Cross-sectional associations between adipose tissue depots and areal bone mineral density in the UK Biobank imaging study.

The relationship between obesity and osteoporosis is poorly understood. In this study, we assessed the association between adiposity and bone. The fat-bone relationship was dependent on sex, body mass index classification, and menopausal status. Results highlight the importance of accounting for direct measures of adiposity (beyond BMI) and menopause status. INTRODUCTION: Assess the relationship between direct measures of adiposity (total body fat mass, visceral adipose tissue, and abdominal subcutaneous adipose tissue) with the whole body and clinically relevant bone sites of the lumbar spine, and femoral neck areal bone mineral density (aBMD) in men and women. METHODS: This cross-sectional analysis was conducted utilizing de-identified data from the UK Biobank on participants (n = 3674) with available dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI) data. Sex-stratified multiple linear regression was used to assess the relationship between adiposity measures and aBMD outcomes, controlling for age, race, total body lean mass (DXA), height, BMI class, physical activity, smoking, menopausal status (women), and hormone use (women). RESULTS: In men, significant interactions were observed between measures of adiposity and BMI on aBMD for the whole body and lumbar spine. Interactions indicated a positive relationship between adiposity and aBMD in men classified as normal weight, but an inverse relationship in men with elevated BMI. In women, significant interactions between adiposity measures and menopausal status were observed primarily for the whole body and femoral neck aBMD bone outcomes which indicated a negative relationship between adiposity and aBMD in premenopausal women, but a positive relationship in postmenopausal women. CONCLUSION: Total body adiposity, abdominal subcutaneous adipose tissue, and visceral adipose tissue were all significantly associated with aBMD in both men and women. The strength and direction of association were dependent on sex, BMI classification, and menopausal status (women).

Intraspecific trait variation in plants: a renewed focus on its role in ecological processes.

BACKGROUND: Investigating the causes and consequences of intraspecific trait variation (ITV) in plants is not novel, as it has long been recognized that such variation shapes biotic and abiotic interactions. While evolutionary and population biology have extensively investigated ITV, only in the last 10 years has interest in ITV surged within community and comparative ecology. SCOPE: Despite this recent interest, still lacking are thorough descriptions of ITV's extent, the spatial and temporal structure of ITV, and stronger connections between ITV and community and ecosystem properties. Our primary aim in this review is to synthesize the recent literature and ask: (1) How extensive is intraspecific variation in traits across scales, and what underlying mechanisms drive this variation? (2) How does this variation impact higher-order ecological processes (e.g. population dynamics, community assembly, invasion, ecosystem productivity)? (3) What are the consequences of ignoring ITV and how can these be mitigated? and (4) What are the most pressing research questions, and how can current practices be modified to suit our research needs? Our secondary aim is to target diverse and underrepresented traits and plant organs, including anatomy, wood, roots, hydraulics, reproduction and secondary chemistry. In addressing these aims, we showcase papers from the Special Issue. CONCLUSIONS: Plant ITV plays a key role in determining individual and population performance, species interactions, community structure and assembly, and ecosystem properties. Its extent varies widely across species, traits and environments, and it remains difficult to develop a predictive model for ITV that is broadly applicable. Systematically characterizing the sources (e.g. ontogeny, population differences) of ITV will be a vital step forward towards identifying generalities and the underlying mechanisms that shape ITV. While the use of species means to link traits to higher-order processes may be appropriate in many cases, such approaches can obscure potentially meaningful variation. We urge the reporting of individual replicates and population means in online data repositories, a greater consideration of the mechanisms that enhance and constrain ITV's extent, and studies that span sub-disciplines.

Dose-response relationship of temozolomide, determined by the Pig-a, comet, and micronucleus assay.

