A new genus and family of sejine mites (Acari, Parasitiformes, Mesostigmata, Sejoidea) based on new species from Lord Howe Island and Brazil, and a redescription of Sejus americanus (Banks, 1902).
The Sejoidea currently contains three families (Sejidae, Ichthyostomatogasteridae, Uropodellidae) of enigmatic mesostigmatic mites with a mixture of characters of general distribution in the Parasitiformes (e.g., hypertrichy, tarsus IV with an intercalary sclerite bearing a pair of ventral setae, archispermous mating system) and derived character states both unique (e.g., distinctive female sterno-gential region; first hypostomal setae adjacent and more or less membranous) and apparently convergent with other Mesostigmata (e.g., 2-tined palpal apotele, reduced dorsal sclerotisation in the adult, phoretic deutonymph). In this paper, I review the characters defining the Sejoidea; propose a new genus, Reginacharlottia gen. nov. based on two new species: one from Lord Howe Island, New South Wales, Australia (R. lordhowensis sp. nov.) and one from Bahia State, Brazil (R. braziliensis sp. nov.) and erect a new family, Reginacharlottiidae fam. nov. to accommodate them. These new species share a number of unusual characters not otherwise known in the Sejida, including a plumose interdigital cheliceral excrescence, a highly reduced female genital shield, and a highly modified anal region covered by a pair of hypertrophied preanal setae; the postanal seta is absent. Adult female R. lordhowensis carry up to a dozen eggs that enclose fully developed larvae; the larvae also lack the postanal seta, but have a unique pygidial tubercle that may act as an egg burster. In addition, the female of Sejus americanus (Banks, 1902) is redescribed and the male described for the first time. Sejus species tend to be more typical of the warmer parts of the world, but S. americanus extends well into the boreal forest of Alberta, Canada (56 degrees N). A key to separate the families of Sejoidea is provided.


Outcomes in patients with metastatic renal cell cancer treated with individualized sunitinib therapy: correlation with dynamic microbubble ultrasound data and review of the literature.
Increased sunitinib exposure (area under the curve) is associated with better outcome in metastatic renal cell cancer. Recommendations for dose modification do not take this into account. A treatment strategy, based on individual patient toxicity, was developed to maximize dose and minimize time without therapy for patients who could not tolerate the standard sunitinib schedule of 50mg given for 28 days with a 14-day break (50mg, 28/14). A single-center retrospective review was conducted on patients with metastatic renal cell cancer treated from October 2005 to March 2010. Dose/schedule modifications (DSM) were done to keep toxicity (hematological, fatigue, skin, and gastrointestinal) at ≤ grade 2. DSM-1 was 50mg, 14 days on/7 days off with individualized increases in days on treatment. DSM-2 was 50mg, 7 days on/7 days off with individualized increase in days on treatment. DSM-3 was 37.5mg with individualized 7-day breaks. DSM-4 was 25mg with individualized 7-day breaks. Multivariable analysis was performed for outcome as a function of patient and treatment variables. Overall, 172 patients were included in the analysis. Most patients had clear cell histology (79.1%) with sunitinib given as a first-line therapy in 59%. The DSM-1 and 2 and DSM-3 and 4 groups had a progression-free survival (PFS) (10.9-11.9 mo) and overall survival (OS) (23.4-24.5 mo) that was significantly better than the PFS (5.3 mo; P<0.001) and OS (14.4 mo; P = 0.03 and 0.003) for the standard schedule (50mg, 28/14). DCE-US in a subset of patients showed that maximum antiangiogenic activity was achieved after 14 days on therapy. Individualized sunitinib scheduling based on toxicity may improve PFS and OS. This hypothesis is supported by several other respective data that are reviewed. A confirmatory prospective trial is ongoing.


Synthesis and in vitro carbonic anhydrases and acetylcholinesterase inhibitory activities of novel imidazolinone-based benzenesulfonamides.
New imidazolinone-based benzenesulfonamides 3a-e and 4a-e were synthesized in three steps and their chemical structures were confirmed by 1 H NMR (nuclear magnetic resonance), 13 C NMR, and high-resolution mass spectrometry. The benzenesulfonamides used were sulfacetamide (3a, 4a), sulfaguanidine (3b, 4b), sulfanilamide (3c, 4c), sulfadiazine (3d, 4d), sulfamerazine (3e), and sulfathiazole (4e). The compounds were evaluated against carbonic anhydrase (CA) and acetylcholinesterase (AChE) enzymes to obtain possible drug candidate/s. The lead compounds of the series were 3a and 4a against human CA (hCA) I, whereas 3d and 4a were leads against hCA II in terms of Ki values. Series 4 includes more effective CAs inhibitors than series 3 (except 3d). Series 4 compounds having a nitro group (except 4d) were 3.3-4.8 times more selective inhibitors than their corresponding analogues 3a-d in series 3, in which hydrogen was located in place of the nitro group, by considering Ki values against hCA II. Compounds 3c and 4c, where the sulfanilamide moiety is available, were the leads in terms of AChE inhibition with the lowest Ki values. The use of secondary sulfonamides was a more effective modification on CA inhibition, whereas the primary sulfonamide was the effective substitution in terms of AChE inhibitory potency.


[Problems of variability in weightlessness].
The genetic (cytogenetic) effects of microgravity have been under study for about 30 years. This line of research developed through three periods. Initially, biologists raised the question whether microgravity may act as a lethal factor or a strong mutagen. Many flight experiments gave a negative answer to it. The major goal of the second period was to identify the effects of microgravity at the chromosomal and cellular levels. Such effects, statistically significant although small in value, were detected in Tradescantia paludosa and Drosophila melanogaster microspores. These findings were confirmed by American and--later--by European investigators. The third period addresses the entire problem of variability in microgravity. This approach can be implemented on the basis of a comprehensive program of research that will include experiments at different levels: from the gene to the population level. The basic objective of the program is to clarify the role of the genetic apparatus in the adaptation of living systems to microgravity and, consequently, to determine the role of gravity in the evolution of life on the Earth.


Natural history of periodontitis: Disease progression and tooth loss over 40 years.
To assess long-term attachment and periodontitis-related tooth loss (PTL) in untreated periodontal disease over 40 years. Data originated from the natural history of periodontitis study in Sri Lankan tea labourers first examined in 1970. In 2010, 75 subjects (15.6%) of the original cohort were re-examined. PTL over 40 years varied between 0 and 28 teeth (mean 13.1). Four subjects presented with no PTL, while 12 were edentulous. Logistic regression revealed attachment loss as a statistically significant covariate for PTL (p < .004). Markov chain analysis showed that smoking and calculus were associated with disease initiation and that calculus, plaque, and gingivitis were associated with loss of attachment and progression to advanced disease. Mean attachment loss <1.81 mm at the age of 30 yielded highest sensitivity and specificity (0.71) to allocate subjects into a cohort with a dentition of at least 20 teeth at 60 years of age. These results highlight the importance of treating early periodontitis along with smoking cessation, in those under 30 years of age. They further show that calculus removal, plaque control, and the control of gingivitis are essential in preventing disease progression, further loss of attachment and ultimately tooth loss.


Neisseria dumasiana sp. nov. from human sputum and a dog's mouth.
Three independent isolates of Gram-reaction-negative cocci collected from two New York State patients and a dog's mouth in California were subjected to a polyphasic analysis. The 16S rRNA gene sequence similarity among these isolates is 99.66 to 99.86 %. The closest species with a validly published name is Neisseria zoodegmatis (98.7 % 16S rRNA gene sequence similarity) with six additional species of the genus Neisseria with greater than 97 % similarity. Average nucleotide identity (ANI) and genome-to-genome distance calculator (GGDC 2.0) analysis on whole genome sequence data support the three novel isolates as being from a single species that is distinct from all other closely related species of the genus Neisseria. Phylogenetic analysis of 16S rRNA gene sequences and ribosomal multilocus sequence typing (rMLST) indicate the novel species belongs in the genus Neisseria. This assignment is further supported by the predominant cellular fatty acids composition of C16 : 0, summed feature 3 (C16 : 1ω7c/C15 : 0iso 2-OH), and C18 : 1ω7c, and phenotypic characters. The name Neisseria dumasiana sp. nov. is proposed, and the type strain is 93087T (=DSM 104677T=LMG 30012 T).


Teaching invasive perinatal procedures: assessment of a high fidelity simulator-based curriculum.
Learning curves pose a difficult problem in the teaching of technical skills: how do you teach procedural skills without compromising patients' health? A simulator-based curriculum has been designed to minimize the risks to patients undergoing amniocentesis by shifting the learning curve away from patients and into the laboratory. This study evaluated the effectiveness of a high-fidelity simulator-based curriculum in improving the performance of amniocentesis by obstetric trainees. Thirty trainees received a course on the practice of amniocentesis. The curriculum consisted of a lecture, a syllabus, and a hands-on training session with the simulator. Pre- and post-training performance were evaluated with two rating scales. Training and performance evaluation were completed using the same simulator. The effectiveness of the simulator-based workshop and the effect of year of training were assessed using a two-way analysis of variance. Performance scores improved from a mean score of 55% to 94% using checklist scoring and from 57% to 88% using global ratings. The two-way analysis of variance revealed a significant effect of training (F1,60 = 43.57; P < 0.001) accounting for 45% of the variance in scores, and a significant effect of experience level (F2,60 = 9.16; P < 0.001) accounting for 25% of the variance in scores. A comprehensive curriculum based on a high-fidelity simulator was effective at improving skills demonstrated on the simulator. The challenge remains to establish that skills acquired on a simulator are transferable to the clinical setting.


