A role for Sp and nuclear receptor transcription factors in a cardiac hypertrophic growth program.
During cardiac hypertrophy, the chief myocardial energy source switches from fatty acid beta-oxidation (FAO) to glycolysis-a reversion to fetal metabolism. The expression of genes encoding myocardial FAO enzymes was delineated in a murine ventricular pressure overload preparation to characterize the molecular regulatory events involved in the alteration of energy substrate utilization during cardiac hypertrophy. Expression of genes involved in the thioesterification, mitochondrial import, and beta-oxidation of fatty acids was coordinately down-regulated after 7 days of right ventricular (RV) pressure overload. Results of RV pressure overload studies in mice transgenic for the promoter region of the gene encoding human medium-chain acyl-CoA dehydrogenase (MCAD, which catalyzes a rate-limiting step in the FAO cycle) fused to a chloramphenicol acetyltransferase reporter confirmed that repression of MCAD gene expression in the hypertrophied ventricle occurred at the transcriptional level. Electrophoretic mobility-shift assays performed with MCAD promoter fragments and nuclear protein extracts prepared from hypertrophied and control RV identified pressure overload-induced protein/DNA interactions at a regulatory unit shown previously to confer control of MCAD gene transcription during cardiac development. Antibody "supershift" studies demonstrated that members of the Sp (Sp1, Sp3) and nuclear hormone receptor [chicken ovalbumin upstream promoter transcription factor (COUP-TF)/erbA-related protein 3] families interact with the pressure overload-responsive unit. Cardiomyocyte transfection studies confirmed that COUP-TF repressed the transcriptional activity of the MCAD promoter. The DNA binding activities and nuclear expression of Sp1/3 and COUP-TF in normal fetal mouse heart were similar to those in the hypertrophied adult heart. These results identify a transcriptional regulatory mechanism involved in the reinduction of a fetal metabolic program during pressure overload-induced cardiac hypertrophy.


Influences of interpolation error, electrode geometry, and the electrode-tissue interface on models of electric fields produced by deep brain stimulation.
Deep brain stimulation (DBS) is an established therapy for movement disorders, but the fundamental mechanisms by which DBS has its effects remain unknown. Computational models can provide insights into the mechanisms of DBS, but to be useful, the models must have sufficient detail to predict accurately the electric fields produced by DBS. We used a finite-element method model of the Medtronic 3387 electrode array, coupled to cable models of myelinated axons, to quantify how interpolation errors, electrode geometry, and the electrode-tissue interface affect calculation of electrical potentials and stimulation thresholds for populations of model nerve fibers. Convergence of the potentials was not a sufficient criterion for ensuring the same degree of accuracy in subsequent determination of stimulation thresholds, because the accuracy of the stimulation thresholds depended on the order of the elements. Simplifying the 3387 electrode array by ignoring the inactive contacts and extending the terminated end of the shaft had position-dependent effects on the potentials and excitation thresholds, and these simplifications may impact correlations between DBS parameters and clinical outcomes. When the current density in the bulk tissue is uniform, the effect of the electrode-tissue interface impedance could be approximated by filtering the potentials calculated with a static lumped electrical equivalent circuit. Further, for typical DBS parameters during voltage-regulated stimulation, it was valid to approximate the electrode as an ideal polarized electrode with a nonlinear capacitance. Validation of these computational considerations enables accurate modeling of the electric field produced by DBS.


[Reporting of patient injuries--the supervisory authority's use of sanctions].
When health care leads to serious adverse events that result in (or could have resulted in) injuries to patients, hospitals are obliged to report this to The Norwegian Board of Health Supervision in the Counties. The purpose of this study was to quantify how many cases were instigated on the basis of reports sent to the supervisory authority and to what extent health personnel were sanctioned because of them. Reports received by The Norwegian Board of Health Supervision in the Counties (in the period 1.07.2002- 30.06.2007) and cases instigated by the National Board of Health (on basis of the reports) in the period 1.01.2003-31.12.2007. The supervisory authority received 9268 reports in the period. 443 (4.7 %) of them led to instigation of cases and 19 of these (2 of the reports) resulted in formal sanctioning of health personnel (13 of the sanctions were to physicians; 12 received a warning and one lost her specialist license). The Board of Health Supervision seems to have quite different thresholds for instigating report-based cases in the various counties. Health personnel seem to have little reason to fear that reports on (potential) adverse events will lead to sanctions from the supervisory authority. However, the Board of Health Supervision in the Counties should have a more predictable practice concerning instigation of report-based cases.


Optimizing evapotranspiration and crop irrigation requirements of tropical forages cropping systems in Southern Brazil.
Crop irrigation requirements are usually estimated based on crop evapotranspiration (ETc) as determined by the reference evapotranspiration (ETo) and crop coefficient (Kc). There is a lack of knowledge on the irrigation requirements of tropical forage crops in Brazil, contrasting with the increasing use of irrigation in pastures. The effort of this study was to investigate what would be the water needs of tropical forages in Southern Brazil, based on a robust experimental database. The study was carried out in São Paulo State-Brazil using different forages species and their combinations [Guinea grass (GG); Guinea grass + black oat + ryegrass (GOR); Bermuda grass (BG), and Bermuda + black oat + ryegrass (BOR)]. The experimental fields were fully irrigated, and the Kc values were derived from ETc measurements on lysimeters; ETo was estimated using daily data from a nearby weather station and the standard FAO56 parameterization. Mean daily ETc values for GG, GOR, BG and BOR were 4.1, 2.9, 3.6, and 3.4 mm, respectively, and respective mean Kc values were 0.99, 0.90, 1.0, and 0.94. Average Kc values for all plots decreased as ETo increased, producing a negative Kc-ETo relationship, mainly when ETo reached values greater than 5 mm d-1. This was most likely due to internal plant stomatal resistance to vapor release from the leaves diffusing to the atmosphere at high ETo. So, the time-based Kc curves described by FAO 56 manual should be adjusted for the analyzed crops considering different ranges of ETo to improve the required irrigation depth.


Effects of metal binding on solubility and resistance of physiological prions depend on tissues and glycotypes.
Prion diseases entail the conversion of a normal host-encoded prion protein (PrP(C)) into an infectious isoform (PrP(Sc)). Various PrP(C) types differing in banding profiles and detergent solubility are present in different tissues, but only few PrP(Sc) types have been generated although PrP(C) acts as substrate. We hypothesize that distinct PrP(C) subtypes may be converted more efficiently to PrP(Sc) than others. One prerequisite for the analysis is the identification of the PrP(C) subtypes present in the protein complexes. Metal binding to PrP(C) is one of the most prominent features of the protein which induces increased proteolysis resistance and structural changes which might play an important role in the conversion process. Here we analyzed the metal-induced structural PrP(C) transformation of two different Triton X-100 soluble PrP(C) types derived from human platelets and brains by changes in protein solubility. We found that zinc and copper rendered approximately half of total PrP(C) and mainly un- and low-glycosylated PrP(C) to the Triton insoluble fraction. Our results indicate the presence of at least two distinct PrP(C) subtypes by metal interactions. The differentiation of high and low soluble metal bound PrP(C) offers precious information about PrP(C) protein composition and provides approaches for analyzing the transformation efficiency to PrP(Sc).


Magnetic resonance imaging assessment of the alar ligaments in whiplash injuries: a case-control study.
Case-control study. To use high-resolution magnetic resonance imaging (MRI) in assessing signal intensity areas in the alar ligaments. Conflicting evidence exists whether areas of high signal intensity in the alar ligament on MRI are more frequent in whiplash patients than in noninjured control subjects. A case-control designed study of 173 subjects included one group with persistent whiplash associated disorder Grade I-II after a car accident (n = 59), one with chronic nontraumatic neck pain (n = 57) and one group without neck pain or previous neck trauma (n = 57). High-resolution proton-weighted MRI in 3 planes was used. The images were independently evaluated by two experienced neuroradiologists who were blinded to patient history and group allocation. The alar ligaments were evaluated according to a 4-point grading scale; 0 = low signal intensity throughout the entire cross section area, 1 = high signal intensity in one third or less, 2 = high signal intensity in one-third to two thirds, and 3 = high signal intensity in two thirds or more of the cross section area. Alar ligament changes Grade 0 to 3 were seen in all 3 diagnostic groups. Areas of high signal intensity (Grade 2-3) were found in at least one alar ligament in 49% of the patients in the whiplash associated disorder Grade I-II group, in 33% of the chronic neck pain group and in 40% of the control group (chi, P = 0.22). CONCLUSION.: The previously reported assumption that these changes are due to a trauma itself is not supported by this study. The diagnostic value and the clinical relevance of magnetic resonance detectable areas of high intensity in the alar ligaments are questionable.


Toward optimization of the linker substructure common to transthyretin amyloidogenesis inhibitors using biochemical and structural studies.
To develop potent and highly selective transthyretin (TTR) amyloidogenesis inhibitors, it is useful to systematically optimize the three substructural elements that compose a typical TTR kinetic stabilizer: the two aryl rings and the linker joining them. Herein, we evaluated 40 bisaryl molecules based on 10 unique linker substructures to determine how these linkages influence inhibitor potency and selectivity. These linkers connect one unsubstituted aromatic ring to either a 3,5-X 2 or a 3,5-X 2-4-OH phenyl substructure (X = Br or CH 3). Coconsideration of amyloid inhibition and ex vivo plasma TTR binding selectivity data reveal that direct connection of the two aryls or linkage through nonpolar E-olefin or -CH 2CH 2- substructures generates the most potent and selective TTR amyloidogenesis inhibitors exhibiting minimal undesirable binding to the thyroid hormone nuclear receptor or the COX-1 enzyme. Five high-resolution TTR.inhibitor crystal structures (1.4-1.8 A) provide insight into why such linkers afford inhibitors with greater potency and selectivity.


