A comprehensive review on the utilization of biopolymer hydrogels to encapsulate and protect probiotics in foods.
Probiotics must survive in foods and passage through the human mouth, stomach, and small intestine to reach the colon in a viable state and exhibit their beneficial health effects. Probiotic viability can be improved by encapsulating them inside hydrogel-based delivery systems. These systems typically comprise a 3D network of cross-linked polymers that retain large amounts of water within their pores. This study discussed the stability of probiotics and morphology of hydrogel beads after encapsulation, encapsulation efficiency, utilization of natural polymers, and encapsulation mechanisms. Examples of the application of these hydrogel-based delivery systems are then given. These studies show that encapsulation of probiotics in hydrogels can improve their viability, provide favorable conditions in the food matrix, and control their release for efficient colonization in the large intestine. Finally, we highlight areas where future research is required, such as the large-scale production of encapsulated probiotics and the in vivo testing of their efficacy using animal and human studies.


Retrospective study of etiologic agents associated with nonsuppurative meningoencephalitis in stranded cetaceans in the canary islands.
Nineteen natural cases of etiologically undetermined encephalitides in free-ranging cetaceans were studied retrospectively. Histological examination of the brains revealed variable degrees of nonsuppurative encephalitis or meningoencephalitis, characterized predominantly by perivascular lymphohistiocytic infiltrates. A PCR assay was used on brain and other available tissues to detect the presence of morbillivirus, herpesvirus, West Nile virus, Toxoplasma gondii, and Brucella spp. In addition, immunohistochemical (IHC) staining was performed on selected tissues to determine the presence of morbilliviral antigens. Six animals (5 striped dolphins and 1 common dolphin) showed IHC and/or molecular evidence of morbilliviral antigens and/or genomes, mainly in brain tissue. Conventional nested PCR detected herpesviral DNA in brain tissue samples from two striped dolphins. There was no evidence of West Nile virus, T. gondii, or Brucella spp. in any of the brain tissue samples examined. The information presented here increases the number of confirmed morbillivirus-positive cases within the Canarian archipelago from two previously reported cases to eight. Furthermore, a new nested-PCR method for the detection of morbillivirus is described here. Regarding herpesvirus, the phylogenetic analysis performed in the current study provides valuable information about a possible pathogenic branch of cetacean alphaherpesviruses that might be responsible for some fatal cases worldwide.


Increased expression of miR-1179 inhibits breast cancer cell metastasis by modulating Notch signaling pathway and correlates with favorable prognosis.
MicroRNAs (miRNAs) play a key role in the regulation of gene expression. In this study, we aimed to identify the clinical values of miR-1179 and to investigate the potential molecular mechanisms in breast cancer (BC). RT-PCR was used to detect the expression levels of miR-1179 in both BC tissues and cell lines. We analyzed the association between the miR-1179 levels and clinicopathological factors and patient prognosis. The proliferation ability of miR-1179 on BC cells was assessed by MTT and colony formation assay. The role of miR-1179 in BC cells migration and invasion was measured by transwell assays. Western blot analysis was used to quantify the expression of the molecular biomarkers of the Notch signaling pathway. Our results showed that miR-1179 expression was frequently downregulated in BC tissues and cell lines. Clinicopathologic analysis revealed that low miR-1179 expression is correlated with lymph node metastasis, advanced clinical stage and shorter overall survival. Multivariable Cox proportional hazards regression analysis suggested that increased miR-1179 expression was an independent prognostic factor of overall survival in BC patients. Gain-of-function assay indicated that the overexpression of miR-1179 significantly suppressed BC cells proliferation, migration and invasion. Mechanistically, miR-1179 up-regulation inhibited the expression of Notch 1, Notch 4 and Hes1, indicating that miR-1179 could suppress the activation of the Notch signaling pathway. We showed that miR-1179 was a tumor suppressor that may serve as a novel potential prognostic biomarker or molecular therapeutic target for BC.


The role of the c-mos gene in the 8;21 translocation in human acute myeloblastic leukemia.
The human c-mos proto-oncogene is located on chromosome 8 at band q22, close to the breakpoint in the t(8;21) (q22;q22) chromosome rearrangement. This translocation is associated with acute myeloblastic leukemia, subgroup M2. The c-myc gene, another proto-oncogene, has been mapped to 8q24. The breakpoint at 8q22 separates these genes, as determined by in situ hybridization of c-mos and c-myc probes. The c-mos gene remains on the 8q-chromosome and the c-myc gene is translocated to the 21q+ chromosome. Southern blot analysis of DNA from bone marrow cells of four patients with this translocation showed no rearrangement of c-mos.


Further links between the maximum hardness principle and the hard/soft acid/base principle: insights from hard/soft exchange reactions.
Ayers, Parr, and Pearson recently showed that insight into the hard/soft acid/base (HSAB) principle could be obtained by analyzing the energy of reactions in hard/soft exchange reactions, i.e., reactions in which a soft acid replaces a hard acid or a soft base replaces a hard base [J. Chem. Phys., 2006, 124, 194107]. We show, in accord with the maximum hardness principle, that the hardness increases for favorable hard/soft exchange reactions and decreases when the HSAB principle indicates that hard/soft exchange reactions are unfavorable. This extends the previous work of the authors, which treated only the "double hard/soft exchange" reaction [P. K. Chattaraj and P. W. Ayers, J. Chem. Phys., 2005, 123, 086101]. We also discuss two different approaches to computing the hardness of molecules from the hardness of the composing fragments, and explain how the results differ. In the present context, it seems that the arithmetic mean of fragment softnesses is the preferable definition.


Beta-thalassemia in association with a new delta-chain hemoglobin variant [delta116(g18)Arg-->Leu]: implications for carrier screening and prenatal diagnosis.
We describe a complicated genetic counseling and prenatal diagnostic case involving an East Indian couple that had lost two consecutive pregnancies. Hemoglobinopathy screening was conducted to investigate the possibility of Hb Bart's hydrops fetalis or Hb H hydrops fetalis. The initial work-up indicated that alpha-thalassemia was not a contributing factor, with both parents being carriers of single gene deletions (-alpha(3.7)/alphaalpha). However, the Hb electrophoresis results indicated that the couple might be at risk for having children with Hb E/Hb Lepore disease. Subsequent DNA testing demonstrated that the father carried the Hb E mutation, but failed to confirm that the mother carries the Hb Lepore deletion. Sequence analysis revealed that the mother was heterozygous for a common East Indian beta(0)-thalassemia mutation, yet had a normal level of Hb A(2). The mother also carried a previously unreported missense mutation of the delta-globin gene, in cis with the beta(0)-thalassemia mutation, which gave rise to the minor Hb variant originally misidentified as Hb Lepore. This case illustrates the importance of comprehensive molecular analyses for accurate assessment of genetic risks for hemoglobinopathy syndromes.


The unsuitability of the uridine incorporation assay for the measurement of phagocytosis of Escherichia coli.
The uridine incorporation technique for assaying phagocytosis is based on the fact that polymorphonuclear leucocytes are impermeable to labelled uridine, and therefore ingested bacteria inside phagocytic vacuoles will be unable to take it up. Extracellular bacteria, including those adherent to the phagocytic cell surface, can do so however. Differences in uptake between bacteria alone and in the presence of phagocytic cells can be used to measure ingestion. The present paper describes the application of this technique to Escherichia coli O-86 as the test organism. It appears that with this test species, the method is unsuccessful, because exposure of the non-ingested bacteria to some soluble product of the triggered polymorphonuclear leucocytes causes a large increase in their uridine uptake rates, over that of the control bacteria. The nature of the product responsible is unknown. It is unconnected with change in the pH of the medium, is heat stable, and is only produced by polymorphonuclear leucocytes which are actively phagocytosing. It may be that a release of phagolysosome contents is responsible.


Teambuilding and leadership training in an internal medicine residency training program.
The purpose of this report is to describe and evaluate the impact of a 1-day retreat focused on developing leadership skills and teambuilding among postgraduate year 1 residents in an internal medicine residency. A group of organizers, including members of the staff, the chief medical residents, administrative individuals in the residency office, and an internal organizational development consultant convened to organize an off-site retreat with activities that would provide experiential learning regarding teamwork and leadership, including a "reef survival exercise" and table discussions regarding the characteristics of ideal leaders. In addition, several energizing activities and recreational free time was provided to enhance the interaction and teamwork dimensions of the retreat. To evaluate the impact of the retreat, attendees completed baseline and follow-up questionnaires regarding their experience of the retreat. Attendees universally regarded the retreat as having value for them. Comparison of baseline to postretreat responses indicated that attendees felt that the retreat enhanced their abilities to be better physicians, resident supervisors, and leaders. Follow-up responses indicated significant increases in attendees' agreement that good leaders challenge the process, make decisions based on shared visions, allow others to act, recognize individual contributions, and serve as good role models. Results on the survival exercise indicated a high frequency with which team-based decisions surpassed individual members' decisions, highlighting the importance and value of teamwork to attendees. Our main findings were that: participants universally found this 1-day retreat beneficial in helping to develop teamwork and leadership skills and the experiential learning aspects of the retreat were more especially highly rated and highlighted the advantages of teamwork. In the context that this 1-day retreat was deemed useful by faculty and residents alike, further study is needed to assess the impact of this learning on actual clinical practice and the durability of these lessons.


Light-induced division and genomic synchrony in phototrophically growing cultures of Rhodopseudomonas sphaeroides.
An experimental procedure for rapidly obtaining cell populations of phototrophically growing Rhodopseudomonas sphaeroides which display division and genomic synchrony has been developed. The basis of the procedure resides with the normal physiological response displayed by cells of R. sphaeroides that have been subjected to an immediate decrease in incident light intensity. After an abrupt high- to low-light transition of an asynchronously dividing cell population, an immediate cessation of increases in culture turbidity, total cell number, and net accumulations of culture deoxyribonucleic acid and phospholipid occurs. Total cell number remains constant for 2.5 h after the transition to low light, after which time, it undergoes a sharp increase. Reinitiation of high-light conditions of growth 1 h subsequent to this increase in total cell number results in a cell population possessing a high degree of division and genomic synchrony. A characterization of this procedure, together with a demonstration of its utility for studies on intracytoplasmic membrane assembly, is presented.


