ABSTRACT
The emergence and evolution of engineering biology, and its potential to address multiple global challenges is associated with the rise of biofoundries. These innovation intermediaries are facilities that employ advanced automation and computational analytics to accelerate engineering biology applications. Yet, for biofoundries to fully achieve their promise of generating applications that address grand societal challenges, they need to meet three key challenges: translation of research technology and its commercialization, attention to sustainability, and responsible innovation. Using web content analysis and interviews, this paper explores the functions and capabilities undertaken by existing public biofoundries, the extent to which they address these three challenges, and opportunities and models for enhancement. We also probe the roles undertaken by three other contrasting types of innovation intermediaries to identify practices and opportunities for integration and partnering with public biofoundries. We find that public biofoundries exhibit relatively strong capabilities for research translation, whereas efforts toward sustainability and responsibility are generally less prominent. For biofoundry enhancement, we propose an organisational model based on external partnering where public biofoundries are positioned as intermediaries within regional innovation systems. The framework put forward is reproducible and could be used in other contexts for assessing innovation intermediary organisational functions and capabilities toward meeting societal challenges.
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The authors explore opportunities, challenges, and strategies to translate and responsibly scale innovative biobased technologies to build more sustainable bioeconomies. The pandemic and other recent disruptions increased exposure to issues of resilience and regional imbalance, highlighting a need for production and consumption regimes centred more on local biobased resources and dispersed production. The authors review potential biobased technology strategies and identify promising and feasible options for the United Kingdom. Initial landscape and bibliometric analysis identified 50 potential existing and emerging biobased technologies, which were assessed for their ability to fulfil requirements related to biobased production, national applicability, and economic-, societal-, and environmental-benefits, leading to identification of 18 promising biobased production technologies. Further analysis and focus-group discussion with industrial, governmental, academic, agricultural, and social stakeholders, identified three technology clusters for targeted assessment, drawing on cellulose-, lignin-, and seaweed feedstocks. Case studies were developed for each cluster, addressing conversations around sustainable management, use of biomass feedstocks, and associated environmental-, social-, and economic challenges. Cases are presented with discussion of insights and implications for policy. The approach presented is put forward as a scalable assessment method that can be useful in prompting, informing, and advancing discussion and deliberation on opportunities and challenges for biobased transformations.
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AIMS: Elevated fasting blood glucose in gestational diabetes (GDM) is a key predictor of high birthweight babies and adverse pregnancy outcomes but is hard to treat. We implemented a simple, patient-led, insulin dose titration algorithm aiming to improve fasting glycaemic control in GDM. METHODS: In women with GDM, initiating basal insulin, we recommended a daily four-unit dose increase after every fasting glucose value ≥5.0 mmol/mol (90 mg/dl). This approach augmented our pre-existing intensive (weekly) specialist nursing input. Using a before-and-after retrospective observational study design, we examined insulin doses and glucose values at 36 weeks gestation and maternal and neonatal outcomes in 105 women completing pregnancy before and 93 women after the intervention. RESULTS: The baseline characteristics of women in the before and after groups were the same. Women initiated on insulin after implementation (n = 30 before, n = 43 after) achieved substantially higher doses at 36 weeks (53 vs. 36 units/day; 0.56 vs. 0.37 units/kg/day; p = 0.027). 36-week mean fasting glucose was lower in those on insulin after implementation (4.6 vs. 5.1 mmol/L [83 vs. 92 mg/dl]; p = 0.031). Birthweight was significantly reduced (birthweight Z-scores 0.34 vs. 0.92; p = 0.005). There was no significant difference in macrosomia (after; 2% vs. before; 17% p = 0.078) or caesarean sections (after; 33% vs. before; 47%; p = 0.116). No women experienced severe hypoglycaemia. There were no outcome differences before versus after intervention in women not treated with insulin. CONCLUSIONS: Patient-led daily insulin titration in gestational diabetes leads to higher insulin dose use lower fasting glucose and is associated with lower birthweight without causing significant hypoglycaemia.
