Search

Abstract Background The aim of this study was to increase the accessibility and accelerate the breakdown of lignocellulosic biomass to methane in an anaerobic fermentation system by mechanical cotreatment: milling during fermentation, as an alternative to conventional pretreatment prior to biological deconstruction. Effluent from a mesophilic anaerobic digester running with unpretreated senescent switchgrass as the predominant carbon source was collected and subjected to ball milling for 0.5, 2, 5 and 10 min. Following this, a batch fermentation test was conducted with this material in triplicate for an additional 18 days with unmilled effluent as the ‘status quo’ control. Results The results indicate 0.5 – 10 min of cotreatment increased sugar solubilization by 5– 13% when compared to the unmilled control, with greater solubilization correlated with increased milling duration. Biogas concentrations ranged from 44% to 55.5% methane with the balance carbon dioxide. The total biogas production was statistically higher than the unmilled control for all treatments with 2 or more minutes of milling (α = 0.1). Cotreatment also decreased mean particle size. Energy consumption measurements of a lab-scale mill indicate that longer durations of milling offer diminishing benefits with respect to additional methane production. Conclusions Cotreatment in anaerobic digestion systems, as demonstrated in this study, provides an alternative approach to conventional pretreatments to increase biogas production from lignocellulosic grassy material.

Interprofessional collaboration among speech-language pathology, physical therapy, and occupational therapy is considered to promote best practice in rehabilitation as it can enhance efficiency, patient outcomes, and clinician and patient satisfaction. Although clinician experiences with interprofessional collaboration have been studied in each of the rehabilitation professions separately, limited research has been conducted on the shared attitudes or experiences across speech-language pathology, physical therapy, and occupational therapy. The purpose of this study was to understand speech-language pathologist, physical therapist, and occupational therapist experiences of interprofessional collaborations. We conducted an exploratory cross-sectional online survey study. The survey included Likert-scale questions and open-ended questions that probed clinicians' general experiences with interprofessional practice and views and beliefs regarding barriers and facilitators to interprofessional collaboration. Responses from 213 clinician respondents were analyzed using descriptive quantitative methods and a qualitative content analysis. The results revealed overlap in attitudes and experiences across speech-language pathology, physical therapy, and occupational therapy about barriers and benefits to interprofessional collaboration. Perceived respect differed among the professions, with speech-language pathologists more frequently reporting that their role is often misunderstood or undervalued by other rehabilitation professionals. These results may guide future research focused upon the predictors of successful interprofessional collaborations and interactions. [ABSTRACT FROM AUTHOR]

BACKGROUND: The recalcitrance of cellulosic biomass is widely recognized as a key barrier to cost-effective biological processing to fuels and chemicals, but the relative impacts of physical, chemical and genetic interventions to improve biomass processing singly and in combination have yet to be evaluated systematically. Solubilization of plant cell walls can be enhanced by non-biological augmentation including physical cotreatment and thermochemical pretreatment, the choice of biocatalyst, the choice of plant feedstock, genetic engineering of plants, and choosing feedstocks that are less recalcitrant natural variants. A two-tiered combinatoric investigation of lignocellulosic biomass deconstruction was undertaken with three biocatalysts (Clostridium thermocellum, Caldicellulosiruptor bescii, Novozymes Cellic® Ctec2 and Htec2), three transgenic switchgrass plant lines (COMT, MYB4, GAUT4) and their respective nontransgenic controls, two Populus natural variants, and augmentation of biological attack using either mechanical cotreatment or cosolvent-enhanced lignocellulosic fractionation (CELF) pretreatment. RESULTS: In the absence of augmentation and under the conditions tested, increased total carbohydrate solubilization (TCS) was observed for 8 of the 9 combinations of switchgrass modifications and biocatalysts tested, and statistically significant for five of the combinations. Our results indicate that recalcitrance is not a trait determined by the feedstock only, but instead is coequally determined by the choice of biocatalyst. TCS with C. thermocellum was significantly higher than with the other two biocatalysts. Both CELF pretreatment and cotreatment via continuous ball milling enabled TCS in excess of 90%. CONCLUSION: Based on our results as well as literature studies, it appears that some form of non-biological augmentation will likely be necessary for the foreseeable future to achieve high TCS for most cellulosic feedstocks. However, our results show that this need not necessarily involve thermochemical processing, and need not necessarily occur prior to biological conversion. Under the conditions tested, the relative magnitude of TCS increase was augmentation > biocatalyst choice > plant choice > plant modification > plant natural variants. In the presence of augmentation, plant modification, plant natural variation, and plant choice exhibited a small, statistically non-significant impact on TCS.

