Sexual Violence, Genital Cytokines, and Colposcopy Findings: A Cross-Sectional Study of Women Engaged in Sex Work in Mombasa, Kenya.

BACKGROUND: Sexual violence (SV) increases HIV susceptibility in a sustained manner. This study evaluated genital cytokines and colposcopy findings in women reporting both recent and more remote SV.Methods: A cross-sectional study of HIV-1 negative Kenyan women who engage in sex work (WESW) was performed. Cervicovaginal fluid was collected by menstrual cup and cytokines (IFNγ, TNFα, IL-1ß, IL-6, IL-10, MIP-1α, MIP-1ß and CXCL10) measured using chemiluminescence. Cervical injury was assessed by colposcopy. Associations between recent (≤30 days prior), more remote (>30 days prior) and no (reference category) SV exposure and cytokine concentrations were evaluated using linear regression. RESULTS: Among 282 participants, 25 (8.9%) reported recent SV and 123 (43.6%) reported more remote SV. Only two cytokines (IL-10 and CXCL10) were associated with the 3-category SV variable in bivariable modeling at the pre-specified cut-off (p < 0.2) and carried forward. In multivariable analyses, more remote SV (ß = 0.72, 95% CI 0.06, 1.38; p = 0.03), but not recent SV (ß = 0.20, 95%CI -0.99, 1.39; p = 0.74) was associated with cervicovaginal IL-10 compared to no SV. Recent (ß = 0.36, 95% CI -0.94, 1.67; p = 0.58) and more remote (ß = 0.51, 95% CI -0.21, 1.24; p = 0.16) SV were not associated with CXCL10 compared to no SV. Cervical epithelial friability (χ2 = 1.3, p = 0.51), erythema (χ2 = 2.9, p = 0.24), vascular disruption (χ2 = 1.4; p = 0.50), epithelial disruption (χ2 = 2.6, p = 0.27), or any colposcopy finding (χ2 = 1.2, p = 0.54) were not associated with SV category by chi-square test. CONCLUSIONS: The mechanism linking SV to sustained increases in HIV susceptibility may not be related to persistent genital inflammation or injury.

The relationship between alcohol availability and drink-driving policies and admissions to substance use disorder treatment during pregnancy.

OBJECTIVE: Pregnancy-specific alcohol policies are widely adopted yet have limited effectiveness and established risks. It is unknown whether general population alcohol policies are effective during pregnancy. This study investigated associations between general population policies and alcohol treatment admission rates for pregnant people specifically. METHOD: Data are from the Treatment Episodes Data Set: Admissions and state-level policy data for 1992-2019 (n=1,331 state-years). The primary outcome was treatment admissions where alcohol was the primary substance, and the secondary outcome included admissions where alcohol was any substance. There were five policy predictors: 1) Government spirits monopoly, 2) Ban on Sunday sales, 3) Grocery store sales, 4) Gas station sales, and 5) Blood alcohol concentration (BAC) laws. Covariates included poverty, unemployment, per capita cigarette consumption, state and year fixed effects, and state-specific time trends. RESULTS: In models with alcohol as the primary substance, prohibiting spirits sales in grocery stores (vs. allowing heavy beer and spirits) had lower treatment admission rates [IRR=0.88, 95% CI: 0.78-0.99, p=0.028]. States with BAC laws at 0.10% (vs. no law) had higher treatment admission rates [IRR=1.24, 95% CI: 1.08-1.43, p=0.003]. When alcohol was any substance, prohibiting spirits sales in grocery stores (vs. allowing heavy beer and spirits) was again associated with lower treatment admission rates [IRR=0.89, 95% CI: 0.80-0.98, p=0.021], but there was no association for BAC laws. CONCLUSIONS: Restrictions on grocery store spirits sales and BAC laws were associated with lower and higher alcohol treatment admission rates among pregnant people, respectively, suggesting general population alcohol policies are relevant for pregnant people's treatment utilization.