Restoring Colistin Sensitivity and Combating Biofilm Formation: Synergistic Effects of Colistin and Usnic Acid against Colistin-Resistant Enterobacteriaceae.
Colistin (COL), the last line of defense in clinical medicine, is an important therapeutic option against multidrug-resistant Gram-negative bacteria. In this context, the emergence of colistin-resistant (COL-R) bacteria mediated by broad-spectrum efflux pumps, mobile genetic elements, and biofilm formation poses a significant public health concern. In response to this challenge, a novel approach of combining COL with usnic acid (UA) has been proposed in this study. UA is a secondary metabolite derived from lichens and is well-known for its anti-inflammatory properties. This study aimed to investigate the synergistic effects of UA and COL against COL-R Enterobacteriaceae both in vitro and in vivo. The exceptional synergistic antibacterial activity exhibited by the combination of COL and UA was demonstrated by performing a comprehensive set of assays, including the checkerboard assay, time-dependent killing assay, and Live/Dead bacterial cell viability assay. Furthermore, crystal violet staining and scanning electron microscopy assays revealed the inhibitory effect of this combination on the biofilm formation. Mechanistically, the combination of UA and COL exacerbated cell membrane rupture, induced DNA damage, and generated a significant amount of reactive oxygen species, which ultimately resulted in bacterial cell death. In addition, erythrocyte hemolysis and cell viability tests confirmed the biocompatibility of the combination. The evaluation of the COL/UA combination in vivo using Galleria mellonella larvae and a mouse infection model showed a significant improvement in the survival rate of the infected larvae as well as a reduction in the bacterial load in the mouse thigh muscle. These findings, for the first time, provide strong evidence for the potential application of COL/UA as an effective alternative therapeutic option to combat infections caused by COL-R Enterobacteriaceae strains.


The effects of morphine and nalorphine-like drugs in the nondependent, morphine-dependent and cyclazocine-dependent chronic spinal dog.
A series of morphine-like and nalorphine-like drugs were studied in the nondependent, morphine-dependent and cyclazocine-dependent chronic spinal dog. In the nondependent dog, three profiles of activity were found which could be utilized to distinguish between morphine, WIN 35, 197-2 and cyclazocine. Propiram, a prototypic partial agonist of the morphine type, produced morphine-like effects in nondependent dogs and both precipitated and suppressed abstinence in cyclazocine-dependent dogs as was needed to precipitate abstinence in morphine-dependent dogs. WIN 35, 197-2, a strong agonist in the guinea-pig ileum which has been shown to be resistant to antagonism by naloxone, neither precipitated nor suppressed morphine abstinence but suppressed cyclazocine abstinence. In the nondependent dog, it depressed the flexor reflex but not skin twitch reflex. Cyclazocine altered reflex activity much like WIN 35, 197-2 but produced tachycardia, tachypnea, mydriasis and canine delirum. The morphine and cyclazocine precipitated and withdrawal abstinence syndromes were qualitatively different. Twenty times as much naltrexone was needed to precipitate abstinence in morphine-dependent dogs. Nalorphine both precipitated and suppressed cyclazocine abstinence and appeared to be a partial agonist of the nalorphine-type. Morphine suppressed the cyclazocine abstinence syndrome. Cross-tolerance was not observed in ketocyclazocine-dependent dogs. These data are consistent with the hypothesis that there are strong and partial agonists of the mu and kappa types, and further, that physical dependence on morphine and cyclazocine is mediated through different receptors. WIN 35, 197-2 appears to be a pure strong agonist of the kappa type. Cyclazocine is a mu antagonist and mixed kappa and sigma agonist.


In situ RT-PCR detection of Epstein-Barr virus immediate-early transcripts in CD4+ and CD8+ T lymphocytes.
AIDS-related Epstein-Barr virus (EBV)-associated T cell lymphomas are emerging as a new, distinct histopathological entity. The pathway whereby EBV infects T cells as well as the initial EBV transcriptional program in T cells has not been established. In order to shed light on the early events of the EBV infection of T cells, we have used in situ reverse transcription based polymerase chain reaction (RT-PCR) to study the initial EBV transcriptional program in homogeneous CD4+ and CD8+ lymphocytes. Following EBV infection, Epstein-Barr nuclear antigen (EBNA) expression could be detected in T rosetting CD4+ and CD8+ T lymphocytes. Only a few cells showed viral capsid antigen (VCA). EBV immediate-early gene transcripts (BZLF1, BRLF1, and BMLF1) encoded in the BamHI Z, R, and M fragments could be detected by in situ RT-PCR in the EBV producer cell line B95.8. Both BZLF1 and BRLF1 immediate-early transcripts, but not BMLF1 transcript, could be detected in individual CD4+ and CD8+ T cells infected with EBV. Demonstration of EBV mRNA transcripts encoding immediate-early transcriptional transactivators in EBV-infected T cells provides the first evidence for a possible mechanism whereby EBV could contribute to T cell proliferation and EBV-associated T cell malignancies.


Assessment of Thiel-Embalmed Cadavers as a Teaching Tool for Oral Anatomy and Local Anesthesia.
The aim of this study was to determine whether Thiel-embalmed cadavers would provide a useful anatomy teaching tool for topics that cannot be approached using formalin-fixed cadavers such as oral cavity examination and maxillary anesthesia. The suitability of Thiel-embalmed bodies for performing oral examinations was assessed by asking first-year dental and dental hygiene students at a dental school in Ireland to identify oral structures on a classmate and on a Thiel-embalmed body. The study was conducted in 2016. The ease of location was compared in the two settings, and their quality was assessed on the cadavers. The suitability of Thiel-embalmed cadavers to teach maxillary anesthesia was assessed by students' performing mock injections at five adjacent sites daily for five consecutive days, followed by inspection of the gingival surface by experienced anatomists and dentists. Data were obtained from 57 students, but only the 54 forms that were fully completed were analyzed, for an overall response rate of 85.7%. The results showed that most oral structures were more difficult to locate on cadavers. The texture and appearance of features in the cadavers were rated at a midpoint between realistic and unrealistic. The relative inexperience of the participants, the accumulation of fixative in the oral cavity, and discoloration were mentioned as potential confounding factors. Visual analysis of images obtained following repeated injections revealed no deterioration of the tissue. Importantly, the puncture marks appeared to reduce over time, suggesting that the gingival tissue maintains some elasticity following Thiel fixation. These findings suggest that Thiel-embalmed cadavers may be a useful tool to provide students more time to localize and study aspects of the oral cavity. Likewise, the recoiling capacity of gingival tissue suggests that Thiel-embalmed cadavers may provide an ideal tool for teaching injection technique of local anesthetics.


Effects of flavonoids from Semen Cuscutae on the reproductive system in male rats.
To evaluate the effects of the flavonoids extracted from the Semen Cuscutae (FSC) on the reproductive and endocrine functions in male rats. (1) FSC were obtained from the semen of Cuscuta sinensis Lam through solvent extraction and polyamide columnar chromatography; (2) Effect of FSC on the reproductive organs was assessed in immature rats. Rats were administered FSC through gastric gavage at a dose of 300 mg/kg per day for 7 days and the weights of testis, epididymis, seminal vesicle and pituitary gland were then observed; (3) To observe the effect of FSC on the reproductive endocrine function: same dose level of FSC was given to male rats of different age groups for 7 days; on day 8, the plasma testosterone (T), estradiol (E2) and LH were determined by RIA, the specific binding of LH was estimated and the testes were weighed. (4) Effect of FSC on LH secretion was assessed in vitro on cultured adenohypophysis. (5) Effect of FSC on T secretion was assessed in vitro on Leydig cell culture. FSC increased the weights of testis, epididymis and pituitary gland, and stimulated T and LH secretion both in vitro and in immature rats. FSC invigorates the reproductive system and reproductive endocrine function in male rats.


RNA Expression Profiling Reveals Differentially Regulated Growth Factor and Receptor Expression in Redirected Cancer Cells.
Tumorigenic cells can be redirected to adopt a normal phenotype when transplanted into cleared mammary fat pads of juvenile female mice in specific ratios with normal epithelial cells. The redirected tumorigenic cells enter stem cell niches and provide progeny that differentiate into all mammary epithelial subtypes. We have developed an in vitro model that mimics the in vivo phenomenon. The shift in phenotype to redirection should be accomplished through a return to a normal gene expression state. To measure this shift, we interrogated the transcriptome of various in vitro model states in search for casual genes. For this study, expression of growth factors, cytokines, and their associated receptors was examined. In all, we queried 251 growth factor and cytokine-related genes. We found numerous growth factor and cytokine genes whose expression levels switched from expression levels seen in cancer cells to expression levels observed in normal cells. The comparisons of gene expression between normal mammary epithelial cells, tumor-derived cells, and redirected cancer cells have revealed insight into active and inactive growth factors and cytokines in cancer cell redirection.


Trends in anecdotal fox sightings in Tasmania accounted for by psychological factors.
There has been little evaluation of anecdotal sightings as a means to confirm new incursions of invasive species. This paper explores the potential for equivocal information communicated by the media to account for patterns of anecdotal reports. In 2001, it was widely reported that red foxes (Vulpes vulpes) had been deliberately released in the island state of Tasmania (Australia), although this claim was later revealed to be baseless. Regardless, by 2013 a total of 3153 anecdotal fox sightings had been reported by members of the public, which implied their distribution was wide. For each month in 2001-2003, we defined a monthly media index (MMI) of fox-related media coverage, an index of their relative seasonal abundance (abundance), and a factor denoting claims of fox evidence (claimed evidence) regardless of its evidentiary quality. We fitted a generalized linear model with Poisson error for monthly totals of anecdotal sightings with factors of year and claimed evidence and covariates of MMI, abundance, and hours of darkness. The collective effect of psychological factors (MMI, claimed evidence, and year) relative to biophysical factors (photoperiod and abundance) was highly significant (χ2 = 122.1, df = 6, p < 0.0001), whereas anticipated changes in abundance had no significant influence on reported sightings (p = 0.15). An annual index of fox media from 2001 to 2010 was strongly associated with the yearly tally of anecdotal sightings (p = 0.018). The odds ratio of sightings ranked as reliable by the fox eradication program in any year decreased exponentially at a rate of 0.00643 as the total number of sightings increased (p < 0.0001) and was indicative of an observer-expectancy bias. Our results suggest anecdotal sightings are highly susceptible to cognitive biases and when used to qualify and quantify species presence can contribute to flawed risk assessments.


