Population-based epidemiology of rotavirus hospitalisations in Switzerland

BACKGROUND: Rotaviruses (RV) are the most common cause of dehydrating gastroenteritis requiring hospitalisation in children <5 years of age. A new generation of safe and effective RV vaccines is available. Accurate data describing the current burden of RV disease in the community are needed to devise appropriate strategies for vaccine usage. METHODS: Retrospective, population-based analysis of RV hospitalisations in children <5 years of age during a 5-year period (1999-2003) in a both urban and rural area inhabited by 12% of the Swiss population. RESULTS: Of 406 evaluable cases, 328 were community-acquired RV infections in children <5 years of age. RV accounted for 38% of all hospitalisations for gastroenteritis. The overall hospitalisation incidence in the <5-year-old was 1.5/1000 child-years (peak incidence, 2.6/1000 child-years in children aged 13-24 months). The incidence of community-acquired RV hospitalisations was significantly greater in children of non-Swiss origin (3.0 vs. 1.1/1000 child-years, relative risk 2.7; 95% CI 2.2-3.4), who were younger, but tended to be less severely dehydrated on admission than Swiss children. In comparison with children from urban areas, RV hospitalisation incidence was significantly lower among those residing in the remote mountain area (0.71 vs. 1.71/1000 child years, relative risk 2.2, 95% CI 1.6-3.1). CONCLUSION: Population-based RV hospitalisation incidence was low in comparison with other European countries. Significantly greater hospitalisation rates among children living in urban areas and those from non-Swiss families indicate that factors other than the severity of RV-induced dehydration are important driving forces of hospital admission.

Stable transduction of bovine TLR4 and bovine MD-2 into LPS-nonresponsive cells and soluble CD14 promote the ability to respond to LPS

The interaction of bovine cells with lipopolysaccharide (LPS) was explored using human embryo kidney (HEK) 293 cell line stably transduced with bovine toll-like receptor-4 (TLR4) alone or in combination with bovine MD-2. These lines and mock-transduced HEK293 cells were tested by flow cytometry for LPS-fluorescein isothiocyanate (LPS-FITC) binding, nuclear factor kappa B (NFkappaB) activation, interleukin-8 (IL-8) production and interferon-beta mRNA expression/interferon (IFN) type I production. Whereas bovine TLR4 was sufficient to promote binding of high concentrations of LPS-FITC, both bovine TLR4 and MD-2 were required for activation by LPS, as assessed by NFkappaB activation and IL-8 production. Induction of IFN bioactivity was not observed in doubly transduced HEK293 cells, and no evidence for IFN-beta mRNA induction in response to LPS was obtained, although cells responded by IFN-beta mRNA expression to stimulation by Sendai virus and poly-inosinic acid-poly-cytidylic acid (poly(I:C)). Cells stably transduced with both bovine TLR4 and bovine MD-2 responded to LPS by IL-8 production, in decreasing order, in the presence of fetal bovine serum (FCS), of human serum, and of human serum albumin (HSA). The reduced activity in the presence of HSA could be restored by the addition of soluble CD14 (sCD14) but not of LPS binding protein (LBP). This is in contrast to macrophages which show a superior response to LPS in the presence of HSA when compared with macrophages stimulated by LPS in the presence of FCS. This suggests that macrophages but not HEK293 cells express factors rendering LPS stimulation serum-independent. Stably double-transduced cells reacted, in decreasing order, to LPS from Rhodobacter sphaeroides, to LPS from Escherichia coli, to synthetic lipd-IVa (compound 406), to diphosphoryl-lipid-A (S. minnesota) and to monophosphoryl-lipid-A (S. minnesota). They failed to react to the murine MD-2/TLR4 ligand taxol. This resembles the reactivity of bovine macrophages with regard to sensitivity (ED(50)) and order of potency but is distinct from the reactivity pattern of other species. This formally establishes that in order to react to LPS, cattle cells require serum factors (e.g. sCD14) and cell-expressed factors such as MD-2 and TLR4. The cell lines described are the first of a series expressing defined pattern recognition receptors (PRR) of bovine origin. They will be useful in the study of the interaction of the bovine TLR4-MD-2 complex and Gram-negative bovine pathogens, e.g. the agents causing Gram-negative bovine mastitis.