Temozolomide (TMZ), a monofunctional alkylating agent, was selected as a model compound to determine its quantitative genotoxic dose-response relationship in different tissues (blood, liver, and jejunum) and endpoints [Pig-a-, comet-, and micronucleus assay (MNT)] in male rats. TMZ was administered p.o. over 5 consecutive days (day 1-5), followed by a treatment-free period of 50 days (day 6-56) and a final administration prior to necropsy (day 57-59). TMZ showed a dose-dependent increase in DNA damage in all interrogated endpoints. A statistically significant increase in Pig-a mutant phenotypes was observed on day 44 starting at 7.5 mg/kg/day for mutant reticulocytes (for RETCD59-) and at 3.75 mg/kg/day for mutant red blood cells (RBCCD59-), respectively. In addition, a statistically significant increase in cytogenetic damage, as measured by micronucleated reticulocytes, was observed starting at 3.75 mg/kg/day on day 3 and 1.5 mg/kg/day on day 59. DNA strand breaks, as detected by the comet assay, showed a dose-dependent and statistically significant increase in liver, blood, and jejunum starting at doses of 3.75, 3.75, and 7.5 mg/kg/day, respectively. The dose-response relationships of the Pig-a, MNT, and comet data were analyzed for possible points of departure (PoD) using the benchmark-dose (BMD) software PROAST with different critical effect sizes (CES) (BMD0.1, BMD0.5, BMD1, and BMD1SD). Overall, PoD values show a high concordance between different tissues and endpoints, underlining the suitability of this experimental design to explore quantitative dose-response relationships in a variety of different tissues and endpoints, while minimizing animal use.

Long-term efficacy of combined phacoemulsification plus trabeculectomy versus phacoemulsification plus excimer laser trabeculotomy.

Background Combined cataract and glaucoma procedures, and minimally-invasive glaucoma surgery in particular, have gained increasing interest over the past few years. The aim of this study was to compare the long-term efficacy of combined phaco-trabeculectomy (Phaco-Trab) and combined phacoemulsification plus excimer laser trabeculotomy (Phaco-ELT). Patients and Methods Retrospective, non-randomised, comparative, interventional case series of consecutive patients after Phaco-Trab and Phaco-ELT at the University Hospital of Zurich and the Talacker Eye Center Zurich in Switzerland. Inclusion criteria were diagnosis of glaucoma plus vision-impairing coexisting cataract. Primary outcome measures were change in intraocular pressure (IOP), number of anti-glaucoma drugs (AGDs), and best-corrected visual acuity (BCVA) 1 year and 4 years after the procedure. Secondary outcome measures were surgical complications and requirement of postoperative interventions. Success was defined based on the criteria of the Tube-versus-Trabeculectomy study. Results Mean age was 76.1 ± 8.6 years (29.2 % males; 47.8 % right eyes). Phaco-Trab (n = 62) decreased median IOP from 22.8 to 13.0 at 1 year and to 14.0 mmHg at 4 years. AGDs were reduced from 2 drugs to 0 AGDs at 1 year and 4 years. Median BCVA improved from 0.2 logMAR to 0.0 logMAR at 1 year and 4 years. Phaco-ELT (n = 51) lowered median IOP from 19.0 to 15.0 at 1 year and to 14.0 mmHg (p = 0.002) at 4 years. AGDs were reduced from 2 drugs to 1 AGD at 1 year and 4 years (p = 0.002). BCVA improved from 0.4 logMAR to 0.1 logMAR after 1 year and 4 years. If not stated otherwise, all changes compared to baseline were highly significant (p < 0.001). No perioperative complications occurred; postoperative interventions were performed in 74 % of Phaco-Trab patients. Conclusion Both surgical procedures reduced IOP and AGDs and improved BCVA significantly and persistently during the entire follow-up period of 4 years with a good safety profile. This study validates Phaco-ELT as an option when post-operative target pressure in the mid-teens would be adequate, whereas Phaco-Trab would be the treatment of choice when IOP in the low teens is desired.

Semiautomated quantitative image analysis of glomerular immunohistochemistry markers desmin, vimentin, podocin, synaptopodin and WT-1 in acute and chronic rat kidney disease models.

