Cytotoxicity by human adherent cells: oxygen-dependent and -independent cytotoxic reactions by different cell populations.
Human adherent cells, obtained by EDTA reversible adherence to plastic, are potent effectors in cell-mediated cytotoxicity. Spontaneous cytotoxicity in a 2-hr assay against K562 target cells was shown to be largely mediated by contaminating natural killer (NK) cells. Treatment of adherent cells with NK-specific monoclonal antibody anti-Leu-11 plus complement abolished almost completely the spontaneous cytotoxicity. Spontaneous cytotoxicity by adherent cells was also reduced when the phorbol ester PMA was present in the assay. On the other hand, PMA induced a cytotoxic response in NK-cell depleted adherent cells after prolonged 18 hr incubation. The cell population responsible for this dichotomous effect of PMA on adherent cell-mediated cytotoxicity was shown to be monocytes, as revealed by monoclonal antibody treatment. Pure NK cell preparations were not affected by PMA in their cytolytic capacities. Reactive oxygen species are not involved in NK-cell mediated cytotoxicity, while PMA stimulated the monocytes to exert cytolysis and suppressed NK cells by the generation of these highly toxic oxygen products. Hydrogen peroxide especially seemed to be the mediator in this oxygen-dependent monocyte-mediated cytotoxicity and NK-cell suppression.


Adenovirus endocytosis via alpha(v) integrins requires phosphoinositide-3-OH kinase.
Integrins mediate cell adhesion and motility on the extracellular matrix, yet they also promote viral attachment and/or entry. Evidence is presented that adenovirus internalization by alpha(v) integrins requires activation of phosphoinositide-3-OH kinase (PI3K), whereas alpha(v) integrin-mediated cell motility depends on the ERK1/ERK2 mitogen-activated protein kinase pathway. Interaction of adenovirus with alpha(v), integrins induced activation of PI3K. Pharmacologic or genetic disruption of endogenous PI3K activity blocked adenovirus internalization and virus-mediated gene delivery yet had no effect on integrin-mediated cell adhesion or motility. Therefore, integrin ligation engages distinct signaling pathways that promote viral endocytosis or cell movement.


Radiation exposure of a population due to diagnostic x-ray examinations: some critical remarks.
From the figures and the statistics obtained from radiological examinations carried out annually, the 'mean annual bone marrow dose' or the annual 'genetically significant gonadal dose' of a population can be calculated. In this study the irradiation parameters corresponded approximately to those reported by some 200 doctors. The testes and ovarian doses were measured with TL dosemeters inside a phantom; the bone marrow dose was determined using the same dosemeters inserted at 55 points in the phantom. The measured values were finally computer transformed into the mean doses per examination that would have been obtained had each measurement been carried out using the parameters to which x-ray units are actually set by doctors. The use of different methods for determining gonadal dose makes it practically impossible to draw conclusions about possible over-utilisation of radiological procedures in the country in question. The same applies for the average exposure per inhabitant, i.e. the sum of the experimentally determined gonadal doses of all the people examined by radiology in one year, divided by the population of a country. It would therefore be greatly appreciated if a certain amount of standardisation as regards measuring methods and the selection of irradiation parameters could be introduced at international level.


Steps towards empowerment: an examination of colleges, health services and universities.
In Australia, nursing educators work across three main contexts - training colleges, health services and universities. Because the pace of change for nursing has increased dramatically and the curriculum is becoming even more crowded, educators in these contexts are likely to be experiencing work-related stress. This study investigated this issue utilising a purposive sampling strategy to interview a cross section of nurse educators and those supporting educators. Eighteen in-depth interviews were completed, which included fourteen nurse educators and four key stakeholders. Qualitative analysis revealed that regardless of context, nurse educators found their role rewarding but there are common challenges. These included: Work role pressures, a non-validating culture, the pace of change, isolation and concern for the profession. There are also differences amongst the cohorts. Finally, participants elaborated on specific solutions to these problems and there is strong support for the establishment of a national community of practice to bring diverse educators together to share, support, extend and evaluate each others' work.


Data Self-Recalibration and Mixture Mass Fingerprint Searching (DASER-MMF) to enhance protein identification within complex mixtures.
A novel algorithm based on Data Self-Recalibration and a subsequent Mixture Mass Fingerprint search (DASER-MMF) has been developed to improve the performance of protein identification from online 1D and 2D-LC-MS/MS experiments conducted on high-resolution mass spectrometers. Recalibration of 40% to 75% of the MS spectra in a human serum dataset is demonstrated with average errors of 0.3 +/- 0.3 ppm, regardless of the original calibration quality. With simple protein mixtures, the MMF search identifies new proteins not found in the MS/MS based search and increases the sequence coverage for identified proteins by six times. The high mass accuracy allows proteins to be identified with as little as three peptide mass hits. When applied to very complex samples, the MMF search shows less dramatic performance improvements. However, refinements such as additional discriminating factors utilized within the search space provide significant gains in protein identification ability and indicate that further enhancements are possible in this realm.


Routine rapid Mycobacterium species assignment based on species-specific allelic variation in the 65-kilodalton heat shock protein gene (hsp65).
To assess the utility of automated DNA sequencing strategies for Mycobacterium species assignment and surrogate rifampin susceptibility testing of Mycobacterium tuberculosis complex isolates in a hospital-based clinical microbiology laboratory. Consecutive patient specimens (n = 161) cultured in BACTEC 12B medium (growth index of 50 or greater) or on solid media (Löwenstein-Jensen) were analyzed. A 360-bp segment of a gene (hsp65) encoding a 65-kd heat shock protein was sequenced to identify species-specific allelic polymorphism. Identification of sequence variation in the rpoB gene encoding the beta subunit of RNA polymerase was used as a surrogate method to assess rifampin susceptibility in M tuberculosis complex isolates. The automated DNA sequencing strategies rapidly identified virtually all mycobacteria (158 [98%] of 161) to the species level and unambiguously characterized the region of rpoB that contains mutations responsible for rifampin resistance in M tuberculosis strains. With few exceptions, DNA sequence-based species assignment data agreed with diagnostic information obtained by conventional methods. All discrepancies were due to ambiguous biochemical test data or interpretation. The rifampin susceptibility phenotype was correctly predicted for all strains by rpoB sequencing. Rapid mycobacterial species assignment based on hsp65 sequencing can be routinely performed in a hospital diagnostic microbiology laboratory setting. The method is especially useful for identification of fastidious organisms, such as Mycobacterium genavense. Sequencing of the rifampin-resistance-determining region of rpoB provides a convenient surrogate strategy for predicting rifampin susceptibility in M tuberculosis complex isolates.


Morphological and biochemical effects of food deprivation during the early development of Pacific red snapper Lutjanus peru.
We report the effects of food deprivation on the early development of Pacific red snapper Lutjanus peru during the first days of development. The point of no return (PNR) was determined using the feeding incidence after a delay in first feeding. The gradual deterioration of the larvae during food deprivation was recorded using morphometric, histological, enzymatic and biochemical analysis. The time to reach the PNR was 120 h after hatching. Morphologically, the total length, muscle height, head length, tail length and pectoral angle showed the biggest reductions and their growth coefficients changed significantly during food deprivation. Histologically, enterocyte height also was reduced significantly. The protein concentration and activities of the digestive enzymes trypsin, cathepsin-like and lipase showed a significant decrease; meanwhile, amylase activity remained constant during food deprivation. The concentration of total essential free amino acids (EFAAs) decreased significantly while that of the nonessential free amino acids (NEFAAs) remain stable during food deprivation. The most abundant EFAAs were lysine, leucine, isoleucine and valine; the most abundant NEFAAs were alanine, glycine and glutamate, suggesting a more prominent role as energy substrates. At the time of the PNR the concentration of almost all the free amino acids showed a significant decrease. Early food deprivation has a significant impact on the morphology and biochemical characteristics of L. peru. These results suggest that initial feeding of L. peru should begin within 3 days of yolk sac depletion to avoid the PNR. Further studies are necessary to confirm and validate the characters identified in this study as biomarkers of starvation under culture conditions and evaluate their possible utility in ichthyoplankton surveys.


Detection of pemphigus autoantibodies by IIF and ELISA tests in patients with pemphigus vulgaris and foliaceus and in healthy relatives.
Pemphigus is a life-threatening, autoimmune blistering disease, mediated by IgG autoantibodies. The aim of our study was to assess the usefulness of a new enzyme-linked immunosorbent assay (ELISA) in detecting circulating pemphigus autoantibodies, and to compare its sensitivity and specificity with the indirect immunofluorescence (IIF) test. We also established the frequency of occurrence of pemphigus autoantibodies in relatives of our patients. IIF and ELISA tests were performed in 24 patients with pemphigus vulgaris, 13 with pemphigus foliaceus, 56 healthy relatives, and 50 controls, selected according to sex and age. The obtained results revealed high specificity and sensitivity of ELISA, comparable to the IIF test, especially in patients who were in the active stage of the disease. We also showed that the profile of anti-Dsg 1 and/or anti-Dsg 3 autoantibodies is associated with the clinical variant of pemphigus. The frequency of occurrence of pemphigus autoantibodies in the relatives (24/55) performed by IIF was significantly higher (p<0.001) than in the controls (0/50). The same antibodies detected by ELISA (11/56) were less frequent. In clinically doubtful cases, in which autoantibodies titres by IIF are equal on both substrates (monkey and guinea pig esophagus), the assessment of the exact antibody profile (anti-Dsg 1 and/or anti-Dsg 3) is important to establish the subtype of pemphigus. The frequency of pemphigus antibody occurrence in healthy relatives seems not to be incidental, but further studies should be performed to explain this phenomenon.


Analyzing influencing factors to scale up agroforestry systems in Colombia: A comparative ex-ante assessment of cacao farming and cattle ranching in two regions.
Agroforestry systems (AFS) are proved to enhance sustainable land management. Thus, there is increasing demand for effective ways to scale up AFS so that more people can benefit. Consequently, this study assesses the scaling-up potential of agroforestry systems (AFS) using cacao farming and cattle ranching in Caquetá and Cesar, Colombia, as examples. An ex-ante assessment using the ScalA tool is conducted through interviews with AFS experts from institutions promoting AFS. Using a comparative approach, results reveal that AFS have different scaling-up potential depending on the type of farming system and location characteristics. In our case, it is slightly higher for cacao farming than for cattle ranching in both regions and it is higher in Caquetá than in Cesar for both systems. Factors hindering the scaling-up potential for both regions are economic conditions at the local and regional levels since there is a lack of stable and differentiated markets to absorb AFS products. In contrast, the scaling-up potential in both regions is increased by the factors related to the capacity of the organizations that promote AFS and the attitudes of local communities toward them. The study generates information about factors that may hinder or foster AFS scaling-up, including not just the capacities and mechanisms to promote them but also the enabling conditions. This contributes to prioritizing AFS interventions and better allocating their resources to increase their chances of successful scaling-up. The online version contains supplementary material available at 10.1007/s10457-022-00730-1.


