Biochemical mechanism of release of atrial natriuretic polypeptide.
To define transmembrane and intracellular mechanisms of production and release of atrial natriuretic polypeptide (ANP) in the absence of mechanical atrial stretch, we studied the direct effects of physiological stimuli on isolated adult rat atrial myocytes maintained under tissue culture. Although stimulation of beta-adrenergic receptors on the surface of atrial myocytes by isoproterenol did not affect ANP release, adrenergic alpha-1 receptor stimulation by methoxamine enhanced ANP release with reciprocal intracellular ANP reduction. When muscarinic receptors were stimulated by acetylcholine, ANP release was accelerated and intracellular ANP reduced. The activation of the phosphatidylinositol system, which is a common pathway for muscarinic and alpha-1 adrenergic receptor stimulation, was thus considered to regulate ANP release, but not ANP production.


Applying concepts of generalizability theory on data from experimental pain studies to investigate reliability.
This work demonstrates how full modelling power in statistically mixed models can be used to study generalizability (reliability) coefficients of advanced data from human experimental pain studies utilizing placebo data from drug screening trials. This can be used to help optimizing outcome parameters from existing data sets.


Effects of plant age and extraction conditions on the properties of homoserine dehydrogenase isolated from maize seedlings.
Homoserine dehydrogenase (EC 188.8.131.52) was extracted from shoots of etiolated seedlings of Zea mays L. which had been grown for periods ranging from three to thirteen days. Both the amount of enzyme extracted and its regulatory properties, as measured by the sensitivity of the enzyme to inhibition by the feedback modulator, l-threonine, were found to be a function of seedling age and extraction conditions. Equivalent amounts of enzyme with similar properties could be isolated from young seedlings under a variety of conditions. Extraction media containing comparatively low concentrations of the buffer component and a high concentration of dithioerythritol were found to be required for optimum extraction of the enzyme from shoots of seedlings grown longer than four days and from leaves of light-grown plants. In the absence of dithioerythritol, diminished regulatory control was observed to be a direct function of seedling age. Evidence of rapid desensitization of the enzyme during extraction was obtained from experiments in which dithioerythritol was added to extracts prepared in the absence of a thiol compound. Therefore, previous observations of growth-dependent desensitization in a number of plants could be due to incomplete extraction or to changes in cellular factors which inactivate and/or alter the enzyme. Whether the enzyme itself becomes increasingly susceptible to alteration during seedling growth remains to be established.


Pancreatic lymphoepithelial cysts express CEA and can contain mucous cells: potential pitfalls in the preoperative diagnosis.
Pancreatic lymphoepithelial cysts are rare benign cysts that cannot be reliably differentiated from neoplastic mucinous cysts preoperatively. Although elevated cyst fluid carcinoembryonic antigen (CEA) levels support a diagnosis of a mucinous cyst, the finding of increased CEA levels in lymphoepithelial cysts prompted this study. Nine resected lymphoepithelial cysts were examined for expression of CEA, carbohydrate antigen (CA) 19-9, CK7, p63, PAS-D and a panel of mucins. The pathology data were correlated with clinical information, including serum, cyst fluid and imaging studies. By computed tomography scan, although most lymphoepithelial cysts appeared cystic, 23% were described as masses. The endoscopic ultrasound findings were variable, but the lymphoepithelial cysts tended to be hypoechoic cystic lesions or masses. On cytology, 44% of the cysts had squamous cells, 67% had glandular cells and 56% had atypical cells. The cysts were resected because of size ≥3 cm (89%), symptoms (44%) and/or elevated cyst fluid CEA levels (33%). The cyst fluid CEA levels in the three cysts tested were >450 ng/ml. Histopathologically, all cysts were lined by mature, stratified squamous-type cells and produced keratin. Mucous cells were present in 78% of the cysts. The immunohistochemical profile of the squamous lining was CK7+, p63+, MUC1+, MUC4+, MUC2-, MUC5AC- and MUC6-. Even though lymphoepithelial cysts are lined by squamous-type epithelium, all our resected lymphoepithelial cysts expressed CEA and/or CA19-9, many contained mucous cells, and three exhibited markedly elevated cyst fluid CEA levels. Although cyst fluid CEA levels >200 ng/ml support the diagnosis of mucinous neoplasms, this study emphasizes the need for clinicians and pathologists to recognize that lymphoepithelial cysts can mimic neoplastic mucinous cysts clinically, radiographically and on cyst fluid CEA analysis.


Preference for cannibalism and ontogenetic constraints in competitive ability of piscivorous top predators.
Occurrence of cannibalism and inferior competitive ability of predators compared to their prey have been suggested to promote coexistence in size-structured intraguild predation (IGP) systems. The intrinsic size-structure of fish provides the necessary prerequisites to test whether the above mechanisms are general features of species interactions in fish communities where IGP is common. We first experimentally tested whether Arctic char (Salvelinus alpinus) were more efficient as a cannibal than as an interspecific predator on the prey fish ninespine stickleback (Pungitius pungitius) and whether ninespine stickleback were a more efficient competitor on the shared zooplankton prey than its predator, Arctic char. Secondly, we performed a literature survey to evaluate if piscivores in general are more efficient as cannibals than as interspecific predators and whether piscivores are inferior competitors on shared resources compared to their prey fish species. Both controlled pool experiments and outdoor pond experiments showed that char imposed a higher mortality on YOY char than on ninespine sticklebacks, suggesting that piscivorous char is a more efficient cannibal than interspecific predator. Estimates of size dependent attack rates on zooplankton further showed a consistently higher attack rate of ninespine sticklebacks compared to similar sized char on zooplankton, suggesting that ninespine stickleback is a more efficient competitor than char on zooplankton resources. The literature survey showed that piscivorous top consumers generally selected conspecifics over interspecific prey, and that prey species are competitively superior compared to juvenile piscivorous species in the zooplankton niche. We suggest that the observed selectivity for cannibal prey over interspecific prey and the competitive advantage of prey species over juvenile piscivores are common features in fish communities and that the observed selectivity for cannibalism over interspecific prey has the potential to mediate coexistence in size structured intraguild predation systems.


A service evaluation to explore Māori experiences of direct-acting antiviral hepatitis C treatment in Aotearoa New Zealand.
Hepatitis C, and its associated life-limiting sequalae, disproportionately affect Māori. Despite availability of fully funded effective and well-tolerated oral direct-acting anti-viral agents (DAA), many in New Zealand remain untreated. This service evaluation aimed to explore the experiences of Māori who have received DAA treatment for hepatitis C, and their ideas for service improvement. This qualitative service evaluation recruited eligible participants (Māori, 18 years+, DAA treatment since February 2019) through health care providers. Semi-structured interviews were undertaken over the telephone with consenting participants. General inductive analysis was used to generate themes contextualising findings within cultural contexts for Māori, as aligned with Māori methodological research practices. Twelve participants were interviewed. The physical and mental impact hepatitis C can have, and that treatment with DAA leads to improvement in these domains, were highlighted. Proactivity by health professionals was valued, including the benefit of wrap-around services to keep people connected throughout the treatment journey, with participants articulating the ability to self-advocate when needs were not met by other services. Findings can be used to enhance the development of further hepatitis C treatment services, based on Māori experiences of treatment and self-identified solutions for improvement in hepatitis C care.


Mutant Potential Ubiquitination Sites in Dur3p Enhance the Urea and Ethyl Carbamate Reduction in a Model Rice Wine System.
Ubiquitination can significantly affect the endocytosis and degradation of plasma membrane proteins. Here, the ubiquitination of a Saccharomyces cerevisiae urea plasma membrane transporter (Dur3p) was altered. Two potential ubiquitination sites, lysine residues K556 and K571, of Dur3p were predicted and replaced by arginine, and the effects of these mutations on urea utilization and formation under different nitrogen conditions were investigated. Compared with Dur3p, the Dur3pK556R mutant showed a 20.1% decrease in ubiquitination level in yeast nitrogen base medium containing urea and glutamine. It also exhibited a >75.8% decrease in urea formation in yeast extract-peptone-dextrose medium and 41.3 and 55.4% decreases in urea and ethyl carbamate formation (a known carcinogen), respectively, in a model rice wine system. The results presented here show that the mutation of Dur3p ubiquitination sites could significantly affect urea utilization and formation. Modifying the ubiquitination of specific transporters might have promising applications in rationally engineering S. cerevisiae strains to efficiently use specific nitrogen sources.


Cutaneous lesions and disorders in healthy neonates and their relationships with maternal-neonatal factors: a cross-sectional study.
Cutaneous lesions are very common in neonates. Although a number of studies have reported on their incidence, very little is known about the factors that influence them. We set out to investigate a large population of neonates with the aims of achieving an overall picture of neonatal skin manifestations, and examining their relationships with various maternal, neonatal and perinatal factors. This study was conducted on neonates born at the Department of Obstetrics and Gynaecology at the University of Szeged between June 2013 and July 2015. A total of 4658 consecutive infants underwent a whole-body skin examination within the first 72 hours of extrauterine life. The official neonatal medical charts were used to collect data on the history of the participating neonates and on maternal factors. 74.35% of the neonates exhibited at least one skin manifestation. The major diagnosis groups were transient, benign cutaneous lesions; vascular lesions; traumatic, iatrogenic, congenital or acquired disorders with skin injuries; pigmented lesions; and developmental abnormalities or benign skin tumours. The relationships between the skin findings and six neonatal or maternal factors were examined: gender, gestational age and birth weight of the neonates; maternal age and the number of previous pregnancies of the mothers, and mode and circumstances of the delivery. We found several significant correlations between the examined maternal/neonatal factors and the occurrence of birthmarks and neonatal skin disorders. Of course, further studies are required to confirm and better understand these associations.


Development and validation of the Alcohol Myopia Scale.
Alcohol myopia theory conceptualizes the ability of alcohol to narrow attention and how this demand on mental resources produces the impairments of self-inflation, relief, and excess. The current research was designed to develop and validate a scale based on this framework. People who were alcohol users rated items representing myopic experiences arising from drinking episodes in the past month. In Study 1 (N = 260), the preliminary 3-factor structure was supported by exploratory factor analysis. In Study 2 (N = 289), the 3-factor structure was substantiated with confirmatory factor analysis, and it was superior in fit to an empirically indefensible 1-factor structure. The final 14-item scale was evaluated with internal consistency reliability, discriminant validity, convergent validity, criterion validity, and incremental validity. The alcohol myopia scale (AMS) illuminates conceptual underpinnings of this theory and yields insights for understanding the tunnel vision that arises from intoxication.


