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Unpacking early infant male circumcision decision-making using qualitative findings from Zimbabwe
No full textAbstract
Background
Early infant male circumcision (EIMC) has been identified as a key HIV prevention intervention. Exploring the decision-making process for adoption of EIMC for HIV prevention among parents and other key stakeholders is critical for designing effective demand creation interventions to maximize uptake, roll out and impact in preventing HIV. This paper describes key players, decisions and actions involved in the EIMC decision-making process.
Methods
Two complementary qualitative studies explored hypothetical and actual acceptability of EIMC in Zimbabwe. The first study (conducted 2010) explored hypothetical acceptability of EIMC among parents and wider family through focus group discussions (FGDs, n\u2009= \u200924). The follow-up study (conducted 2013) explored actual acceptability of EIMC among parents through twelve in-depth interviews (IDIs), four FGDs and short telephone interviews with additional parents ( n\u2009= \u200995). Short statements from the telephone interviews were handwritten. FGDs and IDIs were audio-recorded, transcribed and translated into English. All data were thematically coded.
Results
Study findings suggested that EIMC decision-making involved a discussion between the infant\u2019s parents. Male and female participants of all age groups acknowledged that the father had the final say. However, discussions around EIMC uptake suggested that the infant\u2019s mother could sometimes covertly influence the father's decision in the direction she favoured. Discussions also suggested that fathers who had undergone voluntary medical male circumcision were more likely to adopt EIMC for their sons, compared to their uncircumcised counterparts. Mothers-in-law/grandparents were reported to have considerable influence. Based on study findings, we describe key EIMC decision makers and attempt to illustrate alternative outcomes of their key actions and decisions around EIMC within the Zimbabwean context.
Conclusions
These complementary studies identified critical players, decisions and actions involved in the EIMC decision-making process. Findings on who influences decisions regarding EIMC in the Zimbabwean context highlighted the need for EIMC demand generation interventions to target fathers, mothers, grandmothers, other family members and the wider community
Plasma proteome and metabolome characterization of an experimental human thyrotoxicosis model
No full textAbstract
Background
Determinations of thyrotropin (TSH) and free thyroxine (FT
4
) represent the gold standard in evaluation of thyroid function. To screen for novel peripheral biomarkers of thyroid function and to characterize FT
4
-associated physiological signatures in human plasma we used an untargeted OMICS approach in a thyrotoxicosis model.
Methods
A sample of 16 healthy young men were treated with levothyroxine for 8\ua0weeks and plasma was sampled before the intake was started as well as at two points during treatment and after its completion, respectively. Mass spectrometry-derived metabolite and protein levels were related to FT
4
serum concentrations using mixed-effect linear regression models in a robust setting. To compile a molecular signature discriminating between thyrotoxicosis and euthyroidism, a random forest was trained and validated in a two-stage cross-validation procedure.
Results
Despite the absence of obvious clinical symptoms, mass spectrometry analyses detected 65 metabolites and 63 proteins exhibiting significant associations with serum FT
4
. A subset of 15 molecules allowed a robust and good prediction of thyroid hormone function (AUC\u2009=\u20090.86) without prior information on TSH or FT
4
. Main FT
4
-associated signatures indicated increased resting energy expenditure, augmented defense against systemic oxidative stress, decreased lipoprotein particle levels, and increased levels of complement system proteins and coagulation factors. Further association findings question the reliability of kidney function assessment under hyperthyroid conditions and suggest a link between hyperthyroidism and cardiovascular diseases via increased dimethylarginine levels.
Conclusion
Our results emphasize the power of untargeted OMICs approaches to detect novel pathways of thyroid hormone action. Furthermore, beyond TSH and FT
4
, we demonstrated the potential of such analyses to identify new ..
The equity of China\u2019s emergency medical services from 2010\u20132014
No full textAbstract
Background
With the depth development of health care system reform in China, emergency medical services (EMS) is confronted with challenges as well as opportunities. This study aimed to analyze the equity of China\u2019s EMS needs, utilization, and resources distribution, and put forward proposal to improve the equity.
Method
Three emergency needs indicators (mortality rate of cardiovascular and cerebrovascular diseases, harm, and digestive system disease), two utilization indicators (emergency outpatient visits and rate of utilization) and one resource allocation indicator (number of EMS facilities) were collected after the review of the China Statistical Yearbook and the National Disease Surveillance System. Next, EMS related indicators were compared among 31 provinces from the eastern, central, and western regions of the country. Concentration Index (CI) were used to measure the equity of EMS needs and utilization among the western, central, and eastern regions. The Gini coefficient of demographic and geographic distribution of facilities represented the equity of resource allocation.
