Management of Small Vessel Vasculitides.
Inflammation mediated by cells of the immune system and necrosis are the most striking features observed at the histologic level in patients with vasculitides, clinical entities classified according to pathologic findings involving different organs, to etiology, or to size of vessels involved. Small vessel vasculitides (SVV) are a peculiar group of systemic disorders electively involving small intraparenchymal arteries, arterioles, capillaries, or venules and leading to different levels of vascular obstruction, tissue ischemia and risk of infarction; they can be divided into anti-neutrophil cytoplasmic antibody-associated vasculitides and immune complex vasculitides. Despite the significant advances in understanding the whole disease process and pathophysiology of SVV, strong efforts are still needed to draft, share and spread guidelines in the therapeutic management of these protean disorders. After an accurate evaluation of different open or double-blind trials and cohort studies in this review, we analyze the actual medical tools suggested for treating granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis, Henoch-Schönlein purpura, cryoglobulinemic vasculitis, anti-glomerular basement membrane disease and hypocomplementemic urticarial vasculitis.


Activation of the TASK-2 channel after cell swelling is dependent on tyrosine phosphorylation.
The swelling-activated K(+) currents (I(K,vol)) in Ehrlich ascites tumor cells (EATC) has been reported to be through the two-pore domain (K(2p)), TWIK-related acid-sensitive K(+) channel 2 (TASK-2). The regulatory volume decrease (RVD), following hypotonic exposure in EATC, is rate limited by I(K,vol) indicating that inhibition of RVD reflects inhibition of TASK-2. We find that in EATC the tyrosine kinase inhibitor genistein inhibits RVD by 90%, and that the tyrosine phosphatase inhibitor monoperoxo(picolinato)-oxo-vanadate(V) [mpV(pic)] shifted the volume set point for inactivation of the channel to a lower cell volume. Swelling-activated K(+) efflux was impaired by genistein and the Src kinase family inhibitor 4-amino-5-(4-chloro-phenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2) and enhanced by the tyrosine phosphatase inhibitor mpV(pic). With the use of the TASK-2 inhibitor clofilium, it is demonstrated that mpV(pic) increased the volume-sensitive part of the K(+) efflux 1.3 times. To exclude K(+) efflux via a KCl cotransporter, cellular Cl(-) was substituted with NO(3)(-). Also under these conditions K(+) efflux was completely blocked by genistein. Thus tyrosine kinases seem to be involved in the activation of the volume-sensitive K(+) channel, whereas tyrosine phosphatases appears to be involved in inactivation of the channel. Overexpressing TASK-2 in human embryonic kidney (HEK)-293 cells increased the RVD rate and reduced the volume set point. TASK-2 has tyrosine sites, and precipitation of TASK-2 together with Western blotting and antibodies against phosphotyrosines revealed a cell swelling-induced, time-dependent tyrosine phosphorylation of the channel. Even though we found an inhibiting effect of PP2 on RVD, neither Src nor the focal adhesion kinase (FAK) seem to be involved. Inhibitors of the epidermal growth factor receptor tyrosine kinases had no effect on RVD, whereas the Janus kinase (JAK) inhibitor cucurbitacin inhibited the RVD by 40%. It is suggested that the cytokine receptor-coupled JAK/STAT pathway is upstream of the swelling-induced phosphorylation and activation of TASK-2 in EATC.


Grandmothers' familism values, adolescent mothers' parenting efficacy, and children's well-being.
The current study examined intergenerational processes related to familism values among grandmothers, adolescent mothers, and their children. Mexican-origin families (N = 180) participated in in-home interviews during adolescent mothers' third trimester of pregnancy and 10-, 24-, 48-, and 60-months postpartum. Using longitudinal path analyses, we linked grandmothers' familism values and behaviors to adolescent mothers' parenting processes and, in turn, their child's well-being, taking into account developmentally relevant needs of adolescent mothers. Results revealed that grandmothers' familism values before the birth of the baby predicted child-rearing support and communication within the grandmother-adolescent mother dyad after the birth of the baby. Support, but not communication, was in turn predictive of adolescent mothers' parenting self-efficacy, but only at high levels of autonomy granting within the grandmother-adolescent mother dyad. Finally, adolescent mothers' parenting self-efficacy predicted children's greater social competence (48 months old), which in turn, predicted greater academic functioning (60 months old). Our findings shed light on the behavioral correlates of familism values within Mexican-origin families with adolescent mothers and highlight the need to consider factors that are developmentally salient (e.g., autonomy) when understanding how familism behaviors benefit adolescent mothers and their children.


The unique contribution of character strengths to quality of life in persons with multiple sclerosis.
The purpose of this study was to investigate the impact of the 24 character strengths in Peterson and Seligman's (2004) model on quality of life in persons with multiple sclerosis (MS), controlling for more commonly investigated biopsychosocial variables including resilience, social support, personality traits, depression, fatigue, and disability. Six hundred and 24 individuals with MS completed an online survey. Hierarchical regression analysis was used to test the contribution of character strengths over the control variables. The character strengths variables were significantly related to quality of life, even after controlling for the other variables. Individually, appreciation for beauty, gratitude, hope, and zest all significantly contributed to quality of life. The control variables, as a group, were significantly associated with quality of life. Individually, fatigue, depression, resilience, social support from family, conscientiousness, emotional stability, extraversion, and openness all significantly contributed to quality of life. The findings of this study provide support for the development of character strengths interventions to help increase quality of life in individuals with multiple sclerosis. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Segmentability evaluation of back-scattered SEM images of multiphase materials.
Segmentation methods are very useful tools in the Electron Microscopy inspection of materials, enabling the extraction of quantitative results from microscopy images. Back-Scattered Electron (BSE) images carry information of the mean atomic number in the interaction volume and hence can be used to quantify the phase composition in multiphase materials. Since phase composition and proportion affects the material properties and hence its applications, the segmentation accuracy of such images rendered of critical importance for material science. In this work, the notion of segmentability for BSE images is proposed to define the ability of an image to be segmented accurately. This notion can be used to guide the image acquisition process so that segmentability is maximized and segmentation accuracy is ensured. An index is devised to quantify segmentability based on a combination of the modified Fisher Discrimination Ratio and of the second Minkowski functional capturing intensity and spatial aspects of BSE images respectively. The suggested Segmentability Index (SI) is validated in synthetic BSE images which are generated with a novel algorithm allowing the independent control of spatial distribution of phases and their grayscale intensity histograms. Additionally, SI is applied in real-synthetic BSE images, where the real greyscale distributions of Ordinary Portland Cement (OPC) clinker crystallographic phases are used, to demonstrate the ability of SI to indicate the optimum choice of critical image acquisition settings leading to the more accurate segmentation output.


Expression of LMP-1 and Cyclin D1 protein is correlated with an unfavorable prognosis in nasal type NK/T cell lymphoma.
Nasal-type NK/T cell lymphoma (NK/TCL) is an increasingly recognized disease entity of aggressive clinical behavior. The objective of this study was to investigate the correlation between the clinical features of NK/TCL and patient prognosis. Immunohistochemical detection of Epstein-Barr virus (EBV)-associated latent membrane protein (LMP)-1, Cyclin D1 and Bcl-2 protein expression, as well as TUNEL staining, were performed. Of the 58 cases studied, 47 (81%) displayed positive expression of LMP-1 protein, which was associated with the presence of B symptoms and patient prognosis. In addition, high expression of Cyclin D1 and Bcl-2 protein was observed to correlate with poor prognosis and decreased survival. More importantly, LMP-1 and Cyclin D1 appeared to be co-expressed. This, along with other parameters such as clinical stage at diagnosis and enlarged lymph nodes, could be used as an independent prognostic factor for clinical outcome, as the survival rate of NK/TCL patients was closely associated with LMP-1/Cyclin D1 co-expression, advanced clinical stage and lymph node infiltration.


Cortical Representation of Interaural Time Difference Is Impaired by Deafness in Development: Evidence from Children with Early Long-term Access to Sound through Bilateral Cochlear Implants Provided Simultaneously.
Accurate use of interaural time differences (ITDs) for spatial hearing may require access to bilateral auditory input during sensitive periods in human development. Providing bilateral cochlear implants (CIs) simultaneously promotes symmetrical development of bilateral auditory pathways but does not support normal ITD sensitivity. Thus, although binaural interactions are established by bilateral CIs in the auditory brainstem, potential deficits in cortical processing of ITDs remain. Cortical ITD processing in children with simultaneous bilateral CIs and normal hearing with similar time-in-sound was explored in the present study. Cortical activity evoked by bilateral stimuli with varying ITDs (0, ±0.4, ±1 ms) was recorded using multichannel electroencephalography. Source analyses indicated dominant activity in the right auditory cortex in both groups but limited ITD processing in children with bilateral CIs. In normal-hearing children, adult-like processing patterns were found underlying the immature P1 (∼100 ms) response peak with reduced activity in the auditory cortex ipsilateral to the leading ITD. Further, the left cortex showed a stronger preference than the right cortex for stimuli leading from the contralateral hemifield. By contrast, children with CIs demonstrated reduced ITD-related changes in both auditory cortices. Decreased parieto-occipital activity, possibly involved in spatial processing, was also revealed in children with CIs. Thus, simultaneous bilateral implantation in young children maintains right cortical dominance during binaural processing but does not fully overcome effects of deafness using present CI devices. Protection of bilateral pathways through simultaneous implantation might be capitalized for ITD processing with signal processing advances, which more consistently represent binaural timing cues.SIGNIFICANCE STATEMENT Multichannel electroencephalography demonstrated impairment of binaural processing in children who are deaf despite early access to bilateral auditory input by first finding that foundations for binaural hearing are normally established during early stages of cortical development. Although 4- to 7-year-old children with normal hearing had immature cortical responses, adult patterns in cortical coding of binaural timing cues were measured. Second, children receiving two cochlear implants in the same surgery maintained normal-like input from both ears, but this did not support significant effects of binaural timing cues in either auditory cortex. Deficits in parieto-occiptal areas further suggested impairment in spatial processing. Results indicate that cochlear implants working independently in each ear do not fully overcome deafness-related binaural processing deficits, even after long-term experience.


