Rifabutin-based high-dose proton-pump inhibitor and amoxicillin triple regimen as the rescue treatment for Helicobacter pylori.
Rifabutin has been known to be effective in multidrug-resistant Helicobacter pylori-harboring patients undergoing treatment failure for H. pylori infection. To evaluate the efficacy of 7-day treatment regimen consisting rifabutin daily but increasing the dose of amoxicillin and lansoprazole in patients who have failed first and second eradication and to assess the side effect profiles in South Korea. From December 2007 to May 2013, 59 H. pylori-infected patients with two previous eradication failures were enrolled for this study prospectively. The eligible patients were randomly assigned to either group A or B. Group A received lansoprazole 30 mg bid, amoxicillin 1.0 g tid and rifabutin 150 mg bid during 7 days, whereas group B received lansoprazole 60 mg bid, amoxicillin 1.0 g tid and rifabutin 150 mg bid during 7 days. In group A, H. pylori eradication was achieved in 25 (78.1%) of the 32 patients in the ITT analysis and in 25 (80.6%) of the 31 patients in the PP analysis. In group B, H. pylori eradication was achieved in 26 (96.3%) of the 27 patients in the ITT analysis and in 27 (100%) of the 26 patients in the PP analysis. There was statistically significant difference between the two groups in terms of the eradication rates in PP analysis (p = .047), whereas a marginally statistical significance was found in terms of the eradication rates in ITT analysis (p = .051). Reported side effects were mild, and treatment was well tolerated. No major changes in physical examination or in standard laboratory parameters were observed after treatment. Rifabutin-based high-dose proton-pump inhibitor (PPI)-combined therapy as empirical rescue treatment is more effective than standard dose PPI-combined rifabutin-based therapy, safe and best tolerable in third-line therapy in the Korean population. The key to successful rescue therapy with rifabutin-amoxicillin-PPI regimen may be to increase doses of PPI.


Three-axis classification of mouse lung mesenchymal cells reveals two populations of myofibroblasts.
The mesenchyme consists of heterogeneous cell populations that support neighboring structures and are integral to intercellular signaling, but are poorly defined morphologically and molecularly. Leveraging single-cell RNA-sequencing, 3D imaging and lineage tracing, we classify the mouse lung mesenchyme into three proximal-distal axes that are associated with the endothelium, epithelium and interstitium, respectively. From proximal to distal: the vascular axis includes vascular smooth muscle cells and pericytes that transition as arterioles and venules ramify into capillaries; the epithelial axis includes airway smooth muscle cells and two populations of myofibroblasts - ductal myofibroblasts, surrounding alveolar ducts and marked by CDH4, HHIP and LGR6, which persist post-alveologenesis, and alveolar myofibroblasts, surrounding alveoli and marked by high expression of PDGFRA, which undergo developmental apoptosis; and the interstitial axis, residing between the epithelial and vascular trees and sharing the marker MEOX2, includes fibroblasts in the bronchovascular bundle and the alveolar interstitium, which are marked by IL33/DNER/PI16 and Wnt2, respectively. Single-cell imaging reveals a distinct morphology of mesenchymal cell populations. This classification provides a conceptual and experimental framework applicable to other organs.


Role of the connectivity of secondary structure segments in the folding of alpha(1)-antitrypsin.
The native form of serpins (serine protease inhibitors) is metastable, which is critical to their biological functions. Spontaneous conversion from the native form of serpins into a more stable conformation, called the "latent" form, is restricted. To examine whether the connectivity of strand 1 of beta-sheet C to the hydrophobic core is critical to the serpin's preferential folding to the metastable native conformation, we designed a circularly-permuted mutant of alpha(1)-antitrypsin, the prototype serpin, in which strand 1C is disconnected from the hydrophobic core. Conformation of the circular permutant was similar to that of the latent form, as revealed by equilibrium unfolding, limited proteolysis, and spectroscopic properties. Our results support the notion that rapid folding of the hydrophobic core with concomitant incorporation of strand 1C into beta-sheet C traps the serpin molecule into its native metastable conformation.


Cancer care in regional Australia from the health professional's perspective.
This study aimed to identify the factors which health professionals believe influence clinical care and outcomes for people with cancer in regional areas of Australia. Twelve semi-structured interviews were conducted with a variety of health professionals. Interview questions explored health professional's perspectives on barriers to cancer care for patients, factors which influence clinical care, and access to support in regional areas. Data were interpreted using an inductive thematic analysis approach. Two global themes were identified: rural culture and the health system. Within these global themes, health professionals discussed barriers to cancer care in regional areas, predominantly associated with travel, limited workforce, and poor communication within the health system. Participants also noted many positive aspects of cancer care in regional areas, including more personalised care for the patients and faster career progression for professionals. Despite several strategies to improve rural cancer care in recent times, including innovative models of care and increased infrastructure, health professionals still perceive many barriers to cancer care in regional Australia. These are predominantly associated with patient demographics, travel difficulties, and inadequate governance. However, there are also many notable benefits to receiving care in regional areas which have been absent from previous literature. These positive factors should be incorporated in efforts to enhance regional cancer care through the recruitment of health professionals to regional areas and development of regional community support networks.


TOMM40, APOE, and APOC1 in primary progressive aphasia and frontotemporal dementia.
The aim of this study was to investigate the apolipoprotein E (APOE) chromosomal region in frontotemporal lobar degeneration (FTLD), and in particular in primary progressive aphasia (PPA) and the behavioral variant frontotemporal dementia (bvFTD). To this aim, we selected three single-nucleotide polymorphisms (SNPs) rs2075650 and rs157590 (TOMM40), and rs1064725 (APOC1), representative of the linkage disequilibrium (LD) blocks at the 19q13-q13.2 chromosomal region. The SNPs rs429358 and rs7412 forming the APOE polymorphism were also included in the study. The analysis was made in 282 patients with a clinical diagnosis of sporadic FTLD, namely 207 bvFTD and 75 PPA, and 296 cognitively healthy control subjects. LD (r2 = 0.35) between TOMM40 (rs2075650) and APOC1 (rs1064725) was observed in PPA, but not in controls and in bvFTD. Inside this region of 26.9 kb, LD (r2 ≥ 0.50) between TOMM40 (rs2075650) and APOE (rs429358) was observed in bvFTD and in controls, but not in PPA. Inside this region of 16.3 kb, LD (r2 = 0.14) between TOMM40 (rs157590) and APOE (rs429358) was observed in PPA, but not in bvFTD and in controls. Although the genetics of PPA and bvFTD needs further investigation, our results suggested the presence of a different genetic background underlying PPA and bvFTD at the 19q13-q13.2 chromosomal region.


London after Tomlinson. Clinical research.
Sir Bernard Tomlinson's report focuses on London's health services, but his proposals have major implications for the future of clinical research--not just in London but in the United Kingdom as a whole. They must be seen in the context of a widely perceived decline in British research and development which also threatens clinical research. This article examines the implications of Tomlinson's proposals and related strategies and recommends the construction of a research market for the patient costs of clinical research to complement the NHS market for patient services introduced in 1991. These arrangements would help sustain the clinical research base and guarantee excellence.


Categorization of foods as "snack" and "meal" by college students.
The cognitive representation of a food as being a "snack" or a "meal" influences eating behavior. We found previously that subjects who considered a particular food to be a 'snack' ate significantly more calories when tested later than subjects who considered the same foods as a 'meal'. We conducted two surveys to determine the categorization of foods as "snacks" or "meals". Survey 2 included a larger variety of foods with detailed descriptions and a response option of "never tried". Both surveys found that potato chips, crackers, cookies, and nuts were consistently viewed as snacks, while soups, burritos, pizza, and pancakes were consistently viewed as meals. Useful for future research are foods we found that students varied in considering a snack or meal. Survey 1 found that half the respondents viewed toast, cheese on toast, muffins, and French fries as snacks and the other half as meals. Similarly, in Survey 2 potato salad, toast with jam, English muffin, cinnamon rolls, and nachos were categorized almost equally as snack and meal. These foods can be used in studies looking at the effects of categorizing a food as a meal or snack on other behaviors or categorization, while controlling for the food item.


New-Onset Left Bundle Branch Block Induced by Transcutaneous Aortic Valve Implantation.
New-onset left bundle branch block (LBBB) is a specific concern of transcutaneous aortic valve implantation (TAVI) given its estimated incidence ranging from 5% to 65%. This high rate of occurrence is dependent on the type of device used (size and shape), implantation methods, and patient co-morbidities. The appearance of an LBBB after TAVI reflects a very proximal lesion of the left bundle branch as it exits the bundle of His. At times transient, its persistence can lead to permanent pacemaker implantation in 15% to 20% of cases, most often for high-degree atrioventricular block. The management of LBBB after TAVI is currently not defined by international societies resulting in individual centers developing their own management strategy. The potential consequences of LBBB are dysrhythmias (atrioventricular block, syncope, and sudden death) and functional (heart failure) complications. Prompt postprocedural recognition and management (permanent pacemaker implantation) of patients prevents the occurrence of potential complications and may constitute the preferred approach in this frail and elderly population despite additional costs and complications of cardiac pacing. Moreover, the expansion of future indications for TAVI necessitates better identification of the predictive factors for the development of LBBB. Indeed, long-term right ventricular pacing may potentially increase the risk of developing heart failure in this population. In conclusion, it is thus imperative to not only develop new aortic prostheses with a less-deleterious impact on the conduction system but also to prescribe appropriate pacing modes in this frail population.


Anxiety and depression predict poor outcomes in arthroscopic subacromial decompression.
Subacromial impingement is common and frequently treated with arthroscopic subacromial decompression (ASD); however, its efficacy has recently been questioned. Poor surgical outcomes have been associated with anxiety and depression within other orthopedic subspecialties but not within this group of patients. We hypothesized that anxiety and depression are associated with worse outcomes after ASD. A retrospective review of prospectively collected data was carried out of patients undergoing ASD. Inclusion criteria were short-term relief with injection therapy and presence of Hawkins sign. Rotator cuff tears were excluded. Patients completed the Oxford Shoulder Score (OSS), Hospital Anxiety and Depression Scale (HADS), and visual analog scale for pain before and after surgery in outpatient clinic follow-up at 6 weeks and by postal questionnaire at 6 months. The 86 patients who participated in the study were analyzed in 2 groups defined by HADS scores, group A being depressed and group B nondepressed. Both groups had less pain and improved OSS at 6 months; however, group B improved faster with improved scores at 6 weeks, which were maintained to 6 months. Group B had less pain and higher OSS at 6 months than group A. There was strong negative correlation (P < .01) between preoperative HADS score and 6-week and 6-month OSS and HADS scores. There was strong positive correlation (P < .01) between HADS score and 6-week and 6-month pain scores. High preoperative HADS score was negatively correlated to 6-month satisfaction (P < .05). Patients with HADS score >11 before ASD have worse outcomes. This should be taken into account when counseling patients for surgery.


