Beneficial and Harmful Effects of Monoclonal Antibodies for the Treatment and Prophylaxis of COVID-19: Systematic Review and Meta-Analysis.

BACKGROUND: We systematically assessed beneficial and harmful effects of monoclonal antibodies for coronavirus disease 2019 (COVID-19) treatment, and prophylaxis in individuals exposed to severe acute respiratory syndrome coronavirus 2. METHODS: We searched 5 engines and 3 registries until November 3, 2021 for randomized controlled trials evaluating monoclonal antibodies vs control in hospitalized or non-hospitalized adults with COVID-19, or as prophylaxis. Primary outcomes were all-cause mortality, COVID-19-related death, and serious adverse events; hospitalization for non-hospitalized; and development of symptomatic COVID-19 for prophylaxis. Inverse variance random effects models were used for meta-analyses. Grading of Recommendations, Assessment, Development, and Evaluations methodology was used to assess certainty of evidence. RESULTS: Twenty-seven randomized controlled trials were included: 20 in hospitalized patients (n = 8253), 5 in non-hospitalized patients (n = 2922), and 2 in prophylaxis (n = 2680). In hospitalized patients, monoclonal antibodies slightly reduced mechanical ventilation (relative risk [RR] 0.74; 95% confidence interval [CI], 0.60-0.9; I2 = 20%, low certainty of evidence) and bacteremia (RR 0.77; 95% CI, 0.64-0.92; I2 = 7%, low certainty of evidence); evidence was very uncertain about the effect on adverse events (RR 1.31; 95% CI, 1.02-1.67; I2 = 77%, very low certainty of evidence). In non-hospitalized patients, monoclonal antibodies reduced hospitalizations (RR 0.30; 95% CI, 0.17-0.53; I2 = 0%, high certainty of evidence) and may slightly reduce serious adverse events (RR 0.47; 95% CI, 0.22-1.01; I2 = 33%, low certainty of evidence). In prophylaxis studies, monoclonal antibodies probably reduced viral load slightly (mean difference -0.8 log10; 95% CI, -1.21 to -0.39, moderate certainty of evidence). There were no effects on other outcomes. CONCLUSIONS: Monoclonal antibodies had limited effects on most of the outcomes in COVID-19 patients, and when used as prophylaxis. Additional data are needed to determine their efficacy and safety.

Health Within Reach-a Patient-Centered Intervention to Increase Hepatitis B Screening Among Asian Americans: a Randomized Clinical Trial.

BACKGROUND: There are few studies to date of interventions to increase viral hepatitis screening among Asian Americans, who have high rates of chronic hepatitis B (HBV) infection. OBJECTIVE: To develop, implement, and test the efficacy of a mobile application (Hepatitis App) delivered in four languages to increase HBV screening among Asian Americans. DESIGN: Cluster-randomized clinical trial. PARTICIPANTS: Four hundred fifty-two Asian American patients ≥ 18 years of age, who had no prior HBV testing, and received primary care within two healthcare systems in San Francisco, CA. INTERVENTIONS: The intervention group received the Hepatitis App, delivering interactive video education on viral hepatitis in English, Cantonese, Mandarin, or Vietnamese and a provider printout (Provider Alert) and Provider Panel Notification. The comparison group received a mobile application delivering nutrition and physical activity education and Provider Panel Notification. MAIN MEASURES: Primary outcomes were patient-provider discussion about HBV and documentation of a HBV screening test within 3 months post-intervention. Secondary outcome was documentation of an order for a HBV screening test. KEY RESULTS: Participants had a mean age of 57 years and were 64% female, 80% foreign-born, and 44% with limited English fluency. At post-visit, over 80% of intervention participants reported they liked using the Hepatitis App. At 3-month follow-up, the intervention group was more likely than the comparison group (all P < 0.001) to have discussed HBV with their provider (70% vs.16%), have a HBV test ordered (44% vs.10%), and receive a HBV test (38% vs.8%). In multivariable analyses, the intervention odds ratio for HBV test ordering was 7.6 (95% CI: 3.9, 14.8) and test receipt was 7.5 (95% CI: 3.6, 15.5). CONCLUSIONS: A multi-lingual educational intervention using a mobile application in primary care clinics was well received by Asian American patients, enhanced patient-provider communication about HBV, and increased HBV screening. Technology can improve healthcare quality among Asian Americans. TRIAL REGISTRATION: ClinicalTrials.gov NCT02139722 ( https://clinicaltrials.gov/ct2/show/NCT02139722 ).