Successful Treatment with Fusidic Acid in a Patient with Folliculitis Decalvans.
Dear Editor, Folliculitis decalvans (FD) is a rare form of primary neutrophilic cicatricial alopecia. It is a highly distressing disease that affects young and middle-aged adults, with a slight male predominance (1). The most frequent clinical manifestations are follicular pustules and diffuse and perifollicular erythema that heal with centrifugal scarring. Follicular tufting, erosions, and hemorrhagic crusts can also be present, and this alopecia is most often located at the vertex and occipital area. Patients frequently complain about pain, itching, or burning sensations, and the involvement of other body areas is rare (2). The pathogenesis of this disease remains unclear. Staphylococcus aureus and other hair follicle bacteria can often be isolated from the pustules, suggesting the role of a bacterial infection in its etiology. A defect in the host's immune response can also be postulated by reports of familial cases and the appearance of FD in patients with immunity dysfunctions. Other mechanical factors have been suggested, such as structural abnormalities of the follicle or local inflammation (2). Management of this alopecia is difficult and its course is typically chronic and relapsing. The treatment aim is to stop inflammation and further irreversible destruction of hair follicles. Antibiotics remain the first-line therapy, due both to their anti-inflammatory and antimicrobial properties (1). Although topical fusidic acid is widely used as adjuvant treatment, there are few data regarding its oral use. We report a case of folliculitis decalvans successfully treated with oral fusidic acid. Our patient was a 41-year old Cape Verdean woman with a two month history of alopecia with painful, purulent discharge at the vertex of the scalp. The patient was diagnosed with human immunodeficiency virus type 1 (HIV-1) infection 5 years prior and was stable on her regimen of efavirenz, tenofovir, and emtricitabine, with undetectable viral load. She denied application of topical or capillary products. Dermatological examination revealed a patch of cicatricial alopecia with crusts and follicular pustules (Figure 1). Direct microscopic examination and mycological culture showed no fungal element. A diagnosis of folliculitis decalvans was established and the patient was started on oral fusidic acid at a dose of 500 mg three times a day. Betamethasone dipropionate 0.05% and salicylic acid 3% lotion as well as azelaic acid 5% lotion were also applied to the affected area once daily. After two months of treatment, the patient showed clinical improvement, with less erythema and suppuration of the affected scalp. A partial hair regrowth was noted, mainly at the periphery. Subsequently the patient maintained only topical therapy, and no recurrences were observed after 6-months of follow-up. Fusidic acid is useful in the treatment of skin and soft tissue infections, particularly those due to S. aureus, as shown by randomized controlled studies (3). The clinical efficacy of fusidic acid in the treatment of folliculitis decalvans has been reported previously. Bogg was the first to describe this useful effect (4). Sutter also reported good results with fusidic acid used both topically and orally (500 mg three times a day) (5). However, both failed to report the treatment duration or the outcome on discontinuation. Abeck described three patients that responded to a three week oral course of fusidic acid (500 mg three times a day) and to a maintenance treatment with zinc sulfate (4). During the following year, recurrence was observed in only one patient after ending zinc sulfate therapy. Oral antibiotics are frequently used to treat folliculitis decalvans. Tetracyclines and the combination of clindamycin with rifampicin are the most commonly used (2). However, the disease usually progresses when treatment is stopped. Fusidic acid is an anti-staphylococcal drug with few adverse effects. It is highly bioavailable orally, and has a long plasma half-life. Despite years of clinical use in numerous countries, resistance rates remain at low levels to date (6). Since clinical series or cases including ours have shown good results, this drug should not be forgotten when considering treatment options for folliculitis decalvans.


Assessing alexithymia across negative and positive emotions: Psychometric properties of the Polish version of the Perth Alexithymia Questionnaire.
The Perth Alexithymia Questionnaire (PAQ) is a 24-item self-report measure of alexithymia. Originally developed in English, it was designed to try to enable more comprehensive (i.e., facet-level and valence-specific) alexithymia assessments. This study aimed to introduce and validate a Polish version of the PAQ. Our sample were 1,008 people (69.44% females, 30.06% males and 0.50% non-binary) aged 18-78 (M = 29.69, SD = 14.15) from the general community. The PAQ's factor structure was verified with confirmatory factor analysis, and convergent and divergent validity were assessed via relationships with other measures of alexithymia and mental health symptoms. Our results indicated strong factorial validity, conforming to the intended subscale structure. As expected, all PAQ subscales correlated in expected directions with another established alexithymia measure, and markers of depression, anxiety, and stress symptoms. The PAQ showed good discriminant validity in terms of measuring an alexithymia construct that was separable from people's current level of distress. Test-retest and internal consistency reliabilities were also good. Overall, the Polish PAQ therefore appears to have strong psychometric properties. Our findings add to a growing body of literature supporting the validity of the PAQ, and the multidimensional nature of the alexithymia construct, across different nations and languages.


Background, experience of abuse, and mental health among adolescents in out-of-home care: a cross-sectional study of a Swedish high school national sample.
To compare experiences for adverse events, especially sexual abuse, and mental health in a group of high school students in out-of-home care with a representative sample of peers of the same age and similar educational attainment living with their parents. A sample of 5839 students in the third year of Swedish high school, corresponding to a response rate of 59.7%, answered a study specific questionnaire. Data from 41 students living in out-of-home care were compared with data from peers not in out-of-home care in a cross-sectional analyze. Students in out-of-home care had more often an immigrant background and a non-heterosexual orientation, had more often experienced physical and penetrative sexual abuse, and more often sought healthcare for mental problems. Disclosure of sexual abuse was less common, and acts of persuasion or adults' use of their social position was more common among students in out-of-home care. Even where the protective factor 'senior educational attainment' is present, risks for abuse and poor mental health are evident for adolescents in out-of-home care. Disclosure of adversity, when it has occurred, ought to be higher among these adolescents with regular contact with social services, but our findings indicate tendencies for the opposite. We therefore suggest routines to be established to screen for adverse life events and mental health actively, along with general and systematic assessments of adversity and mental health during care.


Aging of the trigeminal blink system.
This study characterizes trigeminal blinks in normal human subjects between 20 and 80 years of age, 60-year-old Parkinson's disease patients, and young and old guinea pigs. In normal humans over 60 years of age, lid-closing duration, and the excitability and latency of the trigeminal reflex blink increase significantly relative to younger subjects. Aged guinea pigs appear to display similar increases in reflex blink duration and latency. Reflex blink amplitude, however, does not change consistently with age. For subjects less than 70 years of age, a unilateral trigeminal stimulus evokes a 37% larger blink in the eyelid ipsilateral to the stimulus than in the contralateral eyelid, but 70-year-olds exhibit blinks of equal amplitude. In all cases, blink duration is identical for the two eyelids. If normal, age-related loss of dopamine neurons explains these trigeminal blink modifications, then Parkinson's disease should exaggerate age-related changes in these blink parameters. Preliminary data show that Parkinson's disease increases blink duration and excitability relative to age-matched control subjects. Thus, it seems likely that normal, age-related loss of dopamine neurons accounts for increases in trigeminal blink excitability and duration. A previously uncharacterized type of trigeminally evoked blink appears after age 40 in humans and in aged guinea pigs. In subjects less than 40 years old, a single trigeminal stimulus elicits a single reflex blink. In subjects over age 40, however, a single stimulus frequently evokes a reflex blink and additional blinks that occur at a fixed interval relative to the preceding blink. These "blink oscillations" may arise from oscillatory processes within trigeminal reflex blink circuits. The presence of exaggerated blink oscillations in subjects with dry eye and benign essential blepharospasm suggests that an alteration of blink oscillation mechanisms plays a critical role in these disorders.


Teflon granuloma in the nasopharynx: a potentially false-positive PET/CT finding.
Positron emission tomography (PET) has become a critical diagnostic tool in the discovery and staging of malignancies in the head and neck. Although PET is accurate for detecting cancer, increased 18 F-fluorodeoxyglucose (FDG) uptake can be seen in healthy tissues such as muscle, fat, and glands and uptake can be seen in tissues affected by inflammation or granulomatous disease. Combined PET and CT (PET/CT) can often overcome these difficulties by fusing anatomic and physiological data, but radiographic findings of some disease processes can be confusing even with fused imaging techniques. We present two cases of FDG uptake in the posterior pharynx, localized by combined PET/CT, which was initially interpreted as squamous cell carcinoma. The increased activity was ultimately attributed to Teflon-induced granulomas. It is important for radiologists to recognize potential causes of false-positive PET/CT findings to improve our diagnostic accuracy and to avoid unnecessary biopsies and surgeries.


Conformational properties of amphotericin B amide derivatives--impact on selective toxicity.
Even though it is highly toxic, Amphotericin B (AmB), an amphipathic polyene macrolide antibiotic, is used in the treatment of severe systemic fungal infections as a life-saving drug. To examine the influence of conformational factors on selective toxicity of these compounds, we have investigated the conformational properties of five AmB amide derivatives. It was found that the extended conformation with torsional angles (phi,psi)=(290 degrees,180 degrees) is a common minimum of the potential energy surfaces (PES) of unsubstituted AmB and its amide derivatives. The extended conformation of the studied compounds allows for the formation of an intermolecular hydrogen bond network between adjacent antibiotic molecules in the open channel configuration. Therefore, the extended conformation is expected to be the dominant conformer in an open AmB (or its amide derivatives) membrane channel. The derivative compounds for calculations were chosen according to their selective toxicity compared to AmB and they had a wide range of selective toxicity. Except for two AmB derivatives, the PES maps of the derivatives reveal that the molecules can coexist in more than one conformer. Taking into account the cumulative conclusions drawn from the earlier MD simulation studies of AmB membrane channel, the results of the potential energy surface maps, and the physical considerations of the molecular structures, we hypothesize a new model of structure-selective toxicity of AmB derivatives. In this proposed model the presence of the extended conformation as the only well defined global conformer for AmB derivatives is taken as the indicator of their higher selective toxicity. This model successfully explains our results. To further test our model, we also investigated an AmB derivative whose selective toxicity has not been experimentally measured before. Our prediction for the selective toxicity of this compound can be tested in experiments to validate or invalidate the proposed model.


Is diabetes mellitus a heart disease equivalent in women? Results from an international study of postmenopausal women in the Raloxifene Use for the Heart (RUTH) Trial.
Several studies have concluded that diabetes mellitus and heart disease carry similar risk for future cardiovascular disease (CVD). Most of these studies were too small to quantify independent risks specific to women. The purpose of this study was to determine whether diabetes mellitus is a coronary heart disease (CHD) risk equivalent for prediction of future CHD and CVD events in women. The Raloxifene Use for the Heart (RUTH) trial was an international, multicenter, double-blind, randomized, placebo-controlled trial of raloxifene and CVD outcomes in 10 101 postmenopausal women selected for high CHD risk. Of these, 3672 had a history of diabetes mellitus without known CHD, and 3265 had a history of CHD without known diabetes mellitus. Cox proportional hazard models were used to compare cardiovascular outcomes in these 2 groups. Mean age at baseline was 67.5 years; median follow-up was 5.6 years. There were 725 deaths, including 450 cardiovascular deaths. In age-adjusted analyses, diabetic women had an increased risk of all-cause mortality compared with women with CHD. Although the overall risk of CHD and CVD was lower in diabetic women compared with women with CHD, the risk of fatal CHD, fatal CVD, and all-cause mortality was similar (hazard ratio [95% confidence interval]: 0.85 [0.65-1.12], 0.99 [0.78-1.25], and 1.18 [0.98-1.42], respectively, after adjusting for age, lifestyle factors, CHD risk factors, statin use, and treatment assignment). In the RUTH trial, diabetes mellitus was a CHD risk equivalent in women for fatal, but not nonfatal, CHD and CVD.