Prevalence of multimorbidity and polypharmacy among adults and older adults: a systematic review.

Multimorbidity (multiple conditions) and polypharmacy (multiple medications) are increasingly common, yet there is a need to better understand the prevalence of co-occurrence. In this systematic review, we examined the prevalence of multimorbidity and polypharmacy among adults (≥18 years) and older adults (≥65 years) in clinical and community settings. Six electronic databases were searched, and 87 studies were retained after two levels of screening. Most studies focused on adults 65 years and older and were done in population-based community settings. Although the operational definitions of multimorbidity and polypharmacy varied across studies, consistent cut-points (two or more conditions and five or more medications) were used across most studies. In older adult samples, the prevalence of multimorbidity ranged from 4·8% to 93·1%, while the prevalence of polypharmacy ranged from 2·6% to 86·6%. High heterogeneity between studies indicates the need for more consistent reporting of specific lists of conditions and medications used in operational definitions.

Circulating tumour mutation detection in triple-negative breast cancer as an adjunct to tissue response assessment.

Circulating tumour DNA (ctDNA) detection via liquid biopsy is an emerging alternative to tissue biopsy, but its potential in treatment response monitoring and prognosis in triple negative breast cancer (TNBC) is not yet well understood. Here we determined the prevalence of actionable mutations detectable in ctDNA using a clinically validated cancer gene panel assay in patients with TNBC, without recurrence at the time of study entry. Sequencing of plasma DNA and validation of variants from 130 TNBC patients collected within 7 months of primary treatment completion revealed that 7.7% had detectable residual disease with a hotspot panel. Among neoadjuvant treated patients, we observed a trend where patients with incomplete pathologic response and positive ctDNA within 7 months of treatment completion were at much higher risk of reduced progression free survival. We propose that a high risk subset of early TNBC patients treated in neoadjuvant therapy protocols may be identifiable by combining tissue response and sensitive ctDNA detection.

Algorithmic Identification of Patients With Aspirin-Exacerbated Respiratory Disease Using an Electronic Health Record.

OBJECTIVE: To determine whether an electronic health record (EHR) system can be used to identify cases of aspirin-exacerbated respiratory disease (AERD) in an area outside of a regional referral center with low rates of aspirin desensitization therapy. STUDY DESIGN: Retrospective chart review single academic tertiary care hospital. SETTING: Single-site academic tertiary care hospital. METHODS: Using Epic's SlicerDicer function, an algorithm was created and applied to all patient charts from 2013 to 2021. The algorithm was as follows: "Allergy/Contraindication to NSAIDs OR aspirin" AND "Diagnosis of Nasal polyp AND "Diagnosis of Asthma." Clinical data including demographics, NSAID reaction, and specialist involvement was collected. RESULTS: A total of 54 potential cases of AERD were identified. Thirty-two were determined to have AERD after chart review, yet 12 of these patients (37.5%) had no mention of AERD within the chart. The 54 patients were stratified into 2 cohorts based on reaction to NSAIDs: respiratory (n = 29) or unspecified (n = 25). Of the patients in the respiratory reaction group, 26 were found to have clinical AERD, demonstrating a positive predictive values (PPV) of 89.7%. The overall PPV was 59.3%. Those with a respiratory reaction to NSAIDS listed in the EHR were more likely to have clinical AERD (odds ratio 27.44; confidence interval 6.08-123.85; p < 0.0001). Only 2 patients (6.3%) underwent aspirin desensitization. CONCLUSION: AERD remains under-diagnosed in the study population. The informatics algorithm presented here has a high positive predictive value for identifying clinical AERD patients in a geographical area with low rates of aspirin desensitization and may aid in identifying candidates for expanded treatment options.

Examining Associations Between Mental Health, IPV Exposure, HIV Risk Behaviors, and PrEP Use in South African Women: An Analysis of Data from the Charisma Study.