Propofol ameliorates acute postoperative fatigue and promotes glucagon-regulated hepatic gluconeogenesis by activating CREB/PGC-1α and accelerating fatty acids beta-oxidation.

Postoperative fatigue (POF) is the most common and long-lasting complication after surgery, which brings heavy burden to individuals and society. Recently, hastening postoperative recovery receives increasing attention, but unfortunately, the mechanisms underlying POF remain unclear. Propofol is a wildly used general anesthetic in clinic, and inspired by the rapid antidepressant effects induced by ketamine at non-anesthetic dose, the present study was undertaken to investigate the anti-fatigue effects and underlying mechanisms of propofol at a non-anesthetic dose in 70% hepatectomy induced POF model in rats. We first showed here that single administration of propofol at 0.1 mg/kg ameliorated acute POF in hepatectomy induced POF rats. Based on metabonomics analysis, we hypothesized that propofol exerted anti-fatigue activity in POF rats by facilitating free fatty acid (FFA) oxidation and gluconeogenesis. We further confirmed that propofol restored the deficit in FFA oxidation and gluconeogenesis in POF rats, as evidenced by the elevated FFA utilization, acetyl coenzyme A content, pyruvic acid content, phosphoenolpyruvic acid content, hepatic glucose output and glycogen storage. Moreover, propofol stimulated glucagon secretion and up-regulated expression of cAMP-response element binding protein (CREB), phosphorylated CREB, peroxlsome prolifeator-activated receptor-γ coactivator-1α (PGC-1α), phosphoenolpyruvate carboxykinade1 and carnitine palmitoltransferase 1A. In summary, our study suggests for the first time that propofol ameliorates acute POF by promoting glucagon-regulated gluconeogenesis via CREB/PGC-1α signaling and accelerating FFA beta-oxidation.

Sustainable bio-bricks prepared with synthetic urine enabled by biomineralization reactions.

In this study, mineralization during brick preparation was performed with ureolytic bacterium, Lysinibacillus fusiformis that use urine as a substrate, omitting the heat that is normally required. Artificial urine for reasons of standardization was used to grow the bacterium for bio-bricks made of clay and cement, but their mineralization was enabled by biological activity instead of by heat. Scanning electron microscopy and energy dispersion X-ray spectroscopy were conducted to analyse the microstructures formed by L. fusiformis that precipitated various minerals in synthetic urine. The brick specimens were tested for compressive strength that was 59% more than control ones, whereas porosity of bio-bricks was 13% compared to 22% of control specimens. The minerals formed in the bio-bricks confirmed as struvite, apatite and calcite by Fourier-transform infrared spectroscopy and X-ray diffraction spectra, were responsible for improved strength and reduced porosity. The research provided evidence in utilizing ureolytic bacteria as a mode to mineralize clay in brick production with the use of (artificial) urine as a substrate.

Efficacy and Safety of Hydroxychloroquine for Hospitalized COVID-19 Patients: A Systematic Review and Meta-Analysis.