Evaluation of anti-oxidant capacity of root of Scutellaria baicalensis Georgi, in comparison with roots of Polygonum multiflorum Thunb and Panax ginseng CA Meyer.
In Chinese communities, regular consumption of Chinese-medicated diets (CMD) (usually in the form of soup) is a traditional practice to promote health and prevent disease development. The overall improvement of health conditions is believed to be correlated with the anti-oxidant potentials of these herbs. Huangqin, roots of Scutellaria baicalensis Georgi (Lamiaceae), is one of the herbs commonly used in CMD. In this study, the anti-oxidant capacities of Huangqin extracts (water, ethanol and ether extracts) were evaluated and compared to commonly used CMD herbs, Heshouwu, roots of Polygonum multiflorum Thunb (Polygonaceae) and Renshen (or Ginseng), roots of Panax ginseng CA Meyer (Araliaceae). The anti-oxidant capacities were measured by using both cell-free assay [ferric reducing/anti-oxidant power (FRAP)] and biological methods [2,2'-azobis-(2-amidinopropane) (AAPH)-induced haemolysis assay and H(2)O(2)-induced cell damage on H9C2 cells]. Additionally, the total phenolic content was measured using Folin-Ciocalteu methods. Water extract of Huangqin has the highest anti-oxidant activities compared to the ethanol and ether extracts. A positive relationship between the anti-oxidant effects and total phenolic contents of extracts was demonstrated. This shows that Huangqin could be an effective dietary anti-oxidant that can be consumed regularly as a functional food for the prevention of oxidant/free radical-related diseases.


Simulation of a MR-PET protocol for staging of head-and-neck cancer including Dixon MR for attenuation correction.
To simulate and optimize a MR protocol for squamous cell cancer of the head and neck (HNSCC) patients for potential future use in an integrated whole-body MR-PET scanner. On a clinical 3T scanner, which is the basis for a recently introduced fully integrated whole-body MR-PET, 20 patients with untreated HNSCC routinely staged with 18F-FDG PET/CT underwent a dedicated MR protocol for the neck. Moreover, a whole-body Dixon MR-sequence was applied, which is used for attenuation correction on a recently introduced hybrid MR-PET scanner. In a subset of patients volume-interpolated-breathhold (VIBE) T1w-sequences for lungs and liver were added. Total imaging time was analyzed for both groups. The quality of the delineation of the primary tumor (scale 0-3) and the presence or absence of lymph node metastases (scale 1-5) was evaluated for CT, MR, PET/CT and a combination of MR and PET to ensure that the MR-PET fusion does not cause a loss of diagnostic capability. PET was used to identify distant metastases. The PET dataset for simulated MR/PET was based on a segmentation of the CT data into 4 classes according to the approach of the Dixon MR-sequence for MR-PET. Standard of reference was histopathology in 19 cases. In one case no histopathological confirmation of a primary tumor could be achieved. Mean imaging time was 35:17 min (range: 31:08-42:42 min) for the protocol including sequences for local staging and attenuation correction and 44:17 min (range: 35:44-54:58) for the extended protocol. Although not statistically significant a combination of MR and PET performed better in the delineation of the primary tumor (mean 2.20) compared to CT (mean 1.40), MR (1.95) and PET/CT (2.15) especially in patients with dental implants. PET/CT and combining MR and PET performed slightly better than CT and MR for the assessment of lymph node metastases. Two patients with distant metastases were only identified by PET. We established a potential MR-protocol to be used for HNSCC patients in a recently introduced MR-PET scanner. The proposed protocol can be performed in an acceptable time frame and did not lead to a loss of diagnostic capability compared to PET/CT.


Annealing of Strontium Titanate Based Thermoelectric Materials by Graphite: Mechanistic Analysis by Spectroscopic and Chromatographic Techniques.
Strontium titanate (SrTiO3 ) based materials are promising for high-temperature thermoelectric applications. In order to enhance their performance, annealing is usually required and carried out under various atmospheres. Annealing with graphite is quite effective, but the mechanism is not yet clear. In this work, we use IR spectroscopy and gas chromatography (GC) to monitor the chemical environment under the annealing conditions (1350 °C for 8 h under 16.9 mL/min N2 with graphite) and quantify the various gases evolved in the process. It is shown that reducing agents, H2 and CO (concentrations peaked at ca. 0.4-0.5 %), are generated from graphite in the annealing process. H2 is produced in carbon gasification reaction, which also generates CO. Additional CO is produced from incomplete combustion of carbon. In the annealing of a La-doped SrTiO3 -based ceramic with graphite, higher levels of H2 O and CO2 are detected, which is resulted from the reduction of the ceramic by H2 and CO, respectively. About 67 % of the oxygen vacancies were created by CO reduction while about 33 % by H2 reduction. The conclusions are well supported by direct weight loss measurements with a difference of less than 6 %.


Antioxidant properties of various solvent extracts of total phenolic constituents from three different agroclimatic origins of drumstick tree (Moringa oleifera Lam.) leaves.
Water, aqueous methanol, and aqueous ethanol extracts of freeze-dried leaves of Moringa oleifera Lam. from different agroclimatic regions were examined for radical scavenging capacities and antioxidant activities. All leaf extracts were capable of scavenging peroxyl and superoxyl radicals. Similar scavenging activities for different solvent extracts of each collection were found for the stable 1,1-diphenyl 2-picrylhydrazyl (DPPH(*)) radical. Among the three different moringa samples, both methanol and ethanol extracts of Indian origins showed the highest antioxidant activities, 65.1 and 66.8%, respectively, in the beta-carotene-linoleic acid system. Nonetheless, increasing concentration of all the extracts had significantly (P < 0.05) increased reducing power, which may in part be responsible for their antioxidant activity. The major bioactive compounds of phenolics were found to be flavonoid groups such as quercetin and kaempferol. On the basis of the results obtained, moringa leaves are found to be a potential source of natural antioxidants due to their marked antioxidant activity. This is the first report on the antioxidant properties of the extracts from freeze-dried moringa leaves. Overall, both methanol (80%) and ethanol (70%) were found to be the best solvents for the extraction of antioxidant compounds from moringa leaves.


Pterostilbene inhibits lung squamous cell carcinoma growth in vitro and in vivo by inducing S phase arrest and apoptosis.
Natural dietary components have become the subject of an increasing amount of interest due to the side effects of anticancer treatment. Pterostilbene, an analog of resveratrol, is primarily found in grapes, and has been suggested to exert antioxidant and anticancer effects in different tumor types. The present study aimed to investigate the antitumor effects and molecular mechanisms of pterostilbene in the human lung squamous cell carcinoma (SqCC) cell line, H520. The results of the present study indicate that pterostilbene significantly reduced cell viability and induced S phase arrest, and that treatment with pterostilbene was associated with the downregulation of cyclin A and cyclin E, as with the upregulation of p21 and p27 expression in H520 cells. In the apoptosis analysis, pterostilbene induced S phase accumulation and the activation of caspase-3, -8 and -9 in H520 cells, potentially through the activation of extrinsic and intrinsic apoptotic pathways. Additionally, the in vivo study demonstrated that pterostilbene effectively inhibited lung SqCC growth in a H520 ×enograft model. Given the in vitro and in vivo antitumor effects of pterostilbene demonstrated in the present study, pterostilbene may serve a novel and effective therapeutic agent to for patients with SqCC.


Early valve replacement for aortic stenosis irrespective of symptoms results in better clinical survival: a meta-analysis of the current evidence.
Patients with severe, but asymptomatic aortic stenosis (AS) present a difficult clinical challenge. The conventional strategy is 'wait for symptoms' approach. However, some observational studies have suggested early aortic valve replacement (AVR) results in better outcome compared to late surgery. There are no randomised controlled trials comparing clinical outcome of early and late AVR. This meta-analysis is to examine the effect of the two approaches on clinical outcome in such patients. We searched the PubMed for published studies on asymptomatic AS and treatment. Four observational studies (N=976 patients) were suitable for inclusion in the analysis. All four studies provided sufficient details. Using the subgroup of asymptomatic patients who underwent early surgery together or separately from the subgroup who had surgery after developing symptoms resulted in ORs of 0.17 and 0.16 respectively (p<0.00001) in favour of early AVR compared with conservational or late surgery. Meta-analysis of the available observational studies has demonstrated highly significant clinical outcome in favour of early AVR compared with late surgery, suggesting that early surgical approach offers substantial survival benefit for severe asymptomatic AS patients.


Evidence against the Detectability of a Hippocampal Place Code Using Functional Magnetic Resonance Imaging.
Individual hippocampal neurons selectively increase their firing rates in specific spatial locations. As a population, these neurons provide a decodable representation of space that is robust against changes to sensory- and path-related cues. This neural code is sparse and distributed, theoretically rendering it undetectable with population recording methods such as functional magnetic resonance imaging (fMRI). Existing studies nonetheless report decoding spatial codes in the human hippocampus using such techniques. Here we present results from a virtual navigation experiment in humans in which we eliminated visual- and path-related confounds and statistical limitations present in existing studies, ensuring that any positive decoding results would represent a voxel-place code. Consistent with theoretical arguments derived from electrophysiological data and contrary to existing fMRI studies, our results show that although participants were fully oriented during the navigation task, there was no statistical evidence for a place code.


Overuse of splenic scoring and computed tomographic scans.
As the most commonly injured abdominal organ in blunt trauma, the management of splenic injury has undergone evolution. The risk of blood transfusions administered in an attempt to save the spleen has lowered the threshold for operation and also expanded the limits for nonoperative management. An in-depth analysis was carried out of risk factors on patients requiring immediate surgery and those who fail non-operative management based on organ injury scaling grading by computed tomographic (CT) scan and operation. The application of nonoperative management in the elderly population and the use of follow-up CT scanning and sonography in the outpatient setting was also examined. Between January of 1991 and June of 1996, 226 consecutive blunt splenic trauma, injured patients at a Level I trauma center were evaluated. All subsequent CT scans and sonograms in the inpatient and outpatient setting were analyzed. The Student's t test, Pearson chi2 analysis with Yates correction, and analysis of variance were used to compare between and among groups. There were 153 men (67.7%), an average age of 34.8 years, an average Injury Severity Score of 24.4, and 28 deaths (12%). There was a significant difference with respect to Injury Severity Score, Glasgow Coma Scale score, Revised Trauma Score, units of packed red blood cells transfused, length of stay, intensive care unit length of stay, mean splenic injury grade, and cost between patients observed initially and those operated on initially. There was no significant difference in age between the two groups. Of 170 patients, 37 patients (22%) who had an initial CT scan underwent immediate exploratory laparotomy. The remaining 133 patients (78%) had nonoperative management; however, 15 patients (11%) failed the period of observation. Five in this group had a laparotomy secondary to other causes and another six were operated on within 24 hours of their injury for their splenic injury. Thus, only four of the nonoperative management patients (3%) actually failed nonoperative splenic management after 24 hours of injury. There were 100 second CT scans obtained. Three of these patients, who had developed hemodynamic instability, required operation for a bleeding spleen. The subsequent CT scan was confirmatory in these three patients who resided in the intensive care unit. All other CT scans and sonograms for clinically unremarkable patients failed to yield any alteration in care based on the scans. Blunt splenic injured patients can be safely observed; however, there are certain risk factors in those requiring immediate surgery and those failing nonoperative management. The CT scan underestimates injury, possibly related to a progression of bleeding found at the time of operation. No outpatient studies altered the course of management. Age also did not influence outcome. Thus, in the dedicated trauma center, nonoperative management of blunt splenic injury patients does not lead to undue morbidity or mortality. Once discharged, follow-up radiographs in asymptomatic patients are not necessary.


