Recent origin of low trabecular bone density in modern humans

Humans are unique, compared with our closest living relatives (chimpanzees) and early fossil hominins, in having an enlarged body size and lower limb joint surfaces in combination with a relatively gracile skeleton (i.e., lower bone mass for our body size). Some analyses have observed that in at least a few anatomical regions modern humans today appear to have relatively low trabecular density, but little is known about how that density varies throughout the human skeleton and across species or how and when the present trabecular patterns emerged over the course of human evolution. Here, we test the hypotheses that (i) recent modern humans have low trabecular density throughout the upper and lower limbs compared with other primate taxa and (ii) the reduction in trabecular density first occurred in early Homo erectus, consistent with the shift toward a modern human locomotor anatomy, or more recently in concert with diaphyseal gracilization in Holocene humans. We used peripheral quantitative CT and microtomography to measure trabecular bone of limb epiphyses (long bone articular ends) in modern humans and chimpanzees and in fossil hominins attributed to Australopithecus africanus, Paranthropus robustus/early Homo from Swartkrans, Homo neanderthalensis, and early Homo sapiens. Results show that only recent modern humans have low trabecular density throughout the limb joints. Extinct hominins, including pre-Holocene Homo sapiens, retain the high levels seen in nonhuman primates. Thus, the low trabecular density of the recent modern human skeleton evolved late in our evolutionary history, potentially resulting from increased sedentism and reliance on technological and cultural innovations

Bone remodeling in a new biomimetic polymer-composite hip stem

Adaptive bone remodeling is an important factor that leads to bone resorption in the surroudning femoral bone and implant loosening. Taking into account this factor in the design of hip implants is of clinical importance, since it allows the prediction of the bone-density redistribution and enables the monitoring of bone adaptation after prosthetic implantation. In this paper adaptive bone remodeling around a new biomimetic polymer-composite based (CF/PA12) hip prosthesis is investigated in order to evaluate the amount of stress shielding and bone resorption. The design concept of this new prosthesis is based on a hollow sub-structure made of hydroxyapatite-coated, continuous carbon fiber (BF) reinforced polyamide 12 (PA12) composite with an internal soft polymer-based core. Strain energy density theory coupled with 3-D Finite Element models are used to predict bone desity redistributions in the femoral bone before and after total hip replacement using both polymer-composite and titanium stems. The result of numerical simulations of bone remodeling revealed that the CF-PA12 composite stem generates an excellent bone density pattern compared to the titanium-based stem, indicating the effectiveness of the composite stem to reduce bone resorption caused by stress shielding phenomenon. This may result in an extended lifetime of Total Hip Replacement (THR).Le remodelage osseux adaptatif est un ph\ue9nom\ue8ne important menant \ue0 une r\ue9sorption du tissu osseux dans lequel est implant\ue9e une tige f\ue9morale, ce qui en affecte la stabilit\ue9. La prise en compte de ce facteur dans la conception des proth\ue8ses de hanche rev\ueat une importance clinique particuli\ue8re en permettant de pr\ue9voir la redistribution de la densit\ue9 min\ue9rale osseuse et d\u2019\ue9valuer l\u2019adaptation osseuse cons\ue9cutive \ue0 la pose de la proth\ue8se. Le pr\ue9sent article traite de l\u2019\ue9valuation du remodelage adaptatif du tissu osseux entourant un nouveau mod\ue8le de proth\ue8se de hanche en polym\ue8re composite FC/PA12 biomim\ue9tique que nous avons effectu\ue9e dans le but de quantifier la r\ue9sorption osseuse par d\ue9viation des contraintes (ph\ue9nom\ue8ne de court-circuitage des contraintes) attribuable \ue0 la proth\ue8se. Recouverte d\u2019hydroxyapatite de calcium, la tige f\ue9morale \ue9tudi\ue9e se compose d\u2019une structure externe creuse monopi\ue8ce en polyamide 12 (PA12) renforc\ue9 de fibre de carbone (FC) dont la cavit\ue9 interne est remplie de polym\ue8re mou. L\u2019utilisation du crit\ue8re de l\u2019\ue9nergie de d\ue9formation minimale et de mod\ue8les 3D d\u2019\ue9l\ue9ments finis nous a permis de pr\ue9dire la distribution de la densit\ue9 min\ue9rale du tissu osseux f\ue9moral avant et apr\ue8s la pose d\u2019une proth\ue8se totale de hanche (PTH) comportant une tige f\ue9morale en polym\ue8re composite ou une tige en titane (Ti). Les r\ue9sultats des simulations num\ue9riques du remodelage osseux r\ue9v\ue8lent que la tige f\ue9morale en polym\ue8re composite FC/PA12 permet le maintien d\u2019une meilleure densit\ue9 min\ue9rale osseuse que la tige en titane, ce qui t\ue9moigne de l\u2019efficacit\ue9 de la tige en polym\ue8re composite \ue0 r\ue9duire la r\ue9sorption osseuse attribuable \ue0 la d\ue9viation des contraintes. Ce mod\ue8le de tige f\ue9morale pourrait donc prolonger la dur\ue9e de vie utile de la proth\ue8se totale de hanche.Peer reviewed: YesNRC publication: Ye

