Single-cell Profiling Uncovers a Muc4-Expressing Metaplastic Gastric Cell Type Sustained by Helicobacter pylori-driven Inflammation.

Mechanisms for Helicobacter pylori (Hp)-driven stomach cancer are not fully understood. In a transgenic mouse model of gastric preneoplasia, concomitant Hp infection and induction of constitutively active KRAS (Hp+KRAS+) alters metaplasia phenotypes and elicits greater inflammation than either perturbation alone. Gastric single-cell RNA sequencing showed that Hp+KRAS+ mice had a large population of metaplastic pit cells that expressed the intestinal mucin Muc4 and the growth factor amphiregulin. Flow cytometry and IHC-based immune profiling revealed that metaplastic pit cells were associated with macrophage and T-cell inflammation. Accordingly, expansion of metaplastic pit cells was prevented by gastric immunosuppression and reversed by antibiotic eradication of Hp. Finally, MUC4 expression was significantly associated with proliferation in human gastric cancer samples. These studies identify an Hp-associated metaplastic pit cell lineage, also found in human gastric cancer tissues, whose expansion is driven by Hp-dependent inflammation. Significance: Using a mouse model, we have delineated metaplastic pit cells as a precancerous cell type whose expansion requires Hp-driven inflammation. In humans, metaplastic pit cells show enhanced proliferation as well as enrichment in precancer and early cancer tissues, highlighting an early step in the gastric metaplasia to cancer cascade.

Agronomic and economic implications of cover crop and phosphorus fertilizer management practices for water quality improvement.

Phosphorus (P) fertilization practices and winter cover crops are promoted to protect water quality yet can potentially influence crop yield and profitability. This study examined the impacts of three P fertilizer management practices (no P, fall broadcast P, and spring injected P) and winter annual cover crop use on yields, net returns, and water quality in a no-till corn-soybean rotation. Treatments were replicated in a 4-yr field study where sediment, total P, and dissolved reactive P (DRP) losses in edge-of-field surface runoff were continuously monitored. Production budgets were developed for each treatment and coupled with water quality data to identify optimal practices and opportunity costs for improving water quality. Applying P fertilizers increased crop yield regardless of application method or cover crop, but the response was more pronounced in corn than soybean. The cover crop reduced corn grain yield in 1 yr with high temperature and low precipitation but did not impact grain yield in the other corn year or either year of soybean. The most profitable treatment was fall broadcast P fertilizer with no cover crop, which also had the greatest total P and DRP losses and near greatest sediment loss. The lowest-cost methods of reducing total P, DRP, and sediment losses were, respectively, no P fertilizer without a cover crop ($47.56 kg-1 total P), spring injected P fertilizer without a cover crop ($56.47 kg-1 DRP), and spring injected P fertilizer with a cover crop ($0.16 kg-1 sediment). Widespread adoption of these practices will likely require monetary incentives.

Reductions in particulate matter concentrations resulting from air filtration: A randomized sham-controlled crossover study.

One-hundred seventy-two households were recruited from regions with high outdoor air pollution (Fresno and Riverside, CA) to participate in a randomized, sham-controlled, cross-over study to determine the effectiveness of high-efficiency air filtration to reduce indoor particle exposures. In 129 households, stand-alone HEPA air cleaners were placed in a bedroom and in the main living area. In 43 households, high-efficiency MERV 16 filters were installed in central forced-air heating and cooling systems and the participating households were asked to run the system on a clean-air cycle for 15 min per hour. Participating households that completed the study received true air filtration for a year and sham air filtration for a year. Air pollution samples were collected at approximately 6-month intervals, with two measurements in each of the sham and true filtration periods. One week indoor and outdoor time-integrated samples were collected for measurement of PM2.5 , PM10 , and ultrafine particulate matter (UFP) measured as PM0.2 . Reflectance measurements were also made on the PM2.5 filters to estimate black carbon. True filtration significantly improved indoor air quality, with a 48% reduction in the geometric mean indoor PM0.2 and PM2.5 concentrations, and a 31% reduction in PM10 . Geometric mean concentrations of indoor/outdoor reflectance values, indicating fraction of particles of outdoor origin remaining indoors, decreased by 77%. Improvements in particle concentrations were greater with continuously operating stand-alone air cleaners than with intermittent central system filtration. Keeping windows closed and increased utilization of the filtration systems further improved indoor air quality.

Bismuth/petroleum gauze plus high density polyethylene vs. bismuth/petroleum gauze: A comparison of donor site healing and patient comfort.

