Countries across Africa are rapidly transitioning from rural to urban societies. The UN projects that 60% of people living in Africa will be in urban areas by 2050, with the urban population on the ...continent tripling over the next 50 years. The challenge of building inclusive and sustainable cities in the context of rapid urbanization is arguably the critical development issue of the 21st Century and creating food secure cities is key to promoting health, prosperity, equity, and ecological sustainability. The expansion of Africa’s urban population is taking place largely in secondary cities: these are broadly defined as cities with fewer than half a million people that are not national political or economic centres. The implications of secondary urbanization have recently been described by the Cities Alliance as “a real knowledge gap”, requiring much additional research not least because it poses new intellectual challenges for academic researchers and governance challenges for policy-makers. International researchers coming from multiple points of view including food studies, urban studies, and sustainability studies, are starting to heed the call for further research into the implications for food security of rapidly growing secondary cities in Africa. This book will combine this research and feature comparable case studies, intersecting trends, and shed light on broad concepts including governance, sustainability, health, economic development, and inclusivity. This is an open access book.
Guanylyl cyclase C (GCC) has been detected only in intestinal mucosa and colon carcinoma cells of placental mammals. However, this receptor has been identified in several tissues in marsupials, and ...its expression has been suggested in tissues other than intestine in placental mammals. Selective expression of GCC by colorectal tumor cells in extraintestinal tissues would permit this receptor to be employed as a selective marker for metastatic disease. Thus, expression of GCC was examined in human tissues and tumors, correlating receptor function with detection by PCR. GCC was detected by ligand binding and catalytic activation in normal intestine and primary and metastatic colorectal tumors, but not in extraintestinal tissues or tumors. Similarly, PCR yielded GCC-specific amplification products with specimens from normal intestine and primary and metastatic colorectal tumors, but not from extraintestinal tissues or tumors. Northern blot analysis employing GCC-specific probes revealed an ≈ 4-kb transcript, corresponding to recombinant GCC, in normal intestine and primary and metastatic colorectal tumors, but not in extraintestinal tissues. Thus, GCC is selectively expressed in intestine and colorectal tumors in humans and appears to be a relatively specific marker for metastatic cancer cells in normal tissues. Indeed, PCR of GCC detected tumor cells in blood from some patients with Dukes B colorectal cancer and all patients examined with Dukes C and D colorectal cancer, but not in that from normal subjects or patients with Dukes A colon carcinoma or other nonmalignant intestinal pathologies.
OBJECTIVE:To utilize Mendelian randomization to estimate the causal association between low serum vitamin D concentrations, increased body mass index (BMI), and pediatric-onset multiple sclerosis ...(MS) using genetic risk scores (GRS).
METHODS:We constructed an instrumental variable for vitamin D (vitD GRS) by computing a GRS for 3 genetic variants associated with levels of 25(OH)D in serum using the estimated effect of each risk variant. A BMI GRS was also created that incorporates the cumulative effect of 97 variants associated with BMI. Participants included non-Hispanic white individuals recruited from over 15 sites across the United States (n = 394 cases, 10,875 controls) and Sweden (n = 175 cases, 5,376 controls; total n = 16,820).
RESULTS:Meta-analysis findings demonstrated that a vitD GRS associated with increasing levels of 25(OH)D in serum decreased the odds of pediatric-onset MS (odds ratio OR 0.72, 95% confidence interval CI 0.55, 0.94; p = 0.02) after controlling for sex, genetic ancestry, HLA-DRB1*15:01, and over 100 non–human leukocyte antigen MS risk variants. A significant association between BMI GRS and pediatric disease onset was also demonstrated (OR 1.17, 95% CI 1.05, 1.30; p = 0.01) after adjusting for covariates. Estimates for each GRS were unchanged when considered together in a multivariable model.
CONCLUSIONS:We provide evidence supporting independent and causal effects of decreased vitamin D levels and increased BMI on susceptibility to pediatric-onset MS.