Clinical field trial examining an implant with a sand-blasted, acid-etched surface

BACKGROUND: Conventionally, endosseous dental implants have required 3 to 6 months of uninterrupted healing based on observations for dental implants that were characterized by a relatively smooth machined surface. Many studies have since demonstrated that implants with a roughened surface resulted in greater bone apposition, earlier bone contact, and a stronger bond between the implant and the bone, suggesting that implants with roughened surfaces could be loaded earlier than 3 to 6 months. Formal clinical studies confirmed that implants with rough surfaces can have abutments placed and be loaded occlusally as early as 6 weeks postplacement. The purpose of this prospective, human clinical investigation was to evaluate a large number of implants with a specific rough surface (sand-blasted acid-etched [SLA]) placed in everyday practice under routine private-practice conditions. METHODS: A prospective, multicenter, human clinical observational study was initiated with the goal of recruiting a minimum of 500 patients and 800 implants. The implants were to be placed and restored in predominantly private-practice settings around the world. Ninety-two practitioners in 16 countries agreed to participate, and 86 followed the study design. Patients had to be in good health, have sufficient bone to encase the implant, and agree to return for recall appointments. Exclusion criteria included heavy smoking (>10 cigarettes a day) and bone augmentation procedures at the implant site. All implants were two-piece (an abutment was to be placed after 6 weeks of healing) and were characterized by the presence of a transmucosal polished collar. Each implant had an SLA surface. All implants were positioned using a non-submerged (single-stage) surgical technique. Survival and success rates were calculated by life-table analyses. RESULTS: A total of 706 patients were enrolled and 1,406 implants were placed. In the final analyses, 590 patients with 990 implants (70.4% of those enrolled) met all inclusion criteria, including placement of an abutment and provisional restoration within 63 days of surgical placement. The majority of implants were 10 and 12 mm long (78.7%) and were placed in type II and III bone (87%). Seventy-three percent of the implants were placed in the mandible, and 27% were placed in the maxilla. The cumulative survival rate was 99.56% at 3 years and 99.26% at 5 years. The overall success rate was 99.12% at 3 years and 97.38% after 5 years. CONCLUSIONS: Under private-practice conditions, implants with an SLA surface could be placed and restored predictably within 6 to 8 weeks. Data from this prospective, multicenter, human observational study reinforced the results of more formal clinical studies and demonstrated that implants with the SLA surface can be restored in patients in approximately half of the time of conventional healing periods.

Impact of a self-developed planning and self-constructed navigation system on skull base surgery: 10 years experience

CONCLUSION: Our self-developed planning and navigation system has proven its capacity for accurate surgery on the anterior and lateral skull base. With the incorporation of augmented reality, image-guided surgery will evolve into 'information-guided surgery'. OBJECTIVE: Microscopic or endoscopic skull base surgery is technically demanding and its outcome has a great impact on a patient's quality of life. The goal of the project was aimed at developing and evaluating enabling navigation surgery tools for simulation, planning, training, education, and performance. This clinically applied technological research was complemented by a series of patients (n=406) who were treated by anterior and lateral skull base procedures between 1997 and 2006. MATERIALS AND METHODS: Optical tracking technology was used for positional sensing of instruments. A newly designed dynamic reference base with specific registration techniques using fine needle pointer or ultrasound enables the surgeon to work with a target error of < 1 mm. An automatic registration assessment method, which provides the user with a color-coded fused representation of CT and MR images, indicates to the surgeon the location and extent of registration (in)accuracy. Integration of a small tracker camera mounted directly on the microscope permits an advantageous ergonomic way of working in the operating room. Additionally, guidance information (augmented reality) from multimodal datasets (CT, MRI, angiography) can be overlaid directly onto the surgical microscope view. The virtual simulator as a training tool in endonasal and otological skull base surgery provides an understanding of the anatomy as well as preoperative practice using real patient data. RESULTS: Using our navigation system, no major complications occurred in spite of the fact that the series included difficult skull base procedures. An improved quality in the surgical outcome was identified compared with our control group without navigation and compared with the literature. The surgical time consumption was reduced and more minimally invasive approaches were possible. According to the participants' questionnaires, the educational effect of the virtual simulator in our residency program received a high ranking.

