Rapamycin impairs endothelial cell function in human internal thoracic arteries.

BACKGROUND Definitive fate of the coronary endothelium after implantation of a drug-eluting stent remains unclear, but evidence has accumulated that treatment with rapamycin-eluting stents impairs endothelial function in human coronary arteries. The aim of our study was to demonstrate this phenomenon on functional, morphological and biochemical level in human internal thoracic arteries (ITA) serving as coronary artery model. METHODS After exposure to rapamycin for 20 h, functional activity of ITA rings was investigated using the organ bath technique. Morphological analysis was performed by scanning electron microscopy and evaluated by two independent observers in blinded fashion. For measurement of endothelial nitric oxide synthase (eNOS) release, mammalian target of rapamycin (mTOR) and protein kinase B (PKB) (Akt) activation, Western blotting on human mammary epithelial cells-1 and on ITA homogenates was performed. RESULTS Comparison of the acetylcholine-induced relaxation revealed a significant concentration-dependent decrease to 66 ± 7 % and 36 ± 7 % (mean ± SEM) after 20-h incubation with 1 and 10 μM rapamycin. Electron microscopic evaluation of the endothelial layer showed no differences between controls and samples exposed to 10 μM rapamycin. Western blots after 20-h incubation with rapamycin (10 nM-1 μM) revealed a significant and concentration-dependent reduction of p (Ser 1177)-eNOS (down to 38 ± 8 %) in human mammary epithelial cells (Hmec)-1. Furthermore, 1 μM rapamycin significantly reduced activation of p (Ser2481)-mTOR (58 ± 11 %), p (Ser2481)-mTOR (23 ± 4 %) and p (Ser473)-Akt (38 ± 6 %) in ITA homogenates leaving Akt protein levels unchanged. CONCLUSIONS The present data suggests that 20-h exposure of ITA rings to rapamycin reduces endothelium-mediated relaxation through down-regulation of Akt-phosphorylation via the mTOR signalling axis within the ITA tissue without injuring the endothelial cell layer.

Risk factors for development of internal neoplasms in koi carp (Cyprinus carpio koi)

Fish, like mammals, can be affected by neoplastic proliferations. As yet, there are only a very small number of studies reporting on the occurrence of tumours in koi carp Cyprinus carpio koi and only sporadic reports on the nature of the tumours or on risk factors associated with their development. Between 2008 and 2012, koi with abdominal swelling were examined pathologically: neoplastic lesions were diagnosed and classified histologically. We evaluated possible risk factors for the development of these internal neoplasms in koi carp in Switzerland, using an online 2-part questionnaire sent to fish keepers with koi affected by internal tumours and to fish keepers who had not previously reported any affected koi. Part 1 addressed all participants and focused on general information about koi husbandry and pond technical data; Part 2 addressed participants that had one or several case(s) of koi with internal tumour(s) between 2008 and 2012, and consisted of specific questions about affected koi. A total of 112 internal tumours were reported by the 353 koi keepers participating in the survey. Analysis of the obtained data revealed that tumour occurrence was significantly associated with the location (indoors vs. outdoors) and volume of the pond, frequency of water changes, origin of the koi, number of koi kept in a Pond and the use of certain pond disinfectant/medication products. Our results contribute to the identification of possible risk factors, which in turn could help to establish prophylactic measures in order to reduce the occurrence of internal neoplasms in koi.

Temporary Internal Fixation for Ligamentous and Osseous Lisfranc Injuries: Outcome and Technical Tip

BACKGROUND Open rather than closed reduction and internal fixation as well as primary definitive arthrodesis are well accepted for ligamentous and osseous Lisfranc injuries. For ligamentous injuries, a better outcome after primary definitive partial arthrodesis has been published. METHODS Of 135 Lisfranc injuries that were treated from 1998 to 2012 with open reduction, temporary internal fixation by screws and plates, and restricted weight bearing in a lower leg cast for 3 months followed by an arch support for another 4 to 6 weeks, 29 ligamentous Lisfranc injuries were available for follow-up. They were compared with 29 osseous Lisfranc injuries matched in age and gender. RESULTS Between the groups, there were no significant differences in average age (39.9 vs 38 years) or in average follow-up time (8.3 vs 9.1 years). Also, no significant differences were seen in the AOFAS midfoot score (84 vs 85.3 points), the FFI pain scale (9.9 vs 14.9 points), SF 36 physical component (56.2 vs 53.9 points), SF 36 mental component (57 vs 56.4 points), or VAS for pain (1.6 vs 1.5 points). The FFI function scale was significantly lower in the ligamentous group (11.6 vs 19.5 points). Radiographically, loss of reduction was recorded 3 times in the ligamentous injuries and 4 times in the osseous injuries. Arthritis was mild/moderate/severe in 5/3/0 ligamentous injuries and in 7/2/1 osseous injuries, requiring 1 definitive secondary Lisfranc arthrodesis in each group. CONCLUSION With longer and conservative postoperative management, open reduction and temporary internal fixation in ligamentous and osseous Lisfranc injuries led to equal medium-term outcome. Inferior outcome in ligamentous injuries was not found. LEVEL OF EVIDENCE Level III, retrospective comparative cohort study.

