Maxillary sinus floor augmentation: comparing osteotome with lateral window immediate and delayed implant placements. An interim report.
A retrospective study was performed to observe clinical outcomes of dental implants placed in augmented maxillary sinuses using an osteotome or a lateral approach technique with synchronous or delayed implant placement. A total of 61 patients were enrolled in the study. The distribution and frequency of sinus augmentation techniques and implant placements were evaluated according to the implant site and Cawood-Howell classifications. The implant survival rates were assessed clinically and radiographically over a minimum of 3 years of follow-up. The number of implants placed was fewer in the molar region compared with the premolar region and was independent of the surgical techniques used. Significantly fewer implants were placed in implant site class D and Cawood-Howell class V. Optimal survival rates were evident in all groups, with no significant changes. The most predictable region for sinus augmentation with simultaneous implant placement was the maxillary premolar area. All 80 implants were successful using either osteotome or lateral approaches to augment the maxillary sinus floor.


Microanatomy of the paired-fin pads of ostariophysan fishes (Teleostei: Ostariophysi).
Members of the teleost superorder Ostariophysi dominate freshwater habitats on all continents except Antarctica and Australia. Obligate benthic and rheophilic taxa from four different orders of the Ostariophysi (Gonorynchiformes, Cypriniformes, Characiformes, and Siluriformes) frequently exhibit thickened pads of skin along the ventral surface of the anteriormost ray or rays of horizontally orientated paired (pectoral and pelvic) fins. Such paired-fin pads, though convergent, are externally homogenous across ostariophysan groups (particularly nonsiluriform taxa) and have been considered previously to be the result of epidermal modification. Histological examination of the pectoral and/or pelvic fins of 44 species of ostariophysans (including members of the Gonorynchiforms, Cypriniformes, Characiformes, and Siluriformes) revealed a tremendous and previously unrecognized diversity in the cellular arrangement of the skin layers (epidermis and subdermis) contributing to the paired-fin pads. Three types of paired-fin pads (Types 1-3) are identified in nonsiluriform ostariophysan fishes, based on differences in the cellular arrangement of the epidermis and subdermis. The paired-fin pads of siluriforms may or may not exhibit a deep series of ridges and grooves across the surface. Two distinct patterns of unculus producing cells are identified in the epidermis of the paired-fin pads of siluriforms, one of which is characterized by distinct bands of keratinization throughout the epidermis and is described in Amphilius platychir (Amphiliidae) for the first time. General histological comparisons between the paired fins of benthic and rheophilic ostariophysan and nonostariophysan percomorph fishes are provided, and the possible function(s) of the paired-fin pads of ostariophysan fish are discussed.


Description of healthcare needs at an episodic clinic in rural southwest Virginia.
The objective of this study was to describe the population served at an episodic clinic in Southwest Virginia to better understand patient needs at a yearly episodic Remote Area Medical (RAM) clinic that provides free healthcare services. The dataset was compiled retrospectively from 2834 medical records from RAM patients between 1 July 2006 and 31 July 2008. Information was de-identified and manually recorded from paper records. The data were analyzed using descriptive statistics and compared to pre-existing estimates from the region. The number and type of services rendered at the RAM clinic each year varied greatly, and was dependent on the availability of staff and supplies. Diabetes, hypertension, and other prevalent diseases were reported, and an overwhelming majority (74%) of patients were overweight or obese. In 2008, 62% of patients were uninsured, 44% had no primary care physician, and a majority of patients were diagnosed with hypertension or poorly managed diabetes. Chronic diseases including obesity, hypertension, diabetes, and arthritis plague the Appalachian region. However, better knowledge of the medically underserved in this region can help address the patient's needs through RAM clinics and other accessible health clinics by increasing patient and physician awareness of available services, decreasing patient waiting time, and improving medical recordkeeping.


Colorectal cancer screening in rural and remote areas: analysis of the National Bowel Cancer Screening Program data for South Australia.
In Australia, colorectal cancer is the second most commonly diagnosed cancer and cause of death from malignant diseases, and its incidence is rising. The aim of this article was to present an analysis of National Bowel Cancer Screening Program (NBCSP) data for rural and remote South Australia (SA), in order to identify geographical areas and population groups that may benefit from targeted approaches to increase participation rates in colorectal cancer screening. De-identified data from the NBCSP (February 2007 to July 2008) were provided by Medicare Australia. Mapping and analysis of the NBCSP data was performed using ESRI ArcGIS (http://www.esri.com/software/arcgis/index.html) and MapInfo (http://slp.pbinsight.com/info/mipro-sem-au). Data were aggregated to postcode and Accessibility/Remoteness Index of Australia (ARIA) and participation was then mapped according to overall participation rates, sex, age, Indigenous status and Socio-Economic Indexes for Areas (SEIFA)-Index of Relative Socio-Economic Disadvantage (IRSD). The participants were South Australians who turned 55 and 65 years between 2007 and 2008 who returned the completed NBCSP test sent to them by Medicare Australia. The overall participation rate was 46.1% in rural and remote SA, although this was statistically significantly different (p<.001) according to sex (46.7% for males and 53.3% for females), age (45.2% for those 55 years, and 52% for those 65 years), socio-economic status (from 43% in 'most deprived' quintile to 50% in 'most affluent' quintile) and remoteness (45.6% for metropolitan, 46% for remote and 48.6% for rural areas). Indigenous participation was 0.5%. The findings of this study suggest lower NBCSP participation rates for people from metropolitan and remote areas, compared with those from rural areas. The uptake of cancer screening is lower for older rural and remote residents, men, Indigenous people, lower socioeconomic groups and those living in the Far North subdivision of SA.


Efficacy and safety of cilostazol based triple antiplatelet treatment versus dual antiplatelet treatment in patients undergoing coronary stent implantation: an updated meta-analysis of the randomized controlled trials.
The aim of this study was to obtain best estimates of the efficacy and safety of cilostazol-based triple antiplatelet therapy (TAPT: aspirin, clopidogrel and cilostazol) compared with dual antiplatelet therapy (DAPT: aspirin and clopidogrel) in patients undergoing coronary stent implantation. We searched the literature to identify all randomized clinical trials examining efficacy and safety of TAPT versus DAPT in patients undergoing coronary stent implantation. Major efficacy outcomes were death, non-fatal myocardial infarction (MI), ischemic stroke and stent thrombosis (ST) and the safety outcome was bleeding. Data were analyzed using the Review Manager 5.0.0 software. A total of 19 trials involving 7,464 patients were included. TAPT and DAPT were associated with similar rates of death, non-fatal MI, ischemic stroke and ST, but compared with DAPT, TAPT had lower rates of target lesion revascularization (TLR) (RR 0.67, 95 % CI 0.56-0.82, P < 0.0001) and target vessel revascularization (TVR) (RR 0.65, 95 % CI 0.55-0.77, P < 0.00001), as well as less late loss of minimal lumen diameter (mean difference -0.14, 95 % CI -0.17--0.11, P < 0.00001), and less binary angiographic restenosis (RR 0.54, 95 % CI 0.45-0.65, P < 0.00001). TAPT and DAPT had similar rates of bleeding, but TAPT had significantly higher rates of headache, palpitation, rash and gastrointestinal side-effects. Cilostazol-based TAPT compared with DAPT is associated with improved angiographic outcomes and decreased risk of TLR and TVR but does not reduce major cardiovascular events and is associated with an increase in minor adverse events.


Short- and long-term memory tasks predict working memory performance, and vice versa.
The Brown-Peterson, operation span, and continual distractor tasks all require people to retain information while performing a distractor task. Scale Independent Memory, Perception, and Learning (SIMPLE), a local relative distinctiveness model, has been fit to aspects of each task and offers the same explanation for each: the distractor task serves to space the items out in time and memory performance depends on the relative distinctiveness of the target item at the time of recall. If this is correct, it follows that performance on all three tasks should correlate, even though the tasks have, at various times, been ascribed to different memory systems, short-term memory, working memory, and long-term memory, respectively. We tested 190 subjects on all three tasks and found that performance on all three tasks is significantly correlated. We then fit the data from each task using SIMPLE. We argue that these results support the relative distinctiveness principle (Surprenant & Neath, 2009). We contrast SIMPLE with other models of the same tasks. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Solubilization of oils or addition of monoglycerides drives the formation of wormlike micelles with an elliptical cross-section in cholesterol-based surfactants: a study by rheology, SANS, and cryo-TEM.
We report the formation of wormlike micelles (WLM) in poly(oxyethylene) cholesteryl ether (ChEO(10)) aqueous solutions by the addition of lipophilic monoglycerides at room temperature (monolaurin (ML), monocaprin (MC), and monocaprylin (MCL)) bearing 12-, 10-, and 8-carbon alkyl chains, respectively. A combination of rheology, small-angle neutron scattering (SANS), and cryo-TEM was used to study their viscoelastic properties and structure. With the successive addition of cosurfactant, a significant increase in viscosity and a clear solidlike behavior is obtained, suggesting the formation of a viscoelastic network of wormlike micelles. Only for MCL is typical Maxwellian behavior obtained. The onset of micellar growth, as detected by the occurrence of solidlike behavior and a significant increase in viscosity, is obtained for 0.30 (1 wt%), 0.34 (1 wt%), and 0.60 (1.5 wt%) cosurfactant/ChEO(10) molar ratios with ML, MC, and MCL, respectively. With ML and MC, extremely long relaxation times (exceeding 20 s) compared to those of MCL are obtained, and zero-shear viscosity values are more than 1 order of magnitude higher than with MCL. These results show that cosurfactants with longer alkyl chain lengths (ML and MC) induce the formation of longer wormlike micelles and do so at lower concentrations. SANS measurements on dilute solutions confirm that the viscoelastic behavior correlates with an increase in contour length and reveals an elliptical cross-section with an axial ratio of around 2. Cryo-TEM images provide visual evidence of the wormlike micelles and confirm the elliptical shape of the cross-section. The addition of small amounts of aliphatic oils (ethyl butyrate, EB, and ethyl caprylate, EC) and cyclic oils (peppermint, PP, and tea tree, TT, oils) to ChEO(10) solutions induces wormlike micelle formation at a lower cosurfactant concentration or even in its absence (for PP, TT, and EC) because of their probable localization in the palisade layer. The viscosity peak and height of the plateau modulus occur at increasing monoglyceride concentration following the order PP ≈ TT > EC > EB > no oil.