Nickel sensitivity in atopics, psoriatics and healthy subjects.
A prospective study of 552 persons was performed to study nickel allergy in atopics, with and without dermatitis, psoriatics and healthy adults. We found no statistically-significant difference in the frequency of nickel allergy between persons with atopic dermatitis, atopics without dermatitis and healthy controls. More females than men gave a history of metal intolerance and gave allergic patch test reactions. A poor correlation between history and patch test reaction was not specific for atopics. Psoriatics had a significantly lower frequency of allergic patch test reactions to nickel than healthy controls or atopics with and without dermatitis. Psoriatics should not be used as controls for atopics in studies of contact dermatitis.


[Sensitization to storage mites--studies of the incidence of sensitivity to storage mites in comparison with house dust mites. Experiences in allergologic ambulatory care].
We examined the prevalence of sensitisation to storage mites and house dust mites in patients attending a pneumologist and allergologist in the office and clinical outpatient department. Our findings show sensitisations to storage mites up to 12%, to house dust mites in 26%. From a total of 3213 patients 914 patients (= 28%) showed positive skin reactions against at least one storage mite. There is a relationship of about 2:1 between house dust mites and storage mites in skin test results. From these data, safe conclusions as to the prevalence of storage mite sensitisation among the general population may not be drawn.


IgG fc N-glycosylation changes in Lambert-Eaton myasthenic syndrome and myasthenia gravis.
N-glycosylation of the immunoglobulin Fc moiety influences its biological activity by, for example, modulating the interaction with Fc receptors. Changes in IgG glycosylation have been found to be associated with various inflammatory diseases. Here we evaluated for the first time IgG Fc N-glycosylation changes in well-defined antibody-mediated autoimmune diseases, that is, the neurological disorders Lambert-Eaton myasthenic syndrome and myasthenia gravis, with antibodies to muscle nicotinic acetylcholine receptors or muscle-specific kinase. IgGs were purified from serum or plasma by protein A affinity chromatography and digested with trypsin. Glycopeptides were purified and analyzed by MALDI-FTICR-MS. Glycoform distributions of both IgG1 and IgG2 were determined for 229 patients and 56 controls. We observed an overall age and sex dependency of IgG Fc N-glycosylation, which was in accordance with literature. All three disease groups showed lower levels of IgG2 galactosylation compared to controls. In addition, LEMS patients showed lower IgG1 galactosylation. Notably, the galactosylation differences were not paralleled by a difference in IgG sialylation. Moreover, the level of IgG core-fucosylation and bisecting N-acetylglucosamine were evaluated. The control and disease groups revealed similar levels of IgG Fc core-fucosylation. Interestingly, LEMS patients below 50 years showed elevated levels of bisecting N-acetylglucosamine on IgG1 and IgG2, demonstrating for the first time the link of changes in the level of bisecting N-acetylglucosamine with disease.


Polymerase Chain Reaction using "V" Shape Thermal Cycling Program.
Polymerase chain reaction (PCR) is the most commonly used technique in molecular biology and diagnostics. To achieve faster PCR reaction time, two strategies were employed by previous studies. That includes improving the thermal ramp rate by developing novel devices to reduce the time wasted on temperature transitions and cutting the holding time in every step, which could even lead to compromise in amplification efficiency. Hence the need to further improve the technique. Methods: A different way to achieve fast DNA amplification is developed by using the previously thought wasted time spent on heating and cooling the samples to finish the amplification. That means the holding time of the three procedures are omitted and this could be carried out on the ordinary PCR thermal cyclers. Results: 2/3 of the amplification time is easily saved, compared to the conventionally used method. Additionally, the reaction time could be further reduced by using longer primers with higher melting temperature (Tm). The record time of the "V" shape Polymerase chain reaction (VPCR) conducted on ordinary PCR machine for amplification of a 98 bp fragment is 8 min. Furthermore, VPCR still retains the merits of traditional PCR technique, including specificity, sensitivity, generality, and compatibility with quantitative detection. Conclusion: It is confirmed that the three procedures of PCR could be completed during the dynamic heating and cooling process when the cyclers are run at a moderate thermal ramp rate. As VPCR described here is based on the current PCR system, it could be implemented in any biological Lab immediately and provide great convenience to the people working in the field of life science and human health.


Cordyceps cicadae polysaccharides ameliorated renal interstitial fibrosis in diabetic nephropathy rats by repressing inflammation and modulating gut microbiota dysbiosis.
Diabetic nephropathy (DN), a complication of diabetes mellitus, has been the leading cause of death in people with chronic kidney disease. This study was conducted to examine the potential health benefits of Cordyceps cicadae polysaccharides (CCP) on kidney injury and renal interstitial fibrosis that occur in DN rats. First, a DN model was established using SD rats fed with a high-fat diet for 8 weeks, then injected with STZ (35 mg/kg) intraperitoneally. The rats were then supplemented with CCP (75, 150 and 300 mg/kg) for 4 weeks. The results indicated that CCP improve insulin resistance and glucose tolerance in DN rats. Furthermore, CCP intervention significantly suppressed the inflammation, renal pathological changes and renal dysfunction, slowing down the progression of renal interstitial fibrosis. Moreover, high-throughput pyrosequencing of 16S rRNA suggested that CCP modulated the dysbiosis of gut microbiota by enhancing the relative abundance and proliferation capacity of probiotics. In vitro, CCP can markedly decrease LPS-induced inflammatory cytokine levels and TGF-β1-induced fibroblast activation. In summary, the results provided evidence that CCP exerted a beneficial effect on tubulointerstitial fibrosis in DN rats by possibly suppressing the inflammatory response and modulating gut microbiota dysbiosis, via blocking the TLR4/NF-κB and TGF-β1/Smad signaling pathway.


The use of multiparametric 18F-fluoro-L-3,4-dihydroxy-phenylalanine PET/MRI in post-therapy assessment of patients with gliomas.
To determine the utility of F-fluoro-L-3,4-dihydroxy-phenylalanine (F-DOPA) PET/MRI versus cross-sectional MRI alone in glioma response assessment and identify whether the two techniques demonstrate different tumour features. F-DOPA PET/MRI studies from 40 patients were analysed. Quantitative PET parameters and conventional MRI features were recorded. Tumour volume was assessed on both PET and MRI. Using dynamic susceptibility contrast perfusion-weighted imaging, maps of cerebral blood flow (CBF) and cerebral blood volume (CBV) were obtained. Within volume of tumours of tumour features and normal-appearing white matter (NAWM) drawn on MRI, standardised uptake value (SUV)max, CBF and CBV were recorded. Presence of residual active tumour was assessed by qualitative visual assessment. Receiver operating characteristic analysis was performed univariately and on parameter combination to analyse ability to determine presence/absence of disease. Reference standard for presence of viable tissue was biopsy or clinical follow-up. Median SUVmax was 3.4 for low-grade glioma (LGG) and 3.3 for high-grade glioma (HGG). There was a significant correlation between PWI parameters and WHO grade (P < 0.001), but no correlation with SUVmax. Median F-DOPA volume was 8216.88 mm for HGG and 6284.94 mm for LGG; MRI volume was 6316.57 mm and 5931.55 mm, respectively. SUVmax analysis distinguished enhancing and nonenhancing components from necrosis and NAWM and demonstrated active disease in nonenhancing regions. Visually, the modalities were concordant in 37 patients. Combining the multiparametric PET/MRI approach with all available data-enhanced detection of the presence of tumour (area under the curve 0.99, P < 0.01). MRI and F-DOPA are complementary modalities for assessment of tumour burden. Matching F-DOPA and MRI in assessing residual tumour volume may better delineate the radiotherapy target volume.


[Electron-beam computed tomography for identification of high-risk persons in primary prevention of coronary heart disease in the United States and its implication for Japan].
Coronary heart disease (CHD) is the leading cause of death in the United States (US). Approximately half of deaths from (CHD) occur out of hospital, most being sudden. The majority of sudden cardiac deaths occur in asymptomatic subjects. Recent lipid-lowering trials in asymptomatic subjects have demonstrated the potential for risk reduction for CHD events by primary prevention. It is, however, generally acknowledged that risk will be underestimated in asymptomatic subjects who fall into the category of intermediate risk by the traditional risk factors. Non-invasive measurements of subclinical atherosclerosis, which is the end result of risk-factor exposure, have the possibility of improving the risk stratification of asymptomatic subjects in intermediate-risk. Electron-beam computed tomography (EBCT) is a non-invasive and highly sensitive means to detect calcification within coronary arterial wall. Coronary artery calcification (CAC) is a recognized marker of atherosclerosis. Atherosclerotic burden of coronary arteries correlates strongly with the amount of CAC measured by EBCT. Studies examining the predictive value of CAC among asymptomatic subjects consistently reported that CAC is a risk for CHD. Two studies reported that unadjusted odds ratios of CAC for CHD were over 20. Incremental value of EBCT over the traditional risk assessment models, however, has not been established. Although CHD mortality in Japan remains uniquely low in industrialized countries, among men aged 30-49, risk factor profiles for CHD are similar between men in the US and Japan, except higher prevalence of cigarette smoking in Japan and higher prevalence of obesity in the US. It is reported that the declining trend in CHD mortality in Japan has recently slowed down in metropolitan areas, especially in men aged 30-49, and that the incidence has increased in middle-aged workers in a metropolitan area. A mortality validation study reported that the differences in CHD mortality between the US and Japan were not as large as suggested by vital statistics. It is, therefore, important to evaluate subclinical atherosclerosis measured by EBCT in men in recent birth cohorts in Japan and compare it to that in men in the US in order to predict future trend in CHD in Japan.