Psychological aftermaths of Covid-19: a study of diagnosed and never diagnosed adults.
A cross-sectional comparative study was conducted from March 2021 to May 2022 in Faisalabad district, Pakistan, to rule out the prevalence and comparison of psychological aftermaths of Covid-19 pandemic for adults with and without a diagnosis for the disease. For data collection, a sample of 218 individuals was recruited through purposive sampling technique. Participants, with and without the diagnosis of Covid-19, experienced significant depression, anxiety, stress, and somatic symptoms amid the pandemic. Further analysis revealed that adults diagnosed with Covid-19 significantly reported more depression (t= 2.76, df = 216, p = .006, Cohen's d=0.37), more stress (t= 3.08, df = 216, p = .002, Cohen's d= 0.41), and more somatic symptoms (t= 10.83, df = 216, p =.000, Cohen's d= 1.46) as compared to adults who were not diagnosed with the disease. Contrary to that, a non-significant difference emerged between both the groups of participants with respect to anxiety (t =0.27, df = 216, p = .783, Cohen's d = 0.03). Adults who directly became the physical victim of Covid- 19 encountered more psychological aftermaths as compared to those who are still physically safe from the disease.


Relapse prevention for chemically addicted adolescents in recovery: so which model works?
In line with international trends, adolescent chemical addiction remains a significant challenge in South African communities, specifically in the Western Cape. Much emphasis is placed on prevention and treatment, while aftercare as part of treatment receives limited attention. Research does highlight specific aftercare needs of addicted adolescents, while literature provides different models of relapse prevention as part of aftercare, aimed at adults. However, the needs of addicted adolescents in recovery and the different models need to be linked. In this article the author first lists specific needs of chemically addicted adolescents, and secondly explores different models of care. Thirdly, functional elements related to the identified needs are identified. Recommendations for a comprehensive aftercare program are made based on the identified functional elements.


A study of the effects of dexclamol as the neuroleptic component in neuroleptanaesthesia.
In a double-blind cross-over study in dogs, dexclamol was compared with droperidol as the neuroleptic component of a neuroleptanalgestic combination. Fentanyl was the narcotic analgessic. Neuroleptanaesthesia was induced with a mixture of the neuroleptic, the analgesic and nitrous oxide in oxygen. Dexclamol 200 microng/kg i.v. was as effective as droperidol at the same dose in inducing neurolepsy and in supplementing nitrous oxide anaesthesia. Changes in heart rate, respiratory rate and rectal temperature in the animals treated with dexclamol were not different from those observed in the animals treated with droperidol. A comparison of the adrenolytic properties of dexclamol and droperidol was made on the isolated rabbit aortic strip. Both compunds produced a parallel shift to the right of the noradrenaline cumulative dose-response curves, indicating competitive antagonism. The pA2 values showed dexclamol to be approximately 15 times less potent than droperidol in inhibiting the noradrenaline-induced contraction of the rabbit aortic strip.


Basal serum tryptase as risk assessment for severe Hymenoptera sting reactions in elderly.
Epidemiologic studies suggest that elderly people are more prone to develop severe anaphylactic reactions. However, the exact cause for this phenomenon remains unclear. To study the role of the serum tryptase as a diagnostic parameter for individual risk evaluation and its impact on the severity of allergic reactions in elderly people. Two hundred and seventy-four consecutive patients visiting the Department of Dermatology, Tübingen, Germany, who were diagnosed with honeybee or wasp venom allergy, were included in the study. Sting reaction severity increased with increased age and tryptase levels (P = 0.001 and P = 0.0003, respectively). Furthermore, we find not only a general increment in tryptase levels in elderly people (P = 0.0001) but also a continuous increase in tryptase concentrations even below the cut-off (11.4 microg/l) with increasing age (P = 0.0026). Our data confirm serum tryptase as a risk factor for severe anaphylactic reaction to hymenoptera stings. Furthermore, we give first evidence that basal serum tryptase levels increase continuously with age and being an indicator for either increased mast cell load or reactivity this can at least partly be responsible for the observed aggravated allergic reactions in elderly people. As those patients are at increased risk for life-threatening anaphylactic reactions, it should be considered to adjust VIT especially in elderly patients with elevated tryptase levels as recommended for patients with mastocytosis by increasing venom doses during VIT and by considering its life-long continuation.


Immunization against Lamb Haemonchosis with a Recombinant Somatic Antigen of Haemonchus contortus (rHcp26/23).
Haemonchosis, caused by the abomasal nematode Haemonchus contortus, is a common parasitic disease of sheep. Our previous results showed that a soluble fraction from adult stages of the nematode (p26/23) induced partial protection against challenge. Recombinant DNA technology was applied to obtain a synthetic protein (rHcp26/23). Immunological assays (ELISA, Western blotting, and immunolocalization), using sera from lambs immunized with p26/23, confirmed the identity of the recombinant protein and demonstrated that the synthetic protein is equivalent to the purified protein employed in the previous immunoprophylaxis studies. Vaccination of lambs with 300 mug of rHcp26/23 and Freund's adjuvant elicited a notable specific antibody response. Immunization did not induce any significant protection after challenge with 16000 infective larvae of H. contortus, and comparable values for parasite faecal egg output, packed cell volume, and abomasal parasite burdens were found in vaccinated and control animals.


Barriers to accessing abortion services and perspectives on using mifepristone and misoprostol at home in Great Britain.
To examine reasons for seeking abortion services outside the formal healthcare system in Great Britain, where abortion is legally available. We conducted a mixed-methods study among women resident in England, Scotland, and Wales who requested at-home medication abortion through online telemedicine initiative Women on Web (WoW) between November 22, 2016, and March 22, 2017. We examined the demographics and circumstances of all women requesting early medication abortion and conducted a content analysis of a sample of their anonymized emails to the service to explore their reasons for seeking help. Over a 4-month period, 519 women contacted WoW seeking medication abortion. These women were diverse with respect to age, parity, and circumstance. One hundred eighty women reported 209 reasons for seeking abortion outside the formal healthcare setting. Among all reasons, 49% were access barriers, including long waiting times, distance to clinic, work or childcare commitments, lack of eligibility for free NHS services, and prior negative experiences of abortion care; 30% were privacy concerns, including lack of confidentiality of services, perceived or experienced stigma, and preferring the privacy and comfort of using pills at home; and 18% were controlling circumstances, including partner violence and partner/family control. Despite the presence of abortion services in Great Britain, a diverse group of women still experiences logistical and personal barriers to accessing care through the formal healthcare system, or prefer the privacy of conducting their abortions in their own homes. Health services commissioning bodies could address existing barriers if supported by policy frameworks. The presence of multiple barriers to accessing abortion care in Great Britain highlights the need for future guidelines to recommend a more woman-centered approach to service provision. Reducing the number of clinic visits and designing services to meet the needs of those living in controlling circumstances are particularly important goals.


Perceived benefits and barriers to joint protection among people with rheumatoid arthritis and occupational therapists. A mixed methods study.
Deciding whether or not to perform a health behaviour is an active decision-making process which has an impact on current and future behaviour and can be influenced by the beliefs both of patients and their healthcare professionals. The aim of this study was to explore rheumatoid arthritis (RA) patients' and occupational therapists' (OTs) perceptions of the benefits of and barriers to performing joint protection (JP). A mixed methods design was used. Questionnaires applied a theoretical framework of key themes to assess the relevance of JP benefits and barriers both to people with RA and OTs. Focused interviews with people with RA then enabled data triangulation. Investigator triangulation was used to check the validity of data interpretation. Ten people with RA and nine OTs participated. From the questionnaires, both groups agreed that highly relevant key themes for JP benefits were physical well-being, potential benefit and personal control. By contrast, the three key themes for JP barriers - negative attitude of others, negative impact on others and taking time from other things - were relevant for the majority of the OTs but not patients. The interviews enabled an understanding of the meaning behind RA patients' ratings, particularly their differences from OTs. People with RA explained JP benefits, and disease acceptance had altered some initial barriers into perceived benefits over time. Emphasizing benefits and identifying individually relevant barriers could be an important communication strategy for OTs in understanding patients' rationale for whether or not to adopt JP methods.


Development of Sustained Release Baricitinib Loaded Lipid-Polymer Hybrid Nanoparticles with Improved Oral Bioavailability.
Baricitinib (BTB) is an orally administered Janus kinase inhibitor, therapeutically used for the treatment of rheumatoid arthritis. Recently it has also been approved for the treatment of COVID-19 infection. In this study, four different BTB-loaded lipids (stearin)-polymer (Poly(d,l-lactide-co-glycolide)) hybrid nanoparticles (B-PLN1 to B-PLN4) were prepared by the single-step nanoprecipitation method. Next, they were characterised in terms of physicochemical properties such as particle size, zeta potential (ζP), polydispersity index (PDI), entrapment efficiency (EE) and drug loading (DL). Based on preliminary evaluation, the B-PLN4 was regarded as the optimised formulation with particle size (272 ± 7.6 nm), PDI (0.225), ζP (-36.5 ± 3.1 mV), %EE (71.6 ± 1.5%) and %DL (2.87 ± 0.42%). This formulation (B-PLN4) was further assessed concerning morphology, in vitro release, and in vivo pharmacokinetic studies in rats. The in vitro release profile exhibited a sustained release pattern well-fitted by the Korsmeyer-Peppas kinetic model (R2 = 0.879). The in vivo pharmacokinetic data showed an enhancement (2.92 times more) in bioavailability in comparison to the normal suspension of pure BTB. These data concluded that the formulated lipid-polymer hybrid nanoparticles could be a promising drug delivery option to enhance the bioavailability of BTB. Overall, this study provides a scientific basis for future studies on the entrapment efficiency of lipid-polymer hybrid systems as promising carriers for overcoming pharmacokinetic limitations.


[Extracorporeal shock-wave lithotripsy of bladder stones in patients with benign prostatic hyperplasia].
In urological department of Moscow Regional Research Clinical Institute, extracorporeal shock-wave lithotripsy (ECSWL) or bladder stones in patients with benign prostatic hyperplasia (BPH) has been made prior to TUR from 1991. This treatment was given to 52 patients aged 54-79 years with prostatic volume 40-120 cm3. Complete or partial fragmentation of the vesical calculi was achieved after 1 to 3 ECSWL sessions (a total of 105 sessions, 2000-3000 impulses a session). Pretreatment with ECSWL of bladder stones significantly facilitates TUR in BPH patients with vesical calculi of big size (2.5 cm and more in diameter). Extracorporeal fragmentation of large stones prior to TUR makes surgery of such patients less traumatic and reduces the risk of intraoperative complications compared to endoscopic cystolithotripsy or cystolithotomy. ECSWL of cystolithes expands indications for drug therapy or thermal non-endoscopic BPH treatment in aged patients with poor somatic status and in young sexually active males rejecting surgery.