[Transcutaneous bilirubinometry and early hospital discharge in low risk newborns with jaundice].
Discharge soon after birth and beginning of therapeutic interventions in jaundiced newborns depends on the assessment of bilirubin serum levels. The comparison between total bilirubin serum levels with transcutaneous bilirubin levels and evaluate utility of a hand held device to measure transcutaneous bilirubin as a diagnostic tool to predict early discharge. Transversal, prolective study. Near simultaneous measurements of serum and transcutaneous bilirubin was undertaken in newborns with birth weight > 2000 grams, gestational age > 36 weeks and extrauterine life under 72 hours. 100 newborns were enrolled, with birth weight 3,135 +/- 499.9 grams, gestational age of 38.85 +/- 1.4 weeks and 45.46 +/- 1.75 hours of life at the time of bilirubin measurement. Correlation coefficient was 0.81 (p < 0.0001). Predischarge quantification of jaundice by transcutaneous bilirubin should be performed in all healthy newborns. Levels under 4.9 mg/dL within first 24 hours of life and values under 7.9 mg/dL between 48 to 72 hours, were considered safely to allow early discharge in newborns studied.


Reproducibility of the NEPTUNE descriptor-based scoring system on whole-slide images and histologic and ultrastructural digital images.
The multicenter Nephrotic Syndrome Study Network (NEPTUNE) digital pathology scoring system employs a novel and comprehensive methodology to document pathologic features from whole-slide images, immunofluorescence and ultrastructural digital images. To estimate inter- and intra-reader concordance of this descriptor-based approach, data from 12 pathologists (eight NEPTUNE and four non-NEPTUNE) with experience from training to 30 years were collected. A descriptor reference manual was generated and a webinar-based protocol for consensus/cross-training implemented. Intra-reader concordance for 51 glomerular descriptors was evaluated on jpeg images by seven NEPTUNE pathologists scoring 131 glomeruli three times (Tests I, II, and III), each test following a consensus webinar review. Inter-reader concordance of glomerular descriptors was evaluated in 315 glomeruli by all pathologists; interstitial fibrosis and tubular atrophy (244 cases, whole-slide images) and four ultrastructural podocyte descriptors (178 cases, jpeg images) were evaluated once by six and five pathologists, respectively. Cohen's kappa for inter-reader concordance for 48/51 glomerular descriptors with sufficient observations was moderate (0.40<kappa≤0.60) for 17 and good (0.60<kappa≤0.80) for 8, for 52% with moderate or better kappas. Clustering of glomerular descriptors based on similar pathologic features improved concordance. Concordance was independent of years of experience, and increased with webinar cross-training. Excellent concordance was achieved for interstitial fibrosis and tubular atrophy. Moderate-to-excellent concordance was achieved for all ultrastructural podocyte descriptors, with good-to-excellent concordance for descriptors commonly used in clinical practice, foot process effacement, and microvillous transformation. NEPTUNE digital pathology scoring system enables novel morphologic profiling of renal structures. For all histologic and ultrastructural descriptors tested with sufficient observations, moderate-to-excellent concordance was seen for 31/54 (57%). Descriptors not sufficiently represented will require further testing. This study proffers the NEPTUNE digital pathology scoring system as a model for standardization of renal biopsy interpretation extendable outside the NEPTUNE consortium, enabling international collaborations.


[Acute abdomen due to eosinophilic gastroenteritis. A study of 2 cases].
Report of two cases of eosinophilic gastroenteritis. In both cases the presentation was an acute abdomen syndrome. The etiological diagnosis was postoperative, because in the preoperative period there were no data characteristic of this entity. Probably this disease is more frequent than reported and although the treatment is medical, there are some cases in which surgery is justified.


Sequence variation in the 18S rRNA gene, a target for PCR-based malaria diagnosis, in Plasmodium ovale from southern Vietnam.
Field surveys of malaria were performed in southern Vietnam by using an acridine orange staining method for rapid diagnosis and a PCR-based, microtiter plate hybridization method for accurate diagnosis. A total of three patients of Plasmodium ovale infection were detected, but PCR-amplified DNA of the P. ovale isolates from two of the patients did not hybridize with the P. ovale-specific probe. Analysis of the target sequence in the 18S rRNA gene indicated that in the DNA of isolates from both patients three nucleotides in the probe region from the typical P. ovale sequence were different, with deletions of two nucleotides and the substitution of one nucleotide. These results may suggest that in addition to molecular biological methods, careful microscopic examination of stained thin blood films is still required in studies of the prevalence of different malaria species.


Multiple intracranial aneurysms followed left atrial myxoma: case report and literature review.
Cerebral aneurysms follows atrial myxoma is a rare neurological complication. We report a patient with multiple cerebral aneurysms three years after resection of left atrial myxoma and further review the literature. The characteristics of these aneurysms are indefinite and variable. They can occur prior or post the resection of cardiac myxoma. "Metastasize and Infiltrate" theory may be the key mechanism in the formation of these aneurysms. Magnetic resonance imaging (MRI), computed tomography (CT) and angiography are useful in the diagnosis while digital subtraction angiography (DSA) is the best choice. There are no definite guidelines for therapy of these aneurysms. Resection of the cardiac myxomas, chemotherapy, radiotherapy, coil embolization and surgical treatment could be helpful.


Influence of Mass and Social Media on Psychobehavioral Responses Among Medical Students During the Downward Trend of COVID-19 in Fujian, China: Cross-Sectional Study.
An extensive amount of information related to the novel coronavirus (COVID-19) pandemic was disseminated by mass and social media in China. To date, there is limited evidence on how this infodemic may influence psychobehavioral responses to the crisis. The aim of this study is to assess the psychobehavioral responses to the COVID-19 outbreak and examine their associations with mass and social media exposure. A cross-sectional study among medical and health sciences students from the Fujian Medical University in Fuzhou, China, was conducted between April 6-22, 2020. A total of 2086 completed responses were received. Multivariable analyses demonstrated that four constructs of the Health Belief Model (HBM)-higher perception of susceptibility (odds ratio [OR] 1.44; 95% CI 1.07-1.94), severity (OR 1.32; 95% CI 1.10-1.59), self-efficacy (OR 1.61; 95% CI 1.21-2.15), and perceived control or intention to carry out prevention measures (OR 1.32; 95% CI 1.09-1.59)-were significantly associated with a higher mass media exposure score, whereas only three constructs-higher perception of severity (OR 1.43; 95% CI 1.19-1.72), self-efficacy (OR 1.85; 95% CI 1.38-2.48), and perceived control or intention to carry out prevention measures (OR 1.32; 95% CI 1.08-1.58)-were significantly associated with a higher social media exposure score. Lower emotional consequences and barriers to carry out prevention measures were also significantly associated with greater mass and social media exposure. Our findings on anxiety levels revealed that 38.1% (n=795; 95% CI 36.0-40.2) of respondents reported moderate-to-severe anxiety. A lower anxiety level was significantly associated with higher mass and social media exposure in the univariable analyses; however, the associations were not significant in the multivariable analyses. In essence, both mass and social media are useful means of disseminating health messages and contribute to the betterment of psychobehavioral responses to COVID-19. Our findings stress the importance of the credibility of information shared through mass and social media outlets and viable strategies to counter misinformation during a pandemic.


DNA typing results from two urban subpopulations of Pakistan.
A population genetic characterization of the Araeen and Raajpoot ethnic subpopulations of Lahore City, Pakistan was undertaken in order to assess the utility of DNA typing for forensic purposes in Pakistani populations. One hundred unrelated individuals from each group were genotyped for four independently assorting loci: HLA DQAI, CSF1PO, TPOX, and TH01. Allele frequencies were calculated, one- and two-locus tests for association were conducted, and the samples were compared by contingency table tests and F-statistic estimation. Although there is expected to be some genetic divergence between the two groups, forensic needs may be satisfied with a single Pakistani database of DNA profiles. The present data suggest that nine independently assorting loci will be sufficient to provide estimated profile probabilities of the order of 10(-9) but a set of 13 loci, as employed in the U.S., would better compensate for the dependencies introduced by family membership and evolutionary history.


Why does Staphylococcus aureus secrete an Enterococcus faecalis-specific pheromone?
The long known fact that Staphylococcus aureus can secrete a peptide (staph-cAM373) which acts as a sex pheromone for strains of E. faecalis carrying the sex pheromone plasmid pAM373 was studied in detail. 85 of 100 independent isolates of S. aureus produced an activity inducing the pAM373 encoded adhesin resulting in a clumping reaction of E. faecalis (i.e. secreted staph-cAM373), but not a single one of 100 independent isolates of coagulase-negative Staphylococci possessed this activity. The production of peptides acting as sex pheromone for E. faecalis was observed only for sex pheromone plasmid pAM373, but not for sex pheromone plasmids pAD1 and pPD1. It was shown that the amount of staph-pAM373 produced during growth paralleled cell mass, therefore this peptide should not be used as a cell density indicator by S. aureus (i.e. has no quorum sensing function). The potential function of staph-cAM373 to trigger gene transfer from Escherichia faecalis to S. aureus is discussed.


Enchondromatosis revisited: new classification with molecular basis.
The so-called "enchondromatoses" are skeletal disorders defined by the presence of ectopic cartilaginous tissue within bone tissue. The clinical and radiographic features of the different enchondromatoses are distinct, and grouping them does not reflect a common pathogenesis but simply a similar radiographic appearance and thus the need for a differential diagnosis. Recent advances in the understanding of their molecular and cellular bases confirm the heterogeneous nature of the different enchondromatoses. Some, like Ollier disease, Maffucci disease, metaphyseal chondromatosis with hydroxyglutaric aciduria, and metachondromatosis are produced by a dysregulation of chondrocyte proliferation, while others (such as spondyloenchondrodysplasia or dysspondyloenchondromatosis) are caused by defects in structure or metabolism of cartilage or bone matrix. In other forms (e.g., the dominantly inherited genochondromatoses), the basic defect remains to be determined. The classification, proposed by Spranger and associates in 1978 and tentatively revised twice, was based on the radiographic appearance, the anatomic sites involved, and the mode of inheritance. The new classification proposed here integrates the molecular genetic advances and delineates phenotypic families based on the molecular defects. Reference radiographs are provided to help in the diagnosis of the well-defined forms. In spite of advances, many cases remain difficult to diagnose and classify, implying that more variants remain to be defined at both the clinical and molecular levels.


