Perfluoroalkyl acids (PFAAs) are persistent environmental pollutants that have been detected in various media including human serum. Due to concerns regarding their bioaccumulation and possible ...negative health effects, an understanding of routes of human exposure is necessary. PFAAs are recalcitrant in many water treatment processes, making drinking water a potential source of human exposure. This study presents the first report on contamination from PFAAs in river and drinking water in Ghana. The targeted PFAAs were perfluoroalkyl carboxylic acids (PFCAs) with C4–14 carbon chain and perfluoroalkane sulphonic acids (PFSAs) with C6, 8, 10. Five PFAA congeners – PFOA, PFOS, PFHxA, PFDA and PFPeA – were commonly detected in river and tap water. The mean concentrations of ∑PFAAs in the Kakum and Pra Rivers were 281 and 398ng/L, while tap water (supplied from the treatment of water from those rivers) contained concentrations of 197 and 200ng/L, respectively. PFOA and PFOS constituted about 99% of the ∑PFAAs. The risk quotient (RQ) attributed to drinking of tap water was estimated at 1.01 and 1.74 for PFOA and PFOS, respectively. For a country that has not produced these compounds, the RQs were unexpectedly high, raising concerns particularly about contamination from such emerging pollutants in local water sources. The study revealed limitations of local tap water treatment in getting rid of these emerging pollutants.
•PFCs are recalcitrant in many water treatment processes, making drinking water a potential source of human exposure.•The study presents the first report on contamination from PFCs in river and drinking water in Ghana•Five PFC congeners – PFOA, PFOS, PFHxA, PFDA and PFPeA – were commonly detected in river and tap water in Ghana•The study revealed limitations of local tap water treatment in getting rid of these emerging pollutants
A sensitization of inositol 1,4,5-trisphosphate receptor (IP3R)–mediated Ca2+ release is associated with oxidative stress in multiple cell types. These effects are thought to be mediated by ...alterations in the redox state of critical thiols in the IP3R, but this has not been directly demonstrated in intact cells. Here, we utilized a combination of gel-shift assays with MPEG-maleimides and LC–MS/MS to monitor the redox state of recombinant IP3R1 expressed in HEK293 cells. We found that under basal conditions, ∼5 of the 60 cysteines are oxidized in IP3R1. Cell treatment with 50 μm thimerosal altered gel shifts, indicating oxidation of ∼20 cysteines. By contrast, the shifts induced by 0.5 mm H2O2 or other oxidants were much smaller. Monitoring of biotin–maleimide attachment to IP3R1 by LC–MS/MS with 71% coverage of the receptor sequence revealed modification of two cytosolic (Cys-292 and Cys-1415) and two intraluminal cysteines (Cys-2496 and Cys-2533) under basal conditions. The thimerosal treatment modified an additional eleven cysteines, but only three (Cys-206, Cys-767, and Cys-1459) were consistently oxidized in multiple experiments. H2O2 also oxidized Cys-206 and additionally oxidized two residues not modified by thimerosal (Cys-214 and Cys-1397). Potentiation of IP3R channel function by oxidants was measured with cysteine variants transfected into a HEK293 IP3R triple-knockout cell line, indicating that the functionally relevant redox-sensitive cysteines are predominantly clustered within the N-terminal suppressor domain of IP3R. To our knowledge, this study is the first that has used proteomic methods to assess the redox state of individual thiols in IP3R in intact cells.
Distribution of HIV self-test kits by trained lay people in the community has resulted in increased uptake of HIV testing services among the targeted populations. However, little data exists on the ...experiences and challenges faced by trained lay people while distributing the kits.
This qualitative study was conducted in Kasensero fishing community, Rakai, Uganda, in September 2019. We purposely selected 18 out of 34 peer-leaders that participated in a peer-led HIV self-testing intervention to participate in a post-intervention qualitative evaluation. The main intervention included identification and training of lay people in the community ('peer-leaders') to distribute HIV self-test kits to pre-selected members of their social network. Data for this study were collected at the end of the intervention. Data were collected on peer-leaders' experiences in distributing the kits, challenges experienced during distribution and suggestions on how to improve peer-led HIV self-testing in typical fishing communities in the future. Data were analyzed manually following a thematic framework approach.
Of the 18 peer-leaders, eleven (61.1%) were aged 20-24 years while thirteen (72.2%) had secondary education. Most (n = 15) of the peer-leaders reported that they found it easier to distribute the kits to their social network members, with most of them distributing the kits at the social network members' homes or at their own homes. HIV self-test kits were distributed at varying times (e.g. in the afternoon) depending on the agreement reached between the peer-leader and their social network member. A few peer-leaders reported that some of their social network members initially hesitated to accept the kits while other peer-leaders reported that they spent a 'lot of time' explaining the HIV self-testing procedures to some of their illiterate members. Peer-leaders argued for supervised HIV self-testing for illiterate people and the need to continuously follow-up social network members to check if they tested for HIV.
A majority of the peer-leaders successfully distributed the kits to their social network members save for a few who experienced challenges. These findings suggest that lay people can be trained as effective HIV self-test kits distributors to improve the distribution of kits in the community.
