Engineering ligament scaffolds based on PLA/graphite nanoplatelet composites by 3D printing or braiding

The development of scaffolds for tissue-engineered growth of the anterior cruciate ligament (ACL) is a promising approach to overcome the limitations of current solutions. This work proposes novel biodegradable and biocompatible scaffolds matching the mechanical characteristics of the native human ligament. Poly(L-lactic acid) (PLA) scaffolds reinforced with graphite nano-platelets (PLA+EG) as received, chemically functionalized (PLA+f-EG), or functionalized and decorated with silver nanoparticles [PLA+((f-EG)+Ag)], were fabricated by conventional braiding and using 3D-printing technology. The dimensions of both braided and 3D-printed scaffolds were finely controlled. The results showed that the scaffolds exhibited high porosity (>60%), pore interconnectivity, and pore size suitable for ligament tissue ingrowth, with no relevant differences between PLA and composite scaffolds. The wet state dynamic mechanical analysis at 37 °C revealed an increase in the storage modulus of the composite constructs, compared to neat PLA scaffolds. Either braided or 3D-printed scaffolds presented storage modulus values similar to those found in soft tissues. The tailorable design of the braided structures, as well as the reproducibility, the high speed, and the simplicity of 3D-printing allowed to obtain two different scaffolds suitable for ligament tissue engineering.This research was funded by FCT through the National Funds Reference UIDB/05256/2020 and UIDP/05256/2020, the FCT and European Program FEDER/COMPETE through the project PTDC/BTM-MAT/28123/2017, and the FCT, European Union and European Social Fund (FSE) through the PhD Grant Reference SFRH/BD/138244/2018

Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: A pooled analysis of 1018 population-based measurement studies with 88.6 million participants

© The Author(s) 2018. Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure. Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20-29 years to 70-79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probittransformed) prevalence of raised blood pressure and age-group- and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure. Results: In 2005-16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the highincome Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association. Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups

Global variations in diabetes mellitus based on fasting glucose and haemogloblin A1c

Fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c) are both used to diagnose diabetes, but may identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening had elevated FPG, HbA1c, or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardised proportion of diabetes that was previously undiagnosed, and detected in survey screening, ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the agestandardised proportion who had elevated levels of both FPG and HbA1c was 29-39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global gap in diabetes diagnosis and surveillance.peer-reviewe

Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants

Background Hypertension can be detected at the primary health-care level and low-cost treatments can effectively control hypertension. We aimed to measure the prevalence of hypertension and progress in its detection, treatment, and control from 1990 to 2019 for 200 countries and territories. Methods We used data from 1990 to 2019 on people aged 30–79 years from population-representative studies with measurement of blood pressure and data on blood pressure treatment. We defined hypertension as having systolic blood pressure 140 mm Hg or greater, diastolic blood pressure 90 mm Hg or greater, or taking medication for hypertension. We applied a Bayesian hierarchical model to estimate the prevalence of hypertension and the proportion of people with hypertension who had a previous diagnosis (detection), who were taking medication for hypertension (treatment), and whose hypertension was controlled to below 140/90 mm Hg (control). The model allowed for trends over time to be non-linear and to vary by age. Findings The number of people aged 30–79 years with hypertension doubled from 1990 to 2019, from 331 (95% credible interval 306–359) million women and 317 (292–344) million men in 1990 to 626 (584–668) million women and 652 (604–698) million men in 2019, despite stable global age-standardised prevalence. In 2019, age-standardised hypertension prevalence was lowest in Canada and Peru for both men and women; in Taiwan, South Korea, Japan, and some countries in western Europe including Switzerland, Spain, and the UK for women; and in several low-income and middle-income countries such as Eritrea, Bangladesh, Ethiopia, and Solomon Islands for men. Hypertension prevalence surpassed 50% for women in two countries and men in nine countries, in central and eastern Europe, central Asia, Oceania, and Latin America. Globally, 59% (55–62) of women and 49% (46–52) of men with hypertension reported a previous diagnosis of hypertension in 2019, and 47% (43–51) of women and 38% (35–41) of men were treated. Control rates among people with hypertension in 2019 were 23% (20–27) for women and 18% (16–21) for men. In 2019, treatment and control rates were highest in South Korea, Canada, and Iceland (treatment >70%; control >50%), followed by the USA, Costa Rica, Germany, Portugal, and Taiwan. Treatment rates were less than 25% for women and less than 20% for men in Nepal, Indonesia, and some countries in sub-Saharan Africa and Oceania. Control rates were below 10% for women and men in these countries and for men in some countries in north Africa, central and south Asia, and eastern Europe. Treatment and control rates have improved in most countries since 1990, but we found little change in most countries in sub-Saharan Africa and Oceania. Improvements were largest in high-income countries, central Europe, and some upper-middle-income and recently high-income countries including Costa Rica, Taiwan, Kazakhstan, South Africa, Brazil, Chile, Turkey, and Iran. Interpretation Improvements in the detection, treatment, and control of hypertension have varied substantially across countries, with some middle-income countries now outperforming most high-income nations. The dual approach of reducing hypertension prevalence through primary prevention and enhancing its treatment and control is achievable not only in high-income countries but also in low-income and middle-income settings

Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)

From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions

Nova abordagem para regeneração de ligamento à base de nanocompósitos de grafeno

Tese de doutoramento em Science and Engineering of Polymers and CompositesLigament injuries are frequent and often require surgical reconstruction with auto-/ allografts, with severe limitations that have prompted a growing interest in the development of tissue-engineered scaffolds for ligament regeneration. Polylactic acid (PLA) is a biocompatible/biodegradable polymer with acceptable mechanical properties and routinely used for several medical applications. It may be reinforced with nanoparticles such as few-layer graphene to enhance the mechanical performance and provide other functionalities. Micronized graphite nanoplatelets (EG) may be covalently functionalized (f-EG) maintaining the excellent mechanical properties and providing adequate chemistry to bond with PLA, establishing strong interfaces that will enhance stress-transfer from polymer to reinforcement. Anchoring on f-EG a controlled concentration of silver nanoparticles ((f-EG)+Ag) may be beneficial for tissue regeneration by preventing bacterial adhesion and accelerating the healing process. The present work targeted the production of novel biodegradable and biocompatible graphenebased scaffolds, with controlled dimensions, as well as mechanical properties that match the requirements of the native human ligaments. Two alternative manufacturing techniques were investigated, one based on braiding, the other using 3D printing. To reach this goal, composite filaments of PLA reinforced with (f-EG)+Ag were produced by twin screw extrusion and melt-drawing, with enhanced mechanical performance for textile-engineered and 3D-printed ligament scaffolds. The composite filaments and scaffolds were extensively characterized by relevant techniques, being suitable for tendon/ligament tissue engineering applications. Scaffolds based on a medical grade PLA containing 0.5 wt.% of (f-EG)+Ag were produced by 3D printing. (f-EG)+Ag exhibited antibacterial properties against Staphylococcus aureus and Escherichia coli , an important feature for the healing process and prevention of bacterial infections. The scaffolds’ structure, biodegradation, and mechanical properties confirm their suitability for tendon and ligament regeneration. The PLA+[(f-EG)+Ag] scaffolds were nontoxic, and showed the ability to maintain the tenogenic commitment of human tendon-derived cells, with an increase in the gene expression of specific tendon/ligament-related markers. The results demonstrate the possibility for easy, cost-effective and personalized 3D-printed scaffolds with great potential applications for tendon and ligament regeneration.As lesões do ligamento são frequentes e envolvem muitas vezes reconstruções cirúrgicas com auto/alo-enxertos. Esta estratégia apresenta várias limitações potenciando o desenvolvimento de scaffolds que propiciem a regeneração do ligamento. O poliácido láctico (PLA) é um polímero biocompatível e biodegradável, com razoáveis propriedades mecânicas e amplamente usado na área médica. Este polímero pode ser reforçado com nanopartículas como grafeno multi-camada para melhorar a performance mecânica e conferir outras funcionalidades. As nanoplaquetas de grafite micronizada (EG) podem ser funcionalizadas covalentemente (f-EG) mantendo as excelentes propriedades mecânicas, providenciando uma química adequada para uma ligação com o PLA e assim, estabelecer interfaces fortes que irão melhorar a transferência de carga do polímero para o material de reforço. A ancoragem a f-EG de uma concentração controlada de nanopartículas de prata ((f-EG)+Ag) pode ser benéfica para a regeneração de tecidos, prevenindo a adesão bacteriana e acelerando o processo de cicatrização. Este trabalho tem como objetivo a produção de scaffolds à base de grafeno, biodegradáveis e biocompatíveis, com dimensões controladas e propriedades mecânicas que cumpram os requisitos dos ligamentos humanos nativos. Foram investigados dois métodos alternativos de produção, entrançado e impressão 3D. Assim, foram produzidos por extrusão e estiramento filamentos compósitos de PLA+[(f- EG)+Ag], com performance mecânica melhorada, para a produção de scaffolds . Os filamentos e os scaffolds compósitos foram extensamente caracterizados, sendo adequados para regeneração de ligamento/tendão. Foram também produzidos scaffolds de PLA de grau médico reforçado com 0.5 wt.% de (f-EG)+Ag, por impressão 3D. (f-EG)+Ag exibiu propriedades antibacterianas em relação a Staphylococcus aureus e Escherichia coli , uma importante caraterística para a prevenção de infeções bacterianas e para o processo de cura. A estrutura, biodegradação e propriedades mecânicas dos scaffolds confirmam a sua adequabilidade para regenerar ligamentos e tendões. Os scaffolds de PLA+[(f- EG)+Ag] não são tóxicos, e mostraram capacidade de manter a predisposição tenogénica de células humanas derivadas do tendão, com aumento da expressão genética de marcadores específicos de tendão/ligamento. Os resultados demostram a possibilidade de obter scaffolds por impressão 3D de forma fácil, económica e personalizada com grande potencial para regeneração de tendão/ligamento.I wish to acknowledge the Fundação para a Ciência e Tecnologia (FCT, Portugal), European Union and European Social Fund for providing the PhD Grant References SFRH/BD/138244/2018 and COVID/BD/153245/2023, which allowed the pursuit of this work, and for granting funding to permit the presentation of results at international conferences

