Simultaneous pharmacokinetic modeling of unbound and total darunavir with ritonavir in adolescents: a substudy of the SMILE trial.

Darunavir (DRV) is an HIV protease inhibitor commonly used as part of antiretroviral treatment regimens globally for children and adolescents. It requires a pharmacological booster, such as ritonavir (RTV) or cobicistat. To better understand the pharmacokinetics (PK) of DRV in this younger population and the importance of the RTV boosting effect, a population PK substudy was conducted within SMILE trial, where the maintenance of HIV suppression with once daily integrate inhibitor + darunavir/ritonavir in children and adolescents is evaluated. A joint population PK model that simultaneously used total DRV, unbound DRV, and total RTV concentrations was developed. Competitive and non-competitive models were examined to define RTV's influence on DRV pharmacokinetics. Linear and non-linear equations were tested to assess DRV protein binding. A total of 443 plasma samples from 152 adolescents were included in this analysis. Darunavir PK was best described by a one-compartment model first-order absorption and elimination. The influence of RTV on DRV pharmacokinetics was best characterized by ritonavir area under the curve on DRV clearance using a power function. The association of non-linear and linear equations was used to describe DRV protein binding to alpha-1 glycoprotein and albumin, respectively. In our population, simulations indicate that 86.8% of total and unbound DRV trough concentrations were above 0.55 mg/L [10 times protein binding-adjusted EC50 for wild-type (WT) HIV-1] and 0.0243 mg/L (10 times EC90 for WT HIV-1) targets, respectively. Predictions were also in agreement with observed outcomes from adults receiving 800/100 mg DRV/r once a day. Administration of 800/100 mg of DRV/r once daily provides satisfactory concentrations and exposures for adolescents aged 12 years and older.

Towards personalized management of early esophageal adenocarcinoma.

PURPOSE OF REVIEW: This review aims to discuss recent advancements in the endoscopic management of early esophageal adenocarcinoma (T1 EAC). RECENT FINDINGS: Patients with high-risk EAC (defined by the presence of deep submucosal invasion, and/or lymphovascular invasion, and/or poor differentiation) have a higher risk of lymph node metastases than those with low-risk EAC. However, more recent, endoscopically-focused studies report a lower risk of lymph node metastases and distant metastases for high-risk EAC than previously assumed. Instead of referring all high-risk EAC patients for esophagectomy after a radical endoscopic resection, an alternative approach involving regular upper endoscopy with endoscopic ultrasound may allow for detection of intra-luminal recurrence and lymph node metastases at an early and potentially curable stage. SUMMARY: Endoscopic resection of mucosal and submucosal EAC might prove to be safe and curative for selected cases in the future, when followed by a strict follow-up protocol. Despite the promising results of preliminary studies, there is an ongoing need for personalized strategies and new risk stratification methods to decide on the best management for individual patients with high-risk T1 EAC.

The impact of higher protein dosing on outcomes in critically ill patients with acute kidney injury: a post hoc analysis of the EFFORT protein trial.

BACKGROUND: Based on low-quality evidence, current nutrition guidelines recommend the delivery of high-dose protein in critically ill patients. The EFFORT Protein trial showed that higher protein dose is not associated with improved outcomes, whereas the effects in critically ill patients who developed acute kidney injury (AKI) need further evaluation. The overall aim is to evaluate the effects of high-dose protein in critically ill patients who developed different stages of AKI. METHODS: In this post hoc analysis of the EFFORT Protein trial, we investigated the effect of high versus usual protein dose (≥ 2.2 vs. ≤ 1.2 g/kg body weight/day) on time-to-discharge alive from the hospital (TTDA) and 60-day mortality and in different subgroups in critically ill patients with AKI as defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria within 7 days of ICU admission. The associations of protein dose with incidence and duration of kidney replacement therapy (KRT) were also investigated. RESULTS: Of the 1329 randomized patients, 312 developed AKI and were included in this analysis (163 in the high and 149 in the usual protein dose group). High protein was associated with a slower time-to-discharge alive from the hospital (TTDA) (hazard ratio 0.5, 95% CI 0.4-0.8) and higher 60-day mortality (relative risk 1.4 (95% CI 1.1-1.8). Effect modification was not statistically significant for any subgroup, and no subgroups suggested a beneficial effect of higher protein, although the harmful effect of higher protein target appeared to disappear in patients who received kidney replacement therapy (KRT). Protein dose was not significantly associated with the incidence of AKI and KRT or duration of KRT. CONCLUSIONS: In critically ill patients with AKI, high protein may be associated with worse outcomes in all AKI stages. Recommendation of higher protein dosing in AKI patients should be carefully re-evaluated to avoid potential harmful effects especially in patients who were not treated with KRT. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov (NCT03160547) on May 17th 2017.

