improvements in women with stress urinary incontinence.
To determine whether changes in questionnaire scores on symptoms and condition-specific quality of life reflect clinically relevant improvements in women with stress urinary incontinence (SUI). We retrospectively analyzed questionnaires collected during a randomized controlled trial in women with SUI, that received pelvic floor muscle training (PFMT) in two different formats. We included 218 women that answered validated self-assessment questionnaires at baseline and at a 4-month follow-up. We registered changes on two questionnaires, the International Consultation on Incontinence Modular Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) and the Lower Urinary Tract Symptoms Quality of Life (ICIQ-LUTSqol). We compared these score changes to responses from the Patient Global Impression of Improvement (PGI-I) questionnaire. Differences were analyzed with the Spearman rho and one-way-ANOVA. The minimum important difference (MID) was the mean change in score for women that experienced a small improvement. The PGI-I correlated significantly to both the ICIQ-UI SF (r = 0.547, P < 0.0001) and ICIQ-LUTSqol (r = 0.520, P < 0.0001). Thus, larger reductions in symptoms or quality of life scores were associated with greater impressions of improvement. The changes in ICIQ-UI SF and ICIQ-LUTSqol scores were significant across all PGI-I groups from "no change" to "very much improved" (P < 0.05). The MIDs were 2.52 (SD 2.56) for ICIQ-UI SF and 3.71 (SD 4.95) for ICIQ-LUTSqol. The change in ICIQ-UI SF and ICIQ-LUTSqol scores after PFMT reflected clinically relevant improvements in women with SUI. The MIDs established for this population may facilitate future research, treatment evaluations, and comparisons between studies.


Sex, linkage disequilibrium and patterns of parasitism in three species of cyclically parthenogenetic Daphnia (Cladocera: Crustacea).
To gain insight into genetic variation for resistance to parasites, this study assayed clonal variation in cyclically parthenogenetic Daphnia magna with respect to parasitic infection. Samples were collected from natural populations, and the allozyme phenotypes of infected hosts were compared to those of uninfected hosts. Differences between the clonal composition of the infected and uninfected class were evident in only two of 16 populations examined. This result stands in contrast to a study of species in the D. pulex and D. longispina species complexes, where clonal variation for infection was found in 12 of 25 populations (Little & Ebert, 1999). Considering all populations from both studies, associations between host genotype and infection were typically evident only in populations that showed low genotypic diversity and evidence of genetic disequilibria, with D. magna showing the least amount of disequilibria. This pattern is compatible with at least two possibly overlapping hypotheses. First, it may be that those populations lacking clonal variation for infection experienced weaker parasite-mediated selection. We can not rule out variation in selection pressure as an explanation, but found no evidence that the prevalence or intensity of parasitism differed either among species, or between those populations which showed clonal variation for infection and those that did not. Second, it could be that some populations, especially those of D. magna, have more frequent sexual recruitment than others. Sexual recombination breaks up gene combinations which are in linkage disequilibrium, and our method to detect clonal variation for resistance relies on linkage between genetic markers (allozymes) and resistance loci. Past work on Daphnia has shown that the level of sexual recruitment (which is in turn mediated by habitat permanency) is indeed commonly linked to the occurrence of genetic disequilibria. Our results may thus underestimate the prevalence of clonal variation for infection (especially for D. magna), because most of the populations analysed appeared to have high levels of sexual recruitment and therefore lacked the linkage disequilibrium that underlies associations between allozymes and susceptibility.


Resurfacing of the patella in young patients.
The results of prosthetic resurfacing of the patella in 15 knees of 14 patients who ranged in age from 18 to 38 years at the time of surgery have been presented. The results were excellent in two knees, good in one knee, fair in eight knees, and poor in four knees. No mechanical failures occurred. The follow-up period ranged from 6 weeks to 8 years. I believe that the use of prosthetic resurfacing of the patella should be limited to patients, regardless of age, who have grade 3 or 4 chondromalacia of the patella and extremely poor quadriceps function. These are patients who have remained grossly symptomatic in spite of continuous conservative and/or surgical treatment for a period of at least 2 years.


Comparative study of subjective fatigue between automatic transmission bus drivers and manual transmission bus drivers.
The difference in the physiological condition of drivers of manual transmission buses (MTB) and automatic transmission buses (ATB) was examined from the viewpoint of occupational health. This study was based on a self-administered questionnaire which involved items concerning subjective fatigue complaints. No differences in the mental fatigue and stress between MTB drivers and ATB drivers were observed. Although ATB drivers tended to feel less physical fatigue than MTB drivers, the difference was not statistically significant. From these results, it was suggested that there was little difference in the subjective fatigue between ATB drivers and MTB drivers.