A synthetic enzyme built from DNA flips 107 lipids per second in biological membranes.
Mimicking enzyme function and increasing performance of naturally evolved proteins is one of the most challenging and intriguing aims of nanoscience. Here, we employ DNA nanotechnology to design a synthetic enzyme that substantially outperforms its biological archetypes. Consisting of only eight strands, our DNA nanostructure spontaneously inserts into biological membranes by forming a toroidal pore that connects the membrane's inner and outer leaflets. The membrane insertion catalyzes spontaneous transport of lipid molecules between the bilayer leaflets, rapidly equilibrating the lipid composition. Through a combination of microscopic simulations and fluorescence microscopy we find the lipid transport rate catalyzed by the DNA nanostructure exceeds 107 molecules per second, which is three orders of magnitude higher than the rate of lipid transport catalyzed by biological enzymes. Furthermore, we show that our DNA-based enzyme can control the composition of human cell membranes, which opens new avenues for applications of membrane-interacting DNA systems in medicine.


[Use of the immunoperoxidase method for the rapid detection of togaviruses, orthopoxviruses and their antibodies].
The successful application of the immunoperoxidase method of (IP) with light microscopy for rapid detection of certain togaviruses and orthopoxviruses and antibodies to them is described. A comparative evaluation of the IP and immunofluorescent (IF) method for these purposes was performed. The results indicate practically similar sensitivity and specificity of both methods. The detection of viral antigen directly depended upon the infective dose and time of examinations (within 4--12 hours postinoculation). In evaluating the IP method, however, the account should be taken of the fact that it does not require expensive equipment and therefore may be used in any practical laboratory or even under field conditions. Rapid detection of both viral antigens and antiviral antibody by this method opens approaches for its wide application in the future.


Knowledge, attitude and practice survey of bacterial contamination of blood for transfusion in the Democratic Republic of the Congo.
We assessed healthcare worker's knowledge-attitude-practice regarding bacterial contamination of blood products in the Democratic Republic of the Congo. In three hospitals and the National Blood Transfusion Centre (NBTC), two multiple-choice surveys were completed on a tablet computer: one each, for blood bank (31 questions) and for clinical ward staff (20 questions). A score was calculated for 11 overlapping knowledge questions. Among 247 participants (blood bank No.=62, ward No.=185), median (range) knowledge score was 10 (2-19) on a maximum of 20, with blood bank staff (12/20) scoring higher than clinical ward staff (9/20) (p<0.0001). Half (50.2%) of 247 participants recalled previous training in transfusion medicine. Participants had limited understanding of and compliance with NBTC-recommended preventive measures: incorrect assumption that wearing gloves prevents bacterial contamination (83.8%) and that blood banks test donor blood for bacteria (59.9%). Half (50.0%) of blood bank staff did not acknowledge the NBTC-recommended antisepsis procedure, 62.1% did not apply the appropriate number of antisepsis steps, and 32.3% saw no harm in touching the venipuncture site after antisepsis. Presence of bacteria on healthy skin (62.3%) and blood bank fomites (examination gloves: 30.8%, soap: 62.8%) was underestimated. Although 92.4% of clinical ward staff said to easily recognize transfusion reactions, only 15.7% recognized septic reactions and post-transfusion antibiotic treatment practices were not consistent. Challenges reported by blood bank staff and particular for low-resource settings were: frequent power cuts (98.4%), transport of blood products by patient attendants (41.1%), without cooling elements (64.4%), and reuse of finished antiseptic/disinfectant containers (75.4%). The present study points to gaps in knowledge, attitudes, practices along sampling, cold chain and transfusion which can feed customized training and monitoring.


Agomelatine, venlafaxine, and running exercise effectively prevent anxiety- and depression-like behaviors and memory impairment in restraint stressed rats.
Several severe stressful situations, e.g., natural disaster, infectious disease out break, and mass casualty, are known to cause anxiety, depression and cognitive impairment, and preventive intervention for these stress complications is worth exploring. We have previously reported that the serotonin-norepinephrine-dopamine reuptake inhibitor, venlafaxine, as well as voluntary wheel running are effective in the treatment of anxiety- and depression-like behaviors in stressed rats. But whether they are able to prevent deleterious consequences of restraint stress in rats, such as anxiety/depression-like behaviors and memory impairment that occur afterward, was not known. Herein, male Wistar rats were pre-treated for 4 weeks with anti-anxiety/anti-depressive drugs, agomelatine and venlafaxine, or voluntary wheel running, followed by 4 weeks of restraint-induced stress. During the stress period, rats received neither drug nor exercise intervention. Our results showed that restraint stress induced mixed anxiety- and depression-like behaviors, and memory impairment as determined by elevated plus-maze, elevated T-maze, open field test (OFT), forced swimming test (FST), and Morris water maze (MWM). Both pharmacological pre-treatments and running successfully prevented the anxiety-like behavior, especially learned fear, in stressed rats. MWM test suggested that agomelatine, venlafaxine, and running could prevent stress-induced memory impairment, but only pharmacological treatments led to better novel object recognition behavior and positive outcome in FST. Moreover, western blot analysis demonstrated that venlafaxine and running exercise upregulated brain-derived neurotrophic factor (BDNF) expression in the hippocampus. In conclusion, agomelatine, venlafaxine as well as voluntary wheel running had beneficial effects, i.e., preventing the restraint stress-induced anxiety/depression-like behaviors and memory impairment.


Does the public think it is reasonable to wait for more evidence before funding innovative health technologies? The case of PET scanning in Ontario.
Many innovative health technologies do not have a sufficient evidence-base to allow for adequate assessment of their benefits. Funders in several countries have been exploring arrangements that allow for temporary or partial coverage of these technologies, but only as part of a further evaluation. The public's support of arrangements that restrict access to innovative technology until sufficient evidence is available is crucial if these arrangements are going to remain viable. The project's other objective is to examine the lay public's views on a case in which patients' publicly funded access to an innovative health technology is being delayed until there is sufficient evidence to justify a coverage decision. The case considered is the Ontario (Canada) government's decision to restrict access to positron emission tomography (PET) scans until further evidence becomes available. The case was deliberated on by twenty-six members of the Toronto Health Policy Citizens' Council, with a follow-up survey administered to individual council members. The majority of council members agreed that the approach taken by the government was reasonable and in the best interests of its citizens. The council did express concerns regarding certain aspects of the case, including about the length of time it is taking to obtain further evidence. Public support for arrangements that limit access to new technologies will likely vary depending on the details of the specific arrangement being proposed. Deliberative public dialogue can be effectively used to identify cases the general public is most likely to support.


Cumulative incidence of rheumatic fever in an endemic region: a guide to the susceptibility of the population?
Aboriginal Australians in northern Australia are subject to endemic infection with group A streptococci, with correspondingly high rates of acute rheumatic fever and rheumatic heart disease. For 12 communities with good ascertainment, the estimated lifetime cumulative incidence of acute rheumatic fever was approximately 5.7%, whereas over the whole population, with less adequate ascertainment, the cumulative incidence was only 2.7%. The corresponding prevalences of established rheumatic heart disease were substantially less than the cumulative incidences of acute rheumatic fever, at least in part because of poor ascertainment. The cumulative incidence of acute rheumatic fever estimates the proportion of susceptible individuals in endemically exposed populations. Our figures of 2.7-5.7% susceptible are consistent with others in the literature. Such comparisons suggest that the major part of the variation in rheumatic fever incidence between populations is due to differences in streptococcal exposure and treatment, rather than to any difference in (genetic) susceptibility.


Diagnostic implications of parasite-specific immune responses in immunocompromised patients with strongyloidiasis.
Parasite-specific humoral and cellular immune responses were evaluated in in nine immunosuppressed patients with Strongyloides stercoralis infection. Four patients had the disseminated form of the disease, and five had serious manifestations without evidence of hyperinfection. All patients had high levels of immunoglobulin G (IgG) antibodies directed against S. stercoralis larval antigens as detected by the enzyme-linked immunosorbent assay. Seven patients had both elevated total serum IgE and parasite-specific IgE antibodies detected by a modified radioimmunoassay. The hyperinfected patients differed significantly from the nonhyperinfected group in total and specific IgE levels and peripheral eosinophilia but not in specific IgG levels. None of the patients tested exhibited significant in vitro lymphoproliferative responses to parasite antigens. Our results indicated that the possibility of a protective role of IgE and eosinophils in strongyloidiasis deserves further investigation. In addition, we suggest that the enzyme-linked immunosorbent assay for specific IgG antibodies may have an important place in the diagnosis of strongyloidiasis in immunocompetent as well as in immunocompromised patients.


Single cell kinase signaling assay using pinched flow coupled droplet microfluidics.
Droplet-based microfluidics has shown potential in high throughput single cell assays by encapsulating individual cells in water-in-oil emulsions. Ordering cells in a micro-channel is necessary to encapsulate individual cells into droplets further enhancing the assay efficiency. This is typically limited due to the difficulty of preparing high-density cell solutions and maintaining them without cell aggregation in long channels (>5 cm). In this study, we developed a short pinched flow channel (5 mm) to separate cell aggregates and to form a uniform cell distribution in a droplet-generating platform that encapsulated single cells with >55% encapsulation efficiency beating Poisson encapsulation statistics. Using this platform and commercially available Sox substrates (8-hydroxy-5-(N,N-dimethylsulfonamido)-2-methylquinoline), we have demonstrated a high throughput dynamic single cell signaling assay to measure the activity of receptor tyrosine kinases (RTKs) in lung cancer cells triggered by cell surface ligand binding. The phosphorylation of the substrates resulted in fluorescent emission, showing a sigmoidal increase over a 12 h period. The result exhibited a heterogeneous signaling rate in individual cells and showed various levels of drug resistance when treated with the tyrosine kinase inhibitor, gefitinib.