The utility of electronic health record-based hygiene notes for chlorhexidine bathing practice evaluation.
Unreliable compliance with infection prevention procedures necessitates an analysis of contributing factors. A retrospective study explored utility of 3236 nursing hygiene notes in the electronic healthcare record system (EHR). This 2012-2013 study identified defects in the chlorhexidine (CHG) bathing practice for a hospital unit. The overall compliance with CHG bathing was 22.99%. Patients with length of stay less than 3 days, in most cases, did not have documentation for CHG bathing. Patient refusal to bathe was the most prevalent documented reason (66%) of the unsuccessful initial and repeated offers to bathe. The regular staff were statistically less successful in convincing patients to bathe. The 1455 notes produced by the regular staff (n = 10) demonstrated a significantly higher failure rate (56.08%) to execute this procedure in comparison with 1770 notes documented by the 246 temporary staff (31.19% failure rate) (P value <0.001) . This analysis yielded three main insights: lack of the CHG documentation in a large number of short admissions; inconsistent use of CHG baths; and presence of workarounds due to patient refusals to bathe. The study concluded that EHR structured and unstructured data can unlock the opportunity for identifying hidden defects and inform decision-makers about the need for change.


Poor outcome in estrogen receptor-positive breast cancers predicted by loss of plexin B1.
A common characteristic of mammary carcinomas is an inverse relationship between the estrogen receptor (ER) status and the proliferative activity of the tumor. Yet, a subset of ER-positive breast cancers is characterized by a high proliferation, suggesting malfunctions in ER responsiveness that influence the biological and therapeutic behavior of tumor cells. The expression of several ER-dependent genes seems to be dysregulated among those "uncoupled" tumors. One of those genes is plexin B1, a cell-surface receptor for the semaphorin Sema4D (CD 100). However, the biological role of plexin B1 in breast cancer is largely unknown. Expression data of plexin B1 were obtained from Affymetrix microarray analysis of n = 119 breast cancer specimens. Validation was done by quantitative real-time PCR and protein expression was evaluated by immunohistochemistry. Expression data were compared with clinical characteristics as well as follow-up data of the disease. Low plexin B1 expression levels characterize a more aggressive tumor phenotype. The expression of plexin B1 is strongly correlated with the ER status. However, even among ER-positive tumors, loss of plexin B1 is associated with an impaired prognosis of breast cancer patients in both univariate (all patients, P = 0.0062; ER positive, P = 0.0107) and multivariate analyses (all patients, P = 0.032; ER positive, P = 0.022). Immunohistochemistry reveals that the tumor cells themselves and not the endothelial cells are the major source of plexin B1 expression in the tumor. Plexin B1 acts not only as a new important prognostic but should also represent a predictive marker indicating an endocrine resistance. These data give a new insight in markers that could be involved in endocrine dysregulation of breast cancer.


Patient characteristics do not predict the individual response to antihypertensive medication: a cross-over trial.
International guidelines on hypertension management do not agree on whether patient characteristics can be used for the first choice of treatment of uncomplicated essential hypertension. We wanted to identify predictive patient characteristics to the response of two different classes of antihypertensive drugs in patients with newly diagnosed hypertension in primary care. We conducted a prospective, open label, blinded endpoint cross-over trial in 120 patients with a new diagnosis of hypertension from 10 family practices. Patients received 4 weeks of 12.5 mgr hydrochlorothiazide once daily and 4 weeks of 80 mgr valsartan once daily, each followed by a 4-week washout. The sequence of drugs was randomized. Age, sex and menopausal state were recorded at run in and 24 h ambulatory blood pressure, office blood pressure, plasma renin concentration, NT-proBNP, potassium, estimated glomerular filtration rate, urinary albumin, body mass index and waist circumference at each regimen change. The difference in systolic blood pressure response between both study drugs, calculated from mean daytime ambulatory blood pressures, was the main outcome measure. Ninety-eight patients (52% female; median age 53 years) were eligible for per-protocol-analysis. None of the studied variables were predictive for the difference in systolic blood pressure response. Individual systolic blood pressure responses ranged from an increase by 18 mmHg to a decrease of 39 mmHg. In a relevant group of primary care patients with newly diagnosed hypertension, we were unable to detect predictors of treatment response. This study rather supports the United States and European guidelines than the United Kingdom and Dutch guidelines on hypertension.


Analysis of newspaper coverage of active aging through the lens of the 2002 World Health Organization Active Ageing Report: A Policy Framework and the 2010 Toronto Charter for Physical Activity: A Global Call for Action.
As populations continue to grow older, efforts to support the process of aging well are important goals. Various synonyms are used to cover aging well, such as active aging. The World Health Organization published in 2002 the report Active Ageing: A Policy Framework that according to the call for papers, has brought active ageing to the forefront of international public health awareness. The 2010 Toronto Charter for Physical Activity: A Global Call for Action was singled out in the call for papers as a key document promoting physical activity one goal of the 2002 WHO active aging policy framework. Media are to report to the public topics of importance to them. We investigated the newspaper coverage of aging well and synonymous terms such as active aging through the lens of the 2002 WHO active aging policy framework and the 2010 Toronto Charter for Physical Activity. As sources we used the following newspapers: China Daily, The Star (Malaysia), two UK newspapers (The Guardian, The Times), a database of 300 Canadian newspapers (Canadian Newsstand) and a US newspaper (The New York Times). The study generated data answering the following four research questions: (1) how often are the 2002 WHO active aging policy framework and the 2010 Toronto Charter for Physical Activity mentioned; (2) how often is the topic of active aging and terms conveying similar content (aging well, healthy aging, natural aging and successful aging) discussed; (3) which of the issues flagged as important in the 2002 WHO active aging policy framework and the 2010 Toronto Charter for Physical Activity are covered in the newspaper coverage of active aging and synonymous terms; (4) which social groups were mentioned in the newspapers covered. The study found a total absence of mentioning of the two key documents and a low level of coverage of "active aging" and terms conveying similar content. It found further a lack of engagement with the issues raised in the two key documents and a low level of mentioning of socially disadvantages groups. We posit that reading the newspapers we covered will not expose the reader to the two key documents and the issues linked to aging well including the need to increase physical activity.


Pedicle viability as the determinant factor for conversion to free nipple graft.
Women with extremely large breasts have many complaints. Reduction mammaplasty improves shape and relieves physical symptoms and alleviates psychological complaints. Mammaplasty is a an evolving technique; no single method is ideal or suitable for all breasts. Many techniques are advocated for reduction mammaplasty, including the superior, vertical, horizontal, lateral and inferior (the most popular) pedicle techniques. Even after 60 years of development in breast reduction techniques, there are still reported incidences of nipple-areola complex (NAC) necrosis. To assess the perioperative conversion to free nipple graft to prevent the complication of nipple necrosis when pedicle viability is grossly compromised. Between January 2002 and March 2006, 66 patients (132 breasts) underwent reduction mammaplasty using the inferior pedicle technique. The patients presented with breast gigantism and required excision of more than 1000 g of breast tissue per side. The mean patient age was 34.81 years. Patients had neck, shoulder and back pain as well as psychological complaints. Data regarding sternal notch-to-nipple distances and inframammary fold-to-nipple distances were recorded preoperatively and postoperatively. The weights of the excised breast tissue from either side were recorded. Viability of the pedicle flap was carefully monitored through perioperative clinical observation of skin colour, temperature, capillary refill and bleeding characteristics, and reassessed after pedicle folding and placement inside the newly tailored skin envelope. Nonvital NAC, as evaluated by the surgeon during surgery, necessitated conversion to the free nipple graft technique. During the course of the study, two patients (four breasts; 3.03%) exhibited impending gangrene to the NAC, and perioperative conversion to the free nipple graft was performed. In these two patients, the pedicle length ranged from 23 cm to 25 cm, and breast mass reduction ranged from 1950 g to 2250 g. Perioperative conversion to a free nipple-areola graft is always a good and safe option when impending gangrene to the NAC is evident during mammaplasty by inferior pedicle technique.


Periodontal Disease and Risk of Dementia in Medicare Patients with Hepatitis C Virus.
Periodontal disease and hepatitis C virus (HCV) represent chronic infectious states that are common in elderly adults. Both conditions have independently been associated with an increased risk for dementia. Chronic infections are thought to lead to neurodegenerative changes in the central nervous system possibly by promoting a proinflammatory state. This is consistent with growing literature on the etiological role of infections in dementia. Few studies have previously evaluated the association of periodontal disease with dementia in HCV patients. To examine whether periodontal disease increases the risk of developing Alzheimer's disease and related dementias (ADRD) among HCV patients in Medicare claims data. We used Medicare claims data for HCV patients to assess the incidence rate of ADRD with and without exposure to periodontal disease between 2014 and 2017. Cox multivariate regression was used to estimate the association between periodontal disease and development of ADRD, controlling for age, gender, race, ZIP-level income and education, and medical comorbidities. Of 439,760 HCV patients, the incidence rate of ADRD was higher in patients with periodontal diseases compared to those without (10.84% versus 9.26%, p < 0.001), and those with periodontal disease developed ADRD earlier compared to those without periodontal disease (13.99 versus 21.60 months, p < 0.001). The hazard of developing ADRD was 1.35 times higher in those with periodontal disease (95% CI, 1.30 to 1.40, p < 0.001) after adjusting for all covariates, including age. Periodontal disease increased the risk of developing ADRD among HCV patients in a national Medicare claims dataset.


Development of a Donkey Grimace Scale to Recognize Pain in Donkeys (Equus asinus) Post Castration.
The objectives of this study were to establish a donkey ethogram, followed by a donkey grimace scale to be applied to donkeys pre- and post-castration and to test if there was a notable difference in scores based on observer knowledge, gender, and experience, which could reveal possible discomfort/pain. Nine healthy male adult donkeys were surgically castrated. Fifty-four photos were selected from frontal, lateral, and body views taken pre- and post-castration. Observers ranging from minimal to extensive knowledge and levels of experience based on education and hours/month spent with donkeys scored six photos/donkey on a scale of 0-2 (0 = not present, 1 = moderately present, 2 = obviously present). Scores were based on body language and facial parameters: Ears down, ears back, eye white showing, glazed look, orbital tightening, eyes round shape, nostril tension, eyes narrow shape, muzzle tension, and abnormal stance and overall perception of the animal being in pain. Level of experience and knowledge, as well as gender significantly (p < 0.001), affected observers' ability to accurately score images. The study suggests that the most significant indicators of pain in donkeys are overall appearance and abnormal body stance provided their sensitivity, specificity and accuracy values of 63.18%, 62.07%, and 62.60%, respectively.