[Authors].
In Germany, cognitive-behavioral therapy, psychodynamic therapy, and systemic therapy are scientifically and legally approved as suitable procedures for treating mental disorders. While all methods have provided empirical evidence of their effectiveness in adults according to defined criteria of the "Scientific Advisory Board for Psychotherapy" (in German: "Wissenschaftlicher Beirat Psychotherapie"), i. e., the official board which decides upon the formal scientific approval of psychotherapeutic approaches in Germany, an evaluation is lacking for the psychodynamic methods in children and adolescents. Against this background, we evaluated the available empirical data for psychodynamic therapy in children and adolescents based on the methods paper of the "Scientific Advisory Board for Psychotherapy" (2019; version 2.9). Published reviews served as the basis for identifying relevant studies, supplemented by a systematic literature search. We identified 91 potentially relevant studies but could not consider the majority of these due to formal exclusion criteria (mainly not disorder-specific, no control group). Up to 26 of the remaining studies provide evidence of efficacy as defined by the "Scientific Advisory Board for Psychotherapy". These cover 10 of the 18 areas of application as defined by the "Scientific Advisory Board for Psychotherapy". According to our evaluation, the reviewed studies provide empirical evidence for the three most relevant areas of application (i. e., affective disorders; anxiety disorders and obsessive-compulsive disorders; hyperkinetic disorders and conduct disorders). Thus, the available evidence supports the suitability of psychodynamic therapy as a method for the treatment of children and adolescents.


A new species of the genus Lycodon (Serpentes, Colubridae) from Guangxi, China.
A new species of colubrid snake, Lycodon cathaya sp. nov., is described based on two adult male specimens collected from Huaping Nature Reserve, Guangxi, southern China. In a phylogenetic analyses, the new species is shown to be a sister taxon to the clade composed of L. futsingensis and L. namdongensis with low statistical support, and can be distinguished from all known congeners by the significant genetic divergence in the mitochondrial cytochrome b gene fragment (p-distance ≥ 7.9%), and morphologically by the following combination of characters: (1) dorsal scales in 17-17-15 rows, smooth throughout; (2) supralabials eight, third to fifth in contact with eye, infralabials nine; (3) ventral scales 199-200 (plus two preventral scales), subcaudals 78; (4) loreal single, elongated, in contact with eye or not, not in contact with internasals; (5) a single preocular not in contact with frontal, supraocular in contact with prefrontal, two postoculars; (6) maxillary teeth 10 (4+2+2+2); (7) two anterior temporals, three posterior temporals; (8) precloacal plate entire; (9) ground color from head to tail brownish black, with 31-35 dusty rose bands on body trunk, 13-16 on tail; (10) bands in 1-2 vertebral scales broad in minimum width; (11) bands separate ground color into brownish black ellipse patches arranged in a row along the top of body and tail; (12) elliptical patches in 3-6 scales of the vertebral row in maximum width; (13) ventral surface of body with wide brownish black strip, margined with a pair of continuous narrow greyish white ventrolateral lines. With the description of the new species, 64 congeners are currently known in the genus Lycodon, with 16 species occurring in China.


Advances in metered dose inhaler technology: formulation development.
Pressurized metered dose inhalers (MDIs) are a long-standing method to treat diseases of the lung, such as asthma and chronic obstructive pulmonary disease. MDIs rely on the driving force of the propellant, which comprises the bulk of the MDI formulation, to atomize droplets containing drug and excipients, which ideally should deposit in the lungs. During the phase out of chlorofluorocarbon propellants and the introduction of more environmentally friendly hydrofluoroalkane propellants, many improvements were made to the methods of formulating for MDI drug delivery along with a greater understanding of formulation variables on product performance. This review presents a survey of challenges associated with formulating MDIs as solution or suspension products with one or more drugs, while considering the physicochemical properties of various excipients and how the addition of these excipients may impact overall product performance of the MDI. Propellants, volatile and nonvolatile cosolvents, surfactants, polymers, suspension stabilizers, and bulking agents are among the variety of excipients discussed in this review article. Furthermore, other formulation approaches, such as engineered excipient and drug-excipient particles, to deliver multiple drugs from a single MDI are also evaluated.