Body composition in Prader-Willi syndrome: assessment and effects of growth hormone administration.
Children and adults with Prader-Willi syndrome are usually overweight, if not obese. Nevertheless, it is now thought that the body composition exhibited by such individuals is markedly dissimilar to that found in simple obesity. In fact, the body composition typical of Prader-Willi syndrome is actually more characteristic of that found in individuals with growth hormone (GH) deficiency, namely an increased level of adiposity in the limbs in comparison with the trunk and an overall reduction in fat-free mass. This variation in body composition may impact upon the assumptions inherent in many techniques used to measure body size and body composition, such as the use of body mass index and skinfolds. Therefore, it is important that the potential error in body composition assessment is understood by professionals evaluating patients with Prader-Willi syndrome. Accurate assessment of body composition is critical in Prader-Willi syndrome, as a number of recent studies have revealed extremely similar findings relating to the effect of exogenous GH on the body composition of patients with this syndrome. Other notable findings of these studies include significant increases in muscle strength and exercise capacity, which probably result from the changes in body composition. The routine use of exogenous GH to treat this extremely debilitating syndrome should now be considered.


Phytanic acid alpha-oxidation: decarboxylation of 2-hydroxyphytanoyl-CoA to pristanic acid in human liver.
The degradation of the first intermediate in the alpha-oxidation of phytanic acid, 2-hydroxyphytanoyl-CoA, was investigated. Human liver homogenates were incubated with 2-hydroxyphytanoyl-CoA or 2-hydroxyphytanic acid, after which formation of 2-ketophytanic acid and pristanic acid were studied. 2-Hydroxyphytanic acid was converted into 2-ketophytanic acid and pristanic acid. When ATP, Mg2+, and coenzyme A were added to the incubation medium, higher amounts of pristanic acid were formed, whereas the formation of 2-ketophytanic acid strongly decreased. When 2-hydroxyphytanoyl-CoA was used as substrate, there was virtually no 2-ketophytanic acid formation. However, pristanic acid was formed in higher amounts than with 2-hydroxyphytanic acid as substrate. This reaction was stimulated by NAD+ and NADP+. Pristanic acid, and not pristanoyl-CoA was found to be the product of the reaction. These results suggest the existence of two pathways for decarboxylation of 2-hydroxyphytanic acid. The first one, starting from 2-hydroxyphytanic acid, involves the formation of 2-ketophytanic acid with only a small amount of pristanic acid being formed. The second pathway, which starts from 2-hydroxyphytanoyl-CoA, does not involve 2-ketophytanic acid and generates higher amounts of pristanic acid. The first pathway, which is peroxisomally localized, was found to be deficient in Zellweger syndrome, whereas the second pathway, localized in microsomes, was normally active. We conclude that the second pathway is predominant under in vivo conditions.


Analysis of Laser Sensors and Camera Vision in the Shoe Position Inspection System.
Inspection systems are currently an evolving field in the industry. The main goal is to provide a picture of the quality of intermediates and products in the production process. The most widespread sensory system is camera equipment. This article describes the implementation of camera devices for checking the location of the upper on the shoe last. The next part of the article deals with the analysis of the application of laser sensors in this task. The results point to the clear advantages of laser sensors in the inspection task of placing the uppers on the shoe's last. The proposed method defined the resolution of laser scanners according to the type of scanned surface, where the resolution of point cloud ranged from 0.16 to 0.5 mm per point based on equations representing specific points approximated to polynomial regression in specific places, which are defined in this article. Next, two inspection systems were described, where one included further development in the field of automation and Industry 4.0 and with a high perspective of development into the future. The main aim of this work is to conduct analyses of sensory systems for inspection systems and their possibilities for further work mainly based on the resolution and quality of obtained data. For instance, dependency on scanning complex surfaces and the achieved resolution of scanned surfaces.


Knowledge and misconceptions about sexually transmitted infections in married women--perspective from Islamabad.
To study the knowledge of married women regarding existence of sexually transmitted infection (STI) their complications, treatment seeking, ways of preventing STI acquisition and opinion about sex education in schools/colleges and media. The Mother and Child Health Center, a tertiary care hospital in Islamabad. A cross-sectional survey based on sample of convenience was conducted, using a structured questionnaire with both close and open-ended questions. Trained women physician interviewers conducted the interviews after obtaining verbal consent. Out of 218 women approached for interviewing, only two refused to participate in the study. The mean age of the respondents was 28.5 years (range 18-53 years). One hundred and sixty-eight (77.8%) respondents had heard/knew about sexually transmitted infections (STIs). Two hundred and ten (97.2%) respondents had heard/ knew about AIDS and out of these 162 (77.1%) knew that it is also transmitted through sexual contact. One hundred and eighty two (84.2%) felt a need for sex education in the media, both print and electronic and 204 (94.4%) respondents said that they would like to learn more about sexually transmitted infections. One hundred ninety four (98.8%) respondents had heard the Latin term Leukorrhoea. Of these 158 (81.5%) thought it was a gynecological disease. Majority thought it caused weakness. Widespread misperceptions were found to exist, which does not augur well for the effective prevention of STIs in the country. Population based studies are required to study the knowledge and epidemiology of STIs, as well as a need for a health education campaign in the country (JPMA 51:389; 2001).


Accurate control of stoichiometry and doping in barium stannate perovskite oxide nanoparticles.
Barium stannate (BaSnO3) is one of the most promising emerging materials for use as a transparent electrode. However, to date, its synthesis has been proven to be highly irreproducible. In this communication, we present a detailed investigation of the reproducibility issues and provide a robust approach to synthesize BaSnO3 nanomaterials with controlled stoichiometry and doping.


Catalytic dehydrocoupling/dehydrogenation of N-methylamine-borane and ammonia-borane: synthesis and characterization of high molecular weight polyaminoboranes.
The catalytic dehydrocoupling/dehydrogenation of N-methylamine-borane, MeNH(2)·BH(3) (7), to yield the soluble, high molecular weight poly(N-methylaminoborane) (8a), [MeNH-BH(2)](n) (M(W) > 20 000), has been achieved at 20 °C using Brookhart's Ir(III) pincer complex IrH(2)POCOP (5) (POCOP = [μ(3)-1,3-(OPtBu(2))(2)C(6)H(3)]) as a catalyst. The analogous reaction with ammonia-borane, NH(3)·BH(3) (4), gave an insoluble product, [NH(2)-BH(2)](n) (8d), but copolymerization with MeNH(2)·BH(3) gave soluble random copolymers, [MeNH-BH(2)](n)-r-[NH(2)-BH(2)](m) (8b and 8c). The structures of polyaminoborane 8a and copolymers 8b and 8c were further analyzed by ultrahigh resolution electrospray mass spectrometry (ESI-MS), and 8a, together with insoluble homopolymer 8d, was also characterized by (11)B and (1)H solid-state NMR, IR, and wide-angle X-ray scattering (WAXS). The data indicate that 8a-8c are essentially linear, high molecular weight materials and that the insoluble polyaminoborane 8d possesses a similar structure but is of lower molecular weight (ca. 20 repeat units), presumably due to premature precipitation during its formation. The yield and molecular weight of polymer 8a was found to be relatively robust toward the influence of different temperatures, solvents, and adduct concentrations, while higher catalyst loadings led to higher molecular weight materials. It was therefore unexpected that the polymerization of 7 using 5 was found to be a chain-growth rather than a step-growth process, where high molecular weights were already attained at about 40% conversion of 7. The results obtained are consistent with a two stage polymerization mechanism where, first, the Ir catalyst 5 dehydrogenates 7 to afford the monomer MeNH═BH(2) and, second, the same catalyst effects the subsequent polymerization of this species. A wide range of other catalysts based on Ru, Rh, and Pd were also found to be effective for the transformation of 7 to polyaminoborane 8a. For example, polyaminoborane 8a was even isolated from the initial stage of the dehydrocoupling/dehydrogenation of 7 with [Rh(μ-Cl)(1,5-cod)](2) (2) as the catalyst at 20 °C, a reaction reported to give the N,N,N-trimethyl borazine, [MeN-BH](3), under different conditions (dimethoxyethane, 45 °C). The ability to use a variety of catalysts to prepare polyaminoboranes suggests that the synthetic strategy should be applicable to a broad range of amine-borane precursors and is a promising development for this new class of inorganic polymers.


Liquid enteral diets induce bacterial translocation by increasing cecal flora without changing intestinal motility.
The aim of this study was to determine the contribution of intestinal motility and cecal bacterial overgrowth to liquid diet-induced bacterial translocation (BT). Three different commercially available liquid diets were offered to mice for 1 week. BT to the mesenteric lymph nodes (MLN), spleen, and liver were examined as well as cecal bacterial counts and populations, small bowel length and weight, and histopathologic changes in the ileal and jejunal mucosa. In addition, the effect of the various diets on intestinal motility was measured by the transit index of a charcoal mixture introduced into the stomach. The incidence of BT to the mesenteric lymph nodes was significantly and similarly increased (p < .05) in mice fed Vivonex (30%), Ensure (30%), and Osmolite (33%) compared with chow-fed controls (0%). Compared with chow-fed controls, all three liquid diets were associated with the development of cecal bacterial overgrowth (p < .01). There were no significant changes in the transit index for the three liquid diet groups compared with the chow-fed controls. BT to the MLN was induced by all three liquid diets tested, casting some doubts as to their role in preventing BT in clinical use. BT was associated with a statistically significant increase in cecal bacterial count but was not associated with gut motility changes in this model. In fact, no significant changes in intestinal motility were noted in all groups tested.