The early years: hirschsprung disease and health-related quality of life.

PURPOSE: Chronic diseases are notorious in the way that they interfere with many aspects of a child's development, and this holds true for children with Hirschsprung disease (HD). The present research aims to (1) determine whether the health-related quality of life (HRQoL) of HD children differs from healthy paediatric populations; and (2) explore the relationship between HD children's HRQoL and psychosocial outcomes of parents. METHODS: Using a cross-sectional survey study design, children's HRQoL was assessed using the Pediatric Quality of Life Inventory (PedsQL), while parental psychosocial outcomes were measured using the Patient-Reported Outcomes Measurement Information System (PROMIS) anxiety and depression short-forms, Family Management Measure (FaMM), and Parent Experience of Child Illness. Surveys were administered over telephone to parents of 48 Australian children treated for HD (87.5% male, median age 4.5 years) during the period May to November 2021. RESULTS: While postoperative HRQoL of HD children was comparable to that of healthy age-matched controls, psychosocial quality of life of HD children was significantly poorer (mean difference = 3.40, CI [0.05, 6.76]). All parental outcome measures were significantly correlated with the PedsQL (r = - 0.77-0.67, p < 0.05) in expected directions, with FaMM subscales (except parent mutuality) demonstrating the most variation (R2 = 0.41-0.59). Of note, 31.3% of parents reported moderate to severe symptoms of anxiety on the PROMIS. CONCLUSION: Despite overall positive results for children, parents reported elevated symptoms of anxiety. This study highlights the importance of long-term follow-up care for HD patients and their families.

Impaired Insulin Signaling Mediated by the Small GTPase Rac1 in Skeletal Muscle of the Leptin-Deficient Obese Mouse.

Insulin-stimulated glucose uptake in skeletal muscle is mediated by the glucose transporter GLUT4. The small GTPase Rac1 acts as a switch of signal transduction that regulates GLUT4 translocation to the plasma membrane following insulin stimulation. However, it remains obscure whether signaling cascades upstream and downstream of Rac1 in skeletal muscle are impaired by obesity that causes insulin resistance and type 2 diabetes. In an attempt to clarify this point, we investigated Rac1 signaling in the leptin-deficient (Lepob/ob) mouse model. Here, we show that insulin-stimulated GLUT4 translocation and Rac1 activation are almost completely abolished in Lepob/ob mouse skeletal muscle. Phosphorylation of the protein kinase Akt2 and plasma membrane translocation of the guanine nucleotide exchange factor FLJ00068 following insulin stimulation were also diminished in Lepob/ob mice. On the other hand, the activation of another small GTPase RalA, which acts downstream of Rac1, by the constitutively activated form of Akt2, FLJ00068, or Rac1, was partially abrogated in Lepob/ob mice. Taken together, we conclude that insulin-stimulated glucose uptake is impaired by two mechanisms in Lepob/ob mouse skeletal muscle: one is the complete inhibition of Akt2-mediated activation of Rac1, and the other is the partial inhibition of RalA activation downstream of Rac1.

State health policies and interest in PrEP: evidence from Google Trends.

This study investigated the association between interest in Pre-exposure Prophylaxis (PrEP) in the US using Google Health Trends as a source of big data and state policy variables of Medicaid expansions under the Affordable Care Act (ACA) and initiation of PrEP Assistance Programs (PrEP-AP). As of December 2019, thirty-three states and the District of Columbia have accepted federal Medicaid funding provided through the ACA to expand eligibility to low-income adults. Among these expansion states, eight states also implemented PrEP-AP, a program that finances PrEP. A difference-in-differences approach estimated how changes in Google search for PrEP before and after the expansion differed across expansion and non-expansion states. Analyses also gauged whether the magnitude of the correlation between Medicaid expansions and Google searches was higher in states that also initiated PrEP-AP. Findings indicated that the Medicaid expansions were associated with a higher share of Google searches for PrEP keywords (ß=1.536, S.E. =.36, p<.001). Moreover, the magnitude of correlation for some keywords was higher in states that also implemented PrEP-APs.