Eradication of HIV-1 (HIV) is hindered by stable viral reservoirs. Viral latency is epigenetically regulated. While the effects of histone acetylation and methylation at the HIV long-terminal repeat ...(LTR) have been described, our knowledge of the proviral epigenetic landscape is incomplete. We report that a previously unrecognized epigenetic modification of the HIV LTR, histone crotonylation, is a regulator of HIV latency. Reactivation of latent HIV was achieved following the induction of histone crotonylation through increased expression of the crotonyl-CoA-producing enzyme acyl-CoA synthetase short-chain family member 2 (ACSS2). This reprogrammed the local chromatin at the HIV LTR through increased histone acetylation and reduced histone methylation. Pharmacologic inhibition or siRNA knockdown of ACSS2 diminished histone crotonylation-induced HIV replication and reactivation. ACSS2 induction was highly synergistic in combination with either a protein kinase C agonist (PEP005) or a histone deacetylase inhibitor (vorinostat) in reactivating latent HIV. In the SIV-infected nonhuman primate model of AIDS, the expression of ACSS2 was significantly induced in intestinal mucosa in vivo, which correlated with altered fatty acid metabolism. Our study links the HIV/SIV infection-induced fatty acid enzyme ACSS2 to HIV latency and identifies histone lysine crotonylation as a novel epigenetic regulator for HIV transcription that can be targeted for HIV eradication.
Open globe injuries can lead to substantial visual morbidity and lifelong sequelae. Interventions to reduce the burden of open globe injuries in the United States require a better understanding of ...these injuries through well-designed epidemiologic investigations.
To examine the incidence, common injury mechanisms, and economic burden of open globe injuries in the United States.
This retrospective, cross-sectional study of US nationwide emergency department (ED) data assessed all ED visits of patients with a primary diagnosis of open globe injury in the Nationwide Emergency Department Sample (NEDS) from January 1, 2006, to December 31, 2014. Data analysis was performed from August 29, 2018, to November 11, 2019.
Annual incidence of open globe injuries by age, sex, mechanism of injury, and concomitant diagnosis, as well as median charges associated with open globe injuries and variables associated with hospitalization.
A total of 124 989 ED visits for open globe injuries were assessed, with an incidence of 4.49 per 100 000 population in the United States from 2006 to 2014 (mean SD age of study participants, 37.7 22.5 years; 94 078 75.3% male). The incidence was highest in 2006 (5.88 per 100 000 population) and decreased by 0.3% per month between 2006 and 2014 (incidence rate ratio, 0.99; 95% CI, 0.99-0.99; P < .001). Open globe injuries occurred in 37 060 individuals (30.6%) of low socioeconomic status. The most common injury mechanism was being struck by or against an object or person (40 119 of all 124 989 injury mechanisms 32.1%). Open globe injuries associated with falls increased 6.6% between 2006-2010 and 2011-2015 (95% CI, 1.04-1.08; P < .001) and were the most common injury mechanism in individuals older than 70 years. The total cost associated with open globe injuries was $793 million. The cost of ED visits increased from $865 during 2006-2010 to $1557 during 2011-2015. Inpatient costs similarly increased from $21 527 during 2006-2010 to $30 243 during 2011-2015.
The incidence of open globe injuries in the United States decreased from 2006 to 2014. Although the data are from 5 to 13 years ago, these findings appear to provide valuable information for targeting preventive measures toward individuals at highest risk; targeting young men with lower socioeconomic status and individuals 70 years or older at an increased risk of falls may help lower the incidence of open globe injuries.
A variety of optical applications rely on the absorption and reemission of light. The quantum yield of this process often plays an essential role. When the quantum yield deviates from unity by ...significantly less than 1%, applications such as luminescent concentrators and optical refrigerators become possible. To evaluate such high performance, we develop a measurement technique for luminescence efficiency with sufficient accuracy below one part per thousand. Photothermal threshold quantum yield is based on the quantization of light to minimize overall measurement uncertainty. This technique is used to guide a procedure capable of making ensembles of near-unity emitting cadmium selenide/cadmium sulfide (CdSe/CdS) core-shell quantum dots. We obtain a photothermal threshold quantum yield luminescence efficiency of 99.6 ± 0.2%, indicating nearly complete suppression of nonradiative decay channels.
Determining the epidemiology of eye-related emergency department (ED) visits on a national level can assist policymakers in appropriate allocation of resources.
To study ED visits related to ocular ...conditions for all age groups across the United States.
Nationally representative data from the US Nationwide Emergency Department Sample (NEDS) were used to analyze ED visits from January 1, 2006, to December 31, 2011 (6 years). All patients with eye problems presenting to EDs across the United States were eligible for inclusion. A weighted count of 11 929 955 ED visits were categorized as possibly emergent (emergent), unlikely to be emergent (nonemergent), or could not be determined. Data were analyzed from March 1 to May 30, 2015.
Population-based incidence rates of eye-related ED visits, incidence rates of eye injuries, relative proportions of emergent vs nonemergent eye-related ED visits among different age groups, and independent factors associated with emergent vs nonemergent visits.