Livelihoods in Transition: Changing Land Use Strategies and Ecological Implications in a Post Soviet Setting (Kyrgyzstan)

The sudden independence of Kyrgyzstan from the Soviet Union in 1991 led to a total rupture of industrial and agricultural production. Based on empirical data, this study seeks to identify key land use transformation processes since the late 1980s, their impact on people's livelihoods and the implication for natural resources in the communes of Tosh Bulak and Saz, located in the Sokuluk River Basin on the northern slope of the Kyrgyz Range. Using the concept of the sustainable livelihood approach as an analytical framework, three different livelihood strategies were identified: (1) An accumulation strategy applied by wealthy households where renting and/or buying of land is a key element; they are the only household category capable of venturing into rain fed agriculture. (2) A preserving strategy involving mainly intermediate households who are not able to buy or rent additional agricultural land; very often they are forced to return their land to the commune or sell it to wealthier households. (3) A coping strategy including mainly poor households consisting of elderly pensioners or headed by single mothers; due to their limited labour and economic power, agricultural production is very low and hardly covers subsistence needs; pensions and social allowances form the backbone of these livelihoods. Ecological assessments have shown that the forage productivity of remote high mountain pastures has increased from 5 to 22 per cent since 1978. At the same time forage productivity on pre-mountain and mountain pastures close to villages has generally decreased from 1 to 34 per cent. It seems that the main avenues for livelihoods to increase their wealth are to be found in the agricultural sector by controlling more and mainly irrigated land as well as by increasing livestock. The losers in this process are thus those households unable to keep or exploit their arable land or to benefit from new agricultural land. Ensuring access to land for the poor is therefore imperative in order to combat rural poverty and socio-economic disparities in rural Kyrgyzstan.

Differential expression of ABC transporters and their regulatory genes during lactation and dry period in bovine mammary tissue

ATP-binding cassette (ABC) transporters play a pivotal role in human physiology, and mutations in these genes often result in severe hereditary diseases. ABC transporters are expressed in the bovine mammary gland but their physiological role in this organ remains elusive. Based on findings in the context of human disorders we speculated that candidate ABC transporters are implicated in lipid and cholesterol transport in the mammary gland. Therefore we investigated the expression pattern of selected genes that are associated with sterol transport in lactating and nonlactating mammary glands of dairy cows. mRNA levels from mammary gland biopsies taken during lactation and in the first and second week of the dry period were analysed using quantitative PCR. Five ABC transporter genes, namely ABCA1, ABCA7, ABCG1, ABCG2 and ABCG5, their regulating genes LXRalpha, PPARgamma, SREBP1 and the milk proteins lactoferrin and alpha-lactalbumin were assessed. A significantly enhanced expression in the dry period was observed for ABCA1 while a significant decrease of expression in this period was detected for ABCA7, ABCG2, SREBP1 and alpha-lactalbumin. ABCG1, ABCG5, LXRalpha, PPARgamma and lactoferrin expression was not altered between lactation and dry period. These results indicate that candidate ABC transporters involved in lipid and cholesterol transport show differential mRNA expression between lactation and the dry period. This may be due to physiological changes in the mammary gland such as immigration of macrophages or the accumulation of fat due to the loss of liquid in the involuting mammary gland. The current mRNA expression analysis of transporters in the mammary gland is the prerequisite for elucidating novel molecular mechanisms underlying cholesterol and lipid transfer into milk.

Increased cytotoxic T-lymphocyte epitope variant cross-recognition and functional avidity are associated with hepatitis C virus clearance

Hepatitis C virus (HCV) clearance has been associated with reduced viral evolution in targeted cytotoxic T-lymphocyte (CTL) epitopes, suggesting that HCV clearers may mount CTL responses with a superior ability to recognize epitope variants and prevent viral immune escape. Here, 40 HCV-infected subjects were tested with 406 10-mer peptides covering the vast majority of the sequence diversity spanning a 197-residue region of the NS3 protein. HCV clearers mounted significantly broader CTL responses of higher functional avidity and with wider variant cross-recognition capacity than nonclearers. These observations have important implications for vaccine approaches that may need to induce high-avidity responses in vivo.