Screening of seaweeds in the East China Sea as potential bio-monitors of heavy metals.
Seaweeds are good bio-monitors of heavy metal pollution and have been included in European coastal monitoring programs. However, data for seaweed species in China are scarce or missing. In this study, we explored the potential of seaweeds as bio-monitor by screening the natural occurring seaweeds in the "Kingdom of seaweed and shellfish" at Dongtou Islands, the East China Sea. Totally, 12 seaweed species were collected from six sites, with richness following the sequence of Rhodophyta > Phaeophyta > Chlorophyta. The concentration of heavy metals (Cu, Cr, Ni, Zn, Pb, Cd, As) in the seaweeds was determined, and the bioaccumulation coefficient was calculated. A combination of four seaweeds, Pachydictyon coriaceum, Gelidium divaricatum, Sargassum thunbergii, and Pterocladiella capillacea, were proposed as bio-monitors due to their high bioaccumulation capabilities of specific heavy metals in the East China Sea and hence hinted the importance of using seaweed community for monitoring of pollution rather than single species. Our results provide first-hand data for the selection of bio-monitor species for heavy metals in the East China Sea and contribute to selection of cosmopolitan bio-monitor communities over geographical large area, which will benefit the establishment of monitoring programs for coastal heavy metal contamination.


A novel advance directives course provides a transformative learning experience for medical students.
Inadequate physician training may be a barrier to physician-patient discussions of advance directives (ADs). The purpose of this study was to determine the effects of an ADs course, which includes completing a directive, on medical students' perceived knowledge of and preparedness for discussing ADs with patients. All 4th-year medical students completed a 10-hr bioethics course comprising interactive lecture and small-group discussion formats. Curriculum content included ethical and legal aspects of ADs. An 8-item survey with free-text entry was administered 1 month after course completion. Internal consistency reliability of survey scores was determined. Two authors independently coded the free-text comments and reached consensus on underlying themes. Of the 89 students who completed the survey (response rate 80%), 87 (98%) felt more knowledgeable and 88 (99%) better equipped to counsel patients about ADs. Forty-two (47%) reported they had counseled others to complete ADs during the month after the course. Internal consistency reliability of survey scores was very good (Cronbach's alpha =.78). Dominant themes of responses to the question, "What was the most eye opening, troubling, or difficult aspect about filling out your advance directive?" included difficulties articulating wishes, legal language, selecting a surrogate, and facing mortality. These findings suggest an ADs course that includes completing a directive enhances medical students' empathy for and preparedness to discuss ADs with patients.


Restorative Qualities of and Preference for Natural and Urban Soundscapes.
Psychological restoration in urban agglomerations has become a growing challenge. Although scientific proof of the significance of nature is irrefutable, an increase in built-up areas has led to a decrease in urban greenery. Thus, a growing need for restorativeness in urban surroundings has emerged. To investigate whether positively evaluated sonic environments, represented by natural and urban sounds, have comparable restorative qualities we conducted two studies. The aim of the first (Study 1) was to explore the restorative qualities of positively assessed natural and urban sounds. Participants (N = 88) were asked to listen and to rate 22 recordings (each 1 min long) either from natural or urban environments. In the second (Study 2) we investigated whether positively evaluated sonic environments (natural and urban), demand for restoration (feeling relaxed or fatigued) and company (being alone or with a friend) affect the restorative qualities of natural and urban soundscapes. After reading assigned scenarios (feeling relaxed or fatigued; being alone or with a friend), participants (N = 120) were asked to imagine a walk in presented sonic environments and to complete forms (one for each sonic environment) concerning the restorative qualities of given soundscapes (natural and urban). Top five recordings of natural and urban sonic environments were selected from Study 1 and combined into a 154-s soundtrack, to provide a background for the imagined walks in both settings. Our findings confirmed that natural sounds are perceived more favorably than urban recordings. Even when only the most positively assessed soundscapes were compared, nature was still perceived as being more restorative than urban areas. Company of a friend was found to be more beneficial in the urban surroundings, particularly when there was no need for restoration.


Meta-analysis of the effects of academic interventions and modifications on student behavior outcomes.
The current study examined the effect of academic interventions and modifications on behavioral outcomes in a meta-analysis of 32 single-case design studies. Academic interventions included modifying task difficulty, providing instruction in reading, mathematics, or writing, and contingent reinforcement for academic performance. There was an overall small to moderate effect (ϕ = .56) on behavioral outcomes, with a stronger effect on increasing time on task (ϕ = .64) than on decreasing disruptive behavior (ϕ = .42). There was a small effect for using a performance-based contingent reinforcer (ϕ = .48). Interventions completed in an individual setting resulted in a moderate to large effects on behavior outcomes. Results of the current meta-analysis suggest that academic interventions can offer both positive academic and behavioral outcomes. Practical implications and suggestions for future research are included. (PsycINFO Database Record


Effects of micromolar concentrations of free calcium ions on the reduction of heart mitochondrial NAD(P) by 2-oxoglutarate.
1. The reduction of mitochondrial NAD(P) by 2-oxoglutarate was monitored as a measure of 2-oxoglutarate dehydrogenase activity in its intramitochondrial locale. In the absence of ADP, steady-state reduction of NAD(P) by 0.5 mM-2-oxoglutarate in the presence of 0.5 mM-L-malate was markedly increased by extramitochondrial Ca2+, with 50% activation at pCa 6.58, when the Na+ concentration was 10 mM, the Pi concentration ws 5 mM and the added Mg2+ concentration was 1 mM. Omission of Pi resulted in 50% activation at pCa 6.77; omission of Mg2+ resulted in 50% activation at pCA greater than or equal to 7.3. 2. The activation of 2-oxoglutarate dehydrogenase could be reversed on addition of an excess of EGTA. The rate of inactivation was dependent on the concentration of Na+, with K0.5 2.5 mM, which is consistent with the rate of withdrawal of Ca2+ from the mitochondria being the limiting factor. 3. The steady-state reduction of cytochrome c by 2-oxoglutarate (0.5 mM) also showed a marked dependence on pCa in the absence of ADP; in the presence of an excess of ADP, no such effect of Ca2+ was detectable. 4. Mitochondria from the hearts of senescent rats showed an undiminished rate of dehydrogenase activation by Ca2+ but a rate of inactivation by excess EGTA that was diminished by 40%. Direct studies of Ca2+ egress with Arsenazo III confirmed a decrement in rate with old age. 5. Studies of 2-oxoglutarate dehydrogenase activity as a function of the mitochondrial context of Ca2+, as measured by atomic-absorption spectrophotometry, showed half-maximal activation at a mitochondrial content of 1.0 nmol of Ca2+/mg of protein, and saturation at 3 nmol/mg. 6. These findings support the model advanced by Denton, Richards & Chin [(1978) Biochem. J. 176, 899-906], of a control of the tricarboxylate cycle by intramitochondrial Ca2+, and demonstrate the range of mitochondrial Ca2+ content over which this may occur. In addition, they raise the possibility of a disturbance of this control mechanism in old age.


The phenotypic spectrum and genotype-phenotype correlations in 106 patients with variants in major autism gene CHD8.
CHD8, a major autism gene, functions in chromatin remodelling and has various roles involving several biological pathways. Therefore, unsurprisingly, previous studies have shown that intellectual developmental disorder with autism and macrocephaly (IDDAM), the syndrome caused by pathogenic variants in CHD8, consists of a broad range of phenotypic abnormalities. We collected and reviewed 106 individuals with IDDAM, including 36 individuals not previously published, thus enabling thorough genotype-phenotype analyses, involving the CHD8 mutation spectrum, characterization of the CHD8 DNA methylation episignature, and the systematic analysis of phenotypes collected in Human Phenotype Ontology (HPO). We identified 29 unique nonsense, 25 frameshift, 24 missense, and 12 splice site variants. Furthermore, two unique inframe deletions, one larger deletion (exons 26-28), and one translocation were observed. Methylation analysis was performed for 13 patients, 11 of which showed the previously established episignature for IDDAM (85%) associated with CHD8 haploinsufficiency, one analysis was inconclusive, and one showing a possible gain-of-function signature instead of the expected haploinsufficiency signature was observed. Consistent with previous studies, phenotypical abnormalities affected multiple organ systems. Many neurological abnormalities, like intellectual disability (68%) and hypotonia (29%) were observed, as well as a wide variety of behavioural abnormalities (88%). Most frequently observed behavioural problems included autism spectrum disorder (76%), short attention span (32%), abnormal social behaviour (31%), sleep disturbance (29%) and impaired social interactions (28%). Furthermore, abnormalities in the digestive (53%), musculoskeletal (79%) and genitourinary systems (18%) were noted. Although no significant difference in severity was observed between males and females, individuals with a missense variant were less severely affected. Our study provides an extensive review of all phenotypic abnormalities in patients with IDDAM and provides clinical recommendations, which will be of significant value to individuals with a pathogenic variant in CHD8, their families, and clinicians as it gives a more refined insight into the clinical and molecular spectrum of IDDAM, which is essential for accurate care and counselling.


ATR controls the UV-related upregulation of the CDKN1A mRNA in a Cdk1/HuR-dependent manner.
Ultraviolet (UV) light is a carcinogenic agent that upregulates the expression of several genes involved in various cellular processes, including cell cycle checkpoints and apoptosis. The universal cyclin-dependent kinase inhibitor p21(WAF1/Cip1) plays major roles in these processes, and the level of its corresponding message increases several times in response to UV-induced DNA damage. This upregulation is mainly posttranscriptional owing to HuR-dependent mRNA stabilization. Since the protein kinase Atr plays major roles during the cellular response to UV damage, we sought to investigate its possible implication in the stabilization of the p21(WAF1/Cip1) coding mRNA. We have shown that the UV-dependent accumulation of the CDKN1A mRNA is indeed under the control of the Atr protein kinase. Upon UV damage, Atr allows nuclear-cytoplasmic shuttling of the HuR protein, which binds the CDKN1A mRNA and reduces its turnover. This ATR-dependent effect is mediated through UV-related phosphorylation/inactivation of the Cdk1 protein kinase by Atr, which leads to the dissociation of HuR from Cdk1. Indeed, inhibition or shRNA specific knockdown of CDK1 in ATR-deficient cells enhanced the cytoplasmic level of HuR and restored the CDKN1A mRNA upregulation in response to UV damage. These results show that ATR stabilizes the CDKN1A message in response to UV damage through Cdk1-related cytoplasmic accumulation of HuR.