Subject(s)
Diabetes, Gestational , Hyperglycemia , Hypoglycemia , Birth Weight , Blood Glucose , Diabetes, Gestational/drug therapy , Female , Glucose , Glycemic Control , Humans , Hyperglycemia/drug therapy , Hypoglycemia/chemically induced , Hypoglycemia/drug therapy , Hypoglycemia/prevention & control , Infant, Newborn , Insulin/therapeutic use , PregnancyABSTRACT
Transglycanases are enzymes that remodel the primary cell wall in plants, potentially loosening and/or strengthening it. Xyloglucan endotransglucosylase (XET; EC 2.4.1.207), ubiquitous in land plants, is a homo-transglucanase activity (donor, xyloglucan; acceptor, xyloglucan) exhibited by XTH (xyloglucan endotransglucosylase/hydrolase) proteins. By contrast, hetero-trans-ß-glucanase (HTG) is the only known enzyme that is preferentially a hetero-transglucanase. Its two main hetero-transglucanase activities are MLG : xyloglucan endotransglucosylase (MXE) and cellulose : xyloglucan endotransglucosylase (CXE). HTG is highly acidic and found only in the evolutionarily isolated genus of fern-allies, Equisetum. We now report genes for three new highly acidic HTG-related XTHs in E. fluviatile (EfXTH-A, EfXTH-H and EfXTH-I). We expressed them heterologously in Pichia and tested the encoded proteins' enzymic activities to determine whether their acidity and/or their Equisetum-specific sequences might confer high hetero-transglucanase activity. Untransformed Pichia was found to secrete MLG-degrading enzyme(s), which had to be removed for reliable MXE assays. All three acidic EfXTHs exhibited very predominantly XET activity, although low but measurable hetero-transglucanase activities (MXE and CXE) were also detected in EfXTH-H and EfXTH-I. We conclude that the extremely high hetero-transglucanase activities of Equisetum HTG are not emulated by similarly acidic Equisetum XTHs that share up to 55.5% sequence identity with HTG.
Subject(s)
Equisetum/genetics , Glycosyltransferases/genetics , Plant Proteins/genetics , Amino Acid Sequence , Equisetum/metabolism , Glycosyltransferases/chemistry , Glycosyltransferases/metabolism , Phylogeny , Plant Proteins/chemistry , Plant Proteins/metabolism , Sequence Alignment , Substrate SpecificityABSTRACT
Cell walls are important structural components of plants, affecting both the bioaccessibility and subsequent digestibility of the nutrients that plant-based foods contain. These supramolecular structures are composed of complex heterogeneous networks primarily consisting of cellulose, and hemicellulosic and pectic polysaccharides. The composition and organization of these different polysaccharides vary depending on the type of plant tissue, imparting them with specific physicochemical properties. These properties dictate how the cell walls behave in the human gastrointestinal tract, and how amenable they are to digestion, thereby modulating nutrient release from the plant tissue. This short narrative review presents an overview of our current knowledge on cell walls and how they impact nutrient bioaccessibility and digestibility. Some of the most relevant methods currently used to characterize the food matrix and the cell walls are also described.
ABSTRACT
Covering: Up to 2019Phenolic cross-links and phenolic inter-unit linkages result from the oxidative coupling of two hydroxycinnamates or two molecules of tyrosine. Free dimers of hydroxycinnamates, lignans, play important roles in plant defence. Cross-linking of bound phenolics in the plant cell wall affects cell expansion, wall strength, digestibility, degradability, and pathogen resistance. Cross-links mediated by phenolic substituents are particularly important as they confer strength to the wall via the formation of new covalent bonds, and by excluding water from it. Four biopolymer classes are known to be involved in the formation of phenolic cross-links: lignins, extensins, glucuronoarabinoxylans, and side-chains of rhamnogalacturonan-I. Lignins and extensins are ubiquitous in streptophytes whereas aromatic substituents on xylan and pectic side-chains are commonly assumed to be particular features of Poales sensu lato and core Caryophyllales, respectively. Cross-linking of phenolic moieties proceeds via radical formation, is catalyzed by peroxidases and laccases, and involves monolignols, tyrosine in extensins, and ferulate esters on xylan and pectin. Ferulate substituents, on xylan in particular, are thought to be nucleation points for lignin polymerization and are, therefore, of paramount importance to wall architecture in grasses and for the development of technology for wall disassembly, e.g. for the use of grass biomass for production of 2nd generation biofuels. This review summarizes current knowledge on the intra- and extracellular acylation of polysaccharides, and inter- and intra-molecular cross-linking of different constituents. Enzyme mediated lignan in vitro synthesis for pharmaceutical uses are covered as are industrial exploitation of mutant and transgenic approaches to control cell wall cross-linking.
