Lifespan changes in the index of cephalization

This study compares the lifespan changes in respect to several brain-body weight parameters between several rat strains and human population groups. In the rat, following an initial potential decline, these parameters remain essentially constant throughout the lifespan. In the human, following a similar postnatal decline, there is a further progressive decline after about age 50. However, this decline with age disappears when correction is made for percent body fat. Thus, while both brain and body weight decline with age in humans, they do not decline proportionately. In both species brain and body weights are greater in males than in females, but when the data are translated into the several brain-body parameters females generally show higher indices than males, and this correlates with their superior longevity. These findings are discussed in respect to the role of the brain in aging.     

Association between renal cystic lesions and bilateral Wilms’ tumours

Objectives

Evaluate a potential association between Wilms’ tumour (WT) and renal cystic lesions.

Methods

Digital records and imaging files of consecutive patients diagnosed with WT between 2004 and 2014 were retrospectively reviewed under an Institutional Review Board waiver of informed consent. The locations of renal cysts seen on US, CT, and/or MRI were recorded and compared with the locations of newly developed WT.

Results

A total of 48 patients (mean age 3 years 9 months) presented with newly diagnosed WT in the study period. Mean follow-up was 4.5 (range 1–10) years. WT was unilateral in 40 children, bilateral in 8. Renal cysts were identified in only one of the forty patients (2.5 %) with unilateral disease – in the contralateral kidney. In contrast, renal cysts were found in seven of eight patients with bilateral WT (87.5 %), in two of whom, new tumours developed in the same location where cysts had been seen on previous imaging studies.

Conclusions

Renal cystic lesions in patients with Wilms’ tumour should be regarded as potential tumour precursors, and followed with frequent imaging.

Key Points

? Cortical renal cystic lesions have a high association with bilateral Wilms’ tumour. ? In children with Wilms’ tumour renal cysts are possible tumour precursors. ? MRI appears to be the best modality in depicting the cortical cysts.

     

Evaluation of recombinant human bone morphogenetic protein-2 on the repair of alveolar ridge defects in baboons

BACKGROUND: The objective of this study was to evaluate alveolar ridge augmentation following surgical implantation of recombinant human bone morphogenetic protein-2 (rhBMP-2) using two novel space-providing carrier technologies in the baboon (Papio anubis) model. METHODS: Standardized alveolar ridge defects ( approximately 15 x 8 x 5 mm) were surgically produced in maxillary and mandibular edentulous areas in four baboons. The defect sites were implanted with rhBMP-2 (0.4 mg/mL) in a tricalcium phosphate/hydroxyapatite/ absorbable collagen sponge composite (TCP/HA/ACS) or calcium phosphate cement (alpha-BSM). Control treatments were TCP/HA/ACS and ?-BSM without rhBMP-2 and sham surgery. Stainless steel pins were placed at the mid-apical and coronal level of the defect sites to provide landmarks for clinical measurements pre- and post-implantation. Impressions were obtained pre- and postimplantation to determine changes in alveolar ridge volume. Radiographic registrations were obtained pre- and post-implantation. Block sections of the defect sites were harvested at week 16 postimplantation and processed for histometric analysis including new bone area and bone density. Statistical comparisons between treatments were made using a mixed effect generalized linear model using least squares estimation. RESULTS: The carrier systems without rhBMP-2 provided a modest ridge augmentation. The addition of rhBMP-2 resulted in an almost 2-fold increase in alveolar ridge width, including a greater percentage of trabecular bone and a higher bone density compared to controls (P < or =0.05) without significant differences between the two rhBMP-2 protocols. CONCLUSIONS: TCP/HA/ACS and alphaBSM appear to be suitable carrier technologies for rhBMP-2. Alveolar augmentation procedures using either technology combined with rhBMP-2, rather than stand-alone therapies, may provide clinically relevant augmentation of alveolar ridge defects for placement of endosseous dental implants.     

Persistent regional downregulation in mitochondrial enzymes and upregulation of stress proteins in swine with chronic hibernating myocardium

Hibernating myocardium is accompanied by a downregulation in energy utilization that prevents the immediate development of ischemia during stress at the expense of an attenuated level of regional contractile function. We used a discovery based proteomic approach to identify novel regional molecular adaptations responsible for this phenomenon in subendocardial samples from swine instrumented with a chronic LAD stenosis. After 3 months (n=8), hibernating myocardium was present as reflected by reduced resting LAD flow (0.75+/-0.14 versus 1.19+/-0.14 mL x min(-1) x g(-1) in remote) and wall thickening (1.93+/-0.46 mm versus 5.46+/-0.41 mm in remote, P<0.05). Regionally altered proteins were quantified with 2D Differential-in-Gel Electrophoresis (2D-DIGE) using normal myocardium as a reference with identification of candidates using MALDI-TOF mass spectrometry. Hibernating myocardium developed a significant downregulation of many mitochondrial proteins and an upregulation of stress proteins. Of particular note, the major entry points to oxidative metabolism (eg, pyruvate dehydrogenase complex and Acyl-CoA dehydrogenase) and enzymes involved in electron transport (eg, complexes I, III, and V) were reduced (P<0.05). Multiple subunits within an enzyme complex frequently showed a concordant downregulation in abundance leading to an amplification of their cumulative effects on activity (eg, "total" LAD PDC activity was 21.9+/-3.1 versus 42.8+/-1.9 mU, P<0.05). After 5-months (n=10), changes in mitochondrial and stress proteins persisted whereas cytoskeletal proteins (eg, desmin and vimentin) normalized. These data indicate that the proteomic phenotype of hibernating myocardium is dynamic and has similarities to global changes in energy substrate metabolism and function in the advanced failing heart. These proteomic changes may limit oxidative injury and apoptosis and impact functional recovery after revascularization.     

Search for quantitative trait loci of atopy-associated immune responses using allergen-specific IgG1 as an "endophenotype"

Inherited atopic diseases of humans arise from adverse adaptive humoral responses to noninfectious environmental allergens. We previously reported that allergen-specific IgG1 provides more reliable heritability estimates for responses to allergens than total IgE. Genome scans were done for 91 Caucasian nuclear families with history of atopy for total IgE and IgG1 produced against a common major allergen from house dust mite, Der p 1. Suggestive associations for Der p 1-IgG1 production were found at 7 quantitative trait loci (QTL) (logarithm of the odds, LOD > or = 1.23; p < or = 0.009) with QTL-specific heritabilities of 73%-80%. Scans using total IgE found suggestive associations for 12 QTLs (LOD > or = 1.44; p < or = 0.004), but QTL-specific heritabilities only in the range of 30%-35%. Allergen-specific IgG1 is a suitable "endophenotype" to be used in searches for genes associated with atopy-associated humoral immune responses to common aeroallergens.     

Impact of stimulus signal-to-noise ratio on prepulse inhibition of acoustic startle

Prepulse inhibition (PPI) of the human acoustic startle response is reduced in the presence of background noise of a sufficient intensity, possibly due to a reduction in signal-to-noise ratio (prepulse intensity relative to background noise). We examined this hypothesis by varying prepulse intensity and background noise intensity in order to hold three different signal-to-noise ratios constant (5, 15, and 25 dB(A) above background noise intensity). The results showed that signal-to-noise ratio proved to be a more important factor than absolute stimulus intensity in determining the degree of PPI of startle eyeblink response magnitude. Therefore, the effectiveness of a prepulse is determined by prepulse salience, not intensity, and this effectiveness is equivalent across a range of physical intensities.