Informative structure priors: joint learning of dynamic regulatory networks from multiple types of data.
We present a method for jointly learning dynamic models of transcriptional regulatory networks from gene expression data and transcription factor binding location data. Models are automatically learned using dynamic Bayesian network inference algorithms; joint learning is accomplished by incorporating evidence from gene expression data through the likelihood, and from transcription factor binding location data through the prior. We propose a new informative structure prior with two advantages. First, the prior incorporates evidence from location data probabilistically, allowing it to be weighed against evidence from expression data. Second, the prior takes on a factorable form that is computationally efficient when learning dynamic regulatory networks. Results obtained from both simulated and experimental data from the yeast cell cycle demonstrate that this joint learning algorithm can recover dynamic regulatory networks from multiple types of data that are more accurate than those recovered from each type of data in isolation.


Anomalous left main coronary artery: case series of different courses and literature review.
Background. Congenital anomalies of the coronary arteries are a cause of sudden cardiac death. Of the known anatomic variants, anomalous origination of a coronary artery from an opposite sinus of Valsalva (ACAOS) remains the main focus of debate. Case Series. We present three cases, all presenting to our facility within one week's time, of patients with newly discovered anomalous origination of the left coronary artery from the right sinus of Valsalva (L-ACAOS). All patients underwent cardiac computed tomography for evaluation of coronary anatomy along with other forms of functional testing. Despite the high risk nature of two of the anomalies, the patients are being treated medically without recurrence of symptoms. Summary. After review of the literature, we have found that the risk of sudden cardiac death in patients with congenital coronary anomalies, even among variants considered the highest risk, may be overestimated. In addition, the exact prevalence of coronary anomalies in the general population is currently underestimated. A national coronary artery anomaly registry based on cardiac computed tomography and invasive coronary angiography data would be helpful in advancing our understanding of these cardiac peculiarities. The true prevalence of congenital coronary anomalies and overall risk of sudden cardiac death in this population are not well known. Surgical intervention remains the mainstay of therapy in certain patients though recent investigations into the pathophysiology of these abnormalities have shown that the risk of surgery may outweigh the minimal reduction in risk of sudden cardiac death.


A review of forty-five years study of Hiroshima and Nagasaki atomic bomb survivors. Hyperparathyroidism.
An epidemiological survey on hyperparathyroidism (HPT) among A-bomb survivors in Hiroshima has been conducted since August 1986. The results are summarized based on proceedings of meetings. The survey demonstrated that the prevalence rate of HPT increased with A-bomb radiation dose. Further analysis is now under way on the relationship between HPT prevalence and radiation dose, sex and age, the results of which will be published in the near future.


Nonlinear coupling between the two oscillation modes of a dc SQUID.
We make a detailed theoretical description of the two-dimensional nature of a dc SQUID, analyzing the coupling between its two orthogonal phase oscillation modes. While it has been shown that the mode defined as "longitudinal" can be initialized, manipulated, and measured, so as to encode a quantum bit of information, the mode defined as "transverse" is usually repelled at high frequency and does not interfere in the dynamics. We show that, using typical parameters of existing devices, the transverse mode energy can be made of the order of the longitudinal one. In this regime, we can observe a strong coupling between these modes, described by a Hamiltonian providing a wide range of interesting effects, such as conditional quantum operations and entanglement. This coupling also creates an atomiclike structure for the combined two mode states, with a V-like scheme.


Transcatheter aortic valve implantation for recurrent Valsalva sinus re-dissection and severe aortic regurgitation shortly after surgery for type-A aortic dissection.
Delayed aortic regurgitation following Valsalva sinus re-dissection is a well-known complication that can occur at any time after surgery for type-A aortic dissection without root replacement. We describe a case of acute type-A dissection in an 81-year-old lady successfully treated with aortic valve resuspension and ascending aorta replacement with a 28-mm vascular graft. A month later, the patient was readmitted for worsening heart failure and a transthoracic echocardiogram showed severe aortic regurgitation secondary to non-coronary Valsalva sinus re-dissection and non-coronary aortic valve leaflet prolapse also confirmed at computed tomography scan. The patient successfully underwent a transfemoral transcatheter aortic valve implantation with a 29-mm CoreValve Evolut R and concomitant planned extracorporeal membrane oxygenation support.


Expression of phenotypes in hybrid somatic cells derived from the nervous system.
The techniques of somatic cell hybridization allow a genetic analysis of differentiated functions of mammalian cells in vitro. Clonal lines of mouse neuroblastoma cells expressing a variety of differentiated neuroectodermal functions have been fused to L cells not expressing these functions. The resulting NL hybirds, on a clonal basis, express a variety of parental and non-parental phenotypes. Some hybrid clones inherit the ability to synthesize the neurotransmitter acetylcholine (Ach) (expression of high levels of choline acetyltransferase, CAT) while others do not. The ability to synthesize Ach and the ability to degrade this neurotransmitter (high levels of acetylcholinesterase activity, AChE) appear to segregate independently in NL hybrid progeny.--When a a variety of clonal cell lines replicating in culture are fused to cells freshly derived from the embryonic nervous system, interesting phenotypes result in the hybrid progeny. Neuroblastoma x rodent nervous tissue hybrids express AChE and in a few instances have developed the ability to synthesize CAT. Transformed human fibroblasts fused to normal rodent nervous tissue yield hybrid progeny that retain human and segregate mouse chromosomes and isozymes. No expression of differentiated functions has yet been found in these latter hybrids but they are useful for mapping mouse genes.


Effect of selective ablation of proliferating mammary epithelial cells on MNU induced rat mammary tumorigenesis.
Proliferating cells within the terminal end buds of the virgin female rat mammary gland are the most susceptible to chemical carcinogen induced tumorigenesis. We hypothesized that selective ablation of proliferating cells in the mammary gland would reduce mammary tumor incidence upon carcinogen challenge. Selective ablation of proliferating cells was achieved by intraductal injections of Adv-RSV-tk and gancyclovir administration. Despite efficient viral transduction of the thymidine kinase protein and the apparent elimination of >90% of the proliferating cells, the rats exhibited a higher incidence of MNU induced mammary tumors arising with shorter latency as compared to control animals. Several possible explanations of the puzzling relationship between elimination of cycling cells and increased tumor incidence are discussed and alternative strategies for the prevention of breast cancer are proposed.


Ultrasound indoor positioning system based on a low-power wireless sensor network providing sub-centimeter accuracy.
This paper describes the TELIAMADE system, a new indoor positioning system based on time-of-flight (TOF) of ultrasonic signal to estimate the distance between a receiver node and a transmitter node. TELIAMADE system consists of a set of wireless nodes equipped with a radio module for communication and a module for the transmission and reception of ultrasound. The access to the ultrasonic channel is managed by applying a synchronization algorithm based on a time-division multiplexing (TDMA) scheme. The ultrasonic signal is transmitted using a carrier frequency of 40 kHz and the TOF measurement is estimated by applying a quadrature detector to the signal obtained at the A/D converter output. Low sampling frequencies of 17.78 kHz or even 12.31 kHz are possible using quadrature sampling in order to optimize memory requirements and to reduce the computational cost in signal processing. The distance is calculated from the TOF taking into account the speed of sound. An excellent accuracy in the estimation of the TOF is achieved using parabolic interpolation to detect of maximum of the signal envelope at the matched filter output. The signal phase information is also used for enhancing the TOF measurement accuracy. Experimental results show a root mean square error (rmse) less than 2 mm and a standard deviation less than 0.3 mm for pseudorange measurements in the range of distances between 2 and 6 m. The system location accuracy is also evaluated by applying multilateration. A sub-centimeter location accuracy is achieved with an average rmse of 9.6 mm.


Failure to release iron from transferrin in a Chinese hamster ovary cell mutant pleiotropically defective in endocytosis.
A Chinese hamster ovary cell mutant defective in the receptor-mediated endocytosis of several unrelated ligands (Robbins, A. R., S. S. Peng, and J. L. Marshall, 1983, J. Cell Biol., 96:1064-1071) failed to accumulate iron provided in the form of diferric transferrin. Analysis of the steps of the transferrin cycle indicated that binding and internalization of transferrin proceeded normally in mutant cells. However, the mutant appeared unable to dissociate iron from transferrin, as evidenced by release of diferric transferrin from the mutant versus apotransferrin from the parent. Uptake of ferric ions from the growth medium was enhanced in the mutant.


[Anesthesiologic support of videothorascopic operations in children with pleural empyema].
Total anesthesia for videothoracoscopic operations in children with pleural empyema is difficult because of severe clinical status and single-lung ventilation. Hemodynamics, blood gases, and oxygen transport were studied in 35 children aged 1.5-14 years with ASA class II-III. Total anesthesia with diprivan (propofol) in combination with fentanyl and myorelaxant mivacurium was used. The modes of single-lung ventilation depended on bronchial intubation type.