[Therapy modalities used in tuberculosis in a French Department. The Bas-Rhin, 1965-77].
An analysis of treatment methods was carried out on 8,116 subjects suffering from all forms of tuberculosis, notified from 1965 to 1976 to the Bas-Rhin Tuberculosis Register and not kept in the active card index longer than the 31 dec. 1977 (because they were cured, dead or lost from sight). Only the cases of respiratory tuberculosis not bacteriologically proven notified during the first period (1965 to 1969) were not included in the study. In the annual cohorts the proportion of patients treated in hospital for more than 15 days, as cell as the mean length of hospital stay and duration of antituberculous chemotherapy, has considerably decreased. The drugs most often used for notified patients from 1965 to 1969 were Isoniazid, Streptomycin and P.A.S. For patients notified between 1970 and 1976, Rifampicin, Isoniazid and Ethambutol were most common. Triple therapy was used most often, 66,8% for the first period, 52.6% for the second. At the end of the second year of follow up the proportion cured rose from 26% of the cases surveilled for the first cohort (1965-1969) to 51% for the second (1970 to 1974) and 61% for the third (1975-1976). As for the death rate, this progressively declined from 4,3% to 2,4% and 1,6%. Finally the prevalence and incidence of bacteriologically proven tuberculosis has decreased strikingly in the general population of the Bas-Rhin since 1965. In addition there was a progressive diminution in the ratio of these two indices (2,4 in 1965 and 1,2 in 1979) conveying the real efficacy of these treatment regimes.


Crohn's disease presented by episiotomy dehiscence and perineal fistula.
A case of Crohn's disease is described which was first manifested by episiotomy dehiscence and perineal fistula after an instrumental delivery. The female newborn showed a congenital rectovaginal fistula and hexadactylia. Differential diagnosis and possible relationship between both fistulas are discussed.


Treatment of congenital swan neck deformity with dynamic tenodesis of proximal interphalangeal joint.
Congenital swan neck deformities in seven fingers of two patients were treated by transfer of the flexor digitorum superficialis tendon to a tendon graft which was attached the extensor aponeurosis over the middle phalanx. The tendon transfer is protected for at least 2 months by a modified Murphy splint.


Polycythemia.
Plethora ('a morbid condition due to excess of red corpuscles') has been recognized since antiquity as a manifestation of disease. The use of leeches and blood letting, which was for centuries the mainstay of therapy in many clinical situations, reflected the importance then attached to having too much blood. Greater knowledge has achieved greater precision, so that measurement of packed cell volume (PCV) or hematocrit now defines polycythemia (> 0.51 in men and > 0.48 in women, when blood is sampled without venous occlusion). Clinical and laboratory investigations, mainly in the last 30 years, have enabled the subdivision of polycythemia into different subtypes of radically different etiology which will be described in this Chapter. The last decade, however, has seen the advancing edge of research in this field passing from clinical and routine laboratory testing to studies of cellular proliferation at the molecular level. Detailed understanding is, however, as always elusive, with each new finding revealing deeper layers which in turn need elucidation. The field of polycythemia is nevertheless moving slowly into the molecular era.


[The influence of thyroid hormones on homocysteine and atherosclerotic vascular disease].
Several reports have appeared in the literature proving that hypothyroidism is associated with increased risk for cardiovascular disease, especially coronary heart disease. This increased risk for premature atherosclerosis is supported by autopsy and epidemiological studies in patients with thyroid hormone deficiency. Hypothyroid patients have increased diastolic blood pressure (as a result of increased systemic vascular resistance), altered lipid profile (elevated levels of total cholesterol, LDL-cholesterol and apolipoprotein B). More recently homocysteine, C-reactive protein, increased arterial stiffness, endothelial dysfunction and altered coagulation parameters have been recognized as a "new" risk factors for atherosclerosis in patients with thyroid hormone deficiency. The plasma total homocysteine concentration, an independent risk factor for atherosclerosis, is moderately elevated in overtly hypothyroid patients and it decreases with thyroid replacement therapy. Several experimental study have shown that hypothyroidism affects folate metabolism and the enzymes involved in the remetylation pathway of homocysteine (particularly 5,10-methylenotetrahydrofolate reductase - MTHFR). In hypothyroid condition the hepatic activity of flavoenzyme - MTHFR, is decreased. Thyroid hormone may affect the availability of FMN and FAD - necessary for stabilizing MTHFR. An impairment of enzyme involved in transsulfuration pathway is suggested. The increased serum creatinine level in hypothyroidism probably reflects a reduced glomerular filtration rate, which is linked to impaired renal homocysteine clearance and hyperhomocysteinemia.


Sex in the Time of COVID-19: Patterns of Sexual Behavior Among LGBTQ+ Individuals in the U.S.
The SARS-CoV-2 virus, the pathogen which causes COVID-19, has left an indelible impact on the daily lives of individuals in the USA. This study sought to explore the sexual behaviors among people in the LGBTQ+ population at the onset of the pandemic. Behaviors were explored across sub-groups of the population. The study employed data from an internet survey about the impact of COVID-19 on LGBTQ+ identified individuals conducted between May and July 2020. The final sample was comprised of 1090 participants from across the USA. Overall, sexual activity and the number of sexual partners decreased after March 13, 2020 (as compared to before this date) across all sexual orientation groups; however, living situation and partnership status supported sexual activity. Gay and bisexual men living with a partner or a spouse (AOR = 2.20, p = .023) and those living with a non-romantic roommate or friend (AOR = 2.88, p = .004) reported more sexual activity. For both cisgender lesbian and bisexual women and transgender and non-binary individuals, those who were married or in a domestic partnership (AOR = 4.54, p < .001; AOR = 9.97, p < .001, respectively) and those in a committed relationship (AOR = 3.54, p = .001; AOR = 8.46, p < .001, respectively) reported more sexual activity. Additionally, cisgender lesbian and bisexual women living with their partner or spouse (AOR = 2.14, p = .044) reported more sexual activity. When examining the number of sexual partners, cisgender lesbian and bisexual women and transgender and non-binary individuals in a committed relationship (AOR = 0.31, p < 0.001; AOR = 0.26, p = .004, respectively) and those living with a partner or spouse (AOR = 0.30, p = .002; AOR = 0.25, p = .028, respectively) were less likely to report two or more sexual partners. Examining the changes in sexual activity and number of sexual partners helps us better identify the effects of COVID-19 on intimate relationships and sexual behaviors. Furthermore, this study may help develop clinical best practices to facilitate risk-reduction strategies for LGBTQ+ populations when engaging in sexual activity within a communicable disease framework. Current guidance on sexual activity within a pandemic has created a unique opportunity for sex-positive public health messaging that protects individual health while also offering a framework for conversations about risk mitigation that is applicable for both COVID-19 and STI/HIV prevention.


Who cares? Patients' descriptions of age-related aspects of cancer and care in Stockholm.
This exploratory study examines the situation of a heterogeneous group of 46 cancer patients from one general hospital in the Stockholm area who were diagnosed with a malignant disease in 1987. Forty-six patients were interviewed to determine how they experience and cope with their sickness. Although age-related issues were not directly addressed by the interviewer, they were frequently commented upon by the respondents. A questionnaire was also used to quantify various psychosocial aspects of the individual's cancer experience. Quantitative and qualitative data were used in a complementary fashion. The patients interviewed ranged in age from 29 to 88 years (median 61). Issues related to age were frequently addressed spontaneously by the interviewed persons, which led to further exploration of age-related aspects of care. Although few age-related differences in symptom distress were found, some differences were seen in patients' perceptions of the response of the professional health-care system. The older patients related that they have less quantitative contact with specialized formal resources, and perceive less sense of engagement and concern from the professional health-care sector. The qualitative analysis suggests that age may be used by patients as an explanatory factor in a variety of situations, functioning as a means of "making sense" of sickness experiences.


Differential eNOS-signalling by platelet subpopulations regulates adhesion and aggregation.
In addition to maintaining haemostasis, circulating blood platelets are the cellular culprits that form occlusive thrombi in arteries and veins. Compared to blood leucocytes, which exist as functionally distinct subtypes, platelets are considered to be relatively simple cell fragments that form vascular system plugs without a differentially regulated cellular response. Hence, investigation into platelet subpopulations with distinct functional roles in haemostasis/thrombosis has been limited. In our present study, we investigated whether functionally distinct platelet subpopulations exist based on their ability to generate and respond to nitric oxide (NO), an endogenous platelet inhibitor. Utilizing highly sensitive and selective flow cytometry protocols, we demonstrate that human platelet subpopulations exist based on the presence and absence of endothelial nitric oxide synthase (eNOS). Platelets lacking eNOS (approximately 20% of total platelets) fail to produce NO and have a down-regulated soluble guanylate cyclase-protein kinase G (sGC-PKG)-signalling pathway. In flow chamber and aggregation experiments eNOS-negative platelets primarily initiate adhesion to collagen, more readily activate integrin αIIbβ3 and secrete matrix metalloproteinase-2, and form larger aggregates than their eNOS-positive counterparts. Conversely, platelets having an intact eNOS-sGC-PKG-signalling pathway (approximately 80% of total platelets) form the bulk of an aggregate via increased thromboxane synthesis and ultimately limit its size via NO generation. These findings reveal previously unrecognized characteristics and complexity of platelets and their regulation of adhesion/aggregation. The identification of platelet subpopulations also has potentially important consequences to human health and disease as impaired platelet NO-signalling has been identified in patients with coronary artery disease.


[Obstetrical study of the pelvis: a historical overview].
The female pelvis is fundamental to life itself, but it took ages to grasp this truism. During Antiquity, physicians had no need for the concepts of pelvic dystocia and cephalopelvic disproportion. When Aranzo (16th century), a practising physician, stated that a disproportion between the size of the fetus and that of the bony pelvis was the main culprit of difficult labor, his suggestion was overlooked, so much so that it was Hendrik van Deventer (1701) who came to be coined "father of the pelvic theory". The need for an accurate knowledge of the dimensions of the maternal pelvis and of the fetal skull became imperative in the middle of the 18th century, when forceps extraction had become popular. Levret, but above all William Smellie, made valuable contributions to the pelvic theory, which, however, were weakened by Baudelocque's fallacies concerning the intrinsic value of external pelvimetry. After the first quarter of the 19th century, the epicenter of scientific obstetrics moved to Germany and Austria, and German-speaking practitioners, e.g. Michaelis, Litzmann, and the Naegele, deepened our insight in the mechanism of labor. After the discovery of the X-rays (1895), the use of instrumental pelvimetry declined, but the clinical breakthrough of radiopelvimetry was delayed until the twenties of this century. Radiopelvimetry, a very valuable technique indeed, dispensed a large number of mothers from undergoing abdominal delivery. However, awareness of the hazards of fetal-maternal exposure to ionizing radiation pushed ante- and intrapartum radiopelvimetry from the scene. Thanks to the progress of chemistry, pharmacology and electronics, "dynamic pelvimetry" became the fad, heralded by what is called "active management of labour". The fetus now assumed the role of "dynamic pelvimeter". The historical circle was closed.