Relative damping improves linear mass-spring models of goal-directed movements.
A limitation of a simple linear mass-spring model in describing goal directed movements is that it generates rather slow movements when the parameters are kept within a realistic range. Does this imply that the control of fast movements cannot be approximated by a linear system? In servo-control theory, it has been proposed that an optimal controller should control movement velocity in addition to position. Instead of explicitly controlling the velocity, we propose to modify a simple linear mass-spring model. We replaced the damping relative to the environment (absolute damping) with damping with respect to the velocity of the equilibrium point (relative damping). This gives the limb a tendency to move as fast as the equilibrium point. We show that such extremely simple models can generate rapid single-joint movements. The resulting maximal movement velocities were almost equal to those of the equilibrium point, which provides a simple mechanism for the control of movement speed. We further show that peculiar experimental results, such as an 'N-shaped' equilibrium trajectory and the difficulties to measure damping in dynamic conditions, may result from fitting a model with absolute damping where one with relative damping would be more appropriate. Finally, we show that the model with relative damping can be used to model subtle differences between multi-joint interceptions. The model with relative damping fits the data much better than a version of the model with absolute damping.


Severe and extensive neonatal hearing loss in cats results in auditory cortex plasticity that differentiates into two regions.
We examined the response characteristics of primary auditory cortex (A1) neurons in adult cats partially but extensively deafened by ototoxic drugs 2-8 days after birth. The damage evoked extensive A1 topographic map reorganization as also found by others, but a novel finding was that in the majority of cats with low-frequency edges to the cochlear lesion, the area of reorganization segregated into two areas expressing the same novel frequency inputs but differentiated by neuronal sensitivity and responsiveness. Immediately adjacent to normal A1 is an approximately 1.2-mm-wide area of reorganization in which sensitivity and responsiveness to sound are similar to that in normal A1 in the same animals and in unlesioned adult animals. Extending further into deprived A1 is a more extensive area of reorganization where neurons have poorer sensitivity and responsiveness to new inputs. These two areas did not differ in response-area bandwidth and response latency. We interpret these novel changes as the cortical consequences of severe receptor organ lesions extending to low-frequency cochlear regions. We speculate that the two areas of A1 reorganization may reflect differences in the transcortical spatial distribution of thalamo-cortical and horizontal intracortical connections. Qualitatively similar changes in response properties have been seen after retinal lesions producing large areas of visual cortical reorganization, suggesting they might be a general consequence of receptor lesions that deprive large regions of cortex of normal input. These effects may have perceptual implications for the use of cochlear implants in patients with residual low-frequency hearing.


Impact of an electronic cigarette on smoking reduction and cessation in schizophrenic smokers: a prospective 12-month pilot study.
Cigarette smoking is a tough addiction to break. This dependence is the most common dual diagnosis for individuals with schizophrenia. Currently three effective drugs are approved for smoking cessation: nicotine replacement therapy (NRT), varenicline and bupropion. However, some serious side effects of varenicline have been reported, including depression, suicidal thoughts, and suicide. The use of bupropion also has side effects. It should not be used by people who have epilepsy or any condition that lowers the seizure threshold, nor by people who take a specific class of drugs called monoamine oxidase inhibitors. Hence, there are pharmacodynamic reason to believe they could precipitate or exacerbate psychosis. For its capacity to deliver nicotine and provide a coping mechanism for conditioned smoking cues by replacing some of the rituals associated with smoking gestures, electronic-cigarettes may reduce nicotine withdrawal symptoms without serious side effects. Our recent work with ECs in healthy smokers not intending to quit consistently show surprisingly high success rates. We hypothesised that these positive findings could be replicated in difficult patients with schizophrenia This tool may help smokers with schizophrenia remain abstinent during their quitting attempts or to reduce cigarette consumption. Efficacy and safety of these devices in long-term smoking cessation and/or smoking reduction studies have never been investigated for this special population. In this study we monitored possible modifications in smoking habits of 14 smokers (not intending to quit) with schizophrenia experimenting with the "Categoria" e-Cigarette with a focus on smoking reduction and smoking abstinence. Study participants were invited to attend six study visits: at baseline, week-4, week-8, week-12 week-24 and week 52. Product use, number of cigarettes smoked, carbon monoxide in exhaled breath (eCO) and positive and negative symptoms of schizophrenia levels were measured at each visit. Smoking reduction and abstinence rates were calculated. Adverse events were also reviewed. Sustained 50% reduction in the number of cig/day at week-52 was shown in 7/14 (50%) participants; their median of 30 cig/day decreasing significantly to 15 cig/day (p = 0.018). Sustained smoking abstinence at week-52 was observed in 2/14 (14.3%) participants. Combined sustained 50% reduction and smoking abstinence was shown in 9/14 (64.3%) participants. Nausea was observed in 2/14 (14.4%) of participants, throat irritation in 2/14 (14.4%) of participants, headache in 2/14 (14.4%) of participants , and dry cough in 4/14 (28.6%) of participants. However, these adverse events diminished substantially by week-24. Overall, one to two cartridges/day were used throughout the study. Positive and negative symptoms of schizophrenia are not increased after smoking reduction/cessation in patients using e-cigarettes. We have shown for the first time that the use of e-cigarette substantially decreased cigarette consumption without causing significant side effects in chronic schizophrenic patients who smoke not intending to quit. This was achieved without negative impacts on the symptoms of schizophrenia as assessed by SAPS and SANS symptoms scales.


Determinants of Suicidality and of Treatment Modalities in a Community Psychiatry Sample of Asylum Seekers.
A high prevalence of mental illness has been reported in asylum seekers. The present cross-sectional study examined suicidal thoughts, treatment modalities (outpatient crisis intervention, inpatient care), and their determinants in asylum seekers (n = 119) and permanent residents (n = 120) attending the same outpatient clinic in Geneva, Switzerland. The most frequent diagnoses were depressive disorders (64.7%) and posttraumatic stress disorder (34.5%) in asylum seekers and psychotic (55.0%) and depressive disorders (33.3%) in permanent residents. The frequency of suicidal thoughts was similar in both groups (>30%). Asylum seekers benefited from outpatient crisis intervention more frequently than residents did (26.9% vs. 5.8%), whereas inpatient care was less frequent (25.2% vs. 44.2%). In asylum seekers, acute suicidal thoughts were associated with increased frequency of outpatient crisis interventions, and, suicidal thoughts, psychosis, or personality disorders were associated with higher rates of hospitalization. Documenting clinical characteristics and service utilization of asylum seekers is a prerequisite to organizing targeted interventions.


Role of the metF and metJ genes on the vitamin B12 regulation of methionine gene expression: involvement of N5-methyltetrahydrofolic acid.
The repression of MetE synthesis in Escherichia coli by vitamin B12 is known to require the MetH holoenzyme (B12-dependent methyltransferase) and the metF gene product. Experiments using trimethoprim, an inhibitor of dihydrofolate reductase, show that the MetF protein is not directly involved in the repression, but that N5-methyltetrahydrofolic acid (N5-methyl-H4-folate), the product of the MetF enzymatic reaction is required. Since the methyl group from N5-methyl-H4-folate is normally transferred to the MetH holoenzyme to form a methyl-B12 enzyme, the present results suggest that a methyl-B12 enzyme is involved in the vitamin B12 repression of metE expression. Other results argue against the possibility that a methyl-B12 enzyme functions in this repression solely by decreasing the cellular level of homocysteine, which is required for MetR activation of metE expression. Experiments with metJ mutants show that the MetJ protein mediates about 50% of the repression of metE expression by B12 but is totally responsible for the regulation of metF expression by vitamin B12.


[Rehabilitation of patients after suturing perforated duodenal ulcer].
516 patients with perforated duodenal ulcer were operated, 396 of them underwent palliative operations. Long-term results were studied in 237 patients. Determination of individual sensitivity to H2-blockers of histamine receptors with 24 hour pH-metry demonstrated tendency towards reduction of therapeutic effect time, and in 17-18% cases--resistance development. Individual selection of drugs with diet, obligative antihelicobacter therapy with eradication control permit to reduce ulcer recurrence rate from 65.5 to 4.8%. Success depends on organisation of rehabilitation and prophylactic treatment.


Tetherin is an exosomal tether.
Exosomes are extracellular vesicles that are released when endosomes fuse with the plasma membrane. They have been implicated in various functions in both health and disease, including intercellular communication, antigen presentation, prion transmission, and tumour cell metastasis. Here we show that inactivating the vacuolar ATPase in HeLa cells causes a dramatic increase in the production of exosomes, which display endocytosed tracers, cholesterol, and CD63. The exosomes remain clustered on the cell surface, similar to retroviruses, which are attached to the plasma membrane by tetherin. To determine whether tetherin also attaches exosomes, we knocked it out and found a 4-fold reduction in plasma membrane-associated exosomes, with a concomitant increase in exosomes discharged into the medium. This phenotype could be rescued by wild-type tetherin but not tetherin lacking its GPI anchor. We propose that tetherin may play a key role in exosome fate, determining whether they participate in long-range or short-range interactions.


Individual transcriptional activity of estrogen receptors in primary breast cancer and its clinical significance.
To predict the efficacy of hormonal therapy at the individual-level, immunohistochemical methods are used to analyze expression of classical molecular biomarkers such as estrogen receptor (ER), progesterone receptor (PgR), and HER2. However, the current diagnostic standard is not perfect for the individualization of diverse cases. Therefore, establishment of more accurate diagnostics is required. Previously, we established a novel method that enables analysis of ER transcriptional activation potential in clinical specimens using an adenovirus estrogen response element-green fluorescence protein (ERE-GFP) assay system. Using this assay, we assessed the ERE transcriptional activity of 62 primary breast cancer samples. In 40% of samples, we observed that ER protein expression was not consistent with ERE activity. Comparison of ERE activity with clinicopathological information revealed that ERE activity was significantly correlated with the ER target gene, PgR, rather than ER in terms of both protein and mRNA expression. Moreover, subgrouping of Luminal A-type breast cancer samples according to ERE activity revealed that ERα mRNA expression correlated with ER target gene mRNA expression in the high-, but not the low-, ERE-activity group. On the other hand, the low-ERE-activity group showed significantly higher mRNA expression of the malignancy biomarker Ki67 in association with disease recurrence in 5% of patients. Thus, these data suggest that ER expression does not always correlate with ER transcriptional activity. Therefore, in addition to ER protein expression, determination of ERE activity as an ER functional marker will be helpful for analysis of a variety of diverse breast cancer cases and the subsequent course of treatment.