Illness and efficiency of health services delivery in a district hospital.
Demographic data, medical problems and diagnosis, and efficiency of laboratory investigations and drug administration were evaluated in all patients admitted to an adult medical ward over a one month period at a district hospital in Kenya. The results show that the medical ward serves a poor, cosmopolitan population in the economically productive age range. Mental disorders (16%), symptoms and ill-defined conditions (16%), and infective and parasitic disease (15%) were the most common diagnoses. Out of 999 orders and/or results, 357 were delayed, interrupted, never done, or never received. Factors that affect medical education and efficiency of health services delivery at a district hospital are identified and discussed.


Large cell neuroendocrine carcinoma of the gallbladder: report of two cases.
We report two cases of primary large cell neuroendocrine carcinoma (LCNEC) of the gallbladder, which, to the best of our knowledge, represent the first description of this entity. One of the tumors consisted entirely of LCNEC, whereas the second tumor was composed of LCNEC and the more common intestinal-type adenocarcinoma. Both tumors were morphologically similar to their pulmonary counterpart and were characterized by large cells with prominent nucleoli, coarse chromatin, and a high mitotic rate. The cells showed an organoid growth pattern with rosette formation and frequent areas of necrosis. Panendocrine markers were expressed in a variable proportion of tumor cells in both cases, and one of the cases also showed focal positivity for type 2 somatostatin receptors. One of the tumors followed a rapidly fatal course despite aggressive surgical treatment and chemotherapy administration, and the second patient is still alive and disease-free 12 months after surgery. The description of these two cases of LCNEC of the gallbladder is significant for two reasons. From an academic standpoint, we now know that all the neuroendocrine tumors described in other organs can arise de novo in the gallbladder. More importantly, however, the recognition of this rare tumor type carries important clinical implications in regard to the use of chemotherapeutic agents and supplemental treatments (for example, somatostatin analogs).


Objectively measured physical activity and psychosocial functioning in young children: The GECKO Drenthe cohort.
The global trend in inactivity in children may be related to psychosocial problems. We investigated the cross-sectional association between physical activity (PA) levels and psychosocial functioning in 3.4-7.3-year-old children. Children from the Dutch GECKO birth cohort (N = 898; 51.6% boys) had PA levels assessed objectively by accelerometry (ActiGraph GT3X) for at least three days. Linear regression analysis was used for associations with psychosocial functioning (parent report of the Strengths and Difficulties Questionnaire), controlling for gender, age and socio-economic status. Higher total and moderate-to-vigorous PA levels (MVPA) were associated with higher Total Difficulty scores, and sedentary time to lower Total Difficulty scores. More time spent in MVPA was significantly associated to "hyperactivity/inattention" in both boys (Standardized BBOYS = 0.192) and girls (Std.BGIRLS = 0.139) whereas for the time in sedentary behaviour, a reverse association was found only in boys (Std.BBOYS = -0.230). In boys only, more time in MVPA (Std.BBOYS = 0.154) and less time in sedentary behaviour (Std.BBOYS = -0.147), were significant determinants for 'behavioural problems'. When using objectively measured PA, parents report more hyperactivity/inattention and behavioural problems in the more active children, and less in the more sedentary children, most clearly for boys. High levels of PA might be an indicator of psychosocial problems in young children.


Molecular pathophysiology of pancreatitis.
Though hereditary pancreatitis is a very rare form of pancreatitis, the discovery of the gene for hereditary pancreatitis provides important implications for pancreatitis in general. A premature activation of trypsinogen is likely to occur not infrequently in our daily life as the onset of the disease is well advanced before a drinking habit starts. It probably goes unnoticed in normal individuals because normal inhibitory mechanisms described above prevent the development of pancreatitis. Any disorders or agents that cause abnormalities in this natural protective mechanism can cause pancreatitis. Genotype-phenotype analyses of CFTR mutations in chronic pancreatitis are necessary to establish the relationship between CFTR and this disease. It remains to be shown how a reduction of functional CFTR causes chronic pancreatitis.


Wafer-scale synthesis of two-dimensional ultrathin films.
Two-dimensional (2D) materials, consisting of atomically thin layered crystals, have attracted tremendous interest due to their outstanding intrinsic properties and diverse applications in electronics, optoelectronics, and catalysis. The large-scale growth of high-quality ultrathin 2D films and their utilization in the facile fabrication of devices, easily adoptable in industrial applications, have been extensively sought after during the last decade; however, it remains a challenge to achieve these goals. Herein, we introduce three key concepts: (i) the microwave assisted quick (∼1 min) synthesis of wafer-scale (6-inch) anisotropic conducting ultrathin (∼1 nm) amorphous carbon and 2D semiconducting metal chalcogenide atomically thin films, (ii) a polymer-assisted deposition process for the synthesis of wafer-scale (6-inch) 2D metal chalcogenide and pyrolyzed carbon thin films, and (iii) the surface diffusion and epitaxial self-planarization induced synthesis of wafer-scale (2-inch) single crystal 2D binary and large-grain 2D ferromagnetic ternary metal chalcogenide thin films. The proposed synthesis concepts can pave a new way for the manufacture of wafer-scale high quality 2D ultrathin films and their utilization in the facile fabrication of devices.


Assessing competence in health professionals' use of motivational interviewing: A systematic review of training and supervision tools.
To conduct a systematic review of instruments for assessing the competency of therapists in motivational interviewing (MI) for training purposes. A search of Medline, Emcare, CINAHL, Scopus, Proquest, and Web of Science databases yielded 20,313 articles, of which 105 were included in the review. Data were summarised in terms of the instruments' development, adherence to MI principles, administration characteristics, psychometric properties, advantages, and disadvantages. Twelve instruments were identified. Tools tended to be better at covering simpler MI techniques. Differences in administration burden allow users to choose between briefer but cheaper and more detailed yet costly tools. Psychometric testing was often limited, and even if more extensive, the quality was often inconsistent. Although each tool tended to have relatively unique advantages (e.g. use of client ratings), they shared common disadvantages (e.g. lack of psychometric testing). A number of tools can be used to assess MI competency, each with their own strengths but notable weaknesses that should be considered by potential users. There is a need to further test existing tools before creating new ones, due to the repetition of the same limitations. Standardised guidelines should also be created to ensure each tool meets the same quality standards.


[Anuria caused by mercury poisoning (apropos of 15 cases)].
15 cases of acute renal failure following ingestion of bichloride of mercury were studied at Pahlavi medical center, university of Teheran, between 1962 and 1972. All the patients admitted suicide attempts. All had oliguria and uremia except one, in whom oliguria was moderate without azotemia. There were four deaths among the 15 patients, three of them with gastrointestinal hemorrhage; secondery infection and the prolonged acute uremia probably were the cause of death in another one. Early administration of B. A. L. and early frequent hemodialysis helps to support the patient through the period of oliguria and possibly to remove the mercury B.A.L. Complex. Although the mortality of mercury intoxication has decreased, gastrointestinal hemorrhages and secondery infections make its prognosis still unfavorable.


Anesthesia in children with mastocytosis--a case based review.
Mastocytosis is a rare heterogeneous disease of bone marrow origin which arises as a consequence of abnormal growth and/or accumulation of clonal mast cells in one or more organs. Sixty-five percent of patients with mastocytosis are children in whom it usually regresses around puberty. Adult patients with mastocytosis have been identified as at high risk of widespread mast cell degranulation in the perioperative period, this finding has not been reported in pediatric patients. This information has been repeated in mastocytosis websites where it has the potential to cause disproportionate alarm in parents. We considered our experience of six children with mastocytosis together with a review of the literature to examine other reports of anesthesia in children with mastocytosis. Our literature search found 57 general anesthetics in 39 children with mastocytosis. In addition, we searched for information about current consensus in diagnosis, classification and treatment of mastocytosis and in vitro and in vivo studies looking at mast cell behavior in response to drugs commonly used during anesthesia. The literature search revealed that general anesthesia has precipitated life threatening complications in adult patients with systemic mastocytosis (SM) but no such complications have been described in children with mastocytosis. Our own experience with children with mastocytosis is of uneventful anesthesia. Advances in the understanding of the genetic basis of mastocytosis suggest that pediatric cutaneous mastocytosis (CM) and SM are different entities. SM in children is extremely rare and is associated with elevated baseline serum tryptase. There are few reports of anesthesia in this group. The risks for most pediatric patients are overstated by mastocytosis websites. Most pediatric patients with CM do not appear to be at risk of widespread mast cell degranulation during anesthesia but because of the small number of cases reported, the risk cannot be ascertained with confidence. Children with SM and a high baseline serum tryptase (marker of mast cell burden) may merit extra precautions but experience in this subgroup is even more limited. Drugs which cause minimal histamine release can be selected from the range of drugs available in most pediatric centers without compromise to technique.


Plant protein hydrolysates: preparation of defined peptide fractions promoting growth and production in animal cells cultures.
A new approach was applied with the aim at producing plant protein hydrolysates less heterogeneous and less contaminated with nonpeptide substances than are the presently available digests. A significant reduction of nonprotein contaminants was achieved by extraction of the plant material, soy flour or wheat flour, with acetone prior to isolation of the protein. Enzymes of nonanimal origin, papain or Pronase, were used for protein hydrolysis. The components of the hydrolysates were resolved by low-pressure liquid chromatography. Separation of peptide fractions and of remaining nonpeptide contaminants was achieved using small-pore size-exclusion chromatography matrices, Sephadex G-15 or Biogel P-2. Individual peptide fractions, both from soy protein and from wheat gluten, varied substantially in their growth-promoting and production-enhancing activities when tested on a mouse hybridoma culture in protein-free medium. The highest enhancement of viable cell density in batch cultures was 180% of control, and the highest enhancement of final immunoglobulin concentration was more than 230% of control. The existence of marked differences in activity of individual peptide fractions leads to a suggestion that the hydrolysates may provide peptides exerting specific positive effects on cultured animal cells.