Intimate partner violence (IPV) has been associated with poorer mental health outcomes and increased human immunodeficiency virus (HIV) risk behaviors. We examine the relations between IPV, mental health symptomology (defined as psychological distress and alcohol misuse), and engagement in HIV risk behaviors among a sample of South African women who participated in a randomized controlled trial of CHARISMA, an intervention to increase women's agency to use oral pre-exposure prophylaxis (PrEP) safely and consistently as well as mitigate relationship challenges. We also examined the impact of trial participation on women's mental health, as well as the impact of psychological distress on the effectiveness of the CHARISMA intervention. Mental health symptomology and IPV exposure were prevalent and associated with some HIV risk and protective behaviors. Trial participation reduced psychological distress. There was no evidence for mental health symptomology impacting the effectiveness of the CHARISMA intervention.

Prolidase deficiency, a rare inborn error of immunity, clinical phenotypes, immunological features, and proposed treatments in twins.

BACKGROUND: Prolidase deficiency (PD) is an autosomal recessive inborn multisystemic disease caused by mutations in the PEPD gene encoding the enzyme prolidase D, leading to defects in turnover of proline-containing proteins, such as collagen. PD is categorized as a metabolic disease, but also as an inborn error of immunity. PD presents with a range of findings including dysmorphic features, intellectual disabilities, recurrent infections, intractable skin ulceration, autoimmunity, and splenomegaly. Despite symptoms of immune dysregulation, only very limited immunologic assessments have been reported and standard therapies for PD have not been described. We report twin females with PD, including comprehensive immunologic profiles and treatment modalities used. CASE PRESENTATION: Patient 1 had recurrent infections in childhood. At age 13, she presented with telangiectasia, followed by painful, refractory skin ulcerations on her lower limbs, where skin biopsy excluded vasculitis. She had typical dysmorphic features of PD. Next-generation sequencing revealed pathogenic compound heterozygous mutations (premature stop codons) in the PEPD gene. Patient 2 had the same mutations, typical PD facial features, atopy, and telangiectasias, but no skin ulceration. Both patients had imidodipeptiduria. Lymphocyte subset analysis revealed low-normal frequency of Treg cells and decreased frequency of expression of the checkpoint molecule CTLA-4 in CD4+ TEM cells. Analysis of Th1, Th2, and Th17 profiles revealed increased inflammatory IL-17+ CD8+ TEM cells in both patients and overexpression of the activation marker HLA-DR on CD4+ TEM cells, reflecting a highly activated proinflammatory state. Neither PD patient had specific antibody deficiencies despite low CD4+CXCR5+ Tfh cells and low class-switched memory B cells. Plasma IL-18 levels were exceptionally high. CONCLUSIONS: Immunologic abnormalities including skewed frequencies of activated inflammatory CD4+ and CD8+ TEM cells, decreased CTLA-4 expression, and defects in memory B cells may be a feature of immune dysregulation associated with PD; however, a larger sample size is required to validate these findings. The high IL-18 plasma levels suggest underlying autoinflammatory processes.

Benefits of tailored disease management in improving tremor, white matter hyperintensities, and liver enzymes in a child with heterozygous X-linked ornithine transcarbamylase deficiency.

