Estimating the burden of disease attributable to childhood and maternal undernutrition in South Africa in 2000

Objectives. To estimate the disease burden attributable to being underweight as an indicator of undernutrition in children under 5 years of age and in pregnant women for the year 2000. Design. World Health Organization comparative risk assessment (CRA) methodology was followed. The 1999 National Food Consumption Survey prevalence of underweight classified in three low weight-for-age categories was compared with standard growth charts to estimate population-attributable fractions for mortality and morbidity outcomes, based on increased risk for each category and applied to revised burden of disease estimates for South Africa in 2000. Maternal underweight, leading to an increased risk of intra-uterine growth retardation and further risk of low birth weight (LBW), was also assessed using the approach adopted by the global assessment. Monte Carlo simulation-modelling techniques were used for the uncertainty analysis. Setting. South Africa. Subjects. Children under 5 years of age and pregnant women. Outcome measures. Mortality and disability-adjusted life years (DALYs) from protein- energy malnutrition and a fraction of those from diarrhoeal disease, pneumonia, malaria, other non- HIV/AIDS infectious and parasitic conditions in children aged 0 - 4 years, and LBW. Results. Among children under 5 years, 11.8% were underweight. In the same age group, 11 808 deaths (95% uncertainty interval 11 100 - 12 642) or 12.3% (95% uncertainty interval 11.5 - 13.1%) were attributable to being underweight. Protein-energy malnutrition contributed 44.7% and diarrhoeal disease 29.6% of the total attributable burden. Childhood and maternal underweight accounted for 2.7% (95% uncertainty interval 2.6 - 2.9%) of all DALYs in South Africa in 2000 and 10.8% (95% uncertainty interval 10.2 - 11.5%) of DALYs in children under 5. Conclusions. The study shows that reduction of the occurrence of underweight would have a substantial impact on child mortality, and also highlights the need to monitor this important indicator of child health. South African Medical Journal Vol. 97 (8) Part 2 2007: pp. 733-73

Calcitriol suppression of parathyroid hormone fails to improve skeletal properties in an animal model of chronic kidney disease

BACKGROUND: Chronic kidney disease (CKD) leads to complex metabolic changes and an increased risk of fracture. Currently, calcitriol is the standard of care as it effectively suppresses parathyroid hormone (PTH) levels in CKD patients. While calcitriol and its analogs improve BMD and reduce fractures in the general population, the extension of these benefits to patients with advanced kidney disease is unclear. Here, the impact of calcitriol on the skeleton was examined in the setting of reduction in PTH. METHODS: Male Cy/+ rats, a PKD-like CKD model, were treated with either vehicle or calcitriol for 5 weeks. Their normal littermates served as controls. Animals were assessed for changes in mineral metabolism and skeletal parameters (microCT, histology, whole bone mechanics and bone quality). RESULTS: PTH levels were significantly higher (12-fold) in animals with CKD compared to normal controls. CKD animals also exhibited negative changes in bone structural and mechanical properties. Calcitriol treatment resulted in a 60% suppression of PTH levels in animals with CKD. Despite these changes, it had no impact on bone volume (cortical or cancellous), bone turnover, osteoclast number or whole bone mechanical properties. CONCLUSIONS: These data indicate that while calcitriol effectively lowered PTH in rats with CKD, it did little to prevent the negative effects of secondary hyperparathyroidism on the skeleton

Raloxifene improves skeletal properties in an animal model of cystic chronic kidney disease

Patients with chronic kidney disease (CKD) have an increased risk of fracture. Raloxifene is a mild antiresorptive agent that reduces fracture risk in the general population. Here we assessed the impact of raloxifene on the skeletal properties of animals with progressive CKD. Male Cy/+ rats that develop autosomal dominant cystic kidney disease were treated with either vehicle or raloxifene for five weeks. They were assessed for changes in mineral metabolism and skeletal parameters (microCT, histology, whole-bone mechanics, and material properties). Their normal littermates served as controls. Animals with CKD had significantly higher parathyroid hormone levels compared with normal controls, as well as inferior structural and mechanical skeletal properties. Raloxifene treatment resulted in lower bone remodeling rates and higher cancellous bone volume in the rats with CKD. Although it had little effect on cortical bone geometry, it resulted in higher energy to fracture and modulus of toughness values than vehicle-treated rats with CKD, achieving levels equivalent to normal controls. Animals treated with raloxifene had superior tissue-level mechanical properties as assessed by nanoindentation, and higher collagen D-periodic spacing as assessed by atomic force microscopy. Thus, raloxifene can positively impact whole-bone mechanical properties in CKD through its impact on skeletal material properties