[Display omitted] • Non-treated sugarcane bagasse can be solubilized by Clostridium thermocellum. • Cotreatment led to a 1.8-fold increase in total carbohydrate solubilization. • Thermoanaerobacterium thermosaccharolyticum can withstand cotreatment conditions. • Coculturing and cotreatment increased overall product formation by 2-fold. • The hemicellulose fractional solubilization was higher under cotreatment conditions. Cotreatment, mechanical disruption of lignocellulosic biomass during microbial fermentation, is a potential alternative to thermochemical pretreatment as a means of increasing the accessibility of lignocellulose to biological attack. Successful implementation of cotreatment requires microbes that can withstand milling, while solubilizing and utilizing carbohydrates from lignocellulose. In this context, cotreatment with thermophilic, lignocellulose-fermenting bacteria has been successfully evaluated for a number of lignocellulosic feedstocks. Here, cotreatment was applied to sugarcane bagasse using monocultures of the cellulose-fermenting Clostridium thermocellum and cocultures with the hemicellulose-fermenting Thermoanaerobacterium thermosaccharolyticum. This resulted in 76 % carbohydrate solubilization (a 1.8-fold increase over non-cotreated controls) on 10 g/L solids loading, having greater effect on the hemicellulose fraction. With cotreatment, fermentation by wild-type cultures at low substrate concentrations increased cumulative product formation by 45 % for the monoculture and 32 % for the coculture. These findings highlight the potential of cotreatment for enhancing deconstruction of sugarcane bagasse using thermophilic bacteria. [ABSTRACT FROM AUTHOR]

Objective: Renal toxicity and ototoxicity are considered as the main side effects of aminoglycoside antibiotics, such as gentamicin. The present study aimed to investigate the effect of co-treatment by origanum vulgare extract on the gentamicin-induced renal toxicity. Methods: Adult male Wistar rats in the weight range of 200 to 250 grams were randomly assigned into four groups (n = 8): control, renal toxicity (with the intraperitoneal injection of gentamicin [100 mg/kg/day], for eight days), co-treatment with OV extract and gentamicin vehicle (with the intraperitoneal injection of normal saline and OV extract gavage [40 mg/kg], for eight days), co-treatment with OV ethanolic extract (with the intraperitoneal injection of gentamicin [100 mg/kg/day] and OV extract gavage [40 mg/kg]), for eight days. The amount of urea, creatinine, sodium, potassium, and osmolality were measured in the plasma and urine samples. The left kidney was used for the histological study and the right kidney was used to measure MDA and FRAP. Results: treatment with OV ethanolic extract significantly decreased the blood concentrations of creatinine, urea, the absolute excretion of sodium, the fractional excretion of sodium and potassium, and MDA, compared with the renal toxicity group. Besides, co-treatment with ethanolic extract of origanum Vulgare significantly increased creatinine clearance, urinary osmolality, and FRAP, compared with the renal toxicity group. Conclusion: The oral co-treatment with ethanolic extract of origanum vulgare has a protective effect on gentamicin-induced renal toxicity. This effect can be induced by reducing the oxidative stress caused by free radicals and reducing the amount of lipid peroxidation caused by gentamicin.

Objective: Effects of cotreatment with Urtica dioica (UD) methanolic leaf extract on gentamicin (GM)-induced acute kidney injury were evaluated in rats. Materials and Methods: Male Wistar rats (n=32) were separated into four groups. Gentamicin (100 mg/kg/day, IP) was injected for eight days with or without UD methanolic extract (200 mg/kg/day, gavage). The renal blood flow (RBF) and systolic blood pressure of rats were recorded. Concentration of creatinine, blood urea nitrogen (BUN), sodium, and potassium and osmolarity were measured in the urine and plasma samples. Oxidative stress level was determined by assessment of the levels of antioxidant power (FRAP) and lipid peroxidation (MDA) in the renal tissue. The renal injury and histopathological changes in the kidney were determined by microscopic evaluations. Results: Administration of UD extract along with GM, compared to GM group, significantly decreased the amounts of plasma creatinine and BUN, urinary sodium excretion, fractional excretion of sodium and potassium, and MDA levels but significantly increased creatinine clearance, urine osmolarity, renal blood flow and FRAP levels. Conclusion: The cotreatment of UD extract can attenuate renal injury of GM by reduction of oxidative stress, lipid peroxidation, and oxygen free radicals. The potential nephroprotective effects of UD extract are probably mediated via its antioxidant and anti-inflammatory activity.