Butylphthalide Inhibits Autophagy and Promotes Multiterritory Perforator Flap Survival.
Multiterritory perforator flap is an important plastic surgery technique, yet its efficacy can be limited by partial necrosis at the choke Ⅱ zone. Butylphthalide (NBP) has been used for many diseases but has not been studied in the multiterritory perforator flap. With the effect of NBP, we observed increasing in capillary density, inhibition of autophagy and oxidative stress, and a reduction in apoptosis of cells, all consistent with increased flap survival. However, the protective effect of NBP on multiterritory perforator flap was lost following administration of the autophagy agonist rapamycin (Rap). Through the above results, we assumed that NBP promotes flap survival by inhibiting autophagy. Thus, this study has found a new pharmacological effect of NBP on the multiterritory perforator by inhibiting autophagy to prevent distal postoperative necrosis and exert effects on angiogenesis, oxidative stress, and apoptosis within the flap.


[FACTORS OF ADHESION OF BIFIDOBACTERIA].
Data on fimbrial and afimbrial adhesion factors of bifidobacteria are presented. Pili-like structures, their composition and conditions of formation in various species of bifidobacteria are described. Several sugar-lytic enzymes serve as afimbrial adhesins in bifidobacteria. Transaldolase and enolase are detected in bifidobacteria on cells' surface. Transaldolase ensures binding of bifi- dobacteria with mucin and their auto-aggregation. Surface enolase has an affinity to plasminogen, thus.bifidobacteria obtain a surface-bound protein with proteolytic activity. Molecular structures giving bifidobacteria hydrophobic properties are described - surface lipoprotein Bop A and lipoteichoic acids.


Effects of Caffeine Intake on Cognitive Performance Related to Total Sleep Deprivation and Time on Task: A Randomized Cross-Over Double-Blind Study.
It is widely admitted that both total sleep deprivation (TSD) and extended task engagement (Time-On-Task, TOT) induce a cognitive fatigue state in healthy subjects. Even if EEG theta activity and adenosine both increase with cognitive fatigue, it remains unclear if these modifications are common mechanisms for both sustained attention and executive processes. We performed a double-blind counter-balanced (placebo (PCBO) and caffeine (CAF) - 2×2.5 mg/kg/24 h)) study on 24 healthy subjects (33.7 ± 5.9 y). Subjects participated in an experimental protocol including an habituation/training day followed by a baseline day (D0 and D1) and a total sleep deprivation (TSD) day beginning on D1 at 23:00 until D2 at 21:00. Subjects performed the psychomotor vigilance test (PVT) assessing sustained attention, followed by the executive Go-NoGo inhibition task and the 2-NBack working memory task at 09:15 on D1 and D2. We showed differential contributions of TSD and TOT on deficits in sustained attention and both executive processes. An alleviating effect of caffeine intake is only observed on sustained attention deficits related to TSD and not at all on TOT effect. The caffeine dose slows down the triggering of sustained attention deficits related to TOT effect. These results suggest that sustained attention deficits induced by TSD rely on the adenosinergic mechanism whereas TOT effect observed for both sustained attention and executive would not.


Will there always be an institution? I: the impact of epidemiological trends.
In this two-part series of articles, it is predicted that institutions will be phased out because of five trends: development of nonresidential community services; new conceptualizations of and attitudes toward residential services; increased usage of individual rather than group residential placements; provision of small, specialized group residences; and a decline in the incidence and prevalence of severe and profound retardation due to reduction in the birthrate of high risk groups, improvement of health services for the population generally and for high risk groups specifically, increased practice of abortion, general environmental betterment, and early childhood education. In this (first) part, the impact of the predicted epidemiological trends upon residential services is discussed.


Report of a human autopsy case in maxillary sinuses augmented using a synthetic bone substitute: Micro-computed tomographic and histologic observations.
This study of a human autopsy case aimed to characterize the histologic and micro-computed tomographic results of maxillary sinus augmentation using a synthetic bone substitute and simultaneous implant placement at 6 years. This report is based on the whole-body donation of a 62-year-old male patient who died due to bladder cancer. Implants had been placed in conjunction with sinus augmentation using a mixture of biphasic calcium phosphate and autogenous bone into both maxillary sinuses 6 years prior to the body donation. The maxillary sinus areas containing implants were gently removed from the cadaver and scanned using high-resolution micro-computed tomography. Samples were sectioned, prepared for undecalcified histologic slides and stained with haematoxylin-eosin. The augmented volume was observed up to the apex of the implants, which were successfully osseointegrated. Cross-sectional micro-computed tomographic views revealed that the bone-substitute particles were embedded in radiopaque-mineralized tissues showing a trabecular pattern around the implants. The histologic analysis revealed mature lamellar bone surrounding the remaining bone-substitute particles as well as well-organized bone marrow spaces in the augment bone area and around the dental implants. This human autopsy study histologically confirmed the presence of successful bone formation and long-term volume stability after sinus augmentation using biphasic calcium phosphate and simultaneous implant placement.


Association between chronic viral hepatitis infection and breast cancer risk: a nationwide population-based case-control study.
In Taiwan, there is a high incidence of breast cancer and a high prevalence of viral hepatitis. In this case-control study, we used a population-based insurance dataset to evaluate whether breast cancer in women is associated with chronic viral hepatitis infection. From the claims data, we identified 1,958 patients with newly diagnosed breast cancer during the period 2000-2008. A randomly selected, age-matched cohort of 7,832 subjects without cancer was selected for comparison. Multivariable logistic regression models were constructed to calculate odds ratios of breast cancer associated with viral hepatitis after adjustment for age, residential area, occupation, urbanization, and income. The age-specific (<50 years and ≥50 years) risk of breast cancer was also evaluated. There were no significant differences in the prevalence of hepatitis C virus (HCV) infection, hepatitis B virus (HBV), or the prevalence of combined HBC/HBV infection between breast cancer patients and control subjects (p = 0.48). Multivariable logistic regression analysis, however, revealed that age <50 years was associated with a 2-fold greater risk of developing breast cancer (OR = 2.03, 95% CI = 1.23-3.34). HCV infection, but not HBV infection, appears to be associated with early onset risk of breast cancer in areas endemic for HCV and HBV. This finding needs to be replicated in further studies.


Hedgehog pathway inhibitor HhAntag691 is a potent inhibitor of ABCG2/BCRP and ABCB1/Pgp.
HhAntag691 (GDC-0449), a low-molecular weight inhibitor of the tumor-promoting hedgehog (Hh) signaling pathway, has been used to treat medulloblastoma in animal models and has recently entered clinical trials for a variety of solid tumors. Here, we show that HhAntag691 inhibits multiple ATP-binding cassette (ABC) transporters. ATP-binding cassette transporters are within a family of membrane proteins, the overexpression of which is associated with multidrug resistance, a major impediment to successful cancer treatment. HhAntag691 is a potent inhibitor of two ABC transporters, ABCG2/BCRP and ABCB1/Pgp, and is a mild inhibitor of ABCC1/MRP1. In ABCG2-overexpressing HEK293 cells, HhAntag691 increased retention of the fluorescent ABCG2 substrate BODIPY-prazosin and resensitized these cells to mitoxantrone, an antineoplastic ABCG2 substrate. In Madin-Darby canine kidney II cells engineered to overexpress Pgp or MRP1, HhAntag691 increased the retention of calcein-AM and resensitized them to colchicine. HhAntag691 also resensitized human non-small cell lung carcinoma cells NCI-H460/par and NCI-H460/MX20, which overexpress ABCG2 in response to mitoxantrone, to mitoxantrone, and to topotecan or SN-38. The IC(50) values of HhAntag691 for inhibition of ABCG2 and Pgp were approximately 1.4 and approximately 3.0 microM, respectively. Because ABC transporters are highly expressed at the blood-brain barrier and on many tumor cells, they contribute significantly to treatment failure of many types of cancer, particularly of those within the neuraxis. In addition to its effect on Hh signaling, the ability of HhAntag691 and related compounds to inhibit two key ABC transporters could contribute to their effectiveness in treating malignancies.


Dendritic cells in pathogen recognition and induction of immune responses: a functional genomics approach.
At the 38th Annual Meeting of the Society for Leukocyte Biology held in Oxford this year, the biology of dendritic cells (DCs) and macrophages was discussed. In particular, functional genomics approaches were presented to investigate transcriptional changes during microbe and phagocytes interactions. Here, we report functional genomics studies likely to be of interest to the Journal of Leukocyte Biology readers with a particular emphasis on DC biology. DCs are professional antigen-presenting cells, which are essential for the initiation and regulation of natural killer, T, and T regulatory cell responses. Immature DCs, resident in peripheral sites, are specialized in antigen capture and continually sample soluble and particulate antigens in their local environment. DCs express receptors for cytokines, chemokines, endogenous danger signals, and microbial structures. The interactions between DCs and microorganism are complex, but progress in the past few years has shed light on several aspects of these processes. Infectious disease is the result of an intimate relationship between pathogens and hosts. Thus, understanding the cross-talk between host and pathogen is essential to improve our knowledge of infectious disease. Functional genomics and proteomics applied to DCs and macrophage biology are now providing powerful tools to dissect, at the molecular level, host-pathogen interactions.