Subject(s)
Cell Wall/chemistry , Phenols/chemistry , Plants/chemistry , Carbohydrate SequenceABSTRACT
BACKGROUND: Men who have sex with men (MSM) and transgender women in Sub-Saharan Africa are subjected to high levels of sexual behavior-related stigma, which may affect mental health and sexual risk behaviors. MSM and transgender women who are open about, or have disclosed their sexual behaviors appear to be most affected by stigma. Characterizing the mechanism of action of stigma in potentiating HIV-risks among these key populations is important to support the development of interventions. METHODS: In this study, a total of 532 individuals were recruited across Eswatini (Swaziland) through chain-referral-sampling from October - December 2014, including 419 cisgender MSM and 109 transgender women. Participants were surveyed about demographics, stigma, outness of same-sex practices to family members and healthcare workers, and mental and sexual health. This study used latent class analysis (LCA) to determine latent constructs of stigma/outness, and used multinomial logistic regression to determine associations with underlying constructs and sexual risk behaviors. RESULTS: Three latent classes emerged: 1) Those who reported low probabilities of stigma (55%; 276/502); 2) Those who reported high probabilities of stigma including physical violence and fear/avoidance of healthcare, and were not "out" (11%; 54/502); and 3) Those who reported high probabilities of stigma including verbal harassment and stigma from family and friends, and were "out" (34%; 172/502). Relative to the "low stigma" class, participants from an urban area (adjusted odds ratio [AOR] = 2.78, 95% Confidence Interval [CI] = 1.53-5.07) and who engaged in condomless anal sex (AOR = 1.85, 95% CI = 1.17-2.91) were more likely to belong to the "high stigma, 'out'" class. In contrast, those who had a concurrent male or female partner were more likely to belong to the "high stigma, not 'out'" class AOR = 2.73, 95% CI = 1.05-7.07). Depression was associated with membership in both high-stigma classes (AOR = 3.14, 95% CI = 1.50-6.55 "not out", AOR = 2.42, 95% CI = 1.51-3.87 "out"). CONCLUSIONS: Sexual behavior stigma at a community level is associated with individual-level risk behaviors among MSM and transgender women, and these associations vary by level of outness about sexual practices. Achieving sufficient coverage of evidence-based stigma interventions may be key to realizing the potential impact of HIV prevention and treatment interventions for MSM and transgender women in Eswatini.
Subject(s)
Homosexuality, Male/psychology , Self Disclosure , Sexual and Gender Minorities/psychology , Social Stigma , Transgender Persons/psychology , Adult , Eswatini , Female , Humans , Latent Class Analysis , Logistic Models , Male , Middle Aged , Surveys and Questionnaires , Unsafe Sex , Young AdultABSTRACT
Daprodustat, a small-molecule inhibitor of prolyl hydroxylases, prevents breakdown of hypoxia-inducible factor (HIF), leading to increased transcription of HIF-responsive genes. This randomized, placebo-controlled study evaluated the safety, tolerability, and pharmacokinetics of a topical formulation of daprodustat in healthy volunteers (intact skin) and in patients with diabetic foot ulcers (DFUs) following single and/or 14-day repeat-dose administration. In the diabetic patients, exploratory assessments of wound area, volume, and depth were made to qualitatively assess effectiveness. Systemic absorption via topical application was limited across doses up to 1.0% at 100 mg/cm2 for 14 days. Systemic pharmacokinetics were quantifiable in a few samples from a few patients. Because only sporadic concentrations were observed versus pharmacokinetic profiles, pharmacokinetic parameters were not determined. Wound area, depth, and volume showed consistent but weak improvements in the treatment arm; however, the variability in response and small sample size of the standard-of-care and placebo arms limited the ability to assess trends in wound healing compared with the daprodustat arm. Overall, topically applied daprodustat was well tolerated, raised no safety concerns, and provided limited to nonquantifiable systemic exposures. The healing of DFUs will need to be evaluated in studies designed to test this hypothesis over a longer treatment duration.
