The global burden of women's cancers: a grand challenge in global health.

Every year, more than 2 million women worldwide are diagnosed with breast or cervical cancer, yet where a woman lives, her socioeconomic status, and agency largely determines whether she will develop one of these cancers and will ultimately survive. In regions with scarce resources, fragile or fragmented health systems, cancer contributes to the cycle of poverty. Proven and cost-effective interventions are available for both these common cancers, yet for so many women access to these is beyond reach. These inequities highlight the urgent need in low-income and middle-income countries for sustainable investments in the entire continuum of cancer control, from prevention to palliative care, and in the development of high-quality population-based cancer registries. In this first paper of the Series on health, equity, and women's cancers, we describe the burden of breast and cervical cancer, with an emphasis on global and regional trends in incidence, mortality, and survival, and the consequences, especially in socioeconomically disadvantaged women in different settings.

Effect of daily lithium chloride administration on bone mass and strength in growing broiler chickens.

The objective was to determine the effects of oral lithium chloride supplementation on bone strength and mass in broiler chickens. Ninety-six broilers were assigned to 1 of 2 treatment groups (lithium chloride or control; n=48/treatment). Beginning at 1 or 3 wk of age, chickens were administered lithium chloride (20 mg/kg body weight) or water daily by oral gavage. At 6 wk of age, chickens were euthanized and bone and muscle samples were collected. A 24 h lithium chloride (20 mg/kg body weight) challenge determined that serum lithium chloride increased within 2 h and cleared the system within 24 h, demonstrating the effective delivery of lithium chloride. Treatment did not influence body weight (P≥0.20) or feed intake (P≥0.81), demonstrating that lithium chloride did not negatively affect broiler growth. To determine bone strength, 3-point bending was performed on the femora and tibiae obtained from control and lithium chloride-treated birds in the 1 wk group. Lithium chloride-treated birds had a 22% reduction in stiffness compared with control in the femora (P=0.02) without a corresponding reduction in elastic modulus. No differences were observed in yield or ultimate load and in the corresponding calculations of stresses (P≥0.26). The toughness of tibiae was not altered in lithium chloride compared with control (P=0.11). Bone length and micro-CT imaging were performed on the tibiae of control and lithium chloride groups. No differences (P≥0.52) in bone length, cortical or trabecular bone volume, trabecular thickness, number, or spacing were observed. Lithium chloride treatment did not affect pectoralis muscle color or lipid oxidation (P>0.05). In conclusion, lithium chloride treatment in broilers did not negatively affect growth or meat quality. A reduction in bone stiffness of the femur with lithium chloride treatment was observed, however unlike the mouse model, the dosages of lithium chloride used in the current study did not result in anabolic effects on broiler long bones.

Analyzing the Outcomes of COVID-19 Infection on Patients With Comorbidities: Insights From Hospital-Based Study.

Introduction COVID-19 exhibits a broad spectrum of clinical manifestations, ranging from asymptomatic or mild cases to severe respiratory distress and, in some instances, fatal outcomes. The pre-existing inflammatory state in the patient prior to exposure to COVID-19, which could be because of any etiology or comorbidity, has been associated with prolonged morbidity, and adverse outcomes like increased mortality have been found. This study endeavors to investigate the principal risk factors linked to the morbidity and mortality of COVID-19, such as age, gender, and co-morbidities such as hypertension, diabetes mellitus, and others. Material and methods Patient demographic data like age, gender, and co-morbidities like diabetes mellitus, hypertension, respiratory illness, and coronary artery diseases, cerebrovascular accident was observed. The patient clinical profile, hematological, inflammatory markers at the time of admission, and outcome were noticed. Patients were divided into two groups - patients with comorbidity and those without comorbidity. Results In each cohort of COVID-19 patients, comprising those with and without comorbidities, there were 145 participants. The mean age of patients without comorbidities was found to be 49.97 years, whereas the mean age of those with comorbidities was 64.35 years. Within the comorbidity group, males formed the majority, accounting for 77.2% of the cohort; in the group without comorbidity also males predominated, representing 68.3% of the participants. Hypertension was the most common co-morbidity (89.7%), followed by diabetes mellitus (39.3%), and ischemic heart disease (8.3%). The multivariate logistic regression analysis for prediction of mortality showed hypothyroidism with odds ratio (OR) of 336.26 and confidence intervals (CI) (1.19-9477.13), ischemic heart disease with OR of 320.94 (CI 3.19-3237.4) and presence greater than two co-morbidities with OR of 42.14 (CI 1.34-1325.76). Cox regression analysis showed a statistically significant hazard ratio of 0.294 in patients with greater than two co-morbidities. Conclusion Hypothyroidism, ischemic heart disease, and the presence of multiple comorbid conditions were associated with the severity of COVID-19 illness and mortality.