Result
During 2010\u20132014 , the CI of cardiovascular and cerebrovascular disease mortality changed from positive to negative, which indicates that the concentrated trend transferred from richer regions to the poorer area. Injury mortality (CI: range from\u2009\u2212\u20090.1241to \u22120.1504) and digestive disease mortality (CI: range from\u2009\u2212\u20090.1921 to\u2009\u2212\u20090.2279) consistently concentrated in the poorer region, and the inequity among regions became more obviously year-by-year. The utilization of EMS (CI: range from 0.1074 to 0.0824) showed an improvement; however, the inequity reduced gradually. The EMS facilities distribution by population (Gini coefficient: range from 0.0922 to 0.1200) showed high equitability but the EMS facilities distribution by geography (Gini coefficient: range from 0.0922 to 0.1200) suggested a huge gap between regions because the Gini coefficients were greater than 0.5 in the past 5 years.
Conclusion
There are some inequities of needs, utilization, and resource allocation in the China EMS. The government needs to stick to the principle of increasing investment in poorer regions, perfecting ambulance configuration and improving health workers\u2019 professional skills to improve the equity and quality of EMS
Increased leptin/adiponectin ratio relates to low-normal thyroid function in metabolic syndrome
No full textAbstract
Background
Low-normal thyroid function within the euthyroid range may contribute to increased atherosclerosis susceptibility. The leptin/adiponectin (L/A) ratio is associated with cardiovascular disease and reflects adipose tissue dysfunction. Relationships of the L/A ratio with low-normal thyroid function are unknown.
Methods
Relationships of thyroid stimulating hormone (TSH) and free thyroxine (free T
4
) with leptin, adiponectin and the L/A ratio in euthyroid subjects were documented in 67 fasting subjects with metabolic syndrome (Mets) and 86 euthyroid subjects without MetS (TSH and free T
4
levels within the institutional reference range).
Results
Neither plasma leptin nor adiponectin was significantly correlated with TSH or free T
4
in subjects with and without MetS. In the whole group, high sensitivity C-reactive protein (hs-CRP) was positively correlated with the L/A ratio ( r \u2009=\u20090.485, P \u2009<\u20090.001). Notably, the L/A ratio was positively correlated with TSH in subjects with MetS ( r \u2009=\u20090.252, P \u2009=\u20090.040) but not in subjects without MetS ( r \u2009= \u22120.068, P \u2009=\u20090.54; interaction term, P \u2009=\u20090.027). In MetS subjects, the L/A ratio remained positively related with TSH after adjustment for age, sex, diabetes status, hs-CRP and the use of antihypertensive and glucose lowering medication (\u3b2\u2009=\u20090.283, P \u2009=\u20090.018), as well as after adjustment for individual MetS components (\u3b2\u2009=\u20090.294, P \u2009=\u20090.020).
Conclusions
In the context of MetS, a higher TSH within the euthyroid range confers an increased L/A ratio, a proposed marker of atherosclerosis susceptibility and adipocyte dysfunction
Proteome changes in the small intestinal mucosa of growing pigs with dietary supplementation of non-starch polysaccharide enzymes
No full textAbstract
Background
Non-starch polysaccharide enzymes (NSPEs) have long been used in monogastric animal feed production to degrade non-starch polysaccharides (NSPs) to oligosaccharides in order to promote growth performance and gastrointestinal (GI) tract health. However, the precise molecular mechanism of NSPEs in the improvement of the mammalian small intestine remains unknown.
Methods
In this study, isobaric tags were applied to investigate alterations of the small intestinal mucosa proteome of growing pigs after 50\ua0days of supplementation with 0.6% NSPEs (mixture of xylanase, \u3b2-glucanase and cellulose) in the diet. Bioinformatics analysis including gene ontology annotation was performed to determine the differentially expressed proteins. A protein fold-change of\u2009\u2265\u20091.2 and a P -value of\u2009<\u20090.05 were selected as thresholds.