Empathic Accuracy in Female Adolescents with Conduct Disorder and Sex Differences in the Relationship Between Conduct Disorder and Empathy.
Research on empathy in youth with Conduct Disorder (CD) has primarily focused on males, with the few studies that have investigated empathy in females relying on questionnaire measures. Our primary aim was to investigate whether females with CD show empathy deficits when using a more ecologically-valid task. We used an empathic accuracy (EA) paradigm that involved watching videos of actors recalling emotional experiences and providing continuous ratings of emotional intensity (assessing EA), naming the emotion expressed (emotion recognition), and reporting whether they shared the emotion expressed (affective empathy). We compared 23 females with CD and 29 typically-developing (TD) adolescents aged 13-18 years. The CD sample was divided into subgroups with higher (CD/CU+) versus lower (CD/CU-) levels of callous-unemotional traits. Females with CD did not differ from TD females in EA or emotion recognition but exhibited reduced affective empathy responses (ps < 0.01, rs ≥ 0.39). The CD/CU+ and CD/CU- subgroups did not differ on any empathy measure. We also assessed for sex differences in CD-empathy associations by comparing the present data with archive data from males. CD adolescents exhibited impairments in EA relative to their TD counterparts overall (p < 0.05, ηp2 = 0.06), but there was no sex-by-diagnosis interaction. While females with CD were only impaired in affective empathy, males with CD exhibited emotion recognition and affective empathy deficits. This study demonstrates that females with CD show relatively specific impairments in affective empathy on an ecologically-valid task, whereas males with CD display more global empathic difficulties.


The difference in translaminar pressure gradient and neuroretinal rim area in glaucoma and healthy subjects.
Purpose. To assess differences in translaminar pressure gradient (TPG) and neuroretinal rim area (NRA) in patients with normal tension glaucoma (NTG), high tension glaucoma (HTG), and healthy controls. Methods. 27 patients with NTG, HTG, and healthy controls were included in the prospective pilot study (each group consisted of 9 patients). Intraocular pressure (IOP), intracranial pressure (ICP), and confocal laser scanning tomography were assessed. TPG was calculated as the difference of IOP minus ICP. ICP was measured using noninvasive two-depth transcranial Doppler device. The level of significance P < 0.05 was considered significant. Results. NTG patients had significantly lower IOP (13.7(1.6) mmHg), NRA (0.97(0.36) mm(2)), comparing with HTG and healthy subjects, P < 0.05. ICP was lower in NTG (7.4(2.7) mmHg), compared with HTG (8.9(1.9) mmHg) and healthy subjects (10.5(3.0) mmHg); however, the difference between groups was not statistically significant (P > 0.05). The difference between TPG for healthy (5.4(7.7) mmHg) and glaucomatous eyes (NTG 6.3(3.1) mmHg, HTG 15.7(7.7) mmHg) was statistically significant (P < 0.001). Higher TPG was correlated with decreased NRA (r = -0.83; P = 0.01) in the NTG group. Conclusion. Translaminar pressure gradient was higher in glaucoma patients. Reduction of NRA was related to higher TPG in NTG patients. Further prospective studies are warranted to investigate the involvement of TPG in glaucoma management.


Th17 cytokines: novel potential therapeutic targets for COPD pathogenesis and exacerbations.
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease of the airways caused mainly by cigarette smoke exposure. COPD progression is marked by exacerbations of the disease, often associated with infections. Recent data show the involvement in COPD pathophysiology of interleukin (IL)-17 and IL-22, two cytokines that are important in the control of lung inflammation and infection. During the initiation and progression of the disease, increased IL-17 secretion causes neutrophil recruitment, leading to chronic inflammation, airways obstruction and emphysema. In the established phase of COPD, a defective IL-22 response facilitates pathogen-associated infections and disease exacerbations. Altered production of these cytokines involves a complex network of immune cells and dysfunction of antigen-presenting cells. In this review, we describe current knowledge on the involvement of IL-17 and IL-22 in COPD pathophysiology at steady state and during exacerbations, and discuss implications for COPD management and future therapeutic approaches.


The elemental diet.
The elemental diet is a precisely formulated, predigested liquid diet capable of providing adequate nutrition for growth, development and tissue repletion in normal and debiliatated patients. It can be used as the sole means of nutritional support for a variety of gastrointestinal problems provided that there is an adequate length of small intestine with functioning mucosa. The elemental diet also can be used to supplement either intravenous or other enteral feedings to prevent a chronic hypocaloric state. Although safer and less complicated to administer than its intravenous counterpart, there are, nonetheless, certain important policies which must be rigidly observed to assure successful treatment and to prevent complications. Similar to intravenous hyperalimentation, administration is best carried out under the auspices of experienced and interested personnel who have a specific interest in surgical nutrition.


The effects of low power laser light at 661 nm on wound healing in a scratch assay fibroblast model.
Wound treatment, especially for chronic and infected wounds, has been a permanent socio-economical challenge. This study aimed to investigate the ability of red light at 661 nm to accelerate wound healing an in vitro wound model using 3T3 fibroblasts. The purpose is further specified in clarifying the mechanisms of wound closure by means of intracellular ROS production, proliferation and migration of cells, and cellular orientation. Illumination effects of red light from a diode laser (661 nm) at different doses on 3T3 cell viability was assessed via MTT assay and tested in a scratch wound model. Wound closure rates were calculated by image analysis at 0, 24, and 48 h after laser treatment. ROS production was monitored and quantified immediately and 24 h after the treatment by fluorescence microscopy. Cellular orientation was quantified by image analysis. No phototoxic energy doses used and increased cell viability in most of the groups. Scratch assay revealed an energy interval of 3 - 4.5 J/cm2 that promote higher wound healing rate 24 h post treatment. An increase in ROS production was also observed 24 h post irradiation higher in the group with the highest wound healing rate. Also, cellular orientation toward the margin of the wound was observed and quantified after irradiation. Low power laser light at 661 nm activated both the migration and proliferation in the in vitro model used, providing evidence that it could also accelerate wound healing in vivo. Also, ROS production and cellular orientation seem to play an important role in wound healing process.


I've lost the person I used to be--experiences of the consequences of fatigue following myocardial infarction.
Fatigue has been found to be the most frequent and bothersome symptom after myocardial infarction (MI), influencing health-related quality of life negatively. Moreover, fatigue after MI has been described as incomprehensible due to its unpredictable occurrence and lack of relationship to physical effort. The aim of this study is therefore to explore persons' experiences of consequences of fatigue and their strategies for dealing with it 2 months after MI. In total, 18 informants, aged 42-75 years, participated in the study. Interviews were conducted and analysed using constructivist grounded theory methodology. Grounded in the data, the main consequence of fatigue, as illustrated in the core category, was: I've lost the person I used to be. It indicates a sense of reduced ability to manage daily life due to experiences of fatigue. The core category was developed from the four categories: involuntary thoughts, certainties replaced with question marks, driving with the handbrake on and just being is enough. Furthermore, attempts to relieve fatigue were limited. These findings indicate that patients with symptoms of fatigue should be supported in developing relief strategies, for example, rest and sleep hygiene as well as physical activity. In conclusion, the results show that fatigue can be understood in light of the concepts "comprehensibility" and "manageability." They also indicate that, working from a person-centered perspective, health-care professionals can support patients experiencing post-MI fatigue by giving them opportunities to straighten out the question marks and by inviting them to discuss involuntary thoughts and feelings of being restricted in their daily life functioning.


An overview of the predictors of symptomatic urinary tract infection among nursing students.
Urinary tract infection (UTI) is the most common infection experienced by humans after respiratory and gastro-intestinal infections, and also the most common cause of nosocomial infections for patients admitted to hospitals indeed UTIs are the most frequent bacterial infection in women. The aim was to determine the prevalence of UTI and to identify factors associated with an increased risk of UTI among nursing students. The cross-sectional study involved 177 unmarried nursing students aged 18-30 years studying in the SRMSIMS, Nursing College Bareilly. A structured questionnaire was used, and study subjects were asked regarding the symptoms of UTI in the previous 3 months. Chi-square test and Univariate Logistic Regression was used to analyze the data. The overall prevalence of UTI was found to be 19.8% (35/177). Rural background, inadequate water intake, and unsatisfactory toilet habits were found to be strong predictors of UTI. There is an urgent need to sensitize the nursing students regarding the growing need of the issue so that they themselves become aware in addition to raising the awareness of other high-risk groups.


Better arthritis care: What training do community-based health professionals need to improve their care of people with arthritis? A Delphi study.
The aim of the present study was to identify the competencies that non-specialist community-based nurses and allied health professionals (AHPs) need to enable them to assess, care for and manage arthritis appropriately. A Delphi survey with an expert panel of 43 rheumatology specialists and expert patients was used to identify the competencies needed by community-based nurses and AHPs to enable them to improve their care of people with arthritis. The process was informed by feedback from focus groups with arthritis patients, community-based nurses and AHPs. The core competencies in arthritis care needed by non-specialist community-based nurses and AHPs were identified. The key goals identified were to increase the understanding of arthritis and its impact on patients' lives, and to increase the ability to help patients to self-manage their condition and access support. Competencies included an understanding of the pathology underlying inflammatory and non-inflammatory arthritis, the ability to distinguish between the two and the ability to recognize early warning signs, with an emphasis on osteoarthritis (OA), rheumatoid arthritis, gout and septic arthritis. Essential competencies included the ability to engage in shared decision making, goal setting and signposting, to provide patients with education and information and to make appropriate referrals. Health professionals working in the community commonly encounter arthritis as a presenting problem or as a co-morbidity. The quality of care provided to people with inflammatory arthritis and OA in the community is currently variable. The present study identified the core competencies that all community-based nurses and AHPs should have in relation to OA and inflammatory arthritis.