INTRODUCTION: Skin grafting continues to be a fundamental component of burn treatment and inherently, a donor site must be created and treated. Burn surgeons agree that specific dressings may have a significant affect on donor site healing, but we have no consensus as to which dressing provides maximum benefit. METHODS: Retrospective analysis of prospectively collected data from an observational, within-patient controlled assessment of a practice pattern intervention. The project compared donor sites treated with high-density polyethylene plus an overlying layer of bismuth/petroleum gauze to donor sites treated with bismuth/petroleum gauze alone. The primary endpoint was patient reported pain using a standard visual analog scale from 0 (no pain) to 10 (worst possible pain). A 2-point reduction in pain was considered clinically significant. Healing was defined as complete detachment of the dressings and> 95% wound re-epitheliazation. RESULTS: A total of 30 patients were observed and analyzed. Both dressings were associated with a mean pain rating of 6 out of 10 (STD= ± 2) and a median pain rating of 6 out of 10 (range = 0-10). Additionally, both dressings were associated with a mean healing time of 20 days (SEM=1.1). The subjective dressing preference showed that a majority of patients had no preference between the two modalities (n = 20). However, when an actual preference was stated (n = 10), bismuth/petroleum gauze alone was preferred by 9 out of 10 patients. CONCLUSION: Clinically and subjectively, we found no discernible differences between the 2 dressing regimens. Thus, bismuth/petroleum gauze alone is the more cost effective dressing choice. Our burn center continues to use bismuth/petroleum gauze alone as its standard of care for donor site dressings and will continue to try to define the optimal donor site dressing.

Exploring Religiosity and Spirituality in the Sexual Decision-Making of Black Gay and Bisexual Men.

Many Black gay and bisexual men (BGBM) practice consistent religious worship and spirituality in order to cope with social challenges. This study utilized data from in-depth qualitative interviews conducted to explore personal meanings of religiosity and spirituality and how these constructs affect partner choices and sexual behaviors among BGBM. Interviews were conducted with 26 BGBM in Los Angeles, California, from September to November 2015. In-depth interviews yielded themes related to BGBM's understanding of religiosity and spirituality and how their personal beliefs influenced their partner choices and sexual risks. Implications for church-based and community-based interventions are discussed.

Correlates of Sexual Coercion among People Who Inject Drugs (PWID) in Los Angeles and San Francisco, CA.

Experiences of coerced or forced sex have been associated with risk for HIV infection for all adults and may be more common for gays, lesbians, bisexuals (GLB) and people who inject drugs (PWID). In this study, we explored factors associated with prior 12-month experiences of forced or coerced sex among a sample of PWID, with a focus on sexual orientation and gender. PWID (N = 772) from Los Angeles and San Francisco were recruited using targeted sampling methods in 2011-2013 and surveyed on a range of items related to demographics, drug use, HIV risk, and violence, including experiences of forced or coerced sex in the prior 12 months. In this racially/ethnically diverse, mostly homeless, and low-income sample of PWID, 25% of participants were female and 15% identified as GLB. Sexual coercion was reported by 9% of gay and bisexual men, 8% of heterosexual females, 5% of lesbians and bisexual women, and less than 1% of heterosexual men. In multivariate analyses, compared to heterosexual males, gay or bisexual males (adjusted odds ratio [AOR] = 10.68; 95% confidence interval [CI] = 2.03, 56.23), and heterosexual females (AOR = 9.69; 95% CI = 2.04, 45.94) had increased odds of coerced sex in the prior 12 months. Having a paying sex partner (AOR = 3.49; 95% CI = 1.42, 8.54) or having had forced sex prior to the age of 16 by someone at least five years older (AOR = 4.74; 95% CI = 1.88, 11.93) also elevated the odds of coercive sex. Sexual coercion is common among PWID, but especially for gay and bisexual men and heterosexual females. Efforts to reduce sexual violence among PWID are urgently needed.

Impact of Nitrogen Application Rate on Switchgrass Yield, Production Costs, and Nitrous Oxide Emissions.

