A survey of paediatric HIV programmatic and clinical management practices in Asia and sub-Saharan Africa--the International epidemiologic Databases to Evaluate AIDS (IeDEA)

INTRODUCTION There are limited data on paediatric HIV care and treatment programmes in low-resource settings. METHODS A standardized survey was completed by International epidemiologic Databases to Evaluate AIDS paediatric cohort sites in the regions of Asia-Pacific (AP), Central Africa (CA), East Africa (EA), Southern Africa (SA) and West Africa (WA) to understand operational resource availability and paediatric management practices. Data were collected through January 2010 using a secure, web-based software program (REDCap). RESULTS A total of 64,552 children were under care at 63 clinics (AP, N=10; CA, N=4; EA, N=29; SA, N=10; WA, N=10). Most were in urban settings (N=41, 65%) and received funding from governments (N=51, 81%), PEPFAR (N=34, 54%), and/or the Global Fund (N=15, 24%). The majority were combined adult-paediatric clinics (N=36, 57%). Prevention of mother-to-child transmission was integrated at 35 (56%) sites; 89% (N=56) had access to DNA PCR for infant diagnosis. African (N=40/53) but not Asian sites recommended exclusive breastfeeding up until 4-6 months. Regular laboratory monitoring included CD4 (N=60, 95%), and viral load (N=24, 38%). Although 42 (67%) sites had the ability to conduct acid-fast bacilli (AFB) smears, 23 (37%) sites could conduct AFB cultures and 18 (29%) sites could conduct tuberculosis drug susceptibility testing. Loss to follow-up was defined as >3 months of lost contact for 25 (40%) sites, >6 months for 27 sites (43%) and >12 months for 6 sites (10%). Telephone calls (N=52, 83%) and outreach worker home visits to trace children lost to follow-up (N=45, 71%) were common. CONCLUSIONS In general, there was a high level of patient and laboratory monitoring within this multiregional paediatric cohort consortium that will facilitate detailed observational research studies. Practices will continue to be monitored as the WHO/UNAIDS Treatment 2.0 framework is implemented.

DNA-multiporhyrinic systems: promising objects for materials science

Porphyrin-containing materials are attractive objects for advanced light-harvesting systems [1]. Despite existence of numerous approaches to arrange porphyrines in a controlled and programmed way and therefore mimic natural photosynthetic systems, the problem of porphyrin`s arraying remains challenging [2]. Herein, we present an approach based on using DNA as a scaffold to hold porphyrines together. The whole spectroscopic investigation of the compounds containing several porphyrines and a possibility of their usage as molecular blocks for functional supramolecular architectures is discussed [3].

2D supramolecular polymers: nanosized, water-soluble "sheets"

Self – assembly is a powerful tool for the construction of highly organized nanostructures [1]. Therefore, the possibility to control and predict pathways of molecular ordering on the nanoscale level is a critical issue for the production of materials with tunable and adaptive macroscopic properties. Herein, we demonstrate that designed molecule Py3 forms dimensionally - defined supramolecular assemblies under thermodynamic conditions in water [2]. To study Py3 self-assembly, we carried out whole set of spectroscopic and microscopic experiments. The factors influencing stability, morphology and behavior of «nanosheets» in multicomponent systems are discussed

Inheritance of ectopic ureters in Entlebucher Mountain Dogs

To test the hypothesis of a heritable base of ectopic ureters (EU) in Entlebucher Mountain Dogs (EMD) and to elucidate associated risk factors and mode of inheritance of the disease, 565 EMD were clinically investigated and population genetic analyses performed. Based on the location of the most caudal termination of the ureteral openings, 552 EMD were classified into three phenotype groups trigone, intravesically and extravesically ectopic based on results of abdominal sonography, urethra-cystoscopy and/or contrast-enhanced computed tomography. One-third (32.9%) of the phenotyped animals had normal terminations of both ureters in the bladder trigone, 47.3% had at least one intravesicular ectopic termination and 19.8% had at least one extravesicular ectopic termination. Multivariate mixed logistic regression revealed gender as a risk factor associated with EU as males were more often affected than females. Complex segregation analysis indicated a hereditary basis for EU in EMD and the involvement of a major gene in the occurrence of the extravesicular EU phenotype.