Subject(s)
Barbiturates/administration & dosage , Barbiturates/pharmacokinetics , Diabetic Foot/drug therapy , Glycine/analogs & derivatives , Administration, Topical , Adult , Aged , Barbiturates/adverse effects , Drug Administration Schedule , Female , Glycine/administration & dosage , Glycine/adverse effects , Glycine/pharmacokinetics , Healthy Volunteers , Humans , Male , Middle Aged , Standard of CareABSTRACT
MAIN CONCLUSION: Evidence is presented that cotton fibre adhesion and middle lamella formation are preceded by cutin dilution and accompanied by rhamnogalacturonan-I metabolism. Cotton fibres are single cell structures that early in development adhere to one another via the cotton fibre middle lamella (CFML) to form a tissue-like structure. The CFML is disassembled around the time of initial secondary wall deposition, leading to fibre detachment. Observations of CFML in the light microscope have suggested that the development of the middle lamella is accompanied by substantial cell-wall metabolism, but it has remained an open question as to which processes mediate adherence and which lead to detachment. The mechanism of adherence and detachment were investigated here using glyco-microarrays probed with monoclonal antibodies, transcript profiling, and observations of fibre auto-digestion. The results suggest that adherence is brought about by cutin dilution, while the presence of relevant enzyme activities and the dynamics of rhamnogalacturonan-I side-chain accumulation and disappearance suggest that both attachment and detachment are accompanied by rhamnogalacturonan-I metabolism.
Subject(s)
Gossypium/metabolism , Polysaccharides/metabolism , Cotton Fiber , Gene Expression Profiling , Gene Expression Regulation, Plant , Glucans/metabolism , Xylans/metabolismABSTRACT
Cellulose fibers can be freed from the cell-wall skeleton via high-shear homogenization, to produce cellulose nanofibers (CNF) that can be used, for example, as the reinforcing phase in composite materials. Nanofiber production from agro-industrial byproducts normally involves harsh chemical-pretreatments and high temperatures to remove noncellulosic polysaccharides (20-70% of dry weight). However, this is expensive for large-scale processing and environmentally damaging. An enzyme-only pretreatment to obtain CNF from agro-industrial byproducts (potato and sugar beet) was developed with targeted commercial enzyme mixtures. It is hypothesized that cellulose can be isolated from the biomass, using enzymes only, due to the low lignin content, facilitating greater liberation of CNF via high-shear homogenization. Comprehensive Microarray Polymer Profiling (CoMPP) measured remaining extractable polysaccharides, showing that the enzyme-pretreatment was more successful at removing noncellulosic polysaccharides than alkaline- or acid-hydrolysis alone. While effective alone, the effect of the enzyme-pretreatment was bolstered via combination with a mild high-pH pretreatment. Dynamic rheology was used to estimate the proportion of CNF in resultant suspensions. Enzyme-pretreated suspensions showed 4-fold and 10-fold increases in the storage modulus for potato and sugar beet, respectively, compared to untreated samples. A greener yet facile method for producing CNF from vegetable waste is presented here.
Subject(s)
Biotechnology/methods , Cellulose/analogs & derivatives , Industrial Waste , Nanofibers/chemistry , Vegetables/chemistry , Beta vulgaris/chemistry , Biocatalysis , Hydrolysis , Solanum tuberosum/chemistryABSTRACT
Bridging immunoassays commonly used to detect and characterize immunogenicity during biologic development do not provide direct information on the presence or development of a memory anti-drug antibody (ADA) response. In this study, a B cell ELISPOT assay method was used to evaluate pre-existing ADA for anti-TNFR1 domain antibody, GSK1995057, an experimental biologic in treatment naive subjects. This assay utilized a 7-day activation of PBMCs by a combination of GSK1995057 (antigen) and polyclonal stimulator followed by GSK1995057-specific ELISPOT for the enumeration of memory B cells that have differentiated into antibody secreting cells (ASC) in vitro. We demonstrated that GSK1995057-specific ASC were detectable in treatment-naïve subjects with pre-existing ADA; the frequency of drug-specific ASC was low and ranged from 1 to 10 spot forming units (SFU) per million cells. Interestingly, the frequency of drug-specific ASC correlated with the ADA level measured using an in vitro ADA assay. We further confirmed that the ASC originated from CD27+ memory B cells, not from CD27--naïve B cells. Our data demonstrated the utility of the B cell ELISPOT method in therapeutic protein immunogenicity evaluation, providing a novel way to confirm and characterize the cell population producing pre-existing ADA. This novel application of a B cell ELISPOT assay informs and characterizes immune memory activity regarding incidence and magnitude associated with a pre-existing ADA response.