For money or service?: a cross-sectional survey of preference for financial versus non-financial rural practice characteristics among Ghanaian medical students.

BACKGROUND: Health worker shortage and maldistribution are among the biggest threats to health systems in Africa. New medical graduates are prime targets for recruitment to deprived rural areas. However, little research has been done to determine the influence of workers' background and future plans on their preference for rural practice incentives and characteristics. The purpose of this study was to identify determinants of preference for rural job characteristics among fourth year medical students in Ghana. METHODS: We asked fourth-year Ghanaian medical students to rank the importance of rural practice attributes including salary, infrastructure, management style, and contract length in considering future jobs. We used bivariate and multivariate ordinal logistic regression to estimate the association between attribute valuation and students' socio-demographic background, educational experience, and future career plans. RESULTS: Of 310 eligible fourth year medical students, complete data was available for 302 students (97%). Students considering emigration ranked salary as more important than students not considering emigration, while students with rural living experience ranked salary as less important than those with no rural experience. Students willing to work in a rural area ranked infrastructure as more important than students who were unwilling, while female students ranked infrastructure as less important than male students. Students who were willing to work in a rural area ranked management style as a more important rural practice attribute than those who were unwilling to work in a rural area. Students studying in Kumasi ranked contract length as more important than those in Accra, while international students ranked contract length as less important than Ghanaian students. CONCLUSIONS: Interventions to improve rural practice conditions are likely to be more persuasive than salary incentives to Ghanaian medical students who are willing to work in rural environments a priori. Policy experiments should test the impact of these interventions on actual uptake by students upon graduation.

Willingness to work in rural areas and the role of intrinsic versus extrinsic professional motivations - a survey of medical students in Ghana.

BACKGROUND: Retaining health workers in rural areas is challenging for a number of reasons, ranging from personal preferences to difficult work conditions and low remuneration. This paper assesses the influence of intrinsic and extrinsic motivation on willingness to accept postings to deprived areas among medical students in Ghana. METHODS: A computer-based survey involving 302 fourth year medical students was conducted from May-August 2009. Logistic regression was used to assess the association between students' willingness to accept rural postings and their professional motivations, rural exposure and family parental professional and educational status (PPES). RESULTS: Over 85% of students were born in urban areas and 57% came from affluent backgrounds. Nearly two-thirds of students reported strong intrinsic motivation to study medicine. After controlling for demographic characteristics and rural exposure, motivational factors did not influence willingness to practice in rural areas. High family PPES was consistently associated with lower willingness to work in rural areas. CONCLUSIONS: Although most Ghanaian medical students are motivated to study medicine by the desire to help others, this does not translate into willingness to work in rural areas. Efforts should be made to build on intrinsic motivation during medical training and in designing rural postings, as well as favour lower PPES students for admission.

Rural practice preferences among medical students in Ghana: a discrete choice experiment.