Intraductal papillary neoplasms of the bile duct: stepwise progression to carcinoma involves common molecular pathways

Intraductal papillary neoplasms of the bile duct are still poorly characterized regarding (1) their molecular alterations during the development to invasive carcinomas, (2) their subtype stratification and (3) their biological behavior. We performed a multicenter study that analyzed these issues in a large European cohort. Intraductal papillary neoplasms of the bile duct from 45 patients were graded and subtyped using mucin markers and CDX2. In addition, tumors were analyzed for common oncogenic pathways, and the findings were correlated with subtype and grade. Data were compared with those from 22 extra- and intrahepatic cholangiocarcinomas. Intraductal papillary neoplasms showed a development from preinvasive low- to high-grade intraepithelial neoplasia to invasive carcinoma. Molecular and immunohistochemical analysis revealed mutated KRAS, overexpression of TP53 and loss of p16 in low-grade intraepithelial neoplasia, whereas loss of SMAD4 was found in late phases of tumor development. Alterations of HER2, EGFR, β-catenin and GNAS were rare events. Among the subtypes, pancreato-biliary (36%) and intestinal (29%) were the most common, followed by gastric (18%) and oncocytic (13%) subtypes. Patients with intraductal papillary neoplasm of the bile duct showed a slightly better overall survival than patients with cholangiocarcinoma (hazard ratio (cholangiocarcinoma versus intraductal papillary neoplasm of the bile duct): 1.40; 95% confidence interval: 0.46-4.30; P=0.552). The development of biliary intraductal papillary neoplasms of the bile duct follows an adenoma-carcinoma sequence that correlates with the stepwise activation of common oncogenic pathways. Further large trials are needed to investigate and verify the finding of a better prognosis of intraductal papillary neoplasms compared with conventional cholangiocarcinoma.

Expatriates-Training = Expatriates-Einsatzerfolg? Eine Metaanalyse

Diese Studie untersucht im Rahmen einer Metaanalyse den Zusammenhang zwischen dem Training und dem Einsatzerfolg von Expatriates. Bisherige Metaanalysen zu diesem Thema haben mehrheitlich Studien mit einem Fokus auf Soldaten, Ärzten und Schülern berücksichtigt. Um weitere Erkenntnisse auf Unternehmensebene zu gewinnen, berücksichtigt diese Metananalyse 28 Studien, die alle einen Fokus auf Managern haben. Die Ergebnisse zeigen einen positiven und signifikanten Effekt von Training auf die Arbeitszufriedenheit und das Commitment von Expatriates. Weiterhin zeigen die Ergebnisse, dass Training die Abbruchabsicht von Expatriates verringert. Betrachtet man Anpassung als Erfolgskriterium, so besteht kein signifikanter Zusammenhang zwischen Training und Arbeits- und Interaktionsanpassung. Hinsichtlich der kulturellen Anpassung zeigen die Ergebnisse lediglich einen schwachen Zusammenhang.

Technical complications and failures of zirconia-based prostheses supported by implants followed up to 7 years: a case series.

PURPOSE To evaluate technical complications and failures of zirconia-based fixed prostheses supported by implants. MATERIALS AND METHODS Consecutive patients received zirconia-based single crowns (SCs) and fixed dental prostheses (FDPs) on implants in a private clinical setting between 2005 and 2010. One dentist performed all surgical and prosthetic procedures, and one master technician performed and coordinated all laboratory procedures. One-piece computer-aided design/ computer-assisted manufacture technology was used to fabricate abutments and frameworks, which were directly connected at the implant level, where possible. All patients were involved in a recall maintenance program and were finally reviewed in 2012. Data on framework fractures, chipping of veneering ceramics, and other technical complications were recorded. The primary endpoint was failure of the prostheses, ie, the need for a complete remake. A life table analysis was calculated. RESULTS A total of 289 implants supported 193 zirconia-based prostheses (120 SCs and 73 FDPs) in 127 patients (51 men, 76 women; average age: 62.5 ± 13.4 years) who were reviewed in 2012. Twenty-five (13%) prostheses were cemented on 44 zirconia abutments and 168 (87%) prostheses were screw-retained directly at the implant level. Fracture of 3 frameworks (1 SC, 2 FDPs) was recorded, and significant chipping resulted in the remake of 3 prostheses (1 SC, 2 FDPs). The 7-year cumulative survival rate was 96.4% ± 1.99%. Minor complications comprised 5 loose screws (these were retightened), small chips associated with 3 prostheses (these were polished), and dislodgement of 3 prostheses (these were recemented). Overall, 176 prostheses remained free of technical problems. CONCLUSIONS Zirconia-based prostheses screwed directly to implants are clinically successful in the short and medium term.