Stand- and tree-level determinants of the drought response of Scots pine radial growth.
Characterizing the responses of key tree species to extreme climatic events may provide important information for predicting future forest responses to increased climatic variability. Here we aimed at determining which tree- and stand-level attributes were more closely associated with the effect of a severe drought on the radial growth of Scots pine, both in terms of immediate impact and recovery after the drought event. Our dataset included tree-ring series from 393 plots located close to the dry limit of the species range. Time series analysis and mixed-effects models were used to study the growth of each tree and its detailed response to a severe drought event that occurred in 1986. Our results showed that the radial growth responses of Scots pine were determined primarily by tree-level characteristics, such as age and previous growth rate, and secondarily by stand basal area and species richness, whereas local climate had a relatively minor effect. Fast-growing trees were more severely affected by the drought and retained proportionally lower growth rates up to three years after the episode. In absolute terms, however, fast-growing trees performed better both during and after the event. Older trees were found to be less resilient to drought. The effect of stand basal area and species richness indicated that competition for resources worsened the effects of drought, and suggested that the effect of interspecific competition may be particularly detrimental during the drought year.


Focal intra-cavotricuspid isthmus atrial tachycardias occurring after typical atrial flutter ablation: incidence and electrocardiographic and electrophysiological characteristics.
Focal atrial tachycardias (ATs) from the septal cavotricuspid isthmus (CTI) occurring after successful CTI ablation can mimic typical atrial flutter (tAFL). This study investigated the incidence, and electrocardiographic and electrophysiological characteristics of these ATs. Among 1082 consecutive patients undergoing successful CTI ablation without any congenital heart diseases, 7 were diagnosed with focal ATs originating from the septal CTI that occurred a median of 74 days after the CTI ablation. The electrocardiographic characteristics of the ATs were similar to those of the tAFLs. The AT's cycle length was never shorter than and often similar to that of tAFLs. The activation patterns along the tricuspid annulus during the ATs were the same as those of tAFLs in 4 patients with foci adjacent to the CTI line, and centrifugal from foci around the coronary sinus (CS) ostium in 3. Entrainment pacing from the lateral CTI during the ATs revealed a manifest fusion and long post-pacing interval. Entrainment pacing from the lateral CTI during the ATs revealed that the atrial electrograms recorded from the CS and high-lateral right atrium were orthodromically captured, while that from the proximal CS revealed that the atrial electrograms recorded from the CS and lateral right atrium were antidromically captured without manifest fusion. Focal intra-CTI ATs with a microreentrant mechanism very rarely occurred after successful CTI ablation. The electrocardiographic and electrophysiological characteristics of these ATs were similar to those of tAFLs. Overdrive pacing from the lateral CTI and proximal CS was helpful for distinguishing these ATs from recurrent tAFLs.


Phenotypic and functional characteristics of monocyte-derived dendritic cells from patients with myelodysplastic syndromes.
We have compared the phenotypic and functional characteristics of dendritic cells (DC) generated in vitro from the peripheral blood mononuclear fraction of myelodysplastic syndrome (MDS) patients (four refractory anaemia, four refractory anaemia with excess of blasts) with DCs generated in a similar way from eight healthy donors. After 10 d of culture in the presence of GM-CSF and IL-4, reduced numbers and percentages of DCs were obtained in MDS subjects. MDS DCs exhibited significantly lower expression of CD1a, CD54, CD80 and MHC class II molecules. Their ability to stimulate T lymphocytes in an allogeneic mixed leucocyte reaction was reduced in comparison to normal subjects. Furthermore, MDS DCs also showed a reduced receptor-mediated endocytosis as demonstrated by FITC-dextran uptake. Simultaneous fluorescence in situ hybridization (FISH) and immunophenotypic analysis demonstrated that MDS DCs have the same cytogenetic abnormality of the malignant clone. Taken together these findings indicate that, in MDS, DCs are part of the malignant clone and exhibit a deficient antigen uptake and presentation.


Determination of saccharides in biological materials by high-performance anion-exchange chromatography with pulsed amperometric detection.
High-performance anion-exchange chromatography (HPAEC) coupled with pulsed amperometric detection (PAD) under alkaline conditions (pH 9-13) separates aminosaccharides, neutral saccharides and glycuronic acids based upon their molecular size, saccharide composition and glycosidic linkages. Carbohydrates were extracted by utilizing 0.5 M H2SO4 (neutral monosaccharides), 0.25 M H2SO4 coupled with enzyme catalysis (glycuronic acids) and 3 M H2SO4 (aminosaccharides). Solid-phase extraction with strong cation and strong anion resins was used to partition the cationic aminosaccharides and anionic glycuronic acids and to deionize acid extracts for neutral saccharides. Separation was conducted on a medium-capacity anion-exchange column (36 mequiv.) utilizing sodium hydroxide (5-200 mM and sodium acetate (0-250 mM) as the mobile phase. The saccharides were detected by oxidation at a gold working electrode with triple-pulsed amperometry. HPAEC-PAD was found superior to high-performance liquid chromatography with refractive index (RI) detection for neutral monosaccharides and aminosaccharides and to low-wavelength UV detection for glycuronic acids in terms of resolution and sensitivity. HPAEC-PAD was not subject to interferences as was the case for low UV detection (210 nm) or RI analyses and was highly selective for mono- and aminosaccharides and glycuronic acids. The use of HPAEC-PAD was applied for the determination of the saccharide composition of organic materials (plant residues, animal wastes and sewage sludge), microbial polymers and soil.


Repair of large nasal septal perforation with titanium membrane: report of 10 cases.
The aim of the study was to study a new treatment to repair large nasal septal perforation with medical titanium membrane. Ten patients with septal perforation underwent repair with open rhinoplasty approach using titanium membrane. The perforation of nasal septum in 10 patients was closed satisfactorily. During our followup period (mean, 1 year), the titanium membrane was mucosalized, and this technique led to persistent closing of perforation. Repair of septal perforation with titanium membrane yields excellent results.


Psychometric Evaluation of the Nine-Item Problematic Internet Use Questionnaire (PIUQ-9) in Nine European Samples of Internet Users.
Objectives: The nine-item Problematic Internet Use Questionnaire (PIUQ-9) is a brief self-report screening instrument for problematic internet use. The main objective of the present study was to explore the psychometric properties of the PIUQ-9 among nine different language-based samples of European internet users (Italian, German, French, Polish, Turkish, Hungarian, English, and Greek). Methods: The total sample comprised 5,593 internet users (38.1% men), aged between 18 and 87 years (M = 25.81; SD = 8.61). Via online recruitment, participants completed the PIUQ-9, the Brief Symptom Inventory (BSI) and items about time spent online. Results: Confirmatory factor analysis demonstrated that the bifactor model with one general factor (i.e., general problem) and two-specific factors (i.e., obsession and neglect + control disorder) yielded acceptable or good fit indices in all subsamples except for one. The common variance index in the bifactor model indicated that the general problem factor explained from 57.0 to 76.5% of common variance, which supports the presence of a strong global factor. According to the multiple indicators multiple causes (MIMIC) model, psychiatric symptoms had a moderate-to-strong direct effect on the general problem factor in all subsamples, ranging from β = 0.28 to β = 0.52 supporting the construct validity of the scale. Furthermore, in a majority of the subsamples, time spent online during the weekend had considerably higher effect sizes on the general problem factor than time spent online during weekdays. Conclusion: The present study highlights the appropriate psychometric properties of the PIUQ-9 across a number of European languages and cultures.


Interaction of glutathione depletion and psychotropic drug treatment in prepulse inhibition in rats and mice.
Oxidative stress has been implicated in several psychiatric illnesses, including schizophrenia. Glutathione is the brain's primary antioxidant and decreased levels of brain glutathione are reported in schizophrenia. Prepulse inhibition (PPI) is a measure of sensory gating, and PPI is reduced in schizophrenia. This study aimed to investigate the effects of brain glutathione depletion on PPI regulation. Rats and mice were treated with the glutathione-depleting agent, 2-cyclohexene-1-one (CHX), and tested for baseline PPI and its disruption by treatment with amphetamine and MK-801. Treatment with CHX caused significant depletion of GSH in frontal cortex and striatum of rats and mice. Baseline PPI and startle were not altered. However, the disruption of PPI after treatment with amphetamine was absent in CHX-treated rats. In contrast, the effect of MK-801 was not altered by CHX-treatment, nor was there any effect of CHX treatment in mice. These data show an interaction of glutathione depletion with the effects of amphetamine treatment on PPI in rats. This effect could reflect loss of plasticity in PPI regulation caused by the additive effects of CHX-induced glutathione depletion and additional oxidative stress caused by amphetamine-induced dopamine release. The significance of these results for schizophrenia is discussed.


Does light inhibit ethylene production in leaves?
The effect of light on the rate of ethylene production was monitored using two different techniques-leaf segments incubated in closed flasks versus intact plants in a flow-through open system. Three different plants were used, viz sunflower (Helianthus annuus), tomato (Lycopersicon esculentum), and soybean (Glycine max). Experiments were conducted both in the presence and absence of 1-aminocyclopropane-1-carboxylic acid (ACC).The results obtained indicate that, in all three species studied, light strongly inhibits ethylene production when cut leaf segments are incubated in the presence of ACC in closed flasks. When ethylene measurements are made with ACC-sprayed intact plants using a continuous flow system, the effect of light on ethylene production is only marginal. In leaf segments of sunflower and soybean incubated only in distilled H(2)O in closed flasks, light promotes ethylene production. In tomato, there is no difference between the rate of ethylene production between light and darkness under such conditions. When measurements are made with intact plants in a continuous flow system, the rate of ethylene production is almost identical in light and darkness, in the three plants studied.It is concluded that the effect of light on cut leaf segments incubated in the presence of ACC in closed flasks can be attributed to the techniques used for these measurements. Light has little effect on ethylene production by intact plants in an open system.