Adenoid cystic carcinoma of the salivary glands.
Among 334 malignant tumours of the salivary glands 62 (18.6%) were adenoid cystic carcinomas. Although this tumour grows slowly, local recurrence and metastatic spread, particularly to lung, are common. The recommended treatment is surgical excision followed by radiotherapy. Postoperative irradiation reduces the frequency of local recurrence caused by residual microscopic disease. The 5- to 10-year actuarial survival rates were 77% and 57%, respectively. Local and regional recurrence can be eradicated by aggressive treatment, either by radical operation or a combination of operation and irradiation.


Identification of a Frizzled-like cysteine rich domain in the extracellular region of developmental receptor tyrosine kinases.
In Drosophila, members of the Frizzled family of tissue-polarity genes encode proteins that appear to function as cell-surface receptors for Wnts. The Frizzled genes belong to the seven transmembrane class of receptors (7TMR) and have on their extracellular region a cysteine-rich domain that has been implicated as the Wnt binding domain. This region has a characteristic spacing of ten cysteines, which has also been identified in FrzB (a secreted antagonist of Wnt signaling) and Smoothened (another 7TMR, which is involved in the hedgehog signalling pathway). We have identified, using BLAST, sequence similarity between the cysteine-rich domain of Frizzled and several receptor tyrosine kinases, which have roles in development. These include the muscle-specific receptor tyrosine kinase (MuSK), the neuronal specific kinase (NSK2), and ROR1 and ROR2. At present, the ligands for these developmental tyrosine kinases are unknown. Our results suggest that Wnt-like ligands may bind to these developmental tyrosine kinases


Establishing a Multidisciplinary Cavernous Carotid Injury Simulation to Train Neurosurgical, Otolaryngology, and Anesthesia Residents.
Carotid artery injuries are serious complications of endoscopic endonasal surgery. As these occur rarely, simulation training offers an avenue for technique and algorithm development in resident learners. This study develops a realistic cadaveric model for the training of crisis resource management in the setting of cavernous carotid artery injury. An expanded endonasal approach and right cavernous carotid injury is performed on a cadaveric head. The cadaver's right common carotid artery is cannulated and connected to a perfusion pump delivering pressurized simulated blood. A simulation mannequin is incorporated into the model to allow for vital sign feedback. Surgical and anesthesia resident learners are tasked with obtaining vascular control with a muscle patch technique and medical management over the course of 3 clinical scenarios with increasing complexity. Crisis management instructions for an endoscopic endonasal approach to the cavernous carotid artery and blood pressure control were provided to the learners prior to beginning the simulation. An independent reviewer evaluated the learners on communication skills, crisis management algorithms, and implementation of appropriate skill sets. After each scenario, residents were debriefed on how to improve technique based on evaluation scores in areas of situational awareness, decision-making, communications and teamwork, and leadership. After the simulation, learners provided feedback on the simulation and this data was used to improve future simulations. The benefit of this cadaveric model is ease of set-up, cost-effectiveness, and reproducibility.


Health issues in the Arab American community. Commentary on tobacco: the world's leading cause of cancer.
Cancer incidence is on the rise in many regions of the world, including the Middle East, where incidence rates for both men and women are increasing. Like many regions of the world, increased tobacco use, combined with other factors, is driving cancer incidence in the Middle East. Tobacco, the only consumer product proven to kill more than half of its regular users, will be responsible for 4.9 million deaths worldwide this year alone. That burden is fairly evenly shared by industrialized and developing nations today but, if current trends continue, the cancer burden in the developing world will more than triple in the next 25 years, resulting in a global total of 10 million deaths worldwide each year. Seven million of these deaths will occur in the developing world, in nations least prepared to deal with the financial, social, and political consequences of this global public health tragedy. In the Arab world, lung cancer is already occurring with increasing frequency, particularly among men.


Finite element analysis of cutting balloon expansion in a calcified artery model of circular angle 180°: Effects of balloon-to-diameter ratio and number of blades facing calcification on potential calcification fracturing and perforation reduction.
Calcified artery lesions cause stent under-expansion and increase the risk of in-stent restenosis and stent thrombosis. Cutting balloons facilitate the fracturing of calcification prior to stent implantation, although vessel dissection and perforation are potential issues. In clinical practice, calcifications having maximum calcium angles ≤ 180° are rarely fractured during conventional balloon angioplasty. We hypothesize that the lesion/device diameter ratio and the number of blades facing a non-circular calcified lesion may be crucial for fracturing the calcification while avoiding vessel injury. The geometries of the cutting balloons were constructed and their finite-element models were generated by folding and wrapping the balloon model. Numerical simulations were performed for balloons with five different diameters and two types of blade directions in a 180° calcification model. The calcification expansion ability was distinctly higher when two blades faced the calcification than when one blade did. Moreover, when two blades faced the calcification model, larger maximum principal stresses were generated in the calcification even when using undersized balloons with diameters reduced by 0.25 or 0.5 mm from the reference diameter, when compared with the case where one blade faced the calcified model and a balloon of diameter equal to the reference diameter was used. When two blades faced the calcification, smaller stresses were generated in the artery adjacent to the calcification; further, the maximum stress generated in the artery model adjacent to the calcification under the rated pressure of 12 atm when employing undersized balloons was smaller than that when only one blade faced the calcification and when lesion-identical balloon diameters were used under a nominal pressure of 6 atm. Our study suggested that undersized balloons of diameters 0.25 or 0.5 mm less than the reference diameter might be effective in not only expanding the calcified lesion but also reducing the risk of dissection.


[Microcarcinoidosis of the stomach. Diffuse hyperplasia of endocrine c ells and multiple polyp-like carcinoids].
A diffuse peptide microcarcinoidosis was observed both in a 56-year-old man with chronic atrophic gastritis and in a 33-year-old female with chronic atrophic gastritis and pernicious anaemia. Besides hyperplasia of endocrine cells at the base of gastric fundus and corpus mucosa with infiltration of the mucosal muscular layer multiple macro- and micropolyp carcinoids were present. In both cases serotonin was demonstrated immunohistochemically in the intestinal metaplastic mucosal changes, in the microcarcinoidosis foci and in the carcinoids. However, no appropriate clinical symptomatology was observed. The diagnosis can already be made by biopsy which must be deep enough and include gastric mucosa containing the mucosal muscular layer. Should gastric carcinoid be established histologically the other macroscopically normal mucosa must also be biopsied for exclusion of diffuse microcarcinoidosis as intermediate form of a multiple carcinoid. In such a case treatment consists of total gastrectomy.


Patient management during extradural anaesthesia for obstetrics.
A review of some policies of clinical practice, adopted in the light of experience, is presented. These include the inadvisability of attempting to obtain a precise segmental block during the first stage of labour; the urgent need to avoid compression of the inferior vena cava by the uterus during labour and at the time of delivery; a preference for the routine use of bupivacaine in concentration of 0.375%, and for the plain solution irrespective of the concentration employed; and the advocacy of providing lumbar extradural analgesia in cases of breech presentation and multiple pregnancy. The list of contraindications has been considerably reduced during the past few years.


Role Of CO2 Laser & Microdebrider In The Treatment Of Juvenile Onset Recurrent Respiratory Papillomatosi.
To compare the efficacy of two main treatment modalities of microdebrider and carbon dioxide laser excision for juvenile onset recurrent respiratory papillomatosis. The retrospective study was conducted in May 2021 at the Combined Military Hospital, Kharian, Pakistan, and comprised data from July 1, 2007, to January 31, 2020, of patients of either gender aged 2-12 years who were treated for juvenile onset recurrent respiratory papillomatosis either with microdebrider excision in group A or carbon dioxide laser excision in group B. Extent and severity of disease was documented as per the Derkay-Coltrera grading system. Data was analysed using SPSS 20. Of the 39 patients, 23(59%) were girls and 16(41%) were boys. The overall mean age at the time of procedure was 6.62±2.06 years. Group A had 22(56.4%) subjects; 15(68.2%) girls and 7(31.8%) boys, while group B had 17(43.6%) cases; 8(47%) girls and 9(53%) boys. The mean operative time for group A was 40.91±11.50 minutes and for group B it was 60.59±19.51 minutes. Postoperative breathing and oedema status was better for group A (p<0.05), while there was no significant difference regarding postoperative pain, residual disease and repeat surgeries (p>0.05). Microdebrider was found to be superior to carbon dioxide laser excision in the treatment of juvenile onset recurrent respiratory papillomatosis.


[Depending on exposure, functional state of left ventricle in combined cardiovascular disease among chronic uranium intoxication patients].
State of left heart contractility in patients having IHD and AH during long-term period of chronic uranium intoxication depends on duration of exposure to toxic radiation factor. The authors revealed left ventricle myocardium weight decreased by 11.7% on exposure up to 10 years and that decreased by 18.9% on the exposure over 10 years, when compared to the reference group. Longer length of service was connected with higher share of patients with pathologic remodelling of left ventricle, mostly due to increased concentric remodelling.


Occult bacteremia in children with simple febrile seizures.
The controversy surrounding the diagnostic workup for simple febrile seizures has centered around the lumbar puncture. This focus has obscured the potential importance of other tests. A retrospective study was performed to determine the frequency of occult bacteremia in simple febrile seizures. In a pediatric emergency department, we identified 115 cases of simple febrile seizures in children treated as outpatients. Blood cultures were performed in 93 (81%) of 115 patients; five (5.4%) were positive. Children were less likely to have blood cultures performed if they were older than 24 months or had a medical history of simple febrile seizures. However, neither age nor history of febrile seizures affected the risk of bacteremia. These data suggest that patients with simple febrile seizures are at approximately the same risk for bacteremia as children with fever alone. Patients with simple febrile seizures should be treated in the same manner as other patients of the same age with regard to the performance of blood cultures.