Results
Dietary supplementation of NSPEs improved the growth performance of growing pigs. Most importantly, a total of 90 proteins were found to be differentially abundant in the small intestinal mucosa between a control group and the NSPE group. Up-regulated proteins were related to nutrient metabolism (energy, lipids, protein and mineral), immunity, redox homeostasis, detoxification and the cell cytoskeleton. Down-regulated proteins were primarily related to transcriptional and translational regulation. Our results indicate that the effect of NSPEs on the increase of nutrient availability in the intestinal lumen facilitates the efficiency of nutrient absorption and utilization, and the supplementation of NSPEs in growing pigs also modulates redox homeostasis and enhances immune response during simulating energy metabolism due to a higher uptake of nutrients in the small intestine.
Conclusions
These findings have important implications for understanding the mechanisms of NSPEs on the small intestine of pigs, which provides new information for the better utilization of this feed additive in the future
Hexokinase 2 drives glycogen accumulation in equine endometrium at day 12 of diestrus and pregnancy
No full textAbstract
Background
Secretion of histotroph during the prolonged pre-implantation phase in mares is crucial to pregnancy maintenance, manifested as increased embryonic loss in mares with age-related endometrial degeneration. Glycogen content of uterine histotroph is higher during the progesterone-dominated phase of the estrous cycle in mares, but regulatory mechanisms are not well understood.
Methods
mRNA expression of glycogen-metabolizing enzymes (HK1, HK2, GSK3B, GYS1, PEPCK, PKM, PYGM) in endometrial samples were compared among mares in anestrus, estrus, and at Day 12 of diestrus and pregnancy. In addition, hexokinase 2 (HK2) activity was assessed using a colorimetric assay.
Results
HK2 was the key regulator of glycogen accumulation during diestrus and pregnancy; hexokinase transcript abundance and enzyme activity were significantly higher during diestrus and pregnancy than estrus and anestrus. In addition, despite similar relative transcript abundance, hexokinase activity was significantly greater in the pregnant versus diestrous endometrium. Therefore, we inferred there was regulation of hexokinase activity through phosphorylation, in addition to its regulation at the transcriptional level during early pregnancy. Based on immunohistochemistry, HK2 was localized primarily in luminal and glandular epithelial cells, with weaker staining in stromal cells.
Conclusion
Among glycogen metabolizing enzymes identified, expression of HK2 was significantly greater during the progesterone-dominated phase of the cycle
Serum reference value of two potential doping candidates\u2014myostatin and insulin-like growth factor-I in the healthy young male
No full textAbstract
Background
Myostatin negatively regulates muscle growth, and its inhibition by suitable proteins can increase muscle bulk and exercise performance. However, the reference values of serum myostatin in athletes performing strength training are still lacking.
Methods
A cross-sectional study\ua0recruiting28 male collegiate athletes performing strength training and 29 age-matched normal controls\ua0was conducted.
The serum concentration of myostatin and insulin-like growth factor 1 (IGF-1), grip strength, and body composition were the main outcome measures. We used regression models to analyze the correlation between serum markers and the physiological parameters. The athlete group had greater height, weight, body mass index (BMI), fat mass percentage, fat-free mass, muscle mass, waist girth, grip strength, and estimated daily energy expenditure.
Results
The IGF-1 concentration was higher in the athlete group (324\u2009\ub1\u200980 vs. 263\u2009\ub1\u2009134\ua0ng/ml), but the myostatin levels did not differ (12.1\u2009\ub1\u20093.7 vs. 12.4\u2009\ub1\u20093.5\ua0ng/ml). The reference value for IGF-1 among the healthy young males was 293\u2009\ub1\u2009114\ua0ng/ml, correlated with age and height; the value for myostatin was 12.3\u2009\ub1\u20093.6\ua0ng/ml, correlated negatively with BMI, fat mass percentage, and waist girth after adjustment for age.
Conclusion
Myostatin level is negatively related to fat percentage, and serum IGF-1 is positively related to height. The reference values could provide a basis for future doping-related study
The ribosomal transcription units of Haplorchis pumilio and H. taichui and the use of 28S rDNA sequences for phylogenetic identification of common heterophyids in Vietnam
No full textAbstract
Background
Heterophyidiasis is now a major public health threat in many tropical countries. Species in the trematode family Heterophyidae infecting humans include Centrocestus formosanus , Haplorchis pumilio , H. taichui , H. yokogawai , Procerovum varium and Stellantchasmus falcatus. For molecular phylogenetic and systematic studies on trematodes, we need more prospective markers for taxonomic identification and classification. This study provides near-complete ribosomal transcription units (rTU) from Haplorchis pumilio and H. taichui and demonstrates the use of 28S rDNA sequences for identification and phylogenetic analysis.