We report the case of a 19-month-old girl with late-onset ornithine transcarbamylase (OTC) deficiency initially referred to gastroenterology for intermittent vomiting lasting a year and abnormal liver enzymes (AST 730 U/L [reference range 26-55 U/L]; ALT 1213 U/L [reference range 11-30 U/L]) without hepatomegaly. While the patient was hospitalized for liver biopsy, intermittent tremors of the upper extremities with varying severity were noted. The patient was presumed to have hyperammonemia secondary to acute liver failure and was discharged after 5 days; follow-up monitoring led to readmission 7 days later. A brain MRI showed nonspecific bilateral pericallosal and bifrontal white matter FLAIR hyperintensities. These findings raised suspicion for a metabolic disease and prompted a genetics consultation. After inconclusive biochemical testing and worsening clinical status, rapid whole genome sequencing results were obtained identifying a novel, de novo, likely pathogenic, variant c.608C > T (p.Ser203Phe) in the OTC gene. The patient was promptly started on an oral nitrogen scavenger, citrulline supplementation, and protein restriction. Ammonia and glutamine levels normalized within 1 month of treatment and have stayed within the goal ranges with continued tailoring of treatment. Her parents noted resolution of vomiting and improved mood stability. Liver enzymes normalized after 2 months of treatment. The tremor, identified as asterixis, improved and a repeat brain MRI 3 months after the initial imaging showed near-complete resolution of previous white matter hyperintensities.

Impact of the 21-Gene Recurrence Score Assay on the Treatment of Estrogen Receptor-Positive, HER2-Negative, Breast Cancer Patients With 1-3 Positive Nodes: A Prospective Clinical Utility Study.

PURPOSE: The use of the 21-gene Recurrence Score (RS) assay is emerging in node-positive estrogen receptor (ER)+ HER2-negative breast cancer (BC), particularly as initial data from the RxPONDER trial are now available. We investigated the impact of the RS result on adjuvant treatment decisions in such patients. PATIENTS AND METHODS: This prospective, multi-center study enrolled patients with ER+, HER2-negative BC and 1 to 3 positive nodes (microscopic [N1mi] or macroscopic [N1]). Treating oncologists documented treatment recommendations/plan before and after knowing the RS result. Sample size was determined assuming an overall treatment change rate (from chemohormonal therapy [CHT] to hormone therapy [HT] and vice-versa) of ≥30%. RESULTS: The study included 84 patients across 5 regional cancer centers, of whom 82 underwent 21-gene testing (77%, N1 disease; 63% grade 2 tumors). Of the RS-tested patients, 60%, 33%, and 7% had RS 0 to 17, 18 to 30, and 31 to 100, respectively. In 43 patients (52%), treatment changed post-RS: 40 patients (49%) from CHT to HT and 3 patients (4%) from HT to CHT. The net change was a 45% reduction in chemotherapy use. Treatment recommendation changes were consistent with the RS result. In RS 0 to 17 patients, the only documented change was from CHT to HT (27 patients). In RS 18-30 patients, change was noted in both directions (CHT-to-HT, 13 patients; HT-to-CHT, 3 patients). No treatment change was reported for the RS 31 to 100 patients, all of whom were recommended CHT pre-testing. CONCLUSION: Our results support the clinical utility of the RS assay in ER+ HER2-negative BC with 1 to 3 positive nodes.

Hyperexcitability and brain morphological differences in mice lacking the cystine/glutamate antiporter, system xc.

System xc- (Sxc- ) is a heteromeric antiporter (L-cystine/L-glutamate exchanger) expressed predominately on astrocytes in the central nervous system. Its activity contributes importantly to the maintenance of the ambient extracellular glutamate levels, as well as, to cellular redox homeostasis. Since alterations in glutamate levels and redox modifications could cause structural changes, we analyzed gross regional morphology of thionin-stained brain sections and cellular and subcellular morphology of Golgi-Cox stained layer V pyramidal neurons in the primary motor cortex (PM1) of mice naturally null for SLC7A11 (SLC7A11sut/sut )-the gene that encodes the substrate specific light chain (xCT) for Sxc- . Intriguingly, in comparison to age- and sex-matched wild-type (SLC7A11+/+ ) littermate controls, we found morphologic changes-including increased dendritic complexity and mushroom spine area in males and reduced corpus callosum and soma size in females-that have previously been described, in each case, as morphological correlates of excitability. Consistent with this, we found that both male and female SLC7A11sut/sut mice had lower convulsive seizure thresholds and greater seizure severity than their sex-matched wild-type (SLC7A11+/+ ) littermates after acute challenge with two pharmacologically distinct chemoconvulsants: the Glu receptor agonist, kainic acid (KA), or the GABAA receptor antagonist, pentylenetetrazole (PTZ). These results suggest that the loss of Sxc- signaling in males and females perturbs excitatory/inhibitory (E/I) balance in vivo, potentially through its regulation of cellular and subcellular morphology.