Clinical assessment of the shoulder.
The shoulder joint is complex in structure and functionality. It is often difficult to assess clinically due to the great variety of associated pathology. This article presents an overview of the anatomy of the shoulder region and associated pathologies, whilst providing a summary of the clinical examination of the shoulder and associated 'special tests'. A full history is vital when assessing shoulder pathology. No particular test is fully sensitive or specific alone and accuracy varies between both clinicians and patients alike. Assessment of the shoulder should be conducted systematically with a range of tests combined.


Management and Outcomes of Acute Surgical Patients at a District Hospital in Uganda with Non-physician Emergency Clinicians.
Acute surgical care services in rural Sub-Saharan Africa suffer from human resource and systemic constraints. Developing emergency care systems and task sharing aspects of acute surgical care addresses many of these issues. This paper investigates the degree to which specialized non-physicians practicing in a dedicated Emergency Department contribute to the effective and efficient management of acute surgical patients. This is a retrospective review of an electronic quality assurance database of patients presenting to an Emergency Department in rural Uganda staffed by non-physician clinicians trained in emergency care. Relevant de-identified clinical data on patients admitted directly to the operating theater from 2011 to 2014 were analyzed in Microsoft Excel. Overall, 112 Emergency Department patients were included in the analysis and 96% received some form of laboratory testing, imaging, medication, or procedure in the ED, prior to surgery. 72% of surgical patients referred by ED received preoperative antibiotics, and preoperative fluid resuscitation was initiated in 65%. Disposition to operating theater was accomplished within 3 h of presentation for 73% of patients. 79% were successfully followed up to assess outcomes at 72 h. 92% of those with successful follow-up reported improvement in their clinical condition. The confirmed mortality rate was 5%. Specialized non-physician clinicians practicing in a dedicated Emergency Department can perform resuscitation, bedside imaging and laboratory studies to aid in diagnosis of acute surgical patients and arrange transfer to an operating theater in an efficient fashion. This model has the potential to sustainably address structural and human resources problems inherent to Sub-Saharan Africa's current acute surgical care model and will benefit from further study and expansion.


Studies on RNA ligase activity in the brain and liver cells of mouse.
RNA ligase in eukaryotic mammalian cells was studied by using mouse brain and liver cell extracts as enzyme sources and Oligo A as substrates. RNA ligase activity was determined by measuring the formation of alkaline phosphate-resistant product from 5'-32P-terminated Oligoribonucleotides. Under appropriate conditions, the activity of this enzyme in brain and liver cells may vary between 16-49 mU/ml. The joining way between donor and acceptor is 5'-P----3'-OH. Further studies were carried out by using synthetic UpCpU and 32pNp as substrates and crude enzyme preparations from extracts of cell nuclei of brain and liver as enzyme sources. RNA ligase activity was examined by homochromatography and autoradiography. A clear joining product was demonstrated and then isolated from the reaction mixture by DEAE-Sephadex A25 column chromatography. The eluted fractions were identified by DEAE-cellulose thin layer chromatography. The joining product was hydrolyzed either with KOH or with alkaline phosphatase, the autoradiographic spot of the product disappeared. In this case the joining way between donor and acceptor is 3'-P----5'-OH instead of 5'P----3'-OH. All this indicated that in extracts of mouse brain and liver cells most probably exists some other kind of RNA ligase, which differs from the T4 RNA ligase in the joining way.


Signalment, clinical presentation, and diagnostic findings in 122 dogs with spinal arachnoid diverticula.
Most information about spinal arachnoid diverticula (SADs) in dogs has been retrieved from relatively small case series. The aim of this study was to describe this disease in a larger number of dogs. Description of the signalment, clinical presentation, and imaging findings of a large number of dogs with SADs. One hundred and twenty-two dogs with SADs. Retrospective case series study. All medical records were searched for a diagnosis of SAD. The diagnosis was made based on myelography, computed tomography myelography (CT-m), or magnetic resonance imaging (MRI). In the 122 dogs, 125 SADs were identified. Sixty-five were located in the cervical region and 60 in the thoracolumbar region. A higher body weight was significantly associated with a cervical localization of the SAD (P < .001). Ninety-five dogs were male and 27 dogs were female. Male dogs were significantly overrepresented (P < .0001). The most commonly affected breed was the Pug dog. Previous or concurrent spinal disorders, in the near proximity of the diagnosed SAD, were seen in 26 dogs. Eight of 13 French Bulldogs and 7 of 21 Pug dogs with SADs had a previous or concurrent spinal disease, whereas other spinal disorders occurred in only 1 of 17 Rottweilers with SADs. Pug dogs and French Bulldogs might have a predisposition for SAD development. In a large percentage of these dogs, a concurrent spinal disorder, which might predispose to SAD formation, was diagnosed. The high prevalence in male dogs warrants further investigation.


Increased vaccine-specific T cell frequency after peptide-based vaccination correlates with increased susceptibility to in vitro stimulation but does not lead to tumor regression.
Although in vitro sensitization assays have shown increased melanoma Ag (MA)-specific CTL reactivity after vaccination with MA peptides, clinical responses have been uncommon. This paradox questions whether data obtained from the in vitro stimulation and expansion of T cells lead to an overestimation of the immune response to vaccines. Using HLA/peptide tetramer (tHLA), we enumerated MA-specific T cell precursor frequency (TCPF) directly in PBMC from 23 melanoma patients vaccinated with gp100:209-217(210M) (g209-2M) peptide. Vaccine-specific TCPF was higher in postvaccination PBMC from seven of seven patients treated with peptide alone and four of five patients treated with peptide plus IL-12 (range of postvaccination TCPF, 0.2-2.4% and 0.2-2.5%, respectively). The increased TCPF correlated with enhanced susceptibility to in vitro stimulation with the relevant epitope. Paradoxically, no increase in postvaccination TCPF was observed in most patients who had been concomitantly treated with IL-2 (1 of 11 patients; range of postvaccination TCPF, 0.02-1.0%), a combination associated with enhanced rates of tumor regression. The lack of increase in TCPF seen in these patients corresponded to inability to elicit expansion of vaccine-specific T cells in culture. This study shows that a peptide-based vaccine can effectively generate a quantifiable T cell-specific immune response in the PBMC of cancer patients, though such a response does not associate with a clinically evident regression of metastatic melanoma.


Integrating patients' views into health technology assessment: Analytic hierarchy process (AHP) as a method to elicit patient preferences.
Patient involvement is widely acknowledged to be a valuable component in health technology assessment (HTA) and healthcare decision making. However, quantitative approaches to ascertain patients' preferences for treatment endpoints are not yet established. The objective of this study is to introduce the analytic hierarchy process (AHP) as a preference elicitation method in HTA. Based on a systematic literature review on the use of AHP in health care in 2009, the German Institute for Quality and Efficiency in Health Care (IQWiG) initiated an AHP study related to its HTA work in 2010. The AHP study included two AHP workshops, one with twelve patients and one with seven healthcare professionals. In these workshops, both patients and professionals rated their preferences with respect to the importance of different endpoints of antidepressant treatment by a pairwise comparison of individual endpoints. These comparisons were performed and evaluated by the AHP method and relative weights were generated for each endpoint. The AHP study indicates that AHP is a well-structured technique whose cognitive demands were well handled by patients and professionals. The two groups rated some of the included endpoints of antidepressant treatment differently. For both groups, however, the same six of the eleven endpoints analyzed accounted for more than 80 percent of the total weight. AHP can be used in HTA to give a quantitative dimension to patients' preferences for treatment endpoints. Preference elicitation could provide important information at various stages of HTA and challenge opinions on the importance of endpoints.


Body Mobility and Attention Networks in 6- to 7-Year-Old Children.
Learning in 6- to 7-year-old children is strongly influenced by three functions of attention: alertness, orienting, and executive control. These functions share a close relationship with body mobility, such as the posture adopted or a request to stay still during tasks. The aim of this study (ClinicalTrials.gov) was to analyze the influence of body posture (standing versus sitting) and the influence of these imposed postures compared to a free body mobility on attention functions in 6- to 7-year-old children. Twenty-one children (11 girls) with a mean age of 6.7±0.6years performed the Attention Network Test for Children in three-body mobility conditions: sitting still, standing still, and free to move. Three attentional scores were calculated which would separately reflect performance of alertness, orienting, and executive control. Overall, no difference in alertness performance was found between the three bodily mobility conditions. In addition, our results suggest a general poor orienting performance in children, whatever the body mobility condition, which might be related to their young age. Finally, children improved their executive control performance when they stood still, probably due to an improvement in arousal and mental state.


Quantitative assessment of in-solution digestion efficiency identifies optimal protocols for unbiased protein analysis.
The majority of mass spectrometry-based protein quantification studies uses peptide-centric analytical methods and thus strongly relies on efficient and unbiased protein digestion protocols for sample preparation. We present a novel objective approach to assess protein digestion efficiency using a combination of qualitative and quantitative liquid chromatography-tandem MS methods and statistical data analysis. In contrast to previous studies we employed both standard qualitative as well as data-independent quantitative workflows to systematically assess trypsin digestion efficiency and bias using mitochondrial protein fractions. We evaluated nine trypsin-based digestion protocols, based on standard in-solution or on spin filter-aided digestion, including new optimized protocols. We investigated various reagents for protein solubilization and denaturation (dodecyl sulfate, deoxycholate, urea), several trypsin digestion conditions (buffer, RapiGest, deoxycholate, urea), and two methods for removal of detergents before analysis of peptides (acid precipitation or phase separation with ethyl acetate). Our data-independent quantitative liquid chromatography-tandem MS workflow quantified over 3700 distinct peptides with 96% completeness between all protocols and replicates, with an average 40% protein sequence coverage and an average of 11 peptides identified per protein. Systematic quantitative and statistical analysis of physicochemical parameters demonstrated that deoxycholate-assisted in-solution digestion combined with phase transfer allows for efficient, unbiased generation and recovery of peptides from all protein classes, including membrane proteins. This deoxycholate-assisted protocol was also optimal for spin filter-aided digestions as compared with existing methods.