Results
The near-complete ribosomal transcription units (rTU), consisting of 18S, ITS1, 5.8S, ITS2 and 28S rRNA genes and spacers, from H. pumilio and H. taichui from human hosts in Vietnam, were determined and annotated. Sequence analysis revealed tandem repetitive elements in ITS1 in H. pumilio and in ITS2 in H. taichui. A phylogenetic tree inferred from 28S rDNA sequences of 40 trematode strains/species, including 14 Vietnamese heterophyid individuals, clearly confirmed the status of each of the Vietnamese species: Centrocestus formosanus, Haplorchis pumilio , H. taichui , H. yokogawai , Procerovum varium and Stellantchasmus falcatus . However, the family Heterophyidae was clearly not monophyletic, with some genera apparently allied with other families within the superfamily Opisthorchioidea (i.e. Cryptogonimidae and Opisthorchiidae). These families and their constituent genera require substantial re-evaluation using a combination of morphological and molecular data. Our new molecular data will assist in such studies.
Conclusions
The 28S rDNA sequences are conserved among individuals within a species but varied between genera. Based on analysis of 40 28S rDNA sequences representing 19 species in the superfamily Opisthorchioidea and an outgroup taxon ( Alaria alata , family Diplostomidae), six common human pathogenic heterophyids were identified and clearly resolved. The phylogenetic tree inferred from these sequences again confirmed anomalies in molecular placement of some members of the family Heterophyidae and demonstrates the need for reappraisal of the entire superfamily Opisthorchioidea. The new sequences provided here supplement those already available in public databases and add to the array of molecular tools that can be used for the diagnosis of heterophyid species in human and animal infections
An evaluation of the evolution of the gene structure of dystroglycan
No full textAbstract
Background
Dystroglycan (DG) is an adhesion receptor complex composed of two non-covalently associated subunits, transcribed from a single gene. The extracellular \u3b1-DG is highly and heterogeneously glycosylated and binds with high affinity to laminins, and the transmembrane \u3b2-DG binds intracellular dystrophin. Multiple cellular functions have been proposed for DG, notwithstanding that its role in skeletal muscle appears central as demonstrated by both primary and secondary severe muscular dystrophic phenotypes collectively known as dystroglycanopathies. We recently analysed the molecular phylogeny of the DG core protein and identified the \u3b1/\u3b2 interface, transmembrane and cytoplasmic domains of \u3b2-DG as the most conserved region. It was also identified that the IG2_MAT_NU region has been independently duplicated in multiple lineages.
Results
To understand the evolution of dystroglycan in more depth, we investigated dystroglycan gene structure in 35 species representative of the phyla in which dystroglycan has been identified (i.e., all metazoan phyla except Ctenophora). The gene structure of three exons and two introns is remarkably conserved. However, additional lineage-specific introns were identified, which interrupt the coding sequence at distinct points, were identified in multiple metazoan groups, most prominently in ecdysozoans.
Conclusions
A coding DNA sequence (CDS) intron that interrupts the encoding of the IG1 domain is universally conserved and this intron is longer in gnathostomes (jawed vertebrates) than in other metazoans. Lineage-specific gain of additional introns has occurred notably in ecdysozoans, where multiple introns interrupt the large 3\u2032 exon. More limited intron gain has also occurred in placozoa, cnidarians, urochordates and the DG paralogues of lamprey and teleost fish
Glutamic acid promotes monacolin K production and monacolin K biosynthetic gene cluster expression in Monascus
No full textAbstract
This study investigated the effects of glutamic acid on production of monacolin K and expression of the monacolin K biosynthetic gene cluster. When Monascus M1 was grown in glutamic medium instead of in the original medium, monacolin K production increased from 48.4 to 215.4\ua0mg\ua0l
\u22121
, monacolin K production increased by 3.5 times. Glutamic acid enhanced monacolin K production by upregulating the expression of mokB - mokI ; on day 8, the expression level of mokA tended to decrease by Reverse Transcription-polymerase Chain Reaction. Our findings demonstrated that mokA was not a key gene responsible for the quantity of monacolin K production in the presence of glutamic acid. Observation of Monascus mycelium morphology using Scanning Electron Microscope showed glutamic acid significantly increased the content of Monascus mycelium, altered the permeability of Monascus mycelium, enhanced secretion of monacolin K from the cell, and reduced the monacolin K content in Monascus mycelium, thereby enhancing monacolin K production