We systematically reviewed the efficacy and safety of hydroxychloroquine as treatment for hospitalized COVID-19. Randomized controlled trials (RCTs) evaluating hydroxychloroquine as treatment for hospitalized COVID-19 patients were searched until 2nd of December 2020. Primary outcomes were all-cause mortality, need of mechanical ventilation, need of non-invasive ventilation, ICU admission and oxygen support at 14 and 30 days. Secondary outcomes were clinical recovery and worsening, discharge, radiological progression of pneumonia, virologic clearance, serious adverse events (SAE) and adverse events. Inverse variance random effects meta-analyses were performed. Thirteen RCTs (n=18,540) were included. Hydroxychloroquine total doses ranged between 2000 and 12,400 mg; treatment durations were from 5 to 16 days and follow up times between 5 and 30 days. Compared to controls, hydroxychloroquine non-significantly increased mortality at 14 days (RR 1.07, 95%CI 0.92-1.25) or 30 days (RR 1.08, 95%CI 1.00-1.16). Hydroxychloroquine did not affect other primary or secondary outcomes, except SAEs that were significantly higher than the control (RR 1.24, 95%CI 1.05-1.46). Eleven RCTs had high or some concerns of bias. Subgroup analyses were consistent with main analyses. Hydroxychloroquine was not efficacious for treating hospitalized COVID-19 patients and caused more severe adverse events. Hydroxychloroquine should not be recommended as treatment for hospitalized COVID-19 patients.

Renal Denervation for Uncontrolled and Resistant Hypertension: Systematic Review and Network Meta-Analysis of Randomized Trials.

Comparative efficacy and safety of renal denervation (RDN) interventions for uncontrolled (UH) and resistant hypertension (RH) is unknown. We assessed the comparative efficacy and safety of existing RDN interventions for UH and RH. Six search engines were searched up to 1 May 2020. Primary outcomes were mean 24-h ambulatory and office systolic blood pressure (SBP). Secondary outcomes were mean 24-h ambulatory and office diastolic blood pressure (DBP), clinical outcomes, and serious adverse events. Frequentist random-effects network meta-analyses were used to evaluate effects of RDN interventions. Twenty randomized controlled trials (RCTs) (n = 2152) were included, 15 in RH (n = 1544) and five in UH (n = 608). Intervention arms included radiofrequency (RF) in main renal artery (MRA) (n = 10), RF in MRA and branches (n = 4), RF in MRA+ antihypertensive therapy (AHT) (n = 5), ultrasound (US) in MRA (n = 3), sham (n = 8), and AHT (n = 9). RF in MRA and branches ranked as the best treatment to reduce 24-h ambulatory, daytime, and nighttime SBP and DBP versus other interventions (p-scores: 0.83 to 0.97); significant blood pressure effects were found versus sham or AHT. RF in MRA+AHT was the best treatment to reduce office SBP and DBP (p-scores: 0.84 and 0.90, respectively). RF in MRA and branches was the most efficacious versus other interventions to reduce 24-h ambulatory SBP and DBP in UH or RH.

Protective effects of dietary fish-oil supplementation on skin inflammatory and oxidative stress biomarkers induced by fine particulate air pollution: a pilot randomized, double-blind, placebo-controlled trial.

BACKGROUND: Exposure to fine particulate matter (with an aerodynamic diameter ≤ 2·5 µm, PM2·5 ) air pollution has been associated with skin-related diseases or disorders. OBJECTIVES: To evaluate the potential skin-protective effects of fish-oil supplementation against PM2·5 exposure. MATERIALS AND METHODS: This is an exploratory analysis based on a pilot randomized, double-blind, placebo-controlled trial among 65 healthy young adults between September 2017 and January 2018 in Shanghai, China. We randomly assigned participants to take either fish oil or placebo 2·5 g daily for four consecutive months. Four rounds of skin D-Squame® tape samples were collected in the last 2 months, and five secondary biomarkers of skin inflammation and oxidative stress were measured. Fixed-site PM2·5 concentrations on campus were measured in real time. We used linear mixed-effect models to analyse the associations between short-term PM2·5 exposure and biomarkers in each group. RESULTS: The 24-h average PM2·5 concentration was 34·68 ± 15·83 µg m-3 . There were generally weaker associations between PM2·5 and biomarkers in the fish-oil group than in the placebo group, but the associations and the between-group differences varied by biomarkers and lag periods. Compared with the placebo group, for a 10-µg m-3 increase in PM2·5 concentration, the increments of interleukin-1α and carbonyl protein in the fish-oil group were 41·55% smaller [95% confidence interval (CI) 4·61-78·48%] at lag 0-48 h and 22·01% smaller (95% CI 11·25-32·77%) at lag 0-24 h, respectively. No significant between-group differences were observed for other biomarkers. CONCLUSIONS: This study suggested that dietary fish-oil supplementation may improve biomarkers of skin inflammation and oxidative-stress response to short-term PM2·5 exposure.