Determinants of life satisfaction among migrants in South Africa: an analysis of the GCRO's quality of life survey (2009-2021).
Migrant populations in any country are a vulnerable group, and psycho-demographic research measuring life satisfaction has been used to assess migrants' well-being in developed and developing countries. However, South Africa, with its high influx of migrant populations, has investigated these topical concerns from the perspective of xenophobia, with mixed findings. However, no, or very few studies have examined life satisfaction among migrants in South Africa. This study, therefore, extends previous literature by examining the determinants of life satisfaction among South Africa's internal and international migrant populations. We conducted a cross-sectional study from the 2009 to 2021 Gauteng City-Region Observatory (GCRO) Quality of Life (QoL) surveys among migrant populations in two ways: a full sample and a gender-stratified sample. A sample of male and female migrants ranging from 15 to 49 years of age were recruited into this study. Cantril's Self-Anchoring Ladder Life Satisfaction scale captured their life satisfaction alongside relevant social demographic factors. Descriptive statistics were applied for the data analysis of the demographic factors. Bivariate and multivariate logistics regression analyses were conducted to assess the associations and the predictive factors of life satisfaction among migrants, both internal and international. The key findings were the gender distribution of life satisfaction, showing that more international (male - 66.0% and female - 67.1%) migrants reported having a thriving life satisfaction than internal migrants (male - 61.7% and female - 61.5%). Findings from the Pearson correlation coefficient revealed a significant association between the individual, household, and community factors by migrant status (ρ < 0.05). However, the probit coefficients revealed that individual factors (age 48+: AOR = 2.18, 95% CI: 1.13, 3.23, and secondary/higher education: AOR = 1.1., 95% CI: 0.01, 1.19) and household factors (two persons living in households (H/H): AOR = 1.05, 95% CI: 0.50, 1.10), and community factors (international migrant status: AOR = 2.12, 95% CI: 0.08, 2.16) significantly increase the prediction of higher odds of life satisfaction by gender among migrants. The ordered logit coefficients also showed that individual factors (middle and high income and having health insurance) and household factors (receiving SASSA social grant) predicted the highest life satisfaction among migrants (internal and international). We found substantial evidence that individual-, household-, and community-level factors were associated with life satisfaction among migrants. In particular, the pattern of life satisfaction varied slightly between male and female migrants, as well as with migrant status in South Africa. These findings collectively may provide helpful information for policymakers and practitioners to optimise interventions for migrant populations to improve their life satisfaction. Evidence from this study also calls on the government of South Africa to begin tracking the life satisfaction of its nationals, whether migrants or not.


Numbers and functional lateralization: A visual half-field and dichotic listening study in proficient bilinguals.
Potential links between language and numbers and the laterality of symbolic number representations in the brain are still debated. Furthermore, reports on bilingual individuals indicate that the language-number interrelationships might be quite complex. Therefore, we carried out a visual half-field (VHF) and dichotic listening (DL) study with action words and different forms of symbolic numbers used as stimuli to test the laterality of word and number processing in single-, dual-language and mixed -task and language- contexts. Experiment 1 (VHF) showed a significant right visual field/left hemispheric advantage in response accuracy for action word, as compared to any form of symbolic number processing. Experiment 2 (DL) revealed a substantially reversed effect - a significant right ear/left hemisphere advantage for arithmetic operations as compared to action word processing, and in response times in single- and dual-language contexts for number vs. action words. All these effects were language independent. Notably, for within-task response accuracy compared across modalities significant differences were found in all studied contexts. Thus, our results go counter to findings showing that action-relevant concepts and words, as well as number words are represented/processed primarily in the left hemisphere. Instead, we found that in the auditory context, following substantial engagement of working memory (here: by arithmetic operations), there is a subsequent functional reorganization of processing single stimuli, whether verbs or numbers. This reorganization - their weakened laterality - at least for response accuracy is not exclusive to processing of numbers, but the number of items to be processed. For response times, except for unpredictable tasks in mixed contexts, the "number problem" is more apparent. These outcomes are highly relevant to difficulties that simultaneous translators encounter when dealing with lengthy auditory material in which single items such as number words (and possibly other types of key words) need to be emphasized. Our results may also shed a new light on the "mathematical savant problem".


Effects of indomethacin on plasma renin activity in the conscious rat.
The role of prostaglandins in the control of renin release in vivo was evaluated in the conscious rat. Indomethacin suppressed urinary prostaglandin E2 (PGE2) excretion from 5.3 +/- 0.5 to 2.6 +/- 0.5 ng/3 h (P less than 0.001). Basal plasma renin activity (PRA) fell from 6.20 +/- 1.07 to 2.98 +/- 0.45 ng . ml-1 . h-1 (P less than 0.02). Indomethacin suppressed PRA stimulated by furosemide, insulin-induced hypoglycemia, hydralazine, isoproterenol, arachidonic acid, and sodium-free diet, whereas PRA stimulated by PGE2 was not suppressed by indomethacin. The suppression of PRA by indomethacin in the sodium-deplete state rules out sodium retention as the mechanism of action of indomethacin. These results indicate that inhibition of prostaglandin synthesis by indomethacin partially blocks the renin response to several of the known stimulators, suggesting that prostaglandins may play a pivotal role in the control of renin release.


Nitrate leaching in an Andisol treated with different types of fertilizers.
Nitrate (NO3) leaching was studied in an Andisol treated with four N fertilizers (SC: swine compost, CU: coated urea, AN: ammonium N, or NF: no fertilizer) for 7 years. Sweet corn (Zea mays L.) was grown in summer, followed by Chinese cabbage (Brassica rapa L. var. amplexicaulis) or cabbage (Brassica oleracea L. var. capitata) in autumn each year. In chemical fertilizer plots treated with AN or CU, NO(3)-N concentrations in soil water at 1-m depth increased markedly in the summer of the second year and fluctuated between 30 and 60 mg l(-1). In the SC plot, NO(3)-N concentration started increasing in the fourth year, reaching the same level as in the AN and CU plots in the late period of the experiment. In the NF plot, NO(3)-N concentration was about 10 mg l(-1) for the first 4 years and decreased to 5 mg l(-1). The potential NO(3)-N concentrations by an N and water balance equation satisfactorily predicted NO(3)-N concentration in the AN and CU plots, but substantially overestimated that in the SC plot, presumably because a large portion of N from SC first accumulated in soil in the organic form. Our results indicate that, under the Japanese climate (Asian monsoon), excessive N from chemical fertilizers applied to Andisols can cause substantial NO3 leaching, while compost application is promising to establish high yields and low N leaching during a few years but would cause the same level of NO3 leaching as in chemically fertilized plots over longer periods.


Urticarial eruption associated with rheumatic fever in a child.
The classic description of erythema marginatum is of a few asymptomatic erythematous patches or plaques with a characteristic central clearing which may coalesce and develop a polycyclic configuration. We report a boy with a urticarial eruption without the classic lesions of erythema marginatum in whom the diagnosis of rheumatic fever was subsequently made. Histology of the urticarial lesions revealed a mixed, superficial, perivascular infiltrate with prominent eosinophils. Rheumatic fever should be considered in children with fever and urticaria-like eruptions even in the absence of the classically described erythema marginatum.


Digital Subtraction Angiography Image Features under the Deep Learning Algorithm in Cardiovascular Interventional Treatment and Nursing for Vascular Restenosis.
The objective of this study was to explore the application value of digital subtraction angiography (DSA) images optimized by deep learning algorithms in vascular restenosis patients undergoing cardiovascular intervention and their nursing efficacy. In this study, a network model for removing artifacts was constructed based on a deep algorithm. 60 patients with coronary artery restenosis were selected as the research objects, and they were randomly divided into the CTA group guided by CT angiography (CTA) and digital subtraction angiography (DSA) group, with 30 cases in each group. The antiartifact network model constructed based on the depth algorithm was applied to the images of CTA and DSA for experiments. After cardiovascular intervention and clinical pathway nursing intervention, it was found that the diameter stenosis rate in the DSA group decreased from 65.82 ± 12.9% to 4.7 ± 1.3%, and the area stenosis rate decreased from 88.4 ± 14.3% to 5.4 ± 1.7%. During the follow-up period of 3-24 months, 3 out of 46 lesions in the DSA group showed restenosis, so the restenosis rate was 6.5%, which was significantly lower than the 18.4% in the CTA group (P < 0.05). In the DSA group, there was 1 case of bleeding, 0 case of hematoma, 2 cases of urinary retention, and 0 case of hypotension, so the total incidence of adverse reactions was 10%, which was significantly lower than the 30% of the CTA group (P < 0.05). The high-sensitivity C-reactive protein (hs-CRP) levels of the two groups of patients were 3.58 ± 2.02 mg/L and 4.36 ± 3.11 mg/L before surgery and 3.49 ± 2.18 mg/L and 4.57 ± 3.4 mg/L after the surgery. The postoperative hs-CRP level in the CTA group was slightly lower than that before the surgery and the postoperative hs-CRP level in the DSA group was slightly higher than that before the surgery, but they were not statistically significant (P > 0.05). The hs-CRP level of the DSA group before and after the surgery was slightly higher than that of the CTA group, but there was no significant difference (P > 0.05). In summary, the network model based on the deep learning algorithm can remove the artifacts in DSA images and present high-quality clear images, and convolutional neural network (CNN) algorithms had a strong ability to automatically learn features in the field of medical image processing and were worthy of being widely used and popularized. In addition, the DSA-guided intervention can reduce the rate of vascular stenosis in patients, showing low probability of postoperative restenosis and adverse reactions and a good clinical effect.


Alcoholism and alleles of the human D2 dopamine receptor locus. Studies of association and linkage.
The association of the A1 allele of the D2 dopamine receptor gene with alcoholism was examined by comparing 32 unrelated white alcoholics with 25 unrelated white controls and by analysis of 17 nuclear families in multigenerational pedigrees of alcoholics in whom the A1 allele was segregating. All subjects had structured psychiatric interviews. Clinical assessment and genotyping were carried out independently. Thirteen (41%) of the 32 alcoholics carried the A1 allele compared with three (12%) of the 25 controls. The association with the A1 allele was significant when controls were compared with a subset of 10 alcoholics with severe medical problems (60% vs 12%), but not less severe cases. However, regardless of clinical severity or subtype, there was no evidence of linkage or cosegregation of the A1 allele and increased susceptibility to alcoholism in informative pedigrees. The possible association in the general population without linkage in families may be explained either by chance variation in our small samples or a modifying effect of the A1 allele that increases severity. Further study of the role of the D2 receptor gene in alcoholism is warranted.