Menstrual blood transplantation for ischemic stroke: Therapeutic mechanisms and practical issues.
Cerebrovascular diseases are a major cause of death and long-term disability in developed countries. Tissue plasmin activator (tPA) is the only approved therapy for ischemic stroke, strongly limited by the short therapeutic window and hemorrhagic complications, therefore excluding most patients from its benefits. The rescue of the penumbra area of the ischemic infarct is decisive for functional recovery after stroke. Inflammation is a key feature in the penumbra area and it plays a dual role, improving injury in early phases but impairing neural survival at later stages. Stem cells can be opportunely used to modulate inflammation, abrogate cell death and, therefore, preserve neural function. We here discuss the possible role of stem cells derived from menstrual blood as restorative treatment for stroke. We highlight the availability, proliferative capacity, pluripotentiality and angiogenic features of these cells and explore their present and future experimental and clinical applications.


Epitope changes on the haemagglutinin molecule of recently isolated H1N1 influenza viruses.
We have studied changes of epitopes on the haemagglutinin molecule (HA) of H1N1 influenza viruses isolated between 1977 and 1986. For this purpose monoclonal antibodies (MAbs) were raised against the HA of the influenza A/England/333/80 and A/Yamagata/120/86 strain viruses. In order to define the amino acid residues responsible for the change of epitopes, we prepared several HA cDNAs modified by site-directed mutagenesis and cloned them into a simian virus 40 expression vector (SVHA). The substitution of glycine with serine at position 125c (suffix indicates presence in H1 but not in H3 subtype HAs) on the HA of the influenza A/USSR/90/77 strain virus resulted in the loss of epitope 110 (epitopes were named after MAbs) and created new epitopes 139 and 15, which were observed on the HA of A/England/333/80 and a few isolates from 1983. These new epitopes disappeared from the HA in some of the isolates in 1983 and most of the isolates in 1984 and 1986. The disappearance of epitopes 139 and 15 seems to be associated with the loss of epitope W18, which was identified on the HA of A/USSR/90/77. We suggested previously that amino acid residue 189 was involved in epitope W18. We therefore expressed an HA protein with two amino acid substitutions at positions 189 and 125c and found that the conversion of glutamine to lysine at position 189 in SVHA-67 prevented the expression of epitopes 139 and 15.


d-Amphetamine-induced anorexia and motor behavior after chronic treatment in rats: relationship with changes in the number of catecholamine receptor sites in the brain.
No tolerance to the anorectic activity of d-amphetamine was found in rats given two daily injections of 1.25 mg/kg for 28 days. Such rats also presented no changes in the number of binding sites for serotonin and catecholamines in various brain areas. A 28-day treatment with 10 mg/kg d-amphetamine twice daily caused a significant reduction in the number of binding sites for 3H-dihydroalprenolol (beta adrenergic receptor ligand) in hippocampus, and 3H-spiroperidol (dopamine receptor ligand) in striatum and nucleus accumbens. This treatment did not modify the anorectic effect of 1.25 mg/kg of amphetamine but it markedly reduced the motor hyperactivity induced by this treatment and completely blocked the stereotyped licking and biting induced by apomorphine. Amphetamine stereotypy was not significantly reduced but disappeared faster in chronically treated rats. The possible reasons for the different results (tolerance or sensitization) reported by various authors on changes in amphetamine's effects on motor behaviour during chronic treatment are discussed.


Integrating Data Transformation in Principal Components Analysis.
Principal component analysis (PCA) is a popular dimension reduction method to reduce the complexity and obtain the informative aspects of high-dimensional datasets. When the data distribution is skewed, data transformation is commonly used prior to applying PCA. Such transformation is usually obtained from previous studies, prior knowledge, or trial-and-error. In this work, we develop a model-based method that integrates data transformation in PCA and finds an appropriate data transformation using the maximum profile likelihood. Extensions of the method to handle functional data and missing values are also developed. Several numerical algorithms are provided for efficient computation. The proposed method is illustrated using simulated and real-world data examples.


[The use of high-energy electrons in the treatment of malignant orbital tumors (author's transl)].
Tumors of the anterior part of the orbita can be irradiated with high-energy electrons using a special eye tube with a central plexiglass stick to protect the eye. In eight patients suffering from lymphatic orbital tumors, complete remission was achieved after a dose of 3000 rad.


Purification and properties of ArfI, an alpha-L-arabinofuranosidase from Cytophaga xylanolytica.
An alpha-L-arabinofuranosidase (alpha-L-arabinofuranoside arabinofuranohydrolase [EC 126.96.36.199]; referred to below as ArfI) from Cytophaga xylanolytica XM3 was purified 85-fold by anion-exchange and hydrophobic interaction column chromatography. The native enzyme had a pI of 6.1 and an apparent molecular mass of 160 to 210 kDa, and it appeared to be a trimer or tetramer consisting of 56-kDa subunits. With p-nitrophenyl-alpha-L-arabinofuranoside as the substrate, the enzyme exhibited a K(m) of 0.504 mM and a Vmax of 319 mumol.min-1.mg of protein-1, and it had optimum activity at pH 5.8 and 45 degrees C. ArfI was relatively stable over a pH range of 4 to 10 and at temperatures up to 45 degrees C, and it retained nearly full activity when stored at 4 degrees C for periods as long as 24 months. The enzyme also released arabinose from 4-methylumbelliferyl-alpha-L-arabinofuranoside, as well as from rye, wheat, corn cob, and oat spelt arabinoxylans and sugar beet arabinan, but not from arabinogalactan. ArfI showed no hydrolytic activity toward a range of p-nitrophenyl- or 4-methylumbelliferyl-glycosides other than arabinoside, for which it was entirely specific for the alpha-L-furanoside configuration. ArfI interacted synergistically with three partially purified endoxylanase fractions from C. xylanolytica in hydrolyzing rye arabinoxylan. However, cell fractionation studies revealed that ArfI was largely, if not entirely, cytoplasmic, so its activity in vivo is probably most relevant to hydrolysis of arabinose-containing oligosaccharides small enough to pass through the cytoplasmic membrane. Antibodies prepared against purified ArfI also cross-reacted with arabinofuranosidases from other freshwater and marine strains of C. xylanolytica, as well as with some proteins that did not possess arabinofuranosidase activity. To our knowledge, this is the first alpha-L-arabinofuranosidase to be purified and characterized from any gliding bacterium.


Impact of the COVID-19 Health Crisis on Key Populations at Higher Risk for, or Living With, HIV or Hepatitis C Virus and People Working With These Populations: Multicountry Community-Based Research Study Protocol (EPIC Program).
Information concerning the impact of the COVID-19 health crisis on populations most affected by HIV and hepatitis C virus (HCV; or key populations [KP]), and those working with these populations in community settings, is limited. Community-based organizations working in the field of HIV and viral hepatitis are well placed to identify and meet the new needs of KP owing to the health crisis. This study aims to describe the development and implementation of an exploratory and descriptive multicountry, community-based research program, EPIC (Enquêtes Pour évaluer l'Impact de la crise sanitaire covid en milieu Communautaire), within an international network of community-based organizations involved in the response to HIV and viral hepatitis. The EPIC program aimed to study the impact of the COVID-19 health crisis on KP or people living with HIV or HCV and people working with these populations at the community level (community health workers [CHWs]) and to identify the key innovations and adaptations in HIV and HCV services. A general protocol and study documents were developed and shared within the Coalition PLUS network. The protocol had a built-in flexibility that allowed participating organizations to adapt the study to local needs in terms of the target population and specific themes of interest. Data were collected using surveys or interviews. From July 2020 to May 2022, a total of 79 organizations participated in the EPIC program. Across 32 countries, 118 studies were conducted: 66 quantitative (n=12,060 among KP or people living with HIV or people living with HCV and n=811 among CHWs) and 52 qualitative (n=766 among KP or people living with HIV or people living with HCV and n=136 among CHWs). The results of the EPIC program will provide data to describe the impact of the health crisis on KP and CHWs and identify their emerging needs. Documentation of innovative solutions that were put into place in this context may help improve the provision of services after COVID-19 and for future health crises. DERR1-10.2196/45204.


Continuous therapy with certolizumab pegol maintains remission of patients with Crohn's disease for up to 18 months.
The safety and efficacy of maintenance therapy with the anti-tumor necrosis factor certolizumab pegol has not been reported beyond 6 months. We assessed the long-term efficacy, safety, and immunogenicity of continuous versus interrupted maintenance therapy with subcutaneous certolizumab pegol in patients with Crohn's disease. Patients who responded to induction therapy at week 6 of the PEGylated Antibody Fragment Evaluation in Crohn's Disease: Safety and Efficacy (PRECiSE) 2 trial were assigned randomly to groups given certolizumab pegol (continuous) or placebo (drug-interruption) during weeks 6 to 26. Patients who completed PRECiSE 2 were eligible to enter PRECiSE 3, an ongoing, prospective, open-label extension trial in which patients have received certolizumab pegol (400 mg) every 4 weeks for 54 weeks to date, and were not offered the option to increase their dose. Disease activity was measured by the Harvey-Bradshaw Index. Harvey-Bradshaw Index responses at week 26 for the continuous and drug-interruption groups were 56.3% and 37.6%, respectively; corresponding remission rates were 47.9% and 32.4%, respectively. Of patients responding at week 26, response rates at week 80 after the start of PRECiSE 2 in the continuous and drug-interruption groups were 66.1% and 63.3%, respectively; among patients in remission at week 26, week 80 remission rates were 62.1% and 63.2%, respectively. More patients in the drug-interruption group developed antibodies against certolizumab pegol (and had lower plasma concentrations of certolizumab pegol) than the continuously treated group. Certolizumab pegol effectively maintains remission of Crohn's disease for up to 18 months. Continuous therapy is more effective than interrupted therapy.


Comparison between multiview videofluoroscopy and nasendoscopy of velopharyngeal movements.
The videofluoroscopic and nasopharyngoscopic observations of velopharyngeal movements during speech were compared in 80 subjects with hypernasal speech. An endviewing flexible fiberoptic endoscope was used for nasopharyngoscopic examination. This failed to demonstrate movements of the lateral pharyngeal walls that were videofluoroscopically documented in one third of the patients. In the cases of disagreement, the angle of view was impaired because of the presence of adenoid tissue. The misinterpretation at nasopharyngoscopy was explained by an unfavorable observation position of the flexible scope and failure to pass it further into the pharynx. Conclusions are satisfactory that videofluoroscopy is an indispensable procedure for assessing velopharyngeal function.