Five different glomerular immunohistochemistry markers were evaluated and compared in four different acute and chronic rat kidney disease models. Progression of glomerular or podocyte damage was shown in the puromycin aminonucleoside nephrosis (PAN) and Zucker fatty/spontaneously hypertensive heart failure F1 hybrid (ZSF1) rat model. Progression and prevention of glomerular damage was demonstrated in the Zucker diabetic fatty (ZDF) and Dahl salt-sensitive (Dahl SS) rat. Immunohistochemistry was performed for desmin, vimentin, podocin, synaptopodin and Wilms tumor protein-1 (WT-1), and evaluation of glomerular immunohistochemistry markers was done by semiautomated quantitative image analysis. We found desmin and WT-1 as the most sensitive markers for podocyte damage in both acute and chronic glomerular damage followed by vimentin, podocin and synaptopodin. We were able to demonstrate that early podocyte damage as shown by increased desmin and vimentin staining together with either a phenotypic podocyte change or podocyte loss (reduced numbers of WT-1-stained podocytes) drives the progression of glomerular damage. This is followed by a reduction in podocyte-specific proteins such as podocin and synaptopodin. Our report describes the different sensitivity of glomerular or podocyte markers and gives future guidance for the selection of the most sensitive markers for efficacy testing of new drugs as well as for the selection of tissue-based toxicity markers for glomerular or podocyte injury. In addition to functional clinical chemistry markers, desmin and WT-1 immunohistochemistry offers reliable and valuable data on the morphologic state of podocytes.

Increasing incidence of non-O157 Shiga toxin-producing Escherichia coli (STEC) in Michigan and association with clinical illness.

Infection with Shiga toxin-producing Escherichia coli (STEC) by serotypes other than O157 (non-O157) have been increasingly reported in the United States. This increase in reporting is primarily due to the improvements in diagnostic tests. We analysed 1497 STEC cases reported in Michigan from 2001 to 2012. A significant increase in the number of non-O157 STEC cases was observed over time, and similar incidence rates were observed for O157 and non-O157 STEC cases in certain time periods. The odds of hospitalization was two times higher in O157 STEC cases relative to non-O157 STEC cases when adjusted for age and gender, suggesting that O157 STEC causes more severe clinical outcomes in all age groups. The use of population-based surveillance to better define trends and associations with disease severity are critical to enhance our understanding of STEC infections and improve upon current prevention and control efforts.

Cytotoxic and apoptotic effects of recombinant subtilase cytotoxin variants of shiga toxin-producing Escherichia coli.

In this study, the cytotoxicity of the recently described subtilase variant SubAB2-2 of Shiga toxin-producing Escherichia coli was determined and compared to the plasmid-encoded SubAB1 and the chromosome-encoded SubAB2-1 variant. The genes for the respective enzymatic active (A) subunits and binding (B) subunits of the subtilase toxins were amplified and cloned. The recombinant toxin subunits were expressed and purified. Their cytotoxicity on Vero cells was measured for the single A and B subunits, as well as for mixtures of both, to analyze whether hybrids with toxic activity can be identified. The results demonstrated that all three SubAB variants are toxic for Vero cells. However, the values for the 50% cytotoxic dose (CD50) differ for the individual variants. Highest cytotoxicity was shown for SubAB1. Moreover, hybrids of subunits from different subtilase toxins can be obtained which cause substantial cytotoxicity to Vero cells after mixing the A and B subunits prior to application to the cells, which is characteristic for binary toxins. Furthermore, higher concentrations of the enzymatic subunit SubA1 exhibited cytotoxic effects in the absence of the respective B1 subunit. A more detailed investigation in the human HeLa cell line revealed that SubA1 alone induced apoptosis, while the B1 subunit alone did not induce cell death.

Morphologic assessment of thoracic deformities for the preoperative evaluation of pectus excavatum by magnetic resonance imaging.