Long-term outcomes after percutaneous revascularization of complex coronary bifurcation lesions using a dedicated self-expanding biolimus-eluting stent system.
To evaluate long-term clinical outcomes after treatment of complex bifurcation lesions with the AXXESS dedicated self-expanding biolimus A9-eluting bifurcation stent. Between 2004 and 2013, 123 patients with complex bifurcation lesions were treated in a single-center with the AXXESS stent in the proximal main vessel (MV) and additional drug-eluting stents in branches when required. Median follow-up was 5 years. Primary endpoint was the rate of major adverse cardiac events (MACE). Secondary endpoints included MACE components (cardiac death, non-periprocedural clinical myocardial infarction [MI], target lesion revascularization [TLR] and definite/probable stent thrombosis [ST]) as well as all-cause death, target vessel revascularization (TVR) and non-TVR. During follow-up, 11 (8.9%) patients experienced a MACE, of whom 2 (1.6%) suffered cardiac death, 2 (1.6%) had a non-periprocedural clinical MI requiring TLR, and 7 (5.7%) underwent elective TLR. No definite/probable ST was observed. All-cause death occurred in 9 (7.3%) patients, TVR in 11 (8.9%) and non-TVR in 11 (8.9%). Patients treated for left main (LM) bifurcation lesions were more likely to experience MACE than non-LM bifurcation lesions (25% vs. 6.5%, p = 0.04). Percutaneous revascularization of complex bifurcation lesions with the AXXESS stent is safe and provides excellent long-term results, especially in non-LM lesions.


Intracranial myeloid metaplasia: diagnosis by CT and Fe52 scans and treatment by cranial irradiation.
A patient with longstanding agnogenic myeloid metaplasia developed a progressive dementia. CT scanning demonstrated multiple intracranial masses, and a Fe52 bone marrow scan demonstrated erythroid activity within the masses and confirmed the suspicion of extra-medullary hematopoiesis. A potentially hazardous biopsy was avoided, and a course of cranial irradiation was administered, resulting in regression of the masses and clearing of the patient's dementia. Fe52 scintigraphy provides a specific and useful diagnostic approach which may eliminate the need for invasive procedures.


Implicit learning deficit in children with Duchenne muscular dystrophy: Evidence for a cerebellar cognitive impairment?
This study aimed at comparing implicit sequence learning in individuals affected by Duchenne Muscular Dystrophy without intellectual disability and age-matched typically developing children. A modified version of the Serial Reaction Time task was administered to 32 Duchenne children and 37 controls of comparable chronological age. The Duchenne group showed a reduced rate of implicit learning even if in the absence of global intellectual disability. This finding provides further evidence of the involvement of specific aspects of cognitive function in Duchenne muscular dystrophy and on its possible neurobiological substrate.


[Patients' experiences with and attitudes to generic substitution].
The aim of this study was to assess patient experiences with and attitudes to generic substitution. Patients who had purchased three to seven, or eight or more, different prescription medicines during the last six months were compared. Both groups were mailed a questionnaire about generic substitution. The response rate was 73% (281/386), the average age of respondents was 66. There was a correlation between patients remembering that information had been provided by their physicians and subsequent generic substitution. Out of 138 patients who had experienced generic substitution, 50 patients (36%) reported one or more negative experiences, 21% an altogether negative experience. About 41% of the patients would not switch given no personal economic insertives. There were no significant correlations between experiences with generic substitution and age, gender, number of different drugs used, information provided by the physician or by the pharmacy staff. About 78% of the patients are satisfied with generic substitution although 1/3 report one or more negative experiences. In order to raise patient satisfaction, there is a need for increased economic incentives and a strategy whereby physicians, pharmacies and official authorities cooperate on information to the public.


[Glycoproteins: their biological and clinical significance. I (author's transl)].
Increasing knowledge on structure, biosynthesis and catabolism of glycoproteins have given new insights on the patho-biochemical and clinical significance of these macromolecules. The most important results and conclusions are summarized in this review. 1. The terminal sugars of glycoproteins--N-acetylneuraminic acid (NANA) and L-fucose--as well as the penultimate galactose molecule have important functions in cell interaction, adhesion and recognition. Moreover, these carbohydrates mediate the migration and distribution of cells and it is believed that they are essential part of the feto-maternal "immunological barrier". 2. Evidence indicating that the composition and pattern of plasma membrane glycoproteins is associated with tumour growth and metastatic formation is accumulating. Moreover, the determination of serum glycosyltransferase activity is gaining increasing interest, because the level of these enzymes is substantially elevated in patients with neoplastic disease. 3. Diseases of the autoimmunosystem are likely linked to a disturbed glycoprotein metabolism. The clinical importance is underlined by studies on immunotherapy of tumours.


The evaluation of coronary artery-to-pulmonary artery fistula in adulthood on 256-slice CT coronary angiography: Comparison with coronary catheter angiography and transthoracic echocardiography.
To review the imaging features of coronary artery-to-pulmonary artery fistula (CPAF) on CT coronary angiography (CTCA) and evaluate its diagnostic performance compared with coronary catheter angiography (CCA) and transthoracic echocardiography (TTE). We retrospectively reviewed with a diagnosis of CPAF from among 19855 consecutive CCTA performed with 256-slice MDCT scanner for suspected coronary artery disease. CT images were evaluated for - origin, number, size and course (tubular/worm-like dilation/significant aneurysm formation/wall attachment sign) of fistula vessels, drainage site, drainage site imaging features (pierced sign, isodensity sign, smoke sign, jet sign), and main pulmonary artery (MPA) enlargement. 25 patients of CPAF also underwent CCA and 47 patients underwent TTE. There were 72 patients with CPAF (0.36%) in our study, of which 44 were men and 28 were women, with mean age of 55.8 ± 13.2 years (range 22-85 years). CPAF originated from conus artery, left anterior descending artery (LAD), combined conus artery and LAD in 55, 67, 50 cases, respectively. Tubular dilation, worm-like dilation and aneurysm was seen in 14, 58 and 35 cases, respectively. Wall attachment sign was noted in 69 cases. All the cases demonstrated only a single drainage site, with left lateral wall, left anterolateral, anterior, right lateral and right anterolateral walls of MPA in 44, 21, 5, 1 and 1 cases, respectively. The mean diameter of the fistula drainage site was 2.6 ± 1.3 mm. Pierced sign, jet sign, smoke sign, isodensity sign was seen in 72, 46, 41 and 24 cases, respectively. MPA enlargement was seen in 20 patients. CCA showed CPAF in only 20 cases among 25 patients; while TTE showed CPAF in only 9 patients among 47 patients. CTCA is competent in detecting and characterizing CPAF with an excellent diagnostic performance as the first imaging modality of choice, which is valuable for giving a distinct and intuitive explanation to patients and physicians and making an objective and exact assessment for further management.


Infrared spectroscopic study of lipid interaction in stratum corneum treated with transdermal absorption enhancers.
To develop a transdermal drug delivery system, it is necessary to search for effective modulators to act as permeation enhancers and evaluate its mechanisms of action. It has been suggested that attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) is a useful tool for evaluating the functional group interaction of the intercellular lipids in the stratum corneum. The purpose of this study is elucidation of the effect of the transdermal permeation enhancers on the intercellular lipid in hairless rat stratum corneum using the ATR-FTIR. Firstly, to confirm the frequencies related to the intercellular lipid in stratum corneum, CH(2) asymmetric and symmetric vibrations were clearly related to the intercellular lipids. In intact stratum corneum, the blue shift of CH(2) asymmetric and symmetric stretching vibrations begins at about 40 degrees C and remarkable change is induced at 50 degrees C. The administration of l-menthol causes disorder of the intercellular lipids in stratum corneum similar to that of heat application. The disordering of intercellular lipid lattices in stratum corneum induced by the l-menthol might be related to the enhancing effect of l-menthol. The results provide information for the development of novel transdermal drug delivery systems.


Policy, practice and decision making for zoonotic disease management: water and Cryptosporidium.
Decision making for zoonotic disease management should be based on many forms of appropriate data and sources of evidence. However, the criteria and timing for policy response and the resulting management decisions are often altered when a disease outbreak occurs and captures full media attention. In the case of waterborne disease, such as the robust protozoa, Cryptosporidium spp, exposure can cause significant human health risks and preventing exposure by maintaining high standards of biological and chemical water quality remains a priority for water companies in the UK. Little has been documented on how knowledge and information is translated between the many stakeholders involved in the management of Cryptosporidium, which is surprising given the different drivers that have shaped management decisions. Such information, coupled with the uncertainties that surround these data is essential for improving future management strategies that minimise disease outbreaks. Here, we examine the interplay between scientific information, the media, and emergent government and company policies to examine these issues using qualitative and quantitative data relating to Cryptosporidium management decisions by a water company in the North West of England. Our results show that political and media influences are powerful drivers of management decisions if fuelled by high profile outbreaks. Furthermore, the strength of the scientific evidence is often constrained by uncertainties in the data, and in the way knowledge is translated between policy levels during established risk management procedures. In particular, under or over-estimating risk during risk assessment procedures together with uncertainty regarding risk factors within the wider environment, was found to restrict the knowledge-base for decision-making in Cryptosporidium management. Our findings highlight some key current and future challenges facing the management of such diseases that are widely applicable to other risk management situations.


Practical recommendation for rash and diarrhea management in Indian patients treated with tyrosine kinase inhibitors for the treatment of non-small cell lung cancer.
Tyrosine kinase inhibitors (TKIs) are a pharmaceutical class of small molecules, orally available with manageable safety profile, approved worldwide for the treatment of several neoplasms, including lung, breast, kidney and pancreatic cancer as well as gastro-intestinal stromal tumours and chronic myeloid leukaemia. In recent years, management of lung cancer has been moving towards molecular-guided treatment, and the best example of this new approach is the use of the tyrosine kinase inhibitors (TKIs) in patients with mutations in the epidermal growth factor receptor (EGFR). The identification of molecular predictors of response can allow the selection of patients who will be the most likely to respond to these tyrosine kinase inhibitors (TKIs). Gastrointestinal (GI) adverse events (AEs) are frequently observed in patients receiving EGFR tyrosine kinase inhibitor therapy and are most impactful on the patient's quality of life. Dermatologic side effects are also relatively common among patients treated with EGFR inhibitors. Evidence has emerged in recent years to suggest that the incidence and severity of rash, positively correlated with response to treatment.These skin disorders are generally mild or moderate in severity and can be managed by appropriate interventions or by reducing or interrupting the dose. Appropriate and timely management make it possible to continue a patient's quality of life and maintain compliance; however if these adverse events (AEs) are not managed appropriately, and become more severe, treatment cessation may be warranted compromising clinical outcome. Strategies to improve the assessment and management of TKI related skin AEs are therefore essential to ensure compliance with TKI therapy, thereby enabling patients to achieve optimal benefits. This article provides a consensus on practical recommendation for the prevention and management of diarrhoea and rash in Non-Small Cell Lung Cancer (NSCLC) patients receiving TKIs.