Analyzing Recent Coronary Heart Disease Mortality Trends in Tunisia between 1997 and 2009.

BACKGROUND: In Tunisia, Cardiovascular Diseases are the leading causes of death (30%), 70% of those are coronary heart disease (CHD) deaths and population studies have demonstrated that major risk factor levels are increasing. OBJECTIVE: To explain recent CHD trends in Tunisia between 1997 and 2009. METHODS: DATA SOURCES: Published and unpublished data were identified by extensive searches, complemented with specifically designed surveys. ANALYSIS: Data were integrated and analyzed using the previously validated IMPACT CHD policy model. Data items included: (i)number of CHD patients in specific groups (including acute coronary syndromes, congestive heart failure and chronic angina)(ii) uptake of specific medical and surgical treatments, and(iii) population trends in major cardiovascular risk factors (smoking, total cholesterol, systolic blood pressure (SBP), body mass index (BMI), diabetes and physical inactivity). RESULTS: CHD mortality rates increased by 11.8% for men and 23.8% for women, resulting in 680 additional CHD deaths in 2009 compared with the 1997 baseline, after adjusting for population change. Almost all (98%) of this rise was explained by risk factor increases, though men and women differed. A large rise in total cholesterol level in men (0.73 mmol/L) generated 440 additional deaths. In women, a fall (-0.43 mmol/L), apparently avoided about 95 deaths. For SBP a rise in men (4 mmHg) generated 270 additional deaths. In women, a 2 mmHg fall avoided 65 deaths. BMI and diabetes increased substantially resulting respectively in 105 and 75 additional deaths. Increased treatment uptake prevented about 450 deaths in 2009. The most important contributions came from secondary prevention following Acute Myocardial Infarction (AMI) (95 fewer deaths), initial AMI treatments (90), antihypertensive medications (80) and unstable angina (75). CONCLUSIONS: Recent trends in CHD mortality mainly reflected increases in major modifiable risk factors, notably SBP and cholesterol, BMI and diabetes. Current prevention strategies are mainly focused on treatments but should become more comprehensive

Forecasting Tunisian type 2 diabetes prevalence to 2027: validation of a simple model.

BACKGROUND: Most projections of type 2 diabetes (T2D) prevalence are simply based on demographic change (i.e. ageing). We developed a model to predict future trends in T2D prevalence in Tunisia, explicitly taking into account trends in major risk factors (obesity and smoking). This could improve assessment of policy options for prevention and health service planning. METHODS: The IMPACT T2D model uses a Markov approach to integrate population, obesity and smoking trends to estimate future T2D prevalence. We developed a model for the Tunisian population from 1997 to 2027, and validated the model outputs by comparing with a subsequent T2D prevalence survey conducted in 2005. RESULTS: The model estimated that the prevalence of T2D among Tunisians aged over 25 years was 12.0% in 1997 (95% confidence intervals 9.6%-14.4%), increasing to 15.1% (12.5%-17.4%) in 2005. Between 1997 and 2005, observed prevalence in men increased from 13.5% to 16.1% and in women from 12.9% to 14.1%. The model forecast for a dramatic rise in prevalence by 2027 (26.6% overall, 28.6% in men and 24.7% in women). However, if obesity prevalence declined by 20% in the 10 years from 2013, and if smoking decreased by 20% over 10 years from 2009, a 3.3% reduction in T2D prevalence could be achieved in 2027 (2.5% in men and 4.1% in women). CONCLUSIONS: This innovative model provides a reasonably close estimate of T2D prevalence for Tunisia over the 1997-2027 period. Diabetes burden is now a significant public health challenge. Our model predicts that this burden will increase significantly in the next two decades. Tackling obesity, smoking and other T2D risk factors thus needs urgent action. Tunisian decision makers have therefore defined two strategies: obesity reduction and tobacco control. Responses will be evaluated in future population surveys