Cross-sectional evaluation of clinical parameters to select high prevalence populations for periodontal disease: the site comparative severity methodology.
Epidemiological studies have shown strong evidence that periodontal disease does not affect all subjects in the same manner. There are subjects and sites with higher risk for disease progression. This study tested parameters to select "a priori" sites and subjects potentially at risk. The data from periodontal clinical examinations of 2273 subjects was used. The clinical loss of attachment was measured in 6 sites per tooth. Using computer software, the patients were distributed into 14 age groups, with intervals of 5 years, from 11 years to greater than 75 years of age. The measure of each site was compared with the average and the median values of the subject age group, with the results indicating site comparative severity (SCS). Three global parameters were calculated: parameter 1 (P1)--percentage of sites with clinical attachment loss >or= 4 mm; parameter 2 (P2)--percentage of sites with clinical attachment loss >or= 7 mm; parameter 3 (P3)--percentage of sites with clinical attachment loss surpassing the median value for the age group by 100% or more. There were 1466 (65%) females and 807 (35%) males. Most subjects had P1, P2 and P3 values less than 30%. Parameter 3 allowed a division of the sample similar to that of Parameters 1 and 2, with the advantage of analyzing the subject in relation to his/her age group. It was suggested that the methodology of SCS is useful for selecting a population with a high disease prevalence, and that cut-off lines between 10% and 20% would be appropriate for using Parameter 3.


Quality of life in short adults.
The use of (costly) growth hormone (GH) treatment in short children is often justified by the assumption that short stature considerably reduces quality of life in adults. We tested this assumption in 5 groups of short adults: 25 patients with isolated GH deficiency; 17 male patients with childhood onset renal failure; 25 women with Turner syndrome and 26 patients who were presented as a child to a paediatrician for idiopathic short stature. A group of 44 short individuals with presumably idiopathic short stature, who had not been presented to a paediatrician for short stature, was sampled from the general population ('normal shorts'). We measured quality of life in terms of socio-economic variables, the Nottingham Health Profile and time trade-off. The mean height of most groups was close to the 3rd percentile. The chance of having a partner was low for all groups, except for the normal shorts. Problems with job application were only reported in Turner syndrome. The scores on the Nottingham Health Profile were all within the normal range, but GH-deficient adults had a higher score on the domain energy than normal shorts. Women with Turner syndrome, individuals with renal failure, and those with idiopathic short stature had a wish to be taller, with an estimated reduction in quality of life of 2-4% (time trade-off). As the normal shorts did not show any sign of a reduced quality of life, we falsify the assumption of a direct relation between short stature and quality of life. The complaints of patients with idiopathic short stature around the 3rd percentile seem to be the result of unsuccessful coping strategies.


Response of macaque bronchiolar epithelium to ambient concentrations of ozone.
Recently, we reported that exposure to ambient concentrations of ozone, near the U.S. National Ambient Air Quality Standard (0.12 ppm), induced significant nasal epithelial lesions in a non-human primate, the bonnet monkey. The present study defines the effects of ambient concentrations of ozone on the surface epithelium lining respiratory bronchioles and on the underlying bronchiolar interstitium in these same monkeys. Bonnet monkeys were exposed to filtered air or to 0.15 or 0.30 ppm ozone 8 hours/day for 6 or 90 days. At the end of exposures, monkeys were anesthetized and killed by exsanguination. Microdissected bronchiolar airways of infusion-fixed lungs were evaluated morphometrically by light microscopy and quantitatively by scanning and transmission electron microscopy for ozone-induced epithelial changes. Hyperplasia of nonciliated, cuboidal epithelial cells and intraluminal accumulation of macrophages characterized ozone-induced lesions in respiratory bronchioles. There were no significant differences in epithelial thickness or cell numbers among ozone-exposed groups. Ozone-exposed epithelium was composed of 80% cuboidal and 20% squamous cells compared with 40% cuboidal and 60% squamous cells in filtered air controls. In addition, the arithmetic mean thickness of the surface epithelium, a measure of tissue mass per unit area of basal lamina, was significantly increased in all of the ozone-exposed groups. The number of cuboidal epithelial cells per surface area of basal lamina was increased above control values by 780% after 6 days exposure to 0.15 ppm, 777% after 90 days to 0.15 ppm, and 996% after 90 days exposure to 0.30 ppm. There was also a significant ozone-induced increase in the thickness of the bronchiolar interstitium that was due to an increase in both cellular and acellular components. These results demonstrate that exposure to low ambient concentrations of ozone, near the current. National Ambient Air Quality Standard, induces pulmonary lesions in primates. The alterations do not appear to be concentration- or time-dependent, suggesting that the current National Ambient Air Quality Standard may be at or above the threshold for deep lung injury in primates.


Intraocular pressure--the cardiac connection.
A retrospective analysis of graphic intraocularpulse waves (IOPW) taken with a pneumotonograph (PTG) revealed abrupt elevations of intraocular pressure (IOP) in a strict-time relationship with the onset of spontaneous or sustained cardiac tachyarrhythmias. This may be explained as a consequence of an increase in central venous pressure from the "back" pressure effect of abnormal diastolic indexes of cardiac function rather than the forward systolic forces (including systolic blood pressure that usually are depressed under these circumstances). Given the frequency of cardiac arrhythmias in the general population, we suggest that continuous graphic IOP tracings, such as with the PTG, will reflect overall IOP levels better than those obtained, for example, by a quick-acting noncontact tonometer. Abnormal indexes of diastolic cardiac function found in many forms of heart disease, including the aging process, merit further consideration as a potential cardiovascular factor affecting ocular pressure dynamics in other circumstances.


Marine methylotrophs revealed by stable-isotope probing, multiple displacement amplification and metagenomics.
The concentrations of one-carbon substrates that fuel methylotrophic microbial communities in the ocean are limited and the specialized guilds of bacteria that use these molecules may exist at low relative abundance. As a result, these organisms are difficult to identify and are often missed with existing cultivation and gene retrieval methods. Here, we demonstrate a novel proof of concept: using environmentally-relevant substrate concentrations in stable-isotope probing (SIP) incubations to yield sufficient DNA for large-insert metagenomic analysis through multiple displacement amplification (MDA). A marine surface-water sample was labelled sufficiently by incubation with near in situ concentrations of methanol. Picogram quantities of labelled (13)C-DNA were purified from caesium chloride gradients, amplified with MDA to produce microgram amounts of high-molecular-weight DNA (<or= 40 kb) and cloned to produce a fosmid library of > 10 000 clones. Denaturing gradient gel electrophoresis (DGGE) demonstrated minimal bias associated with the MDA step and implicated Methylophaga-like phylotypes with the marine metabolism of methanol. Polymerase chain reaction screening of 1500 clones revealed a methanol dehydrogenase (MDH) containing insert and shotgun sequencing of this insert resulted in the assembly of a 9-kb fragment of DNA encoding a cluster of enzymes involved in MDH biosynthesis, regulation and assembly. This novel combination of methodology enables future structure-function studies of microbial communities to achieve the long-desired goal of identifying active microbial populations using in situ conditions and performing a directed metagenomic analysis for these ecologically relevant microorganisms.


How do trained raters take context factors into account when assessing GP trainee communication performance? An exploratory, qualitative study.
Communication assessment in real-life consultations is a complex task. Generic assessment instruments help but may also have disadvantages. The generic nature of the skills being assessed does not provide indications for context-specific behaviour required in practice situations; context influences are mostly taken into account implicitly. Our research questions are: 1. What factors do trained raters observe when rating workplace communication? 2. How do they take context factors into account when rating communication performance with a generic rating instrument? Nineteen general practitioners (GPs), trained in communication assessment with a generic rating instrument (the MAAS-Global), participated in a think-aloud protocol reflecting concurrent thought processes while assessing videotaped real-life consultations. They were subsequently interviewed to answer questions explicitly asking them to comment on the influence of predefined contextual factors on the assessment process. Results from both data sources were analysed. We used a grounded theory approach to untangle the influence of context factors on GP communication and on communication assessment. Both from the think-aloud procedure and from the interviews we identified various context factors influencing communication, which were categorised into doctor-related (17), patient-related (13), consultation-related (18), and education-related factors (18). Participants had different views and practices on how to incorporate context factors into the GP(-trainee) communication assessment. Raters acknowledge that context factors may affect communication in GP consultations, but struggle with how to take contextual influences into account when assessing communication performance in an educational context. To assess practice situations, raters need extra guidance on how to handle specific contextual factors.


[Health surveillance based on social and health indicators (corrected)].
The proposal of Health Surveillance is a techno-assistance model that is still in construction in Brazil. To implement the Health Surveillance proposition, the healthcare professionals have to be prepared to capture and understand the epidemiologic and social profiles of the population. The goal of this study was to identify and classify information about social and health indicators available on the Internet to be used by healthcare professionals. One is about a literature review, performed in several databases. The results show that there is a wide range of information related of health indicators on the Internet, although all this information is a limited instrument for healthcare professionals. The level of aggregation and the focus in morbimortality make the utilization of these databases difficult within the proposal of Health Surveillance. The conclusion of this study notes that research findings based on social and health indicators must be made available in Internet.


A preliminary analysis of the immunoglobulin genes in the African elephant (Loxodonta africana).
The genomic organization of the IgH (Immunoglobulin heavy chain), Igκ (Immunoglobulin kappa chain), and Igλ (Immunoglobulin lambda chain) loci in the African elephant (Loxodonta africana) was annotated using available genome data. The elephant IgH locus on scaffold 57 spans over 2,974 kb, and consists of at least 112 V(H) gene segments, 87 D(H) gene segments (the largest number in mammals examined so far), six J(H) gene segments, a single μ, a δ remnant, and eight γ genes (α and ε genes are missing, most likely due to sequence gaps). The Igκ locus, found on three scaffolds (202, 50 and 86), contains a total of 153 V(κ) gene segments, three J(κ) segments, and a single C(κ) gene. Two different transcriptional orientations were determined for these V(κ) gene segments. In contrast, the Igλ locus on scaffold 68 includes 15 V(λ) gene segments, all with the same transcriptional polarity as the downstream J(λ)-C(λ) cluster. These data suggest that the elephant immunoglobulin gene repertoire is highly diverse and complex. Our results provide insights into the immunoglobulin genes in a placental mammal that is evolutionarily distant from humans, mice, and domestic animals.