From 2006 to 2011, 11 929 955 ED visits (male patients, 54.2%; mean SD age, 31 22 years) for ocular problems across the United States were categorized as emergent (41.2%), nonemergent (44.3%), or could not determine (14.5%). Corneal abrasions (13.7%) and foreign body in the external eye (7.5%) were the leading diagnoses in the emergent category. More than 4 million visits were for conjunctivitis (28.0%), subconjunctival hemorrhages (3.0%), and styes (3.8%). Emergent visits were significantly more likely to occur among males (odds ratio OR, 2.00; 95% CI, 2.00-2.01), patients in the highest income quartile (OR, 1.47; 95% CI, 1.46-1.49), older patients (OR, 2.38; 95% CI, 2.38-2.44), and patients with private insurance (OR, 1.29; 95% CI, 1.28-1.30). Mean annual inflation-adjusted charges for all eye-related ED visits totaled $2.0 billion.
Across the United States, nonemergent conditions accounted for almost half of all eye-related ED visits. Interventions to facilitate management of these cases outside the ED could make ED resources more available for truly emergent ophthalmic and medical issues.
Uridine-disphosphate glucuronosyl transferase (UGT) enzymes catalyze the formation of glucuronide conjugates of phase II metabolism. Methods for absolute quantification of UGT1A1 and UGT1A6 were ...previously established utilizing stable isotope peptide internal standards with liquid chromatography–tandem mass spectrometry (LC–MS/MS). The current method expands upon this by quantifying eight UGT1A isoforms by nanobore high-performance liquid chromatography (HPLC) coupled with a linear ion trap time-of-flight mass spectrometer platform. Recombinant enzyme digests of each of the isoforms were used to determine assay linearity and detection limits. Enzyme expression level in human liver, kidney, and intestinal microsomal protein was determined by extrapolation from spiked stable isotope standards. Intraday and interday variability was <25% for each of the enzyme isoforms. Enzyme expression varied from 3 to 96 pmol/mg protein in liver and intestinal microsomal protein digests. Expression levels of UGT1A7, 1A8, and 1A10 were below detection limits (<1 pmol/mg protein) in human liver microsome (HLMs). In kidney microsomes the expression of UGT1A3 was below detection limits, but levels of UGT1A4, 1A7, 1A9, and 1A10 protein were higher relative to that of liver, suggesting that renal glucuronidation could be a significant factor in renal elimination of glucuronide conjugates. This novel method allows quantification of all nine UGT1A isoforms, many previously not amenable to measurement with traditional methods such as immunologically based assays. Quantitative measurement of proteins involved in drug disposition, such as the UGTs, significantly improves the ability to evaluate and interpret in vitro and in vivo studies in drug development.
Adolescent girls and young women (AGYW) are at increased risk of sexually transmitted infections (STIs). We assessed sexual-risk behaviours and HIV and syphilis prevalence among AGYW in Uganda to ...inform the design of target-specific risk-reduction interventions.
This analysis utilizes data from 8,236 AGYW aged 10-24 years, collected in 20 districts, between July and August 2018. AGYW engaged in sexual-risk behaviour if they: a) reported a history of STIs; or b) had their sexual debut before age 15; or c) engaged in sex with 2+ partners in the past 12 months; or c) did not use or used condoms inconsistently with their most recent partners. We diagnosed HIV using DetermineTM HIV-1/2, Stat-PakTM HIV-1/2 and SD Bioline. We used SD Bioline Syphilis test kits to diagnose syphilis and Treponema Pallidum Hemagglutination Assay for confirmatory syphilis testing. Comparison of proportions was done using Chi-square (χ2) tests. Data were analysed using STATA (version 14.1).
Of 4,488 AGYW (54.5%) that had ever had sex, 12.9% (n = 581) had their sexual debut before age 15; 19.1% (n = 858) reported a history of STIs. Of those that had ever had sex, 79.6% (n = 3,573) had sex in the 12 months preceding the survey; 75.6% (n = 2,707) with one (1) and 24.2% (n = 866) with 2+ partners. Condom use with the most recent sexual partner was low, with only 20.4% (n = 728) reporting consistent condom use while 79.6% (n = 2,842) reported inconsistent or no condom use. In-school AGYW were significantly less likely to have ever had sex (35.6% vs. 73.6%, P<0.001), to have had sexual debut before age 15 (7.7% vs. 15.5%, P<0.001) or to engage in sex with 2+ partners (5.3% vs. 15.8%, P<0.001). Consistent condom use was significantly higher among in-school than out-of-school AGYW (40.1% vs. 12.7%, P<0.001). Overall, 1.7% (n = 143) had HIV while 1.3% (n = 104) had syphilis. HIV and syphilis prevalence was higher among out-of-school than in-school AGYW (HIV: 2.6% vs. 0.9%; syphilis: 2.1% vs. 0.5%, respectively).
In-school AGYW engaged in more protective sexual behaviors and had less HIV and syphilis than their out-of-school counterparts. These findings suggest a need for target-specific risk-reduction interventions stratified by schooling status.
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