The cause of birth is associated with neonatal prognosis in late preterm singletons.
Recent studies have shown that the cause of very preterm births may be related to neonatal morbidity and mortality. Even though these risks are lower among late preterm births, this group accounts for the vast majority of all preterm births. The objective of this study was to evaluate the relation of neonatal morbidity and mortality to the cause of late preterm birth. This retrospective observational cohort study included all women who gave birth to liveborn singletons from 34 to 36 weeks+6 days of gestation in a French level III maternity hospital in the 5-year period 2013-2017. The causes of preterm delivery were divided into 6 mutually exclusive groups. The main outcome was a composite neonatal morbidity criterion, defined by at least one among the following criteria: neonatal respiratory distress, neurological complications, neonatal sepsis, severe necrotizing enterocolitis, and neonatal hypoglycemia. We analyzed the association between cause of preterm delivery and neonatal morbidity after adjustment for gestational age and antenatal corticosteroid therapy. The reference group was preterm labor, defined by spontaneous preterm labor with intact membranes. During the study period, there were a total of 27 110 births, including 1114 singleton births at 34 to 36 weeks of gestation + 6 days (4.1%). Among the 968 late preterm births included, the risk of neonatal morbidity in the group with preterm premature rupture of membranes (PPROM) was similar to that in the preterm labor (reference) group: adjusted odds ratio (aOR) 1.2 (95% CI, 0.8-1.8). All the other causes of late preterm birth were associated with a higher risk of neonatal morbidity than the reference group: aOR 2.0 [95% CI, 1.1-3.5] for hypertensive disorders without suspected fetal growth restriction (FGR) (9.1% of cases), aOR 2.4 [95% CI, 1.4-4.2] for hypertensive disorders with suspected FGR (8.9%), aOR 4.2 [95% CI, 2.2-8.0] for suspected FGR without hypertensive disorders (5.8%), and aOR 4.4 [95% CI, 2.2-8.8] for vaginal bleeding related to abnormal placental insertion (4.7%). Among infants born from 34 to 36 weeks + 6 days of gestation, PPROM and preterm labor had similar risks of neonatal morbidity, while the other causes were associated with a risk of neonatal morbidity at least twice that with preterm labor.


Transcriptional response of bathypelagic marine bacterioplankton to the Deepwater Horizon oil spill.
The Deepwater Horizon blowout released a massive amount of oil and gas into the deep ocean between April and July 2010, stimulating microbial blooms of petroleum-degrading bacteria. To understand the metabolic response of marine microorganisms, we sequenced ≈ 66 million community transcripts that revealed the identity of metabolically active microbes and their roles in petroleum consumption. Reads were assigned to reference genes from ≈ 2700 bacterial and archaeal taxa, but most assignments (39%) were to just six genomes representing predominantly methane- and petroleum-degrading Gammaproteobacteria. Specific pathways for the degradation of alkanes, aromatic compounds and methane emerged from the metatranscriptomes, with some transcripts assigned to methane monooxygenases representing highly divergent homologs that may degrade either methane or short alkanes. The microbial community in the plume was less taxonomically and functionally diverse than the unexposed community below the plume; this was due primarily to decreased species evenness resulting from Gammaproteobacteria blooms. Surprisingly, a number of taxa (related to SAR11, Nitrosopumilus and Bacteroides, among others) contributed equal numbers of transcripts per liter in both the unexposed and plume samples, suggesting that some groups were unaffected by the petroleum inputs and blooms of degrader taxa, and may be important for re-establishing the pre-spill microbial community structure.


LATE CHOROIDAL NEOVASCULAR COMPLICATIONS IN A PATIENT TREATED FOR RETINOBLASTOMA. A CASE REPORT.
Case report of choroidal neovascularization (CNV) detection in patient who was treated for bilateral retinoblastoma in early childhood. Patient at 1.5 years of age treated for endophytic retinoblastoma stage 4 (according to the Reese-Ellsworth classification) bilaterally, with a positive mutation in the Rb1 gene. After undergoing bilateral retinal laser treatment and 6 cycles of systemic chemotherapy, the tumor remained inactive without other complications. At the age of 14, the boy developed visual impairment in his left eye with metamorphosis. Based on a local finding and other auxiliary examinations, he was diagnosed with CNV in the macular area at the interface of the tumor scar and the healthy retina of the left eye. After three applications of anti-VEGF (antibodies blocking vascular endothelial growth factor) substance intravitreally (bevacizumab 1.2 mg), there was a reduction in CNV and also an improvement in visual function.


Immunomagnetic selection of purified monocyte and lymphocyte populations from peripheral blood mononuclear cells following cryopreservation.
Cryopreservation is a method commonly used to store human blood samples. We sought to determine if cryopreserved peripheral blood mononuclear cells (PBMC) could be separated effectively into distinct populations by using monoclonal antibodies and immunomagnetic microspheres. PBMC obtained from healthy blood donors and from human immunodeficiency virus-infected subjects were cryopreserved for as long as 18 months. Recovered cells were separated into CD14+ monocytes and CD4+ T-cell subsets by immunomagnetic selection. Flow cytometry analysis indicated >95% depletion of monocytes from PBMC following immunomagnetic selection with anti-CD14. A highly enriched population of CD4+ T cells was obtained from the CD14-depleted cell fraction by using an anti-CD4 monoclonal antibody and detachable immunomagnetic beads. The CD4+ T cells were subsequently separated into CD4+ CD45RO and CD4+ CD45RA fractions. Each fraction contained >90% enrichment for the respective subpopulation and <5% of the reciprocal subpopulation. No significant differences in cell surface expression of leukocyte markers, in efficiency of selection of PBMC subpopulations, or in mitogen-induced proliferation were detected in freshly isolated or cryopreserved cells. Efficient recovery of cryopreserved specimens means that targeted assays can be performed on selected, prospectively stored samples once clinical endpoints have been achieved.


Influence of isoflurane on ischaemic heart disease in patients with coronary steal prone anatomy.
It is postulated that patients with ischaemic heart disease (IHD) and coronary steal prone anatomy (CSPA) may develop myocardial ischaemia under isoflurane anaesthesia. This study was conducted in 50 patients undergoing coronary artery bypass grafting. Among these 10 patients (20%) had CSPA, as evidenced by coronary angiography. Anaesthesia was induced with fentanyl, midazolam and thiopentone and maintained with isoflurane in oxygen after endotracheal intubation. Patients were continuously monitored with automated ST segment analysis of electrocardiogram (ECG) and transoesophageal echocardiography (TEE). The end-tidal concentration of isoflurane was maintained at 1.2%, which is equal to one minimum alveolar concentration. Haemodynamic parameters were maintained within 20% of baseline values with either the use of phenylephrine or increasing the depth of anaesthesia by using midazolam and fentanyl. ST changes were measured after 80 ms of J-point in ECG and TEE monitored for occurrence of new regional wall motion abnormalities during the study period. ST changes more than +/-1.0 mm were considered as an indication of myocardial ischaemia. Out of 10 patients having CSPA, 50% developed significant ECG changes during isoflurane anaesthesia at an endtidal concentration of 1.2%. In patients not having CSPA new ischaemia was not observed. Our study indicates necessity of close monitoring of patients with IHD and CSPA during isoflurane anaesthesia to identify new ischaemia and institute appropriate measures.


Huge inflammatory myofibroblastic tumor of pleura with concomitant nuchal fibroma.
Inflammatory myofibroblastic tumor (IMT) is a rare benign neoplasm. It is a challenging disease because the symptoms and radiologic findings are diverse and nonspecific. Although pulmonary IMT is the most common form, pleural origin is an extremely rare clinical entity. Nuchal fibroma (NF) is another rare benign neoplasm. We report herein a case of pleural IMT with concomitant NF in a 15-year-old girl. To the best of our knowledge, this is the first report suggesting an association between IMT and NF, and our case had the largest reported intrathoracic IMT. Moreover, we found a possible association between IMT and increased CA-125 levels.


Unilateral lung edema: effects on pulmonary gas exchange, hemodynamics, and pulmonary perfusion distribution.
Two types of unilateral lung edema in sheep were characterized regarding their effects on pulmonary gas exchange, hemodynamics, and distribution of pulmonary perfusion. One edema type was induced with aerosolized HCl (0.15 M, pH 1.0) and the other with NaCl (0.15 M, pH 7.4). Both aerosols were nebulized continuously for 4 h into left lungs. In HCl-treated animals, pulmonary gas exchange deteriorated [from a partial arterial O(2) pressure-to-inspired O(2) fraction ratio (Pa(O(2))/FI(O(2))) of 254 at baseline to 187 after 4 h HCl]. In addition, pulmonary artery pressure and total pulmonary vascular resistance increased (from 16 to 19 mmHg and from 133 to 154 dyn. s. cm(-5), respectively). In NaCl-treated animals, only the central venous pressure significantly increased (from 7 to 9 mmHg). Distribution of pulmonary perfusion (measured with fluorescent microspheres) changed differently in both groups. After HCl application, 6% more blood flow was directed to the treated lung, whereas, after NaCl, 5% more blood flow was directed to the untreated lung. HCl and NaCl treatment both induce an equivalent lung edema, but only HCl treatment is associated with gas exchange alteration and tissue damage. Redistribution of pulmonary perfusion maintains gas exchange during NaCl treatment and decreases it during HCl inhalation.


Bell's palsy associated with IFN-alpha and ribavirin therapy for hepatitis C virus infection.
First-line therapy for hepatitis C virus (HCV) infection comprises interferon-alpha (IFN-alpha) and ribavirin for 6 or 12 months. Mild complications of therapy are common, but more serious complications are rare. Three patients with chronic HCV infection, acquired through injecting drug use, developed idiopathic facial paralysis (Bell's palsy) during therapy, with spontaneous resolution after withdrawal of treatment. Large-scale cohort studies reveal that IFNs are associated rarely with neurologic complications, and only one previous report has linked IFN-alpha therapy and Bell's palsy. We postulate that IFN-alpha therapy led to a breakdown of peripheral tolerance to myelin sheath antigens, leading to neuropathy, just as IFN-alpha therapy can cause autoimmune thyroiditis through breakdown of tolerance to native thyroid antigens.


Large-scale genetic perturbations reveal regulatory networks and an abundance of gene-specific repressors.
To understand regulatory systems, it would be useful to uniformly determine how different components contribute to the expression of all other genes. We therefore monitored mRNA expression genome-wide, for individual deletions of one-quarter of yeast genes, focusing on (putative) regulators. The resulting genetic perturbation signatures reflect many different properties. These include the architecture of protein complexes and pathways, identification of expression changes compatible with viability, and the varying responsiveness to genetic perturbation. The data are assembled into a genetic perturbation network that shows different connectivities for different classes of regulators. Four feed-forward loop (FFL) types are overrepresented, including incoherent type 2 FFLs that likely represent feedback. Systematic transcription factor classification shows a surprisingly high abundance of gene-specific repressors, suggesting that yeast chromatin is not as generally restrictive to transcription as is often assumed. The data set is useful for studying individual genes and for discovering properties of an entire regulatory system.