Natural Photosensitizers in Constructed Unit Process Wetlands: Photochemical Characterization and Inactivation of Pathogen Indicator Organisms.

Dissolved organic matter (DOM) is a natural photosensitizer that contributes to the inactivation of microbial pathogens. In constructed treatment wetlands with open water areas DOM can promote sunlight disinfection of wastewater effluent, but a better understanding of DOM spectroscopic and photochemical properties and how they are impacted by different unit process wetlands is needed to inform design. The goals of this study were: (1) to investigate whether DOM isolates realistically represent the photochemistry of the source DOM in its original water and (2) to observe how changes of DOM along a treatment wetland affect its photochemistry, including pathogen inactivation. A pilot scale unit process wetland was studied that consisted of three different cells (open water, cattail, and bulrush) fed by secondary wastewater effluent. DOM was isolated using solid-phase extraction (SPE), photochemically characterized, and compared to the original water samples and standard DOMs. For MS2 coliphage, a virus indicator, the most efficient photosensitizer was the wastewater DOM isolated from the influent of the wetland, while for the bacterial indicator Enterococcus faecalis, inactivation results were comparable across wetland isolates. SPE resulted in isolation of 47% to 59% of whole water DOM and enriched for colored DOM. Singlet oxygen precursors were efficiently isolated, while some excited triplet state precursors remained in the extraction discharge. DOM processing indicators such as SUVA254, SUVA280, and spectral slopes including E2/ E3 ratios were reflected in the isolates. Photoinactivation of MS2 was significantly lower in both the reconstituted water samples and isolates compared to the original water sample, possibly due to disturbance of the trans-molecular integrity of DOM molecules by SPE that affects distance between MS2 and DOM sites with locally higher singlet oxygen production. For E. faecalis, results were similar in original water samples and isolates. Higher sorption of DOM to E. faecalis was roughly correlated with higher photoinactivation rates. To enhance sunlight disinfection in unit process wetlands, there is no advantage to placing open water cells after vegetated cells, as passage through the vegetated cells led to increased light absorption and lower singlet oxygen and triplet-state quantum yields and steady state concentrations.

Colorectal cancer beliefs, knowledge, and screening among Filipino, Hmong, and Korean Americans.

BACKGROUND: To the authors' knowledge, there are few studies to date regarding colorectal cancer (CRC) beliefs, knowledge, and screening among multiple Asian American populations, who are reported to have lower CRC screening rates compared with white individuals. The current study was performed to assess knowledge and beliefs regarding the causes of CRC, its prevention, and factors associated with CRC screening among 3 Asian American groups. METHODS: The authors conducted an in-language survey with Filipino (Honolulu, Hawaii), Hmong (Sacramento, California), and Korean (Los Angeles, California) Americans aged 50 to 75 years who were sampled through social networks. Bivariate and multivariable analyses were conducted to assess factors associated with CRC screening. RESULTS: The sample of 981 participants was 78.3% female and 73.8% reported limited proficiency in English. Few of the participants were aware that age (17.7%) or family history (36.3%) were risk factors for CRC; 6.2% believed fate caused CRC. Only 46.4% of participants knew that screening prevented CRC (74.3% of Filipino, 10.6% of Hmong, and 55.8% of Korean participants; P<.001). Approximately two-thirds of participants reported ever having undergone CRC screening (76.0% of Filipino, 72.0% of Hmong, and 51.4% of Korean participants; P<.001) and 48.6% were up to date for screening (62.2% of Filipino, 43.8% of Hmong, and 41.4% of Korean participants; P<.001). Factors found to be significantly associated with ever screening were being Korean (compared with Filipino), having a family history of CRC, having health insurance or a regular source of health care, and knowing that a fatty diet caused CRC. Believing that fate caused CRC and that praying prevented it were found to be negatively associated with ever screening. Factors associated with being up to date for CRC screening included being born in the United States, having a family history of CRC, and having access to health care. CONCLUSIONS: Knowledge regarding the causes of CRC and its prevention among Filipino, Hmong, and Korean individuals is low. However, health care access, not knowledge or beliefs, was found to be a key determinant of CRC screening. Cancer 2018;124:1552-9. © 2018 American Cancer Society.