Snake venom components enhance pain upon subcutaneous injection: an initial examination of spinal cord mediators.
Snakebites are a relevant public health problem in Central and South America. Snake bite envenomations cause intense pain, not relieved by anti-venom. The fangs of many species are short, causing subcutaneous injection. Fangs of larger species inflict subcutaneous or intramuscular envenomation. To understand pain induced by subcutaneous venom, this study examined spinal mechanisms involved in pain-enhancing effects of subcutaneous Lys49 and Asp49 secretory phospholipase-A(2) (sPLA2), two components of Bothrops asper snake venom showing highly different enzymatic activities. Unilateral intraplantar sPLA2-Lys49 (catalytically inactive) or sPLA2-Asp49 (catalytically active) into rat hindpaws each induced mechanical hyperalgesia (Randall-Selitto test), whereas only catalytically active sPLA2-Asp49 caused mechanical allodynia (von Frey test). Effects induced by both sPLA2s were inhibited by intrathecal fluorocitrate, a reversible glial metabolic inhibitor. In support, immunohistochemical analysis revealed activation of dorsal horn astrocytes and microglia after intraplantar injection of either sPLA2. Spinal proinflammatory cytokines, nitric oxide, and prostanoids each appear to be involved in the pain-enhancing effects of these sPLA2s. Blockade of interleukin-1 (IL1) inhibited hyperalgesia induced by both sPLA2s, while leaving allodynia unaffected. Blockade of tumor necrosis factor reduced responses to sPLA2-Asp49. An inhibitor of neuronal nitric oxide synthase, 7-nitroindazole (7-NI), inhibited hyperalgesia induced by both sPLA2s, without interfering with allodynia induced by sPLA2-Asp49. On the other hand, L-N(6)-(1-iminoethyl)lysine (L-NI), an inhibitor of the inducible nitric oxide synthase, did not alter any sPLA2-induced effect. Lastly, celecoxib, an inhibitor of cyclooxygenase-2, attenuated sPLA2 actions. These data provide the first evidence of spinal mediators involved in pain facilitation induced by subcutaneous venoms.


The Quiescent Metabolic Phenotype of Glioma Stem Cells.
Glioblastoma (GBM) is the most common primary malignant brain tumor in humans and, even with aggressive treatment that includes surgical resection, radiation (IR), and chemotherapy administration, prognosis is poor due to tumor recurrence. There is evidence that within GBMs a small number of glioma stem-like cells (GSLCs) exist, which are thought to be therapy resistant and are thus capable of repopulating a tumor after treatment. Like most cancers, GBMs largely employ aerobic glycolysis to create ATP, a phenomenon known as the Warburg Effect. There is no consensus on the metabolic characteristics of cancer stem cells. GSLCs have been shown to rely more heavily on oxidative phosphorylation, but there is also evidence that cancer stem cells can adapt their metabolism by fluctuating between energy pathways or acquiring intermediate metabolic phenotypes. We hypothesized that the metabolism of GSLCs differs from that of differentiated GBM tumor cell lines, and that the steady state metabolism would be differentially altered following radiation treatment. We evaluated the oxygen consumption rate, extracellular acidification rate, and metabolic enzyme levels of GBM cell lines and GSLCs before and after irradiation using extracellular flux assays. We also measured absolute metabolite levels in these cells via mass spectroscopy with and without radiation treatment. GSLCs were found to be significantly more quiescent in comparison to adherent GBM cell lines, highlighted by lower glycolytic and maximal respiratory capacities as well as lower oxygen consumption and extracellular acidification rates. Analysis of individual metabolite concentrations revealed lower total metabolite concentrations overall but also elevated levels of metabolites in different energy pathways for GSLCs compared to GBM cell lines. Additionally, the metabolism of both GSLCs and GBM cell lines were found to be altered by IR. While there is not one metabolic alteration that distinguishes irradiated GSLC metabolism from that of GBM cell lines, therapies targeting more metabolically quiescent tumor cells and thus the resistant GSLC population may increase a cancer's sensitivity to radiotherapy.


Evaluation of a Diverse, Worldwide Collection of Wild, Cultivated, and Landrace Pepper (Capsicum annuum) for Resistance to Phytophthora Fruit Rot, Genetic Diversity, and Population Structure.
Pepper is the third most important solanaceous crop in the United States and fourth most important worldwide. To identify sources of resistance for commercial breeding, 170 pepper genotypes from five continents and 45 countries were evaluated for Phytophthora fruit rot resistance using two isolates of Phytophthora capsici. Genetic diversity and population structure were assessed on a subset of 157 genotypes using 23 polymorphic simple sequence repeats. Partial resistance and isolate-specific interactions were identified in the population at both 3 and 5 days postinoculation (dpi). Plant introductions (PIs) 640833 and 566811 were the most resistant lines evaluated at 5 dpi to isolates 12889 and OP97, with mean lesion areas less than Criollo de Morelos. Genetic diversity was moderate (0.44) in the population. The program STRUCTURE inferred four genetic clusters with moderate to very great differentiation among clusters. Most lines evaluated were susceptible or moderately susceptible at 5 dpi, and no lines evaluated were completely resistant to Phytophthora fruit rot. Significant population structure was detected when pepper varieties were grouped by predefined categories of disease resistance, continent, and country of origin. Moderately resistant or resistant PIs to both isolates of P. capsici at 5 dpi were in genetic clusters one and two.


Artesunate and erythropoietin synergistically improve the outcome of experimental cerebral malaria.
Cerebral malaria (CM) is a severe neurological syndrome in humans and the main fatal cause of malaria. In malaria epidemic regions, despite appropriate anti-malarial treatment, 10-20% of deaths still occur during the acute phase. This is largely attributable to poor treatment access, therapeutic complexity and drug resistance; thus, developing additional clinical adjunctive therapies is an urgent necessity. In this study, we investigated the effect of artesunate (AST) and recombinant human erythropoietin (rhEPO) using an experimental cerebral malaria (ECM) model-C57BL/6 mice infected with Plasmodium berghei ANKA (PbA). Treatment with the combination of AST and rhEPO reduced endothelial activation and improved the integrity of blood brain barrier, which led to increased survival rate and reduced pathology in the ECM. In addition, this combination treatment down-regulated the Th1 response during PbA infection, which was correlated with the reduction of CCL2, TNF-α, IFN-γ, IL-12, IL-18, CXCL9 and CXCL10 levels, leading to reduced accumulation of pathogenic T cells in the brain. Meanwhile, AST and rhEPO combination led to decreased maturation and activation of splenic dendritic cells, expansion of regulatory T cells, and increased IL-10 and TGF-β production. In conclusion, these data provide a theoretical basis for clinical adjunct therapy with rhEPO and AST in human cerebral malaria patients.


Mirau-based line-field confocal optical coherence tomography for three-dimensional high-resolution skin imaging.
Line-field confocal optical coherence tomography (LC-OCT) is a recently introduced high-resolution imaging modality based on a combination of low-coherence optical interferometry and reflectance confocal optical microscopy with line illumination and line detection. Capable of producing three-dimensional (3D) images of the skin with cellular resolution, in vivo, LC-OCT has been mainly applied in dermatology and dermo-cosmetology. The LC-OCT devices capable of acquiring 3D images reported so far are based on a Linnik interferometer using two identical microscope objectives. In this configuration, LC-OCT cannot be designed to be a very compact and light device, and the image acquisition speed is limited. The objective of this work was to develop a more compact and lighter LC-OCT device that is capable of acquiring images faster without significant degradation of the resolution and with optimized detection sensitivity. We developed an LC-OCT device based on a Mirau interferometer using a single objective. Dynamic adjustment of the camera frequency during the depth scan is implemented, using a faster camera and a more powerful light source. The reflectivity of the beam-splitter in the Mirau interferometer was optimized to maximize the detection sensitivity. A galvanometer scanner was incorporated into the device for scanning the illumination line laterally. A stack of adjacent B-scans, constituting a 3D image, can thus be acquired. The device is able to acquire and display B-scans at 17 fps. 3D images with a quasi-isotropic resolution of ∼1.5 μm (1.3, 1.9, and 1.1 μm in the x , y, and z directions, respectively) over a field of 940 μm × 600 μm × 350 μm (x × y × z) can be obtained. 3D imaging of human skin at cellular resolution, in vivo, is reported. The acquisition rate of the B-scans, at 17 fps, is unprecedented in LC-OCT. Compared with the conventional LC-OCT devices based on a Linnik interferometer, the reported Mirau-based LC-OCT device can acquire B-scans ∼2 times faster. With potential advantages in terms of compactness and weight, a Mirau-based device could easily be integrated into a smaller and lighter handheld probe for use by dermatologists in their daily medical practice.


Ischemic Stroke in Nonvalvular Atrial Fibrillation at Warfarin Initiation: Assessment via a Large Insurance Database.
Stroke risk may increase shortly after warfarin initiation in nonvalvular atrial fibrillation patients. Because of the brief period and limited number of events, large samples are needed to study this effect. We compared 30-day rates of ischemic stroke between nonvalvular atrial fibrillation patients initiating warfarin to nonwarfarin comparators using an insurance claims database. We identified nonvalvular atrial fibrillation patients via 1 inpatient/2 outpatient diagnosis claims from the MarketScan database, January 1, 2009, to December 31, 2010. We studied patients initiating warfarin using prescription claims and 1:1 matched 22 669 initiators to comparators based on age, sex, diagnosis date, and warfarin propensity score. Follow-up began on initiation date; patients were censored at discontinuation/switch of therapy, disenrollment, or end of the study. The median follow-up was 415 days. Cox regression was used to study differences in ischemic stroke risks between warfarin initiators and comparators while controlling for important prognostic factors. Warfarin initiators were generally similar to comparators in clinical features but had higher CHADS2 scores (1.26 versus 1.19). The first 30-day ischemic stroke rate was higher among warfarin initiators than comparators (1.47%/y (27/1836) versus 0.98%/y (18/1837); P=0.18) but lower subsequently (0.81%/y [134/16 543] versus 1.09%/y [406/37 248]; P=0.002). Multivariable regression confirmed a significant interaction between follow-up and warfarin use with the adjusted hazard ratios (95% confidence intervals) for warfarin/comparator as 1.46 (0.80-2.65) in the first 30 days and 0.70 (0.57-0.85) afterward. Warfarin effect was qualitatively different in the first 30 days after initiation than subsequently. This is consistent with a modest increase in stroke risk occurring briefly after starting warfarin.