: Mobility and speech-language impairments and limitations in adults with neurological conditions manifest not in isolated anatomical components but instead in the individual-environment system and are task-dependent. Optimization of function thus requires interprofessional care to promote participation in meaningful life areas within appropriate task and environmental contexts. Cotreatment guidelines (ie, the concurrent intervention of disciplines) were established by the physical therapy, occupational therapy, and speech-language and hearing professional organizations nearly 2 decades ago to facilitate seamless interprofessional care. Despite this, cotreatment between physical therapy and speech therapy remains limited. The purpose of this Perspective article is to encourage physical therapists and speech-language pathologists to increase interprofessional collaboration through cotreatment in the management of adults with neurological conditions. Evidence from pediatrics and basic motor control literature points toward reciprocal interactions between speech-language and mobility. We provide recommendations for clinical practice with an emphasis on the gains each discipline can provide the other. This Perspective is rooted in the International Classification of Functioning, Disability and Health model and ecological theory. Impact: The goals of speech therapy and physical therapy are complementary and mutually supportive. Enhanced cotreatment, and collaboration more generally, between physical therapists and speech-language pathologists in the management of adults with neurological conditions can augment task-relevant conditions to improve function. [ABSTRACT FROM AUTHOR]

Wastewater and landfill leachate treatment processes have the potential to generate nitrous oxide (N 2 O) and methane (CH 4), both significant greenhouse gases (GHG). However, little is known about these emissions when a combined treatment approach (wastewater with leachate) is utilized. This study aimed to assess the emissions of these gases and nutrient removal in an anaerobic/aerobic/anoxic sequencing batch reactor (SBR) employed for treating wastewater with landfill leachate (1% v/v). Leachate contributes significantly to the removal of organic matter and nutrients, primarily phosphorus. The production and emission of N 2 O occurred during the aerobic phase, whereas CH 4 was produced in the anaerobic and anoxic phases. This gas was emitted at the beginning of the aerobic phase and in the end of anoxic phase. The emission factors obtained in this work were 0.0108 and 0.0119 kg N 2 O-N per kg TN influent and 0.000225 and 0.000253 kg CH 4 -C per kg COD influent with and without landfill leachate, respectively. Regarding CO 2 -equivalent, the N 2 O was the major contributor, accounting for 99% of the emitted GHG by the process. Further studies are required; however, the main findings of this study suggest that this system may be appropriate when lower GHG emissions are required. [Display omitted] • The performance of anaerobic/aerobic/anoxic SBR was not impacted by adding of 1% leachate into wastewater. • The introduction of leachate increased significantly the N 2 O production and emissions. • CH 4 production and emission were similar in two experiments (processes with and without leachate). • N 2 O was the major contributor to CO 2 -equivalent emissions (90%) in two experiments. • Emission factors from these two systems were lower than those cited by the IPCC protocols. [ABSTRACT FROM AUTHOR]

Background Chronic infection by Staphylococcus aureus drives pathogenesis in important clinical settings, such as recurrent pulmonary infection in cystic fibrosis and relapsing infection in osteomyelitis. Treatment options for intracellular S. aureus infection are limited. Rifampin, a lipophilic antibiotic, readily penetrates host cell membranes, yet monotherapy is associated with rapid antibiotic resistance and development of severe adverse events. Antibiotic cotreatment can reduce this progression, yet efficacy diminishes as antibiotic resistance develops. ML141 and simvastatin inhibit S. aureus invasion through host-directed rather than bactericidal mechanisms. Objective To determine whether cotreatment of ML141 or of simvastatin with rifampin would enhance rifampin efficacy. Methods Assays to assess host cell invasion, host cell viability, host cell membrane permeability, and bactericidal activity were performed using the human embryonic kidney (HEK) 293-A cell line infected with S. aureus (29213) and treated with vehicle control, simvastatin, ML141, rifampin, or cotreatment of simvastatin or ML141 with rifampin. Results We found cotreatment of ML141 with rifampin reduced intracellular infection nearly 85% when compared to the no treatment control. This decrease more than doubled the average 40% reduction in response to rifampin monotherapy. In contrast, cotreatment of simvastatin with rifampin failed to improve rifampin efficacy. Also, in contrast to ML141, simvastatin increased propidium iodide (PI) positive cells, from an average of 10% in control HEK 293-A cells to nearly 20% in simvastatin-treated cells, indicating an increase in host cell membrane permeability. The simvastatin-induced increase was reversed to control levels by cotreatment of simvastatin with rifampin. Conclusion Taken together, rifampin efficacy is increased through host-directed inhibition of S. aureus invasion by ML141, while efficacy is not increased by simvastatin. Considerations regarding novel therapeutic approaches may be dependent on underlying differences in pharmacology.