Evolution and clinical pathologic correlations of de novo donor-specific HLA antibody post kidney transplant.
The natural history for patients with de novo donor-specific antibodies (dnDSA) and the risk factors for its development have not been well defined. Furthermore, clinical and histologic correlation with serologic data is limited. We studied 315 consecutive renal transplants without pretransplant DSA, with a mean follow-up of 6.2 ± 2.9 years. Protocol (n = 215) and for cause (n = 163) biopsies were analyzed. Solid phase assays were used to screen for dnDSA posttransplant. A total of 47 out of 315 (15%) patients developed dnDSA at a mean of 4.6 ± 3.0 years posttransplant. Independent predictors of dnDSA were HLA-DRβ1 MM > 0 (OR 5.66, p < 0.006); and nonadherence (OR 8.75, p < 0.001); with a strong trend toward clinical rejection episodes preceding dnDSA (OR 1.57 per rejection episode, p = 0.061). The median 10-year graft survival for those with dnDSA was lower than the No dnDSA group (57% vs. 96%, p < 0.0001). Pathology consistent with antibody-mediated injury can occur and progress in patients with dnDSA in the absence of graft dysfunction and furthermore, nonadherence and cellular rejection contribute to dnDSA development and progression to graft loss.


A comparison of four direct geometry time-of-flight spectrometers at the Spallation Neutron Source.
The Spallation Neutron Source at Oak Ridge National Laboratory now hosts four direct geometry time-of-flight chopper spectrometers. These instruments cover a range of wave-vector and energy transfer space with varying degrees of neutron flux and resolution. The regions of reciprocal and energy space available to measure at these instruments are not exclusive and overlap significantly. We present a direct comparison of the capabilities of this instrumentation, conducted by data mining the instrument usage histories, and specific scanning regimes. In addition, one of the common science missions for these instruments is the study of magnetic excitations in condensed matter systems. We have measured the powder averaged spin wave spectra in one particular sample using each of these instruments, and use these data in our comparisons.


The effect of upflow air velocity on the structure of aerobic granules cultivated in a sequencing batch reactor.
The effect of upflow air velocity on the formation and structure of aerobic granules was studied in three column sequencing batch reactors. Upflow aeration would be the major cause of hydrodynamic shear force in the column reactor. Results showed that high upflow air velocity resulted in more compact, denser, rounder, stronger and smaller aerobic granules, while high biomass retention in the reactor was achieved. It was found that high upflow air velocity could induce granular sludge to secrete more cell polysaccharides which in turn contributed to the compact and strong structure. It appears from this study that the structure of aerobic granules could be controlled by manipulating the upflow air velocity.


Laser Desorption/Ionization Mass Spectrometry (LDI-MS) of Lipids with Iron Oxide Nanoparticle-Coated Targets.
Iron oxide nanoparticle (NP)-coated target plates were employed for the direct detection and analysis of low molecular weight lipids by laser desorption/ionization (LDI) mass spectrometry (MS). We have demonstrated that the use of the iron oxide NP-coated target provides a simple, direct, and rapid detection method for lipid standards and epidermal surface lipids without any cumbersome sample pretreatment as well as mass spectra that are free of background matrix peaks. Lipid standards (1-stearoyl-sn-glycero-3-phosphocholine, 1,2-dioleoyl-sn-glycerol, 1-palmitoyl-2-oleoyl-3-linoleoyl-rac-glycerol, 1,2-distearoyl-sn-glycero-3-phosphocholine) were detected as either protonated or cationated species. Clean MS/MS spectra for each lipid were also successfully obtained. Pre-MS surface cleaning of the target plates with UV-ozone treatment successfully removed organic contaminants that would interfere with the mass spectra especially in the low molecular weight region. Preliminary application of the presented target plate to the detection of endogenous lipids in latent fingerprints showed promising results and for potential use in the visualization and chemical composition determination of latent fingerprints by nanoparticle assistance.


Possible association between interleukin-1β gene and schizophrenia in a Japanese population.
Several lines of evidence have implicated the pro-inflammatory cytokine interleukin-1beta (IL-1β) in the etiology of schizophrenia. Although a number of genetic association studies have been reported, very few have systematically examined gene-wide tagging polymorphisms. A total of 533 patients with schizophrenia (302 males: mean age ± standard deviation 43.4 ± 13.0 years; 233 females; mean age 44.8 ± 15.3 years) and 1136 healthy controls (388 males: mean age 44.6 ± 17.3 years; 748 females; 46.3 ± 15.6 years) were recruited for this study. All subjects were biologically unrelated Japanese individuals. Five tagging polymorphisms of IL-1β gene (rs2853550, rs1143634, rs1143633, rs1143630, rs16944) were examined for association with schizophrenia. Significant difference in allele distribution was found between patients with schizophrenia and controls for rs1143633 (P = 0.0089). When the analysis was performed separately in each gender, significant difference between patients and controls in allele distribution of rs1143633 was observed in females (P = 0.0073). A trend towards association was also found between rs16944 and female patients with schizophrenia (P = 0.032). The present study shows the first evidence that the IL-1β gene polymorphism rs1143633 is associated with schizophrenia susceptibility in a Japanese population. The results suggest the possibility that the influence of IL-1β gene variations on susceptibility to schizophrenia may be greater in females than in males. Findings of the present study provide further support for the role of IL-1β in the etiology of schizophrenia.


Statins versus placebo for people with chronic obstructive pulmonary disease.
Chronic obstructive pulmonary disease (COPD) is a common, preventable, and treatable respiratory disease. COPD exacerbations are associated with worse quality of life, increased hospitalisations, and increased mortality. Currently available pharmacological interventions have variable impact on exacerbation frequency. The anti-inflammatory effects of statins may lead to decreased pulmonary and systemic inflammation, resulting in fewer exacerbations of COPD. Several observational studies have shown potential benefits of statins for patients with COPD. This review aims to evaluate available evidence on benefits and harms associated with statin therapy compared with placebo as adjunct therapy for patients with COPD. Primary objectives include the following.• To determine whether statins reduce mortality rates in COPD.• To determine whether statins reduce exacerbation frequency, improve quality of life, or improve lung function in COPD.• To determine whether statins are associated with adverse effects. We identified trials from the Cochrane Airways Trials Register, which contains studies identified through multiple electronic searches and handsearches of other sources. We also searched trial registries and reference lists of primary studies. We conducted the most recent search on 20 May 2019. Parallel, randomised controlled trials recruiting adults with COPD. We used standard methods as expected by Cochrane. Prespecified primary outcomes were number of exacerbations, all-cause mortality, and COPD-specific mortality. Eight studies including 1323 participants with COPD were included in the review. Participants had a mean age of 61.4 to 72 years, and most were male (median 73.4%). Mean baseline forced expiratory volume in one second (FEV₁) ranged from 41% to 90% predicted. All studies compared moderate- or high-intensity statin therapy versus placebo. The duration of treatment ranged from 12 weeks to 36 months.We found no statistically significant difference between statins and placebo in our primary outcome of number of exacerbations per person-year (mean difference (MD) -0.03, 95% confidence interval (CI) -0.25 to 0.19, 1 trial, 877 participants), including number of exacerbations requiring hospitalisation per person-year (MD 0.00, 95% CI -0.10 to 0.10, 1 trial, 877 exacerbations). This evidence was of moderate quality after downgrading for unclear risk of bias. Our primary outcomes of all-cause mortality (odds ratio (OR) 1.03, 95% CI 0.61 to 1.74, 2 trials, 952 participants) and COPD-specific mortality (OR 1.25, 95% CI 0.38 to 4.13, 1 trial, 877 participants) showed no significant difference between statins and placebo, with wide confidence intervals suggesting uncertainty about the precision of the results. This evidence was of low quality after downgrading for unclear risk of bias and imprecision.Results of the secondary outcomes analysis showed no clear differences between statins and placebo for FEV₁ (% predicted) (MD 1.18, 95% CI -2.6 to 4.97, 6 trials, 325 participants) but did show a statistically significant improvement in FEV₁/forced vital capacity (FVC) (MD 2.66, 95% CI 0.12 to 5.2; P = 0.04; 6 trials, 325 participants). A sensitivity analysis excluding two trials at high risk of bias showed no statistically significant difference in FEV₁/FVC (MD 2.05, 95% CI -0.87 to -4.97; P = 0.17; 4 trials, 255 participants). We also found no significant differences between the two groups in functional capacity measured by six-minute walk distance in metres (MD 1.79, 95% CI -52.51 to 56.09, 3 trials, 71 participants), with wide confidence intervals suggesting uncertainty about the precision of the results. Results show no clear difference in quality of life, which was reported in three trials, and a slight reduction in C-reactive protein (CRP) in the intervention group, which was statistically significant (MD -1.03, 95% CI -1.95 to -0.11; I² = 0%, P = 0.03; 3 trials, 142 participants). We noted a significant reduction in interleukin (IL)-6 in the intervention group (MD -2.11, 95% CI -2.65 to -1.56; I² = 0%, P ≤ 0.00001; 2 trials, 125 participants). All trials mentioned adverse events and indicated that statins were generally well tolerated. One study reported adverse events in detail and indicated that rates of all non-fatal adverse events (the number of serious adverse events per person-year) were similar in both groups (0.63 ± 1.56 events (intervention group) and 0.62 ± 1.48 events (control group); P > 0.20) for all comparisons, except for non-fatal serious adverse events involving the gastrointestinal tract, which were more frequent in the intervention group (in 30 patients (0.05 events per person-year) vs 17 patients (0.02 events per person-year); P = 0.02). Another trial lists the total numbers and percentages of adverse events in the intervention group (12 (26%)) and in the control group (21 (43%)) and of serious adverse events in the intervention group (4 (9%)) and in the control group (3 (6%)).The other trials stated that researchers found no significant adverse effects of statins but did not report adverse events in detail. A small number of trials providing low- or moderate-quality evidence were suitable for inclusion in this review. They showed that use of statins resulted in a reduction in CRP and IL-6, but that this did not translate into clear clinical benefit for people with COPD. Further randomised controlled trials are needed to explore this topic.