A Case Study of the Response of Immunogenic Gluten Peptides to Sourdough Proteolysis.

Celiac disease is activated by digestion-resistant gluten peptides that contain immunogenic epitopes. Sourdough fermentation is a potential strategy to reduce the concentration of these peptides within food. However, we currently know little about the effect of partial sourdough fermentation on immunogenic gluten. This study examined the effect of a single sourdough culture (representative of those that the public may consume) on the digestion of immunogenic gluten peptides. Sourdough bread was digested via the INFOGEST protocol. Throughout digestion, quantitative and discovery mass spectrometry were used to model the kinetic release profile of key immunogenic peptides and profile novel peptides, while ELISA probed the gluten's allergenicity. Macrostructural studies were also undertaken. Sourdough fermentation altered the protein structure, in vitro digestibility, and immunogenic peptide release profile. Interestingly, sourdough fermentation did not decrease the total immunogenic peptide concentration but altered the in vitro digestion profile of select immunogenic peptides. This work demonstrates that partial sourdough fermentation can alter immunogenic gluten digestion, and is the first study to examine the in vitro kinetic profile of immunogenic gluten peptides from sourdough bread.

JMJD6 Dysfunction Due to Iron Deficiency in Preeclampsia Disrupts Fibronectin Homeostasis Resulting in Diminished Trophoblast Migration.

The mechanisms contributing to excessive fibronectin in preeclampsia, a pregnancy-related disorder, remain unknown. Herein, we investigated the role of JMJD6, an O2- and Fe2+-dependent enzyme, in mediating placental fibronectin processing and function. MALDI-TOF identified fibronectin as a novel target of JMJD6-mediated lysyl hydroxylation, preceding fibronectin glycosylation, deposition, and degradation. In preeclamptic placentae, fibronectin accumulated primarily in lysosomes of the mesenchyme. Using primary placental mesenchymal cells (pMSCs), we found that fibronectin fibril formation and turnover were markedly impeded in preeclamptic pMSCs, partly due to impaired lysosomal degradation. JMJD6 knockdown in control pMSCs recapitulated the preeclamptic FN phenotype. Importantly, preeclamptic pMSCs had less total and labile Fe2+ and Hinokitiol treatment rescued fibronectin assembly and promoted lysosomal degradation. Time-lapse imaging demonstrated that defective ECM deposition by preeclamptic pMSCs impeded HTR-8/SVneo cell migration, which was rescued upon Hinokitiol exposure. Our findings reveal new Fe2+-dependent mechanisms controlling fibronectin homeostasis/function in the placenta that go awry in preeclampsia.

The effect of baking time and temperature on gluten protein structure and celiac peptide digestibility.

Previous work has shown that baking induces structural changes within the gluten macropolymer (GMP) that reduce gluten protein digestibility. The precise nature of these structural changes within dough/bread, and how they alter the in vitro release profile of immunogenic gluten peptides that activate celiac disease is unknown. This work examined the effect of dough baking temperature and duration on the GMP's structure and the release profile of immunogenic gluten peptides. Dough was baked at either 150 °C or 230 °C for 25, 35 or 45 min. The structure of the GMP within the resulting loaves was defined and compared using confocal microscopy, quantitative protein network analysis, gliadin protein extractability (HPLC) and determination of the free thiol content. Both bread and dough were digested in vitro (INFOGEST) and the release profile of six immunogenic gluten peptides (including the immunodominant 33mer) defined using quantitative mass spectrometry. Higher baking temperatures and longer durations increased the degree of intermolecular disulfide bonds between the sulfur-rich gliadins and GMP backbone. The thermal load did not alter the GMP macrostructure, but significant differences between bread and dough were observed. Baking altered the concentration and release profile of the immunogenic gluten peptides throughout in vitro digestion causing the digestion of immunogenic gluten peptides differed between raw and heat-treated bread.