Abstract Background Milling during fermentation, termed cotreatment, has recently been proposed as an alternative to thermochemical pretreatment as a means to increase the accessibility of lignocellulosic biomass to biological attack. A central premise of this approach is that partial solubilization of biomass changes the slurry’s physical properties such that milling becomes more impactful and more feasible. A key uncertainty is the energy required to mill partially fermented biomass. To inform both of these issues, we report rheological characterization of small-particle, corn stover slurries undergoing fermentation by Clostridium thermocellum. Results Fermented and unfermented corn stover slurries were found to be shear-thinning and well described by a power law model with an exponent of 0.10. Plastic viscosity of a slurry, initially at 16 wt.% insoluble solids, decreased as a result of fermentation by a factor of 2000, with the first eightfold reduction occurring in the first 10% of carbohydrate conversion. Large amplitude oscillatory shear experiments revealed only minor changes to the slurry’s rheological fingerprint as a result of fermentation, with the notable change being a reduction in the critical strain amplitude needed for the onset of nonlinearity. All slurries were found to be elastoviscoplastic, with the elastic/viscous crossover at roughly 100% strain amplitude. Conclusions Whereas prior biomass rheology studies have involved pretreated feedstocks and solubilization mediated by fungal cellulase, we report results for feedstocks with no pretreatment other than autoclaving and for solubilization mediated by C. thermocellum. As observed in prior studies, C. thermocellum fermentation results in a dramatic decrease in viscosity. The magnitude of this decrease, however, is much larger starting with unpretreated feedstock than previously reported for pretreated feedstocks. LAOS measurements provide a detailed picture of the rheological fingerprint of the material. Viscosity measurements confirm the hypothesis that the physical character of corn stover slurries changes dramatically during fermentation by C. thermocellum, and indicate that the energy expended on overcoming slurry viscosity will be far less for partially fermented corn stover than for unfermented corn stover.

Abstract Background The approach to acromegalic patients with persistent acromegaly after surgery and inadequate response to first-generation somatostatin receptor ligands (SRLs) should be strictly tailored. Current options include new pituitary surgery and/or radiosurgery, or alternative medical treatment with SRLs high dose regimens, pegvisomant (PEG) as monotherapy, or combined therapy with the addition of PEG or cabergoline to SRLs. A new pharmacological approach includes pasireotide, a second-generation SRL approved for patients who do not adequately respond to surgery and/or for whom surgery is not an option. No reports on efficacy and safety of combined therapy with pasireotide and pegvisomant (PEG) in acromegaly are available. Case presentation Here we report the case of a 41-year-old acromegalic man with a mixed GH/PRL pituitary adenoma post-surgical resistant to first-generation SRLs both alone and in combination with cabergoline and PEG who achieved biochemical and tumor control with the combined triple treatment with pasireotide, PEG and cabergoline without adverse events and with a good compliance to treatment. Conclusions Twelve months of therapy with pasireotide, PEG and cabergoline proved to be safe and effective in this particular patient and the clinical improvement of disease resulted in an improved compliance to treatment.