Isoprene Epoxydiol-Derived Sulfated and Nonsulfated Oligomers Suppress Particulate Mass Loss during Oxidative Aging of Secondary Organic Aerosol.

Acid-driven multiphase chemistry of isoprene epoxydiols (IEPOX) with inorganic sulfate aerosols contributes substantially to secondary organic aerosol (SOA) formation, which constitutes a large mass fraction of atmospheric fine particulate matter (PM2.5). However, the atmospheric chemical sinks of freshly generated IEPOX-SOA particles remain unclear. We examined the role of heterogeneous oxidation of freshly generated IEPOX-SOA particles by gas-phase hydroxyl radical (•OH) under dark conditions as one potential atmospheric sink. After 4 h of gas-phase •OH exposure (∼3 × 108 molecules cm-3), chemical changes in smog chamber-generated IEPOX-SOA particles were assessed by hydrophilic interaction liquid chromatography coupled with electrospray ionization high-resolution quadrupole time-of-flight mass spectrometry (HILIC/ESI-HR-QTOFMS). A comparison of the molecular-level compositional changes in IEPOX-SOA particles during aging with or without •OH revealed that decomposition of oligomers by heterogeneous •OH oxidation acts as a sink for •OH and maintains a reservoir of low-volatility compounds, including monomeric sulfate esters and oligomer fragments. We propose tentative structures and formation mechanisms for previously uncharacterized SOA constituents in PM2.5. Our results suggest that this •OH-driven renewal of low-volatility products may extend the atmospheric lifetimes of particle-phase IEPOX-SOA by slowing the production of low-molecular weight, high-volatility organic fragments and likely contributes to the large quantities of 2-methyltetrols and methyltetrol sulfates reported in PM2.5.

Testing a digitally distributed method to recruit a network of community organizations to fight the consequences of the drug epidemic: A study in 13 American states.

To mitigate the opioid epidemic, a concerted effort to educate, prevent, diagnose, treat, and engage residents is required. In this study, a digitally distributed method to form a large network of organizations was tested with 99 counties in regions with high vulnerability to hepatitis C virus (HCV). The method involved a cascade of contacts going from email to phone calls, to videoconferencing and measuring the number of contacts required, amount of time taken, and the proportion of success at recruiting at least one community organization per county. A recruitment period of 5 months and 2118 contact attempts led to the recruitment of organizations from 73 out of our 99 target counties. Organizations belonging to health departments required more attempts and time to recruit but ultimately enrolled at higher rates than did other organizations such as coalitions and agencies. Organizations from counties more (vs. less) vulnerable to HCV outbreaks required more attempts to recruit and, using multiple recruitment methods (e.g., emails, phone calls, and Zoom meetings), improved enrollment success. Overall, this method proved to be successful at remotely engaging a large-scale network of communities with different levels of risk within a large geographic region.

Territorywide Study of Early Coronavirus Disease Outbreak, Hong Kong, China.

Initial cases of coronavirus disease in Hong Kong were imported from mainland China. A dramatic increase in case numbers was seen in February 2020. Most case-patients had no recent travel history, suggesting the presence of transmission chains in the local community. We collected demographic, clinical, and epidemiologic data from 50 patients, who accounted for 53.8% of total reported case-patients as of February 28, 2020. We performed whole-genome sequencing to determine phylogenetic relationship and transmission dynamics of severe acute respiratory syndrome coronavirus 2 infections. By using phylogenetic analysis, we attributed the community outbreak to 2 lineages; 1 harbored a common mutation, Orf3a-G251V, and accounted for 88.0% of the cases in our study. The estimated time to the most recent common ancestor of local coronavirus disease outbreak was December 24, 2019, with an evolutionary rate of 3.04 × 10-3 substitutions/site/year. The reproduction number was 1.84, indicating ongoing community spread.

Growth-defense trade-offs and yield loss in plants with engineered cell walls.