Clerodendron inerme protects cellular integrity during 7,12-dimethylbenz[A]-anthracene induced hamster buccal pouch carcinogenesis.
Aim of the present study was to investigate the protective effect of Clerodendron inerme on cellular integrity by measuring the status of glycoconjugates, lipids, osmotic fragility, and membrane bound enzyme activity in 7,12-dimethylbenz (a) anthracene (DMBA)-induced oral carcinogenesis. Oral squamous cell carcinoma was induced in the buccal pouch of Syrian golden hamsters by painting with 0.5% DMBA in liquid paraffin thrice a week for 14 weeks. The levels of glycoconjugates, lipids, osmotic fragility and membrane bound enzyme activity were analyzed by using specific colorimetric methods. We observed 100% tumor formation in DMBA painted hamsters. Altered glycoconjugates and lipid pattern were observed in DMBA painted hamsters as compared to control hamsters. Erythrocytes from DMBA painted hamsters were more fragile than those from control hamsters. The activity of membrane bound enzyme (Na(+) K(+) ATPase) decreased in DMBA painted hamsters as compared to control hamsters. Oral administration of aqueous leaf extract of Clerodendron inerme (CiALet) at a dose of 500 mg/kg body weight significantly prevented the tumor formation and histopathological abnormalities as well as normalized the above said biochemical variables in DMBA painted hamsters. Our results thus demonstrate the protective effect of Clerodendron inerme on cellular integrity during DMBA induced oral carcinogenesis.


Nasopharyngeal carcinoma: recognizing the radiographic features in children.
Children often present with enlargement of the nasopharyngeal soft tissues, which is usually due to benign hypertrophy of adenoids. The objective of this report is to emphasize that, although rare, nasopharyngeal carcinoma (NPC) does occur in children and can be diagnosed reliably when certain key radiographic features are recognized. The presenting scans of 11 patients with biopsy proven NPC were reviewed retrospectively by a CAQ-certified neuroradiologist. The age range was 12-17 years (median 15 years). Fifteen scans were reviewed, including 8 CT scans of the neck with intravenous contrast and 7 MR scans of the nasopharynx without and with gadolinium. All 11 patients had a nasopharyngeal mass. The nasopharyngeal mass had invaded the central skull base in 10 patients (91%). Widening of the petroclival fissure was present in 8 (73%) patients; all except one patient had accompanying skull base invasion. The tumor had extended into the adjacent parapharyngeal space in 6 (55%), the pterygopalatine fossa in 2 (18%), and the masticator space in 2 (18%). Unilateral cervical lymphadenopathy was present in 4 (36%) and bilateral in 7 (64%). Lateral retropharyngeal lymphadenopathy that measured greater than 1 cm in maximal transverse dimension was present in 10 (91%). Pediatric NPC is generally not suspected clinically until late into the disease process. Awareness that NPC can occur in children should prompt careful evaluation for distinctive radiographic features. Earlier diagnosis may then direct the patient to timely appropriate therapy when these key radiographic features are present and recognized.


Narcolepsy Type 1 Is Associated with a Systemic Increase and Activation of Regulatory T Cells and with a Systemic Activation of Global T Cells.
Narcolepsy is a rare neurologic disorder characterized by excessive daytime sleepiness, cataplexy and disturbed nocturnal sleep patterns. Narcolepsy type 1 (NT1) has been shown to result from a selective loss of hypothalamic hypocretin-secreting neurons with patients typically showing low CSF-hypocretin levels (<110 pg/ml). This specific loss of hypocretin and the strong association with the HLA-DQB1*06:02 allele led to the hypothesis that NT1 could be an immune-mediated pathology. Moreover, susceptibility to NT1 has recently been associated with several pathogens, particularly with influenza A H1N1 virus either through infection or vaccination. The goal of this study was to compare peripheral blood immune cell populations in recent onset pediatric NT1 subjects (post or non-post 2009-influenza A H1N1 vaccination) to healthy donors. We demonstrated an increased number of central memory CD4+ T cells (CD62L+ CD45RA-) associated to an activated phenotype (increase in CD69 and CD25 expression) in NT1 patients. Percentage and absolute count of regulatory T cells (Tregs) in NT1 patients were increased associated with an activated phenotype (increase in GITR and LAP expression), and of activated memory phenotype. Cytokine production by CD4+ and CD8+ T cells after activation was not modified in NT1 patients. In H1N1 vaccinated NT1 patients, absolute counts of CD3+, CD8+ T cells, and B cells were increased compared to non-vaccinated NT1 patients. These results support a global T cell activation in NT1 patients and thus support a T cell-mediated autoimmune origin of NT1, but do not demonstrate the pathological role of H1N1 prophylactic vaccination. They should prompt further studies of T cells, particularly of Tregs (such as suppression and proliferation antigen specific assays, and also T-cell receptor sequencing), in NT1.


The assessment of carcass traits of Awassi lambs by real-time ultrasound at different body weights and sexes.
The objectives of this experiment were to evaluate the accuracy of ultrasonography to measure subcutaneous fat thickness (SFT) and LM traits (area, depth, and width) in live Awassi lambs of different sexes, predict actual SFT and LM traits without damage to the carcass, and improve carcass classification. Data were obtained from ultrasound scans of 20 female and 10 male lambs. Female lambs were randomly divided into light (FL; n = 10) and heavy (FH; n = 10) finishing groups. Slaughter weights of lambs in FL were 30 kg and for FH and male groups were 40 kg. Subcutaneous fat thickness and LM traits, cross-sectional area between the 12th and 13th rib were measured using real-time ultrasound in vivo and on the carcass after slaughter. All ultrasound and carcass measurements were different (P > 0.05) except carcass yield and carcass LM width in female lambs (FL and FH). Between different sex groups, all ultrasound and carcass measurements were the same except ultrasound SFT (USFT; P = 0.04) and carcass SFT (CSFT; P = 0.03). Significant correlation coefficients were between USFT and CSFT (0.93, P < 0.01; 0.76, P = 0.02), ultrasound LM depth (ULMD) and carcass LM depth (CLMD; 0.64, P = 0.05; 0.77, P < 0.01), and ultrasound LM area (ULMA) and carcass LM area (CLMA; 0.88, 0.84; P < 0.01) for female lambs in FL and FH groups. Also, similar correlations were determined significantly between USFT and CSFT (0.84, P < 0.01; 0.76, P = 0.02), ULMD and CLMD (0.69, P = 0.03; 0.77, P < 0.01), and ULMA and CLMA (0.88, 0.84; P < 0.01) for male lambs in male and FH groups. The introduction of USFT and ULMA as independent variables in addition to BW in the multiple regression equations further improved the variations for CSFT (88, 75, and 81%) and CLMA (78, 90, and 80%) for lambs in FL, FH, and male groups, respectively, whereas no improvement was observed for cold carcass weight with the exception of the FH group and carcass yield. These results indicate that in vivo USFT and ULMA in association with BW could be used to estimate CSFT, CLMA, and cold carcass weight ultrasound findings about LM, and SFT can be included to the selection programs for different BW and sex of Awassi lambs.


All-Cause and Cause-Specific Risk of Emergency Transport Attributable to Temperature: A Nationwide Study.
Although several studies have estimated the associations between mortality or morbidity and extreme temperatures in terms of relative risk, few studies have investigated the risk of emergency transport attributable to the whole temperature range nationwide.We acquired data on daily emergency ambulance dispatches in all 47 prefectures of Japan from 2007 to 2010. We examined the relationship between emergency transport and temperature for each prefecture using a Poisson regression model in a distributed lag nonlinear model with adjustment for time trends. A random-effect multivariate meta-analysis was then applied to pool the estimates at the national level. Attributable morbidity was calculated for high and low temperatures, which were defined as those above or below the optimum temperature (ie, the minimum morbidity temperature) and for moderate and also extreme temperatures, which were defined using cutoffs at the 2.5th and 97.5th temperature percentiles.A total of 15,868,086 cases of emergency transport met the inclusion criteria. The emergency transport was attributable to nonoptimal temperature. The median minimum morbidity percentile was in the 79th percentile for all causes, the 96th percentile for cardiovascular disease, and the 92th percentile for respiratory disease. The fraction attributable to low temperature was 6.94% (95% eCI: 5.93-7.70) for all causes, 17.93% (95% eCI: 16.10-19.25) for cardiovascular disease, and 12.19% (95% eCI: 9.90-13.66) for respiratory disease, whereas the fraction attributable to high temperature was small (all causes = 1.01%, 95% eCI: 0.90-1.11; cardiovascular disease = 0.10%, 95% eCI: 0.04-0.14; respiratory disease = 0.29%, 95% eCI: 0.07-0.50). The all-cause morbidity risk that was attributable to temperature was related to moderate cold, with an overall estimate of 6.41% (95% eCI: 5.47-7.20). Extreme temperatures were responsible for a small fraction, which corresponded to 0.57% (95% eCI: 0.50-0.62) for extreme low temperature and 0.29% (95% eCI: 0.26-0.32) for extreme high temperature. The same trends were observed for cardiovascular and respiratory diseases.The majority of temperature-related emergency transport burden was attributable to lower temperature. The effect of extremely high or low temperatures was markedly lower than that attributable to moderately nonoptimal temperatures.


Characterization of population structure from the mitochondrial DNA vis-à-vis language and geography in Papua New Guinea.
Situated along a corridor linking the Asian continent with the outer islands of the Pacific, Papua New Guinea has long played a key role in understanding the initial peopling of Oceania. The vast diversity in languages and unique geographical environments in the region have been central to the debates on human migration and the degree of interaction between the Pleistocene settlers and newer migrants. To better understand the role of Papua New Guinea in shaping the region's prehistory, we sequenced the mitochondrial DNA (mtDNA) control region of three populations, a total of 94 individuals, located in the East Sepik Province of Papua New Guinea. We analyzed these samples with a large data set of Oceania populations to examine the role of geography and language in shaping population structure within New Guinea and between the region and Island Melanesia. Our results from median-joining networks, star-cluster age estimates, and population genetic analyses show that while highland New Guinea populations seem to be the oldest settlers, there has been significant gene flow within New Guinea with little influence from geography or language. The highest genetic division is between Papuan speakers of New Guinea versus East Papuan speakers located outside of mainland New Guinea. Our study supports the weak language barriers to genetic structuring among populations in close contact and highlights the complexity of understanding the genetic histories of Papua New Guinea in association with language and geography.