Acid mine drainage (AMD) is a persistent and extensive source of water pollution and ecological degradation. Cotreating municipal wastewater (MWW) with AMD using existing infrastructure at conventional wastewater treatment plants (WWTPs) may serve as a potential option for AMD abatement. However, commonly elevated iron and aluminum concentrations and low pH of AMD could negatively impact various processes at a WWTP. The focus of this mini review was on determining how cotreating MWW with AMD could impact the solids handling processes at a WWTP. While no studies have explored the solids that could be generated during cotreatment in a WWTP, numerous articles separately discuss the solids generated during AMD or MWW treatment. Reviewing this literature revealed that iron and aluminum, common metals in AMD, are already present in MWW sludge and typically benefit most solids handling processes. The addition of AMD would elevate iron and aluminum concentration but would likely result in improved sludge dewatering, removal of odor-causing compounds during processing, and a decreased bioavailability of trace metals and water-soluble P in land applications. This review concludes that cotreating MWW with moderate to low volumes (<50%) of AMD at WWTPs will have minimal impact on, and likely improve, solids handling processes. [ABSTRACT FROM AUTHOR]

Objective: Effects of cotreatment with Urtica dioica (UD) methanolic leaf extract on gentamicin (GM)-induced acute kidney injury were evaluated in rats. Materials and Methods: Male Wistar rats (n=32) were separated into four groups. Gentamicin (100 mg/kg/day, IP) was injected for eight days with or without UD methanolic extract (200 mg/kg/day, gavage). The renal blood flow (RBF) and systolic blood pressure of rats were recorded. Concentration of creatinine, blood urea nitrogen (BUN), sodium, and potassium and osmolarity were measured in the urine and plasma samples. Oxidative stress level was determined by assessment of the levels of antioxidant power (FRAP) and lipid peroxidation (MDA) in the renal tissue. The renal injury and histopathological changes in the kidney were determined by microscopic evaluations. Results: Administration of UD extract along with GM, compared to GM group, significantly decreased the amounts of plasma creatinine and BUN, urinary sodium excretion, fractional excretion of sodium and potassium, and MDA levels but significantly increased creatinine clearance, urine osmolarity, renal blood flow and FRAP levels. Conclusion: The cotreatment of UD extract can attenuate renal injury of GM by reduction of oxidative stress, lipid peroxidation, and oxygen free radicals. The potential nephroprotective effects of UD extract are probably mediated via its antioxidant and antiinflammatory activity. [ABSTRACT FROM AUTHOR]

Cilostazol (an inhibitor of phosphodiesterase type III) has potent anti-inflammatory effects, and celecoxib (a COX-2 specific inhibitor) has been reported to improve the unsatisfactory profile of NSAIDs. This study investigated the synergistic anti-arthritic potential of a multitarget-based cotreatment, in which cilostazol was used as an add-on therapy for celecoxib, using the synovial fibroblasts of RA patients (RASFs). Increased COX-2 protein expression and PGE2 synthesis by LPS (1 μg/ml) were significantly and synergistically attenuated by cotreatment with 3 μM cilostazol and 30 μM celecoxib, whereas monotherapy with either cilostazol or celecoxib showed little effects. IL-10 mRNA levels in LPS-treated RASFs were moderately increased by pretreating cilostazol (1–10 μM) or celecoxib (10–50 μM) monotherapy, but 3 μM of cilostazol add-on for 30 μM celecoxib treatment synergistically increased IL-10 mRNA levels and IL-10 release to culture media. Cilostazol and celecoxib cotreatment similarly showed synergistic increase in SOCS3 mRNA levels. Accordingly, LPS-induced increases in IL-1β and IL-6 mRNA and TNF-α release were significantly and synergistically diminished by cilostazol and celecoxib cotreatment. Moreover, synovial cell proliferation was significantly suppressed by cotreatment. Summarizing, cotreatment with cilostazol and celecoxib exhibited a synergistic increase in IL-10 production and SOCS3 expressions, thereby resulted in synergistic decreases in IL-1β mRNA, IL-6 mRNA expression and TNF-α synthesis in association with synergistic decreases in COX-2 and PGE2 protein expression in the RA synovial fibroblasts. In conclusion, these observations suggest low concentrations of cilostazol and celecoxib cotreatment may ensure a synergistic anti-arthritic potential. [ABSTRACT FROM AUTHOR]