Gendered racial microaggressions and black college women: A cross-sectional study of depression and psychological distress.
Objective: We assessed the association between gendered racism, the simultaneous experience of sexism and racism, depression, and psychological distress in Black college women using an intersectional instrument, the gendered racial microaggression scale. Participants: Black college women enrolled at a predominantly white institution (PWI) in the southeastern U.S. (N = 164, response rate = 77%, mean age 21.67). Methods: We used a cross-sectional survey to explore the impact of stress appraisal and frequency of gendered racial microaggressions on depression and psychological distress using validated scales. Results: 30% reported depression and 54% reported severe psychological distress. Correlations indicate significant relationships between gendered racism, depression and psychological distress, with the strongest relation reported between the frequency of gendered racism to depression. Regression analyses suggest significant relationships between gendered racism, depression and psychological distress. Conclusion: Gendered racism has significant bearing on the mental health of Black college women attending a PWI. Implications for interventions are discussed.


A heterologous expression system for bovine lens transmembrane main intrinsic protein (MIP) in Nicotiana tabacum plants.
We have developed a heterologous expression system for transmembrane lens main intrinsic protein (MIP) in Nicotiana tabacum plant tissue. A native bovine MIP26 amplicon was subcloned into an expression cassette under the control of a constitutive Cauliflower Mosaic Virus promoter, also containing a neomycin phosphotransferase operon. This cassette was transformed into Agrobacterium tumefaciens by triparental mating and used to infect plant tissue grown in culture. Recombinant plants were selected by their ability to grow and root on kanamycin-containing media. The presence of MIP in the plant tissues was confirmed by PCR, RT-PCR and immunohistochemistry. A number of benefits of this system for the study of MIP will be discussed, and also its application as a tool for the study of heterologously expressed proteins in general.


Effects of low doses of endothelin-1 on basal vascular tone and autoregulatory vasodilation in canine coronary microcirculation in vivo.
The plasma level of endothelin-1 (ET-1) increases in several cardiovascular disorders. The present study examined whether threshold doses of ET-1 affect vascular tone and autoregulatory vasodilation during a reduction in perfusion pressure in the coronary microcirculation in vivo. In anesthetized open-chest dogs, arterial microvessels in the epimyocardium were observed through a microscope equipped with a floating objective. In 6 dogs, ET-1 (10(-13) to 10(-8)mol/L) was superfused onto the epimyocardium in a cumulative fashion. In another set of dogs (n= 16), the perfusion pressure of the observed vascular bed was reduced to 60 mmHg (mild stenosis) and to 40 mmHg (severe stenosis) by a hydraulic occluder, and the microvascular responses were observed in the presence (n=9) or absence (n=7) of ET-1 (10(-12) or 10(-11) mol/L). ET-1 > or =10(-11) mol/L constricted coronary arterioles (< or =100 microm in diameter) and small arteries (>100 microm in diameter) in a dose-dependent fashion. ET-1 of 10(-12) mol/L affected neither the basal diameters nor the dilation of vessels during the pressure reduction. ET-1 of 10(-11) mol/L decreased the diameters of arterioles and small arteries before and during the mild and severe stenosis. However, ET-1 did not attenuate the percentage dilation of arterioles from the baseline in response to the mild and severe stenosis. The data indicates the following: (1) ET-1 at doses > or =10(-11) mol/L similarly constricts coronary arterioles and small arteries; (2) ET-1 at 10(-11) mol/L, which is slightly higher than the pathophysiological plasma level, increases the basal vascular tone, but does not attenuate the autoregulatory vasodilation of the coronary microcirculation.


Transcriptional profile of spinal dynorphin-lineage interneurons in the developing mouse.
Mounting evidence suggests that the spinal dorsal horn (SDH) contains multiple subpopulations of inhibitory interneurons that play distinct roles in somatosensory processing, as exemplified by the importance of spinal dynorphin-expressing neurons for the suppression of mechanical pain and chemical itch. Although it is clear that GABAergic transmission in the SDH undergoes significant alterations during early postnatal development, little is known about the maturation of discrete inhibitory "microcircuits" within the region. As a result, the goal of this study was to elucidate the gene expression profile of spinal dynorphin (pDyn)-lineage neurons throughout life. We isolated nuclear RNA specifically from pDyn-lineage SDH interneurons at postnatal days 7, 21, and 80 using the Isolation of Nuclei Tagged in Specific Cell Types (INTACT) technique, followed by RNA-seq analysis. Over 650 genes were ≥2-fold enriched in adult pDyn nuclei compared with non-pDyn spinal cord nuclei, including targets with known relevance to pain such as galanin (Gal), prepronociceptin (Pnoc), and nitric oxide synthase 1 (Nos1). In addition, the gene encoding a membrane-bound guanylate cyclase, Gucy2d, was identified as a novel and highly selective marker of the pDyn population within the SDH. Differential gene expression analysis comparing pDyn nuclei across the 3 ages revealed sets of genes that were significantly upregulated (such as Cartpt, encoding cocaine- and amphetamine-regulated transcript peptide) or downregulated (including Npbwr1, encoding the receptor for neuropeptides B/W) during postnatal development. Collectively, these results provide new insight into the potential molecular mechanisms underlying the known age-dependent changes in spinal nociceptive processing and pain sensitivity.


A novel cell-surface antigen expressed on most leukocytes and a minor cortisone-resistant population of thymocytes in rats: characterization by monoclonal antibodies.
A cell-surface antigen on rat lympho-hemopoietic cells was determined by using a monoclonal antibody, R2-1B3 (1B3). The 1B3 antibody, when tested for its reactivity with different hemopoietic cells by cytofluorography with a FACS analyzer, labeled more than 80% of lymph node, spleen, and bone marrow cells and 10-20% of thymus cells. Cytofluorographic analysis performed on purified rat T cells, B cells, macrophages, and granulocytes demonstrated that the antigen defined by 1B3 was readily detectable on all of these cell types, with the greatest expression on B cells. A minor population of thymocytes that were labeled by 1B3 appeared to be cortisone-resistant and were located mainly in the thymic medulla. These 1B3 positive thymic cells seemed to be functionally more mature than 1B3-negative thymus cells as suggested by the fact that the cytotoxic treatment of thymus cells with 1B3 antibody and complement (C) resulted in significant reduction of their responsiveness to phytomitogens and lymphokines derived from concanavalin A (con A) activated rat spleen cell cultures. Immunochemical data showed that 1B3 antibody recognized the broad ill-defined band with a molecular weight of 32K to 47K daltons as estimated by SDS-polyacrylamide gel electrophoresis. These data indicate that the 1B3 defined antigen is distinct from other, previously reported, antigens on rat lymphoid cells including leukocyte-common (L-C) and MRC OX-22 antigens, and that this 1B3 antibody is a useful reagent for analyzing the intrathymic differentiation of T cells in rats.


Synaptic potentials recorded by the sucrose-gap method from the rabbit superior cervical ganglion.
1. Compound ganglionic potentials evoked by stimulation of the preganglionic nerves to the superior cervical ganglion of the rabbit were recorded by the sucrose-gap method.2. When the distal part of the ganglion was bathed in flowing isotonic sucrose solution or sodium-deficient solutions, ganglionic action potentials were no longer evoked, only large synaptic potentials.3. The compound synaptic potential, which remained unaltered for more than 1 h, originated in a population of cells at the interface between the Krebs and sucrose solutions. Hexamethonium reduced the size but did not alter the time course of the synaptic potential.4. It is suggested that a higher concentration of sodium ions is required for the generation of ganglionic action potentials than for either conduction in the postganglionic axons or production of synaptic potentials.5. When lithium replaced sodium in the solution bathing the distal part of the ganglion, the synaptic potential was greatly reduced in amplitude. Impulse propagation in the postganglionic axons was only slightly impaired when lithium replaced sodium in the solution bathing the axons.6. A quantitative assessment of the potency of the ganglion-blocking drugs nicotine, pentolinium, hexamethonium and pempidine was made by measuring the depression of the synaptic potentials produced by bathing the distal part of the ganglion in flowing isotonic sucrose solution. The concentrations which produced a 50% depression were 8.1 muM nicotine, 26.5 muM pentolinium, 111 muM hexamethonium and 22.2 muM pempidine.


Effects of nonstructural carbohydrate concentration in alfalfa on fermentation and microbial protein synthesis in continuous culture.
Insufficient readily fermentable energy combined with extensive degradation of proteins in alfalfa (Medicago sativa L.) may result in poor forage N utilization by ruminants. Using the inherent genetic variability and differences between harvests, our objective was to compare the effect of contrasting concentrations of nonstructural carbohydrates (NSC) in alfalfa on rumen fermentation and microbial protein synthesis. Individual genotypes of the alfalfa cultivar AC Caribou grown near Québec City, Québec, Canada, were harvested at the vegetative and early flowering stages, dried at 55 degrees C, ground, and analyzed for soluble carbohydrates (fructose + sucrose + glucose + pinitol) and starch. Approximately 20 genotypes having, respectively, the highest and lowest NSC concentrations were pooled to constitute 2 contrasted 1-kg forage samples. Samples of high- (17.9% DM) and low- (7.4% DM) NSC alfalfa were respectively allocated to separate dual-flow fermenters in a completely randomized design with 3 replications. Rumen inoculum was obtained from 4 ruminally fistulated cows in early lactation that were fed a TMR with a 50:50 forage to concentrate ratio. A 10-d incubation period was used, with the first 6 d serving as an adaptation period followed by 4 d of sampling with solid and liquid dilution rates in the fermenters set at approximately 2.0 and 4.3%/h, respectively. High versus low NSC concentration in alfalfa significantly enhanced the apparent digestibility of OM (59.1% for high-NSC alfalfa vs. 54.4% for low-NSC alfalfa) and DM (60.0 vs. 54.3%) and the true digestibility of DM (74.1 vs. 64.7%). Increasing NSC concentration in alfalfa (high vs. low) significantly decreased ruminal pH (6.85 vs. 7.08) and NH(3)-N concentration (26.0 vs. 33.6 mg/dL) and increased total VFA concentration (94.9 vs. 83.0mM). Molar proportions of acetate, isobutyrate, and isovalerate significantly decreased, whereas molar proportions of propionate and butyrate significantly increased with high-NSC alfalfa, resulting in a more glucogenic fermentation. More importantly, microbial N flow (263 vs. 230 mg/d) and bacterial N efficiency (41.1 vs. 29.6% of available N), measured using (15)N as a microbial marker, both significantly increased with the high-NSC alfalfa. These results indicate that increasing the concentration of NSC in alfalfa promotes a glucogenic fermentation and enhances microbial N synthesis in the rumen.