Subject(s)
Antibodies/immunology , B-Lymphocytes/immunology , Biological Products/immunology , Immunoassay/methods , Immunologic Memory , Antibodies/blood , Antibody-Producing Cells/immunology , B-Lymphocytes/cytology , Cell Differentiation , Enzyme-Linked Immunosorbent Assay , Humans , Leukocytes, Mononuclear/immunology , Receptors, Tumor Necrosis Factor, Type I/immunology , Tumor Necrosis Factor Receptor Superfamily, Member 7/immunologyABSTRACT
Impaired skin wound healing is a significant comorbid condition of diabetes that is caused by poor microcirculation, among other factors. Studies have shown that angiogenesis, a critical step in the wound healing process in diabetic wounds, can be promoted under hypoxia. In this study, an angiogenesis-promoting topical treatment for diabetic wounds, which promotes angiogenesis by mimicking a hypoxic environment via inhibition of prolyl hydroxylase resulting in elevation or maintenance of hypoxia-inducible factor, was investigated utilizing a custom-built multimodal microscopy system equipped with phase-variance optical coherence tomography (PV-OCT) and fluorescence lifetime imaging microscopy (FLIM). PV-OCT was used to track the regeneration of the microvasculature network, and FLIM was used to assess the in vivo metabolic response of mouse epidermal keratinocytes to the treatment during healing. Results show a significant decrease in the fluorescence lifetime of intracellular reduced nicotinamide adenine dinucleotide, suggesting a hypoxic-like environment in the wounded skin, followed by a quantitative increase in blood vessel density assessed by PV-OCT. Insights gained in these studies could lead to new endpoints for evaluation of the efficacy and healing mechanisms of wound-healing drugs in a setting where delayed healing does not permit available methods for evaluation to take place.
Subject(s)
Angiogenesis Inducing Agents/pharmacology , Diabetes Mellitus, Experimental/diagnostic imaging , Diabetes Mellitus, Experimental/physiopathology , Microscopy , Wound Healing/drug effects , Administration, Topical , Angiogenesis Inducing Agents/administration & dosage , Animals , Cell Hypoxia/drug effects , Diabetes Mellitus, Experimental/pathology , Keratinocytes/drug effects , Keratinocytes/pathology , Mice , Microvessels/drug effects , Microvessels/physiopathologyABSTRACT
BACKGROUND: Stigma involves discrediting a person or group based on a perceived attribute, behaviour or reputation associated with them. Sex workers (SW) and men who have sex with men (MSM) are key populations who are often at increased risk for the acquisition and transmission of HIV and who are affected by stigma that can negatively impact their health and well-being. Although stigma was included as an indicator in the US National HIV/AIDS Strategic Plan and there have been consultations focused on adding a stigma indicator within PEPFAR and the Global Fund in relation to potentiating HIV risks among key populations, there remains limited consensus on the appropriate measurement of SW- or MSM-associated stigma. Consequently, this systematic review summarizes studies using quantitative, qualitative, or mixed methods approaches to measure stigma affecting sex workers and men who have sex with men. METHODS AND FINDINGS: This systematic review included English, French, and Spanish peer-reviewed research of any study design measuring SW- or MSM-associated stigma. Articles were published from January 1, 2004 to March 26, 2014 in PsycINFO, PubMed, EMBASE, CINAHL Plus, Global Health, and World Health Organization Global Health Library Regional Indexes. Of the 541 articles reviewed, the majority measured stigma toward MSM (over 97%), were conducted in North America, used quantitative methods, and focused on internalized stigma. CONCLUSIONS: With the inclusion of addressing stigma in several domestic and international HIV strategies, there is a need to ensure the use of validated metrics for stigma. The field to date has completed limited measurement of stigma affecting sex workers, and limited measurement of stigma affecting MSM outside of higher income settings. Moving forward requires a concerted effort integrating validated metrics of stigma into health-related surveys and programs for key populations.