Background: The approach to acromegalic patients with persistent acromegaly after surgery and inadequate response to first-generation somatostatin receptor ligands (SRLs) should be strictly tailored. Current options include new pituitary surgery and/or radiosurgery, or alternative medical treatment with SRLs high dose regimens, pegvisomant (PEG) as monotherapy, or combined therapy with the addition of PEG or cabergoline to SRLs. A new pharmacological approach includes pasireotide, a second-generation SRL approved for patients who do not adequately respond to surgery and/or for whom surgery is not an option. No reports on efficacy and safety of combined therapy with pasireotide and pegvisomant (PEG) in acromegaly are available. Case presentation: Here we report the case of a 41-year-old acromegalic man with a mixed GH/PRL pituitary adenoma post-surgical resistant to first-generation SRLs both alone and in combination with cabergoline and PEG who achieved biochemical and tumor control with the combined triple treatment with pasireotide, PEG and cabergoline without adverse events and with a good compliance to treatment. Conclusions: Twelve months of therapy with pasireotide, PEG and cabergoline proved to be safe and effective in this particular patient and the clinical improvement of disease resulted in an improved compliance to treatment. [ABSTRACT FROM AUTHOR]

Background: Feedstock recalcitrance is the most important barrier impeding cost-efective production of cellulosic biofuels. Pioneer commercial cellulosic ethanol facilities employ thermochemical pretreatment and addition of fungal cellulase, relecting the main research emphasis in the ield. However, it has been suggested that it may be possible to process cellulosic biomass without thermochemical pretreatment using thermophilic, cellulolytic bacteria. To further explore this idea, we examine the ability of various biocatalysts to solubilize autoclaved but otherwise unpretreated cellulosic biomass under controlled but not industrial conditions. Results: Carbohydrate solubilization of mid-season harvested switchgrass after 5 days ranged from 24 % for Caldicellulosiruptor bescii to 65 % for Clostridium thermocellum, with intermediate values for a thermophilic horse manure enrichment, Clostridium clarilavum, Clostridium cellulolyticum, and simultaneous sacchariication and fermentation (SSF) featuring a fungal cellulase cocktail and yeast. Under a variety of conditions, solubilization yields were about twice as high for C. thermocellum compared to fungal cellulase. Solubilization of mid-season harvested switchgrass was about twice that of senescent switchgrass. Lower yields and greater dependence on particle size were observed for Populus as compared to switchgrass. Trends observed from data drawn from six conversion systems and three substrates, including both time course and end-point data, were (1) equal fractional solubilization of glucan and xylan, (2) no biological solubilization of the non-carbohydrate fraction of biomass, and (3) higher solubilization for three of the four bacterial cultures tested as compared to the fungal cellulase system. Brief (5 min) ball milling of solids remaining after fermentation of senescent switchgrass by C. thermocellum nearly doubled carbohydrate solubilization upon reinnoculation as compared to a control without milling. Greater particle size reduction and solubilization were observed for milling of partially fermented solids than for unfermented solids. Physical disruption of cellulosic feedstocks after initiation of fermentation, termed cotreatment, warrants further study. Conclusions: While the ability to achieve signiicant solubilization of minimally pretreated switchgrass is widespread, a ivefold diference between the most and least efective biocatalyst--feedstock combinations was observed. Starting with nature's best biomass-solubilizing systems may enable a reduction in the amount of non-biological processing required, and in particular substitution of cotreatment for pretreatment. [ABSTRACT FROM AUTHOR]