Evaluation of the surface roughness of zirconia ceramics after different surface treatments.
This study aimed to investigate the effects of different mechanical surface treatments of pre-sintered zirconium oxide (ZrO2) in an attempt to improve its bonding potential. One hundred and twenty IPS e-max ZirCAD (Ivoclar Vivadent) pre-sintered zirconia blocks (7 mm diameter, 3 mm height) received six different surface treatments (n = 20): Group C was untreated (control); Group E was Er:YAG laser irradiated; Group N was Nd:YAG laser irradiated; Group SB was sandblasted, Group SN was sandblasted and Nd:YAG laser irradiated; and Group SE was sandblasted and Er:YAG laser irradiated. After the surface treatments, the average surface roughness (Ra, µm) of each specimen was determined with a profilometer, then all the specimens were sintered. The surface roughness values were analysed through one-way ANOVA and Tukey's test. Changes in the morphological characteristics of ZrO2 were examined through scanning electron microscopy (SEM). Sintered sandblasted, Er:YAG laser treatment, sandblasted + Er:YAG laser and sandblasted + Nd:YAG laser irradiation resulted in a rougher surface than the other treatments. Nd:YAG laser irradiation alone was not effective in altering the zirconia surface morphology.


Studies on plant regeneration and somaclonal variation in Saintpaulia ionantha Wendl. (African violet).
Efficient plant regeneration of Saintpaulia ionantha (African violet) has been obtained in the present study. MS medium supplemented with 1.0 mg L(-1) IAA and 2.0 mg L(-1) Zeatin resulted in 100% shoot regeneration and induced the highest number of shoots (average 15.0 +/- 0.8 shoots per explant) after being cultured for 8 weeks. The above hormone combination was optimum for shoot regeneration. Most of Saintpaulia ionantha plantlets derived from tissue culture system could be hardened and transferred to the greenhouse conditions with 84.0 +/- 1.6% success rate. However, regenerated plantlets of Saintpaulia ionantha (even after 12-months-old) failed to flower. Morphological characters of regenerated plantlets of Saintpaulia ionantha were observed and compared with in vivo (intact) plants. Regenerated plantlets showed some differences in morphological characters, such as height and leaf size, texture and colour, but the plantlets showed no variation in leaf arrangement and leaf margin. However, the morphological characters of the regenerated plantlets were found to be unstable.


Determination of the the H3 factor in hydrogen isotope ratio monitoring mass spectrometry.
The H3 factor, K, is a parameter required in high-precision, mass spectrometric analyses of hydrogen isotopic abundances. When H2 is used as the sample gas, R* = R - Ki2, where R* is the true HD/H2 ratio, R is the observed (mass 3)/(mass 2) ion-current ratio, and i2 is the ion current at mass 2. Four different methods for the determination of K were defined and tested under conditions characteristic of isotope ratio monitoring systems. Three of these were peak-based. The fourth employed steady flows of H2 from a conventional inlet system. Results obtained using the latter method were more precise (standard deviation of K = 0.1 versus approximately 0.6 ppm mV(-1) for the peak-based methods). However, use of the resulting values of K for correction of isotope ratio monitoring GC/MS results led to systematic errors as large as 9 per thousand, whereas use of the peak-based values led to no systematic errors. Values of K were only weakly dependent on the pressure of He, declining approximately 5% for each 10-fold increase in P(He). Small variations in partial pressures of H2O and CH4, potential contaminants under isotope ratio monitoring conditions, had no significant effect on values of K.


IkappaB kinase beta promotes cell survival by antagonizing p53 functions through DeltaNp73alpha phosphorylation and stabilization.
ΔNp73α, a dominant-negative inhibitor of p53 and p73, exhibits antiapoptotic and transforming activity in in vitro models and is often found to be upregulated in human cancers. The mechanisms involved in the regulation of ΔNp73α protein levels in normal and cancer cells are poorly characterized. Here, we show that that IκB kinase beta (IKKβ) increases ΔNp73α protein stability independently of its ability to activate NF-κB. IKKβ associates with and phosphorylates ΔNp73α at serine 422 (S422), leading to its accumulation in the nucleus, where it binds and represses several p53-regulated genes. S422A mutation in ΔNp73α abolished IKKβ-mediated stabilization and inhibition of p53-regulated gene expression. Inhibition of IKKβ activity by chemical inhibitors, overexpression of dominant-negative mutants, or gene silencing by siRNA also resulted in ΔNp73α destabilization, which under these conditions was rapidly translocated into the cytoplasm and degraded by a calpain-mediated mechanism. We also present evidence for the IKKβ and ΔNp73α cross talk in cancer-derived cell lines and primary cancers. Our data unveil a new mechanism involved in the regulation of the p73 and p53 network.


Inhibitory control test for the diagnosis of minimal hepatic encephalopathy.
Minimal hepatic encephalopathy (MHE) is difficult to diagnose. The Inhibitory Control Test (ICT) measures response inhibition and has diagnosed MHE with 90% sensitivity and specificity in a selected population; high lure and low target rates indicated poor ICT performance. We studied the reliability and validity of ICT for MHE diagnosis. ICT was compared with a psychometric battery (standard psychometric tests [SPT]) for MHE diagnosis and overt hepatic encephalopathy (OHE) prediction. ICT was administered twice for test-retest reliability, before/after transvenous intrahepatic portosystemic shunting (TIPS), and before/after yogurt treatment. The time taken by 2 medical assistants (MA) to administer ICT was recorded and compared with that of a psychologist for cost analysis. One hundred thirty-six cirrhotic patients and 116 age/education-matched controls were studied. ICT (>5 lures) had 88% sensitivity for MHE diagnosis with 0.902 area under the curve for receiver operating characteristic. MHE-positive patients had significantly higher ICT lures (11 vs 4, respectively, P = .0001) and lower targets (92% vs 97%, respectively, P = .0001) compared with MHE-negative patients. The test/retest reliability for ICT lures (n = 50, r = 0.90, P = .0001) was high. ICT and SPT were equivalent in predicting OHE (21%). ICT lures significantly worsened after TIPS (n = 10; 5 vs 9, respectively; P = .02) and improved after yogurt supplementation (n = 18, 10 vs 5, respectively; P = .002). The MAs were successfully trained to administer ICT; the time required for test administration and the associated costs were smaller for ICT than for SPT. ICT is a sensitive, reliable, and valid test for MHE diagnosis that can be administered inexpensively by MAs.


Menthol-Induced Cutaneous Vasodilation Is Preserved in Essential Hypertensive Men and Women.
Menthol is a selective transient receptor potential melastatin 8 (TRPM8) channel agonist that induces cutaneous vasodilation in young, normotensive men and women through nitric oxide synthase (NOS)-, endothelium-derived hyperpolarizing factor (EDHF)-, and sensory nerve-mediated mechanisms. Microvascular dysfunction is present in essential hypertension and whether menthol induces vasodilation is men and women with essential hypertension is equivocal. Four intradermal microdialysis fibers were placed in the forearm of 9 essential hypertensive and 10 age-matched normotensive control subjects. Sites were pretreated with lactated Ringer's (control), l-NAME (NOS inhibited), TEA (EDHF inhibited), and lidocaine (sensory nerve inhibited). The microdialysis fibers were then perfused with 7 increasing doses of menthol (0.1-500 mM). Red cell flux in response to menthol was measured with laser Doppler flowmetry. Data were normalized to mean arterial pressure and presented as a percentage of site-specific maximum vasodilation (%CVCmax). At the control site, menthol caused vasodilation in both the normotensive and hypertensive groups (menthol doses 100, 250, and 500 mM; all P < 0.05 compared to baseline). There were no differences between groups (P = 0.58, main effect). There was no effect of either NOS or sensory nerve inhibition on menthol-induced vasodilation in the normotensive group; however, menthol-induced vasodilation was attenuated with NOS and sensory nerve inhibition in the hypertensive group. EDHF inhibition attenuated menthol-induced vasodilation in both groups. Menthol-induced vasodilation has NO, EDHF, and sensory nerve components. Menthol-induced cutaneous vasodilation is preserved in hypertensive subjects. However, the hypertensive subjects exhibited a loss of redundant vasodilator systems.


Gastrointestinal parasites of cats in Denmark assessed by necropsy and concentration McMaster technique.
The large population of feral cats in Denmark may potentially transmit pathogens to household cats and zoonotic parasites to humans. A total of 99 euthanized cats; feral cats (n=92) and household cats with outdoor access (n=7), were collected from March to May 2014 from the Zealand region, Denmark. The sedimentation and counting technique (SCT) was used to isolate helminths and coproscopy was done by concentration McMaster technique (c-McMaster). Overall, 90.1% of the cats were infected and a total of 10 species were recorded by SCT: 5 nematode species: Toxocara cati (84.8%), Ollulanus tricuspis (13.1%), Aonchotheca putorii (7.1%), Paersonema spp. (3.0%), Strongyloides spp. (1.0%); 3 cestodes: Hydatigera taeniaeformis (36.4%), Mesocestoides sp. (3.0%), Dipylidium caninum (1.0%); and 2 trematodes: Cryptocotyle spp. (5.1%) and Pseudamphistomum truncatum (1.0%). O. tricuspis was the second most common gastrointestinal nematode of cats but had the highest intensity of infection. For T. cati, prevalence and worm burden were significantly higher in feral than household cats. No juvenile cats were infected with H. taeniaeformis, and age thus had a significant effect on prevalence and worm burdens of this species. Rural cats had a higher prevalence and worm burden of A. putorii than urban cats. By c-McMaster, ascarid, capillarid, strongylid or taeniid type eggs were found in 77.9% of the cats while Cystoisospora felis was found in 2.1%. The sensitivity of the c-McMaster was 82.5% for T. cati but 26.5% for taeniid eggs, using the SCT as gold standard. A positive correlation between faecal egg counts and worm burdens was seen for T. cati, but not for taeniid eggs (assumed to be H. taeniaeformis). Coprological examination also detected the eggs of extraintestinal Capillariidae species including Eucoleus aerophilus and Eucoleus boehmi, but further necropsy studies are needed to confirm these findings.