Subject(s)
Homosexuality, Male , Sex Workers , Social Stigma , Humans , MaleABSTRACT
BACKGROUND: Female sex workers (FSWs) are disproportionately affected by HIV, even in the context of broadly generalised HIV epidemics such as South Africa. This has been observed in spite of the individual and population-level benefits of HIV treatment. We characterise the HIV care cascade among FSWs and relationships with antiretroviral therapy (ART) use. METHODS: FSWs ≥18â years were recruited through respondent-driven sampling into a cross-sectional study in Port Elizabeth, South Africa. Participants completed questionnaires and received HIV and syphilis testing; CD4 counts were assessed among women living with HIV. Engagement in the HIV care cascade is described, and correlates of self-reported ART use among treatment-eligible previously diagnosed FSWs were estimated using robust Poisson regression. RESULTS: Between October 2014 and April 2015, 410 FSWs participated in study activities. Overall, 261/410 were living with HIV (respondent-driven sampling-weighted prevalence 61.5% (95% bootstrapped CI 54.1% to 68.0%)). Prior diagnosis of HIV was relatively high (214/261, 82%); however, ART coverage among FSWs living with HIV was 39% (102/261). In multivariate analyses, FSWs were less likely to be on ART if they had not disclosed their HIV status to non-paying partners (adjusted prevalence ratio (aPR) 0.43, 95% CI 0.22 to 0.86, where the reference is FSWs without non-paying partners), and also if they engaged in mobile healthcare services (aPR 0.71, 95% CI 0.57 to 0.89). CONCLUSIONS: HIV testing and awareness of HIV status were high, but substantial losses in the cascade occur at treatment initiation. Given that FSWs engaged in mobile HIV testing and peer education programmes have unmet HIV treatment needs, models of decentralised treatment provision such as mobile-based ART care should be evaluated.
Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , Patient Acceptance of Health Care/statistics & numerical data , Sex Workers/psychology , Syphilis/drug therapy , Condoms/statistics & numerical data , Cross-Sectional Studies , Female , HIV Infections/epidemiology , Humans , Prevalence , Sampling Studies , Sexual Behavior , South Africa/epidemiology , Surveys and Questionnaires , Syphilis/epidemiologyABSTRACT
OBJECTIVE: To assess the association between human immunodeficiency virus (HIV) and pregnancy intentions and safer conception knowledge among female sex workers in Port Elizabeth, South Africa. METHODS: This cross-sectional study recruited female sex workers in Port Elizabeth using respondent-driven sampling and completed an interviewer-administered questionnaire alongside HIV testing and counseling. In this secondary analysis, robust Poisson regression was used to model prevalence ratios for positive fertility intentions in this cross-sectional study. Knowledge of safer conception methods by HIV status was compared using Fisher exact tests. RESULTS: Overall 391 women were represented in the analyses. More than 50% had a prior HIV diagnosis, and an additional 12% were diagnosed with HIV during the study. Approximately half (n=185) of the women reported future pregnancy intentions. In univariate analysis, a prior HIV diagnosis was negatively associated with pregnancy intentions as compared with HIV-negative women (prevalence ratio 0.68, 95% confidence interval 0.55-0.85). Only parity remained independently associated with future pregnancy intentions in multivariate regression after controlling for HIV status, age, race, relationship status, and years selling sex. Knowledge of safer conception methods such as timed sex without a condom, preexposure prophylaxis, or self-insemination was low and similar between those with and without future pregnancy plans. CONCLUSION: Pregnancy intentions did not significantly vary according to HIV status. Fertility intentions were high, however, and knowledge of safer conception methods low, suggesting a need to provide female sex workers with advice around options to conceive safely in the context of high HIV prevalence.
Subject(s)
HIV Infections , Intention , Pregnancy Complications, Infectious , Reproductive Behavior , Sex Workers , Adult , Cross-Sectional Studies , Female , HIV Infections/diagnosis , HIV Infections/epidemiology , HIV Infections/psychology , Health Knowledge, Attitudes, Practice , Humans , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/psychology , Prevalence , Sex Workers/psychology , Sex Workers/statistics & numerical data , Sexual Behavior , South Africa/epidemiologyABSTRACT
Transgender people are a diverse population affected by a range of negative health indicators across high-income, middle-income, and low-income settings. Studies consistently document a high prevalence of adverse health outcomes in this population, including HIV and other sexually transmitted infections, mental health distress, and substance use and abuse. However, many other health areas remain understudied, population-based representative samples and longitudinal studies are few, and routine surveillance efforts for transgender population health are scarce. The absence of survey items with which to identify transgender respondents in general surveys often restricts the availability of data with which to estimate the magnitude of health inequities and characterise the population-level health of transgender people globally. Despite the limitations, there are sufficient data highlighting the unique biological, behavioural, social, and structural contextual factors surrounding health risks and resiliencies for transgender people. To mitigate these risks and foster resilience, a comprehensive approach is needed that includes gender affirmation as a public health framework, improved health systems and access to health care informed by high quality data, and effective partnerships with local transgender communities to ensure responsiveness of and cultural specificity in programming. Consideration of transgender health underscores the need to explicitly consider sex and gender pathways in epidemiological research and public health surveillance more broadly.