Data obtained from a nationwide survey of US residences during September and October 2002 are used to investigate household awareness of high-speed Internet access, profile Internet access and use, ...and gain insight into how important always-on, price, speed, installation, and reliability attributes are in their choice of service. Preliminary analysis suggests relatively high awareness of cable modem and DSL availability. Almost 19 percent of the sample have high-speed connectivity, and the mean price paid per month for dial-up and high-speed access is $19.76 and $42.36, respectively. Preference for high-speed access is apparent among households with higher income and college education. About 63 percent of high-speed users have more than five years of online experience, compared to 48 percent of dial-up users, and high-speed users are twice as likely to share music files and photos, bank, trade stocks, and pay bills “many times a week” than dial-up users. Willingness-to-pay estimates indicate reliability of service, speed, and always-on connectivity are important Internet access attributes.
Introduction
Polydrug use involving heroin and benzodiazepines is common. The potential risk of additive pharmacological effects may be associated with poorer outcomes in patients who use ...benzodiazepines together with heroin. The aim of this study was to determine the clinical picture of patients presenting to the emergency department following acute drug toxicity involving heroin and benzodiazepines.
Methods
Exposure information, clinical data and outcome of acute drug toxicity presentations were collected between 1 October 2013 and 30 September 2014 as part of the European Drug Emergencies Network (Euro-DEN) project. The database was interrogated to identify patients who had taken heroin with or without benzodiazepine(s).
Results
A total of 1345 presentations involving acute heroin toxicity were identified: 492 had used one or more non-heroin/benzodiazepine drug and were not further considered in this study; 662 were lone heroin users and 191 had co-used heroin with one or more benzodiazepines. Co-users were more likely than lone heroin users to have reduced respiratory rate at presentation 12.7 ± 4.9 vs 13.6 ± 4.4 (
p
= 0.02) and require admission to hospital 18.3 vs 9.8% (
p
< 0.01). There were no differences in critical care admission rates 3.1 vs 3.9% (
p
= 0.83) or length of stay 4 h 59 min vs 5 h 32 min (
p
= 0.23). The 3 most common benzodiazepines were clonazepam, diazepam, and alprazolam. No differences were observed for clinical features between the three benzodiazepines.
Conclusion
This study shows that co-use of heroin and benzodiazepines is common, although the overall outcomes between co-users of heroin and benzodiazepines and heroin-only users were similar.
Multiple sclerosis (MS) is a heterogeneous disorder with a progressive course that is difficult to predict on a case-by-case basis. Natural history studies of MS have demonstrated that age influences ...clinical progression independent of disease duration.
To determine whether age would be associated with greater CNS injury as detected by magnetization transfer MRI.
Forty MS patients were recruited from out-patient clinics into two groups stratified by age but with similar clinical disease duration as well as thirteen controls age-matched to the older MS group. Images were segmented by automated programs and blinded readers into normal appearing white matter (NAWM), normal appearing gray matter (NAGM), and white matter lesions (WMLs) and gray matter lesions (GMLs) in the MS groups. WML and GML were delineated on T2-weighted 3D fluid-attenuated inversion recovery (FLAIR) and T1 weighted MRI volumes. Mean magnetization transfer ratio (MTR), region volume, as well as MTR histogram skew and kurtosis were calculated for each region.
All MTR measures in NAGM and MTR histogram metrics in NAWM differed between MS subjects and controls, as expected and previously reported by several studies, but not between MS groups. However, MTR measures in the WML did significantly differ between the MS groups, in spite of no significant differences in lesion counts and volumes.
Despite matching for clinical disease duration and recording no significant WML volume difference, we demonstrated strong MTR differences in WMLs between younger and older MS patients. These data suggest that aging-related processes modify the tissue response to inflammatory injury and its clinical outcome correlates in MS.