NAC attenuates LPS-induced toxicity in aspirin-sensitized mouse macrophages via suppression of oxidative stress and mitochondrial dysfunction.
Bacterial endotoxin lipopolysaccharide (LPS) induces the production of inflammatory cytokines and reactive oxygen species (ROS) under in vivo and in vitro conditions. Acetylsalicylic acid (ASA, aspirin) is a commonly used anti-inflammatory drug. Our aim was to study the effects of N-acetyl cysteine (NAC), an antioxidant precursor of GSH synthesis, on aspirin-sensitized macrophages treated with LPS. We investigated the effects of LPS alone and in conjunction with a sub-toxic concentration of ASA, on metabolic and oxidative stress, apoptosis, and mitochondrial function using J774.2 mouse macrophage cell line. Protection from LPS-induced toxicity by NAC was also studied. LPS alone markedly induced ROS production and oxidative stress in macrophage cells. When ASA was added to LPS-treated macrophages, the increase in oxidative stress was significantly higher than that with LPS alone. Similarly, alteration in glutathione-dependent redox metabolism was also observed in macrophages after treatment with LPS and ASA. The combination of LPS and ASA selectively altered the CYP 3A4, CYP 2E1 and CYP 1A1 catalytic activities. Mitochondrial respiratory complexes and ATP production were also inhibited by LPS-ASA treatment. Furthermore a higher apoptotic cell death was also observed in LPS-ASA treated macrophages. NAC pre-treatment showed protection against oxidative stress induced apoptosis and mitochondrial dysfunction. These effects are presumed, at least in part, to be associated with alterations in NF-κB/Nrf-2 mediated cell signaling. These results suggest that macrophages are more sensitive to LPS when challenged with ASA and that NAC pre-treatment protects the macrophages from these deleterious effects.


Integration of pharmacology into a problem-based learning curriculum for medical students.
The purpose of this study is threefold: (1) to describe a method of integration of pharmacology subject matter with other disciplines, in a problem-based learning (PBL) curriculum employed at the Northwest Center for Medical Education (NWCME), Indiana University School of Medicine; (2) to present various evaluation methods employed to assess students' learning of pharmacology knowledge; and (3) to compare the academic performance of students who underwent a traditional curriculum versus the PBL curriculum in terms of class evaluations and the standard national board medical licensure examinations. The PBL curriculum is designed for the first 2 years of medical education and consists of six sequential steps: steps 1 and 2 deal with biochemistry and anatomy respectively; steps 3, 4 and 5 deal with physiology, neuroscience and general pathology/microbiology respectively; and step 6 is a multidisciplinary step, which integrates basic science subjects with clinical medicine, emphasizing the mechanism of disease in an organ-system approach. In the PBL curriculum students start learning pharmacology within 6 months of admission. The content and process of pharmacology are spread across the first and in the second year. The pharmacology content is divided into three segments, each of which is integrated with other basic science subjects that have maximum mutual relevance. The three segments are as follows: the general and systemic pharmacology (50%) was included in step 3; the neuropharmacology and toxicology (35%) part was included in step 4; the third segment consisted of antimicrobial agents, anticancer and antiinflammatory agents (15%) and was included in step 5. The class evaluation of student performance in the PBL curriculum consisted of two elements, the content examinations and the process evaluations, which include the tutorial and the triple-jump evaluations of problem-solving skills. In order to assess the overall academic performance of the PBL curriculum and traditional curriculum groups, three classes of students who took the PBLC were compared with three classes of students who underwent a TC for performance in terms of class grades and scores of National Board examinations (NBMEI and/or USMLE I). The PBL curriculum students performed as well as or better than the TC students as measured by the NMBEI and/or USMLE I. The gain in pharmacology knowledge of PBL students is accompanied by the presence of a positive experience that learning pharmacology is enjoyable. Our experience suggests that the segmental integration approach of instruction coupled with a system of content (internal and external examinations) and process (tutorial and triple-jump) evaluations, as outlined in this paper is a contextualized learning method that offers an effective way of imparting pharmacology knowledge to medical students.


Temporal IgG subclasses response in dogs following vaccination against Leishmania with Leishmune®.
Canine Visceral Leishmaniasis (CVL) is a widespread zoonotic disease with mandatory euthanasia of infected dogs determined by the Brazilian Ministry of Health. Development of vaccines against CVL may provide a prophylactic barrier, but transitory peak of antibody response detected by standard diagnostic techniques in vaccinated dogs may be interpreted as natural infection. Accordingly, the aim of the present study was to sequentially evaluate total and IgG subclasses response between naturally Leishmania-infected and dogs vaccinated with Leishmune(®). A total of 172 mongrel dogs were divided in four groups: Group 1 (G1) with 45 clinically healthy dogs, Group 2 (G2) and Group 3 (G3) with 45 dogs naturally infected by Leishmania sp. each, symptomatic and asymptomatic respectively, and G4 (G4) with 37 healthy dogs submitted to a complete protocol of a commercially available vaccine against CVL, monitored and evaluated in 5 different chronological moments (M0-M4) up to 180 days after M0. Total IgG, IgG1 and IgG2 were unable to differentiate between infected (G2 and G3) and vaccinated (G4) dogs, demonstrating that polyclonal commercial antibodies do not distinguish these groups apart. Total and IgG subclasses antibodies were not detected until 21 days of the second vaccination dose; however, seroconversion was observed on 21 days and sustained positivity up to 6 months after the vaccination start. A peak of antibodies response was observed on 90 days (M3), when results for total IgG, IgG1, IgG2, IgG3 and IgG4 where highly significant when compared to M0 (P<0.0001). Neither total IgG nor IgG1 effectively differentiated between infected (G2 and G3) and vaccinated (G4) dogs. In conclusion, despite dogs may test serologically negative immediately after vaccination against CVL with Leishmune(®), subsequent seroconversion, antibody peak and positivity up to six months may lead vaccinated dogs to be mistakenly identified as naturally infected dogs during this period.


EPH gestosis in Glasgow, 1970.
Perinatal deaths due to EPH gestosis which occurred in Glasgow during 1970 were studied. There was a high frequency of perinatal deaths among babies born to primigravidae below the age of 20 years and to mothers with proteinuria. The majority of the deaths occurred in babies weighing less than or equal to 2,500 g. It is suggested that some of the deaths were avoidable and that a further reduction in perinatal mortality can still be achieved.


An association between paying physician-teachers for their teaching efforts and an improved educational experience for learners.
Medical schools often rely on faculty volunteerism to address clinical teaching needs for students. Increasing time pressures on physicians has made it difficult to secure commitments for clinical instruction. In the 2005-2006 academic year, the Johns Hopkins University School of Medicine (JHUSOM) launched the Colleges Program, recruiting 24 salary-supported physician-faculty to serve as advisors to students as well as teachers of the second year course, 'clinical skills'. We hypothesized that compensating physician educators would have a measurable positive impact on the students' experiences in this course. Students' assessments of paid colleges faculty (CF) preceptors from the 2005-2006 year were compared to those of volunteer preceptors from the two prior years (2003-2005 academic years) along six different teaching parameters linked to the course's objectives. Multivariable regression analysis was used to identify the factors independently associated with higher preceptor scores. Fifty-eight preceptors taught clinical skills over the 3-year study period. The overall response rate for preceptor evaluations by medical learners was 77% (277/359). CF, more likely than volunteer preceptors to have a full-time academic appointment (100 vs 63%, p < .01), have an additional advanced degree (48 vs 15%, p < .01) and prior faculty development training (52 vs 17%, p < .01). Scores for all six evaluation domains were higher for CF compared to those from the two previous years combined (all p < .001). In the fully adjusted regression model, only CF status was independently associated with high preceptor evaluation scores (Odds Ratio 4.3, 95% CI 1.01-18.20). Salary support for teaching efforts in the time-intensive CS course coupled with the prestige of being appointed to the CF was associated with higher student evaluations.


Structural trees for proteins containing phi-motifs.
In the present study, a novel structural motif of proteins referred to as the phi-motif is considered, and two novel structural trees in which the phi-motif is taken as the root structure have been constructed. The simplest phi-motif is formed by three adjacent beta-strands connected by loops and packed in one beta-sheet so that its overall fold resembles the Greek letter phi. Construction of the structural trees and modeling of folding pathways have shown that all structures of the protein superfamilies can be obtained by stepwise addition of alpha-helices and/or beta-strands to the root phi-motif taking into account a restricted set of rules inferred from known principles of protein structure. The structural trees are a good tool for structure comparison, structural classification of proteins, as well as for searching for all possible protein folds and folding pathways.


Transformed sweat gland and nasal epithelial cell lines from control and cystic fibrosis individuals.
We undertook to extend the in vitro lifespan of epithelial cell cultures useful for the study of the cellular defect underlying cystic fibrosis (CF). Primary cultures from sweat glands of four CF and four non-CF and from nasal polyps of one non-CF and two CF individuals were transformed using a chimaeric virus, Ad5/SV40 1613 ori-. The extended lifespans ranged from 20 to more than 250 population doublings beyond that of the primary cultures. Despite some degree of aneuploidy (as assayed by total cellular DNA content) all samples tested retained at least one copy of the region of chromosome 7 containing the CF gene (as assayed by probing with flanking DNA markers). Epithelial characteristics, including an epithelioid morphology, tight junctions and desmosomes, apical microvilli, keratin networks, and dome formation were positive in the majority of cells examined, although variably expressed. All cells tested demonstrated outwardly rectifying chloride channels by patch clamp, with some from non-CF cells responsive to the catalytic subunit of cyclic AMP-dependent protein kinase. The cells were used for DNA transfection assays with selectable marker genes in appropriate vectors, in order to develop methodology for assaying the function of the CF gene product and the effects of mutations.


