Association of pulse pressure,pulse pressure index,and ambulatory arterial stiffness index with kidney function in a cross‐sectional pediatric chronic kidney disease cohort from the CKiD study

The morbidity and mortality of adult and pediatric chronic kidney disease (CKD) and end‐stage renal disease (ESRD) populations are mainly driven by cardiovascular disease (CVD). Improving CVD outcomes focuses on risk assessment of factors including diastolic blood pressure (DBP), systolic blood pressure (SBP), left ventricular mass index (LVMI), pulse pressure (PP), and pulse pressure index (PPi), which is calculated as PP/SBP. These markers are also proven predictors of CKD progression; however, their role in children has not been established. This study aims to evaluate the relationship between PP, PPi, ambulatory arterial stiffness index (AASI), and proteinuria with kidney function in pediatric CKD patients; it is a retrospective analysis of 620 patients (1‐16 years) from the NIDDK Chronic Kidney Disease in Children (CKiD) registry. The authors analyzed data for three separate cohorts: an overall CKD as well as immunological versus non‐immunological cause for CKD groups. An inverse relationship was found between SBP, DBP, and PP with iGFR and LVMI in the overall CKD group. Our immunological CKD subgroup showed significantly higher serum creatinine, SBP, DBP, and PP values with significantly lower serum albumin levels compared to the non‐immunological group. There were no significant differences with iohexol‐based glomerular filtration rate (iGFR), LVMI, PPi, or high‐sensitivity C‐reactive protein (hs‐CRP) between the two groups. A subgroup analysis demonstrated that SBP, DBP, and PP all correlated significantly with LVMI in the immunological CKD patients but not the non‐immunological subgroup. Additionally, AASI data in the overall CKD population were significantly correlated with PP, PPi, and DBP. This study is one of the first to correlate noninvasive measurements of vascular compliance including PP, PPi, and AASI with iGFR and LVMI in a pediatric CKD cohort. Improving our understanding of surrogate markers for early CVD is integral to improving the care of pediatric CKD population as these patients have yet to develop the hard end points of ESRD, heart failure, myocardial infarction, or stroke.     

Religion as a means to assure paternity

The sacred texts of five world religions (Buddhism, Christianity, Hinduism, Islam, and Judaism) use similar belief systems to set limits on sexual behavior. We propose that this similarity is a shared cultural solution to a biological problem: namely male uncertainty over the paternity of offspring. Furthermore, we propose the hypothesis that religious practices that more strongly regulate female sexuality should be more successful at promoting paternity certainty. Using genetic data on 1,706 father-son pairs, we tested this hypothesis in a traditional African population in which multiple religions (Islam, Christianity, and indigenous) coexist in the same families and villages. We show that the indigenous religion enables males to achieve a significantly (P = 0.019) lower probability of cuckoldry (1.3% versus 2.9%) by enforcing the honest signaling of menstruation, but that all three religions share tenets aimed at the avoidance of extrapair copulation. Our findings provide evidence for high paternity certainty in a traditional African population, and they shed light on the reproductive agendas that underlie religious patriarchy.     

Evaluation of Dimensional Accuracy of Panoramic Cross‐Sectional Tomography,Its Ability to Identify the Inferior Alveolar Canal,and Its Impact on Estimation of Appropriate Implant Dimensions in the Mandibular Posterior Region

Objectives: To evaluate the dimensional accuracy of panoramic cross‐sectional tomography, its impact on implant size estimation and its ability in identifying the inferior alveolar canal in the mandibular posterior region. Material and Methods: Eight partially edentulous mandibles with 18 edentulous sites were obtained. Orthopantomograms and tomograms were made and the mandible's outline and the position of mandibular canals on tomograms were traced on a clear acetate paper. Horizontal and vertical magnification factors were calculated. The mandibular height, distance between mandibular canal and alveolar crest, maximum bucco‐lingual width, distance between buccal cortex and mandibular canal, and cortical thickness at the inferior border of the mandible were measured. Potential implant sites were identified and implant sizes were estimated. Location and visibility of mandibular canals were also evaluated. The mandibles were sectioned at each site and all the above mentioned parameters were assessed which served as gold standard. Results: Mean horizontal and vertical magnification factors were 1.47 ± 0.048 and 1.53 ± 0.038. Total height and maximum bucco‐lingual width were underestimated by 1.88% and 1.59%. Crest to canal distance, cortical thickness at the inferior border of the mandible and buccal cortex to mandibular canal were overestimated by 0.59%, 5.16%, and 3.64%. Implant sizes were estimated for 11 sites and changes were recorded at 2 sites between record 1 and record 2. However, there was no disagreement between record 2 and record 3. Of the canals, 61.11% were located lingually and the visibility of mandibular canals was poor in 44.44% of cases. Conclusions: The tomograms were found to be accurate for the measurements in both horizontal and vertical planes and reliable for implant size estimation, taking into consideration proper magnification factors. They were also found to be useful in assessing the location of mandibular canal but were not very effective in discerning it.     

Bruton tyrosine kinase inhibition is a novel therapeutic strategy targeting tumor in the bone marrow microenvironment in multiple myeloma

Bruton tyrosine kinase (Btk) has a well-defined role in B-cell development, whereas its expression in osteoclasts (OCs) further suggests a role in osteoclastogenesis. Here we investigated effects of PCI-32765, an oral and selective Btk inhibitor, on osteoclastogenesis as well as on multiple myeloma (MM) growth within the BM microenvironment. PCI-32765 blocked RANKL/M-CSF-induced phosphorylation of Btk and downstream PLC-γ2 in OCs, resulting in diminished TRAP5b (ED(50) = 17nM) and bone resorption activity. PCI-32765 also inhibited secretion of multiple cytokines and chemokines from OC and BM stromal cell cultures from both normal donors (ED(50) = 0.5nM) and MM patients. It decreased SDF-1-induced migration of MM cells, and down-regulated MIP1-α/CCL3 in MM cells. It also blocked MM cell growth and survival triggered by IL-6 or coculture with BM stromal cells or OCs in vitro. Importantly, PCI-32765 treatment significantly inhibits in vivo MM cell growth (P < .03) and MM cell-induced osteolysis of implanted human bone chips in SCID mice. Moreover, PCI-32765 prevents in vitro colony formation by stem-like cells from MM patients. Together, these results delineate functional sequelae of Btk activation mediating osteolysis and growth of MM cells, supporting evaluation of PCI-32765 as a novel therapeutic in MM.