Controlling Bacterial Pathogens in Water for Reuse: Treatment Technologies for Water Recirculation in the Blue Diversion Autarky Toilet.

The Blue Diversion AUTARKY Toilet is a urine-diverting toilet with on-site treatment. The toilet is being developed to provide a safe and affordable sanitation technology for people who lack access to sewer-based sanitation. Water used for personal hygiene, hand washing, and flushing to rinse urine- and feces-collection bowls is treated, stored, and recycled for reuse to reduce reliance on external water supplies. The system provides an opportunity to investigate hygiene of water for reuse following treatment. Treatment in the toilet includes a Biologically Activated Membrane Bioreactor (BAMBi) followed by a secondary treatment technology. To identify effective secondary treatment, three options, including granular activated carbon (GAC) only, GAC+chlorine (sodium hypochlorite), and GAC+electrolysis are considered based on the bacterial inactivation and growth inhibition efficiency. Four different hygiene-relevant bacteria are tested: Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa, and Salmonella typhimurium. Our evaluation demonstrates that-despite treatment of water with the BAMBi-E. coli, P aeruginosa, and S. typhimurium have the potential to grow during storage in the absence of microbial competition. Including the indigenous microbial community influences bacterial growth in different ways: E. coli growth decreases but P. aeruginosa growth increases relative to no competition. The addition of the secondary treatment options considerably improves water quality. A column of GAC after the BAMBi reduces E. coli growth potential by 2 log10, likely due to the reduction of carbon sources. Additional treatments including chlorination and electrolysis provide further safety margins, with more than 5 log-10 inactivation of E. coli. However, reactivation and/or regrowth of E. coli and P. aeruginosa occurs under in the absence of residual disinfectant. Treatment including the BAMBi, GAC, and electrolysis appear to be promising technologies to control bacterial growth during storage in water intended for reuse.

Lay health educators increase colorectal cancer screening among Hmong Americans: A cluster randomized controlled trial.

BACKGROUND: Asian Americans have lower colorectal cancer (CRC) screening rates than non-Hispanic white individuals. Hmong Americans have limited socioeconomic resources and literacy. The current randomized controlled trial was conducted to determine whether bilingual/bicultural lay health educator (LHE) education could increase CRC screening among Hmong Americans. METHODS: A cluster randomized controlled trial was conducted among Hmong Americans in Sacramento, California. LHEs and recruited participants were randomized to intervention or control groups. The intervention group received CRC education over 3 months delivered by an LHE. The control group received education regarding nutrition and physical activity delivered by a health educator. The outcomes were changes in self-reported ever-screening and up-to-date CRC screening after 6 months. RESULTS: All 329 participants were foreign-born with mostly no formal education, limited English proficiency, and no employment. The majority of the participants were insured and had a regular source of health care. The intervention group experienced greater changes after the intervention than the control group for ever-screening (P = .068) and being up-to-date with screening (P<.0001). In multivariable regression analyses, the intervention group demonstrated a greater increase than the control group in reporting ever-screening (adjusted odds ratio, 1.73; 95% confidence interval, 1.07-2.79) and being up-to-date with screening (adjusted odds ratio, 1.71; 95% confidence interval, 1.26-2.32). Individuals who had health insurance were found to have >4 times the odds of receiving screening, both ever-screening and up-to-date screening. A higher CRC knowledge score mediated the intervention effect for both screening outcomes. CONCLUSIONS: A culturally and linguistically appropriate educational intervention delivered by trained LHEs was found to increase CRC screening in an immigrant population with low levels of education, employment, English proficiency, and literacy. Cancer 2017;98-106. © 2016 American Cancer Society.