Abnormal expression of p27kip1 protein in levator ani muscle of aging women with pelvic floor disorders – a relationship to the cellular differentiation and degeneration

BACKGROUND: Pelvic floor disorders affect almost 50% of aging women. An important role in the pelvic floor support belongs to the levator ani muscle. The p27/kip1 (p27) protein, multifunctional cyclin-dependent kinase inhibitor, shows changing expression in differentiating skeletal muscle cells during development, and relatively high levels of p27 RNA were detected in the normal human skeletal muscles. METHODS: Biopsy samples of levator ani muscle were obtained from 22 symptomatic patients with stress urinary incontinence, pelvic organ prolapse, and overlaps (age range 38–74), and nine asymptomatic women (age 31–49). Cryostat sections were investigated for p27 protein expression and type I (slow twitch) and type II (fast twitch) fibers. RESULTS: All fibers exhibited strong plasma membrane (and nuclear) p27 protein expression. cytoplasmic p27 expression was virtually absent in asymptomatic women. In perimenopausal symptomatic patients (ages 38–55), muscle fibers showed hypertrophy and moderate cytoplasmic p27 staining accompanied by diminution of type II fibers. Older symptomatic patients (ages 57–74) showed cytoplasmic p27 overexpression accompanied by shrinking, cytoplasmic vacuolization and fragmentation of muscle cells. The plasma membrane and cytoplasmic p27 expression was not unique to the muscle cells. Under certain circumstances, it was also detected in other cell types (epithelium of ectocervix and luteal cells). CONCLUSIONS: This is the first report on the unusual (plasma membrane and cytoplasmic) expression of p27 protein in normal and abnormal human striated muscle cells in vivo. Our data indicate that pelvic floor disorders are in perimenopausal patients associated with an appearance of moderate cytoplasmic p27 expression, accompanying hypertrophy and transition of type II into type I fibers. The patients in advanced postmenopause show shrinking and fragmentation of muscle fibers associated with strong cytoplasmic p27 expression

Trace-elemental and multi-isotopic (Sr-Nd-Pb) discrimination of jade in the circum-Caribbean: Implications for pre-colonial inter-island exchange networks