Renin-angiotensin and adrenergic mechanisms in control of blood pressure in fowl.
Many avian species demonstrate atherosclerosis and high blood pressure (BP) that are influenced by age, sex, diet, and environment, but show no arteriosclerosis in small vessels. Thus, we aimed to define neural and humoral control of BP in conscious, 32-wk-old female chickens, Gallus gallus. Mean aortic pressure (determined by chronically implanted catheter) was 137.6 +/- 2.0 mm Hg; heart rate was 295 +/- 4 beats/min. Plasma renin activity (PRA), measured by radioimmunoassay of fowl angiotensin I ([Asp1, Val5, Ser9]AI), and plasma angiotensinogen levels were 3.55 +/- 0.31 ng/ml/hr and 1229 +/- 66 ng/ml respectively. Repeated injection of propranolol (4 to 8 mg/kg/day, i.m.) decreased (p less than 0.01) the BP 19.1 +/- 3.0 mm Hg and heart rate 76 +/- 6 beats/min. Acute infusion of propranolol also markedly reduced BP and heart rate, and increased plasma levels of norepinephrine and epinephrine. SQ 14,225 (20 mg/kg/day) reduced BP (p less than 0.01), but BP returned towards original levels unless a higher dose was given. PRA increased 2- to 6-fold. BP also decreased 31.0 +/- 2.1 mm Hg after reserpine treatment, but not after [Sar1, Ile8]AII. These results suggest that in maintaining BP in fowl the beta-adrenergic function is important, whereas the renin-angiotensin system may not have a primary role.


Regional bone density changes in anterior cruciate ligament deficient knees: a DEXA study.
Bone mineral density (BMD) loss is one of the secondary problems occurring in knee joint after injury of anterior cruciate ligament (ACL). The effect of this injury on BMDs of specific regions is not clear. The aim of this study was to investigate BMD changes in unreconstructed ACL-deficient knees with subregion analysis of dual energy X-ray absorptiometry (DEXA). Precision and reliability studies of DEXA revealed that two region of interests (ROI) in medial condyle, two ROIs in lateral femoral condyle (LFC) and one ROI in medial tibial plateau (MTP) in anteroposterior (AP) DXA view and one ROI for each of distal femur, proximal tibia and patella in lateral view had high reproducibility and reliability. Thirty-two patients with complete ACL ruptures were collected for the study and uninjured sides served as the control. All the patients were male with a mean age of 30 years. Mean duration of ACL rupture was 24 months. There were significant BMD losses in both ROIs of LFC and ROI of MTP in AP view and all three ROIs of lateral view. Greatest BMD losses in AP and lateral views were at MTP and patella respectively. There was a significant association between patellar BMD loss and duration after trauma. Bone bruises in lateral condyle might be the cause of selective involvement of LFC. Periarticular bone mineral loss in ACL-deficient knees has a predilection for the specified region of interest rather than uniform periarticular loss. This may be important for graft fixation or a factor in tunnel enlargement.


Ultrasonic treatment of experimental animal tumours.
Studies on the effects of ultrasound on several solid tumours in experimental animals have indicated that tumour growth rates can be reduced. These data are generally consistent with a thermal mechanism of action. Application of combined ultrasound and X-irradiation have shown that with some experimental animal tumours the radiation dose required to locally control 50% of the tumours can be reduced by ultrasound. These results were also consistent with a thermal mechanism of action hypothesis. Fractionated X-irradiation was not enhanced as much as single dose. Pulsing the ultrasound with the same time-average intensity resulted in the same radiosensitivity enhancement. The combined effects of ultrasound and cancer chemotherapy drugs have been studied in mouse leukaemia. The treatment was applied in vitro with cells in suspension. Subsequent to treatment, the cells were inoculated into host mice and survival was monitored. Cytotoxic action of 5 of 10 drugs studied was enhanced by ultrasound. A thermal mechanism of action apparently was not involved. Cavitation in the suspension probably played a role in the cytotoxic enhancement. Experimental data are consistent with the concept that ultrasound causes rapidly reversible cell damage which, in the presence of cytotoxic drugs, is not so readily reversed and results in significant loss of lethal potential of the malignant cells to the host.


Genetic Evidence for Erythrocyte Receptor Glycophorin B Expression Levels Defining a Dominant Plasmodium falciparum Invasion Pathway into Human Erythrocytes.
Plasmodium falciparum, the parasite that causes the deadliest form of malaria, has evolved multiple proteins known as invasion ligands that bind to specific erythrocyte receptors to facilitate invasion of human erythrocytes. The EBA-175/glycophorin A (GPA) and Rh5/basigin ligand-receptor interactions, referred to as invasion pathways, have been the subject of intense study. In this study, we focused on the less-characterized sialic acid-containing receptors glycophorin B (GPB) and glycophorin C (GPC). Through bioinformatic analysis, we identified extensive variation in glycophorin B (GYPB) transcript levels in individuals from Benin, suggesting selection from malaria pressure. To elucidate the importance of the GPB and GPC receptors relative to the well-described EBA-175/GPA invasion pathway, we used an ex vivo erythrocyte culture system to decrease expression of GPA, GPB, or GPC via lentiviral short hairpin RNA transduction of erythroid progenitor cells, with global surface proteomic profiling. We assessed the efficiency of parasite invasion into knockdown cells using a panel of wild-type P. falciparum laboratory strains and invasion ligand knockout lines, as well as P. falciparum Senegalese clinical isolates and a short-term-culture-adapted strain. For this, we optimized an invasion assay suitable for use with small numbers of erythrocytes. We found that all laboratory strains and the majority of field strains tested were dependent on GPB expression level for invasion. The collective data suggest that the GPA and GPB receptors are of greater importance than the GPC receptor, supporting a hierarchy of erythrocyte receptor usage in P. falciparum.


A science based approach to topical drug classification system (TCS).
The Biopharmaceutics Classification System (BCS) for oral immediate release solid drug products has been very successful; its implementation in drug industry and regulatory approval has shown significant progress. This has been the case primarily because BCS was developed using sound scientific judgment. Following the success of BCS, we have considered the topical drug products for similar classification system based on sound scientific principles. In USA, most of the generic topical drug products have qualitatively (Q1) and quantitatively (Q2) same excipients as the reference listed drug (RLD). The applications of in vitro release (IVR) and in vitro characterization are considered for a range of dosage forms (suspensions, creams, ointments and gels) of differing strengths. We advance a Topical Drug Classification System (TCS) based on a consideration of Q1, Q2 as well as the arrangement of matter and microstructure of topical formulations (Q3). Four distinct classes are presented for the various scenarios that may arise and depending on whether biowaiver can be granted or not.


[Interrelation of familial longevity and the state of the locomotor apparatus].
Relationship was studied between the familial longevity and age changes in the locomotor apparatus. According to the cross-sectional and longitudinal data, the individuals aged over 60 showed a decrease in the factor of familial longevity with pathology of the locomotor apparatus. Changes in clinical and objective data with age appeared to be more pronounced in persons whose families had no long-living relatives. The above changes were more expressed in men.


Model of bacterial band formation in aerotaxis.
Aerotaxis is a particular form of "energy taxis". It is based on a largely elusive signal transduction machinery. In aerotaxis, oxygen dissolved in water plays the role of both attractant (at moderate concentrations) and repellent (at high and low concentrations). Cells swimming from favorable oxygen concentrations into regions with unfavorable concentrations increase the frequency of reversals, turn back into the favorable domain, and become effectively trapped there. At the same time, bacteria consume oxygen, creating an oxygen gradient. This behavior leads to a pattern formation phenomenon: bacteria self-organize into a dense band at a certain distance from the air-water interface. We incorporate experimental observations of the aerotactic bacterium, Azospirillum brasilense, into a mathematical model. The model consists of a system of differential equations describing swimming bacterial cells and diffusing oxygen. The cells' frequency of reversals depends on the concentration of oxygen and its time derivative while oxygen is depleted by the bacteria. We suggest a hypothetical model of energy sensing mediated by aerotactic receptors Aer and Tsr. Computer simulations and analysis of the model equations allow comparisons of theoretical and experimental results and provide insight into the mechanisms of bacterial pattern formation and underlying signal transduction machinery. We make testable predictions about position and density of the bacterial band.


SMAD4-mediated WNT signaling controls the fate of cranial neural crest cells during tooth morphogenesis.
TGFβ/BMP signaling regulates the fate of multipotential cranial neural crest (CNC) cells during tooth and jawbone formation as these cells differentiate into odontoblasts and osteoblasts, respectively. The functional significance of SMAD4, the common mediator of TGFβ/BMP signaling, in regulating the fate of CNC cells remains unclear. In this study, we investigated the mechanism of SMAD4 in regulating the fate of CNC-derived dental mesenchymal cells through tissue-specific inactivation of Smad4. Ablation of Smad4 results in defects in odontoblast differentiation and dentin formation. Moreover, ectopic bone-like structures replaced normal dentin in the teeth of Osr2-IresCre;Smad4(fl/fl) mice. Despite the lack of dentin, enamel formation appeared unaffected in Osr2-IresCre;Smad4(fl/fl) mice, challenging the paradigm that the initiation of enamel development depends on normal dentin formation. At the molecular level, loss of Smad4 results in downregulation of the WNT pathway inhibitors Dkk1 and Sfrp1 and in the upregulation of canonical WNT signaling, including increased β-catenin activity. More importantly, inhibition of the upregulated canonical WNT pathway in Osr2-IresCre;Smad4(fl/fl) dental mesenchyme in vitro partially rescued the CNC cell fate change. Taken together, our study demonstrates that SMAD4 plays a crucial role in regulating the interplay between TGFβ/BMP and WNT signaling to ensure the proper CNC cell fate decision during organogenesis.