OBJECTIVE: To determine how specific job attributes influenced fourth year medical students' stated preference for hypothetical rural job postings in Ghana. METHODS: Based on discussions with medical student focus groups and physicians in practice and in the Ministry of Health, we created a discrete choice experiment (DCE) that assessed how students' stated preference for certain rural postings was influenced by various job attributes: a higher salary, free superior housing, an educational allowance for children, improved equipment, supportive management, shorter contracts before study leave and a car. We conducted the DCE among all fourth year medical students in Ghana using a brief structured questionnaire and used mixed logit models to estimate the utility of each job attribute. FINDINGS: Complete data for DCE analysis were available for 302 of 310 (97%) students. All attribute parameter estimates differed significantly from zero and had the expected signs. In the main effects mixed logit model, improved equipment and supportive management were most strongly associated with job preference (beta = 1.42; 95% confidence interval, CI: 1.17 to 1.66, and beta = 1.17; 95% CI: 0.96 to 1.39, respectively), although shorter contracts and salary bonuses were also associated. Discontinuing the provision of basic housing had a large negative influence (beta = -1.59; 95% CI: -1.88 to -1.31). In models including gender interaction terms, women's preferences were more influenced by supportive management and men's preferences by superior housing. CONCLUSION: Better working conditions were strongly associated with the stated choice of hypothetical rural postings among fourth year Ghanaian medical students. Studies are needed to find out whether job attributes determine the actual uptake of rural jobs by graduating physicians.

Synthesis of C3-symmetric and C4-symmetric amino acid derivatives via Suzuki-Miyaura cross-coupling reaction.

Various non-natural C(3)- and C(4)-symmetric alpha-amino acid derivatives have been synthesized via Suzuki-Miyaura cross-coupling reaction between aromatic iodides or bromide and a suitably protected DL-4-boronophenylalanine derivative.

Design and synthesis of a novel anthracene-based fluorescent probe through the application of the Suzuki-Miyaura cross-coupling reaction.

We report on a simple synthetic route to a novel anthracene-based bis-armed amino acid derivative as a useful fluorescent probe. Various photophysical studies of this amino acid derivative are also described. Here, Suzuki-Miyaura cross-coupling reaction has been used as a key step for carbon-carbon bond formation.

Associations of Physical Activity and Sedentary Behaviour with Vision-Threatening Diabetic Retinopathy in Indonesian Population with Type 2 Diabetes Mellitus: Jogjakarta Eye Diabetic Study in the Community (JOGED.COM).

PURPOSE: To investigate the association of physical activity (PA) and sedentary behaviour with diabetic retinopathy (DR) in type 2 diabetes adults. METHODS: A community-based cross-sectional study of adults with type 2 diabetes. DR was assessed from disc- and macula-centred fundus photograph, and categorised into mild, moderate non-proliferative DR (NPDR), and Vision-Threatening DR (VTDR). Worse eye was used to determine the person's DR severity. PA was assessed using WHO Global Physical Activity Questionnaire (GPAQ). All of the PA components, including daily sitting time, walking distance, sleeping duration, and exercise were converted based on the physical activity ratio and then calculated to obtain the mean physical activity level (PAL). The mean PAL was then classified into sedentary, moderate, and vigorous lifestyle. RESULTS: There were 1116 participants, 43.1% with any DR and 26.3% VTDR. The prevalence of DR/VTDR in sedentary, moderate, and vigorous physical activity group was 41.9%/22.7%, 39.2%/23.9%, and 32.7%/20.4% respectively. A longer duration of daily sedentary lifestyle (>3 hours) was significantly associated with presence of DR (OR 1.66; 95% CI 1.17-2.35; p < 0.01) and VTDR (OR 1.74; 1.16-2.62; p < 0.01). These associations remained significant after adjusting for age, gender, duration of diabetes, systolic blood pressure and physical activity. There was no significant association between sleeping duration, walking distance, and vigorous activity and DR. CONCLUSIONS: In this study, prolonged daily sedentary activity was strongly associated with VTDR. This finding suggests that public health campaign for reducing daily sedentary activities in individuals with type 2 diabetes may offer benefit to reduce the burden of DR and VTDR.