Polycystic Kidneys and GM2 Gangliosidosis-Like Disease in Neonatal Springboks (Antidorcas marsupialis)

Clinical, gross, histopathologic, electron microscopic findings and enzymatic analysis of 4 captive, juvenile springboks (Antidorcas marsupialis) showing both polycystic kidneys and a storage disease are described. Springbok offspring (4 of 34; 12%) were affected by either one or both disorders in a German zoo within a period of 5 years (2008-2013). Macroscopic findings included bilaterally severely enlarged kidneys displaying numerous cysts in 4 animals and superior brachygnathism in 2 animals. Histopathologically, kidneys of 4 animals displayed cystic dilation of the renal tubules. In addition, abundant cytoplasmic vacuoles with a diameter ranging from 2 to 10 μm in neurons of the central and peripheral nervous system, hepatocytes, thyroid follicular epithelial cells, pancreatic islets of Langerhans and renal tubular cells were found in 2 springbok neonates indicative of an additional storage disease. Ultrastructurally, round electron-lucent vacuoles, up to 4 μm in diameter, were present in neurons. Enzymatic analysis of liver and kidney tissue of 1 affected springbok revealed a reduced activity of total hexosaminidase (Hex) with relatively increased HexA activity at the same level of total Hex, suggesting a hexosaminidase defect. Pedigree analysis suggested a monogenic autosomal recessive inheritance for both diseases. In summary, related springboks showed 2 different changes resembling both polycystic kidney and a GM2 gangliosidosis similar to the human Sandhoff disease. Whether the simultaneous occurrence of these 2 entities represents an incidental finding or has a genetic link needs to be investigated in future studies.

Major differences in organization and availability of health care and medicines for HIV/TB coinfected patients across Europe

OBJECTIVES The aim of the study was to investigate the organization and delivery of HIV and tuberculosis (TB) health care and to analyse potential differences between treatment centres in Eastern (EE) and Western Europe (WE). METHODS Thirty-eight European HIV and TB treatment centres participating in the TB:HIV study within EuroCoord completed a survey on health care management for coinfected patients in 2013 (EE: 17 respondents; WE:21; 76% of all TB:HIV centres). Descriptive statistics were obtained for regional comparisons. The reported data on health care strategies were compared with actual clinical practice at patient level via data derived from the TB:HIV study. RESULTS Respondent centres in EE comprised: Belarus (n = 3), Estonia (1), Georgia (1), Latvia (1), Lithuania (1), Poland (4), Romania (1), the Russian Federation (4) and Ukraine (1); those in WE comprised: Belgium (1), Denmark (1), France (1), Italy (7), Spain (2), Switzerland (1) and UK (8). Compared with WE, treatment of HIV and TB in EE are less often located at the same site (47% in EE versus 100% in WE; P < 0.001) and less often provided by the same doctors (41% versus 90%, respectively; P = 0.002), whereas regular screening of HIV-infected patients for TB (80% versus 40%, respectively; P = 0.037) and directly observed treatment (88% versus 20%, respectively; P < 0.001) were more common in EE. The reported availability of rifabutin and second- and third-line anti-TB drugs was lower, and opioid substitution therapy (OST) was available at fewer centres in EE compared with WE (53% versus 100%, respectively; P < 0.001). CONCLUSIONS Major differences exist between EE and WE in relation to the organization and delivery of health care for HIV/TB-coinfected patients and the availability of anti-TB drugs and OST. Significant discrepancies between reported and actual clinical practices were found in EE.

Cardiovascular-renal axis disorders in the domestic dog and cat: a veterinary consensus statement.

OBJECTIVES There is a growing understanding of the complexity of interplay between renal and cardiovascular systems in both health and disease. The medical profession has adopted the term "cardiorenal syndrome" (CRS) to describe the pathophysiological relationship between the kidney and heart in disease. CRS has yet to be formally defined and described by the veterinary profession and its existence and importance in dogs and cats warrant investigation. The CRS Consensus Group, comprising nine veterinary cardiologists and seven nephrologists from Europe and North America, sought to achieve consensus around the definition, pathophysiology, diagnosis and management of dogs and cats with "cardiovascular-renal disorders" (CvRD). To this end, the Delphi formal methodology for defining/building consensus and defining guidelines was utilised. METHODS Following a literature review, 13 candidate statements regarding CvRD in dogs and cats were tested for consensus, using a modified Delphi method. As a new area of interest, well-designed studies, specific to CRS/CvRD, are lacking, particularly in dogs and cats. Hence, while scientific justification of all the recommendations was sought and used when available, recommendations were largely reliant on theory, expert opinion, small clinical studies and extrapolation from data derived from other species. RESULTS Of the 13 statements, 11 achieved consensus and 2 did not. The modified Delphi approach worked well to achieve consensus in an objective manner and to develop initial guidelines for CvRD. DISCUSSION The resultant manuscript describes consensus statements for the definition, classification, diagnosis and management strategies for veterinary patients with CvRD, with an emphasis on the pathological interplay between the two organ systems. By formulating consensus statements regarding CvRD in veterinary medicine, the authors hope to stimulate interest in and advancement of the understanding and management of CvRD in dogs and cats. The use of a formalised method for consensus and guideline development should be considered for other topics in veterinary medicine.