Use of plate fixation without coracoclavicular ligament augmentation for unstable distal clavicle fractures.
The purpose of this study was to evaluate the clinical and radiologic outcomes of unstable distal clavicle fractures treated with anatomic plate fixation without coracoclavicular ligament augmentation and to compare the outcome of Neer type IIA with that of type IIB. Twenty-five patients with unstable distal clavicle fractures who underwent anatomic plate fixation without coracoclavicular ligament augmentation were enrolled prospectively, including 9 patients of Neer type IIA and 16 patients of Neer type IIB. Clinical outcomes were evaluated using Constant and University of California-Los Angeles (UCLA) scores. Coracoclavicular distance was measured on plain radiographs. Bone union was achieved in all patients. Satisfactory clinical and radiologic outcomes were obtained regardless of fracture type. After operation, the mean coracoclavicular distance on the injured side was increased by 10% compared with the uninjured side. However, between the patients who showed an increased coracoclavicular distance >10% (Constant score, 89.4 ± 3.7; UCLA score, 32.6 ± 3) and the patients with increased coracoclavicular distance <10% of the uninjured side (Constant score, 88.7 ± 3.6; UCLA score, 31.9 ± 3), there was no statistically significant difference in clinical outcomes of Constant score (P = .934) and UCLA score (P = .598). In unstable distal clavicle fractures, precontoured anatomic plate fixation without coracoclavicular ligament augmentation showed satisfactory clinical outcomes and high union rates even with a small lateral fragment. Patients who had increased coracoclavicular distance also demonstrated satisfactory shoulder functional outcomes regardless of the fracture type. Therefore, anatomic plate fixation without additional coracoclavicular ligament augmentation can be considered one of the treatment options for unstable distal clavicle fracture. Level IV; Case Series; Treatment Study.


A joint model for mixed and truncated longitudinal data and survival data, with application to HIV vaccine studies.
In HIV vaccine studies, a major research objective is to identify immune response biomarkers measured longitudinally that may be associated with risk of HIV infection. This objective can be assessed via joint modeling of longitudinal and survival data. Joint models for HIV vaccine data are complicated by the following issues: (i) left truncations of some longitudinal data due to lower limits of quantification; (ii) mixed types of longitudinal variables; (iii) measurement errors and missing values in longitudinal measurements; (iv) computational challenges associated with likelihood inference. In this article, we propose a joint model of complex longitudinal and survival data and a computationally efficient method for approximate likelihood inference to address the foregoing issues simultaneously. In particular, our model does not make unverifiable distributional assumptions for truncated values, which is different from methods commonly used in the literature. The parameters are estimated based on the h-likelihood method, which is computationally efficient and offers approximate likelihood inference. Moreover, we propose a new approach to estimate the standard errors of the h-likelihood based parameter estimates by using an adaptive Gauss-Hermite method. Simulation studies show that our methods perform well and are computationally efficient. A comprehensive data analysis is also presented.


Leucine-rich α2 -glycoprotein as a potential biomarker for joint inflammation during anti-interleukin-6 biologic therapy in rheumatoid arthritis.
To investigate whether leucine-rich α2 -glycoprotein (LRG) could be a biomarker for disease activity during interleukin-6 (IL-6) blockade treatment of rheumatoid arthritis (RA). In 59 RA patients who were treated with tocilizumab for 24 weeks, serum LRG levels were determined by enzyme-linked immunosorbent assay. RA disease activity was evaluated by the Clinical Disease Activity Index (CDAI). Receiver operating characteristic (ROC) curve analysis was used to examine the diagnostic performance of LRG and other biomarkers. In monkeys with experimental autoimmune arthritis, swollen joint counts, joint pathologic changes, and blood levels of C-reactive protein (CRP) and LRG were evaluated after treatment with anti-IL-6 receptor antibody. Among tocilizumab-treated RA patients, those with active disease (CDAI >2.8) had significantly higher serum LRG levels compared to those whose disease was in remission. ROC curve analysis suggested that the LRG level was more useful than the CRP or matrix metalloproteinase 3 level or the erythrocyte sedimentation rate in discriminating between remission and active disease during therapy with tocilizumab. In monkeys treated with IL-6 blockade, joint scores were more closely correlated with LRG levels than with CRP levels. Histologic analysis of joints revealed that LRG levels correlated significantly with granulomatous tissue formation, cartilage degeneration, and bone destruction in IL-6 blockade-treated monkeys with low levels of CRP. Under conditions of IL-6 inhibition, LRG was more useful than other biomarkers in discriminating between active and inactive disease in human RA and in detecting joint inflammation in experimental arthritis. LRG may serve as a convenient biomarker for RA disease activity during IL-6 blockade treatment.


The terpene synthase gene family in Gossypium hirsutum harbors a linalool synthase GhTPS12 implicated in direct defence responses against herbivores.
Herbivore-induced terpenes have been reported to function as ecological signals in plant-insect interactions. Here, we showed that insect-induced cotton volatile blends contained 16 terpenoid compounds with a relatively high level of linalool. The high diversity of terpene production is derived from a large terpene synthase (TPS) gene family. The TPS gene family of Gossypium hirsutum and Gossypium raimondii consist of 46 and 41 members, respectively. Twelve TPS genes (GhTPS4-15) could be isolated, and protein expression in Escherichia coli revealed catalytic activity for eight GhTPS. The upregulation of the majority of these eight genes additionally supports the function of these genes in herbivore-induced volatile biosynthesis. Furthermore, transgenic Nicotiana tabacum plants overexpressing GhTPS12 were generated, which produced relatively large amounts of (3S)-linalool. In choice tests, female adults of Helicoverpa armigera laid fewer eggs on transgenic plants compared with non-transformed controls. Meanwhile, Myzus persicae preferred feeding on wild-type leaves over leaves of transgenic plants. Our findings demonstrate that transcript accumulation of multiple TPS genes is mainly responsible for the production and diversity of herbivore-induced volatile terpenes in cotton. Also, these genes might play roles in plant defence, in particular, direct defence responses against herbivores.


In-cell infection: a novel pathway for Epstein-Barr virus infection mediated by cell-in-cell structures.
Epstein-Barr virus (EBV) can infect both susceptible B lymphocytes and non-susceptible epithelial cells (ECs). Viral tropism analyses have revealed two intriguing means of EBV infection, either by a receptor-mediated infection of B cells or by a cell-to-cell contact-mediated infection of non-susceptible ECs. Herein, we report a novel "in-cell infection" mechanism for EBV infection of non-susceptible ECs through the formation of cell-in-cell structures. Epithelial CNE-2 cells were invaded by EBV-infected Akata B cells to form cell-in-cell structures in vitro. Such unique cellular structures could be readily observed in the specimens of nasopharyngeal carcinoma. Importantly, the formation of cell-in-cell structures led to the autonomous activation of EBV within Akata cells and subsequent viral transmission to CNE-2 cells, as evidenced by the expression of viral genes and the presence of virion particles in CNE-2 cells. Significantly, EBV generated from in-cell infected ECs displayed altered tropism with higher infection efficacy to both B cells and ECs. In addition to CNE-2 tumor cells, cell-in-cell structure formation could also mediate EBV infection of NPEC1-Bmi1 cells, an immortalized nasopharyngeal epithelial cell line. Furthermore, efficient infection by this mechanism involved the activation of the PI3K/AKT signaling pathway. Thus, our study identified "in-cell infection" as a novel mechanism for EBV infection. Given the diversity of virus-infected cells and the prevalence of cell-in-cell structures during chronic infection, we speculate that "in-cell infection" is likely a general mechanism for EBV and other viruses to infect non-susceptible ECs.


Serum Vaspin Levels in Gestational Diabetes Mellitus: A Meta-Analysis.
The objective of this study was to evaluate the potential relationship between serum vaspin levels and gestational diabetes mellitus (GDM). The PubMed, EBSCO, Web of Science, the Cochrane Library, and the China National Knowledge Infrastructure (CNKI) database were searched for articles published before December 2022. The publication language was restricted to English and Chinese. A meta-analysis was conducted by combining all studies that met the inclusion and exclusion criteria. Twenty-two studies (1990 women with GDM and 1597 pregnant women without GDM) were ultimately included in this meta-analysis. The meta-analysis showed that the serum vaspin levels are significantly higher in GDM compared with the controls (standardized mean difference: 0.720, 95% confidence interval: 0.440-1.000, Z = 5.041, P < 0.001). Subgroup analyses by stage of pregnancy and body mass index showed results similar to the overall outcome. No publication bias was identified, and the sensitivity analysis confirmed the robustness of the final result. Our results show that the serum vaspin levels are significantly higher in GDM. These findings suggest that high vaspin concentration is closely related to GDM and the serum vaspin levels might be a potential biomarker to indicate risk of GDM, more randomized control trials comparing the expression levels of vaspin between early and standard diagnosis of GDM are needed to strengthen our findings.


Invasive Rhino-Orbito-Cerebral Mucormycosis in Pediatric Patient with Acute Leukemia.
Invasive fungal infections are a life-threatening complication of cancer treatments, especially in hemato-oncological patients. Mucormycosis is the third leading cause of invasive fungal infections after Aspergillus and Candida infections. The first clinical symptoms are usually non-specific, which can lead to a late diagnosis and delayed therapy. The objective of this report is to summarize data in the literature about mucormycosis and to present a case report of a patient with acute lymphoblastic leukemia, who developed this infection at our center. Risk factors for the development of mucormycosis, clinical symptoms, radiology, laboratory results, and outcome were retrospectively evaluated. We describe a 6-years-old female patient with acute lymphoblastic leukemia. During the induction phase of therapy, the patient developed febrile neutropenia and did not respond to therapy with a combination of antibiotics and supportive treatment. Pansinusitis and orbitocellulitis developed. Examination of the biological material revealed that the etiological agent was a Rhizopus sp. The patient was treated with a combination of antimycotic drugs, but the infection disseminated to the central nervous system. She underwent radical surgical resection of the affected tissue. At this time, she is still under treatment with antimycotic and oncology agents, but is in remission of the main diagnosis and in good clinical condition. Mucormycosis is an invasive fungal infection with high morbidity and mortality. Early diagnosis and initiation of effective therapy using a combination of amphotericin B administration and surgery are necessary to obtain a favorable outcome. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.


An investigation into explosive force variation using occlusal bites.
To analyse the relationship between occlusion, posture and athletic performance in 15 professional basketball players. MATERIALS AND METHOD; The athletes were divided into two groups; the 8 subjects in the test group were fitted with retainers and the 7 subjects in the other group were used as control. All of the athletes underwent electromyographic and kinaesiographic examination with Transcutaneous Electrical Nerve Stimulation (TENS) before and after muscular relaxation to identify the myocentric position and to permit individualisation of the retainers. The effect of the intraoral devices on explosive force was evaluated via two functional tests: the countermovement jump (CMJ), and unilateral (UL) and bilateral (BL) stiffness jumps. The functional tests were carried out both before (T0) and immediately after (T1) fitting the retainer in an initial session, and then again, in a second session held two months later both without (T2) and with the retainer in place (T3). Statistical analysis of the data obtained revealed a statistically significant difference between T3 and T0, and between T3 and T2 in the study group, and between T0 and T3 in the control group; no statistically significant differences between the two groups were found. The results of this analysis lead us to conclude that the retainers had no effect on athletic performance, and that the improvement in this criteria noted in both groups in the second session was probably brought about by training.