Long-Term Care of the Pediatric Kidney Transplant Recipient.
Pediatric kidney transplant recipients are distinguished from adult recipients by the need for many decades of graft function, the potential effect of CKD on neurodevelopment, and the changing immune environment of a developing human. The entire life of an individual who receives a transplant as a child is colored by their status as a transplant recipient. Not only must these young recipients negotiate all of the usual challenges of emerging adulthood (transition from school to work, romantic relationships, achieving independence from parents), but they must learn to manage a life-threatening medical condition independently. Regardless of the age at transplantation, graft failure rates are higher during adolescence and young adulthood than at any other age. All pediatric transplant recipients must pass through this high-risk period. Factors contributing to the high graft failure rates in this period include poor adherence to treatment, potentially exacerbated by the transfer of care from pediatric- to adult-oriented care providers, and perhaps an increased potency of the immune response. We describe the characteristics of pediatric kidney transplant recipients, particularly those factors that may influence their care throughout their lives. We also discuss the risks associated with the transition from pediatric- to adult-oriented care and provide some suggestions to optimize the transition to adult-oriented transplant care and long-term outcomes.


Matrix method for the study of wave propagation in one-dimensional general media.
A matrix method which relates the field and its derivative is presented for the study of wave propagation in any type of one-dimensional media. The transfer matrix is obtained from the canonical solutions of Helmholtz equations at normal incidence. The method is applied to different optical systems like a Fabry-Perot cavity formed by uniform fiber Bragg gratings, periodic dielectric structures and different quasi-periodic structures based on Fibonacci and Thue-Morse sequences of layers with constant and variable refractive index.


Pancreatic exocrine insufficiency after non-pancreatic upper gastrointestinal surgery: meta-analysis.
Untreated pancreatic exocrine insufficiency (PEI) results in substantial patient harm. Upper gastrointestinal surgery (bariatric metabolic surgery and oesophagogastric resection) affects the delicate physiology of pancreatic exocrine function and may result in PEI. The aim of this study was to assimilate the literature on incidence, diagnosis, and management of PEI after bariatric metabolic surgery and oesophagogastric resection. A systematic review of PubMed, MEDLINE, and Embase databases identified studies investigating PEI after non-pancreatic upper gastrointestinal surgery. Meta-analyses were undertaken for incidence of PEI and benefit of pancreatic enzyme replacement therapy. Among 1620 patients from 24 studies included in quantitative synthesis, 36.0% developed PEI. The incidence of PEI was 23.0 and 50.4% after bariatric metabolic surgery and oesophagogastric resection respectively. Notably, the incidence of PEI was 44% after biliopancreatic diversion with duodenal switch and 66.2% after total gastrectomy. The most common diagnostic test used was faecal elastase 1 (15 of 31 studies), with less than 200 µg/g being diagnostic of PEI. A total of 11 studies considered the management of pancreatic exocrine insufficiency, with 78.6% of patients responding positively to pancreatic enzyme replacement when it was prescribed. PEI is common after non-pancreatic upper gastrointestinal surgery and patients may benefit from enzyme replacement therapy.


Prevalence of Circadian Misalignment and Its Association With Depressive Symptoms in Delayed Sleep Phase Disorder.
To examine the prevalence of circadian misalignment in clinically diagnosed delayed sleep phase disorder (DSPD) and to compare mood and daytime functioning in those with and without a circadian basis for the disorder. One hundred and eighty-two DSPD patients aged 16-64 years, engaged in regular employment or school, underwent sleep-wake monitoring in the home, followed by a sleep laboratory visit for assessment of salivary dim light melatonin onset (DLMO). Based on the DLMO assessments, patients were classified into two groups: circadian DSPD, defined as DLMO occurring at or after desired bedtime (DBT), or non-circadian DSPD, defined as DLMO occurring before DBT. One hundred and three patients (57%) were classified as circadian DSPD and 79 (43%) as non-circadian DSPD. DLMO occurred 1.66 hours later in circadian DSPD compared to non-circadian DSPD (p < .001). Moderate-severe depressive symptoms (Beck Depression Inventory-II) were more prevalent in circadian DSPD (14.0%) than in non-circadian DSPD (3.8%; p < .05). Relative to non-circadian DSPD patients, circadian DSPD patients had 4.31 times increased odds of at least mild depressive symptoms (95% CI 1.75 to 10.64; p < .01). No group differences were found for daytime sleepiness or function, but DSPD symptoms were rated by clinicians to be more severe in those with circadian DSPD. Almost half of patients clinically diagnosed with DSPD did not show misalignment between the circadian pacemaker and the DBT, suggesting that the reported difficulties initiating sleep at the DBT are unlikely to be explained by the (mis)timing of the circadian rhythm of sleep propensity. Circadian misalignment in DSPD is associated with increased depressive symptoms and DSPD symptom severity.


Bond strength following the application of chlorhexidine on etched enamel.
The purpose of this study was to determine whether the application of chlorhexidine to etched enamel affects the shear bond strength and bracket/adhesive failure modes of orthodontic brackets. Forty recently extracted third molars were cleaned divided into two groups of twenty. The first group was etched with a 37% phosphoric acid gel, and a sealant was applied containing a chlorhexidine varnish. Stainless steel orthodontic brackets were bonded using the Transbond XT bonding system (3M/Unitek). Teeth in the second group were etched and bonded using the same bonding system but without chlorhexidine. A Zwick Universal Testing Machine was used to determine shear bond strengths. There were no significant differences in bond strengths between the chlorhexidine treated teeth (= 11.8 +/- 2.1 MPa) and the controls (= 12.4 +/- 3.1 MPa) (p = 0.129). The Chi Square test evaluating the residual adhesive on the enamel surfaces showed no significant differences (P = 0.136) between the two groups evaluated. The use of a primer containing chlorhexidine does not significantly affect shear bond strength nor the fracture site (bond failure location).


Mismatch negativity and P300 to behaviorally perceptible and imperceptible frequency and intensity contrasts.
Mismatch negativity and the P300 have been investigated as electrophysiological indices of behavioral auditory discrimination of duration. Using an oddball paradigm, responses were evoked to stimuli that had been behaviorally demonstrated to be either perceptible or imperceptible. The results indicated P300 events were present with the perceptible contrast but absent for the imperceptible contrast with all participants, while mismatch negativities were present in approximately 80 and 20% of participants to the perceptible and imperceptible contrasts, respectively. The present study extended the findings by applying the same paradigm to the discrimination of spectral and amplitude contrasts. 10 young adults with normal hearing were participants. Assuming that auditory assessment should involve representation and processing in all acoustic domains (i.e., temporal/duration, spectral/frequency, and amplitude/intensity), the effects seen with temporal contrasts were predicted to be similar for spectral and amplitude contrasts. The findings generally illustrated that the P300 was more accurate than the mismatch negativity in reflecting behavioral discrimination. Together, these studies challenge the use of mismatch negativity as an electrophysiological correlate for behavioral discrimination of auditory perceptible contrasts.


Detection of human metapneumovirus in infants with acute respiratory tract infection.
Both respiratory syncytial virus (RSV) and human metapneumovirus (hMPV), a recently discovered respiratory pathogen classified in the Paramyxoviridae family, have been associated with acute respiratory tract infections (ARTI) in infants. The aim of our study was to determine the incidence and clinical features of hMPV infection in infants presenting with ARTI at a tertiary children's hospital in Greece during the 2007-2008 and 2008-2009 winter seasons. Routine nasal swabs were obtained from 127 infants younger than 12 months of age. The specimens were tested for the presence of hMPV and RSV antigens using validated enzyme-linked immunoassays. The mean age of the studied infants was 3 months (range 19 days to 12 months). hMPV was detected in 8 (6.3%) children, 4 boys and 4 girls, while RSV was detected in 39 (30.7%) children, 22 boys and 17 girls. In 7 children, hMPV was identified as a unique viral pathogen, while only 1 child was co-infected with hMPV and RSV. Bronchiolitis was diagnosed in all hMPV-positive cases, while only two cases required hospitalization and supplemental oxygen therapy. Our results provide further evidence of the importance of hMPV as a pathogen associated with community-acquired ARTI in infants in Greece.


Differential expression of SOX9 in gonads of the sea turtle Lepidochelys olivacea at male- or female-promoting temperatures.
In mouse and chick embryos, the SOX9 gene is down-regulated in genetic females whereas in genetic males it remains in the Sertoli cells. We studied the distribution of SOX9 protein in developing genital ridges of embryos of the sea turtle Lepidochelys olivacea incubated at male- or female-promoting temperatures, using the antibody for detection. At stages 22-24, cells in medullary cords show SOX9 positive nuclei, while coelomic epithelial cells appear negative. At stage 25 however, most medullary cells are SOX9 negative and at the female-promoting temperature, and from stage 26 onwards, SOX9 protein is not detected. At the male-promoting temperature, medullary cords remain SOX9-positive at all stages. These results suggest that SOX9 is up-regulated in Sertoli cells irrespective of primary sex-determining switch. Sex is irreversibly determined at stage 24 or 26 at the male- or female-promoting temperature, respectively (Merchant-Larios et al.,'97). The present results suggest that there is a correlation between SOX9 expression and sex determination in the olive ridley. At the male-promoting temperature, Sertoli cells expressing SOX9 become committed at stage 24 and male sex is determined, whereas at the female-promoting temperature, SOX9 is down-regulated at stage 26 and female sex is determined. J. Exp. Zool. 284:705-710, 1999.


A comparative assessment of univariate longevity measures using zoological animal records.
Comparative biogerontology evaluates cellular, molecular, physiological, and genomic properties that distinguish short-lived from long-lived species. These studies typically use maximum reported lifespan (MRLS) as the index with which to compare traits, but there is a general awareness that MRLS is not ideal owing to statistical shortcomings that include bias resulting from small sample sizes. Nevertheless, MRLS has enough species-specific information to show strong associations with many other species-specific traits, such as body mass, stress resistance, and codon usage. The major goal of this study was to see if we could identify surrogate measures with better statistical properties than MRLS but that still capture inter-species differences in extreme lifespan. Using zoological records of 181 bird and mammal species, we evaluated 16 univariate metrics of aging and longevity, including nonparametric quantile-based measures and parameters derived from demographic models of aging, for three desirable statistical properties. We wished to identify those measures that: (i) correlated well with MRLS when the biasing effects of sample size were removed; (ii) correlated weakly with population size; and (iii) were highly robust to the effects of sampling error. Nonparametric univariate descriptors of the distribution of lifespans clearly outperformed the measures derived from demographic analyses. Mean adult lifespan and quantile-based measures, and in particular the 90th quantile of longevity, performed particularly well, demonstrating far less sensitivity to small sample size effects than MRLS while preserving much of the information contained in the maximum lifespan measure. These measures should take the place of MRLS in comparative studies of lifespan.