Treatment of Partial Thickness Burns: A Prospective, Randomized Controlled Trial Comparing Four Routinely Used Burns Dressings in an Ambulatory Care Setting.

This prospective, randomized controlled trial study compared the effects of four dressings for adult partial thickness burns, focusing on re-epithelialization time and cost effectiveness. Adults with partial thickness burns meeting inclusion criteria were randomized to either Biobrane™, Acticoat™, Mepilex® Ag, or Aquacel® Ag. Primary endpoint for analysis was >95% re-epithelialization. Incremental cost-effectiveness ratios were calculated based on dressing costs. Dominance probabilities between treatment arms were calculated from bootstrap resampling trial data. One hunderd thirty-one partial thickness burn wounds in 119 patients were randomized. Adjusting for sex, age, smoking status, burn mechanism, TBSA, and first aid adequacy, Mepilex® Ag had a reduced time to re-epithelialization compared to Biobrane™ (IRR: 1.26; 95% CI: 1.07-1.48, P < .01). Economic analysis showed that there was a 99%, 71%, and 53% probability that Mepilex® Ag dominated (cheaper and more effective) Biobrane™, Acticoat™, and Aquacel® Ag, respectively. Mepilex® Ag achieved faster re-epithelialization and better cost effectiveness. Patient satisfaction and comfort seems better with Biobrane™ although not reflected within the end outcome of the healed wound. It is the patients' (after extensive education) and clinicians' choice, level of experience, and availability of products in praxis that will guide the decision as to which the product is used individually on which patient.

Universal Healthcare Coverage Does Not Ensure Adherence to Initial Colorectal Cancer Screening Guidelines.

INTRODUCTION: Colorectal cancer is the second leading cause of cancer deaths in the USA, and screening tests are underutilized. The aim of this study was to determine the proportion of individuals at average risk who utilized a recommended initial screening test in a universal healthcare coverage system. MATERIALS AND METHODS: This is a retrospective cohort study of active duty and retired military members as well as civilian beneficiaries of the Military Health System. Individuals born from 1960 to 1962 and eligible for full benefits on their 50th birthday were evaluated. Military rank or rank of benefits sponsor was used to determine socioeconomic status. Adherence to the U.S. Preventive Services Task Force guidelines for initial colorectal cancer screening was determined using "Current Procedural Terminology" and "Healthcare Common Procedure Coding System" codes for colonoscopy, sigmoidoscopy, fecal occult blood test, and fecal immunohistochemistry test. Average risk individuals who obtained early screening ages 47 to 49 were also identified. RESULTS: This study identified 275,665 individuals at average risk. Of these, 105,957 (38.4%) adhered to screening guidelines. An additional 19,806 (7.2%) individuals were screened early. Colonoscopy (82.7%) was the most common screening procedure. Highest odds of screening were associated with being active duty military (odds ratio [OR] 3.63, 95% confidence interval [CI] 3.43 to 3.85), having highest socioeconomic status (OR 2.37, 95% CI 2.31 to 2.44), and having managed care insurance (OR 4.36, 95% CI 4.28 to 4.44). CONCLUSIONS: Universal healthcare coverage does not ensure initial colorectal cancer screening utilization consistent with guidelines no does it eliminate disparities.

Proteomic modelling of gluten digestion from a physiologically relevant food system: A focus on the digestion of immunogenic peptides from wheat implicated in celiac disease.