Stability of Le Fort I maxillary inferior repositioning surgery with rigid internal fixation: a systematic review

The aim of this study was to evaluate the stability of Le Fort I maxillary inferior repositioning surgery in patients with a vertical maxillary deficiency at least 6 months after surgery. The electronic databases were searched to identify all articles reporting the long-term effects of one-piece maxillary inferior repositioning with rigid fixation. Methodological quality was evaluated according to 15 criteria related to study design, measurements, and statistical analysis. Two articles were identified, with a total of 22 patients. The maxilla was repositioned inferiorly from a mean 3.2 to 4.5mm in the anterior part and from a mean 0.1 to 1.8mm in the posterior part. At 6 months post-treatment, absolute relapse of a mean 1.6mm was measured for the anterior part of the maxilla and 0.3mm for the posterior part of the maxilla. The stability of maxillary inferior repositioning surgery could not be confirmed due to the small sample size, unclear diagnosis, and potential confounding factors.

Internal bacterial colonization of implants: association with peri-implant bone loss

OBJECTIVES The aim of the present longitudinal study was to investigate bacterial colonization of the internal implant cavity and to evaluate a possible association with peri-implant bone loss. METHODS A total of 264 paper point samples were harvested from the intra-implant cavity of 66 implants in 26 patients immediately following implant insertion and after 3, 4, and 12 months. Samples were evaluated for Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia, Treponema denticola, and Tannerella forsythia as well as total bacterial counts by real-time PCR. Bone loss was evaluated on standardized radiographs up to 25 months after implant insertion. For the statistical analysis of the data, mixed effects models were fitted. RESULTS There was an increase in the frequency of detection as well as in the mean counts of the selected bacteria over time. The evaluation of the target bacteria revealed a significant association of Pr. intermedia at 4 and 12 months with peri-implant bone loss at 25 months (4 months: P = 0.009; 12 months: P = 0.021). CONCLUSIONS The present study could demonstrate a progressive colonization by periodontopathogenic bacteria in the internal cavities of two-piece implants. The results suggest that internal colonization with Pr. intermedia was associated with peri-implant bone loss.

Internal and external effects on cognition: Evidence from memory training in very preterm-born children and cognition in patients with carotid artery stenosis before and after treatment

The present synopsis aims to integrate one study about memory training in very preterm-born children and two studies about cognition in patients with carotid artery stenosis before and after treatments. Preterm-born children are at increased risk of cognitive deficits and behavioural problems compared with peers born at term. This thesis determined whether memory training would improve cognitive functions in school-age very preterm-born children. Memory strategy training produced significant improvements in trained and non-trained cognitive functions; a core working memory training revealed significant effects on short-term memory and working memory tasks. Six months after training, children in both training groups showed better working memory performance than children in the waiting control group. This is evidence that memory training – an external influence on cognition – induces plastic changes in very preterm-born children. Patients with carotid artery stenosis are known to be at increased risk of cognitive impairment. We showed that patients with symptomatic or asymptomatic carotid artery stenosis were at higher risk for cognitive deficits than expected in a normative sample. This thesis seeks to link cognitive plasticity to internal factors like carotid stenosis. An external factor, which influences blood flow to the brain is the nature of the carotid artery stenosis treatment. Research on the effects of carotid artery stenosis treatment on cognition has produced inconsistent results. We found significant improvement in frontal lobe functions, visual memory and motor speed one year after treatment independent of the treatment type (best medical treatment, carotid artery stenting, carotid artery endarterectomy); providing evidence for ‘treatment-induced’ cognitive plasticity. Baseline performance was negatively associated with improvement in various cognitive functions after training in very preterm-born children and after treatment in patients with carotid artery stenosis. The present synopsis aims to integrate these findings into the current and relevant literature, and discuss consequences as well as methodological considerations resulting from the studies constituting the thesis at hand.

Is family medicine meeting the HIV/AIDS challenge? A national survey of family physicians' beliefs, clinical competence, and experience regarding HIV disease