Predictions of the dynamics of a polygenic character under directional selection.
A quantitative genetic model for the response of the distribution of a single metric trait to directional selection is investigated. Particular attention is paid to the performance of approximations that use only limited information on the initial state of the population, such as the mean, the variance, the skewness and the kurtosis. Selection is imposed according to an exponentially increasing fitness function, populations mate at random, have discrete generations, and all genetic effects are supposed to be additive. Neglecting random drift, qualitatively different predictions for the initial response of a large population that has previously been at a mutation-stabilizing selection balance are derived. These depend on different assumptions about the initial distribution and are compared to the exact dynamics of that model. Linkage disequilibrium can be ignored as long as linkage is not too tight. The mathematical analysis rests on the method of cumulants and of cumulant-generating functions and produces exact equations for the evolution of cumulants in this model. Small populations subject to random drift are shown to respond in a qualitatively different way. The case of small populations is treated, primarily, by Monte Carlo simulations. The consequences of qualitatively different assumptions about maintenance of variation through mutation for the initial response to exponential directional selection are discussed. It is concluded that a significant initial increase in variance is unlikely to be observed in selection experiments if the effective population size is not larger than 500 and if response is caused by additive genes. The present results also apply to weak truncation selection.


Infliximab in pediatric inflammatory bowel disease rapidly decreases fecal calprotectin levels.
To study the response to infliximab in pediatric inflammatory bowel disease (IBD), as reflected in fecal calprotectin levels. Thirty-six pediatric patients with IBD [23 Crohn's disease (CD), 13 ulcerative colitis (UC); median age 14 years] were treated with infliximab. Fecal calprotectin was measured at baseline, and 2 and 6 wk after therapy, and compared to blood inflammatory markers. Maintenance medication was unaltered until the third infusion but glucocorticoids were tapered off if the patient was doing well. At introduction of infliximab, median fecal calprotectin level was 1150 μg/g (range 54-6032 μg/g). By week 2, the fecal calprotectin level had declined to a median 261 μg/g (P < 0.001). In 37% of the patients, fecal calprotectin was normal (< 100 μg/g) at 2 wk. By week 6, there was no additional improvement in the fecal calprotectin level (median 345 μg/g). In 22% of the patients, fecal calprotectin levels increased by week 6 to pretreatment levels or above, suggesting no response (or a loss of early response). Thus, in CD, the proportion of non-responsive patients by week 6 seemed lower, because only 9% showed no improvement in their fecal calprotectin level when compared to the respective figure of 46% of the UC patients (P < 0.05). When treated with infliximab, fecal calprotectin levels reflecting intestinal inflammation normalized rapidly in one third of pediatric patients suggesting complete mucosal healing.


Current status of vascularized composite tissue allotransplantation.
Vascularized composite tissue allotransplantation (VCA) offers treatment options of complex functional deficiencies that cannot be repaired with conventional reconstructive methods. VCAs consist of blocks of functional units comprising different tissue types such as skin, bone, muscle, nerves, blood vessels, tendons, ligaments and others, and are thus substantially different from the composition of organ transplants. The field of VCA has made fascinating progresses in the recent past. Among other VCAs, numerous successful hand, face and limb transplants have been performed in the world. At the same time, specific questions in regard to innate and adaptive immunity, consequences of ischemia/reperfusion injury, immunosuppression, preservation, and regenerative capacity remain. In spite of this, the field is poised to make significant advances in the near future.


An acceptor-shielding strategy of photosensitizers for enhancing the generation efficiency of type I reactive oxygen species and the related photodynamic immunotherapy.
Developing efficient photosensitizers (PSs) that can generate type I reactive oxygen species (ROS) under illumination is considered an effective way to improve photodynamic therapy (PDT) outcomes due to the hypoxic nature of the tumor environment, but also is very challenging. Herein, a new PS of the multiarylpyrrole (MAP) derivative with a typical donor-acceptor structure was synthesized to efficiently generate type I ROS by using an acceptor-shielding strategy in their aggregated state. The enhanced generation mechanism of type I ROS originated from its ultralong triplet lifetime and the narrow singlet-triplet energy gap of the MAP. More importantly, type I ROS can transform protumoral M2 macrophages (M2) into antitumoral M1 macrophages (M1), which showed synergistic immunotherapy in in vivo experiments. Therefore, introducing shielding groups into acceptors provides general guidance for developing efficient PSs in the aggregation state for clinical PDT.


Cancer-risk-related health behaviors and attitudes of older workers. Working Well Research Group.
The National Cancer Institute's Working Well Trial was a randomized controlled trial of a two-year, comprehensive, worksite-based cancer control intervention. Data from 19,582 respondents to the baseline survey were analyzed to determine the relationships between grouped age (18-29, 30-49, 50-54, 55-59, and > 60 years), dietary and smoking behaviors, and attitudes related to participation in health promotion activities. Workers over 50 had more positive health behaviors, stronger beliefs about the value of healthy behavior, and better self-assessed health; they were more likely to hold attitudes associated with participation in worksite health promotion, more positive about work conditions, attributed greater concern about worker health to management, and were more willing to believe that they would be allowed to attend worktime health promotion activities. Age may be an useful variable in targeting worksite cancer control programming. Workers in their 50s could be supported in weight management, since rates of overweight and obesity are higher in this group. Other health behaviors might be addressed for older workers.


Intravenous glucose suppresses glucose production but not proteolysis in extremely premature newborns.
To ascertain whether the inability to suppress glucose production and increase glucose utilization in response to glucose infusion is an inherent characteristic of immature individuals, we determined glucose rate of appearance (R(a)) in minimally stressed, clinically stable, extremely premature infants (approximately 26-wk gestation) at two glucose infusion rates (6.2 +/- 0.4 and 9.5 +/- 0.5 mg/kg per min). We also assessed whether an increase in glucose delivery suppresses proteolysis by measuring the R(a) of phenylalanine and leucine. Glucose R(a) (and utilization) increased significantly at the higher glucose infusion rate (7.9 +/- 0.5 vs. 9.8 +/- 0.6 mg/kg per min). Glucose production persisted at the lower glucose infusion rate but was suppressed to nearly zero at the higher rate (1.7 +/- 0.5 vs. 0.3 +/- 0.1 mg/kg per min). Proteolysis was unaffected by the higher glucose infusion rate as reflected by no change in the rates of appearance of either phenylalanine (96 +/- 5 vs. 95 +/- 3 mumol/kg per h) or leucine (285 +/- 20 vs. 283 +/- 14 mumol/kg per h). Thus, clinically stable, extremely premature infants suppress glucose production and increase glucose utilization in response to increased glucose infusion, demonstrating no inherent immaturity of these processes. In contrast, increasing the rate of glucose delivery results in no change in whole body proteolysis in these infants. The regulation of proteolysis in this population remains to be defined.


Role of magnetic resonance spectroscopy in diagnosis and management of multiple sclerosis.
Application of magnetic resonance spectroscopy (MRS) to study the nature, pathogenesis, tissue injury and therapeutic response of MS patients has altered our view of multiple sclerosis (MS) fundamentally. By offering biochemical analysis of demyelinating lesions and axonal injury, MRS generates objective and quantifiable data on central nervous system tissue and metabolism during pathogenesis of MS. Of these biochemical markers, N-acetylaspartate, which serves as an indicator of neuronal and axonal injury and choline (Cho) peaks which demonstrate cell membrane metabolism, provide a plethora of data on the neuropathology of MS. Based on these findings, MRS provides neuroscientists with a unique diagnostic and prognostic tool to follow MS patients and assess their response to treatment with immunomodulators. MRS findings are so significant that consideration should be given to their routine inclusion as secondary outcome measures in clinical trials of MS patients.


Laparoscopic sacral hysteropexy versus laparoscopic sacrocolpopexy with hysterectomy for pelvic organ prolapse.
Treating pelvic organ prolapse (POP) with uterine conservation and sacral hysteropexy has uncertain subjective and objective outcomes. We sought to compare laparoscopic sacral hysteropexy with laparoscopic sacrocolpopexy/total laparoscopic hysterectomy (TLH with LSC). Clinical data of 34 patients who underwent TLH with LSC and 65 patients who underwent laparoscopic sacral hysteropexy performed by the same group of surgeons between January 2008 and December 2013 were reviewed retrospectively. The primary outcome was subjective satisfaction rate based upon validated questionnaire (Patient Global Impression of Change [PGI-C]). Secondary outcomes were: anatomical cure, impact on quality of life based upon validated questionnaires (pelvic floor distress inventory-short form 20 [PFDI-20], Pelvic Floor Impact Questionnaire 7 [PFIQ-7], and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire-12 [PISQ-12]), surgical complications, and cost. After a mean follow-up of 33 months, the subjective satisfaction rate was significantly higher in the TLH with LSC cohort (92.3% vs 100%; p < 0.001). The POP-Q scores in both groups were significantly improved postoperatively. However, the anatomical cure in the two groups (72.3% vs 88.2%; p = 0.07) did not differ significantly The postoperative PFIQ-7 and PFDI-20 scores were significantly better in the TLH with LSC cohort than in the laparoscopic sacral hysteropexy cohort (p = 0.043 and p = 0.035 respectively). Relative to laparoscopic sacral hysteropexy, the TLH with LSC approach provides similar anatomical results, excellent patient satisfaction, and improved quality of life scores.


Seasonal variation of enteropathogens in infants and preschoolers with acute diarrhea in western Mexico.
The present study estimates the prevalence of some enteropathogens in infants and preschoolers with acute diarrhea. From 2006 to 2007, 5459 consecutive stool samples were evaluated. Cryptosporidium parvum was the parasite identified with the higher frequency (5.1%), followed by Giardia lamblia (1.2%). Campylobacter jejuni was isolated in 858 cases (15.7%) and was the most frequent enteropathogen overall. The rates of C parvum, Shigella, and Salmonella were higher in the summer. Rotavirus had the expected winter peak and it was the third enteropathogen because of its frequency. Overall frequency of stool-reducing substances was 15.6% and was associated with a rotavirus-positive test.