Siliplant1 B-domain precipitates silica spheres, aggregates, or gel, depending on Si-precursor to peptide ratios.
Silica is extensively deposited by plants, however, only little is known about the molecular control over this process. Siliplant1 is the only known plant protein to precipitate biosilica. The protein contains seven repeats made of three domains. One of the domains exhibits a conserved sequence, which catalyzes silica precipitation in vitro. Here, silica was synthesized by the activity of a peptide carrying this conserved sequence. Infrared spectroscopy and thermal gravimetric analyses showed that the peptide was bound to the mineral. Scanning electron microscopy showed that silica-peptide particles of 22 ± 4 nm aggregated to spherical structures of 200-300 nm when the ratio of silicic acid to the peptide was below 183:1 molecules. When the ratio was about 183:1, similar particles aggregated into irregular structures, and silica gel formed at higher ratios. Solid-state NMR spectra indicated that the irregular aggregates were richer in Si-O-Si bonds as well as disordered peptide. Our results suggest that the peptide catalyzed the condensation of silicic acid and the formation of ∼20 nm particles, which aggregated into spheres. Excess of the peptide stabilized surface Si-OH groups that prevented spontaneous Si-O-Si bonding between aggregates. Under Si concentrations relevant to plant sap, the peptide and possibly Siliplant1, could catalyze nucleation of silica particles that aggregate into spherical aggregates.


Evaluation of long-term living conditions in patients treated for localised prostate cancer.
To evaluate the evolution of living conditions (LC) in long-term survivors of localised prostate cancer 10 years after treatment compared with those of a same-age control group from the general population. Two hundred and eighty-seven patients diagnosed with prostate cancer in 2001 were selected in 11 French cancer registries. They were matched with controls randomly selected for age and residency. Both patients and controls completed a self-administered LC questionnaire concerning their familial, social and professional life, and general and specific quality of life (QoL) and anxiety and depression questionnaires. Compared with controls, patients reported more sexual modifications (p < .0001), but without any difference in marital status. Patients' circle of friends was more stable than that of the controls (91% vs. 63%; p < .0001) and patients reported fewer friendship modifications than controls (p < .0006). Their professional and physical activities were also preserved. They reported more anxiolytic intake (p = .002) but did not consult their general practitioner more often. Type of specialist consulted differed in the two groups. Patients treated for localised prostate cancer had the same living conditions as men of the same age. Their social life was satisfying on the whole, albeit they reported more sexual difficulties than their counterparts.


Iron deposit state and risk factors for anemia in the elderly.
To determine the type of anemia, iron deposit and risk factors for anemia in the elderly. A cross-sectional study was conducted among 84 patients admitted to the geriatric inpatient ward of dr. Cipto Mangunkusumo Hospital. The patients underwent anamnesis, administration of a dietary questionnaire which included SQFF and food recording, physical examination, laboratory investigations (blood, urine and benzidine test), chest x-ray, ECG and spirometry. Anemic elderly patients also underwent iron store measurements, including serum iron (SI), total iron binding capacity (TIBC) and serum ferritin (SF). The proportion of anemia was 54.76%. Increased anemia was inversely correlated with increased body mass index (OR 0.870; 95% CI 0.762-0.994), serum albumin (OR 0.285; 95% CI 0.090-0.907) and calorie intake (OR 0.998; 95% CI 0.996-0.999), and positively correlated with renal impairment (OR 2.647; 95% CI 1.084-6.467). Anemia due to chronic disease (ACD) accounted for 21 subjects, 5 subjects with iron deficiency coexisting with ACD, 1 subject with megaloblastic anemia, and the cause of anemia in 19 patients could not be identified due to diagnostic procedural limitation. Most of the anemic elderly subjects had normal iron deposits. As many as 42.1% of the men and 44.4% of the women had elevated iron deposits. The level of hemoglobin, SI, TIBC in ACD patients were lower than in non-ACD patients (Hb 10.4 vs 10.8 g/dl, SI 58.71 vs. 92.38 ug/dl, TIBC 283.11 vs. 288.95 microg/dl). In contrast, serum ferritin levels in ACD patients were higher than in non-ACD (178.26 vs. 111.35 ng/ml). Body mass index, serum albumin, calorie intake and renal impairment are risk factors for anemia in the elderly. Normal iron deposits accounted for 57.9% and 55.6% of anemic elderly men and women with elevated iron deposits.


The influence of polaron formation on exciton dissociation.
A linear tight-binding model was used to examine the yield of exciton dissociation under the influence of the electron-vibration interaction. The system consists of a linear chain, coupled to a single vibration, and electron-vibration interaction is permitted to occur on certain sites. In the presence of this interaction, population tends to localize to build a polaron. The system loses polaron trapping energy to the environment through its coupling to the bath environment, and loses population due to the injection into the electrode at the terminal site. A self-energy term was generated from population injection, and was added to the energy level of the last site, working as a sink function to absorb the electrons and measure the yield. This injection occurs only when the electron energy is inside and around the band. When the electron energy is outside the tight-binding band, population injection is inhibited. Our aim is to investigate the exciton dissociation effected by the competition between polaron formation and population injection, via a process strongly influenced by the inter-site coupling and the electron-vibration interaction.


Clinical and serological analysis of patients with positive anticyclic citrullinated Peptide antibodies referred through a Rheumatology Central Triage System.
Anticitrullinated protein antibodies (ACPA) are a highly specific and sensitive biomarker for the diagnosis of rheumatoid arthritis (RA). Some patients who were found to have a positive ACPA test were referred to our Rheumatology Central Triage (CT; Calgary, Alberta, Canada) for assessment by a rheumatologist. The objectives of our study were to determine the clinical accuracy of ACPA in establishing a diagnosis of RA in a real-time clinical setting. Cases that met 3 criteria were included in the study: (1) referred to the CT over 3 calendar years (n = 20,389), (2) reason for referral was a positive ACPA test (n = 568), and (3) evaluated by a certified rheumatologist (n = 314). An administrative serological database was used to retrieve specific ACPA results. Of patients referred through our CT for evaluation of a positive ACPA test, 57.6% received a diagnosis of RA; the remainder had a variety of other diagnoses, some of which might be considered early RA (9%). The predictive values of ACPA for the diagnosis of RA were increased when rheumatoid factor (RF) results were included in the analysis. When definite and possible RA were combined and the prevalence of moderate/high ACPA was compared to all other individuals, the positive and negative predictive values for moderate/high ACPA for RA were 74.3% and 68.4%, respectively. About 58% of patients with a positive ACPA referred through a triage system for a rheumatologist opinion received a diagnosis of RA at their first visit. RF provides additional useful information to guide the diagnosis and urgency of referral.


Impact of Pre-operative Aerobic Exercise on Cardiometabolic Health and Quality of Life in Patients Undergoing Bariatric Surgery.
Examine the effect of aerobic exercise (EX) combined with standard medical care (SC) (EX + SC) compared to SC alone on cardiometabolic health and quality of life in relation to surgical outcomes. Patients receiving bariatric surgery were match-paired to 30 days of pre-operative SC (n = 7, 1 male, 39.0 ± 5.3 years, body mass index 46.4 ± 3.0 kg/m2; low calorie diet) or EX + SC (n = 7, 0 males, 45.6 ± 4.8 years, body mass index 43.9 ± 4.2 kg/m2; walking 30 min/day, 5 days/week, 65-85% HR peak ). Body mass, waist circumference, cardiorespiratory fitness (VO2peak), high sensitivity C-reactive protein (hs-CRP), cytokeratin 18 (CK18), weight related quality of life (QoL), and a 120 min mixed meal tolerance test (MMTT) was performed to assess arterial stiffness via augmentation index normalized to a heart rate of 75 beats per minute (AIx@75), whole-body insulin sensitivity, and glucose total area under the curve (tAUC) pre- and post-intervention (∼2 days prior to surgery). Length of hospital stay (admission to discharge) was recorded. EX + SC had a greater effect for decreased intake of total calories (P = 0.14; ES = 0.86) compared to SC, but no change in body weight or waist circumference was observed in either group. EX + SC had a greater effect for increased VO2peak (P = 0.24; ES = 0.91) and decreased hs-CRP (P = 0.31; ES = 0.69) compared to SC. EX + SC reduced circulating CK18 (P = 0.05; ES = 3.05) and improved QoL (P = 0.02) compared to SC. Although EX + SC had no statistical effect on arterial stiffness compared to SC, we observed a modest effect size for AIx@75 tAUC (P = 0.36; ES = 0.52). EX + SC had a significantly shorter length of hospital stay (P = 0.05; ES = 1.38) than SC, and a shorter length of hospital stay was associated with decreased sugar intake (r = 0.55, P = 0.04). Decreased AIx@75 tAUC significantly correlated with improved whole-body insulin sensitivity (r = -0.59, P = 0.03) and glucose tAUC (r = 0.57, P = 0.04). EX with SC for 30 days prior to bariatric surgery may be important for cardiometabolic health, quality of life, and surgical outcomes in the bariatric patient.


[Fibromuscular dysplasia. Asymptomatic dissection and occlusion of the basilar artery].
Historically, basilar artery occlusive disease has been considered to convey a poor prognosis and a high mortality rate. In contrast, recently prospective studies have shown a better prognosis. The basilar artery is most commonly affected by atherosclerosis, but may also be affected by embolisms, dissections, aneurysms, and other conditions like fibromuscular dysplasia. The case of a 46 year-old male who was admitted after suffering a transient episode of ataxic gait and dysarthria is reported. Transcranial Doppler showed a stenotic flow in the basilar artery with distal embolic signals. Magnetic resonance (MR) angiography demonstrated an isolated fibromuscular dysplasia of the basilar artery that caused a > 50% stenosis without parenchymal lesions. Oral anticoagulation treatment was initiated. The control MR angiography performed ten months later, and although the patient was asymptomatic, showed a dissection which evolved into a complete occlusion of the basilar artery. Its distal portion was filled via a reverse flow from both posterior communicating arteries. Anticoagulation treatment was discontinued. Fibromuscular dysplasia of the basilar artery is a rare and usually asymptomatic disease. It may develop into a dissection, but the usual clinical presentation is stenosis-related ischemic stroke. Intracranial artery dissections may be further complicated by subarachnoid hemorrhage. Many authors have recommended anticoagulant therapy for fibromuscular dysplasia. Basilar artery occlusion, as this case shows, does not always convey a poor prognosis. This is determined, at least partially, by the presence of good collateral circulation.