Elimination of microglia improves cognitive function following cranial irradiation.

Cranial irradiation for the treatment of brain cancer elicits progressive and severe cognitive dysfunction that is associated with significant neuropathology. Radiation injury in the CNS has been linked to persistent microglial activation, and we find upregulation of pro-inflammatory genes even 6 weeks after irradiation. We hypothesize that depletion of microglia in the irradiated brain would have a neuroprotective effect. Adult mice received acute head only irradiation (9 Gy) and were administered a dietary inhibitor (PLX5622) of colony stimulating factor-1 receptor (CSF1R) to deplete microglia post-irradiation. Cohorts of mice maintained on a normal and PLX5662 diet were analyzed for cognitive changes using a battery of behavioral tasks 4-6 weeks later. PLX5622 treatment caused a rapid and near complete elimination of microglia in the brain within 3 days of treatment. Irradiation of animals given a normal diet caused characteristic behavioral deficits designed to test medial pre-frontal cortex (mPFC) and hippocampal learning and memory and caused increased microglial activation. Animals receiving the PLX5622 diet exhibited no radiation-induced cognitive deficits, and exhibited near complete loss of IBA-1 and CD68 positive microglia in the mPFC and hippocampus. Our data demonstrate that elimination of microglia through CSF1R inhibition can ameliorate radiation-induced cognitive deficits in mice.

[Characteristics of cognitive impairment of different infarct locations among patients after acute ischemic stroke].

OBJECTIVE: To investigate the characteristics of cognitive function changes of different infarct sites among patients after acute ischemic stroke, so as to provide theoretical basis for preventing and treating vascular cognitive dysfunction. METHODS: One hundred and five cases of acute ischemic stroke within fourteen days meeting the standard set were enrolled, and they were tested by Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). And the characteristics of cognitive changes with different infarction sites were analyzed. RESULTS: Patients with acute stroke suffered cognitive impairment.The significantly impaired cognitive domains in MMSE were: graphics execution in patients with left hemisphere infarction (P=0.027); verbal repetition in frontal infarction (P=0.003); short memory (P=0.04) and verbal repetition (P=0.007) in parietal infarction.The significantly impaired cognitive domains in MoCA were: language (P=0.002), naming (P=0.011), attention (P=0.028) and time orientation (P=0.031) in frontal infarction; delayed memory (P<0.001), attention (P=0.041), language (P=0.049) and visual space and executive ability (P=0.049) in parietal infarction; attention in temporal infarction (P=0.045); language (P=0.009) and time orientation (P=0.026) in basal ganglia region infarction. CONCLUSION: Most ischemic stroke patients at acute phase suffered cognitive impairment and the characteristics of cognitive changes differed according to different infarction sites.Comprehensive assessment of cognitive impairment after acute stroke is of great importance.

Life-Cycle Energy Use and Greenhouse Gas Emissions of a Building-Scale Wastewater Treatment and Nonpotable Reuse System.

Treatment and water reuse in decentralized systems is envisioned to play a greater role in our future urban water infrastructure due to growing populations and uncertainty in quality and quantity of traditional water resources. In this study, we utilized life-cycle assessment (LCA) to analyze the energy consumption and greenhouse gas (GHG) emissions of an operating Living Machine (LM) wetland treatment system that recycles wastewater in an office building. The study also assessed the performance of the local utility's centralized wastewater treatment plant, which was found to be significantly more efficient than the LM (79% less energy, 98% less GHG emissions per volume treated). To create a functionally equivalent comparison, the study developed a hypothetical scenario in which the same LM design flow is recycled via centralized infrastructure. This comparison revealed that the current LM has energy consumption advantages (8% less), and a theoretically improved LM design could have GHG advantages (24% less) over the centralized reuse system. The methodology in this study can be applied to other case studies and scenarios to identify conditions under which decentralized water reuse can lower GHG emissions and energy use compared to centralized water reuse when selecting alternative approaches to meet growing water demands.

Sunlight inactivation of fecal indicator bacteria in open-water unit process treatment wetlands: Modeling endogenous and exogenous inactivation rates.