Switchgrass ( L.) has been promoted as a potential feedstock for cellulosic biofuel in the United States. Switchgrass is known to respond to N fertilizer, but optimal rates remain unclear. Given the potential nonlinear response of nitrous oxide (NO) emissions to N inputs, N additions to switchgrass above optimal levels could have large impacts on the greenhouse gas balance of switchgrass-based biofuel. Additionally, N additions are likely to have large impacts on switchgrass production costs. Yield, N removal, and net returns were measured in switchgrass receiving 0 to 200 kg N ha in Manhattan, KS, from 2012 to 2014. Emissions of NO were measured in the 0- to 150-kg N ha treatments. Total emissions of NO increased from 0.2 to 3.0 kg NO-N ha as N inputs increased from 0 to 150 kg N ha. The 3-yr averages of fertilizer-induced emission factors were 0.7, 2.1, and 2.6% at 50, 100, and 150 kg N ha, respectively. Removal of N at harvest increased linearly with increasing N rate. Switchgrass yields increased with N inputs up to 100 to 150 kg N ha, but the critical N level for maximum yields decreased each year, suggesting that N was being applied in excess at higher N rates. Net returns were maximized at 100 kg N ha at both a high and low urea cost (US$394.71 and $945.91 ha, respectively). These results demonstrate that N inputs were necessary to increase switchgrass productivity, but rates exceeding optimal levels resulted in excessive NO emissions and increased costs for producers.

Sexual Positioning Among Men Who Have Sex With Men: A Narrative Review.

Sexual positioning practices among men who have sex with men (MSM) have not received a thorough discussion in the MSM and HIV literature, given that risks for acquiring or transmitting HIV and STIs via condomless anal sex vary according to sexual positioning. MSM bear a disproportionate burden of HIV compared to the general population in the United States; surveillance efforts suggest that HIV and STIs are increasing among domestic and international populations of MSM. We conducted a narrative review, using a targeted literature search strategy, as an initial effort to explore processes through which sexual positioning practices may contribute to HIV/STI transmission. Peer-reviewed articles were eligible for inclusion if they contained a measure of sexual positioning identity and/or behavior (i.e., "top", "bottom," etc.) or sexual positioning behavior (receptive anal intercourse or insertive anal intercourse), or assessed the relationship between sexual positioning identity with HIV risk, anal sex practice, masculinity, power, partner type, or HIV status. A total of 23 articles met our inclusion criteria. This review highlights dynamic psychosocial processes likely underlying sexual decision making related to sexual positioning identity and practices among MSM and MSM who have sex with women (MSMW), and ways these contexts may influence HIV/STI risk. Despite limited focus in the extant literature, this review notes the important role the contextual factors (masculinity stereotypes, power, partner type, and HIV status) likely to play in influencing sexual positioning identity and practices. Through this review we offer an initial synthesis of the literature describing sexual positioning identities and practices and conceptual model to provide insight into important areas of study through future research.

Flame retardant exposures in California early childhood education environments.

Infants and young children spend as much as 50h per week in child care and preschool. Although approximately 13 million children, or 65% of all U.S. children, spend some time each day in early childhood education (ECE) facilities, little information is available about environmental exposures in these environments. We measured flame retardants in air and dust collected from 40 California ECE facilities between May 2010 and May 2011. Low levels of six polybrominated diphenyl ether (PBDE) congeners and four non-PBDE flame retardants were present in air, including two constituents of Firemaster 550 and two tris phosphate compounds [tris (2-chloroethyl) phosphate (TCEP) and tris (1,3-dichloroisopropyl) phosphate (TDCIPP)]. Tris phosphate, Firemaster 550 and PBDE compounds were detected in 100% of the dust samples. BDE47, BDE99, and BDE209 comprised the majority of the PBDE mass measured in dust. The median concentrations of TCEP (319 ng g(-1)) and TDCIPP (2265 ng g(-1)) were similar to or higher than any PBDE congener. Levels of TCEP and TDCIPP in dust were significantly higher in facilities with napping equipment made out of foam (Mann-Whitney p-values<0.05). Child BDE99 dose estimates exceeded the RfD in one facility for children<3 years old. In 51% of facilities, TDCIPP dose estimates for children<6 years old exceeded age-specific "No Significant Risk Levels (NSRLs)" based on California Proposition 65 guidelines for carcinogens. Given the overriding interest in providing safe and healthy environments for young children, additional research is needed to identify strategies to reduce indoor sources of flame retardant chemicals.

Prometheus payment model: application to hip and knee replacement surgery.

The Prometheus Payment Model offers a potential solution to the failings of the current fee-for-service system and various forms of capitation. At the core of the Prometheus model are evidence-informed case rates (ECRs), which include a bundle of typical services that are informed by evidence and/or expert opinion as well as empirical data analysis, payment based on the severity of patients, and allowances for potentially avoidable complications (PACs) and other provider-specific variations in payer costs. We outline the methods and findings of the hip and knee arthroplasty ECRs with an emphasis on PACs. Of the 2076 commercially insured patients undergoing hip arthroplasty in our study, PAC costs totaled $7.8 million (14% of total costs; n = 699 index PAC stays). Similarly, PAC costs were $12.7 million (14% of total costs; n = 897 index PAC stays) for 3403 patients undergoing knee arthroplasty. By holding the providers clinically and financially responsible for PACs, and by segmenting and quantifying the type of PACs generated during and after the procedure, the Prometheus model creates an opportunity for providers to focus on the reduction of PACs, including readmissions, making the data actionable and turn the waste related to PAC costs into potential savings.