Treatment of advanced Parkinson's disease.
Parkinson's disease is a progressive neurological disorder characterized by tremor, bradykinesia, rigidity, gait and postural instability and a variety of nonmotor symptoms. While these and other motor signs typically improve with levodopa, the so-called axial signs, such as dysarthria, dysphagia, postural instability and freezing, and most nonmotor signs, such as depression, cognitive decline and dysautonomia, usually do not respond satisfactorily to levodopa. Furthermore, the use of levodopa may be limited by the development of motor fluctuations, dyskinesias and other adverse effects. This manuscript reviews the medical management of advanced Parkinson's disease, focusing on the treatment of motor fluctuations and dyskinesias and of nonmotor and nonlevodopa responsive symptoms.


Infection reduces return-to-duty rates for soldiers with Type III open tibia fractures.
Infection is a potentially devastating complication following severe lower extremity trauma, but its impact on the outcomes of combat casualties remains unclear. We hypothesize that orthopedic infectious complications will have a negative impact on holistic patient outcome as measured by return-to-duty (RTD) and disability ratings among wounded soldiers. We reviewed the medical records for 115 wounded soldiers who sustained a Type III open tibia fracture and tabulated the prevalence of infectious complications. We searched the Physical Evaluation Board database to determine the disability ratings of soldiers with and without an infection and how many of each group was able to return to active duty service. The average percent disability rating and RTD rates between groups were compared using an unpaired t test and χ test, respectively. Overall, 40% of our cohort had an infectious complication of their fractured limb. Twenty-one soldiers were able to RTD, while 94 could not and were medically retired. Of those medically retired, 44% had an infection. The average percent disability among soldiers with infection was 55%, compared with 47% for those who were not infected (p = 0.1407). Soldiers who experienced any type of infectious complication (p = 0.0470) and having osteomyelitis (p = 0.0335) had a lower chance of RTD compared with those who had no infection. Having a deep soft tissue infection alone showed a strong trend toward decreased RTD rate (p = 0.0558). Infectious complications following severe lower extremity trauma significantly decrease the rate of RTD. In addition, the presence of infectious complications demonstrates a trend toward higher disability ratings in the combat wounded. Prognostic study, level III.


Curriculum-based outdoor learning for children aged 9-11: A qualitative analysis of pupils' and teachers' views.
The relationship between child health, wellbeing and education demonstrates that healthier and happier children achieve higher educational attainment. An engaging curriculum that facilitates children in achieving their academic potential has strong implications for educational outcomes, future employment prospects, and health and wellbeing during adulthood. Outdoor learning is a pedagogical approach used to enrich learning, enhance school engagement and improve pupil health and wellbeing. However, its non-traditional means of achieving curricular aims are not yet recognised beyond the early years by education inspectorates. This requires evidence into its acceptability from those at the forefront of delivery. This study aimed to explore headteachers', teachers' and pupils' views and experiences of an outdoor learning programme within the key stage two curriculum (ages 9-11) in South Wales, United Kingdom. We examine the process of implementation to offer case study evidence through 1:1 interviews with headteachers (n = 3) and teachers (n = 10) and focus groups with pupils aged 9-11 (n = 10) from three primary schools. Interviews and focus groups were conducted at baseline and six months into implementation. Schools introduced regular outdoor learning within the curriculum. This study found a variety of perceived benefits for pupils and schools. Pupils and teachers noticed improvements in pupils' engagement with learning, concentration and behaviour, as well as positive impacts on health and wellbeing and teachers' job satisfaction. Curriculum demands including testing and evidencing work were barriers to implementation, in addition to safety concerns, resources and teacher confidence. Participants supported outdoor learning as a curriculum-based programme for older primary school pupils. However, embedding outdoor learning within the curriculum requires education inspectorates to place higher value on this approach in achieving curricular aims, alongside greater acknowledgment of the wider benefits to children which current measurements do not capture.


[Electrical activity of the rat brain following antenatal hypoxia].
EEG and EPs in the visual and parietal neocortical areas and the hippocampus were studied in freely behaving rats at the age of two-three months after antenatal hypoxia. Increase of spectral power in delta and theta bands and its decrease in alpha and beta bands in the background EEG and in responses to a protracted light stimulation were observed in experimental animals in comparison to control ones. The most pronounced changes were observed in the parietal cortex and hippocampus. The character of changes in latencies and the share of individual EP components recorded point to an accelerated excitation reverberation in neuronal networks in response to afferent stimuli and to a prolongation of after-discharges in the parietal cortex and hippocampus testifying to peculiarity of information processing in these brain structures. On the basis of other authors' data, certain parallelism is supposed to exist between the electrophysiological parameters in experimental animals and some groups of children with mental retardation.


Test method selection, validation against field data, and predictive modelling for impact evaluation of stabilised waste disposal.
In setting criteria for landfill classes in Annex II of the EU Landfill Directive, it proved to be impossible to derive criteria for stabilised monolithic waste due to the lack of information on release and release controlling factors in stabilised waste monofills. In this study, we present a scientific basis, which enables a realistic description of the environmental impact of stabilised waste landfills. The work in progress involves laboratory testing of different stabilisation recipes, pilot scale studies on site and evaluation of field leachate from a full-scale stabilisation landfill. We found that the pHs in run-off and in percolate water from the pilot experiment are both around neutral. The neutral pH in run-off is apparently caused by the rapid atmospheric carbonation of those alkaline constituents that are released. The soil, used as a liner protection layer, controls the release to the subsurface below the landfill. This soil layer buffers pH and binds metals. The modelling results show that the chemistry is understood rather well. Differences between predicted and actual leaching might then be attributed to discrepancies in the description of sorption processes, complexation to organic matter and/or kinetic effects in the leaching tests. We conclude that this approach resulted in a new scientific basis for environmental impact assessment of stabilised waste landfills. The integrated approach has already resulted in a number of very valuable observations, which can be used to develop a sustainable landfill for monolithic waste and to provide guidance for the management of waste to be stabilised (e.g. improved waste mix design).


Identifying the Bridge Between Anxiety Response to COVID-19 and Depression Symptoms in General Population: A Network Analysis.
Previous studies have suggested links between anxiety response to the novel coronavirus (COVID-19) and depression symptoms in general population. However, a symptom-level investigation has not been reported. This study aimed to use network analysis to identify central symptoms and bridge symptoms that link COVID-19 anxiety and depression. Data from 1788 participants were analyzed. Coronavirus anxiety and depression symptoms were measured using the Stress and Anxiety to Viral Epidemics-6 Items Scale and the Patient Health Questionnaire-9, respectively. Network analysis was performed using R. The results revealed 'thoughts of suicide or self-harm' from Patient Health Questionnaire-9 and 'worry about others avoiding me' from Stress and Anxiety to Viral Epidemics-6 Items Scale as bridge symptoms. Findings suggest direct relationship between fear of social isolation and thoughts of suicide or self-harm. 'Feeling tired with little energy' and 'trouble concentrating' are strongly linked to 'thoughts of suicide or self-harm', suggesting these symptoms as risk factors for suicidal or self-injurious thoughts during the pandemic. The findings suggest fear of social isolation as a risk factor for developing thoughts of suicide or self-harm. These results should be taken into account during evaluation of risk of suicide or mental health interventions for the pandemic.


Use of an isolated in situ canine lung perfusion model to evaluate dopamine clearance by the lung.
An isolated in situ lung perfusion model was used to assess dopamine clearance by the lungs in 12 dogs. The preparation consisted of a closed perfusion system in situ, in which systemic arterial blood supply was interrupted. Blood flow to the lungs was maintained at presurgery flow rates. The inflow was restricted to the lungs by the pulmonary arteries and outflow was limited to the pulmonary veins. Pulmonary artery pressure, temperature and pO2 were maintained at physiological levels. After confirmation of a stable base line, one of 3 doses (1, 2, or 5 micrograms/kg/min) of dopamine was infused over 30 min to achieve steady-state blood concentrations, then blood samples were drawn at specified times during and after the infusion. Dopamine plasma concentrations were analyzed by high performance liquid chromatography with electrochemical detection. Dose-dependent disposition of dopamine was observed in both plasma concentration-time profiles and in clearance (20.3 +/- 9.6 ml/min/kg at 5 micrograms/kg/min vs. 41.6 +/- 19.1 ml/min/kg at 1 micrograms/kg/min, P = 0.038). A sham experiment revealed that the blood in this experimental preparation contributed less than 10% to the total clearance of dopamine. This study revealed that our isolated in situ model is an excellent method to evaluate the role of the lungs in drug removal. Furthermore, it confirmed that the lungs contribute to the clearance of dopamine from the body.


A randomized controlled trial to evaluate the effect of incorporating peanuts into an American Diabetes Association meal plan on the nutrient profile of the total diet and cardiometabolic parameters of adults with type 2 diabetes.
According to the American Diabetes Association (ADA), the nutritional goals for patients with type 2 diabetes (T2D) are to achieve an optimal nutrient intake to achieve normoglycemia and a cardioprotective lipid profile. Peanuts are nutrient dense foods that contain high levels of monounsaturated fat (MUFA) and are a natural source of arginine, fiber, phytosterols, resveritrol, niacin, folate, vitamin E and magnesium, which have the potential for improving blood lipids and glycemic control. This study sought to evaluate the effect of a peanut enriched ADA meal plan on the nutrient profile of the total diet and cardiometabolic parameters in adults with T2D. This was a randomized, prospective 24-week parallel-group clinical trial with 60 adults with T2D [age range 34-84 years; body mass index (BMI) range 17.2-48.7 kg/m2]. Subjects consumed an ADA meal plan containing ~20% of energy from peanuts (peanut group) or a peanut-free ADA meal plan (control group). Weight, BMI, waist circumference (WC) and nutrient intake from 24-hour recalls were measured every 4 weeks and fasting blood glucose (FBG), HbA1c and blood lipids were measured every 12 weeks. A mixed-model repeated-measures analysis of covariance was performed to assess the significance of changes in the cardiometabolic parameters. A higher polyunsaturated fat (PUFA) to saturated fat diet ratio and higher intake of MUFA, PUFA, α-tocopherol, niacin and magnesium was observed in the peanut group as compared to the control group (P < 0.01-P = 0.04). Both groups experienced mild reductions in weight, BMI, and WC during the study (P = 0.01-P = 0.03), however there were no differences between the two groups in these measurements or in FBG, HbA1c or blood lipids. For each kilogram of weight loss in the entire cohort there were associations for reductions in WC of 0.48 cm (P < 0.01), FBG of 0.11 mmol/l (P = 0.01) and HbA1c of 0.07% (P < 0.01). Daily consumption of a peanut enriched (46 g/d) ADA meal plan over 24 weeks improves the nutrient profile of the total diet and is compatible with weight management and improvement in specific blood lipids. ClinicalTrials.gov NCT00937222.