OBJECTIVE: To assess whether MRI is a suitable modality for the preoperative assessment and quantification of pectus excavatum. METHODS: A total of 69 patients (57 male, 12 female; median age 15 years, range 5-35 years) with pectus excavatum were evaluated preoperatively using standardized MRI sequences on 1.5- and 3-Tesla systems (T2-HASTE/inspiration and expiration, T1-VIBE, T2-TRUFI free-breathing, T2-BLADE). The MR sequences were analysed for quality semiquantitatively. The Haller index, correction index, sternal rotation angle and asymmetry index were assessed; correlations between these indices and changes in inspiration and expiration were evaluated. RESULTS: T2-HASTE was the best sequence to assess pectus excavatum morphology, with a higher quality at 3 T than at 1.5 T. All indices could be assessed in every patient. A total of 37 patients had a symmetric deformity, 32 patients an asymmetric deformity. The Haller index correlated significantly (p < 0.001) with the correction index, both becoming higher in expiration. The asymmetry index correlated with the sternal rotation angle (p < 0.001) and did not change significantly in expiration (p = 0.28). CONCLUSIONS: Thoracic MRI is suitable for the preoperative evaluation of patients with pectus excavatum. An exact morphologic assessment is possible without radiation exposure as well as the determination of several indices to quantify the deformities.

Shiga toxin-producing E. coli (STEC) in swine: prevalence over the finishing period and characteristics of the STEC isolates.

This descriptive longitudinal study was conducted to investigate the faecal shedding of Shiga toxin-producing E. coli (STEC) in finishing swine and to characterize the swine STEC isolates that were recovered. Three cohorts of finishing swine (n = 50/cohort; total 150 pigs) were included in the longitudinal study. Individual faecal samples were collected every 2 weeks (8 collections/pig) from the beginning (pig age 10 weeks) to the end (pig age 24 weeks) of the finishing period. STEC isolates were recovered in at least one sample from 65·3% (98/150) of the pigs, and the frequency distribution of first-time STEC detection during the finishing period resembled a point-source outbreak curve. Nineteen O:H serotypes were identified among the STEC isolates. Most STEC isolates (n = 148) belonged to serotype O59:H21 and carried the stx 2e gene. One O49:H21 STEC isolate carried the stx 2e and eae genes. High prevalence rates of STEC during the finishing period were observed, and STEC isolates in various non-O157 serogroups were recovered. These data enhance understanding of swine STEC epidemiology, and future research is needed to confirm whether or not swine STEC are of public health concern.

Long-term effect of selective laser trabeculoplasty on intraocular pressure in pseudoexfoliation glaucoma.

BACKGROUND: Selective laser trabeculoplasty has been found to be effective as an adjunct to topical medical therapy in glaucoma. This analysis examines the intraocular pressure lowering effect of laser trabeculoplasty in eyes with pseudoexfoliation on maximum medical therapy. MATERIAL AND METHODS: A retrospective chart review was undertaken of 457 eyes of which 344 underwent a 360° selective laser trabeculoplasty treatment between 2008 and 2013. 94 of these eyes had pseudoexfoliation. Intraocular pressure values were analysed in 3 monthly intervals up to 60 months after selective laser trabeculoplasty. Exclusion criteria were narrow or closed angles as well as uveitic glaucoma and previous intraocular pressure lowering surgery. RESULTS: Patients mean age was 71 years±11.0 SD, 42.7% were male. At time point 12 months after selective laser trabeculoplasty the intraocular pressure lowering effect was significantly greater in eyes with pseudoexfoliation than in eyes without pseudoexfoliation (p=0.01; Mann-Whitney test). Up to 21 months after selective laser trabeculoplasty a significant intraocular pressure reduction of 2.76 mmHg±3.72 SD compared to baseline values could be seen in eyes with pseudoexfoliation (p=0.01; Wilcoxon Test). CONCLUSIONS: In this retrospective study a significant greater intraocular pressure lowering effect of selective laser trabeculoplasty could be seen in eyes with pseudoexfoliation compared to eyes without pseudoexfoliation only at time point 12 months after selective laser trabeculoplasty. Analyses revealed no significant intraocular pressure reduction compared to baseline values after 21 months in eyes with pseudoexfoliation and after 30 months in eyes without pseudoexfoliation.