Minimum sample sizes for identifying chromosomal fragile sites from individuals: Monte Carlo estimation.
A Monte Carlo simulation procedure was used to estimate the exact level of the standardized X2 test statistic (Xs2) for randomness in the FSM methodology for the identification of fragile sites from chromosomal breakage data for single individuals. A random-number generator was used to simulate 10,000 chromosomal breakage data sets, each corresponding to the null hypothesis of no fragile sites for numbers of chromosomal breaks (n) from 1 to 2000 and at three levels of chromosomal band resolution (k). The reliability of the test was assessed by comparisons of the empirical and nominal alpha levels for each of the corresponding values of n and k. These analyses indicate that the sparse and discrete nature of chromosomal breakage data results in large and unpredictable discrepancies between the empirical and nominal alpha levels when fragile site identifications are based on small numbers of breaks (n < 0.5 k). With n > or = 0.5 k, the distribution of Xs2 appears to be stable and non-significant differences in the empirical and nominal alpha levels are generally obtained. These results are inherent to the nature of the data and are, therefore, relevant to any statistical model for the identification of fragile sites from chromosomal breakage data. For FSM identification of fragile sites at alpha = 0.05, we suggest that n > or = 0.5 k is the minimum reliable number of mapped chromosomal breaks per individual.


Uncertain population forecasting.
"Errors in population forecasts arise from errors in the jump-off population and errors in the predictions of future vital rates. The propagation of these errors through the linear (Leslie) growth model is studied, and prediction intervals for future population are developed. For U.S. national forecasts, the prediction intervals are compared with the U.S. Census Bureau's high-low intervals." In order to assess the accuracy of the predictions of vital rates, the authors "derive the predictions from a parametric statistical model and estimate the extent of model misspecification and errors in parameter estimates. Subjective, expert opinion, so important in real forecasting, is incorporated with the technique of mixed estimation. A robust regression model is used to assess the effects of model misspecification."


Safety and efficacy of oral panobinostat plus chemotherapy in patients aged 65 years or younger with high-risk acute myeloid leukemia.
The role of histone deacetylase inhibitors in the treatment of acute myeloid leukemia (AML) is not well characterized. The current study evaluated the safety and efficacy of panobinostat in combination with idarubicin and cytarabine in newly diagnosed patients aged ≤65 years with primary or secondary high-risk AML based on cytogenetic classification. Treatment included fixed dose idarubicin (12 mg/m2/d, IV; day 1-3) and cytarabine (100 mg/m2/d, continuous IV infusion; day 1-7) and escalating oral doses of panobinostat at 15 mg, 20 mg, and 25 mg, thrice weekly starting at week 2 of a 28-day cycle. Forty-six patients were enrolled (primary AML [n = 36], secondary AML [n = 10]). The median age was 55 years. The most common all-grade AEs were diarrhea (54.3%), nausea (39.1%), vomiting, and decreased appetite (each, 21.7%), stomatitis (19.6%), and fatigue (17.4%). The overall response rate was 60.9%, 43.5% achieved a complete remission (CR), and 17.4% achieved CR with incomplete count recovery. The event-free survival at 1-year was 78.3%. Panobinostat in combination with idarubicin and cytarabine demonstrated tolerable safety and efficacy in younger patients with high-risk AML. The recommended phase 2 dose of panobinostat in this combination was 20 mg. ClinicalTrials.gov registry no: NCT01242774, and European Trial Registry EudraCT no: 2009-016809-42.


Comprehensive Model for Epidermal Growth Factor Receptor Ligand Binding Involving Conformational States of the Extracellular and the Kinase Domains.
The epidermal growth factor (EGF) receptor (EGFR) undergoes ligand-dependent dimerization to initiate transmembrane signaling. Although crystallographic structures of the extracellular and kinase domains are available, ligand binding has not been quantitatively analyzed taking the influence of both domains into account. Here, we developed a model explicitly accounting for conformational changes of the kinase and extracellular domains, their dimerizations and ligand binding to monomeric and dimeric receptor species. The model was fitted to ligand binding data of suspended cells expressing receptors with active or inactive kinase conformations. Receptor dimers with inactive, symmetric configuration of the kinase domains exhibit positive cooperativity and very weak binding affinity for the first ligand, whereas dimers with active, asymmetric kinase dimers are characterized by negative cooperativity and subnanomolar binding affinity for the first ligand. The homodimerization propensity of EGFR monomers with active kinase domains is ∼100-times higher than that of dimers with inactive kinase domains. Despite this fact, constitutive, ligand-independent dimers are mainly generated from monomers with inactive kinase domains due to the excess of such monomers in the membrane. The experimental finding of increased positive cooperativity at high expression levels of EGFR was recapitulated by the model. Quantitative prediction of ligand binding to different receptor species revealed that EGF binds to receptor monomers and dimers in an expression-level dependent manner without significant recruitment of monomers to dimers upon EGF stimulation below the phase transition temperature of the membrane. Results of the fitting offer unique insight into the workings of the EGFR.


Intermuscular Bones in Pholidophorus bechei from the Lower Lias of England.
Intermuscular bones, considered the one neomorph which decisively separates the pholidophoroids from the teleosts, have been found in a specimen of Pholidophorus bechei Agassiz, from the Lower Lias of England. It is suggested that intermuscular bones were prevalent among the pholidophoroids.


Evaluation of Dietary Quality Based on Intelligent Ordering System and Chinese Healthy Eating Index in College Students from a Medical School in Shanghai, China.
We intended to precisely evaluate the dietary quality of male and female medical college students using canteen data from the "Intelligent Ordering System" (IOS), combined with the supplemental food frequency questionnaire (SFFQ) and the Chinese Healthy Eating Index (CHEI) in Shanghai, China, to explore the potential factors influencing dietary quality. A total of 283 college students with the average age of 24.67 ± 3.21 years and Body Mass Index of 21.46 ± 3.49 kg/m2 in the medical school were enrolled in this study, and an online questionnaire investigation was conducted to collect the general information, lifestyle behavior, and SFFQ. The dietary data of the study participants from the school canteen were exported from the IOS of the Information Office of Fudan University. The CHEI consists of 17 components and the total score is 100, with a maximum score of each component of 5 or 10. We calculated each component score of the CHEI and aggregated the total score for male and female study participants. The Chi-square test and Wilcoxon rank sum test were employed in comparing the differences between the demographic characteristics and CHEI component scores of males and females. Univariate and multiple linear regression models were employed to examine the potential influencing factors of the total CHEI score. The CHEI median score was 66.65, and the component score for total grains was relatively low. Added sugars was the most overconsumed CHEI component. There were relatively serious deficiencies, based on the CHEI component scores, in fruits, soybeans, fish and seafood, and seeds and nuts in both sexes. Females had significantly higher CHEI scores than males (68.38 versus 64.31). The scores for tubers, total vegetables, dark vegetables, fruits, fish and seafood, dairy, and red meats were significantly higher in females than in males. Influencing factors including sex, education, dietary health literacy, and amount of time spent sedentarily were significantly associated with CHEI score. Our research revealed that the overall dietary quality needs to be further improved for college students at the medical school in Shanghai, China, with low intakes of total grains, fruits, soybeans, fish and seafood, and seeds and nuts, and high intakes of added sugars. Compared with males, females showed higher diet quality and conformed more strongly with the recommended Dietary Guideline for Chinese. Education, dietary health literacy, and amount of time spent sedentarily should be noted for improving the dietary quality of college students.


Intrafibrillar mineralization deficiency and osteogenesis imperfecta mouse bone fragility.
Osteogenesis imperfecta (OI), a brittle bone disease, is known to result in severe bone fragility. However, its ultrastructural origins are still poorly understood. In this study, we hypothesized that deficient intrafibrillar mineralization is a key contributor to the OI induced bone brittleness. To test this hypothesis, we explored the mechanical and ultrastructural changes in OI bone using the osteogenesis imperfecta murine (oim) model. Synchrotron X-ray scattering experiments indicated that oim bone had much less intrafibrillar mineralization than wild type bone, thus verifying that the loss of mineral crystals indeed primarily occurred in the intrafibrillar space of oim bone. It was also found that the mineral crystals were organized from preferentially in longitudinal axis in wild type bone to more randomly in oim bone. Moreover, it revealed that the deformation of mineral crystals was more coordinated with collagen fibrils in wild type than in oim bone, suggesting that the load transfer deteriorated between the two phases in oim bone. The micropillar test revealed that the compression work to fracture of oim bone (8.2 ± 0.9 MJ/m3) was significantly smaller (p < 0.05) than that of wild type bone (13.9 ± 2.7 MJ/m3), while the bone strength was not statistically different (p > 0.05) between the two genotype groups. In contrast, the uniaxial tensile test showed that the ultimate strength of wild type bone (50 ± 4.5 MPa) was significantly greater (p < 0.05) than that of oim bone (38 ± 5.3 MPa). Furthermore, the nanoscratch test showed that the toughness of oim bone was much less than that of wild type bone (6.6 ± 2.2 GJ/m3 vs. 12.6 ± 1.4 GJ/m3). Finally, in silico simulations using a finite element model of sub-lamellar bone confirmed the links between the reduced intrafibrillar mineralization and the observed changes in the mechanical behavior of OI bone. Taken together, these results provide important mechanistic insights into the underlying cause of poor mechanical quality of OI bone, thus pave the way toward future treatments of this brittle bone disease.


Dynamic expression of SMAD3 is critical in osteoblast differentiation of PDMCs.
Human pluripotent stem cells have the potential assist in the identification of genes involved in mammalian development. The human placenta is considered a repository of stem cells, termed placenta‑derived multipotent cells (PDMCs), which are able to differentiate into cells with an osteoblastic phenotype. This plasticity of PDMCs maybe applied clinically to the understanding of osteogenesis and osteoporosis. In the presentstudy, osteoblasts were generated by culturing PDMCs in osteogenic medium. Reverse transcription quantitative polymerase chain reactionand the degree of osteoblast calcification were used to evaluate the efficacy of osteogenesis. The results suggestedthat the expression of mothers against decapentaplegic homolog 3 (SMAD3) increased in the initial stages of osteogenic differentiation but decreased in the later stages. However, osteogenesis was inhibitedwhen the PDMCs overexpressed SMAD3 throughout the differentiation period. In addition, the rate of osteogenic differentiation was decreased when SMAD3 signaling was impaired. In conclusion, SMAD3 serves an important role in osteoblast differentiation and bone formation in a time‑dependent manner. The data from the present study indicate that arapid increase in SMAD3 expression is crucial for osteogenesis and suggest a role for PDMCs in the treatment of patients with osteoporosis.