Initial burden of disease estimates for South Africa, 2000

BACKGROUND This paper describes the first national burden of disease study for South Africa. The main focus is the burden due to premature mortality, i.e. years of life lost (YLLs). In addition, estimates of the burden contributed by morbidity, i.e. the years lived with disability (YLDs), are obtained to calculate disability-adjusted life years (DALYs); and the impact of AIDS on premature mortality in the year 2010 is assessed. METHOD Owing to the rapid mortality transition and the lack of timely data, a modelling approach has been adopted. The total mortality for the year 2000 is estimated using a demographic and AIDS model. The non-AIDS cause-of-death profile is estimated using three sources of data: Statistics South Africa, the National Department of Home Affairs, and the National Injury Mortality Surveillance System. A ratio method is used to estimate the YLDs from the YLL estimates. RESULTS The top single cause of mortality burden was HIV/AIDS followed by homicide, tuberculosis, road traffic accidents and diarrhoea. HIV/AIDS accounted for 38% of total YLLs, which is proportionately higher for females (47%) than for males (33%). Pre-transitional diseases, usually associated with poverty and underdevelopment, accounted for 25%, non-communicable diseases 21% and injuries 16% of YLLs. The DALY estimates highlight the fact that mortality alone underestimates the burden of disease, especially with regard to unintentional injuries, respiratory disease, and nervous system, mental and sense organ disorders. The impact of HIV/AIDS is expected to more than double the burden of premature mortality by the year 2010. CONCLUSION This study has drawn together data from a range of sources to develop coherent estimates of premature mortality by cause. South Africa is experiencing a quadruple burden of disease comprising the pre-transitional diseases, the emerging chronic diseases, injuries, and HIV/AIDS. Unless interventions that reduce morbidity and delay morbidity become widely available, the burden due to HIV/AIDS can be expected to grow very rapidly in the next few years. An improved base of information is needed to assess the morbidity impact more accurately

On the development of extragonadal and gonadal human germ cells

Human germ cells originate in an extragonadal location and have to migrate to colonize the gonadal primordia at around seven weeks of gestation (W7, or five weeks post conception). Many germ cells are lost along the way and should enter apoptosis, but some escape and can give rise to extragonadal germ cell tumors. Due to the common somatic origin of gonads and adrenal cortex, we investigated whether ectopic germ cells were present in the human adrenals. Germ cells expressing DDX4 and/or POU5F1 were present in male and female human adrenals in the first and second trimester. However, in contrast to what has been described in mice, where 'adrenal' and 'ovarian' germ cells seem to enter meiosis in synchrony, we were unable to observe meiotic entry in human 'adrenal' germ cells until W22. By contrast, 'ovarian' germ cells at W22 showed a pronounced asynchronous meiotic entry. Interestingly, we observed that immature POU5F1+ germ cells in both first and second trimester ovaries still expressed the neural crest marker TUBB3, reminiscent of their migratory phase. Our findings highlight species- specific differences in early gametogenesis between mice and humans. We report the presence of a population of ectopic germ cells in the human adrenals during development

Fatigue and microgap behaviour of a three-unit implant-fixed dental prosthesis combining conventional and dynamic abutments

This is an in vitro study composed by a fatigue test followed by an optical microscopy analysis. Dynamic abutments concept, recently introduced on screw-retained implant dental prosthesis, consists on the screw channel customisation according to the individual needs of each rehabilitation. Geometry and tightening torque differences advise the assessment of their mechanical performance. Clarify whether the combination of dynamic and conventional abutments in a three-unit implant-fixed prosthesis has detrimental effects either on the mechanical performance under cyclic loading or on the implant-abutment microgap dimensions. The fatigue test was performed in agreement with the ISO standard 14801. Then on the samples that resisted 5 million cycles, the implant-abutment microgap was measured on dynamic and conventional abutments using optical microscopy. Two unloaded samples were used as control group. The samples supported a load of 1050 N. The implant-abutment microgap measurement did not show statistically significant differences (p=.086) between loaded and unloaded groups, but the loaded conventional abutments showed a significant lower implant-abutment microgap (p=.05) than the loaded dynamic abutments. The combination of conventional and dynamic abutments do not seem to produce a decrease in fatigue resistance to a level below the mastication forces or an increase in the joint dimensions.The study was supported in part by SciTech - Science and Technology for Competitive and Sustainable Industries, and the R&D project was cofinanced by the North Portugal Regional Operational Program ("NORTE2020") and the European Regional Development Fund (FEDER)