Characterisation of microbial attack on archaeological bone

As part of an EU funded project to investigate the factors influencing bone preservation in the archaeological record, more than 250 bones from 41 archaeological sites in five countries spanning four climatic regions were studied for diagenetic alteration. Sites were selected to cover a range of environmental conditions and archaeological contexts. Microscopic and physical (mercury intrusion porosimetry) analyses of these bones revealed that the majority (68%) had suffered microbial attack. Furthermore, significant differences were found between animal and human bone in both the state of preservation and the type of microbial attack present. These differences in preservation might result from differences in early taphonomy of the bones. © 2003 Elsevier Science Ltd. All rights reserved

General and abdominal adiposity and hypertension in eight world regions: a pooled analysis of 837 population-based studies with 7·5 million participants

International audienceSummaryBackground Adiposity can be measured using BMI (which is based on weight and height) as well as indices of abdominal adiposity. We examined the association between BMI and waist-to-height ratio (WHtR) within and across populations of different world regions and quantified how well these two metrics discriminate between people with and without hypertension.MethodsWe used data from studies carried out from 1990 to 2023 on BMI, WHtR and hypertension in people aged 20–64 years in representative samples of the general population in eight world regions. We graphically compared the regional distributions of BMI and WHtR, and calculated Pearson’s correlation coefficients between BMI and WHtR within each region. We used mixed-effects linear regression to estimate the extent to which WHtR varies across regions at the same BMI. We graphically examined the prevalence of hypertension and the distribution of people who have hypertension both in relation to BMI and WHtR, and we assessed how closely BMI and WHtR discriminate between participants with and without hypertension using C-statistic and net reclassification improvement (NRI).FindingsThe correlation between BMI and WHtR ranged from 0·76 to 0·89 within different regions. After adjusting for age and BMI, mean WHtR was highest in south Asia for both sexes, followed by Latin America and the Caribbean and the region of central Asia, Middle East and north Africa. Mean WHtR was lowest in central and eastern Europe for both sexes, in the high-income western region for women, and in Oceania for men. Conversely, to achieve an equivalent WHtR, the BMI of the population of south Asia would need to be, on average, 2·79 kg/m² (95% CI 2·31–3·28) lower for women and 1·28 kg/m² (1·02–1·54) lower for men than in the high-income western region. In every region, hypertension prevalence increased with both BMI and WHtR. Models with either of these two adiposity metrics had virtually identical C-statistics and NRIs for every region and sex, with C-statistics ranging from 0·72 to 0·81 and NRIs ranging from 0·34 to 0·57 in different region and sex combinations. When both BMI and WHtR were used, performance improved only slightly compared with using either adiposity measure alone.InterpretationBMI can distinguish young and middle-aged adults with higher versus lower amounts of abdominal adiposity with moderate-to-high accuracy, and both BMI and WHtR distinguish people with or without hypertension. However, at the same BMI level, people in south Asia, Latin America and the Caribbean, and the region of central Asia, Middle East and north Africa, have higher WHtR than in the other regions

Global variation in diabetes diagnosis and prevalence based on fasting glucose and hemoglobin A1c

International audienceAbstract Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) are both used to diagnose diabetes, but these measurements can identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening, had elevated FPG, HbA1c or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardized proportion of diabetes that was previously undiagnosed and detected in survey screening ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the age-standardized proportion who had elevated levels of both FPG and HbA1c was 29–39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c was more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global shortfall in diabetes diagnosis and surveillance

Global variation in diabetes diagnosis and prevalence based on fasting glucose and hemoglobin A1c

: Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) are both used to diagnose diabetes, but these measurements can identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening, had elevated FPG, HbA1c or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardized proportion of diabetes that was previously undiagnosed and detected in survey screening ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the age-standardized proportion who had elevated levels of both FPG and HbA1c was 29-39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c was more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global shortfall in diabetes diagnosis and surveillance