[Visual outcome after trabeculectomy - a retrospective study]. / Visusentwicklung nach Trabekulektomie - eine retrospektive Studie.

BACKGROUND: Trabeculectomy (TE) is the standard operation for glaucoma. An alternative interventional treatment of glaucoma is the cyclophotocoagulation (CPC). In a data analysis in 2012, a visual loss was found after transscleral CPC. The aim of this study was to investigate the outcome after TE. PATIENTS AND METHODS: 91 patients with pseudoexfoliation (n=38), open angle (n=22), normal tension (n=8), congenital (n=1) and secondary glaucoma (n=22) were included. The follow-up time was 24 months. Intraocular pressure (IOP), best corrected visual acuity (BCVA) and the total number of antiglaucoma drugs (AGD) were recorded. RESULTS: The mean age was 68.18±12.12 years. Mean IOP reduction after 24 months was 14.76±10.62 mmHg (-49%, p<0.001). On average, 2.34±1.17 (-85%, p<0.001) AGDs could be reduced. A mean BCVA decrease of 0.15 logMAR (±0.26, p<0.001) was found. CONCLUSION: TE is a successful method for lowering the IOD. However, postoperative visual loss is possible.

[Epiphyseolysis of the femoral head: new aspects of diagnostics and therapy]. / Epiphyseolysis capitis femoris : Neue Aspekte in Diagnostik und Therapie.

BACKGROUND: Slipped capital femoral epiphysis (SCFE) is the most common hip disease in adolescents and is always surgically treated with the aim to avoid further slippage and to reduce the risk of degenerative arthritis at young age. OBJECTIVES: A summary of the etiology, pathogenesis, clinical features, radiographic imaging and current therapy concepts is given. MATERIAL AND METHODS: A selective review of the literature was performed. RESULTS: With an increasing body mass index in adolescents the incidence of SCFE also increases. The diagnostic routine is comprised of a clinical examination with the evaluation of Drehmann's sign and a radiographic evaluation including anterior-posterior aspect and frog's legs view. In situ stabilization with a single screw is the standard treatment for the most prevalent mild or moderate stable slippages. In cases of acute slippage a gentle reduction maneuver may be attempted. Hardware removal must not be performed before epiphyseal closure. Common bilateral but not simultaneous occurrence of the disease requires prophylactic pinning of the unaffected side by default, at least in central Europe. Various surgical treatment options exist to reduce the femoroacetabular impingement caused by the slippage. CONCLUSIONS: Current treatment algorithms result in satisfactory long-term outcomes. If the risk of developing degenerative arthritis after SCFE may be reduced even more with modern arthroscopic or open surgical procedures to restore the anatomic pre-slip conditions has to be confirmed through further long-term studies. The implementation of programs to prevent obesity in adolescents may also reduce the incidence of SCFE.

[Current care strategies for Duchenne muscular dystrophy]. / Aktuelle Betreuungsstrategien bei Duchenne-Muskeldystrophie.

BACKGROUND: The medical care of patients with Duchenne muscular dystrophy (DMD) is an interdisciplinary and multifaceted task. The vast majority of those affected show a nearly constant course which is reflected in a corresponding stage-oriented treatment concept. Although there is still no causal therapy available for DMD, the course and in particular the quality of life of patients can be decisively improved by established medical practices. THERAPEUTIC STRATEGIES: The orthopedic problems of DMD patients include contractures of the upper and lower extremities as well as sitting instability due to progressive scoliosis with pelvic imbalance. The orthopedic treatment incorporates conservative measures, such as physiotherapy, provision of orthotic devices and wheelchairs as well as surgery to resolve contractures of the lower extremities and surgical stabilization of the spine. Furthermore, in these patients orthopedic surgeons and trauma surgeons are confronted with the treatment and prophylaxis of fractures induced by osteoporosis. An early onset of glucocorticoid therapy markedly delays the loss of motor abilities. TREATMENT ASPECTS: An important aspect in the care of DMD patients is the timely prophylaxis and treatment of respiratory insufficiency with regular sessions of breathing therapy, learning breathing and coughing techniques and the sufficiently early start of non-invasive mechanically assisted ventilation. Of similar relevance are also the early recognition and cardioprotective treatment of cardiomyopathy. CONCLUSION: The orthopedic surgeon accompanies the patient and family through all stages of the disease and must be appropriately informed on current management and treatment strategies even outside the limits of the personal field of specialization.