Associations of peak shifts in age--prevalence for human malarias with bednet coverage.
Effects of bednet coverage (C) on prevalence of malaria were analysed using data from 1990-92 from 9 Papua New Guinean villages. Effects of coverage varied by age, resulting in a shift in age of peak prevalence from 4.7 (C = 0%) to 11.6 (C = 100%) years for Plasmodium falciparum, from 3.4 to 4.9 years for P. vivax and from 11.0 to 16.8 years for P. malariae. In small areas with no bednets the age distribution of P. falciparum parasitaemia was like that of a holoendemic area. Where coverage was complete the pattern corresponded to mesoendemicity. Thus, protracted use of bednets can result in profound changes in the endemicity of malaria even when coverage is incomplete and without insecticide treatment. Average entomological inoculation rates (EIRs) estimated from indoor landing rates on individuals without bednets were 35, 12 and 10 infectious bites per person per annum for P. falciparum, P. vivax and P. malariae, respectively. Logistic regression analyses indicated that the EIR estimate for P. falciparum was related to prevalence of this species independently of effects of bednet coverage. However, the recent EIR still accounted for much less variation than did the bednets. A similar pattern was seen for P. malariae, while there were no significant relationships between the recent EIR and the parasite positivity for P. vivax. It is concluded that short-term variations in inoculation rate are not important determinants of parasite prevalence in this population.


The ribulose monophosphate pathway operon encoding formaldehyde fixation in a thermotolerant methylotroph, Bacillus brevis S1.
The hps and phi genes encoding 3-hexulose-6-phosphate synthase and 6-phospho-3-hexuloisomerase, the key enzymes of the ribulose monophosphate (RuMP) pathway for formaldehyde fixation, were cloned from the chromosomal DNA of a thermotolerant methylotroph, Bacillus brevis S1. Enzyme induction and Northern blot analyses revealed that both the hps and phi genes are induced by methanol or ethanol, and that their expression is controlled polycistronically at the transcription stage. Sequence analysis also suggested that the hps and phi genes constitute an RuMP operon. The gene organization of the RuMP operon and its surrounding region are unique among bacteria possessing the RuMP pathway genes.


Tissue inhibitor of metalloproteinases 3 regulates resolution of inflammation following acute lung injury.
Tissue inhibitor of metalloproteinases 3 (TIMP3) inhibits not only matrix metalloproteinases but also a disintegrin and metalloproteinase domain family members and thus contributes to controlling diverse processes mediated by proteolysis. We used Timp3(-/-) mice to assess the role of this inhibitor in acute lung injury. After bleomycin-induced injury, inflammation, as indicated by the influx of neutrophils in bronchoalveolar lavage (BAL), peaked at 7 days post-injury in the wild-type mice and began to wane thereafter; however, in Timp3(-/-) mice, inflammation persisted up to 28 days. Furthermore, although the level of chemokines in BAL and lung homogenate was similar in both genotypes, BAL from Timp3(-/-) mice 7, 14, and 28 days post-injury had increased neutrophil chemotactic activity compared with wild-type BAL. At day 14, a higher percentage of apoptotic neutrophils were present in wild-type mice compared with Timp3(-/-) mice, further suggesting that TIMP3 constrains continued neutrophil influx. In addition, total matrix metalloproteinase activity was increased in lungs from Timp3(-/-) mice, and treatment of mice with a synthetic inhibitor of metalloproteinases rescued the enhanced neutrophilia phenotype. These data demonstrate that TIMP3 regulates neutrophil influx in the lung following injury through its ability to inhibit metalloproteinase activity and indicates that TIMP3 functions to promote the resolution of inflammation in the lung.


Monitoring proliferative activities of hormone-like odorants in human breast cancer cells by gene transcription profiling and electrical impedance spectroscopy.
The human estrogen receptor alpha (ERα) mediates the proliferative action of hormones in breast cancer cells by regulating the expression of target genes to control cellular functions. Current methodologies do not permit a real-time assessment of these processes in living cells. We overcome this limitation using electrical cell-substrate impedance sensing for measuring ERα-regulated signaling processes indicative of the onset of cell proliferation to target them for compound screenings. We report that hormone like odorants regulate, similarly as natural estrogen, ERα-mediated gene expression involved in mitogenic and developmental processes in MCF7 breast cancer cells. An odorant concentration-dependent switch in cell responses was detectable already 10-15 h post-stimulation, providing rapid quantification of hormonal activity before cell division occurred. Though ERα exhibits complex regulatory roles our non-invasive approach captures its activity for accelerated screenings of compounds promoting breast cancer cell proliferation expanding the analysis of ERα signaling networks.


Internal and external fixation in complex diaphyseal and metaphyseal fractures of the humerus.
The treatment of diaphyseal and metaphyseal fractures of the humerus is often controversial, especially when these fractures are complex and/or unstable (i.e. comminuted, segmental, or with a butterfly fragment). The authors review the indications, advantages, and disadvantages of various open and closed procedures, concluding that a combination of internal and external fixation is a valid treatment for these fractures. The purpose of the external fixation is immediate stabilization of the fracture, which is difficult if not impossible with intramedullary internal fixation alone. Internal fixation devices (Rush rods or "anchor" nails introduced by closed means) make it possible to align the fracture, facilitating application of the external fixator, and at the same time promote rapid healing. Fractures treated by this method healed in an average of 2 1/2 months, without residual functional limitations of the shoulder or elbow.


Influence of preanalytical and analytical factors on the quantification of six regulatory serum proteins.
Background: We analyzed differences in protein concentrations in human blood serum depending on the tube material and the immunoassay platform used. Materials & methods: Blood samples from study participants were collected in glass and polypropylene tubes (n = 292). Serum concentrations of six proteins (BDNF, IGF-1, VEGF-A, TGF-β1, MCP-1 and IL-18) were assessed by using ELISAs (all biomarkers), as well as a novel fully automated immunoassay platform (all but IGF-1, n = 211). Bland-Altman analyses were conducted to investigate intrasample variability of protein concentrations. Results: Tube comparison resulted in mean biases of between -0.45 and -70.64%. Platform comparison revealed mean biases of between 21.04 and -128.10%. Conclusion: Protein concentrations can vary significantly depending on the types of tube and immunoassay used, with protein-specific differences.


Revisiting techniques to evaluate drug permeation through skin.
Investigating the transportation of a drug molecule through various layers of skin and determining the amount of drug retention in skin layers is of prime importance in transdermal and topical drug delivery. The information regarding drug permeation and retention in skin layers aids in optimizing a formulation and provides insight into the therapeutic efficacy of a formulation. This perspective covers various methods that have been explored to estimate drug/therapeutics in skin layers using in vitro, ex vivo, and in vivo conditions. In vitro methods such as diffusion techniques, ex vivo methods such as isolated perfused skin models and in vivo techniques including dermato-pharmacokinetics employing tape stripping, and microdialysis are discussed. Application of all techniques at various stages of formulation development where various local and systemic effects need to be considered. The void in the existing methodologies necessitates improvement in the field of dermatologic research. Standardization of protocols, experimental setups, regulatory guidelines, and further research provides information to select an alternative for human skin to perform skin permeation experiments to increase the reliability of data generated through the available techniques. There is a need to utilize multiple techniques for appropriate dermato-pharmacokinetics evaluation and formulation's efficacy.


[Treatment of traumatic corneal abrasion with contact lens associated with topical nonsteroid anti-inflammatory agent (NSAID) and antibiotic: a safe, effective and comfortable solution].
To evaluate the benefit of using therapeutic soft contact lenses in association with NSAID and antibiotic drops for the treatment of traumatic corneal abrasions. The impact on patient pain and on the incapacity to work are analyzed. The treatment of 176 consecutive patients presenting with traumatic corneal abrasion was evaluated in a prospective study. Therapeutic contact lenses, NSAID drops (diclofenac), and antibiotic drops (tobramycin) without cycloplegia were used. Psychometric evaluation of pain revealed sufficient comfort with this regimen, allowing 123 patients (80.39%) to immediately go back to their occupations. This return to usual occupations varied with the size of the abrasion: it was obtained in 80 patients (93.02%) from the "foreign body" group (size of abrasion < 10 mm2). In the "other etiologie" group, this ability was obtained in 30 of 41 patients (73.17%) presenting an abrasion smaller than 10 mm2, in 6 of 13 patients (46.15%) presenting an abrasion between 10 and 20 mm2, and in 7 of 9 patients (77.78%) presenting an abrasion between 20 and 30 mm2. All the patients with an abrasion longer than 30 mm2 were unable to continue usual occupations. No serious complications appeared during treatment. Treatment of traumatic corneal abrasion with a contact lens associated with topical NSAID drops sufficiently reduced the pain to allow 80.39% of the patients to go return immediately to their normal activities. The combined use of soft contact lenses, NSAID drops, and antibiotic drops without cycloplegia appeared to be an effective treatment for traumatic corneal abrasion.


Novel insights into the role of the mobilome in ecological diversification and success of Staphylococcus haemolyticus as an opportunistic pathogen.
Staphylococcus haemolyticus is a species of coagulase-negative staphylococci that has primarily been studied as a human skin microbiome member and an emerging nosocomial pathogen. Here, we present the first complete genome of S. haemolyticus strains SE3.9, SE3.8 and SE2.14 reported as an endophyte of rice seed. Detailed investigation of the genome dynamics of strains from diverse origins revealed an expanded genome size in clinical isolates, and a role of many insertion sequence (IS) elements in strain diversification. Interestingly, several of the IS elements are also unique or enriched in a particular habitat. Comparative studies also revealed the potential movement of mobile elements from rice endophytic S. haemolyticus to strains from other pathogenic species such as Staphylococcus aureus. The study highlights the importance of ecological studies in the systematic understanding of genome plasticity and management of medically important Staphylococcus species.