Disc Configuration as a Risk and Prognostic Factor in NAION: The Impact of Cup to Disc Ratio, Disc Diameter, and Crowding Index.
Purpose: The presence of the so called disc at risk (a small disc with no cupping) has been considered the main risk factor for the development of non-arteritic anterior ischemic optic neuropathy (NAION). However its role as a prognostic factor has not been studied. Our aim was to determine the weight of disc configuration as a risk and a prognostic factor for NAION. Methods: Case control study. Forty eyes of 40 patients who were diagnosed with NAION between 2008 and 2017, and 120 controls (3 controls for each patient) were included in the study. Disc diameter (DD), cup to disc ratio (CDR), and peripapillar retinal nerve fiber layer thickness (RNFLT) of the non-affected eye were measured using optic coherence tomography (3D OCT 2000, Topcon). Crowding index (CI) was defined as the quotient of average RNFLT and disc area. Mean deviation (MD) at the time of diagnosis and at least three months later was determined using a Humphrey Visual Field Analyzer (SITA standard 24-2 strategy). Visual acuity (VA) was measured using Snellen charts and transformed into LogMAR values. Results: Only CDR was found to be a risk factor for NAION. No correlationship was found between CI and visual loss. Conclusions: DD and CI did not show value as either prognostic or risk factors. Glial tissue may be a part of the content of the optic disc as important as axons. Our results are in line with the latest studies about NAION pathophysiology. Contrary to classic thinking, these papers have not found smaller disc diameters, but smaller values of lamina cribosa depth in NAION patients.


Brain structures and functional connectivity associated with individual differences in Internet tendency in healthy young adults.
Internet addiction (IA) incurs significant social and financial costs in the form of physical side-effects, academic and occupational impairment, and serious relationship problems. The majority of previous studies on Internet addiction disorders (IAD) have focused on structural and functional abnormalities, while few studies have simultaneously investigated the structural and functional brain alterations underlying individual differences in IA tendencies measured by questionnaires in a healthy sample. Here we combined structural (regional gray matter volume, rGMV) and functional (resting-state functional connectivity, rsFC) information to explore the neural mechanisms underlying IAT in a large sample of 260 healthy young adults. The results showed that IAT scores were significantly and positively correlated with rGMV in the right dorsolateral prefrontal cortex (DLPFC, one key node of the cognitive control network, CCN), which might reflect reduced functioning of inhibitory control. More interestingly, decreased anticorrelations between the right DLPFC and the medial prefrontal cortex/rostral anterior cingulate cortex (mPFC/rACC, one key node of the default mode network, DMN) were associated with higher IAT scores, which might be associated with reduced efficiency of the CCN and DMN (e.g., diminished cognitive control and self-monitoring). Furthermore, the Stroop interference effect was positively associated with the volume of the DLPFC and with the IA scores, as well as with the connectivity between DLPFC and mPFC, which further indicated that rGMV variations in the DLPFC and decreased anticonnections between the DLPFC and mPFC may reflect addiction-related reduced inhibitory control and cognitive efficiency. These findings suggest the combination of structural and functional information can provide a valuable basis for further understanding of the mechanisms and pathogenesis of IA.


Efficiency of different formulations of Bradyrhizobium japonicum and effect of co-inoculation of Bacillus subtilis with two different strains of Bradyrhizobium japonicum.
A key constraint in successfully obtaining an effective inoculant is overcoming difficulties in formulating a viable and user-friendly final product and maintaining the microbial cells in a competent state. Co-cultures of rhizobia and PGPR (Plant Growth Promoting Rhizobacteria) are a logical next subject for formulation researchers as they can influence the efficacy of rhizobia. A greenhouse experiment was set to assess the formulation effect of one strain i.e. Bradyrhizobium japonicum, 532c (granules, liquid and broth) and also to determine the efficiency of co-inoculation of Bacillus with two commercial strains of B. japonicum (532c and RCR 3407) on 2 soybean (Glycine max L.) varieties. PCR-RFLP analysis was used to determine the nodule occupancy in each treatment. Most of the inoculants showed increased nodulation and biomass yields (by approximately 2-5 and 4-10 g plant(-1) respectively) as compared to the uninoculated controls. TGx1740-2F showed no significant differences in nodule fresh weights for the formulation effect while the co-inoculants increased the nodule fresh weights by up to 4 g plant(-1). The liquid and granule-based inoculants induced higher biomass yields (4-8 g plant(-1)) suggesting a possible impact of formulation on the effectiveness of the inoculants. The co-inoculants also gave higher yields but showing no significant differences to the rhizobial inoculants. Nodule occupancy was 100 % for the rhizobial inoculants as well as the co-inoculants emphasizing the infectivity and high competitiveness of 532c and RCR 3407 strains despite the high population of indigenous rhizobia.


Impact of screening examinations on survival in familial adenomatous polyposis.
Prophylactic family screening and surgery has improved the outcome of patients with familial adenomatous polyposis (FAP) largely preventing deaths due to colorectal cancer. The present study compared the mortality rates and causes of death of FAP patients diagnosed by symptoms (probands) or by family screening (call-up). The study comprised all 236 FAP patients registered in the Finnish Polyposis Registry until the end of June 1998. There were 116 probands and 120 call-up patients with a median age of 36.8 and 22.8 at diagnosis and median follow-up times of 6.3 and 9.9 years, respectively. Cumulative crude and relative survival estimates were calculated for each group and the causes of death were determined. The life expectancy was significantly better in the call-up group than in the probands after colectomy (P < 0.001). The survival rates of the call-up group equaled those expected for a comparable group in the general population up to 18 years after colectomy. The main cause of death was colorectal cancer accounting for 54 out of 68 deaths: four in the call-up group (all rectal stump cancer) and 50 in probands. Upper GI-tract cancer caused four deaths (periampullary cancer two, stomach cancer two) and two deaths were due to postoperative pulmonary embolism. The survival of FAP patients is significantly improved by prophylactic screening and surgery. Further improvement may be possible by using restorative proctocolectomy instead of colectomy and ileorectal anastomosis and by regular upper GI-tract endoscopic surveillance.


Treatment of CD30-positive systemic mastocytosis with brentuximab vedotin.
Systemic mastocytosis is a myeloproliferative neoplasm with varying presentation that is caused by infiltration of neoplastic mast cells into extracutaneous tissues. Cytoreductive therapy is used to control organ dysfunction in aggressive systemic mastocytosis and is sometimes needed for control of severe refractory symptoms in patients with indolent disease. However, current standard cytoreductive agents are limited by their suboptimal degree and duration of response and associated significant toxicities, highlighting the need for novel treatments for systemic mastocytosis. Recent studies have identified CD30 as a therapeutic target in systemic mastocytosis, as CD30 is expressed on a majority of neoplastic mast cells. In this case series, the clinical outcomes of 4 patients with aggressive or indolent systemic mastocytosis treated with the anti-CD30 antibody-drug conjugate brentuximab vedotin are reported. Two patients showed evidence of a response to treatment with a reduction in disease burden, 1 of which has demonstrated a durable response with ongoing benefit for more than 3 years. Treatment with brentuximab vedotin was well-tolerated with side effects that were effectively managed by dose modifications. The results presented suggest that brentuximab vedotin is active in systemic mastocytosis and can induce durable responses with a manageable toxicity profile.


[Current characteristics of natural nidality of tick-borne encephalitis: new or well forgotten?].
A number specialists' opinion as to which the rise in the incidence of tick-borne encephalitis at the turn of the centuries is due to the new features of the epidemiology of this infection and to global climatic changes is analyzed. There are no objective evidence suggesting the ongoing expansion of a natural habitat of the major vectors--taiga (Ixodes persulcatus) and wood (I. ricinis) ticks and the noticeable increase in their size and virus infection rates. The notion of the recent penetration of ticks into the metropolises where natural focuses have emerged and human beings are infected is inconsistent with the multidescribed facts. There is no significant evidence for the expansion of a nosoarea of tickborne encephalitis. The impact of reformed anthropurgic foci and that of the proportion of town-dwellers in the general structure of morbidity on the epidemic situation have been evaluated. The intensity of an epidemic manifestation of natural foci is always determined by two most important parameters: 1) the loimopotential of foci and 2) the intensity of the population's contact with them. The nature of an interaction between these factors, which has caused a rapid surge of morbidity rates and their subsequent long-time reduction, is considered.


Flexible bronchoscopy during non-invasive positive pressure mechanical ventilation: are two better than one?
Flexible bronchoscopy (FBO) and non-invasive positive pressure ventilation (NIPPV) are largely applied in respiratory and general intensive care units. FBO plays a crucial role for the diagnosis of lung infiltrates of unknown origin and for the treatment of airways obstruction due to bronchial mucous plugging and hemoptysis in critical patients. NIPPV is the first-choice ventilatory strategy for acute respiratory failure (ARF) of different causes as it could be used as prevention or as alternative to the conventional mechanical ventilation (CMV) via endotracheal intubation (ETI). Some clinical scenarios represent contraindications for these techniques such as severe ARF in spontaneous breathing patients for FBO and accumulated tracheo-bronchial secretions in patients with depressed cough for NIPPV. In these contexts, the decision of performing ETI should carefully consider the risk of CMV-correlated complications. An increasing amount of published data suggested the use of FBO during NIPPV in ARF in order to avoid/reduce the need of ETI. Despite a strong rationale for the combined use of the two techniques, there is not still enough evidence for a large-scale application of this strategy in all different clinical scenarios. The majority of the available data are in favor of the "help" given by NIPPV to diagnostic FBO in high-risk spontaneously breathing patients with severe hypoxemia. Preliminary findings report the successful "help" given by early FBO to NIPPV in patients with hypoxemic-hypercapnic ARF who are likely to fail because of hypersecretion. Synergy of FBO and NIPPV application is emerging also to perform ETI in challenging situations, such as predicted difficult laringoscopy and NPPV failure in severely hypoxemic patients. This combined approach should be performed only in centers showing a wide experience with both NIPPV and FBO, where close monitoring and ETI facilities are promptly available.