Posterior pole asymmetry analysis with optical coherence tomography.

BACKGROUND: The aim of this study was to evaluate the reproducibility of the posterior pole asymmetry analysis (PPAA) in glaucomatous eyes and healthy controls in comparison to retinal nerve fiber layer measurements (RNFL) with spectral domain optical coherence tomography (SD-OCT). PATIENTS AND METHODS: Prospectively, in a single session by one operator, three measurements were taken of the retinal thickness with the PPAA and three measurements of the RNFL with the eye-tracker function of the Heidelberg Spectralis SD-OCT. RESULTS: The mean intraclass correlation coefficient (ICC) and lower confidence intervals (in parentheses) for PPAA were 0.98 (0.96) in both healthy (36 eyes) and glaucomatous eyes (26 eyes). Global coefficients of variation (COVs) were between 0.0 and 1.1% in healthy controls and between 0.0 and 1.9% in glaucoma eyes. Global ICCs for RNFL were 0.98 (0.96) in healthy controls and 0.98 (0.97) in glaucoma eyes and global COVs were between 0.0 and 6.8% in healthy controls and between 0.0 and 3.0% in glaucoma eyes. CONCLUSION: Reproducibility of the PPAA was good and exceeds that of established RNFL measurements. Thus, PPAA is an additional useful tool in management of glaucoma.

Long-term efficacy of selective laser trabeculoplasty in patients on prostaglandin therapy.

BACKGROUND: The aim of the study was to analyse the efficacy of selective laser trabeculoplasty in patients on medical therapy and to evaluate a possible influence of prostaglandin therapy on intraocular pressure reduction. PATIENTS AND METHODS: A retrospective chart review was undertaken of patients with ocular hypertension or open angle glaucoma who underwent selective laser trabeculoplasty between 3/2008 and 12/2010. Data were collected preoperatively, on the day of intervention, 1 day, 1 month and then every 3 months post selective laser trabeculoplasty. The main outcome measure was mean intraocular pressure reduction. RESULTS: 109 eyes (76 on prostaglandins) were included. Mean preoperative intraocular pressure was 22.3 ± 4.5 mmHg (prostaglandin naïve) and 19.2 ± 4.8 mmHg (on prostaglandin) (p=0.003). Up to 1 year follow-up, intraocular pressure was statistically significantly reduced in both groups (p ≤ 0.019). Eyes with a higher preoperative intraocular pressure had a greater pressure reduction (Spearman rho=0.387, p=0.002). Eyes naïve to prostaglandins initially had a greater reduction in intraocular pressure, although after 1 year of follow-up the difference was no longer statistically significant. CONCLUSIONS: Selective laser trabeculoplasty significantly reduces intraocular pressure in patients already on medical therapy. A sustained influence of prostaglandin therapy on the efficacy of selective laser trabeculoplasty was not found.

Long-term efficacy of selective laser trabeculoplasty in pseudophakic patients - a "real-life" analysis.