Tensile behavior of cortical bone: dependence of organic matrix material properties on bone mineral content.

A porous composite model is developed to analyze the tensile mechanical properties of cortical bone. The effects of microporosity (volksman's canals, osteocyte lacunae) on the mechanical properties of bone tissue are taken into account. A simple shear lag theory, wherein tensile loads are transferred between overlapped mineral platelets by shearing of the organic matrix, is used to model the reinforcement provided by mineral platelets. It is assumed that the organic matrix is elastic in tension and elastic-perfectly plastic in shear until it fails. When organic matrix shear stresses at the ends of mineral platelets reach their yield values, the stress-strain curve of bone tissue starts to deviate from linear behavior. This is referred as the microscopic yield point. At the point where the stress-strain behavior of bone shows a sharp curvature, the organic phase reaches its shear yield stress value over the entire platelet. This is referred as the macroscopic yield point. It is assumed that after macroscopic yield, mineral platelets cannot contribute to the load bearing capacity of bone and that the mechanical behavior of cortical bone tissue is determined by the organic phase only. Bone fails when the principal stress of the organic matrix is reached. By assuming that mechanical properties of the organic matrix are dependent on bone mineral content below the macroscopic yield point, the model is used to predict the entire tensile mechanical behavior of cortical bone for different mineral contents. It is found that decreased shear yield stresses and organic matrix elastic moduli are required to explain the mechanical behavior of bones with lowered mineral contents. Under these conditions, the predicted values (elastic modulus, 0.002 yield stress and strain, and ultimate stress and strain) are within 15% of experimental data.

Adhesion enhancement of steel fibers to acrylic bone cement through a silane coupling agent.

The use of a silane coupling agent (methacryloxypropyl-trichlorosilane) to improve the mechanical properties of steel fiber-reinforced acrylic bone cements was assessed. Changes to the tensile and fracture properties of bone cements reinforced with silane-coated or uncoated 316L stainless steel fibers of different aspect ratios were studied. Contact-angle measurements indicated that the coupling agent coats the metal surface through room temperature treatments in a short time (within 2 h). Push-out tests indicated that the interfacial shear strength of silane-coated 316L stainless steel rods is 141% higher than the uncoated rods. The elastic moduli, ultimate stresses, and fracture toughness of the silane-coated, steel fiber-reinforced bone cements are significantly higher than the bone cements reinforced with uncoated steel fibers. There were no differences in the tensile mechanical properties of the silane-coated or uncoated, steel fiber-reinforced cements after aging in a physiological saline solution, indicating that the bonding effectiveness is decreased by the intrusion of water at the metal-polymer interface. Because of possible biocompatibility issues with leaching of the silane coupling agent and no long-term mechanical benefit in simulated aging experiments, the use of these agents is not recommended for in vivo use.

Fracture toughness of steel-fiber-reinforced bone cement.

Fractures in the bone-cement mantle (polymethyl methacrylate) have been linked to the failure of cemented total joint prostheses. The heat generated by the curing bone cement has also been implicated in the necrosis of surrounding bone tissue, leading to loosening of the implants. The addition of reinforcements may improve the fracture properties of bone cement and decrease the peak temperatures during curing. This study investigates the changes in the fracture properties and the temperatures generated in the ASTM F451 tests by the addition of 316L stainless steel fibers to bone cement. The influence of filler volume fraction (5-15% by volume) and aspect ratios (19, 46, 57) on the fracture toughness of the acrylic bone cement was assessed. Increasing the volume fraction of the steel fibers resulted in significant increases in the fracture toughness of the steel-fiber-reinforced composite. Fracture-toughness increases of up to 2.63 times the control values were obtained with the use of steel-fiber reinforcements. No clear trend in the fracture toughness was discerned for increasing aspect ratios of the reinforcements. There is a decrease in the peak temperatures reached during the curing of the steel-fiber-reinforced bone cement, though the decrease is too small to be clinically relevant. Large increases in the fatigue life of acrylic bone cement were also obtained by the addition of steel fibers. These results indicate that the use of steel fibers may enhance the durability of cemented joint prostheses.