Pulmonary delivery of influenza vaccine formulations in cotton rats: site of deposition plays a minor role in the protective efficacy against clinical isolate of H1N1pdm virus.
Administration of influenza vaccines to the lungs could be an attractive alternative to conventional parenteral administration. In this study, we investigated the deposition site of pulmonary delivered liquid and powder influenza vaccine formulations and its relation to their immunogenicity and protective efficacy. In vivo deposition studies in cotton rats revealed that, the powder formulation was mainly deposited in the trachea ( ∼ 65%) whereas the liquid was homogenously distributed throughout the lungs ( ∼ 96%). In addition, only 60% of the antigen in the powder formulation was deposited in the respiratory tract with respect to the liquid formulation. Immunogenicity studies showed that pulmonary delivered liquid and powder influenza formulations induced robust systemic and mucosal immune responses (significantly higher by liquids than by powders). When challenged with a clinical isolate of homologous H1N1pdm virus, all animals pulmonary administered with placebo had detectable virus in their lungs one day post challenge. In contrast, none of the vaccinated animals had detectable lung virus titers, except for two out of eight animals from the powder immunized group. Also, pulmonary vaccinated animals showed no or little signs of infection like increase in breathing frequency or weight loss upon challenge as compared to animals from the negative control group. In conclusion, immune responses induced by liquid formulation were significantly higher than responses induced by powder formulation, but the overall protective efficacy of both formulations was comparable. Thus, pulmonary immunization is capable of inducing protective immunity and the site of antigen deposition seems to be of minor relevance in inducing protection.


The Sensitiveness and Fulfillment of Psychological Needs: Medical, Health Care and Students.
As health was defined as a state of complete physical, mental, and social well-being, and not merely an absence of disease or infirmity, the bio-psychosocial paradigm of health and illness attests that curing occurs when the science of medicine (the biomedical and pathos-physiological aspects of disease) and the art of medicine (the psychological, social, and interpersonal aspects of illness) merge into one unified holistic approach to patient care (Hojat, 2007). In this context the relationship between health care professionals and patients also become an indispensable tool in clinical situations to achieve better patient outcomes (Engel, 1990). In our pilot study in year 2009 we try to verify how are the medical students and students of health care (University of Maribor, Faculty of Medicine and Faculty of Health Care) prepared for their sensitive professional relationship in their future. Testing together 211 students (N=157 women, N=57 men), we compared the level of emotional empathy, altruistic love, values, and behaviorof 40 medical students, 118 students of health care and the group of 53 students of economics. Because of their professional choice, we expected that the medical and health care students would have higher empathy and altruism scores than the students of economics. Following the self-determination behavioral theory and its concept of autonomy support (Deci, Ryan, 2000), we anticipated also that the fulfilment of basic psychological needs could be important factor in everyday health care clinical practice. As the fulfilment of needs of autonomy, competence and relatedness could lead to increased autonomy supportive orientation in interactions with other subjects, and can be useful factor that prepare doctors or nurses for active participation in relationship with patients, we verified and compared the included groups also in this way.


Dissociable neural processes during risky decision-making in individuals with Internet-gaming disorder.
Risk-taking is purported to be central to addictive behaviors. However, for Internet gaming disorder (IGD), a condition conceptualized as a behavioral addiction, the neural processes underlying impaired decision-making (risk evaluation and outcome processing) related to gains and losses have not been systematically investigated. Forty-one males with IGD and 27 healthy comparison (HC) male participants were recruited, and the cups task was used to identify neural processes associated with gain- and loss-related risk- and outcome-processing in IGD. During risk evaluation, the IGD group, compared to the HC participants, showed weaker modulation for experienced risk within the bilateral dorsolateral prefrontal cortex (DLPFC) (t = - 4.07; t = - 3.94; PFWE < 0.05) and inferior parietal lobule (IPL) (t = - 4.08; t = - 4.08; PFWE < 0.05) for potential losses. The modulation of the left DLPFC and bilateral IPL activation were negatively related to addiction severity within the IGD group (r = - 0.55; r = - 0.61; r = - 0.51; PFWE < 0.05). During outcome processing, the IGD group presented greater responses for the experienced reward within the ventral striatum, ventromedial prefrontal cortex, and orbitofrontal cortex (OFC) (t = 5.04, PFWE < 0.05) for potential gains, as compared to HC participants. Within the IGD group, the increased reward-related activity in the right OFC was positively associated with severity of IGD (r = 0.51, PFWE < 0.05). These results provide a neurobiological foundation for decision-making deficits in individuals with IGD and suggest an imbalance between hypersensitivity for reward and weaker risk experience and self-control for loss. The findings suggest a biological mechanism for why individuals with IGD may persist in game-seeking behavior despite negative consequences, and treatment development strategies may focus on targeting these neural pathways in this population.


Simple Preoperative Patient-Reported Factors Predict Adverse Outcome After Elective Cranial Neurosurgery.
Patient-reported preoperative factors hold promise in improving the prediction of postoperative adverse events, but they have been poorly studied. To study the role of patient-reported factors in the preoperative risk stratification of elective craniotomy patients. A prospective, unselected cohort of 322 adult patients underwent elective craniotomy in Helsinki, Finland. We preoperatively recorded the American Society of Anesthesiologists (ASA) score, Helsinki ASA score, and 3 questionnaire-based patient-reported factors including overall health status, ability to climb 2 flights of stairs, and cognitive function (Test Your Memory test). Outcome measures comprised in-hospital major and overall morbidity. Receiver-operating characteristic curves served to calculate area under the curve (AUC) values for a composite score of patient-reported factors and both ASA scores with regard to outcomes. In-hospital major and overall morbidity rate was 15.2%. Only preoperatively diminished cognitive function remained a significant predictor of major morbidity after multivariable logistic regression analysis (P < .001, odds ratio 1.1, confidence interval 1.0-1.1). A composite score of our 3 patient-reported factors had a higher AUC (0.675) for major morbidity than original ASA score (0.543) or Helsinki ASA score (0.572). In elderly patients, the composite score had an AUC of 0.726 for major morbidity. Preoperative patient-reported factors had higher sensitivity for detecting major morbidity compared to the ASA scores in this study. Particularly, the simple composite score seems to predict adverse outcomes in elective cranial surgery surprisingly well, especially in the elderly. These results are interesting and worth confirming in other centers.


Optimizing antiepileptic drug treatment in tumoral epilepsy.
Between 30% and 50% of patients with brain tumors first present with a seizure, and up to 30% more will develop seizures later. Therefore, optimal management of these patients requires a rational approach to the use of antiseizure medications. Based on current evidence, prophylactic prescription of long-term antiepileptic drugs (AEDs) in patients with brain tumors in patients who did not present with seizures is not justified. Because of the high risk of recurrence, however, AED treatment should be strongly considered after a single seizure considered to be due to a tumor. Because of the lack of well-controlled randomized trials, the decision on which AED provides the best risk-benefit ratio in the individual patient is based mostly on physician's judgment rather than sound scientific evidence. In patients who may require chemotherapy, a non-enzyme-inducing AED is preferred for initial treatment to minimize the risk of drug interactions that impact adversely on the outcome of anticancer chemotherapy. Several retrospective studies in seizure patients with glioblastoma treated with chemotherapy have provided evidence for a moderately improved survival with the use of valproic acid, possibly due to inhibition of histone deacetylase. However, valproic acid may also increase the hematologic toxicity of antineoplastic drugs, presumably by inhibiting their metabolism, and may independently impair hemostasis, which is of some concern for patients who require surgical intervention. Among newer generation AEDs, levetiracetam has a number of advantageous features, including availability of a parenteral formulation, but other agents such as gabapentin, lamotrigine, oxcarbazepine, topiramate, and zonisamide may also be considered. Potentially more effective treatments targeting specific mechanisms of epileptogenesis and ictogenesis are being investigated. Resection of the tumor, radiation therapy, or chemotherapy can bring refractory seizures under control or prolong the duration of seizure freedom, an effect that does not appear to be necessarily related to removal or shrinkage of the tumor mass. In patients with a successfully treated tumor and an overall good prognosis for long-term survival, gradual discontinuation of AEDs may be considered.


Scenarios of temporal and spatial evolution of hexabromocyclododecane in the North Sea.
Spatial and temporal distribution of the flame retardant hexabromocyclododecane (HBCD) in the North Sea was examined for the period from 1995 to 2005 using a pollutant transport model FANTOM. Model calculations allow conclusions on relevant sinks and fluxes in and out of the North Sea and on the time needed to establish a steady state. Calculations were performed for two additional scenarios with different rates of primary degradation ranging from fast degrading to absolute persistency. Concentrations calculated in the scenarios with degradation are in line with the monitoring data available for HBCD. Concentrations calculated in the "persistent" scenario disagree with measured data. According to our model calculations, steady state is established within months for the water and the top layer sediment with no evidence for a temporal trend, except for the "persistent" scenario, in which concentrations increase continuously in the southeastern part of the North Sea, where hydrographic and circulation characteristics produce areas of converging currents. Our model study enables a better understanding of the fate of HBCD in the North Sea, its potential for transport and overall elimination. We discuss these findings in the light of different concerns for PBT substances.


Immunologic competence of thoracic duct cells. I. Delayed hypersensitivity.
Delayed hypersensitivity was produced in donor Lewis rats by sensitization with soluble protein antigens emulsified in complete Freund's adjuvant. Cells of their thoracic duct lymph were collected for varying periods of time and transferred intravenously to isogenic Lewis recipients. With this model the following conclusions were reached: 1. Delayed hypersensitivity was transferred by thoracic duct cells. 2. The longer the drainage of the thoracic duct, the fewer cells were needed to achieve a successful transfer. With continuing drainage the proportion of small lymphocytes decreased and large cells increased. There was, therefore, a better correlation between successful transfer of delayed hypersensitivity and the number of large cells transfused than between positive skin reactions and transfer of small lymphocytes. 3. Prolonged fistula of the thoracic duct did not diminish the skin reaction of sensitized donors to specific antigen. 4. Delayed hypersensitivity was elicited in recipients 3 wk after transfer of sensitized cells. There was evidence that delayed hypersensitivity was enhanced in recipients, possibly because of prior skin testing. 5. Total body X-irradiation abolished the lesions of passively transferred delayed hypersensitivity. Recovery of positive skin tests was observed 19 to 20 days later. 6. The lesions of delayed hypersensitivity were probably mediated by cells. There was no evidence that a circulating high affinity antibody played a role in this type of immunologic reaction.