An anatomy ontology to represent biological knowledge in Dictyostelium discoideum.

BACKGROUND: Dictyostelium discoideum is a model system for studying many important physiological processes including chemotaxis, phagocytosis, and signal transduction. The recent sequencing of the genome has revealed the presence of over 12,500 protein-coding genes. The model organism database dictyBase hosts the genome sequence as well as a large amount of manually curated information. RESULTS: We present here an anatomy ontology for Dictyostelium based upon the life cycle of the organism. CONCLUSION: Anatomy ontologies are necessary to annotate species-specific events such as phenotypes, and the Dictyostelium anatomy ontology provides an essential tool for curation of the Dictyostelium genome.

Direct protein kinase C-dependent phosphorylation regulates the cell surface stability and activity of the potassium chloride cotransporter KCC2.

The potassium chloride cotransporter KCC2 plays a major role in the maintenance of transmembrane chloride potential in mature neurons; thus KCC2 activity is critical for hyperpolarizing membrane currents generated upon the activation of gamma-aminobutyric acid type A and glycine (Gly) receptors that underlie fast synaptic inhibition in the adult central nervous system. However, to date an understanding of the cellular mechanism that neurons use to modulate the functional expression of KCC2 remains rudimentary. Using Escherichia coli expression coupled with in vitro kinase assays, we first established that protein kinase C (PKC) can directly phosphorylate serine 940 (Ser(940)) within the C-terminal cytoplasmic domain of KCC2. We further demonstrated that Ser(940) is the major site for PKC-dependent phosphorylation for full-length KCC2 molecules when expressed in HEK-293 cells. Phosphorylation of Ser(940) increased the cell surface stability of KCC2 in this system by decreasing its rate of internalization from the plasma membrane. Coincident phosphorylation of Ser(940) increased the rate of ion transport by KCC2. It was further evident that phosphorylation of endogenous KCC2 in cultured hippocampal neurons is regulated by PKC-dependent activity. Moreover, in keeping with our recombinant studies, enhancing PKC-dependent phosphorylation increased the targeting of KCC2 to the neuronal cell surface. Our studies thus suggest that PKC-dependent phosphorylation of KCC2 may play a central role in modulating both the functional expression of this critical transporter in the brain and the strength of synaptic inhibition.

Economic feasibility of no-tillage and manure for soil carbon sequestration in corn production in northeastern Kansas.

This study examined the economic potential of no-tillage versus conventional tillage to sequester soil carbon by using two rates of commercial N fertilizer or beef cattle manure for continuous corn (Zea mays L.) production. Yields, input rates, field operations, and prices from an experiment were used to simulate a distribution of net returns for eight production systems. Carbon release values from direct, embodied, and feedstock energies were estimated for each system, and were used with soil carbon sequestration rates from soil tests to determine the amount of net carbon sequestered by each system. The values of carbon credits that provide an incentive for managers to adopt production systems that sequester carbon at greater rates were derived. No-till systems had greater annual soil carbon gains, net carbon gains, and net returns than conventional tillage systems. Systems that used beef cattle manure had greater soil carbon gains and net carbon gains, but lower net returns, than systems that used commercial N fertilizer. Carbon credits would be needed to encourage the use of manure-fertilized cropping systems.

Cation transport by the neuronal K(+)-Cl(-) cotransporter KCC2: thermodynamics and kinetics of alternate transport modes.