Tensile damage and its effects on cortical bone.

Plexiform bovine bone samples are repeatedly loaded in tension along their longitudinal axis. In order to induce damage in the bone tissue, bone samples are loaded past their yield point. Half of the bone samples from the damaged group were stored in saline to allow for viscoelastic recovery while the others were decalcified. Tensile tests were conducted on these samples to characterize the effects of damage on the mechanical behavior of the organic matrix (decalcified samples) as well as on bone tissue (stored in saline). The ultimate strain of the damaged decalcified bone is 29% higher compared to that of non-damaged decalcified (control) bone. The ultimate stresses as well as the elastic moduli are similar in both decalcified groups. This phenomenon is also observed in other collagenous tissue (tendon and ligament). This may suggest that damage in bone is caused by shear failure of the organic matrix; transverse separation of the collagen molecules or microfibrils from each other. In contrast, there is a trend towards lowered ultimate strains in damaged bone, which is soaked in saline, with respect to control bone samples (not damaged). The damaged bone tissue exhibits a bi-linear behavior in contrast to the mechanical behavior of non-damaged bone. The initial elastic modulus (below 55 MPa) and ultimate strength of damaged bone are similar to that in non-damaged bone.

Experimental and finite element analysis of the rat ulnar loading model-correlations between strain and bone formation following fatigue loading.

The rat forelimb compression model has been used widely to study bone response to mechanical loading. We used strain gages to assess load sharing between the ulna and radius in the forelimb of adult Fisher rats. We used histology and peripheral quantitative computed tomography (pQCT) to quantify ulnar bone formation 12 days after in vivo fatigue loading. Lastly, we developed a finite element model of the ulna to predict the pattern of surface strains during compression. Our findings indicate that at the mid-shaft the ulna carries 65% of the applied compressive force on the forelimb. We observed large variations in fatigue-induced bone formation over the circumference and length of the ulna. Bone formation was greatest 1-2 mm distal to the mid-shaft. At the mid-shaft, we observed woven bone formation that was greatest medially. Finite element analysis indicated a strain pattern consistent with a compression-bending loading mode, with the greatest strains occurring in compression on the medial surface and lesser tensile strains occurring laterally. A peak strain of -5190 microepsilon (for 13.3N forelimb compression) occurred 1-2 mm distal to the mid-shaft. The pattern of bone formation in the longitudinal direction was highly correlated to the predicted peak compressive axial strains at seven cross-sections (r2 = 0.89, p = 0.014). The in-plane pattern of bone formation was poorly correlated to the predicted magnitude of axial strain at 51 periosteal locations (r2 = 0.21, p < 0.001), because the least bone formation was observed where tensile strains were highest. These findings indicate that the magnitude of bone formation after fatigue loading is greatest in regions of high compressive strain.

Changing the structurally effective mineral content of bone with in vitro fluoride treatment.

Bovine femur cortical bone specimens were tested in tension after being treated in vitro for 3 days with sodium fluoride solutions of different molarity (0.145, 0.5, and 2.0M). The treatments alter the mechanical properties of the bone samples with different degrees as compared to control samples (untreated). The mechanical properties of the treated samples have lower elastic modulus, yield and ultimate stress, acoustic impedance and hardness, and higher ultimate strain and toughness as compared to control samples. The observed effects were intensified with the increasing molarity of the treatment solutions. This study shows that the fluoride treatment can be used to investigate the composite behavior of bone tissue by altering the structurally important bone mineral content in a controlled manner.

Nanocomposite magneto-rheological fluids with uniformly dispersed Fe nanoparticles.