Early-Onset Obesity: Unrecognized First Evidence for GNAS Mutations and Methylation Changes.
Early-onset obesity, characteristic for disorders affecting the leptin-melanocortin pathway, is also observed in pseudohypoparathyroidism type 1A (PHP1A), a disorder caused by maternal GNAS mutations that disrupt expression or function of the stimulatory G protein α-subunit (Gsα). Mutations and/or epigenetic abnormalities at the same genetic locus are also the cause of pseudohypoparathyroidism type 1B (PHP1B). However, although equivalent biochemical and radiographic findings can be encountered in these related disorders caused by GNAS abnormalities, they are considered distinct clinical entities. To further emphasize the overlapping features between both disorders, we report the cases of several children, initially brought to medical attention because of unexplained early-onset obesity, in whom PHP1B or PHP1A was eventually diagnosed. Search for GNAS methylation changes or mutations in cohorts of patients with early-onset obesity. Severe obesity had been noted in five infants, with a later diagnosis of PHP1B due to STX16 deletions and/or abnormal GNAS methylation. These findings prompted analysis of 24 unselected obese patients, leading to the discovery of inherited STX16 deletions in 2 individuals. Similarly, impressive early weight gains were noted in five patients, who initially lacked additional Albright hereditary osteodystrophy features but in whom PHP1A due to GNAS mutations involving exons encoding Gsα was diagnosed. Obesity during the first year of life can be the first clinical evidence for PHP1B, expanding the spectrum of phenotypic overlap between PHP1A and PHP1B. Importantly, GNAS methylation abnormalities escape detection by targeted or genome-wide sequencing strategies, raising the question of whether epigenetic GNAS analyses should be considered for unexplained obesity.


Association of Thrombocytopenia, Revascularization, and In-Hospital Outcomes in Patients with Acute Myocardial Infarction.
The impact of thrombocytopenia on revascularization and outcomes in patients presenting with acute myocardial infarction remains poorly understood. We sought to evaluate associations between thrombocytopenia, in-hospital management, bleeding, and cardiovascular outcomes in patients hospitalized for acute myocardial infarction in the United States. Patients hospitalized from 2004 to 2014 with a primary diagnosis of acute myocardial infarction were identified from the National Inpatient Sample. Management of acute myocardial infarction was compared between patients with and without thrombocytopenia. Multivariable logistic regression models were used to estimate odds of in-hospital adverse events stratified by thrombocytopenia and adjusted for demographics, cardiovascular risk factors, comorbidities, and treatment. A total of 6,717,769 patients were hospitalized with a primary diagnosis of acute myocardial infarction, and thrombocytopenia was reported in 219,351 (3.3%). Patients with thrombocytopenia were older, more likely to have other medical comorbidities, were more likely to undergo coronary artery bypass grafting (28.8% vs 8.2%, P < .001), and were less likely to receive a drug-eluting stent (15.5% vs 29.5%, P < .001). After multivariable adjustment, thrombocytopenia was independently associated with nearly twofold increased odds of in-hospital mortality (adjusted odds ratio 1.91; 95% confidence interval, 1.86-1.97). Thrombocytopenia was also independently associated with ischemic stroke, cardiogenic shock, cardiac arrest, and bleeding complications. Patients with thrombocytopenia in the setting of acute myocardial infarction had increased odds of bleeding, cardiovascular outcomes, and mortality compared with patients without thrombocytopenia. Future investigations to mitigate the poor prognosis of patients with acute myocardial infarction and thrombocytopenia are warranted.


Effect of Theobromine Consumption on Serum Lipoprotein Profiles in Apparently Healthy Humans with Low HDL-Cholesterol Concentrations.
Scope: Theobromine is a major active compound in cocoa with allegedly beneficial effect on high-density-lipoprotein-cholesterol (HDL-CH). We have investigated the effect of theobromine (TB) consumption on the concentrations of triglyceride (TG) and cholesterol (CH) in various lipoprotein (LP) subclasses. Methods: In a randomized, double-blind, placebo-controlled, cross-over study, 44 apparently healthy women and men (age: 60 ± 6 years, BMI: 29 ± 3 kg/m2) with low baseline HDL-CH concentrations consumed a drink supplemented with 500 mg/d theobromine for 4 weeks. TG and CH concentrations in 15 LP subclasses were predicted from diffusion-edited 1H NMR spectra of fasting serum. Results: The LP phenotype of the subjects was characterized by low CH concentrations in the large HDL particles and high TG concentrations in large VLDL and chylomicron (CM) particles, which clearly differed from a LP phenotype of subjects with normal HDL-CH. TB only reduced CH concentrations in the LDL particles by 3.64 and 6.79%, but had no effect on TG and CH in any of the HDL, VLDL and CM subclasses. Conclusion: TB was not effective on HDL-CH in subjects with a LP phenotype characterized by low HDL-CH and high TG in VLDL.


High-resolution crystal structure of copper amine oxidase from Arthrobacter globiformis: assignment of bound diatomic molecules as O2.
The crystal structure of a copper amine oxidase from Arthrobacter globiformis was determined at 1.08 Å resolution with the use of low-molecular-weight polyethylene glycol (LMW PEG; average molecular weight ∼200) as a cryoprotectant. The final crystallographic R factor and Rfree were 13.0 and 15.0%, respectively. Several molecules of LMW PEG were found to occupy cavities in the protein interior, including the active site, which resulted in a marked reduction in the overall B factor and consequently led to a subatomic resolution structure for a relatively large protein with a monomer molecular weight of ∼70,000. About 40% of the presumed H atoms were observed as clear electron densities in the Fo - Fc difference map. Multiple minor conformers were also identified for many residues. Anisotropic displacement fluctuations were evaluated in the active site, which contains a post-translationally derived quinone cofactor and a Cu atom. Furthermore, diatomic molecules, most likely to be molecular oxygen, are bound to the protein, one of which is located in a region that had previously been proposed as an entry route for the dioxygen substrate from the central cavity of the dimer interface to the active site.


[Corneal protection in contact lens users].
To evaluate the efficacy of corneoprotective agents (Corneregel and Solcoseryl) in contact lens users. A total of 66 long-term contact lens wearers with dry eye symptoms and varying degrees of corneal epitheliopathy were monitored. All patients used artificial tears, which, however, were not effective enough to suppress manifestations of corneal epitheliopathy and to release the associated discomfort. The therapy was supplemented with Corneregel. The following examination methods were applied: biomicroscopy with fluorescent staining, Norn test, Schirmer's test, advanced tearscopy with digital image analysis of the precorneal tear film lipid layer, corneal confocal microscopy. In all cases the assessment was performed prior to starting Corneregel and repeated in 7 days, 14 days and 1 month. Complete corneal re-epithelization and restoration of the most superficial layer of the epithelium were achieved within 7-14 days. In case of severe initial epitheliopathy the effect of Corneregel was not sufficient and epithelium defects remained. These patients additionally received Solcoseryl Eye Gel. After the treatment course the condition of corneal epithelium ameliorated and contact lens wearing comfort increased. A longer precorneal tear film break-up time indicated an increase of tear film stability. The total tear production did not change significantly. The moistening effect of Corneregel and low-viscosity artificial tears together with intensive regeneration of corneal epithelium enables structural recovery of the epithelial membrane and considerable improvement of the anterior corneal stroma. At the first stage of corneoprotective treatment it is appropriate to use preservative-free artificial tears of low and high viscosity. If the effect of tear substitutive therapy is unsatisfactory it is recommended to prescribe Corneregel and Solcoseryl. The regimen is to be adjusted individually.


Early systemic sclerosis: assessment of clinical and pre-clinical organ involvement in patients with different disease features.
To assess internal organ involvement in early SSc at presentation. One hundred and fifteen patients admitted to a tertiary centre because of RP, who did not present any routinely detectable scleroderma-related internal organ involvement, were investigated for ANA and videocapillaroscopy, and underwent history and physical examination to detect symptoms/signs suggestive of SSc. Patients were then subdivided into three groups: (i) early SSc, constituted by patients without clinical manifestations other than RP, but with scleroderma marker autoantibodies and/or typical capillaroscopic abnormalities; (ii) probable SSc, constituted by patients with the same autoantibody and/or capillaroscopic status as early SSc patients, but with any of the following manifestations: digital ulcers/scars, puffy fingers, arthritis, telangiectasia, dysphagia/heartburn, shortness of breath; (iii) UCTD, constituted by patients with a specific (i.e. disease antibody marker) ANA and capillaroscopic findings plus any disease manifestation. All patients were investigated by lung functional study and B-mode echo-Doppler-cardiography. Patients who consented underwent oesophageal manometry. An inverted mitral E : A ratio (i.e. early scleroderma cardiac involvement) and/or a diffusing lung capacity for CO <80% of the predictive value (i.e. early lung involvement) and/or basal low oesophageal sphincter pressure <15 mmHg (i.e. early oesophageal involvement) were detected in 37/51 probable SSc patients (72%), 8/19 early SSc patients (42%) and 12/45 UCTD patients (27%). A scleroderma-related internal organ involvement was detected in patients from each group and, more importantly, was pre-clinical in a number of cases.


Angiotensin II receptor antagonists (AT1-blockers, ARBs, sartans): similarities and differences.
A survey is presented of the registered non-peptidergic angiotensin II receptor antagonists (AT1 blockers, ARBs, sartans) and their general properties and similarities. Accordingly, their receptor profile, pharmacokinetic and therapeutic applications are discussed. In addition, attention is paid to the individual characteristics of the AT1 blockers now available. A few components of this category offer additional potentially beneficial properties, owing to their pharmacological or metabolic characteristics. Such additional properties are critically discussed for eprosartan, losartan, telmisartan and valsartan.