A pilot-scale open-water unit process wetland was monitored for one year and found to be effective in enhancing sunlight inactivation of fecal indicator bacteria (FIB). The removal of Escherichia coli and enterococci in the open-water wetland receiving non-disinfected secondary municipal wastewater reached 3 logs and 2 logs in summer time, respectively. Pigmented enterococci were shown to be significantly more resistant to sunlight inactivation than non-pigmented enterococci. A model was developed to predict the inactivation of E. coli, and pigmented and non-pigmented enterococci that accounts for endogenous and exogenous sunlight inactivation mechanisms and dark processes. Endogenous inactivation rates were modeled using the sum of UVA and UVB irradiance. Exogenous inactivation was only significant for enterococci, and was modeled as a function of steady-state singlet oxygen concentration. The rate constants were determined from lab experiments and an empirical correction factor was used to account for differences between lab and field conditions. The model was used to predict removal rate constants for FIB in the pilot-scale wetland; considering the variability of the monitoring data, there was general agreement between the modeled values and those determined from measurements. Using the model, we estimate that open-water wetlands at 40° latitude with practical sizes can achieve 3-log (99.9%) removal of E. coli and non-pigmented enterococci throughout the year [5.5 ha and 7.0 ha per million gallons of wastewater effluent per day (MGD), respectively]. Differences in sunlight inactivation rates observed between pigmented and non-pigmented enterococci, as well as between lab-cultured and indigenous wastewater bacteria highlight the challenges of using FIB as model organisms for actual pathogens in natural sunlit environments.

Sunlight inactivation of viruses in open-water unit process treatment wetlands: modeling endogenous and exogenous inactivation rates.

Sunlight inactivation is an important mode of disinfection for viruses in surface waters. In constructed wetlands, for example, open-water cells can be used to promote sunlight disinfection and remove pathogenic viruses from wastewater. To aid in the design of these systems, we developed predictive models of virus attenuation that account for endogenous and exogenous sunlight-mediated inactivation mechanisms. Inactivation rate models were developed for two viruses, MS2 and poliovirus type 3; laboratory- and field-scale experiments were conducted to evaluate the models' ability to estimate inactivation rates in a pilot-scale, open-water, unit-process wetland cell. Endogenous inactivation rates were modeled using either photoaction spectra or total, incident UVB irradiance. Exogenous inactivation rates were modeled on the basis of virus susceptibilities to singlet oxygen. Results from both laboratory- and field-scale experiments showed good agreement between measured and modeled inactivation rates. The modeling approach presented here can be applied to any sunlit surface water and utilizes easily measured inputs such as depth, solar irradiance, water matrix absorbance, singlet oxygen concentration, and the virus-specific apparent second-order rate constant with singlet oxygen (k2). Interestingly, the MS2 k2 in the open-water wetland was found to be significantly larger than k2 observed in other waters in previous studies. Examples of how the model can be used to design and optimize natural treatment systems for virus inactivation are provided.

Sunlight inactivation of MS2 coliphage in the absence of photosensitizers: modeling the endogenous inactivation rate using a photoaction spectrum.

The endogenous sunlight inactivation rates of MS2 coliphage in photosensitizer-free water were measured (kobs) under different light conditions and compared to modeled inactivation rates (kmod) computed using a previously published action spectrum. Experiments were conducted under simulated and natural sunlight. There was generally good agreement between modeled and observed MS2 sunlight inactivation rates in the summer and winter, suggesting that the action spectrum can be used to predict changes in the inactivation rate caused by diurnal and seasonal changes in natural sunlight irradiance. However, we show that a major source of uncertainty in the predictions is the ability to accurately measure or model the comparatively weak and highly variable solar irradiance between 280 and 300 nm, a range to which the inactivation rate is very sensitive. The action spectrum was also used to predict the endogenous inactivation rates of MS2 at different depths in a column of strongly humic-colored [i.e., solar ultraviolet (UV)-attenuating] wetland water under simulated sunlight; we observed fairly good agreement between kobs and kmod, suggesting that the action spectrum can be used to estimate the decrease in the endogenous inactivation rate caused by spectrally selective sunlight attenuation in the water column.