A national sample of family physicians was surveyed to (1) assess family physicians' beliefs about the human immunodeficiency virus (HIV) and individuals at risk for infection, their clinical competence regarding HIV-related issues, and their experiences with HIV disease; (2) present conclusions to the American Academy of Family Physicians (AAFP) to effect the development of an early clinical care protocol and a continuing medical education curriculum; and (3) collect base-line data for use in the evaluation of an early clinical care protocol and a continuing medical education curriculum, in the case that such programs are developed and disseminated. After considering retired or deceased respondents, of the 2,660 physicians surveyed, 1,678 (63.7%) responded. The resulting sample was representative of the active members of the AAFP. About 77% of the respondents were unable to accurately identify the universal precautions for blood and body fluids to prevent occupational transmission of HIV or hepatitis B virus (HBV). Residency trained and board certified physicians expressed fewer "external constraints," such as fear of losing patients, obviating them from providing treatment to individuals with HIV disease (p =.004 and p $<$.001, respectively). These physicians also manifested fewer "internal constraints" to the provision of HIV treatment, such as fear of becoming infected (p $<$.001 and p =.012, respectively). Residency trained physicians also expressed a greater comfort with discussing sexually-related topics with their patients than did non-residency trained physicians (p $<$.001). There were 67.1% of the physicians surveyed who reported never providing treatment to an individual with HIV disease. Residency trained and board certified physicians expressed a greater likelihood to provide treatment to HIV-infected patients (p $<$.001) than non-residency trained and non-board certified physicians.^ Among the various primary care specialties, family medicine is especially vulnerable to the current challenges of HIV/AIDS. These challenges are augmented by the epidemiologic pattern that characterizes AIDS. For the past several years, we have seen AIDS in this country assume a similar pattern to that seen in most other countries; HIV is becoming increasingly prevalent in the heterosexual population as well as in locations removed from metropolitan centers. This current phase of the epidemic generates greater pressures upon primary care physicians, particularly family physicians, to become better acquainted with the means to provide early care to HIV/AIDS patients and to prevent HIV/AIDS among their patients. Family medicine is especially appropriate for providing care to HIV patients because family medicine involves treatment to all age groups and conditions; other primary care specialties focus on limited patient populations or specific conditions. Family physicians should be armed with the expertise to confront HIV/AIDS. However, family physicians' clinical competence and experience with HIV is not known. The data collected in this survey describes their competencies, attitudes, and experiences. ^

Models for Internal Quality Fruit Sorting, Based on Time- Domain Laser Reflectance Spectroscopy (TDRS)

Time domain laser reflectance spectroscopy (TDRS) was applied for the first time to evaluate internal fruit quality. This technique, known in medicine-related knowledge areas, has not been used before in agricultural or food research. It allows the simultaneous non-destructive measuring of two optical characteristics of the tissues: light scattering and absorption. Models to measure firmness, sugar & acid contents in kiwifruit, tomato, apple, peach, nectarine and other fruits were built using sequential statistical techniques: principal component analysis, multiple stepwise linear regression, clustering and discriminant analysis. Consistent correlations were established between the two parameters measured with TDRS, i.e. absorption & transport scattering coefficients, with chemical constituents (sugars and acids) and firmness, respectively. Classification models were built to sort fruits into three quality grades, according to their firmness, soluble solids and acidity.

Ethnobotanical study of the sages used in traditional Valencian medicine and as essential oil: characterization of an endemic Salvia and its contribution to local development

Seven wild and cultivated Salvia species and two Phlomis species, used traditionally in Valencian medicine to treat a variety of external and internal ailments, were studied. New ethnobotanical data are provided, obtained from semistructured interviews with 34 people in the Valencian area. A seasonal characterization of the essential oil of a wild sage, Salvia blancoana Webb & Heldr. subsp. mariolensis Figuerola, by GC-FID and GC-MS was carried out as a means to ensure quality control of endemic traditional species such as this one, which has been commercialized by local industries. A comparison with the essential oil of Salvia lavandulifolia Vahl subsp.lavandulifolia allowed inclusion of the wild sage within the commercial 'Spanish sage' oil.

Diagnosis and treatment of internal parasites,

"This is the first of a series of books on parasitology of domestic animals by Dr. Maurice C. Hall to be published by Veterinary medicine. The entire series will contain about 3000 pages."

Outline of clinical diagnostics of the internal diseases of domestic animals.

Mode of access: Internet.

Use of complementary and alternative medicine and quality of life: changes at the end of life

The purpose of this study was to compare the physical, psychological and social dimensions associated with quality-of-life outcomes over the last year of life, between advanced cancer users and nonusers of complementary and alternative medicine. One hundred and eleven patients were identified through Queensland Cancer Registry records, and followed up every four to six weeks until close to death using standardized protocols. Outcome measures were symptom burden, psychological distress, subjective wellbeing, satisfaction with conventional medicine and need for control over treatment decisions. At the initial interview, 36 (32%) participants had used complementary/ alternative medicine the previous week; mainly vitamins, minerals and tonics and herbal remedies. Among all participants, 53 (48%) used at least one form of complementary/ alternative medicine over the study period. Only six (11%) visited alternative practitioners on a regular basis. Overall, complementary/ alternative medicine users reported higher levels of anxiety and pain, less satisfaction with conventional medicine and lower need for control over treatment decisions compared with nonusers. These differences tend to change as death approaches. A more rigorous assessment of complementary/ alternative medicine use, psychological distress, pain and subjective wellbeing among patients with advanced cancer is needed in the clinical setting.