As a major component of plant secondary cell walls, lignin provides structural integrity and rigidity, and contributes to primary defense by providing a physical barrier to pathogen ingress. Genetic modification of lignin biosynthesis has been adopted to reduce the recalcitrance of lignified cell walls to improve biofuel production, tree pulping properties and forage digestibility. However, lignin-modification is often, but unpredictably, associated with dwarf phenotypes. Hypotheses suggested to explain this include: collapsed vessels leading to defects in water and solute transport; accumulation of molecule(s) that are inhibitory to plant growth or deficiency of metabolites that are critical for plant growth; activation of defense pathways linked to cell wall integrity sensing. However, there is still no commonly accepted underlying mechanism for the growth defects. Here, we discuss recent data on transcriptional reprogramming in plants with modified lignin content and their corresponding suppressor mutants, and evaluate growth-defense trade-offs as a factor underlying the growth phenotypes. New approaches will be necessary to estimate how gross changes in transcriptional reprogramming may quantitatively affect growth. Better understanding of the basis for yield drag following cell wall engineering is important for the biotechnological exploitation of plants as factories for fuels and chemicals.

Ensemble-Based Assimilation of Satellite All-Sky Microwave Radiances Improves Intensity and Rainfall Predictions for Hurricane Harvey (2017).

Ensemble-based data assimilation of radar observations across inner-core regions of tropical cyclones (TCs) in tandem with satellite all-sky infrared (IR) radiances across the TC domain improves TC track and intensity forecasts. This study further investigates potential enhancements in TC track, intensity, and rainfall forecasts via assimilation of all-sky microwave (MW) radiances using Hurricane Harvey (2017) as an example. Assimilating Global Precipitation Measurement constellation all-sky MW radiances in addition to GOES-16 all-sky IR radiances reduces the forecast errors in the TC track, rapid intensification (RI), and peak intensity compared to assimilating all-sky IR radiances alone, including a 24-hr increase in forecast lead-time for RI. Assimilating all-sky MW radiances also improves Harvey's hydrometeor fields, which leads to improved forecasts of rainfall after Harvey's landfall. This study indicates that avenues exist for producing more accurate forecasts for TCs using available yet underutilized data, leading to better warnings of and preparedness for TC-associated hazards in the future.

Early ART-initiation and longer ART duration reduces HIV-1 proviral DNA levels in children from the CHER trial.

BACKGROUND: Reduction of the reservoir of latent HIV-infected cells might increase the possibility of long-term remission in individuals living with HIV. We investigated factors associated with HIV-1 proviral DNA levels in children receiving different antiretroviral therapy (ART) strategies in the children with HIV early antiretroviral therapy (CHER) trial. METHODS: Infants with HIV < 12 weeks old with CD4% ≥ 25% were randomized in the CHER trial to early limited ART for 40 or 96 weeks (ART-40 W, ART-96 W), or deferred ART (ART-Def). For ART-Def infants or following ART interruption in ART-40 W/ART-96 W, ART was started/re-started for clinical progression or CD4% < 25%. In 229 participants, HIV-1 proviral DNA was quantified by PCR from stored peripheral blood mononuclear cells from children who had received ≥ 24 weeks ART and two consecutive undetectable HIV-1 RNA 12-24 weeks apart. HIV-1 proviral DNA was compared between ART-Def and ART-96 W at week 96, and in all arms at week 248. Factors associated with HIV-1 proviral DNA levels were evaluated using linear regression. FINDINGS: Longer duration of ART was significantly associated with lower HIV-1 proviral DNA at both 96 (p = 0.0003) and 248 weeks (p = 0.0011). Higher total CD8 count at ART initiation was associated with lower HIV-1 proviral DNA at both 96 (p = 0.0225) and 248 weeks (p = 0.0398). Week 248 HIV-1 proviral DNA was significantly higher in those with positive HIV-1 serology at week 84 than those with negative serology (p = 0.0042). INTEPRETATION: Longer ART duration is key to HIV-1 proviral DNA reduction. Further understanding is needed of the effects of "immune-attenuation" through early HIV-1 exposure. FUNDING: Wellcome Trust, National Institutes of Health, Medical Research Council.

Effects of wearable ankle robotics for stair and over-ground training on sub-acute stroke: a randomized controlled trial.