Celiac disease is an autoimmune illness activated by gluten peptides produced during gastrointestinal digestion. A simulated in vitro digestion of gluten was conducted to define the profile and kinetic release pattern of immunogenic gluten peptides in a physiologically relevant food matrix. White bread was digested using the INFOGEST in vitro standardised digestion protocol from 0 to 240 min and subsequently analysed by SDS-PAGE, quantitative LC-MS/MS, untargeted LC-MS/MS and ELISA. The release profile of six gluten peptides was defined by quantitative LC-MS/MS; none were detected in the gastric phase, but rapidly peaked in the intestinal phase. These results were corroborated by the ELISA analysis. Untargeted proteomics identified 83 immunogenic peptides. Their qualitative concentrations were defined throughout digestion, demonstrating complex relationships through proteolysis. This analysis suggests immunogenic gluten may peak within the intestinal duodenum and gives new insights into the complexity of gluten digestion from a physiologically relevant food matrix.

Pregnant Women's Acceptability of Alcohol, Tobacco, and Drug Use Screening and Willingness to Disclose Use in Prenatal Care.

PURPOSE: Despite the prevalence of alcohol, tobacco, and other drug (ATOD) use screening as part of prenatal care, pregnant women's perspectives on screening are largely absent from research and clinical practice. This study examines pregnant women's acceptability of ATOD screening and willingness to disclose their ATOD use in prenatal care. METHODS: Pregnant women completed a self-administered survey and structured interview at four prenatal care facilities in Louisiana and Maryland (N = 589). Participants reported the acceptability of screening and their willingness to honestly disclose their ATOD use to their provider. Data were analyzed through descriptive statistics, tests of proportions, simple regression models, and coding of open-ended responses. RESULTS: Nearly all pregnant women found screening acceptable for alcohol (97%), tobacco (98%), and other drug use (97%) during prenatal care. The acceptability of alcohol use screening was higher among those who reported binge drinking (98% vs. 96%; p = .002) and risky alcohol consumption (99% vs. 96%; p = .018). The acceptability of screening for other drugs was higher among women reporting binge drinking (98% vs. 96%; p = .032) and other drug use (98% vs. 96%; p = .058). Almost all pregnant women indicated that they were willing to disclose their alcohol (99%), tobacco (99%), and other drug use (98%) to their provider. CONCLUSIONS: Almost all women considered verbal screening for ATOD use during prenatal care acceptable and indicated that they were willing to honestly disclose their ATOD use. Verbal screening may allow for the opportunity to initiate safe, nonjudgmental conversations about women's substance use, risk, and goals for their ATOD use, pregnancy, and parenting.

A one-century sedimentary record of N- and S-polycyclic aromatic compounds in the Athabasca oil sands region in Canada.

The atmospheric deposition of polycyclic aromatic compounds (PACs) is considered a major pathway to isolated lakes and bogs in the Athabasca oil sands region (AOSR), Canada. However, the suite of PACs measured has been limited. We report the detailed depositional history of nitrogen and sulphur heterocyclic PACs using a 210Pb dated sediment core (1914-2015) near major developments in the AOSR. We observed (1) an exponential growth in the deposition of heterocyclic PACs to recent times with an average doubling time of 12 years, (2) significant breakpoints in PAC fluxes in the mid to late 1980s, and (3) a synchronous increase of PACs with crude oil production (r2 = 0.82, p = 0.001). NPACs were not detected prior to the 1960s in the sediment core studied, suggesting they may hold promise in serving as indicators for atmospheric PAC deposition of industrial origin. Furthermore, a change in heterocyclic PAC distribution profiles beginning in the 1970-1980s, after the onset of mining, resembling a petcoke signature, was also observed. Significant positive correlations (p < 0.05) were observed between heterocyclic PACs, and several metal(loid)s, including priority pollutant elements, chromium and beryllium, and rare earth elements, cerium, lanthanum and yttrium (r2 > 0.75), suggesting the potential of a common source or similar transport and fate mechanisms. Significant negative or no correlations were observed between heterocyclic PACs and other metal(loid)s, including vanadium, total mercury and lead, possibly reflecting the impact of broader regulatory controls introduced in the mid-1970s on some metal(loids) but not on PACs, including the installation of electrostatic precipitators in major upgrader stacks.