Both Cs(+) and NH(4)(+) alter neuronal Cl(-) homeostasis, yet the mechanisms have not been clearly elucidated. We hypothesized that these two cations altered the operation of the neuronal K(+)-Cl(-) cotransporter (KCC2). Using exogenously expressed KCC2 protein, we first examined the interaction of cations at the transport site of KCC2 by monitoring furosemide-sensitive (86)Rb(+) influx as a function of external Rb(+) concentration at different fixed external cation concentrations (Na(+), Li(+), K(+), Cs(+), and NH(4)(+)). Neither Na(+) nor Li(+) affected furosemide-sensitive (86)Rb(+) influx, indicating their inability to interact at the cation translocation site of KCC2. As expected for an enzyme that accepts Rb(+) and K(+) as alternate substrates, K(+) was a competitive inhibitor of Rb(+) transport by KCC2. Like K(+), both Cs(+) and NH(4)(+) behaved as competitive inhibitors of Rb(+) transport by KCC2, indicating their potential as transport substrates. Using ion chromatography to measure unidirectional Rb(+) and Cs(+) influxes, we determined that although KCC2 was capable of transporting Cs(+), it did so with a lower apparent affinity and maximal velocity compared with Rb(+). To assess NH(4)(+) transport by KCC2, we monitored intracellular pH (pH(i)) with a pH-sensitive fluorescent dye after an NH(4)(+)-induced alkaline load. Cells expressing KCC2 protein recovered pH(i) much more rapidly than untransfected cells, indicating that KCC2 can mediate net NH(4)(+) uptake. Consistent with KCC2-mediated NH(4)(+) transport, pH(i) recovery in KCC2-expressing cells could be inhibited by furosemide (200 microM) or removal of external [Cl(-)]. Thermodynamic and kinetic considerations of KCC2 operating in alternate transport modes can explain altered neuronal Cl(-) homeostasis in the presence of Cs(+) and NH(4)(+).

Fractionated stereotactic radiotherapy for acoustic neuromas: preservation of function versus size.

For larger acoustic neuromas the preservation of cranial nerve function following radiosurgery remains a challenge. Fractionated stereotactic radiotherapy (FSR) for acoustic neuromas offers both higher total tumour dose (Gy) and potential sparing of the facial motor, sensory and auditory cranial nerves. Eighty consecutive patients (45 M, 35 F) (age 56.8+/-1.7 years) received FSR for AN and have a median follow up of 1.1 years. A prospective schedule permitted increased fractionation vs. size. For FSR 70 patients having AN < 3.0 cm in diameter had 5 daily fractions of 5 Gy (25 Gy total) and 10 patients having AN > or = 3 cm had 10 daily fractions of 3 Gy (30 Gy total). All treatments were prescribed to the 80% isodose and given via the dedicated 10 MeV accelerator. For both the larger and smaller AN, the percentage decrease in volume was similar. No tumour increased in size, no patient developed facial weakness and hearing was preserved. Using size-dependent fractionation, FSR may result in both tumour control and preservation of normal cranial nerve functions for both large and small AN.

Fractionated stereotactic radiotherapy for acoustic neuromas.

Fractionated stereotactic radiotherapy (FSR) for acoustic neuromas offers both higher tumor dose and potential sparing of the facial and auditory cranial nerve functions. Eighty consecutive patients (45 males and 35 females; age 56.8 +/- 1.7 years) received FSR for acoustic neuromas and had a median follow-up of 2.9 years (range 2.3-6.5 years). For FSR, 70 patients had 5 daily fractions of 5 Gy (25 Gy total) and 10 patients had 10 daily fractions of 3 Gy (30 Gy total). Volume decreased by an average of 18%. No tumor increased in size, no patient developed facial weakness, and hearing was preserved.

Fractionated stereotactic radiotherapy for acoustic neuromas.

PURPOSE: When compared with radiosurgery, fractionated stereotactic radiotherapy for acoustic neuroma (AN) offers escalation of the tumor dose and potential sparing of auditory and facial nerve functions. METHODS AND MATERIALS: Between 1996 and 2001, 249 consecutive patients have received fractionated stereotactic radiotherapy for AN. One hundred twenty-five patients had follow-up >1 year and were the subject of this report. A noninvasive, repeat-fixation mask allowed simulation by way of spiral CT. Two distinct schedules for total dose and fractionation were used. For an AN <3.0 cm in diameter (volume 1.4 +/- 0.2 cm(3)), patients received 25 Gy given in 5 consecutive daily fractions of 5 Gy (111 patients), and for ANs >or=3.0 cm (volume 8.1 +/- 1.2 cm(3)), patients received 30 Gy given in 10 fractions of 3 Gy (14 patients). RESULTS: The percentage of decrease in tumor size was 12% +/- 2% (range 0-100%) vs. 13% +/- 3% (range 0-38%) for the 25 Gy vs. 30 Gy regimens, respectively. No patient had growth of the AN or developed facial weakness. Two patients developed transient decreases in facial sensation. The rates of hearing preservation were similar for the larger and smaller tumors. CONCLUSION: Fractionated stereotactic radiotherapy may preserve normal function and control both small and large ANs.