Relationship of cardiovascular disease to stress and vital exhaustion in an urban, midwestern police department.
This study explored risk factors for cardiovascular disease (CVD) among 336 officers of a Midwestern police force. Instruments used included the Perceived Stress Scale, the Maastricht Questionnaire (measuring vital exhaustion), and a general Health Risk Appraisal. Rates of CVD, hypertension, and hypercholesterolemia were 3%, 28%, and 43%, respectively. The relative risk of hypercholesterolemia for male officers, compared to female officers, was 1.98 (95% confidence interval [CI], 1.10 to 3.56). The officers' average body mass index was 28.6 (SD = 4.9), with 80% being overweight or obese. The average vital exhaustion score was higher for female officers than male officers (p < .05). Bivariate relationships of CVD with perceived stress, vital exhaustion, and age were statistically significant (p < .05). When controlling for age, odds ratios were 1.20 (95% CI, 1.03 to 1.39; p < .05) for perceived stress and 1.31 (95% CI, 1.12 to 1.53; p < .01) for vital exhaustion.


Pharmacokinetics of antimicrobial agents in anuric patients during continuous venovenous haemofiltration.
The optimal drug dosing in anuric patients undergoing continuous haemofiltration is a difficult task. More pharmacokinetic data is needed to derive practical guidelines for dosage adjustments. Drug elimination of various antimicrobial agents (amikacin, amoxycillin, ceftazidime, ciprofloxacin, flucloxacillin, imipenem, netilmicin, penicillin G, piperacillin, sulphamethoxazole, tobramycin, vancomycin) was studied in 24 patients with acute renal failure treated by pump-assisted continuous venovenous haemofiltration (CVVH). Concentrations of serial blood and ultrafiltrate samples were determined by HPLC or by fluorescence polarization immunoassay. Total body clearance (CL) and haemofilter clearance (CLf) rates were determined by standard model-independent equations. Data from published literature on fractions not bound to proteins (fu), non-renal drug clearance fractions (Qo), and normal clearance values (CLn) were used to derive a pharmacokinetic model, taking into account drug removal by ultrafiltration and by non-renal clearance. A total of 37 treatment periods was studied. Blood flow through the haemofilters was 100 ml/min resulting in an average ultrafiltrate flow rate (UFR) of 13.2 +/- 4.6 (range 3.2-22.1) ml/min. Acceptable correlations of calculated and measured haemofilter clearances and total body clearances were obtained. Total body clearance in anuric patients during CVVH is predictable from drug properties, which are generally known. The individual dosage requirements may be calculated by multiplying Qo + fu.UFR/CLn with the dose considered appropriate in the absence of renal impairment.


[Prophylactics of incompetence of the bronchus stump and bronchial fistulas after pneumonectomy].
The article is based on the materials of experimental and clinical investigations of healing the bronchus stump after pneumonectomy depending on different methods of surgical treatment, closure and cover. The course of postoperative period after pneumonectomy is analyzed in 249 patients. A system of prophylactic measures is proposed which considers the main links of pathogenesis of the complication. Using this system (including the modified Overholt method of treatment of the stump, closure with clips and covering with a pericardial pedicle flap as well as rational management of the cavity after pneumonectomy) allowed the frequency of bronchial fistulas to be considerably reduced.


Ultrafast soft X-ray photoelectron spectroscopy at liquid water microjets.
Since the pioneering work of Kai Siegbahn, electron spectroscopy for chemical analysis (ESCA) has been developed into an indispensable analytical technique for surface science. The value of this powerful method of photoelectron spectroscopy (PES, also termed photoemission spectroscopy) and Siegbahn's contributions were recognized in the 1981 Nobel Prize in Physics. The need for high vacuum, however, originally prohibited PES of volatile liquids, and only allowed for investigation of low-vapor-pressure molecules attached to a surface (or close to a surface) or liquid films of low volatility. Only with the invention of liquid beams of volatile liquids compatible with high-vacuum conditions was PES from liquid surfaces under vacuum made feasible. Because of the ubiquity of water interfaces in nature, the liquid water-vacuum interface became a most attractive research topic, particularly over the past 10 years. PES studies of these important aqueous interfaces remained significantly challenging because of the need to develop high-pressure PES methods. For decades, ESCA or PES (termed XPS, for X-ray photoelectron spectroscopy, in the case of soft X-ray photons) was restricted to conventional laboratory X-ray sources or beamlines in synchrotron facilities. This approach enabled frequency domain measurements, but with poor time resolution. Indirect access to time-resolved processes in the condensed phase was only achieved if line-widths could be analyzed or if processes could be related to a fast clock, that is, reference processes that are fast enough and are also well understood in the condensed phase. Just recently, the emergence of high harmonic light sources, providing short-wavelength radiation in ultrashort light pulses, added the dimension of time to the classical ESCA or XPS technique and opened the door to (soft) X-ray photoelectron spectroscopy with ultrahigh time resolution. The combination of high harmonic light sources (providing radiation with laserlike beam qualities) and liquid microjet technology recently enabled the first liquid interface PES experiments in the IR/UV-pump and extreme ultraviolet-probe (EUV-probe) configuration. In this Account, we highlight features of the technology and a number of recent applications, including extreme states of matter and the discovery and detection of short-lived transients of the solvated electron in water. Properties of the EUV radiation, such as its controllable polarization and features of the liquid microjet, will enable unique experiments in the near future. PES measures electron binding energies and angular distributions of photoelectrons, which comprise unique information about electron orbitals and their involvement in chemical bonding. One of the future goals is to use this information to trace molecular orbitals, over time, in chemical reactions or biological transformations.


Case study of virtual reality sepsis management- instructional design and ITEM outcomes.
This case study focuses on the instructional design and outcomes of a virtual reality (VR) application for sepsis management in healthcare education. The instructional design of the VR sepsis application follows five principles adapted from Merrill's instructional design theory and Bloom's taxonomy. The VR simulation is structured to provide a coherent and realistic experience, with instructional materials and feedback incorporated to guide and support the learners. A pilot study was conducted with medical students on clinical placement. Participants experienced the VR sepsis simulation and completed a questionnaire using the Immersive Technology Evaluation Measure (ITEM) to assess their immersion, intrinsic motivation, cognitive load, system usability, and debrief feedback. Descriptive analysis of the data showed median scores indicating high immersion and presence, intrinsic motivation, and perceived learning. However, participants reported a moderately high cognitive load. Comparison with a neutral response to ITEM suggested that users had a significantly higher user experience (p < 0.05) in all domains. This case study highlights the potential of VR in healthcare education and its application in sepsis management. The findings suggest that the instructional design principles used in the VR application can effectively engage learners and provide a realistic learning experience. Further research and evaluation are necessary to assess the impact of VR on learning outcomes and its integration into healthcare education settings.


Plasma glucocorticosteroid and aldosterone levels during physiological and stress conditions in rabbits. II. adult animals.
The pattern of adrenal steroid secretion under basal and stress conditions and the response to tetracosactid (20.0 micrograms/kg body weight) were studied in adult male rabbits. In animals repeatedly stressed by artery puncture, plasma glucocorticosteroid levels were slightly higher than those found in unstressed control animals. The combined stress of repeated exposure to ether vapor for 60 sec, followed by artery puncture, significantly stimulated glucocorticosteroid release, concentrations progressively increasing with the number of ether exposures applied. A much faster and more pronounced stimulation of glucocorticosteroid release was seen in animals treated with 20.0 micrograms/kg body weight tetracosactid. Plasma aldosterone levels in animals stressed by artery puncture were higher, although not significantly, than those of unstressed control animals. Repeated exposure to ether vapor for 60 sec, followed by artery puncture, on the other hand slightly decreased plasma aldosterone concentrations. A strong stimulation of aldosterone release at 20--60 min after injection could be elicited only by intravenous administration of 20.0 micrograms/kg body weight tetracosactid. Because of the insensitivity of the zona glomerulosa cells to increased ACTH levels under stress conditions, it is concluded that ACTH is only of minor importance both under basal and stress conditions in the regulation of aldosterone secretion in the rabbit.


Enantiodivergent Steglich rearrangement of O-carboxylazlactones catalyzed by a chirality switchable helicene containing a 4-aminopyridine unit.
A pseudo-enantiomeric pair of optically switchable helicenes containing a catalytic 4-N-methylaminopyridine (MAP) bottom unit and a C2-symmetric, (10R,11R)-dimethoxymethyl-dibenzosuberane top template was synthesized. They underwent complementary photoswitching at 290 nm (P/M', <1/>99) and 340 nm (P/M', 91/9) and unidirectional thermo-rotation at 130 °C (P/M', >99/<1). They were utilized to catalyze enantiodivergent Steglich rearrangement of O- to C-carboxylazlactones, with formation of either enantiomer with up to 91% ee (R) and 94% ee (S), respectively.


[Mini-invasive surgical procedure to reverse the aging process].
Reduction of the bony structure of the face is the main reason for flabbiness and drooping of the facial soft tissues. Because we do not currently have recourse to restore the lost bony volume, a good possibility is to reestablish an optimal relationship between the soft tissues and the present bony volume. Based on this principle, we have developed the procedure of mini-invasive subperiosteal facial restoration. In this paper we describe the application of this procedure to restore the frontal region. The maneuvers and instrumentation used to perform this procedure through frontal, palpebral or the combination of both approaches are described. Based on the surgical anatomy, orientation and instructions for obtaining the goals of the procedure and to avoid complications are elucidated. Ancillary procedures that may be associated with this procedure are described, as well as detailed postoperative care. Observed complications are noted and a summary of the obtained results, which have shown a high degree of patient and surgeon satisfaction, are reported. Observations from our experience with this method during a 10-year period and the reasons for this being the procedure of our first choice are revealed.


Publishing Biomedical Predication Repository About MeSH Co-Occurrences in MEDLINE.
The construction and publication of predications form scientific literature databases like MEDLINE is necessary due to the large amount of resources available. The main goal is to infer meaningful predicates between relevant co-occurring MeSH concepts manually annotated from MEDLINE records. The resulting predications are formed as subject-predicate-object triples. We exploit the content of MRCOC file to extract the MeSH indexing terms (main headings and subheadings) of MEDLINE. The predications were inferred by combining the semantic predicates from SemMedDB, the clustering of MeSH terms by their associated MeSH subheadings and the frequency of relevant terms in the abstracts of MEDLINE records. The inferring process also obtains and associates a weight to each generated predication. As a result, we published the generated dataset of predications using the Linked Data principles to make it available for future projects.