Effect of bipolar pulsed radiofrequency on refractory chronic cervical radicular pain: A report of two cases.
Despite undergoing transforaminal epidural steroid injection (TFESI), many patients complain of persisting cervical radicular pain. For the management of chronic cervical radicular pain, clinicians are widely applying pulsed radiofrequency (PRF) stimulation to dorsal root ganglions (DRGs). To enhance the effect of PRF stimulation, we conducted bipolar PRF stimulation in 2 patients with chronic cervical radicular pain that was refractory to monopolar PRF and repeated TFESIs. Patients 1 and 2 presented with a numeric rating scale (NRS) score of 7 and 6 for chronic cervical radicular pain, respectively, despite undergoing monopolar PRF and 2 TFESIs. On cervical magnetic resonance imaging, foraminal stenosis at the right C6-7 and right central to right foraminal disc protrusion on C6-7 were observed in patients 1 and 2, respectively. Two patients showed a positive response on diagnostic right C7 selective nerve root block with 0.5 mL of 1% lidocaine. Bipolar PRF stimulation was performed under C-arm fluoroscopy. Two parallel RF cannulas (less than 1 cm apart) were used for DRG stimulation. The PRF treatment was administered at 5 Hz and a 5-ms pulsed width for 360 seconds at 45 V with the constraint that the electrode tip temperature did not exceed 42°C. At the 2-week and 1-month follow-up, after undergoing bipolar PRF, the pain of patient 1 was completely relieved, and at 2, 3, and 6 months, the pain was scored as NRS 2. In patient 2, at the 2-week follow-up after undergoing bipolar PRF, pain severity was reduced from NRS 6 to 2. The effect of bipolar PRF on patient 2 lasted for at least 6 months. No adverse effects were observed in either patient. Application of bipolar PRF to DRGs seems to be an effective and safe technique for treating refractory chronic cervical radicular pain.


Intravenous administration of amphotericin B entrapped in liposomes: induction of high serum levels of TNF alpha.
The rate of objective response to second-line chemotherapy with cyclophosphamide, adriamycin and vincristine increased from 13% to 55% in two consecutive series of patients with small-cell lung cancer when the therapy was potentiated by amphotericin B (2 mg/kg i.v.) entrapped in liposomes (= ampholiposomes). Patients who received ampholiposomes had a rapid and significant (p less than 0.01) increase of serum TNF alpha concentrations (median value: from less than 10 to 261 pg/mL) followed by a rise in serum neopterin and CRP. No major side effects were observed. Administration of ampholiposomes appeared to be a safe method for obtaining relatively high serum levels of TNF alpha that could potentiate anticancer chemotherapy.


U.S. Adolescent and Adult Women's Experiences Accessing and Using Toilets in Schools, Workplaces, and Public Spaces: A Multi-Site Focus Group Study to Inform Future Research in Bladder Health.
The World Health Organization recognizes access to clean and safe toilets as crucial for public health. This study explored U.S. adolescent and adult cisgender women's lived experiences accessing toilets in schools, workplaces, and public spaces. As part of the Prevention of Lower Urinary Tract Symptoms (PLUS) Research Consortium, we conducted 44 focus groups with female participants (n = 360; ages 11-93). Focus groups were stratified by age (11-14, 15-17, 18-25, 26-44, 45-64, 65+) and conducted across 7 geographically diverse U.S. sites from July 2017-April 2018. Using a transdisciplinary approach, we conducted conventional qualitative coding informed by our PLUS conceptual framework and used content analysis processes to identify salient themes. Across settings, toilet access was restricted by "gatekeepers" (i.e., individuals who control access to toilets). In contrast, self-restricting toilet use (deciding not to use the toilet despite biologic need to urinate) was based on internalized norms to prioritize school and job responsibilities over urination. In public spaces, self-restricting use was largely in response to lack of cleanliness. Across the life course, participants perceived gender disparities in the ability to easily access public toilets. Further research is needed to determine if and how these factors impact bladder health across the life course.


Normative data on femoral version.
Femoral version is reported to vary in relation to age, gender and other patient-specific factors. Differences in femoral version are suspected to contribute to the development of hip pathology. However, normative data on pathologic hips has never been reported. To evaluate the femoral version in a large population of patients with symptomatic hip pathology treated with arthroscopy and report differences within this group based on age, gender, bony morphology and other hip-related factors. A prospectively gathered database of 1449 hips was reviewed. All patients underwent pre-operative MRI with measure of femoral version. The average femoral version of the entire population was 8.4+ 9.2°, range -23 to 63. There no statistically significant differences encountered based on age, gender, bony morphology or other hip-related factors. Across all groups, there was wide variation in the femoral version present. Among younger patients, there was trend to have a greater proportion of retroversion. Significant variation in femoral version exists in patients with symptomatic hip pathology. Although the geometry of the proximal femur is commonly described as anteverted, relative retroversion is also frequently encountered.


The role of magnetic resonance imaging in the diagnosis of Alzheimer disease in adults with Down syndrome.
To correlate findings from magnetic resonance imaging (MRI) with neuropathological analysis and clinical assessment of Alzheimer disease in patients with Down syndrome. Case study of 1 elderly man with trisomy 21 and Alzheimer disease who had been followed up prospectively over a 5-year period. The patient was a resident in a supervised community unit and died with end-stage dementia. The MRI changes were correlated with the results of clinical psychopathological analysis and neuropathological brain tissue findings. To our knowledge, this is the first case in which clinical, MRI, and neuropathological data were available in a case involving an elderly patient with Down syndrome and Alzheimer disease. The MRI findings correlated with the clinical deterioration and neuropathological features of Alzheimer disease. Marked changes in temporal and hippocampal regions were found. Magnetic resonance imaging is potentially a valuable tool in the diagnosis of Alzheimer disease in adults with Down syndrome, particularly in individuals for whom standard intellectual assessments are not possible.


Functional disruption of the dystrophin gene in rhesus monkey using CRISPR/Cas9.
CRISPR/Cas9 has been used to genetically modify genomes in a variety of species, including non-human primates. Unfortunately, this new technology does cause mosaic mutations, and we do not yet know whether such mutations can functionally disrupt the targeted gene or cause the pathology seen in human disease. Addressing these issues is necessary if we are to generate large animal models of human diseases using CRISPR/Cas9. Here we used CRISPR/Cas9 to target the monkey dystrophin gene to create mutations that lead to Duchenne muscular dystrophy (DMD), a recessive X-linked form of muscular dystrophy. Examination of the relative targeting rate revealed that Crispr/Cas9 targeting could lead to mosaic mutations in up to 87% of the dystrophin alleles in monkey muscle. Moreover, CRISPR/Cas9 induced mutations in both male and female monkeys, with the markedly depleted dystrophin and muscle degeneration seen in early DMD. Our findings indicate that CRISPR/Cas9 can efficiently generate monkey models of human diseases, regardless of inheritance patterns. The presence of degenerated muscle cells in newborn Cas9-targeted monkeys suggests that therapeutic interventions at the early disease stage may be effective at alleviating the myopathy.


Ultrasound-guided Retroclavicular Approach Versus Costoclavicular Approach of Infraclavicular Brachial Plexus Block for Upper Limb Surgeries.
Regional anesthesia for an upper limb provides many advantages over general anesthesia, especially in orthopedic surgery. This trial aimed to compare a retroclavicular approach to the infraclavicular brachial plexus with a costoclavicular approach in term of needle time, image time, and procedure time, and comparing both with the classic technique for upper limb surgeries guided by ultrasound. Prospective, randomized, single-blinded controlled trial. Minia University, Faculty of Medicine, Anesthesia and Intensive Care Department. Sixty patients of both sees with an American Society of Anesthesiologists Classification of I and II, a BMI (kg/m2) of 20-35, aged from 18-60 years who were scheduled for a forearm or hand surgery under infraclavicular brachial plexus block were divided into 3 parallel equal groups. Group I (RC) received a retroclavicular approach. Group II (CC)received a costoclavicular approach. Group III (CT) received the classic technique. Procedure time, the sum of the imaging and needling times, was our primary outcome. Secondary outcomes were the motor and sensory block success rate 30 minutes postinjection of local anesthesia, duration of motor and sensory block, Visual Analog Score, first analgesic need, total analgesia requirements during the first postoperative 24 hours, and any complications. The procedure and needle times were significantly decreased in the retroclavicular group due to better needle visibility. There was no significant difference regarding sensory and motor block data. The VAS score in the first postoperative 24 hours showed no statistical significance. Regarding analgesic data and patient satisfaction, there was no statistical significance among the 3 studied groups. There were no complications in any of the used approaches. Our trial did not include patients with a BMI > 35. The retroclavicular approach is superior because of its decreased procedure time and needle time than both the costoclavicular approach and classic approach.


Illicit drug use and the genetic overlap with Cannabis use.
The use of illicit substances is correlated, meaning that individuals who use one illicit substance are more likely to also use another illicit substance. This association could (partly) be explained by overlapping genetic factors. Genetic overlap may indicate a common underlying genetic predisposition, or can be the result of a causal association. Polygenic scores for lifetime cannabis use were generated in a sample of Dutch participants (N = 8348). We tested the association of a PGS for cannabis use with ecstasy, stimulants and a broad category of illicit drug use. To explore the nature of the relationship: (1) these analyses were repeated separately in cannabis users and non-users and (2) monozogytic twin pairs discordant for cannabis use were compared on their drug use. The lifetime prevalence was 24.8 % for cannabis, 6.2 % for ecstasy, 6.5 % for stimulants and 7.1 % for any illicit drug use. Significant, positive associations were found between PGS for cannabis use with ecstasy use, stimulants and any illicit drug use. These associations seemed to be stronger in cannabis users compared to non-users for both ecstasy and stimulant use, but only in people born after 1968 and not significant after correction for multiple testing. The discordant twin pair analyses suggested that cannabis use could play a causal role in drug use. The genetic liability underlying cannabis use significantly explained variability in ecstasy, stimulant and any illicit drug use. Further research should further explore the underlying mechanism to understand the nature of the association.