Individualized Running Wheel System with a Dynamically Adjustable Exercise Area and Speed for Rats Following Ischemic Stroke.
BACKGROUND An innovative animal running wheel with an individualized design was implemented for the rehabilitation of rats following ischemic stroke. MATERIAL AND METHODS The design of the running wheel platform included the running wheel and a side plate for exercise area adjustments. A U-curve with a width of 2 cm was drawn on the lower half of the side plate for the dynamic adjustments of five infrared (IR) sensors based on the physical fitness of the rats. The individualized training process for this running wheel consisted of 2 days of free training to record their average and maximum speeds, 3 days of progressive training to determine their exercise areas, and 2 weeks of normal training based on their average speeds, maximum speeds, and exercise areas. Blood samples were obtained from the tail veins of all rats before the operations and on Days 14, 21, and 28 postsurgery to measure cortisol levels. The motor function tests were performed on Days 7 and 28 postsurgery. On Day 28 postsurgery, the rats were sacrificed under anesthesia, and their brains were removed for Nissl and H&E staining. RESULTS On Day 28 after surgery, the motor function, lesion volume, and cell damage of the DEARW and control groups differed significantly, indicating that this device is effective for stroke rehabilitation. CONCLUSIONS The outcomes of the rats that were rehabilitated using the newly designed training system were better than those of their control-group counterparts, indicating the advantages of this designed system.


The Ikaros gene, a central regulator of lymphoid differentiation, fuses to the BCL6 gene as a result of t(3;7)(q27;p12) translocation in a patient with diffuse large B-cell lymphoma.
The BCL6 gene, isolated from the breakpoints of 3q27-associated chromosomal translocations, has been implicated in diffuse large B-cell lymphomas (DLBL). Here we describe the molecular characterization of novel t(3;7)(q27;p12) translocations in 2 patients with DLBL. Molecular genetic analysis of the breakpoint area involving BCL6 revealed the presence of the Ikaros gene, a central regulator of lymphoid differentiation that had been mapped to human chromosome 7 band p13-p11.1. As a molecular consequence of the translocation, the 5' regulatory region of the BCL6 gene was replaced by the putative 5' regulatory region of the Ikaros gene, probably leading to deregulated expression of the BCL6 gene throughout B-cell differentiation. Reverse transcription-polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH) analyses of a patient sample established that the t(3;7)(q27;p12) results in fusion of the Ikaros and BCL6 genes. This study provides the first evidence that the Ikaros gene is rearranged in human hematopoietic malignant disorders. (Blood. 2000;95:2719-2721)


Size and complexity of polyadenylated RNAs induced in tobacco infected with sonchus yellow net virus.
Hybridization of 32P-labeled sonchus yellow net virus (SYNV) RNA to polyadenylated (poly A+) RNA from infected tobacco reveals the presence of four electrophoretically distinct components. These components probably represent five discrete RNA species complementary to SYNV RNA (scRNAs). The scRNAs are smaller than the 13,000 nucleotide (NT) SYNV genome and range in size from 1200 to 6600 NT. Individual recombinant DNA clones derived from SYNV RNA hybridize to at least three and probably four of the scRNAs. These results suggest that each of the scRNAs contains unique sequences with a combined size representing more than 90% of the viral genome. Therefore, the size range and sequence complexity of the scRNAs are as expected for messenger RNAs encoding the four major SYNV polypeptides and the minor "L-protein."


[Effect of caffeine and sidnofen on the blood supply of the brain, kidneys and hindlimbs during antiorthostatism].
The method of hydrogen clearance was used in experiments on anesthetized cats for studying changes in the blood flow in the brain, kidneys and vena cava caudalis under prolonged antiorthostatism (45 degrees) and medication with caffeine and sidnofen. Specific features of the organ blood flow redistribution under the influence of antiorthostatism and the drugs administered before and after placement of the animals in the antiorthostatic position were established.


[Rearrangements of yeast chromosomes revealed by pulsed field gel electrophoresis].
Electrophoretic karyotypes of yeast Saccharomyces cerevisiae integrant strains containing the pYF91 plasmid integrated into the chromosomes I, III, VI, IX, XI were studied. A possibility was demonstrated of visual identification of the chimaeric chromosomes via the molecular weight increase by 13200 bp (the plasmid size) determined by pulsed field gel electrophoresis. Several gamma-rays induced rearrangements of the yeast chimaeric chromosome I causing instability in hybrids were also studied. The deletions induced in the I chromosome were analysed and their size estimated. The technique of pulsed field gel electrophoresis is recommended for determination of insertions and deletions in the chromosomes of yeast Saccharomyces cerevisiae.


Evaluating Ceramic Repair Materials in Terms of Bond Strength and Color Stability.
To evaluate the shear bond strength (SBS) and color stability (ΔE) of four ceramic veneers (VITA VM 9; VITA VM 13; VITA VMK 95; and IPS e.max Ceram) following repair with three different self-adhesive composite resins (Fusio Liquid Dentin; Constic; and Vertise Flow) and BISCO Intraoral Repair Kit + Filtek Supreme (BC + FS). A total of 96 specimens were prepared per ceramic material, and each ceramic group was divided into subgroups according to testing method (32 specimens for color stability analysis and 64 specimens for SBS testing). ΔE and SBS (SBS1 = non-aged, SBS2 = thermally aged) values of the repaired specimens were calculated. One specimen from each of the thermally aged groups was investigated under scanning electron microscopy (SEM). Two-way ANOVA was used to analyze the mean ΔE, SBS1, and SBS2 values. The differences between SBS1 and SBS2 values were analyzed using independent-samples t test. The lowest ΔE values were calculated for Constic (P ≤ .05). The SBS2 values among all groups were lower than the SBS1 values (P ≤ .05). The lowest SBS2 values were observed for Vertise Flow (2.3 ± 1.47 MPa) (P ≤ .05) and were below the acceptable limit of 5 MPa. All of the investigated repair materials in combination with the ceramic veneers exhibited ΔE values that were higher than the clinically acceptable limits. Thermal aging negatively affected the SBS values in all groups (P ≤ .05). All tested self-adhesive composite resins, with the exception of Vertise Flow, could be used instead of a repair kit with flowable composite resin, especially in noncooperative patients, for the purpose of repairing chipping fractures for VITA VM 9, VITA VM 13, and VITA VMK 95 (P > .05).


Analysis of Magnetic Nondestructive Measurement Methods for Determination of the Degradation of Reactor Pressure Vessel Steel.
Nondestructive magnetic measurement methods can be successfully applied to determine the embrittlement of nuclear pressure vessel steel caused by neutron irradiation. It was found in previous works that reasonable correlation could be obtained between the nondestructively measured magnetic parameters and destructively determined ductile-to-brittle transition temperature. However, a large scatter of the measurement points was detected even in the cases of the non-irradiated reference samples. The reason for their scattering was attributed to the local inhomogeneity of material. This conclusion is verified in the present work by applying three different magnetic methods on two sets of Charpy samples made of two different reactor steel materials. It was found that by an optimal magnetic pre-selection of samples, a good, linear correlation can be found between magnetic parameters as well as the ductile-to-brittle transition temperature with low scattering of points. This result shows that neutron irradiation embrittlement depends very much on the local material properties.


Potential new drug targets for osteoporosis.
Osteoporosis is a worldwide health problem with a high prevalence. Agents for the treatment of osteoporosis are classified as either antiresorptive or anabolic. Antiresorptive agents work by inhibiting the activity of osteoclasts and, therefore, reducing bone resorption. Currently available antiresorptive agents include bisphosphonates, selective estrogen-receptor modulators, calcitonin and estrogen. Various novel antiresorptive agents are in development. Receptor activator of nuclear factor kappa B ligand is an important cytokine involved in osteoclast activation; denosumab, a fully human monoclonal antibody to this molecule, has finished a major fracture trial. Assessment is underway of odanacatib--an inhibitor of cathepsin K, which is an osteoclast enzyme required for resorption of bone matrix. Glucagon-like peptide 2 is being evaluated for the prevention of the nocturnal rise in bone resorption without affecting bone formation. Anabolic agents act by stimulating formation of new bone. The only anabolic agent currently available in the US is teriparatide--recombinant human parathyroid hormone (PTH)(1-34)--and recombinant human PTH(1-84) is available in Europe. PTH stimulates osteoblast function and bone formation. Novel anabolic agents in development include: antibodies such as sclerostin and dickkopf-1 that target molecules involved in Wnt signaling, a pathway that regulates gene transcription of proteins that are important for osteoblast function; an antagonist to the calcium-sensing receptor; and an activin receptor fusion protein, which functions as an activin antagonist and has shown promise as an anabolic agent in early human trials.


[Physicians and professionalism. Patients and information].
In the present time, the advances in sciences brought by technology are worshiped. This contributes to dehumanize human relationships. Medical profession is a commitment to oneself, society and social justice. Scientific and humanist formation must coexist during the training of new physicians. The main objective of medical profession is the relationship with patients. Patients have acquired increasing autonomy and a deliberative relationship is the closest to the ideal medical action. The relationship must be based in autonomy, beneficence, lack of maleficence and justice. The patient must receive all the information about his ailment and the diagnostic and therapeutic alternatives in a clear and intelligible language. This will allow to obtain a fully conscious informed consent from the patient. Asking for this consent, gives the patient the opportunity to practice his responsibility and to decide the best for him in a friendly and confident environment. In the middle of science and technology, a close contact with ethics and humanism will allow a better understanding of the integrity of subjects, specially when they are ill.