The molecular genetics of clinal variation: a case study of ebony and thoracic trident pigmentation in Drosophila melanogaster from eastern Australia.
Widespread pigmentation diversity coupled with a well-defined genetic system of melanin synthesis and patterning in Drosophila provides an excellent opportunity to study phenotypes undergoing evolutionary change. Pigmentation variation is highly correlated with different ecological variables and is thought to reflect adaptations to different environments. Several studies have linked candidate genes from Drosophila melanogaster to intra-population variation and interspecific morphological divergence, but less clearly to variation among populations forming pigmentation clines. We characterized a new thoracic trident pigmentation cline in D. melanogaster populations from eastern Australia, and applied a candidate gene approach to explain the majority of the geographically structured phenotypic variation. More melanized populations from higher latitudes tended to express less ebony than their tropical counterparts, and an independent artificial selection experiment confirmed this association. By partitioning temperature dependent effects, we showed that the genetic differences underlying clinal patterns for trident variation at 25 °C do not explain the patterns observed at 16 °C. Changes in thoracic trident pigmentation could be a common evolutionary response to climatically mediated environmental pressures. On the Australian east coast most of the changes appear to be associated with regulatory divergence of the ebony gene but this depends on temperature.


Diagnosis and management of gastric leaks after laparoscopic sleeve gastrectomy for morbid obesity.
Laparoscopic sleeve gastrectomy (LSG) is increasingly being recognised as a valid stand-alone procedure for the surgical management of morbid obesity. The leak rate from the gastric staple line ranges from 1.4% to 20%. From our experience of management of LSG leaks, we have been able to formulate an algorithm-based approach to the management of these patients. All patients referred to our hospital within a 24-month period with a diagnosis of gastric staple line leak in the background of a previous LSG were included in the study. A retrospective case note review was undertaken for these patients and an algorithm formulated. There were fourteen patients in the study. There were four males and ten females. Patients were managed with a combination of laparotomy, laparoscopy, endoscopic covered stenting, percutaneous radiologically guided drainage,jejunal enteric feeding and total parenteral nutrition. In five patients, re-look laparoscopy or laparotomy with washout and drainage was performed. The remaining eight patients were managed conservatively. There were no deaths. Although it is often disappointing when LSG leaks do occur, with adherence to the basic tenets of the surgical management of enterocutaneous fistulae as well as early detection and a high index of suspicion, these complications can be successfully managed using an algorithm-based multi-disciplinary team approach.


A method for understanding some consequences of bringing patient-generated data into health care delivery.
The consequences of personal health record (PHR) phenomena on the health care system are poorly understood. This research measures one aspect of the phenomena--the time-cost impact of patient-generated data (PGD) using discrete event model (DEM) simulation. Little has been written about the temporal and cognitive burden associated with new workflows that include PGD. This pilot study reports the results for time-cost and resource utilization of a ''typical'' ambulatory clinic under varying conditions of PGD burden. PGD effects are modeled with DEM simulation reflecting the sequential relationships, temporal coupling, and impact assumptions within a virtual clinic. Three simulation scenarios of ever-increasing PGD impact are compared to a baseline case of no PGD use. Introduction of PGD resulted in expected increases in cost and resource utilization along with a few key exceptions and unanticipated consequences. Direct and indirect impacts were observed with notable nonlinear, nonadditive, disproportionate, heterogeneous aspects and interactions among consequent labor cost, visit length, workday length, and resource utilization. The middle-impact simulations showed a 29% increase in daily labor costs and 28% shrinkage of the margin between revenues and labor costs. Lengths of both workday and patient visit were extended and less predictable with PGD use. Utilization rates of most staff positions rose. Nurse utilization rates showed greatest increases. Physicians' utilization rates paradoxically stayed relatively unchanged. This analysis contributes to an understanding of the effects of PGD on time and cognitive burdens of physicians, staff, and physical resources. It illustrates the usefulness of DEM simulation for the purpose. Avoidable consequences are exposed quantifiably for both the patient and the clinic. More realistic ways to respond to PGD impact are needed.


Associations between reflux esophagitis and the progression of coronary artery calcification: A cohort study.
Reflux esophagitis (RE) and coronary heart disease (CHD) have common risk factors, including obesity and metabolic syndrome. This study aimed to evaluate the associations between RE and the future CHD risk. This retrospective cohort study included 8,221 participants who were ≥20 years old, and who underwent esophagogastroduodenoscopy and coronary computed tomography (CT) scans during the same visit and subsequent CT scans between 2003 and 2013. RE was defined as the presence of at least Los Angeles classification grade A mucosal break. CT scan was used to determine the coronary artery calcium (CAC) scores. CAC progression was defined as an increase in the CAC score on a subsequent CT scan. RE was present in 984 (12.0%) participants. RE at baseline was associated with CAC progression (odds ratio [OR], 1.253; 95% confidence interval [CI], 1.088-1.444; P = 0.002), and this association persisted after adjusting the model for age, sex, smoking status, and alcohol consumption (OR, 1.175; 95% CI, 1.001-1.378; P = 0.048). This association disappeared when the model was further adjusted for body mass index, diastolic blood pressure, the presence of hypertension, glycated hemoglobin, low-density lipoprotein cholesterol, and triglycerides (OR, 1.088; 95% CI, 0.924-1.281; P = 0.311) which were selected using a stepwise selection procedure from several metabolic variables. Our results suggest that the presence of RE is closely associated with CHD, even though RE is not a direct risk factor for CHD. Metabolic factors may play roles in CAC progression in individuals with RE.


Rhesus Macaque CODEX Multiplexed Immunohistochemistry Panel for Studying Immune Responses During Ebola Infection.
Non-human primate (NHP) animal models are an integral part of the drug research and development process. For some biothreat pathogens, animal model challenge studies may offer the only possibility to evaluate medical countermeasure efficacy. A thorough understanding of host immune responses in such NHP models is therefore vital. However, applying antibody-based immune characterization techniques to NHP models requires extensive reagent development for species compatibility. In the case of studies involving high consequence pathogens, further optimization for use of inactivated samples may be required. Here, we describe the first optimized CO-Detection by indEXing (CODEX) multiplexed tissue imaging antibody panel for deep profiling of spatially resolved single-cell immune responses in rhesus macaques. This 21-marker panel is composed of a set of 18 antibodies that stratify major immune cell types along with a set three Ebola virus (EBOV)-specific antibodies. We validated these two sets of markers using immunohistochemistry and CODEX in fully inactivated Formalin-Fixed Paraffin-Embedded (FFPE) tissues from mock and EBOV challenged macaques respectively and provide an efficient framework for orthogonal validation of multiple antibody clones using CODEX multiplexed tissue imaging. We also provide the antibody clones and oligonucleotide tag sequences as a valuable resource for other researchers to recreate this reagent set for future studies of tissue immune responses to EBOV infection and other diseases.


What is Susac syndrome? - A brief review of articles.
Susac's syndrome (SS) is a clinical triad of encephalopathy, branch retinal artery occlusion and sensorineural hearing loss and maybe due to an immune-mediated endotheliopathy. Because of its rarity and some similarities to other common neurological conditions such as multiple sclerosis and acute disseminated encephalomyelitis, it is often misdiagnosed and therefore mistreated. To the best of our knowledge, there is only one case report from our country with this diagnosis. Here, we have a short discussion on this issue to introduce it to our colleagues and remind it as a differential diagnosis in patients with unexplained encephalopathy.


Goserelin for ovarian protection during breast-cancer adjuvant chemotherapy.
Ovarian failure is a common toxic effect of chemotherapy. Studies of the use of gonadotropin-releasing hormone (GnRH) agonists to protect ovarian function have shown mixed results and lack data on pregnancy outcomes. We randomly assigned 257 premenopausal women with operable hormone-receptor-negative breast cancer to receive standard chemotherapy with the GnRH agonist goserelin (goserelin group) or standard chemotherapy without goserelin (chemotherapy-alone group). The primary study end point was the rate of ovarian failure at 2 years, with ovarian failure defined as the absence of menses in the preceding 6 months and levels of follicle-stimulating hormone (FSH) in the postmenopausal range. Rates were compared with the use of conditional logistic regression. Secondary end points included pregnancy outcomes and disease-free and overall survival. At baseline, 218 patients were eligible and could be evaluated. Among 135 with complete primary end-point data, the ovarian failure rate was 8% in the goserelin group and 22% in the chemotherapy-alone group (odds ratio, 0.30; 95% confidence interval [CI], 0.09 to 0.97; two-sided P=0.04). Owing to missing primary end-point data, sensitivity analyses were performed, and the results were consistent with the main findings. Missing data did not differ according to treatment group or according to the stratification factors of age and planned chemotherapy regimen. Among the 218 patients who could be evaluated, pregnancy occurred in more women in the goserelin group than in the chemotherapy-alone group (21% vs. 11%, P=0.03); women in the goserelin group also had improved disease-free survival (P=0.04) and overall survival (P=0.05). Although missing data weaken interpretation of the findings, administration of goserelin with chemotherapy appeared to protect against ovarian failure, reducing the risk of early menopause and improving prospects for fertility. (Funded by the National Cancer Institute and others; POEMS/S0230 ClinicalTrials.gov number, NCT00068601.).


Collectrin, a homologue of ACE2, its transcriptional control and functional perspectives.
Collectrin is a type I membrane protein and shares significant homology with C-terminal domain of angiotensin-converting enzyme-2 (ACE2). However, collectrin lacks catalytic domain and it suggests the presence of uncharacterized physiological functions of collectrin. Collectrin is transcriptionally regulated by hepatocyte nuclear factor-alpha and -beta and is highly expressed on renal proximal tubules and collecting ducts as well as pancreatic beta-cells. Recent in vitro and in vivo studies demonstrated interesting physiological roles of collectrin related to insulin secretion, formation of primary cilia, renal cyst formation and amino acid transport. The common underlying molecular mechanism may be suggested by the evidence that collectrin binds to SNARE complex by interacting with snapin. Collectrin is involved in the process of vesicle transport and membrane fusion and thus it delivers insulin for exocytosis or various membrane proteins to apical plasmalemma and primary cilia. Collectrin may be the new therapeutic target for various pathological processes such as diabetes, polycystic kidney disease, hypertension and aminoaciduria.