Characterization of a novel form of thymidylate synthase: a heterodimer isolated after specific chemical modification of the immobilized native enzyme.
A novel approach, utilizing covalent chromatography and selective chemical modification, is described for application in studying subunit interactions involved in the catalytic and regulatory mechanisms of certain oligomeric proteins. The specific objective was to prepare and characterize heterodimeric form of thymidylate synthase which would serve as a model for an intermediate stage of the catalytic mechanism in which the active-site cysteine of one subunit would be engaged in covalent catalysis while that of the other subunit would exist in the free sulfhydryl or thiolate anion form. Dimeric Lactobacillus casei thymidylate synthase was subjected to covalent chromatography on thiopropyl Sepharose 6B resin under conditions in which a mixed disulfide linkage was formed with the catalytic sulfhydryl group of just one of the two subunits. Specific chemical modification of the remaining essential sulfhydryl group of the immobilized group enzyme with N-ethylmalemide, followed by cleavage and elution with buffer containing 2-mercaptoethanol, yielded the desired soluble heterodimeric form of the enzyme. The specific activity of this unique form of the enzyme (1.55 units/mg) was approximately 60% that of native protein (2.61 units/mg). Gel electrophoretic analysis of the heterodimeric enzyme, incubated in the presence of FdUMP and 5,10-methylenetetrahydrofolate (CH2H4folate), resulted in the appearance of a single protein band corresponding to the 1:1:1 enzyme-FdUMP-CH2H4folate complex, confirming the new species as dimeric thymidylate synthase containing a single functional active site.(ABSTRACT TRUNCATED AT 250 WORDS)


Interaction of poly-L-lysine with chromatin. Inhibition of in situ priming for Escherichia coli DNA polymerase.
The priming capacity of chromatin of fixed nuclei and chromosomes for exogenous DNA polymerase can be evaluated radioautographically by the incorporation of labeled nucleotides. It had previously been reported that acid fixation or acid treatment of alcohol-fixed tissues led to increased priming when calf thymus DNA polymerases, specific for single-stranded DNA, were used. We employed Escherichia coli DNA polymerase and sequential treatments of the fixed tissue with acid and poly-L-lysine in order to elucidate the mechanism through which the acid effect is produced. Acid treatment enhanced chromatin priming for the E coli DNA polymerase, and saturation of the chromatin with poly-L-lysine strongly inhibited the reaction. This inhibition was reversible through subsequent treatment with acid. Wide differences in priming were observed between cell types of alcohol-fixed chicken blood smears: thrombocyte and lymphocyte nuclei exhibited strong priming ability whereas erythrocyte nuclei failed to support any detectable priming. We conclude that the acid effect is readily interpretable in terms of acid-mediated changes in the association between DNA and protein in the chromatin complex.


Recommendations for postoperative radiotherapy in head & neck squamous cell carcinoma in the presence of flaps: A GORTEC internationally-reviewed HNCIG-endorsed consensus.
Head and neck reconstructive surgery using a flap is increasingly common. Best practices and outcomes for postoperative radiotherapy (poRT) with flaps have not been specified. We aimed to provide consensus recommendations to assist clinical decision-making highlighting areas of uncertainty in the presence of flaps. Radiation, medical, and surgical oncologists were assembled from GORTEC and internationally with the Head and Neck Cancer International Group (HNCIG). The consensus-building approach covered 59 topics across four domains: (1) identification of postoperative tissue changes on imaging for flap delineation, (2) understanding of tumor relapse risks and target volume definitions, (3) functional radiation-induced deterioration, (4) feasibility of flap avoidance. Across the 4 domains, international consensus (median score ≥ 7/9) was achieved only for functional deterioration (73.3%); other consensus rates were 55.6% for poRT avoidance of flap structures, 41.2% for flap definition and 11.1% for tumor spread patterns. Radiation-induced flap fibrosis or atrophy and their functional impact was well recognized while flap necrosis was not, suggesting dose-volume adaptation for the former. Flap avoidance was recommended to minimize bone flap osteoradionecrosis but not soft-tissue toxicity. The need for identification (CT planning, fiducials, accurate operative report) and targeting of the junction area at risk between native tissues and flap was well recognized. Experts variably considered flaps as prone to tumor dissemination or not. Discrepancies in rating of 11 items among international reviewing participants are shown. International GORTEC and HNCIG-endorsed recommendations were generated for the management of flaps in head and neck radiotherapy. Considerable knowledge gaps hinder further consensus, in particular with respect to tumor spread patterns.


Fermentative production of lactic acid from renewable materials: recent achievements, prospects, and limits.
The development and implementation of renewable materials for the production of versatile chemical resources have gained considerable attention recently, as this offers an alternative to the environmental problems caused by the petroleum industry and the limited supply of fossil resources. Therefore, the concept of utilizing biomass or wastes from agricultural and industrial residues to produce useful chemical products has been widely accepted. Lactic acid plays an important role due to its versatile application in the food, medical, and cosmetics industries and as a potential raw material for the manufacture of biodegradable plastics. Currently, the fermentative production of optically pure lactic acid has increased because of the prospects of environmental friendliness and cost-effectiveness. In order to produce lactic acid with high yield and optical purity, many studies focus on wild microorganisms and metabolically engineered strains. This article reviews the most recent advances in the biotechnological production of lactic acid mainly by lactic acid bacteria, and discusses the feasibility and potential of various processes.


Molecular Epidemiology of Methicillin-Resistant Staphylococcus aureus Isolated from Australian Veterinarians.
This work investigated the molecular epidemiology and antimicrobial resistance of methicillin-resistant Staphylococcus aureus (MRSA) isolated from veterinarians in Australia in 2009. The collection (n = 44) was subjected to extensive molecular typing (MLST, spa, SCCmec, dru, PFGE, virulence and antimicrobial resistance genotyping) and antimicrobial resistance phenotyping by disk diffusion. MRSA was isolated from Australian veterinarians representing various occupational emphases. The isolate collection was dominated by MRSA strains belonging to clonal complex (CC) 8 and multilocus sequence type (ST) 22. CC8 MRSA (ST8-IV [2B], spa t064; and ST612-IV [2B], spa variable,) were strongly associated with equine practice veterinarians (OR = 17.5, 95% CI = 3.3-92.5, P < 0.001) and were often resistant to gentamicin and rifampicin. ST22-IV [2B], spa variable, were strongly associated with companion animal practice veterinarians (OR = 52.5, 95% CI = 5.2-532.7, P < 0.001) and were resistant to ciprofloxacin. A single pig practice veterinarian carried ST398-V [5C2], spa t1451. Equine practice and companion animal practice veterinarians frequently carried multiresistant-CC8 and ST22 MRSA, respectively, whereas only a single swine specialist carried MRSA ST398. The presence of these strains in veterinarians may be associated with specific antimicrobial administration practices in each animal species.


[Evaluation of satisfaction with pharmacological treatment in people with hypertension].
Medication satisfaction is a patientcentered measure that helps predict the continuity of treatment, correct use and therapeutic compliance. The objective has been to evaluate the satisfaction with the treatment (ST) of subjects with arterial hypertension (HT) and find out if the type of treatment, the state of health and the personal characteristics are related to the satisfaction. Observational cross-sectional study conducted in the community pharmacy field. A total of 484 users of antihypertensive medication were evaluated (response rate: 81.6%). The ST was evaluated through the Treatment Satisfaction with Medicines. In the statistical analysis, means comparison and correlation tests were used to verify the existence of associations between the ST level and the different variables, considering a significance level of p<0.05. Likewise, a multiple linear regression model was constructed to identify the associated variables avoiding possible confounding factors. In a range of 0-100 the mean ST value was 79.9 (SD=12.9, 95% CI=78.8-81.0). A weak correlation was observed between perceived health score and ST (r=0.145, p=0.001). ST was higher in subjects with controlled BP (82.1 ±12.1 SD vs 77.5 ±13.3 SD, p<0.001), in treated subjects over 5 years (83.5 ± 12.8 SD vs 78.5 ±12.6 SD; p<0.001), in subjects without adverse effects (82.5 ±11.6 SD vs 68.7 ±11.9 SD; p<0.001) and in lower social classes (81.2 ±12.8 SD vs 78.5 ±12.8 SD, p=0.02). It was lower in the non-compliers with the treatment (73.2 ±12.9 vs 82.1 ±12.1, p<0.001). The ST level is acceptable, despite insufficient BP control and the high rate of noncompliance. Satisfaction is conditioned both by effectiveness and by therapeutic adherence, although health status, treatment and personal characteristics also intervene.


Granulocytes as effectors in cell-mediated cytotoxicity of adherent target cells.
In the microassay for cell-mediated immunity, detachment of adherent target cells from the wells occurs to an even greater extent when tested with granulocytes than when tested with lymphocytes. Intact cells are not necessary since the sonic extract from granulocytes causes the same effect. The reaction by granulocytes appears to be mediated by enzymes, and is inhibited by the presence in the wells of hyaluronic acid. Moreover, it is limited to the detachment of adherent target cells, since neither intact nor sonically disrupted granulocytes exhibit cytotoxic activity in the chromium release assay. The detachment of target cells is also inhibited by heparin which may be used to specifically mullify the effect of granulocytes contaminating lymphocyte suspensions.


A new Ixodes species (Acari: Ixodidae), parasite of shrew tenrecs (Afrosoricida: Tenrecidae) in Madagascar.
Abstract : A new tick species belonging to the African subgenus Afrixodes Morel, 1966 of the genus Ixodes Latreille, 1795, namely, Ixodes (Afrixodes) microgalei n. sp., is described. Females of this species are most similar to those of Ixodes colasbelcouri Arthur, 1957 and Ixodes nesomys Uilenberg & Hoogstraal, 1969. The female of the new species can easily be differentiated from I. colasbelcouri by a short spur on coxae IV, and from I. nesomys by longer spurs on coxae I and large punctations on its scutum. Ixodes microgalei is known only from the eastern humid forest of Madagascar, specifically in the Province of Antananarivo, where its females have been collected from several species of shrew tenrecs (Afrosoricida, Tenrecidae), namely, Microgale dobsoni Thomas, Microgale parvula Grandidier, and Microgale soricoides Jenkins.


Anatomy and regulation of the central melanocortin system.
The central melanocortin system is perhaps the best-characterized neuronal pathway involved in the regulation of energy homeostasis. This collection of circuits is unique in having the capability of sensing signals from a staggering array of hormones, nutrients and afferent neural inputs. It is likely to be involved in integrating long-term adipostatic signals from leptin and insulin, primarily received by the hypothalamus, with acute signals regulating hunger and satiety, primarily received by the brainstem. The system is also unique from a regulatory point of view in that it is composed of fibers expressing both agonists and antagonists of melanocortin receptors. Given that the central melanocortin system is an active target for development of drugs for the treatment of obesity, diabetes and cachexia, it is important to understand the system in its full complexity, including the likelihood that the system also regulates the cardiovascular and reproductive systems.


Exercise interventions for dementia and cognitive impairment: the Seattle Protocols.
Research evidence strongly suggests that increased physical exercise may not only improve physical function in older adults but may also improve mood and slow the progression of cognitive decline. This paper describes a series of evidence-based interventions grounded in social-learning and gerontological theory that were designed to increase physical activity in persons with dementia and mild cognitive impairment. These programs, part of a collective termed the Seattle Protocols, are systematic, evidence-based approaches that are unique 1) in their focus on the importance of making regular exercise a pleasant activity, and 2) in teaching both cognitively impaired participants and their caregivers behavioral and problem-solving strategies for successfully establishing and maintaining realistic and pleasant exercise goals. While additional research is needed, initial findings from randomized controlled clinical trials are quite promising and suggest that the Seattle Protocols are both feasible and beneficial for community-residing individuals with a range of cognitive abilities and impairments.