Transient orientation of linear DNA molecules during pulsed-field gel electrophoresis.
The transient orientation of lambda DNA and lambda-DNA oligomers has been measured during pulsed field gel electrophoresis. The DNA becomes substantially aligned parallel to the electric field E. In response to a single rectangular pulse, orientation shows an overshoot with a peak at 1 second, then a small undershoot, and finally a plateau. When the field is turned off, the orientation dissipates in two distinct exponential phases. Field inversion leads to periods of orientation with intervening periods of reduced orientation as the chains reverse direction. Field inversion pulses applied to linear oligomers of lambda-DNA show that orientation responses slow down but increase in amplitude as molecular weight increases, for a given field. Because DNA stretching and alignment parallel to E are expected to correlate with DNA velocity, the velocity in response to a pulsed field is also expected to exhibit an overshoot.


The role of GABRA2 in alcohol dependence, smoking, and illicit drug use in an Australian population sample.
Multiple studies have shown that genetic variation in the alpha-2 subunit of the gamma-aminobutyric acid type A (GABA(A)) receptor (GABRA2) is associated with risk for alcohol dependence. Recent reports have suggested that GABRA2 may exert its influence on dependence through factors such as sensitivity to alcohol's intoxicating effects and that GABRA2 may also contribute to a common underlying genetic vulnerability to both alcohol and drug dependence. The present study tested for association between GABRA2 and alcohol dependence, smoking, and illicit drug use within the Australian population. We genotyped 11 single nucleotide polymorphisms (SNPs) within or flanking GABRA2 in 4597 subjects (34.6% males) from 2618 families comprising 814 monozygotic pairs, 1177 dizygotic pairs, and 627 twins whose co-twin did not participate. Family-based association tests were conducted for binary and quantitative measures of alcohol dependence, smoking, and cannabis and other illicit drug use. We observed evidence of association (p < 0.05) between multiple GABRA2 SNPs and quantitative measures of alcohol dependence, including symptom scores and principal component factor scores from the 9 criteria for DSM-IV alcohol dependence, in the opposite direction to that previously reported. In contrast, GABRA2 was not associated overall with dichotomous measure of alcohol dependence nor with smoking, cannabis, or illicit drug use. The GABRA2 allelic associations found in clinical case-control studies have detectable but minor effects on DSM-defined alcohol dependence in the general community. Systematic comparisons of allelic effects on alcohol dependence in clinical cases and in the general community are required.


Mechanism of action and development of resistance to a new amidino penicillin.
The mechanism of killing of Escherichia coli by a novel beta-lactam antibiotic, an amidino penicillin, has been investigated. This compound converts E. coli to relatively stable spherical forms at low concentration. However, the amidino penicillin caused no alteration in any of those parameters of peptidoglycan synthesis which can be studied. Above 10 mug of the antibiotic per ml the cells began to lyse, and a second mode of killing appeared. Mutants resistant to the amidino penicillin were isolated and several were studied in detail. Three mutant phenotypes were distinguished: (i) spherical shape and hypersensitive to lysis by either amidino penicillin or ampicillin; (ii) spherical shape and normally sensitive to lysis; (iii) rod shape, converted to viable spheres by amidino penicillin and normally sensitive to lysis.


Ten year trends in cardiovascular risk factors in the Federation of bosnia and herzegovina.
Results of routine health statistics show that in the Federation of Bosnia and Herzegovina (FBIH) are the leading causes of death of population are diseases of circulatory system (53% in 2012) namely, cardiomyopathy, heart failure and acute myocardial infarction. This data are red alert for immediate and imminent action. Two cross-sectional population surveys were conducted in 2002 and 2012 in the FBIH among adult population aged 25-64 years for assessment and distribution of major risk factors for cardiovascular diseases (CVD), preferably hypertension, obesity and smoking. Overall prevalence of hypertension among adult population in the FBIH in year 2012 was 41%, similar as in 2002. Prevalence of obesity in 2012 among men was higher compared to 2002, stood at 20.3%, while for women it was 24.1%. Total of 61.3% of men and 35.9% of women said they were daily smokers, while the percentage in 2002 was 49.3% among men and 29.8% among women and the difference was statistically significant. Distributions of the major risk factors for CVD are worsening in the adult population in the FBIH, especially in middle age men, what can result in serious deterioration of health and increased rates of chronic diseases, especially CVD.


raf RBD and ubiquitin proteins share similar folds, folding rates and mechanisms despite having unrelated amino acid sequences.
Recent experimental and theoretical studies in protein folding suggest that the rates and underlying mechanisms by which proteins attain the native state are largely determined by the topological complexity of a specific fold rather than by the fine details of the amino acid sequences. However, such arguments are based upon the examination of a limited number of protein folds. To test this view, we sought to investigate whether proteins belonging to the ubiquitin superfamily display similar folding behavior. To do so, we compared the folding-unfolding transitions of mammalian ubiquitin (mUbi) with those of its close yeast homologue (yUbi), and to those of the structurally related Ras binding domain (RBD) of the serine/threonine kinase raf that displays no apparent sequence homology with the ubiquitin family members. As demonstrated for mUbi [Krantz, B. A., and Sosnick, T. R. (2000) Biochemistry 39, 11696-11701], we show that a two-state transition model with no burst phase intermediate can describe folding of both yUbi and raf RBD. We further demonstrate that (1) all three proteins refold at rates that are within 1 order of magnitude (1800, 1100, and 370 s(-1) for mUbi, raf RBD, and yUbi, respectively), (2) both mUbi and raf RBD display similar refolding heterogeneity, and (3) the folding free energy barriers of both mUbi and raf RBD display a similar temperature dependence and sensitivity to a stabilizing agent or to mutations of a structurally equivalent central core residue. These findings are consistent with the view that rates and mechanisms for protein folding depend mostly on the complexity of the native structure topology rather than on the fine details of the amino acid sequence.


Radiation Protection in Pediatric Radiology: Results of a Survey Among Dutch Hospitals.
A survey about radiation protection in pediatric radiology was conducted among 22 general and seven children's hospitals in the Netherlands. Questions concerned, for example, child protocols used for CT, fluoroscopy and x-ray imaging, number of images and scans made, radiation doses and measures taken to reduce these, special tools used for children, and quality assurance issues. The answers received from 27 hospitals indicate that radiation protection practices differ considerably between general and children's hospitals but also between the respective general and children's hospitals. It is recommended that hospitals consult each other to come up with more uniform best practices. Few hospitals were able to supply doses that can be compared to the national Diagnostic Reference Levels (DRLs). The ones that could be compared exceeded the DRLs in one in five cases, which is more than was expected beforehand.


Thermal mud maturation: organic matter and biological activity.
Many of the therapeutic and cosmetic treatments offered in spas are centred on mud therapy, to moisturize the skin and prevent skin ageing and rheumatic diseases. Thermal mud is a complex matrix composed of organic and inorganic elements which contribute to its functions. It is a natural product derived from the long mixing of clay and thermal water. During its maturation, organic substances are provided by the microalgae, which develop characteristic of the composition of thermal water. The aim of this study was to identify methods for introducing objective parameters as a basis for characterizing thermal mud and assessing its efficacy. Samples of thermal mud were collected at the Saturnia spa, where there are several sulphureous pools. The maturation of the mud was evaluated by organic component determination using extractive methods and chromatographic analysis (HPLC, GC-MS, SPME). We also studied the radical scavenging activity of mud samples at different stages of maturation, in a homogeneous phase, using several tests (DPPH, ORAC, ABTS). We identified several classes of compounds: saturated and unsaturated fatty acids, hydroxyl acids, dicarboxylic acids, ketoacids, alcohols and others. SPME analysis showed the presence of various hydrocarbons compounds (C(11) -C(17)) and long-chain alcohols (C(12) -C(16)). Six or seven months seemed appropriate to complete the process of maturation, and the main effect of maturation time was the increase of lipids. Six-month mud showed the highest activity. The hydrophilic extract was more active than the lipophilic extract. The results indicate that maturation of thermal mud can be followed on the basis of the changes in its organic composition and antioxidant properties along the time. They also highlight the need to develop reference standards for thermal muds in relation to assess their use for therapeutic and cosmetic purposes.


Total synthesis of rapamycin.
For over 30 years, rapamycin has generated a sustained and intense interest from the scientific community as a result of its exceptional pharmacological properties and challenging structural features. In addition to its well known therapeutic value as a potent immunosuppressive agent, rapamycin and its derivatives have recently gained prominence for the treatment of a wide variety of other human malignancies. Herein we disclose full details of our extensive investigation into the synthesis of rapamycin that culminated in a new and convergent preparation featuring a macro-etherification/catechol-templating strategy for construction of the macrocyclic core of this natural product.


Relapsing polychondritis. A case report and literature review.
Relapsing polychondritis is a systemic disorder characterized by recurrent inflammation and degeneration of cartilaginous tissue. The eyes, ears, nose, larynx, trachea, and articular areas are commonly involved. While ocular involvement, hearing, and vestibular dysfunction are frequently present, aortic valve and root disease as well as vasculitis also may occur. While the cause remains unknown, an autoimmune pathogenesis appears likely. Thus, dapsone and/or systemic corticosteroids remain the predominant effective therapies. Another case of relapsing polychondritis with an associated vasculitis syndrome is presented as well as a review of the current literature.