Subject(s)
Global Health/statistics & numerical data , Health Services Needs and Demand/statistics & numerical data , Transgender Persons/statistics & numerical data , Transsexualism/epidemiology , Humans , Mental Disorders/epidemiology , Mental Disorders/etiology , Mental Health/statistics & numerical data , Reproductive Health/statistics & numerical data , Social Stigma , Transgender Persons/psychology , Transsexualism/psychologyABSTRACT
OBJECTIVES: The objective of our study was to measure progress toward the UNAIDS 90-90-90 HIV care targets among key populations in urban areas of 2 countries in West Africa: Burkina Faso and Togo. METHODS: We recruited female sex workers (FSWs) and men who have sex with men (MSM) through respondent-driven sampling. From January to July 2013, 2738 participants were enrolled, tested for HIV, and completed interviewer-administered surveys. We used population-size estimation methods to calculate the number of people who were engaged in the HIV continuum of care. RESULTS: HIV prevalence ranged from 0.6% (2 of 329) of MSM in Kara, Togo, to 32.9% (115 of 350) of FSWs in Bobo Dioulasso, Burkina Faso. Of those confirmed to be HIV infected, a range of 0.0% (0 of 2) of MSM in Kara to 55.7% (64 of 115) of FSWs in Bobo Dioulasso were using ART. Based on population estimates, the percentage gap between HIV-infected people who should be using ART (per the 90-90-90 targets) and those who reported using ART ranged from 31.5% among FSWs in Bobo Dioulasso to 100.0% among MSM in Kara. CONCLUSIONS: HIV service coverage among MSM and FSWs in Burkina Faso and Togo was low in 2013. Interventions for improving engagement of these at-risk populations in the HIV continuum of care should include frequent, routine HIV testing and linkage to evidence-based HIV treatment services. Population-size estimates can be used to inform governments, policy makers, and funding agencies about where elements of HIV service coverage are most needed.
Subject(s)
HIV Infections , Health Services Accessibility , Homosexuality, Male , Sex Workers , Adolescent , Adult , Burkina Faso/epidemiology , Cross-Sectional Studies , Female , HIV Infections/epidemiology , Health Services Accessibility/statistics & numerical data , Humans , Male , Middle Aged , Population Surveillance , Surveys and Questionnaires , Young AdultABSTRACT
Cell walls are metabolically active components of plant cells. They contain diverse enzymes, including transglycanases (endotransglycosylases), enzymes that 'cut and paste' certain structural polysaccharide molecules and thus potentially remodel the wall during growth and development. Known transglycanase activities modify several cell-wall polysaccharides (xyloglucan, mannans, mixed-linkage ß-glucan and xylans); however, no transglycanases were known to act on cellulose, the principal polysaccharide of biomass. We now report the discovery and characterization of hetero-trans-ß-glucanase (HTG), a transglycanase that targets cellulose, in horsetails (Equisetum spp., an early-diverging genus of monilophytes). HTG is also remarkable in predominantly catalysing hetero-transglycosylation: its preferred donor substrates (cellulose or mixed-linkage ß-glucan) differ qualitatively from its acceptor substrate (xyloglucan). HTG thus generates stable cellulose-xyloglucan and mixed-linkage ß-glucan-xyloglucan covalent bonds, and may therefore strengthen ageing Equisetum tissues by inter-linking different structural polysaccharides of the cell wall. 3D modelling suggests that only three key amino acid substitutions (Trp â Pro, Gly â Ser and Arg â Leu) are responsible for the evolution of HTG's unique specificity from the better-known xyloglucan-acting homo-transglycanases (xyloglucan endotransglucosylase/hydrolases; XTH). Among land plants, HTG appears to be confined to Equisetum, but its target polysaccharides are widespread, potentially offering opportunities for enhancing crop mechanical properties, such as wind resistance. In addition, by linking cellulose to xyloglucan fragments previously tagged with compounds such as dyes or indicators, HTG may be useful biotechnologically for manufacturing stably functionalized celluloses, thereby potentially offering a commercially valuable 'green' technology for industrially manipulating biomass.