BACKGROUND: The aim of this study was to report on the course and long-term effect of selective laser trabeculoplasty on intraocular pressure of pseudophakic patients suffering from open angle glaucoma or ocular hypertension with insufficient intraocular pressure lowering despite maximally tolerated topical and systemic intraocular pressure lowering medication. PATIENTS AND METHODS: A retrospective chart review of patients who underwent selective laser trabeculoplasty (360°) between 2008 and 2010 at the University hospital Zurich was undertaken. Intraocular pressure values before intervention, on the day of the intervention, 1 day, 1 month, 3 months and every 3 months up to 43 months after the intervention were analysed with respect to lens status. RESULTS: Out of 153 treated eyes of 111 patients (mean age 70.6 years ± 11.13 SD) 40 were pseudophakic. Mean baseline intraocular pressures were 19.00 mmHg ± 4.61 in the pseudophakic group and 20.12 mmHg ± 4.89 in the phakic group. One month after selective laser trabeculoplasty intraocular pressure reduction measured between -0.33 and -4.10 mmHg (CI 95%) in the pseudophakic group and between -3.64 and -5.58 mmHg (CI 95%) in the phakic group, the difference at this time point was significant (p=0.01). Beyond one month after selective laser trabeculoplasty there was no statistically significant difference in intraocular pressure reduction between pseudophakic and phakic patients. The mean decrease in intraocular pressure from baseline to the last follow-up of 43 months was 0.67 mmHg in the pseudophakic group and 0.25 mmHg in the phakic group (p=0.72). CONCLUSIONS: One month after selective laser trabeculoplasty pseudophakic patients showed a statistically significant diminished reduction of intraocular pressure compared to phakic patients. Later on there was no statistically significant difference in intraocular pressure reduction between pseudophakic and phakic patients. Therefore we conclude that there was no clinically relevant influence of pseudophakia on the long-term effect of selective laser trabeculoplasty.

Effects of the dual PPAR-α/γ agonist aleglitazar on glycaemic control and organ protection in the Zucker diabetic fatty rat.

AIMS: To evaluate the effects of aleglitazar, a dual peroxisome proliferator-activated receptor-α/γ agonist, on the development of diabetes-related organ dysfunction, in relation to glycaemic and lipid changes, in Zucker diabetic fatty (ZDF) rats. METHODS: Six-week-old, male ZDF rats received aleglitazar 0.3 mg/kg/day or vehicle as food admix for 13 weeks (n = 10 per group). Age-matched male Zucker lean rats served as non-diabetic controls. Plasma and renal markers were measured at several time points. Histopathology and quantitative immunohistochemistry were performed at 13 weeks. RESULTS: Glycated haemoglobin (5.4 vs. 9.2%) and blood glucose (8.3 ± 0.3 vs. 26.1 ± 1.0 mmol/l) were significantly reduced at 12 weeks with aleglitazar versus vehicle-treated ZDF rats (both p < 0.01), while aleglitazar preserved near-normal plasma insulin levels. Aleglitazar prevented the development of hypertriglyceridaemia (1.4 ± 0.1 vs. 8.5 ± 0.9 mmol/l) and reduced plasma non-esterified fatty acids (0.09 ± 0.02 vs. 0.26 ± 0.04 mmol/l) relative to vehicle-treated animals (both p < 0.01). Urinary glucose and protein concentrations were significantly reduced at 13 weeks with aleglitazar versus vehicle-treated rats (both p < 0.01). Consistent with its effect on glycaemic control, aleglitazar protected ß-cell morphology, as evidenced by preservation of islet integrity, and reduction of ß-cell apoptosis and islet fibrosis. Aleglitazar prevented renal glomerular hypertrophy, podocyte degeneration, glomerulosclerosis, tubulo-interstitial lesions and development of cataracts. CONCLUSIONS: Aleglitazar strongly improved glycaemic and lipid parameters while protecting key tissues, including the pancreas, kidneys and eyes, against diabetes-associated structural and functional changes in the ZDF rat.

Longitudinal study of Salmonella shedding in naturally infected finishing pigs.