A systematic study of the magnetic and rheological properties of magneto-rheological (MR) fluids containing micron-size and nano-size iron particles is presented. The MR fluids were prepared with hydraulic oil as the carrier liquid and lecithin as an effective surfactant medium that promotes uniform particle dispersion. Magnetic measurements on micron-, hybrid-(nano + micron), and nano-MR fluids clearly indicate that the partial replacement of the micro-size particles by nanoparticles results in a better suspension and robust chain formation under applied external magnetic fields. For nano-MR fluids, the measured yield stress was found to be lower than micron-MR fluids. However, better flow properties and sharper magnetic switching make nanoparticle-based MR fluids appealing for microfluidics device applications where higher yield stress is not required.

The effects of interphase and bonding on the elastic modulus of bone: changes with age-related osteoporosis.

A simple shear lag model is developed to analyze the physics of the stress transfer between the organic and mineral constituents of bone tissue in the presence of an interphase and changes in bonding. The analytical model is developed assuming interactions between overlapped bone mineral platelets. The platelets are assumed to carry the axial stresses while the organic matrix transfers the stresses from one platelet to another by shear. A decrease in the interphase mechanical properties decreases the elastic modulus due to increased shear between the overlapped platelets. A decrease in bonding decreases the elastic modulus due to an increase in the axial stress transferred from the ends of the platelet. The implications of the changes in parameters on the age-related disorders of bone (osteoporois) are discussed. It is suggested that the aspect ratio and volume fraction of the mineral in the remaining bone tissue would increase due to a reduction in the density of the bone. The mechanical properties of the organic are hypothesized to increase due to a reduction in the density of bone leading to an increased tendency for damage within the organic.

Varying the mechanical properties of bone tissue by changing the amount of its structurally effective bone mineral content.

The effect of fluoride ions on the mechanical properties of bone tissue in tension was investigated with an in vitro model. Structurally effective Bone Mineral Content (BMC) of bovine bone tissue was changed by fluoride ion treatment. First, bovine cortical bone specimens were treated with a detergent solution in order to increase the diffusion rates of the treatment ions across the samples. After the initial treatment, different ion solutions were used to treat the tension samples (fluoride, sodium and chloride). Ionic strength and pH were varied. Experimental results showed that the sodium chloride solutions of different ionic strengths, at physiological and high pH, do not affect the mechanical properties of bone tissue in tension. However, uniform fluoride treatment across the samples reduced the mechanical strength of bone tissue by converting small amounts of bone mineral to mostly calcium fluoride. This action reduces the structurally effective BMC and also possibly effects the interface bonding between the bone mineral and the organic matrix of the bone tissue.

Hierarchies of damage induced loss of mechanical properties in calcified bone after in vivo fatigue loading of rat ulnae.

During fatigue loading of whole bone, damage to bone tissue accumulates, coalesces and leads to fractures. Whether damage affects tissue material properties similarly at the nanoscale (less than 1 µm), microscale (less than 1 mm), and whole bone scale has not been fully evaluated. Therefore, in this study, we examine scale-dependent loss of calcified tissue material properties in rat ulnae, after fatigue loading of rat forearms using the forearm compression model. In vivo fatigue loading was conducted on the right forearms until a displacement end-point was reached. The non-fatigued left forearms served as contralateral controls. Subsequently, three-point bending tests to failure on excised ulnae demonstrated a 41% and 49% reduction in the stiffness and ultimate strength as compared to contralateral control ulnae, respectively. Depth-sensing microindentation demonstrated an average decrease in material properties, such as elastic modulus and hardness, of 28% and 29% respectively. Nanoindentation measured elastic modulus and hardness were reduced by 26% and 29% in damaged bone relative to contralateral controls, respectively. The increased loss of whole bone material properties compared to tissue material properties measured using indentation is mainly attributed to the presence of a macrocrack located in the medial compressive region at the site of peak strains. The similar magnitude of changes in material properties by microindentation and nanoindentation is attributed to damage that may originate at an even smaller scale, as inferred from 10% differences in connectivity of osteocyte canaliculi in damaged bone.