Endoscopic treatment modalities for gastroesophageal reflux disease.
A debate has been going for decades between surgeons and gastroenterologists about the treatment of choice for gastroesophageal reflux disease (GERD). The lower esophageal sphincter (LES) has been historically far from the reach of gastroenterologists, who adopted the symptomatic treatment as their approach to reflux disease through reduction of gastric acid. As for surgeons, reaching the LES was only possible by invading the thoracic or abdominal cavity. Although their approach was later refined to become "minimally" invasive, it was still deemed too invasive by others to allow it to be the "gold standard." Simple logic should lead one to think about the "natural route" as the easiest way to reach the LES. This concept has opened the door for the new era of GERD treatment through "endoscopic modality." Seven different techniques are currently being used to treat patients with GERD. We review the mechanism of action, potential side effects, efficacy, durability, and results from the most recent or largest experience of each. This review shows that endoscopic treatment has definitely earned its place as a viable option for GERD treatment in selected patients. With the available data from clinical trials, it is not possible to determine the best modality available, and the endoscopic treatment of choice is to be determined with further studies.


Floral resource availability from groundcover promotes bee abundance in coffee agroecosystems.
Patterns of bee abundance and diversity across different spatial scales have received thorough research consideration. However, the impact of short- and long-term temporal resource availability on biodiversity has been less explored. This is highly relevant in tropical agricultural systems for pollinators, as many foraging periods of pollinators extend beyond flowering of any single crop species. In this study, we sought to understand how bee communities in tropical agroecosystems changed between seasons, and if short- and long-term floral resource availability influenced their diversity and abundance. We used a threshold analysis approach in order to explore this relationship at two time scales. This study took place in a region dominated by coffee agroecosystems in Southern Mexico. This was an ideal system because the landscape offers a range of coffee management regimes that maintain heterogeneity in floral resource availability spatially and temporally. We found that the bee community varies significantly between seasons. There were higher abundances of native social, solitary and managed honey bees during the dry season when coffee flowers. Additionally, we found that floral resources from groundcover, but not trees, were associated with bee abundance. Further, the temporal scale of the availability of these resources is important, whereby short-term floral resource availability appears particularly important in maintaining high bee abundance at sites with lower seasonal complementarity. We argue that in addition to spatial resource heterogeneity, temporal resource heterogeneity is critical in explaining bee community patterns, and should thus be considered to promote pollinator conservation.


Ondansetron and sertraline may interact with 5-HTTLPR and DRD4 polymorphisms to reduce drinking in non-treatment seeking alcohol-dependent women: exploratory findings.
The purpose of this exploratory study was to examine the interaction of 5-HTTLPR and DRD4 exon III polymorphisms with gender in non-treatment seeking alcohol-dependent (AD) individuals while alternately taking ondansetron and sertraline. Evidence suggests that alcohol dependence may be influenced by a genetic interaction that may be gender-specific with temporal changes making pharmacological treatment with serotonergic drugs complex. The main trial was a within-subject double-blind placebo-controlled human laboratory study with 77 non-treatment-seeking AD individuals randomized (55 completed, 49 complete data) to receive 200 mg/day of sertraline or 0.5 mg/day of ondansetron for 3 weeks followed by an alcohol self-administration experiment (ASAE), then placebo for 3 weeks followed by a second ASAE, then receive the alternate drug, in a counterbalanced order, for 3 weeks followed by a third ASAE. Results for men were not significant. Women with the LL 5-HTTLPR genotype receiving ondansetron and SS/SL 5-HTTLPR genotype receiving sertraline (matched), drank significantly fewer drinks per drinking day (DDD) during the 7 days prior to the first and third ASAEs than women receiving the mismatched medication (i.e., sertraline to LL and ondansetron to SS/SL). In a 3-way interaction, 5-HTTLPR alleles by DRD4 alleles by medications, women with the LL genotype who received ondansetron and had DRD4≥7 exon III repeats drank significantly fewer DDD as did SS/SL women who received sertraline but conversely had DRD4<7 repeats in the 7-day period leading up to the first and third ASAEs. Consistent with these data was a significant reduction of milliliters consumed ad libitum during these same ASAEs. These exploratory findings add possible support to gender and genetic differences among AD individuals in response to serotonergic pharmacotherapies. Future trials should be powerful enough to take into account that endophenotypes and a targeting of serotonergic interactions may be essential to successfully treat alcohol dependence.


Preventing and managing cardiometabolic risk: the logic for intervention.
Cardiometabolic risk (CMR), also known as metabolic syndrome or insulin resistance syndrome, comprises obesity (particularly central or abdominal obesity), high triglycerides, low HDL, elevated blood pressure, and elevated plasma glucose. Leading to death from diabetes, heart disease, and stroke, the root cause of CMR is inadequate physical activity, a Western diet identified primarily by low intake of fruits, vegetables, and whole grains, and high in saturated fat, as well as a number of yet-to-be-identified genetic factors. While the pathophysiological pathways related to CMR are complex, the universal need for adequate physical activity and a diet that emphasizes fruits and vegetables and whole grains, while minimizing food high in added sugars and saturated fat suggests that these behaviors are the appropriate focus of intervention.


Genome-wide DNA methylation profile in mungbean.
DNA methylation on cytosine residues is known to affect gene expression and is potentially responsible for the phenotypic variations among different crop cultivars. Here, we present the whole-genome DNA methylation profiles and assess the potential effects of single nucleotide polymorphisms (SNPs) for two mungbean cultivars, Sunhwanogdu (VC1973A) and Kyunggijaerae#5 (V2984). By measuring the DNA methylation levels in leaf tissue with the bisulfite sequencing (BSseq) approach, we show both the frequencies of the various types of DNA methylation and the distribution of weighted gene methylation levels. SNPs that cause nucleotide changes from/to CHH - where C is cytosine and H is any other nucleotide - were found to affect DNA methylation status in VC1973A and V2984. In order to better understand the correlation between gene expression and DNA methylation levels, we surveyed gene expression in leaf tissues of VC1973A and V2984 using RNAseq. Transcript expressions of paralogous genes were controlled by DNA methylation within the VC1973A genome. Moreover, genes that were differentially expressed between the two cultivars showed distinct DNA methylation patterns. Our mungbean genome-wide methylation profiles will be valuable resources for understanding the phenotypic variations between different cultivars, as well as for molecular breeding.


Social Media Effect on Personal Self-Esteem Among the Population in Saudi Arabia.
Background Self-esteem is a self-valuation; it is how people perceive their own worth and how valuable they believe they are to others. In this study, our primary objective was to explore the association between social media use and self-esteem among individuals who actively engage with social media platforms in Saudi Arabia. Method This study involved individuals aged 15 and above who are active social media users residing in Saudi Arabia. The data were collected through an anonymous online cross-sectional survey. Participants were recruited using snowball and convenience sampling method. A questionnaire was administered through Google Forms to collect data from participants. The questionnaire was structured into three sections, which included gathering social and demographic information, assessing personal usage patterns, and evaluating individual self-esteem levels using an Arabic valid version of the Rosenberg Self-Esteem Scale. Results The survey included a total of 2,551 participants. Among them, 51.3% (n = 1,309) were female, 29% (n = 741) fell within the 21-25 age group, 95.7% (n = 2,441) were of Saudi nationality, and 51.6% (n = 1,316) were single. The social media platform most frequently used by participants was TikTok 98.5% (n = 2,512), followed by Facebook 95.7% (n = 2,441), Telegram 89.8% (n = 2,291), YouTube 72.2% (n = 1,942), WhatsApp 66.0% (n = 1,683), and finally, Snapchat 30.7% (n = 1,769). In total, 14.3% (n= 366) have low self-esteem, participants scored around 16.10 ± 1.80, ranging from 5 to 25. The following variables were significantly associated with self-esteem: female sex (83.88% vs 87.52%, X2 = 6.87, p = 0.009), nationality (X2 = 13.507, p < 0.001), marital status (X2 = 12.313, p = 0.006), region (X2 = 18.36, p = 0.001), using Tik Tok (X2 = 4.11, p = 0.043), the frequency of posting comments (X2 = 12.01, p = 0.017), comparing oneself to others (X2 = 27.94, p < 0.001), using social media because of weak personal communication (X2 = 6.56, p = 0.010), using social media to follow news (X2 = 6.89, p = 0.009), and the perceived effect of social media (X2 = 16.28, p < 0.001). Conclusions Our findings revealed that a minority of participants exhibited low self-esteem, and individuals from the Northern region were more likely to report such issues. Sociodemographic factors, including gender, nationality, and marital status, demonstrated associations with self-esteem. Additionally, the frequency of comments, TikTok usage, and peer comparison significantly influenced self-esteem levels.


How I manage acquired pure red cell aplasia in adults.
Pure red cell aplasia (PRCA) is a rare hematological disorder with multiple etiologies. The multifaceted nature of this disease is emphasized by the variety of concomitant clinical features. Classic idiopathic presentation aside, prompt recognition of pathogenetic clues is important because of their diagnostic and therapeutic implications. As a consequence, treatment of PRCA is diverse and strictly dependent on the presented clinical scenario. Here, we propose a series of clinical vignettes that showcase instructive representative situations derived from our routine clinical practice. Using these illustrative clinical cases, we review the diagnostic workup needed for a precise diagnosis and the currently available therapeutic options, discussing their applications in regard to the various PRCA-associated conditions and individual patients' characteristics. Finally, we propose a treatment algorithm that may offer guidance for personalized therapeutic recommendations.


Human cytomegalovirus and herpes simplex type 2 virus in normal and adenocarcinomatous prostate glands.
Normal prostate, benign prostate hypertrophy (BHP), and prostate adenocarcinoma (ACP) biopsy specimens were analyzed for the presence of human cytomegalovirus (HCMV) and herpes simplex virus type 2 (HSV-2)-specific macromolecules. HCMV DNA homologous sequences were detected in 2 of 13 normal prostate, 2 of 9 BHP, and 3 of 10 ACP tissues, and HSV-2 DNA homologous sequences were found in 1 normal prostate tissue and 2 ACP tissues. In situ DNA-RNA hybridizations indicated HCMV-specific RNA in 3 of 8 BHP and 4 of 9 ACP tissues. No positive in situ hybridization for HCMV RNA was observed in normal prostate tissues. Parallel in situ DNA-RNA hybridization localized HSV-2-specific RNA in only 1 of 8 tumor sections. No HSV-2-specific RNA was observed in sections of normal and BHP tissues. Anticomplement immunofluorescence (ACIF) tests of BHP and ACP specimens showed specific HCMV immunofluorescence in 3 of 8 BHP and 4 of 9 ACP tissues. ACIF results correlate closely with in situ hybridization results and imply some degree of HCMV association with prostatic abnormality. The results also suggest that latent HCMV may be harbored by the human prostate gland.