BACKGROUND: Wearable ankle robotics could potentially facilitate intensive repetitive task-specific gait training on stair environment for stroke rehabilitation. A lightweight (0.5 kg) and portable exoskeleton ankle robot was designed to facilitate over-ground and stair training either providing active assistance to move paretic ankle augmenting residual motor function (power-assisted ankle robot, PAAR), or passively support dropped foot by lock/release ankle joint for foot clearance in swing phase (swing-controlled ankle robot, SCAR). In this two-center randomized controlled trial, we hypothesized that conventional training integrated with robot-assisted gait training using either PAAR or SCAR in stair environment are more effective to enhance gait recovery and promote independency in early stroke, than conventional training alone. METHODS: Sub-acute stroke survivors (within 2 months after stroke onset) received conventional training integrated with 20-session robot-assisted training (at least twice weekly, 30-min per session) on over-ground and stair environments, wearing PAAR (n = 14) or SCAR (n = 16), as compared to control group receiving conventional training only (CT, n = 17). Clinical assessments were performed before and after the 20-session intervention, including functional ambulatory category as primary outcome measure, along with Berg balance scale and timed 10-m walk test. RESULTS: After the 20-session interventions, all three groups showed statistically significant and clinically meaningful within-group functional improvement in all outcome measures (p < 0.005). Between-group comparison showed SCAR had greater improvement in functional ambulatory category (mean difference + 0.6, medium effect size 0.610) with more than 56% independent walkers after training, as compared to only 29% for CT. Analysis of covariance results showed PAAR had greater improvement in walking speed than SCAR (mean difference + 0.15 m/s, large effect size 0.752), which was in line with the higher cadence and speed when wearing the robot during the 20-session robot-assisted training over-ground and on stairs. CONCLUSIONS: Robot-assisted stair training would lead to greater functional improvement in gait independency and walking speed than conventional training in usual care. The active powered ankle assistance might facilitate users to walk more and faster with their paretic leg during stair and over-ground walking. TRIAL REGISTRATION: ClinicalTrials.gov NCT03184259. Registered on 12 June 2017.

Atrophy of White Adipose Tissue Accompanied with Decreased Insulin-Stimulated Glucose Uptake in Mice Lacking the Small GTPase Rac1 Specifically in Adipocytes.

Insulin stimulates glucose uptake in adipose tissue and skeletal muscle by inducing plasma membrane translocation of the glucose transporter GLUT4. Although the small GTPase Rac1 is a key regulator downstream of phosphoinositide 3-kinase (PI3K) and the protein kinase Akt2 in skeletal muscle, it remains unclear whether Rac1 also regulates glucose uptake in white adipocytes. Herein, we investigated the physiological role of Rac1 in white adipocytes by employing adipocyte-specific rac1 knockout (adipo-rac1-KO) mice. Subcutaneous and epididymal white adipose tissues (WATs) in adipo-rac1-KO mice showed significant reductions in size and weight. Actually, white adipocytes lacking Rac1 were smaller than controls. Insulin-stimulated glucose uptake and GLUT4 translocation were abrogated in rac1-KO white adipocytes. On the other hand, GLUT4 translocation was augmented by constitutively activated PI3K or Akt2 in control, but not in rac1-KO, white adipocytes. Similarly, to skeletal muscle, the involvement of another small GTPase RalA downstream of Rac1 was demonstrated. In addition, mRNA levels of various lipogenic enzymes were down-regulated in rac1-KO white adipocytes. Collectively, these results suggest that Rac1 is implicated in insulin-dependent glucose uptake and lipogenesis in white adipocytes, and reduced insulin responsiveness due to the deficiency of Rac1 may be a likely explanation for atrophy of WATs.

Biomechanical analysis of subcondylar fracture fixation using miniplates at different positions and of different lengths.

BACKGROUND: Many types of titanium plates were used to treat subcondylar fracture clinically. However, the efficacy of fixation in different implant positions and lengths of the bone plate has not been thoroughly investigated. Therefore, the primary purpose of this study was to use finite element analysis (FEA) to analyze the biomechanical effects of subcondylar fracture fixation with miniplates at different positions and lengths so that clinicians were able to find a better strategy of fixation to improve the efficacy and outcome of treatment. METHODS: The CAD software was used to combine the mandible, miniplate, and screw to create seven different FEA computer models. These models with subcondylar fracture were fixed with miniplates at different positions and of different lengths. The right unilateral molar clench occlusal mode was applied. The observational indicators were the reaction force at the temporomandibular joint, von Mises stress of the mandibular bone, miniplate and screw, and the sliding distance on the oblique surface of the fracture site at the mandibular condyle. RESULTS: The results showed the efficacy of fixation was better when two miniplates were used comparing to only one miniplates. Moreover, using longer miniplates for fixation had better results than the short one. Furthermore, fixing miniplates at the posterior portion of subcondylar region would have a better fixation efficacy and less sliding distance (5.46-5.76 µm) than fixing at the anterolateral surface of subcondylar region (6.10-7.00 µm). CONCLUSION: Miniplate fixation, which was placed closer to the posterior margin, could effectively reduce the amount of sliding distance in the fracture site, thereby achieving greater stability. Furthermore, fixation efficiency was improved when an additional miniplate was placed at the anterior margin. Our study suggested that the placement of miniplates at the posterior surface and the additional plate could effectively improve stability.