Mortality from all cancers of asbestos factory workers in east London 1933-80.
To give the observed and expected deaths due to cancer at all separate sites in asbestos workers in east London, and to analyse these for overall effect and exposure-response trend. The mortality experience of a cohort of over 5000 men and women followed up for over 30 years since first exposure to asbestos has been extracted. There was a large excess of deaths due to cancer (537 observed, 222 expected). Most of these were due to cancer of the lung (232 observed, 77 expected) and pleural (52) and peritoneal (48) mesothelioma. The exposure-response trend for all these three causes was highly significant. There was also an excess of cancer of the colon (27 observed, 15 expected) which was significantly related to exposure. There were significant excesses of cancer of the ovary, of the liver, and of the oesophagus but with no consistent relation to exposure. The excess risk of cancer after exposure to asbestos was mainly due to cancer of the lung and mesothelioma. An exposure related excess of cancer of the colon was also detected but the possibility that some of these deaths may have been peritoneal mesotheliomas could not be excluded. There was no consistent evidence of exposure related excesses at any other site.


Insulin-like growth factor (IGF)-I, IGF-II and IGF type I receptor (IGFR-I) expression in prostatic cancer.
Despite evidence implicating the insulin-like growth factor (IGF) system in the pathogenesis of prostate cancer, its precise role remains unclear. In this study we investigated the differential expression of IGF-I, IGF-II and their type I receptor (IGFR-I) in the epithelium and stroma of prostate neoplastic tissues. Using immunohistochemistry and in situ hybridization techniques, we analyzed 43 paraffin-embedded prostatic samples and compared prostatic cancer (Pca) with prostatic intraepithelial neoplasia (PIN) and its normal adjacent prostate (NAP) counterpart. We then determined a possible correlation of the immunohistochemical and in situ findings with two known prognostic clinical-pathological indices: Gleason score histological tumor grade and TNM clinical stage. In 22 of the 43 frozen prostatectomy specimens, IGF-I, IGF-II and IGFR-I mRNA expression were also evaluated by semiquantitative RT-PCR. Non neoplastic and neoplastic tissues examined contained detectable amounts of epithelial and stromal IGF-I, IGF-II and IGFR-I protein and mRNA; all levels increased significantly from normal tissue to PIN to Pca. In all three areas examined, IGFR-I expression was invariably higher in epithelium than in stroma, whereas expression of IGF ligands differed. In normal prostatic tissue, IGF-I and IGF-II expression was higher in stroma than in epithelium. Conversely, in Pca tissue, both factors were more strongly expressed in epithelial malignant cells. PIN areas showed IGF-I lowest, and IGF-II and IGFR-I levels highest in the epithelium. IGF-II protein and mRNA reached their highest levels in prostate tumors with high Gleason scores. These findings indicate that the IGF system changes as prostate tissue progresses from a normal to a malignant state. Differential expression of certain IGF system components in Pca may be associated with the malignant phenotype and more aggressive tumor behavior. Hence IGFs could serve to predict the outcome of prostatic cancer.


An investigation of the psychological effects of the September 11, 2001, attacks on New York City: developing and implementing research in the acute postdisaster period.
The September 11, 2001, attack on New York City was the largest human-made disaster in United States history. In the first few days after the attack, it became clear that the scope of the attacks (including loss of life, property damage, and financial strain) was unprecedented and that the attacks could result in substantial psychological sequelae in the city population. Researchers at the Center for Urban Epidemiologic Studies at the New York Academy of Medicine designed and implemented an assessment of the mental health of New Yorkers 5-8 weeks after the attacks. To implement this research in the immediate postdisaster period, researchers at the center had to develop, in a compressed time interval, new academic collaborations, links with potential funders, and unique safeguards for study respondents who may have been suffering from acute psychological distress. Results of the assessment contributed to a New York state mental health needs assessment that secured Federal Emergency Management Agency funding for mental health programs in New York City. This experience suggests that mechanisms should be in place for rapid implementation of mental health assessments after disasters.


The effect of Tai Chi Chuan in reducing falls among elderly people: design of a randomized clinical trial in the Netherlands [ISRCTN98840266].
Falls are a significant public health problem. Thirty to fifty percent of the elderly of 65 years and older fall each year. Falls are the most common type of accident in this age group and can result in fractures and subsequent disabilities, increased fear of falling, social isolation, decreased mobility, and even an increased mortality. Several forms of exercise have been associated with a reduced risk of falling and with a wide range of physiological as well as psychosocial health benefits. Tai Chi Chuan seems to be the most promising form of exercise in the elderly, but the evidence is still controversial. In this article the design of a randomized clinical trial is presented. The trial evaluates the effect of Tai Chi Chuan on fall prevention and physical and psychological function in older adults. 270 people of seventy years and older living at home will be identified in the files of the participating general practitioners. People will be asked to participate when meeting the following inclusion criteria: have experienced a fall in the preceding year or suffer from two of the following risk factors: disturbed balance, mobility problems, dizziness, or the use of benzodiazepines or diuretics. People will be randomly allocated to either the Tai Chi Chuan group (13 weeks, twice a week) or the no treatment control group. The primary outcome measure is the number of new falls, measured with a diary. The secondary outcome measures are balance, fear of falling, blood pressure, heart rate, lung function parameters, physical activity, functional status, quality of life, mental health, use of walking devices, medication, use of health care services, adjustments to the house, severity of fall incidents and subsequent injuries. Process parameters will be measured to evaluate the Tai Chi Chuan intervention. A cost-effectiveness analysis will be carried out alongside the evaluation of the clinical results. Follow-up measurements will be collected at 3, 6 and 12 months after randomization. As far as we know this is the first trial in Europe considering Tai Chi Chuan and fall prevention. This project will answer a pragmatic research question regarding the efficacy of Tai Chi Chuan regarding fall reduction.


Serum gastrin and the pepsinogen I/II ratio as markers for diagnosis of premalignant gastric lesions.
Iran is a country with very high incidences of stomach cancer, especially in Northern parts. Here we assessed prognostic value of serum screening biomarkers among people >50 years old for early detection of precancerous lesions in a hot spot for gastric carcinoma in Guilan Province, North Iran. A cross- sectional population-based survey was conducted on 1,390 residents of Lashtenasha city with the mean age (SD) of 61.8 (9.02) years old (50.8% females) to assess the association of gastrin and the pepsinogen (PG) I/II ratio with premalignant gastric lesions. Blood samples were taken for CBC, blood group, and serologic exams (PGI, PGII, and gastrin 17) from each subject. Expert gastroenterologists performed upper GI endoscopy and ROC curves were generated to determine appropriate cutoff points. Mean values of PGI, PGII, PGI/PGII and gastrin were significantly different between patients with and without atrophy or metaplasia (P<0.05). To diagnose atrophy and intestinal metaplasia, a significantly higher AUC was observed for the PGI/PGII ratio (70 and 72%, respectively) compared to the PGI (56, 55%), PGII (63, 64%) and gastrin (59, 61%) (all p<0.001). Biomarker tests such as the PGI/II ratio can be used in the screening and diagnosis of subjects at high gastric cancer risk in our region.


Regulation of mammalian nucleotide metabolism and biosynthesis.
Nucleotides are required for a wide variety of biological processes and are constantly synthesized de novo in all cells. When cells proliferate, increased nucleotide synthesis is necessary for DNA replication and for RNA production to support protein synthesis at different stages of the cell cycle, during which these events are regulated at multiple levels. Therefore the synthesis of the precursor nucleotides is also strongly regulated at multiple levels. Nucleotide synthesis is an energy intensive process that uses multiple metabolic pathways across different cell compartments and several sources of carbon and nitrogen. The processes are regulated at the transcription level by a set of master transcription factors but also at the enzyme level by allosteric regulation and feedback inhibition. Here we review the cellular demands of nucleotide biosynthesis, their metabolic pathways and mechanisms of regulation during the cell cycle. The use of stable isotope tracers for delineating the biosynthetic routes of the multiple intersecting pathways and how these are quantitatively controlled under different conditions is also highlighted. Moreover, the importance of nucleotide synthesis for cell viability is discussed and how this may lead to potential new approaches to drug development in diseases such as cancer.


[Clinical use of a quadruple biochemical marker in the prediction of obstetric complications].
The objective was to evaluate the association of an abnormal second trimester prenatal biochemical screening with the subsecuent development of pregnancy complications in women carrying chromosomally normal fetuses. A prospective study of 123 pregnant patients was performed. Specimens were assayed for alpha-fetoprotein, unconjugated estriol, free alpha hCG, and total hCG. The study included the evaluation of the mean and standard desviation as well as multiple of the median. Six women (4.6%) had positive results. The frequency of pregnancy complications in this group was 33.3%, while in the group with negative screening was 11.1%. As conclusion, positive four marker screening is associated with a adverse pregnancy evolution. However the usefulness of four marker screening for to predict pregnancy complications needs more investigations.