Pre-Planned Cranioplasty Using Computer-Assisted Designed Temporalis Muscle Augmentation in Patients With Decompressive Craniectomy Involving Resection of the Temporalis Muscle.
Decompressive craniectomy (DC) is the last-resort surgical procedure to reduce intracranial pressure and prevent secondary brain injury. Additional resection of the temporalis muscle and fascia can achieve a higher extracranial herniation volume compared to the standard DC technique at the expense of cosmetic problems for the patients. Various methods have been used to augment temporal fossa hollowing. To improve the cosmetic outcome, the authors report a patient who had a skull defect restored using a precisely shaped implant engineered via a computer using the opposite temporalis muscle as a mirror image. Polyether-ether-ketone cranioplasty was performed for the 52-year-old man with temporal hollowing after DC with resection of the temporalis muscle and fascia, due to a ruptured cerebral arteriovenous fistula. The shape of the patient's surgical side was restored and not asymmetrical. The patient was very satisfied. In the case of cranioplasty (CP) in patients with DC with resection of the temporalis muscle, CP with implants that include the opposite muscle may increase patient satisfaction without the risk of additional complications.


The α-tertiary amine motif drives remarkable selectivity for Pd-catalyzed carbonylation of β-methylene C-H bonds.
The selective C-H carbonylation of methylene bonds in the presence of traditionally more reactive methyl C-H and C(sp2)-H bonds in α-tertiary amines is reported. The exceptional selectivity is driven by the bulky α-tertiary amine motif, which we hypothesise orientates the activating C-H bond proximal to Pd in order to avoid an unfavourable steric clash with a second α-tertiary amine on the Pd centre, promoting preferential cyclopalladation at the methylene position. The reaction tolerates a range of structurally interesting and synthetically versatile functional groups, delivering the corresponding β-lactam products in good to excellent yields.


In vivo imaging of lymphocytes in the CNS reveals different behaviour of naïve T cells in health and autoimmunity.
Two-photon laser scanning microscopy (TPLSM) has become a powerful tool in the visualization of immune cell dynamics and cellular communication within the complex biological networks of the inflamed central nervous system (CNS). Whereas many previous studies mainly focused on the role of effector or effector memory T cells, the role of naïve T cells as possible key players in immune regulation directly in the CNS is still highly debated. We applied ex vivo and intravital TPLSM to investigate migratory pathways of naïve T cells in the inflamed and non-inflamed CNS. MACS-sorted naïve CD4+ T cells were either applied on healthy CNS slices or intravenously injected into RAG1 -/- mice, which were affected by experimental autoimmune encephalomyelitis (EAE). We further checked for the generation of second harmonic generation (SHG) signals produced by extracellular matrix (ECM) structures. By applying TPLSM on living brain slices we could show that the migratory capacity of activated CD4+ T cells is not strongly influenced by antigen specificity and is independent of regulatory or effector T cell phenotype. Naïve T cells, however, cannot find sufficient migratory signals in healthy, non-inflamed CNS parenchyma since they only showed stationary behaviour in this context. This is in contrast to the high motility of naïve CD4+ T cells in lymphoid organs. We observed a highly motile migration pattern for naïve T cells as compared to effector CD4+ T cells in inflamed brain tissue of living EAE-affected mice. Interestingly, in the inflamed CNS we could detect reticular structures by their SHG signal which partially co-localises with naïve CD4+ T cell tracks. The activation status rather than antigen specificity or regulatory phenotype is the central requirement for CD4+ T cell migration within healthy CNS tissue. However, under inflammatory conditions naïve CD4+ T cells can get access to CNS parenchyma and partially migrate along inflammation-induced extracellular SHG structures, which are similar to those seen in lymphoid organs. These SHG structures apparently provide essential migratory signals for naïve CD4+ T cells within the diseased CNS.


Concise and stereocontrolled synthesis of the tetracyclic core of daphniglaucin C.
The tetracyclic core of daphniglaucin C was prepared from the known 4-keto-N-Boc methyl-l-prolinate in 15 steps with a cumulative yield of 14.7%. The key steps toward this core motif feature a reductive double bond transposition from an unactivated tertiary allylic alcohol, a Pd-catalyzed Stille coupling, and Dieckmann cyclizations.


A Bayesian Approach to Incorporating Spatiotemporal Variation and Uncertainty Limits into Modeling of Predicted Environmental Concentrations from Chemical Monitoring Campaigns.
Environmental monitoring studies provide key information to assess ecosystem health. Results of chemical monitoring campaigns can be used to identify the exposure scenarios of regulatory concern. In environmental risk assessment (ERA), measured concentrations of chemicals can be used to model predicted environmental concentrations (PECs). As the PEC is, by definition, a predicted variable, it is highly dependent on the underlying modeling approach from which it is derived. We demonstrate the use of Bayesian distributional regression models to derive PECs by incorporating spatiotemporal conditional variances, and limits of quantification (LOQ) and detection (LOD) as de facto data censoring. Model accuracies increase when incorporating spatiotemporal conditional variances, and the inclusion of LOQ and LOD results in potentially more robust PEC distributions. The methodology is flexible, credibly quantifies uncertainty, and can be adjusted to different scientific and regulatory needs. Posterior sampling allows to express PECs as distributions, which makes this modeling procedure directly compatible with other Bayesian ERA approaches. We recommend the use of Bayesian modeling approaches with chemical monitoring data to make realistic and robust PEC estimations and encourage the scientific debate about the benefits and challenges of Bayesian methodologies in the context of ERA.


Self-Sustained Divertor Oscillation Driven by Magnetic Island Dynamics in Torus Plasma.
A new type of self-sustained divertor oscillation is discovered in the Large Helical Device stellarator, where the peripheral plasma is detached from material diverters by means of externally applied perturbation fields. The divertor oscillation is found to be a self-regulation of an isolated magnetic field structure (the magnetic island) width induced by a drastic change in a poloidal inhomogeneity of the plasma radiation across the detachment-attachment transitions. A predator-prey model between the magnetic island width and a self-generated local plasma current (the bootstrap current) is introduced to describe the divertor oscillation, which successfully reproduces the experimental observations.


A novel transposable element-based authentication protocol for Drosophila cell lines.
Drosophila cell lines are used by researchers to investigate various cell biological phenomena. It is crucial to exercise good cell culture practice. Poor handling can lead to both inter- and intra-species cross-contamination. Prolonged culturing can lead to introduction of large- and small-scale genomic changes. These factors, therefore, make it imperative that methods to authenticate Drosophila cell lines are developed to ensure reproducibility. Mammalian cell line authentication is reliant on short tandem repeat (STR) profiling; however, the relatively low STR mutation rate in Drosophila melanogaster at the individual level is likely to preclude the value of this technique. In contrast, transposable elements (TEs) are highly polymorphic among individual flies and abundant in Drosophila cell lines. Therefore, we investigated the utility of TE insertions as markers to discriminate Drosophila cell lines derived from the same or different donor genotypes, divergent sub-lines of the same cell line, and from other insect cell lines. We developed a PCR-based next-generation sequencing protocol to cluster cell lines based on the genome-wide distribution of a limited number of diagnostic TE families. We determined the distribution of five TE families in S2R+, S2-DRSC, S2-DGRC, Kc167, ML-DmBG3-c2, mbn2, CME W1 Cl.8+, and ovarian somatic sheath Drosophila cell lines. Two independent downstream analyses of the next-generation sequencing data yielded similar clustering of these cell lines. Double-blind testing of the protocol reliably identified various Drosophila cell lines. In addition, our data indicate minimal changes with respect to the genome-wide distribution of these five TE families when cells are passaged for at least 50 times. The protocol developed can accurately identify and distinguish the numerous Drosophila cell lines available to the research community, thereby aiding reproducible Drosophila cell culture research.


Patients with H pylori-independent MALT lymphoma are curable with radiotherapy.
After more than two decades of successful laboratory and clinical research, the "new" entity of mucosa-associated lymphoid tissue (MALT) lymphoma is reaching a noble maturity. Large series have demonstrated that most patients diagnosed with MALT lymphoma will be cured with relatively gentle and safe therapies, and evidence-based algorithms guide treatment with relatively minor controversies. The authors of this concise and practical review are well recognized for their important contributions to our current understanding of the disease. Their state-of-the-art review lucidly highlights the pathological, biological, and genetic information that has been


Utilization under children's health insurance programs: children with vs. without chronic conditions.
States planning to expand health insurance for children need information on projected utilization. We examine these issues using data from children's health insurance programs in Pennsylvania. We estimate the average cost of a comprehensive benefit package for a continuously enrolled child during 1994-1995 was about $500 ($1,208 for a child with a chronic condition, and $454 for one without). There was wide variation by type of service. This underestimates the cost of new programs because some very sick children were excluded and because the average monthly cost of a continuously enrolled child is lower than that of a new enrollee.


The Specificity of Cognitive-Motor Dual-Task Interference on Balance in Young and Older Adults.
Standing upright on stable and unstable surfaces requires postural control. Postural control declines as humans age, presenting greater risk of fall-related injury and other negative health outcomes. Secondary cognitive tasks can further impact balance, which highlights the importance of coordination between cognitive and motor processes. Past research indicates that this coordination relies on executive function (EF; the ability to control, maintain, and flexibly direct attention to achieve goals), which coincidentally declines as humans age. This suggests that secondary cognitive tasks requiring EF may exert a greater influence on balance compared to non-EF secondary tasks, and this interaction could be exaggerated among older adults. In the current study, we had younger and older adults complete two Surface Stability conditions (standing upright on stable vs. unstable surfaces) under varying Cognitive Load; participants completed EF (Shifting, Inhibiting, Updating) and non-EF (Processing Speed) secondary cognitive tasks on tablets, as well as a single task control scenario with no secondary cognitive task. Our primary balance measure of interest was sway area, which was measured with an array of wearable inertial measurement unit sensors. Replicating prior work, we found a main effect of Surface Stability with less sway on stable surfaces compared to unstable surfaces, and we found an interaction between Age and Surface Stability with older adults exhibiting significantly greater sway selectively on unstable surfaces compared to younger adults. New findings revealed a main effect of Cognitive Load on sway, with the single task condition having significantly less sway than two of the EF conditions (Updating and Shifting) and the non-EF condition (Processing Speed). We also found an interaction of Cognitive Load and Surface Stability on postural control, where Surface Stability impacted sway the most for the single task and two of the executive function conditions (Inhibition and Shifting). Interestingly, Age did not interact with Cognitive Load, suggesting that both age groups were equally impacted by secondary cognitive tasks, regardless the presence or type of secondary cognitive task. Taken together, these patterns suggest that cognitive demands vary in their impact on posture control across stable vs. unstable surfaces, and that EF involvement may not be the driving mechanism explaining cognitive-motor dual-task interference on balance.