Characterization of a preclinical PET insert in a 7 tesla MRI scanner: beyond NEMA testing

[EN] This study evaluates the performance of the Bruker positron emission tomograph (PET) insert combined with a BioSpec 70/30 USR magnetic resonance imaging (MRI) scanner using the manufacturer acceptance protocol and the NEMA NU 4-2008 for small animal PET. The PET insert is made of 3 rings of 8 monolithic LYSO crystals (50 x 50 x 10 mm(3)) coupled to silicon photomultipliers (SiPM) arrays, conferring an axial and transaxial FOV of 15 cm and 8 cm. The MRI performance was evaluated with and without the insert for the following radiofrequency noise, magnetic field homogeneity and image quality. For the PET performance, we extended the NEMA protocol featuring system sensitivity, count rates, spatial resolution and image quality to homogeneity and accuracy for quantification using several MRI sequences (RARE, FLASH, EPI and UTE). The PET insert does not show any adverse effect on the MRI performances. The MR field homogeneity is well preserved (Diameter Spherical Volume, for 20 mm of 1.98 +/- 4.78 without and -0.96 +/- 5.16 Hz with the PET insert). The PET insert has no major effect on the radiofrequency field. The signal-to-noise ratio measurements also do not show major differences. Image ghosting is well within the manufacturer specifications (<2.5%) and no RF noise is visible. Maximum sensitivity of the PET insert is 11.0% at the center of the FOV even with simultaneous acquisition of EPI and RARE. PET MLEM resolution is 0.87 mm (FWHM) at 5 mm off-center of the FOV and 0.97 mm at 25 mm radial offset. The peaks for true/noise equivalent count rates are 410/240 and 628/486 kcps for the rat and mouse phantoms, and are reached at 30.34/22.85 and 27.94/22.58 MBq. PET image quality is minimally altered by the different MRI sequences. The Bruker PET insert shows no adverse effect on the MRI performance and demonstrated a high sensitivity, sub-millimeter resolution and good image quality even during simultaneous MRI acquisition.We acknowledge the KU Leuven core facility, Molecular Small Animal Imaging Center (MoSAIC), for their support with obtaining scientific data presented in this paper. This work was supported by Stichting tegen Kanker (2015-145, Christophe M. Deroose) and Hercules foundation (AKUL/13/029, Uwe Himmelreich) for the purchase of the PET and MRI equipment respectively. The work was supported by the following funding organizations: European Commission for the PANA project (H2020-NMP-2015-two-stage, grant 686009) and the European ERA-NET project 'CryptoView' (3rd call of the FP7 program Infect-ERA).Gsell, W.; Molinos, C.; Correcher, C.; Belderbos, S.; Wouters, J.; Junge, S.; Heidenreich, M.... (2020). Characterization of a preclinical PET insert in a 7 tesla MRI scanner: beyond NEMA testing. 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A humification-based method toward refining Holocene radiocarbon chronologies: Wetland records from southeastern China

Holocene paleoclimate reconstructions and comparisons largely rely on accurate age-depth modeling. However, uncertainties in chronology, such as those caused by sparse radiocarbon dates, will hamper inter-core comparisons and correlations, and might result in misleading “cause and consequence” conclusions. This study aimed to find a solution to increase the comparability and minimize the uncertainty of wetland chronology as much as possible. Sediment cores were recovered and radiocarbon dated from the Lianhuachi wetland located in Southeastern China. Humification degree and loss-on-ignition (LOI) were determined using colorimetric and combustion methods respectively. Our data were compared with previously published datasets obtained in the same wetland. The results show that independent humification profiles from the Lianhuachi wetland displayed high similarities. This high similarity between the humification profiles allowed us to transfer radiocarbon ages from one core to another using sequence slotting correlation. Applying the humification-based chronology refinement method to all sediment cores resulted in an improvement in the correlation coefficients between the same but independently measured proxy sequences from the wetland, which suggests both the inter- and intra-core comparability was improved. Because determining peat humification degree is easy, inexpensive, and time-saving, we suggest that humification can serve as a tool that can be used to correlate different cores and to transfer published radiocarbon ages within the same wetland (peatland) or in a comparable geological setting, to establish a more robust chronology of these comparable cores. The degree of peat humification can thus serve as a relative dating technique to refine the chronology of wetland (including peatland) records