MR imaging assessment of lumbar intervertebral disk degeneration and age-related changes: apparent diffusion coefficient versus T2 quantitation.
T2 and ADC mappings are 2 quantitative MR imaging tools for assessing IVDD. This study aimed to compare these 2 measures in detecting IVDD and its age-related changes. Thirty-seven asymptomatic volunteers and 28 patients with back pain or sciatica were examined, and their lumbar disk T2 and ADC maps were quantified via sagittal imaging protocols at 1.5T. For all participants, the Pfirrmann system was used by 2 radiologists for grading disks. T2 and ADC values in the inner portion of disks were measured, and their variances in different grades were analyzed by 1-way ANOVA testing. The ability of T2 and ADC measures to differentiate IVDD grades was compared on the basis of their ROC curves. For asymptomatic subjects, the correlations between age and the 2 MR imaging measures were assessed by the Pearson correlation test. Both T2 and ADC values were found to decrease with the increasing Pfirrmann grades except T2 in grade V. Significant T2 differences were seen among grades I-IV, but not between grades IV and V. There were no significant ADC differences among grades I-III. Moreover, the areas under the ROC curves differed significantly (0.95 and 0.67 for T2 and ADC, respectively). Linear regression analysis revealed that T2 yielded more significant correlation with age (r = -0.77) than ADC did (r = -0.37). T2 quantitation provides a more sensitive and robust approach for detecting and characterizing the early stage of IVDD and age-related disk changes.


[The effect of different types of premedication on gastric juice volume and pH].
60 pregnant women and 60 parturients treated with selected surgery were studied according to the influence of different types premedication on the gastric juice volume and pH. Parturients were divided into six groups (AI-AVI) with 10 participants in each one. Groups were comparable for a variety of signs-age, type and duration of the surgical procedure and methods of carrying out the general anaesthesia. Surgically treated patients were also divided into six groups (from B 1 to B), each group containing ten patients with similar symptoms. This makes possible comparison between them. Parturients from group AI were given each 0.007 mg/kg/body weight atropine i.v. 20 min before introduction in anaesthesia; group A II-0.014 mg/kg/body weight metacin; group AIII-0.3 mg/kg/body weight alkosin; group AIV-o.014 mg/kg/body weight metacin and 0.21 mg/kg/body weight dimidrol. Parturients from AV were given each two measure spoons Almagel A per os-an antacid drug-30 min before introduction in anesthesia and 0.007 mg/kg/body weight atropine i.v., introduced 20 min before the beginning of anesthesia. The parturients from group AVI were given each 400 mg H2 blocker (2 tabl.) per os-cimetidine-2 hours before the beginning of anesthesia and atropine 20 min before introduction in anesthesia in the same dosage as for the parturients from group AV. Surgically treated patients from group BI received as a premedication the following drugs 20 min before the beginning of anesthesia: atropine-0.007 mg/kg/body weight, fentanyl-0.001 and droperidol-0.03 mg/kg/body weight introduced i.v. Group BII-geluzil liquid-2 tea spoons 30 min before introduction in anesthesia and atropine i.v. 20 min at the beginning of anesthesia; group BIII received as a premedication dormicum-0.1 mg/kg/body weight and atropine in the same dosage as for the patients from group BII. Group BIV received as a premedication 20 ml 8.4% solution of sodium bicarbonate per os 20 min before the beginning of anesthesia and atropine in the same dosage as the patients from group BIII; BV received 0.003 mg/kg/body weight gastrodin, introduced i.v. 20 min before the beginning of anesthesia. Patients from group BVI received as a premedication for 2 hours before the beginning of anesthesia gastrozepin 2 tabl. (50 mg) per os and atropine in the same dosage as the patients from group BII. Gastric juice was taken by means of nasogastric tubing immediately before premedication, introduction in anesthesia and its end to fix its pH. The volume of gastric juice generated during the surgical procedure was determined before extubation.(ABSTRACT TRUNCATED AT 250 WORDS)


CYP2J2-derived epoxyeicosatrienoic acids suppress endoplasmic reticulum stress in heart failure.
Prolonged endoplasmic reticulum (ER) stress causes apoptosis and is associated with heart failure. Whether CYP2J2 and its arachidonic acid metabolites [epoxyeicosatrienoic acids (EETs)] have a protective influence on ER stress and heart failure has not been studied. Assays of myocardial samples from patients with end-stage heart failure showed evidence of ER stress. Chronic infusion of isoproterenol (ISO) or angiotensin II (AngII) by osmotic mini-pump induced cardiac hypertrophy and heart failure in mice as evaluated by hemodynamic measurements and echocardiography. Interestingly, transgenic (Tr) mice with cardiomyocyte-specific CYP2J2 expression were protected against heart failure compared with wild-type mice. ISO or AngII administration induced ER stress and apoptosis, and increased levels of intracellular Ca(2+). These phenotypes were abolished by CYP2J2 overexpression in vivo or exogenous EETs treatment of cardiomyocytes in vitro. ISO or AngII reduced sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA2a) expression in hearts or isolated cardiomyocytes; however, loss of SERCA2a expression was prevented in CYP2J2 Tr hearts in vivo or in cardiomyocytes treated with EETs in vitro. The reduction of SERCA2a activity was concomitant with increased oxidation of SERCA2a. EETs reversed SERCA2a oxidation through increased expression of antioxidant enzymes and reduced reactive oxygen species levels. Tempol, a membrane-permeable radical scavenger, similarly decreased oxidized SERCA2a levels, restored SERCA2a activity, and markedly reduced ER stress response in the mice treated with ISO. In conclusion, CYP2J2-derived EETs suppress ER stress response in the heart and protect against cardiac failure by maintaining intracellular Ca(2+) homeostasis and SERCA2a expression and activity.


Pesticide exposure as risk factor for non-Hodgkin lymphoma including histopathological subgroup analysis.
We report a population based case-control study of exposure to pesticides as risk factor for non-Hodgkin lymphoma (NHL). Male and female subjects aged 18-74 years living in Sweden were included during December 1, 1999, to April 30, 2002. Controls were selected from the national population registry. Exposure to different agents was assessed by questionnaire. In total 910 (91 %) cases and 1016 (92%) controls participated. Exposure to herbicides gave odds ratio (OR) 1.72, 95% confidence interval (CI) 1.18-2.51. Regarding phenoxyacetic acids highest risk was calculated for MCPA; OR 2.81, 95% CI 1.27-6.22, all these cases had a latency period >10 years. Exposure to glyphosate gave OR 2.02, 95% CI 1.10-3.71 and with >10 years latency period OR 2.26, 95% CI 1.16-4.40. Insecticides overall gave OR 1.28, 95% CI 0.96-1.72 and impregnating agents OR 1.57, 95% CI 1.07-2.30. Results are also presented for different entities of NHL. In conclusion our study confirmed an association between exposure to phenoxyacetic acids and NHL and the association with glyphosate was considerably strengthened.


Iotrolan. The first dimeric non-ionic contrast medium for the subarachnoid space.
Iotrolan was administered to 1400 in-patients and out-patients by intrathecal injection within the framework of the clinical investigation. It was used for studies of the lumbar, thoracic, cervical and intracranial areas. It was compared with metrizamide, iopamidol and iohexol in concentrations of 190, 240 and 300 mg I/ml in controlled double-blind trials. The minimum observation periods were four days including the investigation of clinicochemical, cardiovascular and electroencephalographic parameters, and CT. The incidence and severity of all side effects after Iotrolan were much lower than those after the non-ionic monomers. No epileptogenic incidents or symptoms of a psychosyndrome were observed in any of the cases--not even after prolonged retention in the intracranial fluid spaces.


Analysis of gene coexpression by B-spline based CoD estimation.
The gene coexpression study has emerged as a novel holistic approach for microarray data analysis. Different indices have been used in exploring coexpression relationship, but each is associated with certain pitfalls. The Pearson's correlation coefficient, for example, is not capable of uncovering nonlinear pattern and directionality of coexpression. Mutual information can detect nonlinearity but fails to show directionality. The coefficient of determination (CoD) is unique in exploring different patterns of gene coexpression, but so far only applied to discrete data and the conversion of continuous microarray data to the discrete format could lead to information loss. Here, we proposed an effective algorithm, CoexPro, for gene coexpression analysis. The new algorithm is based on B-spline approximation of coexpression between a pair of genes, followed by CoD estimation. The algorithm was justified by simulation studies and by functional semantic similarity analysis. The proposed algorithm is capable of uncovering both linear and a specific class of nonlinear relationships from continuous microarray data. It can also provide suggestions for possible directionality of coexpression to the researchers. The new algorithm presents a novel model for gene coexpression and will be a valuable tool for a variety of gene expression and network studies. The application of the algorithm was demonstrated by an analysis on ligand-receptor coexpression in cancerous and noncancerous cells. The software implementing the algorithm is available upon request to the authors.


Geotropic Stimulation: Effects on Wound Vessel Differentiation.
Wounded excised shoots of Coleus blumeni (Benth.) were geotropically stimulated by rotation on a klinostat at 3 rev/min at right angles to the horizontal axis and placed alternately in inverted and upright positions at 24-hour intervals. These treatments resulted in the differentiation of significantly greater numbers of wound vessel members. The pattern of wound-vessel formation was altered by rotation on the klinostat but remained unaffected by 24-hour inversion.


Appearance of vegetation in ultraviolet light: absorbing flowers, reflecting backgrounds.
Flowers that uniformly absorb ultraviolet light may contrast strikingly with a bright ultraviolet-reflecting background, such as densely hairy or glaucous foliage, white soils, or the sky. Shadows will not resemble these flowers if the appearance of each in visible light is also considered. Examples are shown from Mexican heliotropiums and Michigan dune plants.