Subject(s)
Cellulose/metabolism , Equisetum/metabolism , Glycoside Hydrolases/chemistry , Glycoside Hydrolases/metabolism , Recombinant Proteins/metabolism , Amino Acid Substitution , Cloning, Molecular , Equisetum/genetics , Evolution, Molecular , Glycoside Hydrolases/genetics , Glycosyltransferases/metabolism , Pichia/genetics , Plant Proteins/chemistry , Plant Proteins/genetics , Plant Proteins/metabolism , Protein Conformation , Recombinant Proteins/genetics , Structural Homology, Protein , Substrate SpecificityABSTRACT
BACKGROUND: Men who have sex with men (MSM) are more likely to be living with HIV than other adult men in low- and middle-income countries. MSM experience barriers to accessing HIV services including a lack of available specialized care, and community-level stigma and discrimination. This study aims to examine the uptake of HIV services at non-governmental and community-based organizations (NGOs/CBOs) to identify ways to improve coverage of HIV prevention and treatment among MSM. METHODS: An Integrated Biological and Behavioral Surveillance (IBBS) survey was conducted in Yaoundé and Douala, Cameroon in 2011 using the respondent driven sampling (RDS) method to recruit and interview 239 MSM in Yaoundé and 272 MSM in Douala. RESULTS: MSM in Yaoundé were statistically significantly more likely to have accessed NGO/CBO services or been reached by an outreach worker in the past 12 months if they had any STI symptoms (aOR 2.17 CI 1.02-4.59. p=0.04), or if they had a larger MSM social network (aOR 1.02 CI 1.01-1.04. p<0.01). MSM in Douala were more likely to have accessed NGO/CBO services or been reached by an outreach worker in the past 12 months if they were living with HIV (aOR 3.60 CI 1.35-9.60. p=0.01), or if they reported higher numbers of male sexual partners (aOR 1.17 CI 1.00-1.36. p=0.046). Compared to men in Douala, MSM in Yaoundé were significantly less likely to have accessed NGO/CBO services or been reached by an outreach worker in the past 12 months (aOR 0.22 CI 0 .14-0.34. p=<0.01). CONCLUSIONS: With appropriate funding and resources, community-based organizations that provide care specifically for MSM can improve access to HIV prevention, treatment, and care services. Additionally, using social networks to reach MSM can connect greater numbers of the population to effective HIV interventions, which will improve health outcomes and decrease onward transmission of HIV.
Subject(s)
HIV Infections/prevention & control , Homosexuality, Male/statistics & numerical data , Adolescent , Adult , Cameroon , Condoms , Cross-Sectional Studies , Humans , Male , Risk Factors , Risk-Taking , Safe Sex , Sexual Partners , Social Stigma , Surveys and Questionnaires , Young AdultABSTRACT
BACKGROUND: Men who have sex with men (MSM) and female sex workers (FSW) are more likely to be living with HIV and experience difficulty accessing HIV health services due to stigma and discrimination. Antiretroviral treatment and sustained viral suppression among individuals living with HIV is the last step in the continuum of HIV care, which has been shown to improve health outcomes and decrease the risk of onward transmission of HIV. METHODS: To calculate the numerator and denominator for antiretroviral therapy (ART) coverage estimates among MSM and FSW living with HIV, the Priority Locations for AIDS Control Efforts methods were modified to include individual quantitative interviews, health service assessment and mapping, and size estimation in 7 cities in Cameroon. MSM and FSW were recruited using peer referral and venue-based sampling. The numerator was calculated from interviews with MSM and FSW. Population size estimation of MSM and FSW was used to determine the denominator. RESULTS: Antiretroviral coverage varied by site from 0% to 25% among HIV infected MSM and FSW. ART provision to the general population was reported at a significantly greater proportion of HIV health centers (56.5%) than ART provision to MSM and FSW populations (13.2%). CONCLUSIONS: The majority of MSM and FSW living with HIV and eligible for treatment in Cameroon are not connected to ART care. Additionally, ART provision for MSM and FSW at HIV health centers is insufficient. Characterizing effective strategies to reach optimal levels of engagement in the continuum of HIV care among MSM and FSW is essential for an AIDS-free generation for Cameroon.