The risks of ubiquinone and ß-carotene deficiency and metabolic disorders in patients with oral cancer.

BACKGROUND: Cancer development is mediated by oxidative stress and inflammation, which may correlate with metabolic disorders. The aim of this study was to evaluate antioxidant vitamins status and metabolic parameters in patients with oral cancer according to tumor-node-metastasis (TNM) stages. METHODS: A total of 194 patients with oral cancer were enrolled in this study. The patients were stratified for four groups according to cancer stages and that the statistics are comparisons across these groups. The levels of antioxidant vitamins (ubiquinone, ß-carotene, vitamin A and E), metabolic parameters, oxidative stress, antioxidant enzymes activity, and inflammatory markers were measured. RESULTS: More than half of the subjects had high blood pressure, central obesity, hyperglycemia, and hyperlipidemia regardless of TNM stage. With regard to antioxidant vitamins status, 46 and 94% of patients had ß-carotene and ubiquinone deficiency, respectively. Patients in T3 and T4 stages had significantly lower antioxidant enzyme (catalase, p = 0.03) activity and higher inflammatory markers levels (high sensitivity C-reactive protein and interleukin-6, p < 0.01) than patients in the other stages. In addition, the level of ß-carotene was negatively associated with waist circumference, and ubiquinone was positively associated with the level of high-density lipoprotein cholesterol (p < 0.05). Higher ß-carotene and ubiquinone levels were negatively associated with hypertriglyceridemia and the risk of metabolic syndrome (p < 0.05). CONCLUSIONS: A high proportion of patients with oral cancer had ubiquinone or ß-carotene deficiency and metabolic disorders. The level of ubiquinone or ß-carotene was negatively associated with the risk of central obesity, hypertriglyceridemia, and metabolic syndrome. Since patients with oral cancer suffer from high oxidative stress and inflammation (particularly in the T3 and T4 stages), supplementation with antioxidant vitamins such as ubiquinone or ß-carotene could be preferentially applied.

Organosulfates in Ambient Aerosol: State of Knowledge and Future Research Directions on Formation, Abundance, Fate, and Importance.

Organosulfates (OSs), also referred to as organic sulfate esters, are well-known and ubiquitous constituents of atmospheric aerosol particles. Commonly, they are assumed to form upon mixing of air masses of biogenic and anthropogenic origin, that is, through multiphase reactions between organic compounds and acidic sulfate particles. However, in contrast to this simplified picture, recent studies suggest that OSs may also originate from purely anthropogenic precursors or even directly from biomass and fossil fuel burning. Moreover, besides classical OS formation pathways, several alternative routes have been discovered, suggesting that OS formation possibly occurs through a wider variety of formation mechanisms in the atmosphere than initially expected. During the past decade, OSs have reached a constantly growing attention within the atmospheric science community with evermore studies reporting on large numbers of OS species in ambient aerosol. Nonetheless, estimates on OS concentrations and implications on atmospheric physicochemical processes are still connected to large uncertainties, calling for combined field, laboratory, and modeling studies. In this Critical Review, we summarize the current state of knowledge in atmospheric OS research, discuss unresolved questions, and outline future research needs, also in view of reductions of anthropogenic sulfur dioxide (SO2) emissions. Particularly, we focus on (1) field measurements of OSs and measurement techniques, (2) formation pathways of OSs and their atmospheric relevance, (3) transformation, reactivity, and fate of OSs in atmospheric particles, and (4) modeling efforts of OS formation and their global abundance.

The human oral cavity microbiota composition during acute tonsillitis: a cross-sectional survey.