A number of epidemiological studies have suggested that cigarette smoking is a risk factor for osteoporosis. Benzo(a)pyrene (BaP) and 7,12-dimethylbenz(a)anthracene (DMBA) are polycyclic aromatic ...hydrocarbons (PAHs) found in the tar fraction of cigarette smoke, as well as in car exhaust and furnace gases. We hypothesized that BaP and DMBA are responsible, through interaction with the aryl hydrocarbon receptor (AhR), for the bone loss and fragility seen in smoking-related osteoporosis. In this study four groups of 9-month-old Sprague-Dawley rats were examined. An intact group served as controls. A second control was the ovariectomized (ovx) group. The third group (ovx + E
2) were ovariectomized and also given a continuous basal dose of estrogen by implanted estrogen pellet (0.085 mg of 17β-estradiol per rat). The fourth group (ovx + E
2 + BaP/DMBA) was ovariectomized with an estradiol pellet, and received subcutaneous injections of 250 μg/kg of BaP/DMBA weekly for 15 weeks. The loss of ovarian function allowed the study of a direct effect of BaP/DMBA on bone while the concomitant estrogen repletion prevented ovx-related bone loss. Dual-energy X-ray absorptiometry (DEXA), histomorphometry, image analysis, and mechanical testing were used to determine the effect of the treatments on bone. The DEXA results showed a significant (
p < 0.05) decrease in bone mineral density compared with intact controls with both ovx alone and with ovx + E
2 + BaP/DMBA treatment. The ovx + E
2 rats were similar to the intact controls. The osteoid parameters showed a significant increase (
p < 0.05) with BaP/DMBA addition vs. intact controls, mimicking the ovx rats. The ovx + E
2 rats had osteoid parameters comparable to those of intact rats. Bone connectivity was decreased in the ovx and ovx + E
2 + BaP/DMBA animals. Connectivity of the ovx + E
2 rats was comparable to that of intact animals. A decrease in failure force was seen in three-point bending for the ovx + E
2 + BaP/DMBA group and in vertebral compression in both the ovx and ovx + E
2 + BaP/DMBA groups vs. intact controls. The mechanical properties of the ovx + E
2 rats were similar to those of intact rats. These results demonstrate that BaP/DMBA causes a loss of bone mass and bone strength, possibly through an increase in bone turnover. This is the first in vivo study linking environmental toxicants, found in the tar fraction of cigarette smoke and in urban air pollution, to loss of bone mass and strength in estrogen-replete ovx rats.
Antihistamines are effective medications that have been used for decades in the management of allergic rhinitis; however, they may be administered or selected in an inappropriate fashion and may be ...the source of drug-related morbidity. Our objective is to present relevant background information and an expert consensus statement on the use of antihistamines in treatment of allergic rhinitis. In July 2002, 14 experts in allergy, clinical immunology, pharmacology, and impairment assessment were invited to participate in a roundtable conference to present current concepts and develop a consensus statement on the clinical management of allergic rhinitis with antihistamines. Many of the antihistamines used to treat allergic rhinitis, as well as the disease itself, may produce sedation, impairment, and reduced quality of life. Allergic rhinitis is more appropriately managed with the relatively nonimpairing second-generation antihistamines (eg, loratadine, desloratadine, cetirizine, and fexofenadine), because older agents (eg, diphenhydramine, chlorpheniramine, and brompheniramine) produce sedation and impairment and worsen sleep architecture. Although there is some debate surrounding the varying degrees of efficacy of second-generation antihistamines, it is known that some agents may produce varying levels of drowsiness or impairment, especially at higher than recommended doses. The differences with regard to safety among the second-generation antihistamines are smaller than are the differences between the first and second generations. A nonsedating, nonimpairing (even at higher than recommended doses), second-generation antihistamine is preferred for all patients, particularly those with a higher risk for the development of adverse effects. We recommend that primary care and specialist physicians, nurse practitioners, physician assistants, pharmacists, and all other health professionals involved in the diagnosis and treatment of allergic rhinitis follow this consensus document and share this information with patients for whom antihistamine therapy is recommended. In addition, further epidemiologic studies on the effects of antihistamines should be performed. (J Allergy Clin Immunol 2003;111:S835-42.)
Somatic cell gene targeting was used to create an isogenic set of human colon cancer cells that differs only in the presence or absence of their endogenous activated beta-catenin oncogene. Affymetrix ...Genechip expression profiling of parental cells and gene-targeted derivatives identified numerous novel genes whose expression was dependent on the presence of oncogenic beta-catenin. The transforming growth factor-beta family member bone morphogenetic protein 4 (BMP4), whose receptor is mutated in a rare inherited gastrointestinal cancer predisposition syndrome, was the most highly differentially expressed gene. Additional experiments revealed that the oncogenic allele of beta-catenin specifically is absolutely required for BMP4 expression and secretion by human cancer cells and that BMP4 is overexpressed and secreted by human colon cancer cells with mutant adenomatous polyposis coli genes. These data identify the presence of regulatory interactions between the Wnt and BMP signaling pathways in cancer pathogenesis, providing an intriguing connection between the sporadic and inherited forms of a common human malignancy.
PDF