Health and health protection of the Polish population. Experience and the future.
This report, drafted by members of a discussion group (Experience and the Future) consisting primarily of Polish physicians, concerns the problems of personal health and of the health care system in Poland in recent years. Data are presented on key indicators of the health of the Polish population, including mortality, incidence rates of viral and infectious diseases, child health, occupational health, care of the disabled, and alcohol consumption, and a program for improving these indicators is set forth. In addition, achievable short- and long-term goals for the health sector are suggested. It is maintained that many of the unsolved problems in Poland's health sector result from its structure. The foundation on which the health pyramid should rest-primary care in local medical institutions--is the weakest element in the system, whereas the top of the pyramid--specialized, technologically oriented hospitals--is given highest priority.


[GRADE guidelines: 12. Developing Summary of Findings tables - dichotomous outcomes].
Summary of Findings (SoF) tables present, for each of the seven (or fewer) most important outcomes, the following: the number of studies and number of participants; the confidence in effect estimates (quality of evidence); and the best estimates of relative and absolute effects. Potentially challenging choices in preparing SoF tables include using direct evidence (which may have very few events) or indirect evidence (from a surrogate) as the best evidence for a treatment effect. If a surrogate is chosen, it must be labeled as substituting for the corresponding patient-important outcome. Another such choice is presenting evidence from low-quality randomised trials or high-quality observational studies. When in doubt, a reasonable approach is to present both sets of evidence; if the two bodies of evidence have similar quality but discrepant results, one would rate down further for inconsistency. For binary outcomes, relative risks (RRs) are the preferred measure of relative effect and, in most instances, are applied to the baseline or control group risks to generate absolute risks. Ideally, the baseline risks come from observational studies including representative patients and identifying easily measured prognostic factors that define groups at differing risk. In the absence of such studies, relevant randomised trials provide estimates of baseline risk. When confidence intervals (CIs) around the relative effect include no difference, one may simply state in the absolute risk column that results fail to show a difference, omit the point estimate and report only the CIs, or add a comment emphasizing the uncertainty associated with the point estimate. KEY STATEMENTS: Summary of Findings (SoF) tables provide succinct; easily digestible presentations of confidence in effect estimates (quality of evidence) and magnitude of effects. SoF tables should present the seven (or fewer) most important outcomes. These outcomes must always be patient-important outcomes and never be surrogates, although surrogates can be used to estimate effects on patient-important outcomes. SoF tables should present the highest quality evidence. When the quality of two bodies of evidence (e.g., randomised trials and observational studies) is similar, SoF tables may include summaries from both. SoF tables should include both relative and absolute effect measures, and separate estimates of absolute effect for identifiable patient groups with substantially different baseline or control group risks.


Productive and economic performance of broiler chickens fed diets with different nutritional levels.
The present study evaluated the productive characteristics, nutrient digestibility, and economic indexes of broiler chickens submitted to diets containing different nutritional levels, and identified advantages for the commercialization of poultry in the griller-type whole chicken model. A total of 180 COBB 500 chicks ™ were distributed in a completely randomized design, in a 2x3 factorial scheme: sex (male and female) and nutritional level (nutritional requirements for male, female or mixed flock); with 6 repetitions of 5 birds each. It was observed effect of the sex factor in the performance and the economic analysis, in which the male chickens presented the highest feed costs, in spite of exhibiting the best feed conversion rates and gross marketability, resulting from greater body weight. Considering nutritional levels, the most outstanding diet was that formulated according to the demands of the females, which did not affect the performance or carcass characteristics of the birds, obtained the highest gross margins with good feeding costs, showed good retention of dry matter and gross energy, regardless of sex. The diet of nutritional requirements of the females provides promising results for the production of broiler chickens. The female birds present marketing advantages in the griller-type chicken model.


Phylogenetic relationships in the genus mus, based on paternally, maternally, and biparentally inherited characters.
Several species in the rodent genus Mus are used as model research organisms, but comparative studies of these mice have been hampered by the lack of a well-supported phylogeny. We used DNA sequences from six genes representing paternally, maternally, and biparentally inherited regions of the genome to infer phylogenetic relationships among 10 species of Mus commonly used in laboratory research. Our sample included seven species from the subgenus Mus; one species each from the subgenera Pyromys, Coelomys, and Nannomys; and representatives from three additional murine genera, which served as outgroups in the phylogenetic analyses. Although each of the six genes yielded a unique phylogeny, several clades were supported by four or more gene trees. Nodes that conflicted between trees were generally characterized by weak support for one or both of the alternative topologies, thus providing no compelling evidence that any individual gene, or part of the genome, was misleading with respect to the evolutionary history of these mice. Analysis of the combined data resulted in a fully resolved tree that strongly supports monophyly of the genus Mus, monophyly of the subgenus Mus, division of the subgenus Mus into Palearctic (M. musculus, M. macedonicus, M. spicilegus, and M. spretus) and Asian (M. cervicolor, M. cookii, and M. caroli) clades, monophyly of the house mice (M. m. musculus, "M. m. molossinus," M. m. castaneus, and M. m. domesticus), and a sister-group relationship between M. macedonicus and M. spicilegus. Other clades that were strongly supported by one or more gene partitions were not strongly supported by the combined data. This appears to reflect a localized homoplasy in one partition obscuring the phylogenetic signal from another, rather than differences in gene or genome histories.


[Volumetric blood flow in the carotid arteries in various forms of cerebrovascular pathology (based on data from two-dimensional Doppler ultrasonography)].
A total of 86 patients with a history of insult in the carotid system and 105 patients with the early clinical forms of cerebrovascular pathology (ECFCVP) were examined for the volumetric blood flow in the general carotid artery (GCA) using two-dimensional dopplerography. In the group of insult patients, the total volumetric blood flow in bot carotid arteries decreased by 13% on the average, in the group with ECFCVP by 8% as compared to the group of healthy persons. The decrease of the blood flow was recorded not only in the presence but also in the lack of the stenosing process in the carotid arteries.


Interoperable atlases of the human brain.
The last two decades have seen an unprecedented development of human brain mapping approaches at various spatial and temporal scales. Together, these have provided a large fundus of information on many different aspects of the human brain including micro- and macrostructural segregation, regional specialization of function, connectivity, and temporal dynamics. Atlases are central in order to integrate such diverse information in a topographically meaningful way. It is noteworthy, that the brain mapping field has been developed along several major lines such as structure vs. function, postmortem vs. in vivo, individual features of the brain vs. population-based aspects, or slow vs. fast dynamics. In order to understand human brain organization, however, it seems inevitable that these different lines are integrated and combined into a multimodal human brain model. To this aim, we held a workshop to determine the constraints of a multi-modal human brain model that are needed to enable (i) an integration of different spatial and temporal scales and data modalities into a common reference system, and (ii) efficient data exchange and analysis. As detailed in this report, to arrive at fully interoperable atlases of the human brain will still require much work at the frontiers of data acquisition, analysis, and representation. Among them, the latter may provide the most challenging task, in particular when it comes to representing features of vastly different scales of space, time and abstraction. The potential benefits of such endeavor, however, clearly outweigh the problems, as only such kind of multi-modal human brain atlas may provide a starting point from which the complex relationships between structure, function, and connectivity may be explored.


Occurrence and distribution of serotypes of the Arizona subgroup of Salmonella strains in the United States from 1967 to 1976.
The Salmonella Arizona subgroup contains gram-negative enteric bacteria that are closely related to other salmonellae biochemically, serologically, and genetically. Although the Arizona subgroup may be isolated from a wide variety of nonhuman and human sources, the arizonae are uncommonly recognized as human pathogens, and surprisingly little is known about their epidemiology. From 1967 through 1976, the Centers for Disease Control received 858 Arizona subgroup cultures from human and nonhuman sources representing 143 different serotypes in 33 somatic groups; several serotypes had not been previously reported. The 374 cultures from humans represent 71 different serotypes; extraintestinal isolates were present in 31 (44%) serotypes. Compared with data from a previous 20 years of surveillance, the proportion of Arizona subgroup strains isolated from stools, blood, and other sites was remarkably stable, but several serotypes showed marked changes in their frequency of isolation. In total, the ratio of extraintestinal to intestinal isolates was 0.37, but marked serotype-specific variation was noted, suggesting differences in virulence associated with serotype.


catena-Poly[{μ3-3,3'-[(1,7-dioxa-4,10-di-aza-cyclo-dodecane-4,10-di-yl)bis-(methyl-ene)]dibenzoato}cobalt(II)].
The title compound, [Co(C24H28N2O6)] n , crystallizes as infinite chains related to one another by inversion centers, giving a centrosymmetric coordination polymer. The Co(II) ion, situated on a twofold rotation axis, forms a complex with the crown-4 moiety of the 3,3'-[(1,7-dioxa-4,10-di-aza-cyclo-do-decane-4,10-di-yl)bis-(meth-ylene)]dibenzoate anion. The dis-torted octahedral coordination sphere of the Co(II) ion is completed by two carboxyl-ate O atoms from two bridging intra-chain ligands. Metallomacrocyclic rings of 16 atoms are present, with each ring containing two Co(II) ions and 14 atoms from the bridging ligands. These units repeat as infinite zigzag chains along [101].


Ecomorphological disparity in an adaptive radiation: opercular bone shape and stable isotopes in Antarctic icefishes.
To assess how ecological and morphological disparity is interrelated in the adaptive radiation of Antarctic notothenioid fish we used patterns of opercle bone evolution as a model to quantify shape disparity, phylogenetic patterns of shape evolution, and ecological correlates in the form of stable isotope values. Using a sample of 25 species including representatives from four major notothenioid clades, we show that opercle shape disparity is higher in the modern fauna than would be expected under the neutral evolution Brownian motion model. Phylogenetic comparative methods indicate that opercle shape data best fit a model of directional selection (Ornstein-Uhlenbeck) and are least supported by the "early burst" model of adaptive radiation. The main evolutionary axis of opercle shape change reflects movement from a broad and more symmetrically tapered opercle to one that narrows along the distal margin, but with only slight shape change on the proximal margin. We find a trend in opercle shape change along the benthic-pelagic axis, underlining the importance of this axis for diversification in the notothenioid radiation. A major impetus for the study of adaptive radiations is to uncover generalized patterns among different groups, and the evolutionary patterns in opercle shape among notothenioids are similar to those found among other adaptive radiations (three-spined sticklebacks) promoting the utility of this approach for assessing ecomorphological interactions on a broad scale.