Dense and strong, hydrothermal-metasomatic jadeitite and jadeite-omphacite rocks were used as tools and adornments throughout the wider Caribbean since initial inhabitation. Regionally, rich sources of jadeitite and jadeite-omphacite jade are known only in Guatemala (north and south of the Motagua Fault Zone), eastern Cuba and the northern Dominican Republic, establishing that humans transported jadeitic material over vast distances. This study validates that geochemical fingerprinting is a viable provenance method for Caribbean pre-colonial jadeitic lithologies. An assemblage of 101 source rocks has been characterised for trace element and combined Sr-Nd-Pb isotope compositions. Four statistical approaches (Principal Component Analysis, t-Distributed Stochastic Neighbour Embedding, Decision Tree, and Multiclass Regression) were assessed, employing source-distinct trace element ratios. A multiclass regression technique based on trace element ratios of immobile high field strength, light to medium rare earth and fluid-mobile, large-ion-lithophile elements is shown to be most effective in discriminating the four source regions. Ninety-one % of the Guatemalan samples can be discriminated from the Dominican and Cuban sources using La/Th, Zr/Hf and Y/Th ratios. Jadeitic rocks cropping out in the Dominican Republic can be distinguished from Cuban jades employing Er/Yb, Nb/Ta and Ba/Rb ratios with 71% certainty. Furthermore, the two Guatemala sources, north and south of the Motagua Fault Zone, can be discriminated by using (among others) Zr/Hf, Ta/Th, La/Sm and Dy/Y ratios with an 89% success rate. This raises the possibility of determining, in detail, former trading and mobility networks between different islands and the Meso- and Central American mainland within the Greater Caribbean. The provenance technique was applied to 19 pre-colonial jade celts excavated from the Late Ceramic Age Playa Grande archaeological site in the northern Dominican Republic. Three artefacts are discriminated as derived from the Guatemalan source, indicating that, despite a source of jade within 25 km, material was traded from Guatemala. The presence of Guatemalan jade in the Playa Grande lithic assemblage provides further evidence of large scale (>3000 km), regional trading and indigenous knowledge transfer networks.This research received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007–2013)/ERC grant agreement No 319209 (ERC-Synergy NEXUS 1492) and the European Union’s Horizon 2020 research and innovation programme under grant agreement No 654208 (Europlanet 2020 RI). We are grateful to the Museo del Hombre Dominicano for providing the Playa Grande samples. Thanks to Richard Smeets, Bas van der Wagt, Kirsten van Zuilen, Bouke Lacet, Eva Kelderman and Quinty Boosten for analytical assistance

A cost effectiveness analysis of salt reduction policies to reduce coronary heart disease in four Eastern Mediterranean countries.

BACKGROUND: Coronary Heart Disease (CHD) is rising in middle income countries. Population based strategies to reduce specific CHD risk factors have an important role to play in reducing overall CHD mortality. Reducing dietary salt consumption is a potentially cost-effective way to reduce CHD events. This paper presents an economic evaluation of population based salt reduction policies in Tunisia, Syria, Palestine and Turkey. METHODS AND FINDINGS: Three policies to reduce dietary salt intake were evaluated: a health promotion campaign, labelling of food packaging and mandatory reformulation of salt content in processed food. These were evaluated separately and in combination. Estimates of the effectiveness of salt reduction on blood pressure were based on a literature review. The reduction in mortality was estimated using the IMPACT CHD model specific to that country. Cumulative population health effects were quantified as life years gained (LYG) over a 10 year time frame. The costs of each policy were estimated using evidence from comparable policies and expert opinion including public sector costs and costs to the food industry. Health care costs associated with CHDs were estimated using standardized unit costs. The total cost of implementing each policy was compared against the current baseline (no policy). All costs were calculated using 2010 PPP exchange rates. In all four countries most policies were cost saving compared with the baseline. The combination of all three policies (reducing salt consumption by 30%) resulted in estimated cost savings of $235,000,000 and 6455 LYG in Tunisia;$39,000,000 and 31674 LYG in Syria; $6,000,000 and 2682 LYG in Palestine and$1,3000,000,000 and 378439 LYG in Turkey. CONCLUSION: Decreasing dietary salt intake will reduce coronary heart disease deaths in the four countries. A comprehensive strategy of health education and food industry actions to label and reduce salt content would save both money and lives

Conducting Environmental Health Research in the Arabian Middle East: Lessons Learned and Opportunities

Background: The Arabian Gulf nations are undergoing rapid economic development, leading to major shifts in both the traditional lifestyle and the environment. Although the pace of change is brisk, there is a dearth of environmental health research in this region

Is there any advantage to combined trastuzumab and chemotherapy in perioperative setting her 2neu positive localized gastric adenocarcinoma?

We report here a 44-year-old Moroccan man with resectable gastric adenocarcinoma with overexpression of human epidermal growth factor receptor 2 (HER2) by immunohistochemistry who was treated with trastuzumab in combination with chemotherapy in perioperative setting. He received 3 cycles of neoadjuvant chemotherapy consisting of trastuzumab, oxaliplatin, and capecitabine. Afterwards, he received total gastrectomy with extended D2 lymphadenectomy without spleno-pancreatectomy. A pathologic complete response was obtained with a combination of trastuzumab and oxaliplatin and capecitabine. He received 3 more cycles of trastuzumab containing regimen postoperatively