Chronic cervical compressive myelopathy in horses: clinical correlations with spinal cord alterations.
Histological examination was performed on the cervical spinal cord from 13 horses with chronic cervical compressive myelopathy of 4 to 29 months duration. Structural alterations were correlated with clinical features. At the level of compression, the spinal cord was grossly deformed. Histological alterations included nerve fibre swelling and degeneration, occasional spheroids, astrocytic gliosis, increased macrophage activity and increased perivascular collagen. Myelin degeneration or loss at the level of the compressive lesion was greatest in the ventral and lateral funiculi and less consistently present in the dorsal funiculi. Asymmetry of lesions in the dorsal funiculi was associated with asymmetry of clinical signs in 5 horses. Histological alterations in areas of Wallerian degeneration were similar to that at the level of spinal cord compression, except that perivascular collagen was not increased. Wallerian degeneration was present cranial to the compressed site in the superficial portions of the lateral funiculi and in the middle of the dorsal funiculi. Caudal to the compressed site it was present in the ventral funiculi adjacent to the ventral median fissure and in the middle of the lateral funiculi. Deformation of the spinal cord did not correlate with the severity or duration of clinical signs but was positively correlated with the amount of perivascular collagen increase. The amount of nerve fibre swelling was not correlated with the severity of clinical signs but was negatively correlated with their duration. A rapid loss of nerve fibres apparently occurred early in the course of compression, since there was a marked decrease in the amount of nerve fibre swelling and Marchi stained degenerating myelin with increasing clinical duration.(ABSTRACT TRUNCATED AT 250 WORDS)


[THE EFFECTIVENESS OF DIAGNOSIS AND TREATMENT OF CEREBROVASCULAR DISORDERS IN HYPERTENSIVE ENCEPHALOPATHY IN ELDERLY PATIENTS BY STUDYING THE CHARACTERISTICS OF CEREBRAL HEMODYNAMICS AND CEREBRAL PERFUSION STATUS].
Intrigue progression of hypertensive encephalopathy (HE) in older patients is that the development of cognitive impairment and high blood pressure underestimated, aslo exist without clinical manifestations. In recent decades convincing proved that the basis for the development of various diseases is cerebral dysfunction systems regulating brain blood flow, including--autoregulation system, which largely affects the blood supply to the brain. This explains the fact that patients with chronic brain ischemia cerebral hemodynamic status largely depends on the condition and stability of the regulatory mechanisms of systemic and cerebral hemodynamics, particularly of systemic blood pressure, regional cerebral blood supply, normalization which, in the early stages of development disorders, prevents of serious complications. In this paper the theoretical generalization and new solution of scientific and practical problems of hypertension influence on the formation of chronic cerebral ischemia in elderly patients on a background of hypertension--specified risk factors and especially the formation of a comprehensive study on the basis of clinical and neurological data, tool sand methods for neuroimaging research developed and improved methods of diagnosis. Found that in elderly patients with HE and HBP observed significant (P < 0.05) increase in the thickness of the intima-media complex was significantly higher (dextra--1.12 ± 0.03 and sinistra--1.11 ± 0.03), than middle-aged patients with hypertension at HE, which constitutes a violation of the elastic properties of the vascular wall. Established correlation data radionuclide study ultrasonic duplex scanning of vessels of the head and neck. A negative correlation of intima-media and severity of lesions according to hypoperfusion of computer tomography single photon emission (r = -0.49; P < 0.05); confirming the progression of HE in elderly patients needs improvement and treatment.


Altered behavior of the snail Biomphalaria glabrata as a result of infection with Schistosoma mansoni.
In this comparative behavioral study, the effect of infection with Schistosoma mansoni on its snail intermediate host Biomphalaria glabrata was investigated. Three groups of snails were compared for their activity: (1) uninfected, (2) infected with male parasites, and (3) infected with female parasites. In solitary movement trials, uninfected snails traveled greater distances at faster rates, explored more surface area, and had shorter rest periods than snails infected with either male or female schistosomes. In Y-maze experiments designed to determine attraction, the uninfected snails more often and more quickly moved toward other snails than the infected individuals. Snails from all 3 groups were more attracted to infected individuals than to uninfected ones. There was no difference in attraction toward snails infected with male or female parasites. These experiments provide evidence that behavioral alterations as a result of infection may lead to aggregation of infected snails in the field. We propose that such an effect may result in enhanced parasite transmission.


Multidimensional Approach to Frailty.
The concept of frailty syndrome (FS) was first described in the scientific literature three decades ago. For a very long time, we understood it as a geriatric problem, recently becoming one of the dominant concepts in cardiology. It identifies symptoms of FS in one in 10 elderly people. It is estimated that in Europe, 17% of elderly people have FS. The changes in FS resemble and often overlap with changes associated with the physiological aging process of the body. Although there are numerous scientific reports confirming that FS is age correlated, it is not an unavoidable part of the aging process and does not apply only to the elderly. FS is a reversible clinical condition. To maximize benefits of frailty-reversing activities for patient with frailty, identification of its determinants appears to be fundamental. Many of the determinants of the FS have already been known: reduction in physical activity, malnutrition, sarcopenia, polypharmacy, depressive symptom, cognitive disorders, and lack of social support. This review shows that insight into FS determinants is the starting point for building both the comprehensive definition of FS and the adoption of the assessment method of FS, and then successful clinical management.


Inhibition of group 1 p21-activated kinases suppresses pancreatic stellate cell activation and increases survival of mice with pancreatic cancer.
Pancreatic cancer remains one of the most lethal of all solid tumors. Pancreatic stellate cells (PSCs) are primarily responsible for the fibrosis that constitutes the stroma and p21-activated kinase 1 (PAK1) may have a role in signalling pathways involving PSCs. This study aimed to examine the role of PAK1 in PSCs and in the interaction of PSCs with pancreatic cancer cells. Human PSCs were isolated using the modified outgrowth method. The effect of inhibiting PAK1 with group 1 PAK inhibitor, FRAX597, on cell proliferation and apoptosis in vitro was measured by thymidine incorporation and annexin V assays, respectively. The effect of depleting host PAK1 on the survival of mice with pancreatic Pan02 cell tumors was evaluated using PAK1 knockout (KO) mice. PAK1 was expressed in isolated PSCs. FRAX597 reduced the activation of PSCs, inhibited PSC proliferation, and increased PSC apoptosis at least in partial by inhibiting PAK1 activity. The decreased expression and activity of PAK1 in PAK1 KO mice tumors was associated with an increased mouse survival. These results implicate PAK1 as a regulator of PSC activation, proliferation and apoptosis. Targeting stromal PAK1 could increase therapeutic response and survival of patients with pancreatic cancer.


Systemic Lupus Erythematosus is a Risk Factor for Complications in Total Joint Arthroplasty.
Systemic Lupus Erythematosus (SLE) has been associated with increased complications following hip and knee arthroplasty. The Purpose of this study was to determine the extent to which SLE is a risk factor in outcomes following total joint arthroplasty (TJA). The nationwide inpatient sample was used to identify a cohort of 505,841 patients who had a total hip arthroplasty (THA) or total knee arthroplasty (TKA) between 2009-2011. Of these patients, 2,284 patients (0.45%) had been previously diagnosed with SLE. The impact of SLE on short-term TJA outcomes was determined using multivariate logistic regression. Differences in discharge destination and length of stay were also evaluated. SLE patients were more likely to have an all-cause medical complication, (OR 1.9, p<0.0001) and more likely to have an all-cause surgical complication (OR 1.3, p<0.0001). SLE patients were four times more likely to become septic in the post-operative period (OR 3.8, p<0.0487). SLE patients were more likely to have a genitourinary complication (OR 1.7, p<0.0001) and bleeding complications requiring transfusion (OR 2.1, p<0.0001). Patients with SLE also had an increased length of stay (0.38 days, p<0.0001) and increased probability of discharging to a facility (OR 2.1, p<0.0001). Patients with SLE had an increased rate of both medical and surgical all-cause complications. Patients were specifically found to be at higher risk for sepsis, genitourinary complications, and blood transfusions. Future risk adjustment models should include SLE as a contributor to medical and surgical complications in the postoperative period.


Chromophores in human skin.
Human skin, especially the epidermis, contains several major solar ultraviolet-radiation- (UVR-) absorbing endogenous chromophores including DNA, urocanic acid, amino acids, melanins and their precursors and metabolites. The lack of solubility of melanins prevents their absorption spectra being defined by routine techniques. Indirect spectroscopic methods show that their spectral properties depend on the stimulus for melanogenesis. The photochemical consequences of UVR absorption by some epidermal chromophores are relatively well understood whereas we lack a detailed understanding of the consequent photobiological and clinical responses. Skin action spectroscopy is not a reliable way of relating a photobiological outcome to a specific chromophore but is important for UVR hazard assessment. Exogenous chromophores may be administered to the skin in combination with UVR exposure for therapeutic benefit, or as sunscreens for the prevention of sunburn and possibly skin cancer.


[Effect of various methods of oxygenation of the small intestine mucosa on the kinetic characteristics of glucose and glycine transport].
Nutrient transport in the small intestine in different conditions of oxygenation of the mucosa in vitro has been studied using original approaches. New experimental data revealed two types of cellular respiration: basolateral and apical ones. Mucosal, serosal and bilateral oxygenations were shown to affect kinetic characteristics (Kt, Vmax) of glucose and glycine active transport in the small intestine. The effect of starvation on the active transport of glucose in the small intestine in different conditions of oxygenation, is discussed. When passing from satiety to starvation state, active accumulation of glucose in the tissue increased during serosal oxygenation and decreased during mucosal and bilateral oxygenation. Characteristic features of functioning of the two types of cellular respiration were investigated in various periods of starvation.


Vasoactive intestinal peptide is critical for circadian regulation of glucocorticoids.
Circadian control of behavior and physiology is a central characteristic of all living organisms. The master clock in mammals resides in the hypothalamus, where the suprachiasmatic nucleus (SCN) synchronizes daily rhythms. A variety of recent evidence indicates that the neuropeptide vasoactive intestinal peptide (VIP) is critical for normal functioning of the SCN. The aim of our study was to examine the possible role of VIP in driving circadian rhythms in the hypothalamic-pituitary-adrenal axis. Circulating ACTH and corticosterone concentrations were determined by round-the-clock sampling under diurnal and circadian conditions. The responsive aspects of the hypothalamic-pituitary-adrenal axis were tested by application of acute stress by footshock and light. We demonstrate that the circadian rhythms in ACTH and corticosterone are lost in VIP-deficient mice. The ability of light to induce a corticosterone response was also compromised in the mutant mice, as was photic induction of Per1 in the adrenal glands. In contrast, the acute stress response was apparently unaltered by the loss of VIP. Thus, our data demonstrate that VIP is essential for the circadian regulation of an otherwise intact hypothalamic-pituitary-adrenal axis.


Biological and biochemical characterization of a somatostatin-producing human carcinoma established by heterotransplantation.
A somatostatin-producing human carcinoma cell line was established by heterotransplantation into athymic nude mice. The original material, which was derived from a colon tumor of a patient who had previously had bilateral ovarian tumors contained 66 ng extractable somatostatin/g tissue. Somatostatin-producing cells could be identified by immunohistochemistry within the first tumor transplants. Although initially the somatostatin concentration was low (14 ng/g) a progressive increase was observed with each successive transplantation so that after 10 passages it reached a level of 127 ng/g tissue. Analysis of tumor extracts by gel filtration and high-performance liquid chromatography indicated that somatostatin-14 was the only molecular form produced by the original and by the transplanted tumor after multiple passages. This result demonstrates that the tumor has the ability to constitutively express the prosomatostatin gene and to process the primary translation product to somatostatin-14.