A 3-year longitudinal study was conducted on a multi-site farrow-to-finish production system. For each of 18 cohorts at three finishing sites, 50 pigs were randomly selected. Faecal samples were collected every 2 weeks for 16 weeks. Salmonella was cultured from 453 (6·6%) of 6836 faecal samples. The pig-level incidence of Salmonella was 20·8% (187/899 pigs). Salmonella prevalence varied between cohorts and within pigs. The adjusted Salmonella prevalence decreased over the finishing period from 6·4% to 0·8%. Intermittent detection of Salmonella was found in more than 50% of pigs that were positive at more than one collection. The finding that the majority of pigs shed intermittently has implications for surveillance and research study design when determining Salmonella status. The variability in shedding over time, as well as between and within cohorts and pigs suggests that there may be time-variant risk factors for Salmonella shedding in swine.

[Transscleral cyclophotocoagulation as primary surgical intervention in glaucoma]. / Transsklerale Zyklophotokoagulation als primäre antiglaukomatöse Operation.

BACKGROUND: The gold standard of surgical interventions in medically uncontrolled glaucoma is trabeculectomy. Cyclophotocoagulation is often performed only as a secondary/tertiary surgery. Since trabeculectomy demands a high degree of postsurgical compliance to achieve satisfying results, some patients do not qualify for trabeculectomy. PATIENTS AND METHODS: During cyclophotocoagulation, the ciliary processes were coagulated using a transscleral diode laser. 49 eyes of 47 patients (25 women and 22 men) were included in our study. Patients were regularly followed up for 24 months. During follow-up, IOP, best corrected visual acuity and number of antiglaucoma drugs were recorded. RESULTS: The mean age was 69.27 ± 14.45 years. The diagnosis was open-angle glaucoma in 15 eyes, pseudoexfoliative glaucoma in 12 eyes, secondary rubeotic glaucoma in 7 eyes and secondary glaucoma without further specification in 15 eyes. On average, cyclophotocoagulation reduced intraocular pressure by 14.45 ± 11.77 mmHg (-42.7%, p < 0.001). Medication could be reduced by 1.31 ± 1.27 (-52%, p < 0.001). On average, visual acuity deteriorated by 0.383 LogMAR (± 0.848, p = 0.004). CONCLUSION: For selected glaucoma patients, cyclophotocoagulation could be an option as primary surgical intervention to lower intraocular pressure.

Decreased bone mineral density in rats rendered follicle-deplete by an ovotoxic chemical correlates with changes in follicle-stimulating hormone and inhibin A.

Bone loss during perimenopause, an estrogen-sufficient period, correlates with elevated serum follicle-stimulating hormone (FSH) and decreased inhibins A and B. Utilizing a recently described ovotoxin-induced animal model of perimenopause characterized by a prolonged estrogen-replete period of elevated FSH, we examined longitudinal changes in bone mineral density (BMD) and their association with FSH. Additionally, serum inhibin levels were assessed to determine whether elevated FSH occurred secondary to decreased ovarian inhibin production and, if so, whether inhibins also correlated with BMD. BMD of the distal femur was assessed using dual-energy X-ray absorptiometry (DXA) over 19 months in Sprague-Dawley rats treated at 1 month with vehicle or 4-vinylcyclohexene diepoxide (VCD, 80 or 160 mg/kg daily). Serum FSH, inhibins A and B, and 17-ß estradiol (E(2)) were assayed and estrus cyclicity was assessed. VCD caused dose-dependent increases in FSH that exceeded values occurring with natural senescence, hastening the onset and prolonging the duration of persistent estrus, an acyclic but E(2)-replete period. VCD decreased serum inhibins A and B, which were inversely correlated with FSH (r(2) = 0.30 and 0.12, respectively). In VCD rats, significant decreases in BMD (5-13%) occurred during periods of increased FSH and decreased inhibins, while BMD was unchanged in controls. In skeletally mature rats, FSH (r(2) = 0.13) and inhibin A (r(2) = 0.15) correlated with BMD, while inhibin B and E(2) did not. Thus, for the first time, both the hormonal milieu of perimenopause and the association of dynamic perimenopausal changes in FSH and inhibin A with decreased BMD have been reproduced in an animal model.