Highly efficient serum-free manipulation of miRNA in human NK cells without loss of viability or phenotypic alterations is accomplished with TransIT-TKO.

Natural killer (NK) cells are innate lymphocytes with functions that include target cell killing, inflammation and regulation. NK cells integrate incoming activating and inhibitory signals through an array of germline-encoded receptors to gauge the health of neighbouring cells. The reactive potential of NK cells is influenced by microRNA (miRNA), small non-coding sequences that interfere with mRNA expression. miRNAs are highly conserved between species, and a single miRNA can have hundreds to thousands of targets and influence entire cellular programs. Two miRNA species, miR-155-5p and miR-146a-5p are known to be important in controlling NK cell function, but research to best understand the impacts of miRNA species within NK cells has been bottlenecked by a lack of techniques for altering miRNA concentrations efficiently and without off-target effects. Here, we describe a non-viral and straightforward approach for increasing or decreasing expression of miRNA in primary human NK cells. We achieve >90% transfection efficiency without off-target impacts on NK cell viability, education, phenotype or function. This opens the opportunity to study and manipulate NK cell miRNA profiles and their impacts on NK cellular programs which may influence outcomes of cancer, inflammation and autoimmunity.

Healthcare costs for abortions performed in ambulatory surgery centers vs office-based settings.

BACKGROUND: Several states require that abortions be provided in ambulatory surgery centers. Supporters of such laws argue that they make abortions safer, yet previous studies have found no differences in abortion-related morbidities or adverse events for abortions performed in ambulatory surgery centers versus office-based settings. However, little is known about how costs of abortions provided in ambulatory surgery centers differ from those provided in office-based settings. OBJECTIVE: To compare healthcare expenditures for abortions performed in ambulatory surgery centers versus office-based settings using a large national private insurance claims database. MATERIALS AND METHODS: A retrospective cohort study compared expenditures for abortions performed in ambulatory surgery centers versus office-based settings. Data on women who had abortions in an ambulatory surgery center or office-based setting between January 1, 2011, and December 31, 2014 were obtained from the MarketScan Commercial Claims and Encounters database. The sample was limited to women who were continuously enrolled in their insurance plans for at least 1 year before and at least 6 weeks after the abortion. Healthcare expenditures were assessed separately for the index abortion and the 6-week period after the abortion. Costs were measured from the perspective of the healthcare system and included all payments to the provider, including insurance company payments and any patient out-of-pocket payments. RESULTS: Overall, 49,287 beneficiaries who had 50,311 abortions met inclusion criteria. Of the included abortions, 47% were first-trimester aspiration, 27% first-trimester medication, and 26% second-trimester or later abortions. Most abortions (89%) were provided in office-based settings, with 11% provided in ambulatory surgery centers. Unadjusted mean index abortion costs were higher in ambulatory surgery centers than in office-based settings ($1704 versus $810; P < .001). After adjusting for patient clinical and demographic characteristics, costs of index abortions were $772 higher (95% confidence interval, $746-$797), total follow-up costs for abortions that had any follow-up care were $1099 higher (95% confidence interval, $1004-$1,195), and total follow-up costs for abortions that had an abortion-related morbidity or adverse event were not significantly different in ambulatory surgery centers compared to office-based settings. There were also no significant differences in the likelihood of having any follow-up care or abortion-related event follow-up care. CONCLUSION: Abortions performed at ambulatory surgery centers are significantly more costly than those performed in office-based settings, with no difference in the likelihood of receiving follow-up care. Laws requiring that abortions be provided in ambulatory surgery centers may only result in increased costs for abortions, with no effect on abortion safety.