FATAL INFECTION OF IRRADIATED WHITE MICE WITH EUROPEAN TYPHUS BY THE INTRA-ABDOMINAL ROUTE.
A fatal infection of irradiated white mice with the Breinl strain of European typhus has been established and passed serially for 22 passages by the intra-abdominal route. Rickettsiae were abundant and easily demonstrable in the moribund or dead mice. The mortality of irradiated mice infected with passage material (peritoneal washings or blood) was nearly 100 per cent as contrasted to no mortality in the control mice given the same dose of x-ray (450 R) and the same volume of fluid intra-abdominally. (The observation period of control mice was arbitrarily limited to 14 days.) After eighteen passages in irradiated mice no increase in virulence for non-irradiated adult mice was detected. After passage in guinea pigs, the rickettsial infection deriving from the mouse passage material was identical with the Breinl strain as judged by fever, cross immunity tests, and brain lesions in sections.


Effect of feedback regarding urinary cotinine and brief tailored advice on home smoking restrictions among low-income parents of children with asthma: a controlled trial.
Since most smoker parents of children with asthma are unable to quit, an alternative measure that would reduce their children's exposure to environmental tobacco smoke (ETS) is to ban smoking in the home. Compared with 136 usual-care controls, 128 intervention-group parents recruited from South Australian pediatric hospital outpatient waiting rooms were given written and verbal feedback about their 1- to 11-year-old child's urinary cotinine-to-creatinine level, information booklets, and two telephone calls encouraging a ban on smoking at home. At 6 months, 49.2% of the intervention group reported having banned smoking in the home compared with 41.9% of controls, but the differential rate of change from baseline was not significant (P = 0.40). At follow-up, there were no significant differences between groups in the percentage reporting bans on smoking in the car, the mean reduction from baseline in total daily consumption or consumption in front of the child, children's urinary cotinine level, or parental smoking cessation. The intervention did not change parents' propensity to create or maintain bans on smoking in their homes or otherwise change smoking habits to reduce their children's exposure to ETS. More intensive interventions may be required to achieve change among low-income smoker parents of children with asthma.


The role of diet in the management of atopic eczema.
The underlying cause of atopic eczema remains unknown but both food intolerance and dietary deficiency--notably of essential fatty acids--may well be exacerbating factors. Studies investigating the involvement of food intolerance have shown that only some children obtain benefit from avoiding milk and eggs. In other cases, the use of an elimination or of a chemically-defined diet followed by challenge with specific foods may allow an effective personalized diet to be devised. Skin-prick tests and measurement of IgE levels have proved to be unreliable predictors of reactions to food. The development of a reliable test to assess food intolerance would represent a significant advance in the treatment of atopic eczema.


Multimodal effects of available drugs for ischemic stroke.
Recent research demonstrates the complexity and variety of pathophysiologic processes underlying cerebral ischemia. This review will focus on the multimodal effects of the various drugs currently used for stroke prevention. The most recent clinical studies of each will also be reviewed, and the implications for clinical use and future research discussed. An evolving approach for stroke prevention will include a combination of antiplatelets, increased use of statins, ACE inhibitors and possibly vitamin therapy.


Reasons for Exclusion from a Smoking Cessation Trial: An Analysis by Race/Ethnicity.
The exclusion criteria of tobacco cessation randomized clinical trials (RCTs) may have unintended consequences on inclusion and cessation disparities. We examined racial/ethnic differences in: a) exclusion from a group-based cessation RCT; and b) reasons for exclusion. Quasi-experimental. Inclusion criteria were self-identification as African American/Black, non-Hispanic White, or Hispanic (any race), adults, minimum five cigarettes/day or carbon monoxide reading of ≥ 8 parts per million (ppm), interest in quitting, and spoke/read English. Data were obtained from a parent trial, which is ongoing and will be completed in 2019. Analyses for our present study on participant screening and enrollment were conducted in 2018. Study ineligibility, and reasons for exclusion (contraindications for nicotine patch use, serious mental illness [SMI, eg, bipolar disorder or schizophrenia], alcohol dependence or illicit drug use, current tobacco treatment, attendance barriers [eg, transportation], and other concerns [eg, aggressive, intoxicated, disruptive, visibly ill]). Of 1,206 individuals screened, 36% were ineligible. The most frequent reasons were SMI (28%), alcohol dependence or drug use (10%), and attendance barriers (7%). Ineligibility was greater among African Americans (42%) and Hispanics (37%), compared with Whites (24%; P<.001). Compared with African Americans and Hispanics, Whites were more likely to be excluded for single reasons, including attendance barriers, and medical conditions (P<.05). African Americans were more than twice as likely as Whites to be excluded for 3 or more reasons (12% vs 5% respectively, P<.05). A notable proportion of smokers were ineligible for this RCT, with SMI as the greatest single cause. Racial/ethnic minorities were more likely to be excluded, with African Americans deemed ineligible for multiple reasons. Findings have implications for RCT generalizability, addressing tobacco disparities and health equity.


Inhibition of epidermal growth factor receptor tyrosine kinase activity in A431 human epidermoid cells following psoralen/ultraviolet light treatment.
One of the more prominent clinical treatments for skin diseases such as psoriasis and vitiligo involves the use of a combination of psoralens and UV light, a procedure referred to as PUVA chemotherapy. This drug regimen markedly alters epidermal cell growth and differentiation. In many cell types, an early cellular event following treatment of cells with PUVA is inhibition of binding of epidermal growth factor (EGF) to its receptor. To examine the mechanism underlying this effect, we used A431 cells, a human epidermal cell line known to express large numbers of EGF receptors. We found that exposure of A431 cells to PUVA caused a dramatic inhibition of EGF-stimulated EGF receptor tyrosine kinase activity. Inhibition required intact cells and did not appear to be mediated by protein kinase C, because this inhibition was apparent in cells in which the enzyme was down-regulated by phorbol ester pretreatment and in cells treated with inhibitors of protein kinase C. Inhibition of tyrosine kinase activity by PUVA was distinct from other inhibitors of EGF receptor function in that it was associated with a rapid increase in the amount of phosphate incorporated into serine residues of the EGF receptor. This suggested that PUVA-induced serine phosphorylation may mediate EGF receptor kinase activity. These results demonstrate that alterations in EGF receptor function may contribute to the therapeutic efficacy of PUVA in photo-chemotherapy.


[Production of biologically active substances of indol nature by bacteria of Azotobacter genus].
A stimulating effect of Azotobacter vinelandii IMB B-7076 bacteria on germination of seeds and formation of germs of different plants has been shown. One of the factors, which determines such phenomenon is the accumulation of biologically active substances in culture medium. The researched bacteria of Azotobacter genus accumulate indoleacetic acid (IAA) in the culture medium. Other substances of indol nature have been identified in the culture medium of these bacteria. It has been shown, using the computer's program PASS that these substances cannot take part in the regulation of plants growth. However 1H-indole-3carboxaldehyde can be characterized by antagonistic activity.


The Social Validity of Telepractice among Spanish-Speaking Caregivers of English Learners: An Examination of Moderators.
The purpose of the present paper was to examine the social validity of telepractice as a service delivery model for Spanish-speaking families of English learners. Quantitative survey methodology was employed to examine 79 caregivers' opinions regarding telepractice and to obtain background information about participants' home environments. Findings revealed that approximately 46% of the participant sample reported being interested in their children receiving services via telepractice. Caregivers reported limited familiarity with telepractice as an option, but were likely to express interest if their child had an identified speech or language disorder or if they were interested in increased access to Spanish language support for their children. In conclusion, although telepractice is not universally accepted among Spanish-speaking families, it appears to be a promising service delivery model. It is recommended that service providers offer thorough information and address common myths when considering telepractice as a service delivery model for families.


Sex-specific neuroprotection by inhibition of the Y-chromosome gene, SRY, in experimental Parkinson's disease.
Parkinson's disease (PD) is a debilitating neurodegenerative disorder caused by the loss of midbrain dopamine (DA) neurons. While the cause of DA cell loss in PD is unknown, male sex is a strong risk factor. Aside from the protective actions of sex hormones in females, emerging evidence suggests that sex-chromosome genes contribute to the male bias in PD. We previously showed that the Y-chromosome gene, SRY, directly regulates adult brain function in males independent of gonadal hormone influence. SRY protein colocalizes with DA neurons in the male substantia nigra, where it regulates DA biosynthesis and voluntary movement. Here we demonstrate that nigral SRY expression is highly and persistently up-regulated in animal and human cell culture models of PD. Remarkably, lowering nigral SRY expression with antisense oligonucleotides in male rats diminished motor deficits and nigral DA cell loss in 6-hydroxydopamine (6-OHDA)-induced and rotenone-induced rat models of PD. The protective effect of the SRY antisense oligonucleotides was associated with male-specific attenuation of DNA damage, mitochondrial degradation, and neuroinflammation in the toxin-induced rat models of PD. Moreover, reducing nigral SRY expression diminished or removed the male bias in nigrostriatal degeneration, mitochondrial degradation, DNA damage, and neuroinflammation in the 6-OHDA rat model of PD, suggesting that SRY directly contributes to the sex differences in PD. These findings demonstrate that SRY directs a previously unrecognized male-specific mechanism of DA cell death and suggests that suppressing nigral Sry synthesis represents a sex-specific strategy to slow or prevent DA cell loss in PD.


Potential arrhythmogenic electrophysiological derangements in canine Purkinje fibers induced by lysophosphoglycerides.
We have recently detected accumulation of lysophosphoglycerides, catabolites of phospholipids, in ischemic myocardium early after coronary occlusion. In the present study we delineated effects of selected concentrations of albumin-bound lysophosphatidyl choline (LPC) comparable to those accompanying ischemia in vivo on action potentials of isolated canine Purkinje fibers. Lysophosphoglycerides induced concentration-dependent (0.75-3.0 mM) decreases in resting membrane potential, overshoot of phase 0, maximal velocity of upstroke (Vmax) of phase 0, and action potential duration. The highest concentrations (2.0-3.0 mM) induced fractionation of the action potential into several components, unresponsiveness to external stimulation, and enhanced automaticity at normal and reduced membrane potentials. LPC induced a rightward shift in the membrane response curve, a 40-fold prolongation of conduction time, and an increase in the ratio of effective refractory period to action potential duration such that the effective refractory period persisted beyond action potential duration, resulting in postrepolarization refractoriness. These electrophysiological alterations were entirely reversible after 70 minutes of perfusion without LPC, with the exception of a persistent depression in the Vmax of phase 0. Lysophosphatidyl ethanolamine (LPE) elicited alterations in action potentials indentical to those elicited by LPC. Furthermore, LPC (3.0 mM) induced comparable alterations in action potentials recorded from isolated rabbit papillary muscles. Since lysophospholipids accumulate early after myocardial ischemia, and since concentrations equivalent to those occurring in vivo induce electrophysiological alterations resembling those seen in ischemic myocardium in vivo, lysophosphoglycerides may be of major importance as biochemical mediators of malignant dysrhythmia induced by ischemia.