Prevalence of Arterial Hypertension and Characteristics of Nocturnal Blood Pressure Profile of Asthma Patients According to Therapy and Severity of the Disease: The BADA Study.
several studies report an increased risk for asthmatic subjects to develop arterial hypertension and the relationship between these two diseases, frequently co-existing, still has some unclear aspects. The BADA (blood pressure levels, clinical features and markers of subclinical cardiovascular damage of asthma patients) study is aimed to evaluate the prevalence of the cardiovascular comorbidities of asthma and their impact on the clinical outcome. The main exclusion criteria were the presence of other respiratory diseases, current smoking, any contraindication to ambulatory blood pressure monitoring (ABPM). The overall percentage of asthmatics having also hypertension was 75% (30 patients) vs. 45% (18 patients) of the control group (p: 0.012). Reduced level of FEV1 (but not inhaled steroid therapy) was associated to newly-diagnosed hypertension (p: 0.0002), higher day SBP levels (p: 0.003), higher day DBP levels (p: 0.03), higher 24 h-SBP levels (p: 0.005) and higher 24h-DBP levels (p: 0.03). The regression analysis performed taking into account sex, age, diabetes, fasting glucose, and body mass index confirms the independent role played by asthma: odds ratio (OR): 3.66 (CI: 1.29-11.1). hypertension is highly prevalent in asthma; the use of ABPM has allowed the detection of a considerable number of unrecognized hypertensives.


Clinical Comparison of Preterm Birth and Spontaneous Preterm Birth in Severe Preeclampsia.
Severe preeclampsia is accompanied by many complications, which is extremely harmful to pregnant women and fetuses. However, in the classification of preterm birth, it is generally divided into spontaneous preterm birth and therapeutic preterm birth, and insufficient attention has been paid to preterm birth in severe preeclampsia. This article aims to explore the clinical difference between preterm birth in severe preeclampsia and spontaneous preterm birth. In the experiment, this paper selected pregnant women who delivered and were treated in a hospital from April 2010 to April 2020 as cases. In terms of grouping, not only are they divided into severe eclampsia group (observation group 1), spontaneous preterm birth group (observation group 2), and general delivery group (control group) according to the cause of premature birth, but also according to the gestational age of severe eclampsia onset, preterm weeks, and other groups. Not only the clinical difference between severe preeclampsia preterm birth and spontaneous preterm birth was compared horizontally, but also the factors affecting the complications of preterm pregnant women, perinatal asphyxia rate, and mortality were longitudinally analyzed. The experimental results in this paper showed that there were significant differences in maternal complications and neonatal mortality between the severe preeclampsia preterm group and the spontaneous preterm group (P < 0.05). In addition, the severe preeclampsia preterm birth group was more harmful than the spontaneous preterm birth group. The complication rate of the severe preeclampsia preterm birth group was 10% higher than that of the spontaneous preterm birth group, and the neonatal mortality rate was 2% higher.


Initial Postoperative Hemoglobin Values and Clinical Outcomes in Transfused Patients Undergoing Noncardiac Surgery.
Intraoperative red blood cell (RBC) transfusion is common, yet transfusion strategies remain controversial as pretransfusion hemoglobin triggers are difficult to utilize during acute bleeding. Alternatively, postoperative hemoglobin values may provide useful information regarding transfusion practices, though optimal targets remain undefined. This is a single-center observational cohort study of adults receiving allogeneic RBCs during noncardiac surgery from 2010 through 2014. Multivariable regression analyses adjusting for patient illness, laboratory derangements, and surgical features were used to assess relationships between initial postoperative hemoglobin values and a primary outcome of hospital-free days. A total of 8060 patients were included. Those with initial postoperative hemoglobin <7.5 or ≥11.5 g/dL had decreased hospital-free days [mean (95% confidence interval [CI]), -1.45 (-2.50 to -0.41) and -0.83 (-1.42 to -0.24), respectively] compared to a reference range of 9.5-10.4 g/dL (overall P value .003). For those with hemoglobin <7.5 g/dL, the odds (95% CI) for secondary outcomes included acute kidney injury (AKI) 1.43 (1.03-1.99), mortality 2.10 (1.18-3.74), and cerebral ischemia 3.12 (1.08-9.01). The odds for postoperative mechanical ventilation with hemoglobin ≥11.5 g/dL were 1.33 (1.07-1.65). Secondary outcome associations were not significant after multiple comparisons adjustment (Bonferroni P < .0056). In transfused patients, postoperative hemoglobin values between 7.5 and 11.5 g/dL were associated with superior outcomes compared to more extreme values. This range may represent a target for intraoperative transfusions, particularly during active bleeding when pretransfusion hemoglobin thresholds may be impractical or inaccurate. Given similar outcomes within this range, targeting hemoglobin at the lower aspect may be preferable, though prospective validation is warranted.


Interpersonal synchrony feels good but impedes self-regulation of affect.
The social benefits of interpersonal synchrony are widely recognized. Yet, little is known about its impact on the self. According to enactive cognitive science, the human self for its stability and regulation needs to balance social attunement with disengagement from others. Too much interpersonal synchrony is considered detrimental for a person's ability to self-regulate. In this study, 66 adults took part in the Body-Conversation Task (BCT), a dyadic movement task promoting spontaneous social interaction. Using whole-body behavioural imaging, we investigated the simultaneous impact of interpersonal synchrony (between persons) and intrapersonal synchrony (within a person) on positive affect and self-regulation of affect. We hypothesized that interpersonal synchrony's known tendency to increase positive affect would have a trade-off, decreasing a person's ability to self-regulate affect. Interpersonal synchrony predicted an increase in positive affect. Consistent with our hypothesis, it simultaneously predicted a weakening in self-regulation of affect. Intrapersonal synchrony, however, tended to oppose these effects. Our findings challenge the widespread belief that harmony with others has only beneficial effects, pointing to the need to better understand the impact of interaction dynamics on the stability and regulation of the human self.


Anti-adherence and bactericidal activity of sphingolipids against Streptococcus mutans.
This study evaluated the anti-biofilm activity of sphingosine, phytosphingosine (PHS), and sphinganine for: (i) anti-adherence activity on hydroxyapatite (HA) surfaces; and (ii) bactericidal activity on different Streptococcus mutans phenotypes (i.e. planktonic cells and cells from a disrupted biofilm). For this, HA discs treated with sphingolipids were incubated with S. mutans and the number of adherent cells was evaluated by both culture and confocal microscopy. Sphinganine strongly inhibited bacterial adherence by 1000-fold compared with an untreated surface. Phytosphingosine and sphingosine inhibited bacterial adherence by eight- and five-fold, respectively, compared with an untreated surface. On saliva-coated HA, sphinganine and PHS inhibited bacterial adherence by 10-fold. Bactericidal activity of sphingolipids was evaluated by culture. For biofilms, the strongest bactericidal activity was exhibited by sphingosine compared with PHS and sphinganine. At a concentration of 12.5 μg ml(-1) , PHS and sphingosine were profoundly effective against planktonic and disrupted biofilms; and sphinganine reduced the number of cells in planktonic form by 100-fold and those derived from a disrupted biofilm by 1000-fold. Atomic force microscopy studies suggested that mechanical stability does not appear to be a factor relevant for anti-fouling activity. The results suggest that sphingolipids may be used to control oral biofilms, especially those loaded with S. mutans.


The effect of a multidisciplinary intervention program for overweight and obese children on cardiorespiratory fitness and blood pressure.
Multidisciplinary intervention programs for overweight and obese children mainly focus on reducing bodyweight and body mass index (BMI), but they may also positively impact blood pressure (BP), and cardiorespiratory fitness (CRF), which is a stronger predictor for all-cause mortality than BMI. To evaluate whether Kids4Fit, a multidisciplinary weight reduction program, has a positive effect on CRF and BP in overweight and obese children in socially deprived areas. A quasi-experimental study design with a waiting list control period including children who participated in a multidisciplinary intervention program of 12 weeks was set-up. Blood pressure measurements and shuttle-run test (SRT) were performed at baseline, at the start of the intervention, at the end of intervention and after 52 weeks. The effect of Kids4Fit on BP and on SRT scores were analyzed using mixed models. A total of 154 children were included [mean age 8.5 years (SD 1.8)]. No significant change was seen in systolic BP percentiles at 52 weeks after start of the Kids4Fit intervention (β 0.08, (95%CI -0.06, 0.22)). Diastolic BP percentiles increased significantly over time (β 0.20 (0.08, 0.31)). Effect plots showed an initial significant increase of the SRT scores but this effect diluted after the intervention. A local multidisciplinary intervention program in deprived areas had a significant positive effect on CRF, but this effect diluted after the intervention. Diastolic BP percentiles significantly increased over time. However, systolic BP did not change over time.


Factors That Influence Linkages to HIV Continuum of Care Services: Implications for Multi-Level Interventions.
Worldwide, the human immunodeficiency virus (HIV) continuum of care involves health promotion providers (e.g., social workers and health educators) linking patients to medical personnel who provide HIV testing, primary care, and antiretroviral treatments. Regrettably, these life-saving linkages are not always made consistently and many patients are not retained in care. To design, test and implement effective interventions, we need to first identify key factors that may improve linkage-making. To help close this gap, we used in-depth interviews with 20 providers selected from a sample of 250 participants in a mixed-method longitudinal study conducted in New York City (2012-2017) in order to examine the implementation of HIV services for at-risk populations. Following a sociomedical framework, we identified provider-, interpersonal- and environmental-level factors that influence how providers engage patients in the care continuum by linking them to HIV testing, HIV care, and other support services. These factors occurred in four domains of reference: Providers' Professional Knowledge Base; Providers' Interprofessional Collaboration; Providers' Work-Related Changes; and Best Practices in a Competitive Environment. Of particular importance, our findings show that a competitive environment and a fear of losing patients to other agencies may inhibit providers from engaging in linkage-making. Our results suggest relationships between factors within and across all four domains; we recommend interventions to modify factors in all domains for maximum effect toward improving care continuum linkage-making. Our findings may be applicable in different areas of the globe with high HIV prevalence.