Multiple abnormalities due to a nonsense mutation in the Alx4 gene.

Patterning of the limb anterior-posterior axes depends on several signals that derive from the three signaling centers of the limb bud. These signals interact to constitute a complex and ordered network that critically contributes to the development of limb buds. Preaxial polydactyly in mouse is predominantly caused by ectopic expression of the zone of polarizing activity or Sonic hedgehog in the anterior region of the limb bud. In this study, we describe an N-ethyl-N-nitrosourea-induced polydactylous mouse (Alx4m1Yzcm) with an extra digit on the anterior aspect of one or two hinddigits. The mutation was mapped to chromosome 2, between markers D2Mit45 and D2Mit184. The Alx4 gene was identified as a potential candidate gene in this location. Sequence analysis of the Alx4 gene for polydactylous heterozygotes revealed an A/T transversion mutation that resulted in substitution of a lysine codon with a stop (nonsense) codon at position 145. Alx4m1Yzcm homozygous mice exhibited multiple abnormalities, including extensive preaxial polydactyly of all four limbs (up to seven digits) and the formation of omphalocele.

Unit Process Wetlands for Removal of Trace Organic Contaminants and Pathogens from Municipal Wastewater Effluents.

Treatment wetlands have become an attractive option for the removal of nutrients from municipal wastewater effluents due to their low energy requirements and operational costs, as well as the ancillary benefits they provide, including creating aesthetically appealing spaces and wildlife habitats. Treatment wetlands also hold promise as a means of removing other wastewater-derived contaminants, such as trace organic contaminants and pathogens. However, concerns about variations in treatment efficacy of these pollutants, coupled with an incomplete mechanistic understanding of their removal in wetlands, hinder the widespread adoption of constructed wetlands for these two classes of contaminants. A better understanding is needed so that wetlands as a unit process can be designed for their removal, with individual wetland cells optimized for the removal of specific contaminants, and connected in series or integrated with other engineered or natural treatment processes. In this article, removal mechanisms of trace organic contaminants and pathogens are reviewed, including sorption and sedimentation, biotransformation and predation, photolysis and photoinactivation, and remaining knowledge gaps are identified. In addition, suggestions are provided for how these treatment mechanisms can be enhanced in commonly employed unit process wetland cells or how they might be harnessed in novel unit process cells. It is hoped that application of the unit process concept to a wider range of contaminants will lead to more widespread application of wetland treatment trains as components of urban water infrastructure in the United States and around the globe.

Stem cell plasticity in muscle and bone marrow.

Recent discoveries have demonstrated the extraordinary plasticity of tissue-derived stem cells, raising fundamental questions about cell lineage relationships and suggesting the potential for novel cell-based therapies. We have examined this phenomenon in a potential reciprocal relationship between stem cells derived from the skeletal muscle and from the bone marrow. We have discovered that cells derived from the skeletal muscle of adult mice contain a remarkable capacity for hematopoietic differentiation. Cells prepared from muscle by enzymatic digestion and 5 day in vitro culture were harvested and introduced into each of six lethally irradiated recipients together with distinguishable whole bone marrow cells. Six and twelve weeks later, all recipients showed high-level engraftment of muscle-derived cells representing all major adult blood lineages. The mean total contribution of muscle cell progeny to peripheral blood was 56%, indicating that the cultured muscle cells generated approximately 10- to 14-fold more hematopoietic activity than whole bone marrow. Although the identity of the muscle-derived hematopoietic stem cells is still unknown, they may be identical to muscle satellite cells, some of which lack myogenic regulators and could respond to hematopoietic signals. We have also found that stem cells in the bone marrow can contribute to cardiac muscle repair and neovascularization after ischemic injury. We transplanted highly purified bone marrow stem cells into lethally irradiated mice that subsequently were rendered ischemic by coronary artery occlusion and reperfusion. The engrafted stem cells or their progeny differentiated into cardiomyocytes and endothelial cells and contributed to the formation of functional tissue.