Nickel Oxide Nanoparticles Improve Soybean Yield and Enhance Nitrogen Assimilation.
Nickel (Ni) is a trace element beneficial for plant growth and development and could improve crop yield by stimulating urea decomposition and nitrogen-fixing enzyme activity. A full life cycle study was conducted to compare the long-term effects of soil-applied NiO nanoparticles (n-NiO), NiO bulk (b-NiO), and NiSO4 at 10-200 mg kg-1 on plant growth and nutritional content of soybean. n-NiO at 50 mg kg-1 significantly promoted the seed yield by 39%. Only 50 mg kg-1 n-NiO promoted total fatty acid content and starch content by 28 and 19%, respectively. The increased yield and nutrition could be attributed to the regulatory effects of n-NiO, including photosynthesis, mineral homeostasis, phytohormone, and nitrogen metabolism. Furthermore, n-NiO maintained a Ni2+ supply for more extended periods than NiSO4, reducing potential phytotoxicity concerns. Single-particle inductively coupled plasma mass spectrometry (sp-ICP-MS) for the first time confirmed that the majority of the Ni in seeds is in ionic form, with only 28-34% as n-NiO. These findings deepen our understanding of the potential of nanoscale and non-nanoscale Ni to accumulate and translocate in soybean, as well as the long-term fate of these materials in agricultural soils as a strategy for nanoenabled agriculture.


Rabies and canine distemper virus epidemics in the red fox population of northern Italy (2006-2010).
Since 2006 the red fox (Vulpes vulpes) population in north-eastern Italy has experienced an epidemic of canine distemper virus (CDV). Additionally, in 2008, after a thirteen-year absence from Italy, fox rabies was re-introduced in the Udine province at the national border with Slovenia. Disease intervention strategies are being developed and implemented to control rabies in this area and minimise risk to human health. Here we present empirical data and the epidemiological picture relating to these epidemics in the period 2006-2010. Of important significance for epidemiological studies of wild animals, basic mathematical models are developed to exploit information collected from the surveillance program on dead and/or living animals in order to assess the incidence of infection. These models are also used to estimate the rate of transmission of both diseases and the rate of vaccination, while correcting for a bias in early collection of CDV samples. We found that the rate of rabies transmission was roughly twice that of CDV, with an estimated effective contact between infected and susceptible fox leading to a new infection occurring once every 3 days for rabies, and once a week for CDV. We also inferred that during the early stage of the CDV epidemic, a bias in the monitoring protocol resulted in a positive sample being almost 10 times more likely to be collected than a negative sample. We estimated the rate of intake of oral vaccine at 0.006 per day, allowing us to estimate that roughly 68% of the foxes would be immunised. This was confirmed by field observations. Finally we discuss the implications for the eco-epidemiological dynamics of both epidemics in relation to control measures.


Dissecting the NUP107 complex: multiple components and even more functions.
The Nuclear Pore Complex (NPC) is a fascinating structure whose functional relevance and complexity attract significant interest. Within the NPC, several different subcomplexes interact with each other to form a highly conserved and stable structure. One of these subcomplexes is the NUP107 complex, constituted by 7-9 members. A wide variety of functions have been ascribed to the NUP107 complex, ranging from NPC assembly to mRNA export to cell differentiation. Recently, genetic dissection of the NUP107 complex has provided novel insight to the assembly of the complex and has, moreover, revealed an unexpected connection with the mitotic spindle assembly checkpoint protein MAD1.


Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study.
One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients. The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference. This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries. Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation. This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P < 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P < 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT. In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV. The study was registered at Clinicaltrials.gov, NCT01601223.


Convex Calibrated Surrogates for the Multi-Label F-Measure.
The F-measure is a widely used performance measure for multi-label classification, where multiple labels can be active in an instance simultaneously (e.g. in image tagging, multiple tags can be active in any image). In particular, the F-measure explicitly balances recall (fraction of active labels predicted to be active) and precision (fraction of labels predicted to be active that are actually so), both of which are important in evaluating the overall performance of a multi-label classifier. As with most discrete prediction problems, however, directly optimizing the F-measure is computationally hard. In this paper, we explore the question of designing convex surrogate losses that are calibrated for the F-measure - specifically, that have the property that minimizing the surrogate loss yields (in the limit of sufficient data) a Bayes optimal multi-label classifier for the F-measure. We show that the F-measure for an s-label problem, when viewed as a 2 s × 2 s loss matrix, has rank at most s 2 + 1, and apply a result of Ramaswamy et al. (2014) to design a family of convex calibrated surrogates for the F-measure. The resulting surrogate risk minimization algorithms can be viewed as decomposing the multi-label F-measure learning problem into s 2 + 1 binary class probability estimation problems. We also provide a quantitative regret transfer bound for our surrogates, which allows any regret guarantees for the binary problems to be transferred to regret guarantees for the overall F-measure problem, and discuss a connection with the algorithm of Dembczynski et al. (2013). Our experiments confirm our theoretical findings.


A data-driven optimization algorithm for differential algebraic equations with numerical infeasibilities.
Support Vector Machines (SVMs) based optimization framework is presented for the data-driven optimization of numerically infeasible Differential Algebraic Equations (DAEs) without the full discretization of the underlying first-principles model. By formulating the stability constraint of the numerical integration of a DAE system as a supervised classification problem, we are able to demonstrate that SVMs can accurately map the boundary of numerical infeasibility. The necessity of this data-driven approach is demonstrated on a 2-dimensional motivating example, where highly accurate SVM models are trained, validated, and tested using the data collected from the numerical integration of DAEs. Furthermore, this methodology is extended and tested for a multi-dimensional case study from reaction engineering (i.e., thermal cracking of natural gas liquids). The data-driven optimization of this complex case study is explored through integrating the SVM models with a constrained global grey-box optimization algorithm, namely the ARGONAUT framework.


The effect of dietary glycemic index on weight maintenance in overweight subjects: a pilot study.
Evidence suggests that a low-glycemic index (LGI) diet has a satiating effect and thus may enhance weight maintenance following weight loss. This study was conducted at Hammersmith Hospital, London, UK, and assessed the effect of altering diet GI on weight-loss maintenance. It consisted of a weight-loss phase and a 4-month randomized weight maintenance phase. Subjects were seen monthly to assess dietary compliance and anthropometrics. Appetite was assessed bimonthly by visual analogue scales while meal challenge postprandial insulin and glucose concentrations were assessed before and after the intervention. Following a median weight loss of 6.1 (interquartile range: 5.2-7.1) % body weight, subjects were randomized to a high-glycemic index (HGI) (n = 19) or LGI (n = 23) diet. Dietary composition differed only in GI (HGI group: 63.7 +/- 9.4; LGI group: 49.7 +/- 5.7, P < 0.001) and glycemic load (HGI group: 136.8 +/- 56.3; LGI group: 89.7 +/- 27.5, P < 0.001). Groups did not differ in body weight (weight change over 4 months, HGI group: 0.3 +/- 1.9 kg; LGI group: -0.7 +/- 2.9 kg, P = 0.3) or other anthropometric measurements. This pilot study suggests that in the setting of healthy eating, changing the diet GI does not appear to significantly affect weight maintenance.


Production, characterization and in vitro testing of HBcAg-specific VHH intrabodies.
Hepatitis B virus (HBV) infections represent a global health problem, since these account for 350 million chronic infections worldwide that result in 500,000-700,000 deaths each year. Control of viral replication and HBV-related disease and mortality are of utmost importance. Because the currently available antiviral therapies all have major limitations, new strategies to treat chronic HBV infection are eagerly awaited. Six single-domain antibodies (VHHs) targeting the core antigen of HBV (HBcAg) have been generated and three of these bound strongly to HBcAg of both subtype ayw and adw. These three VHHs were studied as intrabodies directed towards the nucleus or the cytoplasm of a hepatoma cell line that was co-transfected with HBV. A speckled staining of HBcAg was observed in the cytoplasm of cells transfected with nucleotropic VHH intrabodies. Moreover, an increased intracellular accumulation of hepatitis B e antigen (HBeAg) and a complete disappearance of intracellular HBcAg signal were observed with nuclear targeted HBcAg-specific VHHs. These results suggest that HBcAg-specific VHHs targeted to the nucleus affect HBcAg and HBeAg expression and trafficking in HBV-transfected hepatocytes.


Physiologically relevant measurements of nitric oxide in cardiovascular research using electrochemical microsensors.
Nitric oxide (NO) plays an important role in the regulation of blood flow. Pharmacological tools and a series of other techniques have been developed for studying the NO/L-arginine pathway, but it has proved difficult to make a quantitative link between effect and tissue NO concentration. NO microsensors have been applied with success for the measurement of NO in suspensions of mitochondria and cells, such as platelets and leukocytes, and in cell cultures, which together with other interventions or measurements are particularly useful for the examination of cell signalling related to the NO/L-arginine pathway. In isolated vascular segments, studies using the NO microsensor have defined the relationship between NO concentration and relaxation and revealed residual NO release in the presence of NO synthase inhibitors. Moreover, simultaneous measurements of NO concentration and vasorelaxation in isometric preparations have shown that agonist-induced relaxation is L-arginine dependent and NO release is reduced in hypertension. By placing NO microsensors in catheters, it is possible to measure NO in the living animal and man. This approach has been applied for the measurements of NO concentration in relation to increases in flow, erection, in conditions of hypoxia, and in endotoxemia. However, further methodological development of NO microsensors is necessary to avoid the influence of changes in temperature, pH and oxygen on the measurements.