BACKGROUND: Microbial culture-based investigations of inflamed tonsil tissues have previously indicated enrichment of several microorganisms such as Streptococcus, Staphylococcus and Prevotella. These taxa were also largely reflected in DNA sequencing studies performed using tissue material. In comparison, less is known about the response of the overall oral cavity microbiota to acute tonsillitis despite their role in human health and evidence showing that their compositions are correlated with diseases such as oral cancers. In addition, the influence of subject-specific circumstances including consumption of prescription antibiotics and smoking habits on the microbiology of acute tonsillitis is unknown. METHODS: We collected oral rinse samples from 43 individuals admitted into hospital for acute tonsillitis and 165 non-disease volunteers recruited from the public, and compared their microbial community compositions using 16S rRNA gene sequencing. We assessed the impact of tonsillitis, whether subjects were prescribed antibiotics, the presence of oral abscesses and their smoking habits on community composition, and identified specific microbial taxa associated with tonsillitis and smoking. RESULTS: Oral rinse community composition was primarily associated with disease state (tonsillitis vs non-tonsillitis) although its effect was subtle, followed by smoking habit. Multiple Prevotella taxa were enriched in tonsillitis subjects compared to the non-tonsillitis cohort, whereas the non-tonsillitis cohort primarily showed associations with several Neisseria sequence variants. The presence of oral abscesses did not significantly influence community composition. Antibiotics were prescribed to a subset of individuals in the tonsillitis cohort but we did not observe differences in community composition associated with antibiotics consumption. In both tonsillitis and non-tonsillitis cohorts, smoking habit was associated with enrichment of several Fusobacterium variants. CONCLUSIONS: These findings show that the oral cavity microbial community is altered during acute tonsillitis, with a consistent enrichment of Prevotella during tonsillitis raising the possibility of targeted interventions. It also supports the possible link between smoking, Fusobacteria and oral cancers.

An Online Risk Index for the Cross-Sectional Prediction of New HIV Chlamydia, and Gonorrhea Diagnoses Across U.S. Counties and Across Years.

The present study evaluated the potential use of Twitter data for providing risk indices of STIs. We developed online risk indices (ORIs) based on tweets to predict new HIV, gonorrhea, and chlamydia diagnoses, across U.S. counties and across 5 years. We analyzed over one hundred million tweets from 2009 to 2013 using open-vocabulary techniques and estimated the ORIs for a particular year by entering tweets from the same year into multiple semantic models (one for each year). The ORIs were moderately to strongly associated with the actual rates (.35 < rs < .68 for 93% of models), both nationwide and when applied to single states (California, Florida, and New York). Later models were slightly better than older ones at predicting gonorrhea and chlamydia, but not at predicting HIV. The proposed technique using free social media data provides signals of community health at a high temporal and spatial resolution.

Pediatric reference intervals for 29 Ortho VITROS 5600 immunoassays using the CALIPER cohort of healthy children and adolescents.

BACKGROUND: Accurate reference intervals (RIs) based on a healthy pediatric population are essential for pediatric test result interpretation. The CALIPER project has recruited a large healthy cohort and completed a series of a priori studies to address gaps in pediatric RIs. As immunoassays from different manufacturers for endocrine and special chemistry markers are not standardized and show marked intermethod differences, direct RI studies are needed for each major analytical platform. Here, we report age- and sex-specific pediatric RIs for 29 immunoassays on the Ortho Clinical Diagnostics (Ortho) VITROS® 5600 analyzer. METHODS: Health information and blood samples were collected from healthy pediatric subjects. Using the Ortho VITROS 5600 Integrated System MicroWell Technology, 29 biomarkers were measured. Analyte concentrations were partitioned by age and sex according to the Harris and Boyd method. After removing outliers, age- and sex-specific RIs and corresponding 90% confidence intervals were calculated according to CLSI guidelines. RESULTS: All analytes required age partitioning except ß-human chorionic gonadotropin (ß-hCG), cancer antigen 15-3 (CA15-3), rubella immunoglobulin G (rubella IgG), and vitamin D. Several analytes including estradiol, progesterone, testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), free triiodothyronine (FT3), total triiodothyronine (TT3), total thyroxine (TT4), thyroid uptake, ferritin, intact parathyroid hormone (iPTH), total prostate-specific antigen (tPSA), free prostate-specific antigen (fPSA), cancer antigen 125 (CA125), creatine kinase MB (CK-MB), and myoglobin showed sex differences, observed mostly with the onset of puberty. CONCLUSIONS: Complex reference value trends were observed across the pediatric age range for several biomarkers examined on Ortho VITROS immunoassays. The availability of VITROS immunoassay RIs will enable accurate laboratory test interpretation and diagnosis for the pediatric population. As recommended by the CLSI EP28-A3c guidelines, implementation of these RIs should be validated for each laboratory's local pediatric population.