Increased glycolysis for energy production is necessary for survival of tumor cells and thus represents a selective therapeutic target. We have analyzed in vitro whether inhibition of glycolysis can reduce the viability of human endometrial and ovarian cancer cells and whether it can enhance the antitumor efficacy of GnRH receptor-targeted therapies.Cell viability of ovarian and endometrial cancer cells treated without or with glycolysis inhibitor 2-Deoxy-D-Glucose (2DG) alone or in combination with GnRH-II antagonist [Ac-D2Nal1, D-4Cpa2, D-3Pal3,6,Leu8, D-Ala10]GnRH-II or with cytotoxic GnRH-I agonist AEZS-108 (AN-152) was measured using alamar blue assay. Induction of apoptosis was analyzed using TUNEL assay and quantified by measurement of loss of mitochondrial membrane potential. Apoptotic signaling was measured by quantification of activated caspase-3 by using the Western blot technique.Treatment of endometrial and ovarian cancer cells with glycolysis inhibitor 2DG resulted in a significant decrease of cell viability and a significant increase of apoptosis. Treatment with 2DG in combination with the GnRH-II antagonist or with AEZS-108 resulted in a significant reduced viability compared with single-agent treatments. The observed reduction in viability was due to induction of apoptosis. Also for apoptosis induction, a significant stronger effect in the case of cotreatments compared with single-agent treatments could be observed. These additive effects could be correlated to increased activation of caspase-3.The glycolytic phenotype of human endometrial and ovarian cancer cells can be targeted for therapeutic intervention. In addition, cotreatment of a glycolysis inhibitor with GnRH receptor-targeted therapies might be a suitable therapy for GnRH receptor-positive human endometrial and ovarian cancers. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To assess the prevalence and correlates of antipsychotic polypharmacy (APP) across decades and regions. Methods: Electronic PubMed/Google Scholar search for studies reporting on APP, published from 1970 to 05/2009. Median rates and interquartile ranges (IQR) were calculated and compared using non-parametric tests. Demographic and clinical variables were tested as correlates of APP in bivariate and meta-regression analyses. Results: Across 147 studies (1,418,163 participants, 82.9% diagnosed with schizophrenia [IQR=42-100%]), the median APP rate was 19.6% (IQR=12.9-35.0%). Most common combinations included first-generation antipsychotics (FGAs)+second-generation antipsychotics (SGAs) (42.4%, IQR=0.0–71.4%) followed by FGAs+FGAs (19.6%, IQR=0.0–100%) and SGAs+SGAs (1.8%, IQR=0.0–28%). APP rates were not different between decades (1970–1979:28.8%, IQR=7.5–44%; 1980–1989:17.6%, IQR=10.8–38.2; 1990–1999:22.0%, IQR=11–40; 2000–2009:19.2% IQR=14.4–29.9, p=0.78), but between regions, being higher in Asia and Europe than North America, and in Asia than Oceania (p<0.001). APP increased numerically by 34% in North America from the 1980s 12.7%) to 2000s (17.0%) (p=0.94) and decreased significantly by 65% from 1980 (55.5%) to 2000 (19.2%) in Asia (p=0.03), with non-significant changes in Europe. APP was associated with inpatient status (p<0.001), use of FGAs (p<0.0001) and anticholinergics (<0.001), schizophrenia (p=0.01), less antidepressant use (p=0.02), greater LAIs use (p=0.04), shorter follow-up (p=0.001) and cross-sectional vs. longitudinal study design (p=0.03). In a meta-regression, inpatient status (p<0.0001), FGA use (0.046), and schizophrenia diagnosis (p=0.004) independently predicted APP (N=66, R2 =0.44, p<0.0001). Conclusions: APP is common with different rates and time trends by region over the last four decades. APP is associated with greater anticholinergic requirement, shorter observation time, greater illness severity and lower antidepressant use. [Copyright &y& Elsevier]

The aim of this study is to examine the growth inhibitory effects of methanolic leaf and fruit extracts of L. vulgare on HCT-116 cells over different time periods and their synergistic effect with a Pd(apox) complex. The antiproliferative activity of plant extracts alone or in combination with the Pd(apox) complex was determined using MTT cell viability assay, where the IC50 value was used as a parameter of cytotoxicity. Results show that antiproliferative effects of L. vulgare extracts increase with extension of exposure time, with decreasing IC50 values, except for 72 h where the IC50 values for methanolic leaf extract were lower than for the fruit extract. The Pd(apox) complex alone had a weak antiproliferative effect, but combination with L. vulgare extracts caused stronger effects with lower IC50 values than with L. vulgare extracts alone. The type of cell death was explored by fluorescence microscopy using the acridin orange/ethidium bromide method. Treatments with plant extracts caused typical apoptotic morphological changes in HCT-116 cells and co-treatments with Pd(apox) complex caused higher levels of apoptotic cells than treatment with plant extracts alone. The results indicate that L. vulgare is a considerable source of natural bioactive substances with antiproliferative activity on HCT-116 cells and which have a substantial synergistic effect with the Pd(apox) complex. [ABSTRACT FROM AUTHOR]

After its discovery in the middle of the last century, calcitonin was quickly recognized as an extremely powerful inhibitor of osteoclast activity. Such a potent action prompted its use in Paget's disease, and determined its status as an elective anti-osteoporotic therapeutic. Over the years, however, its use has steadily declined, often because of costs and tachyphylaxis in calcitonin-induced responses, paralleled by the emergence of (cheaper) biphosphonates that now have wide diffusion and application. Modern technologies enable cheaper production costs for calcitonin; in addition, prednisolone and other glucocorticoids might impede the instauration of tachyphylaxis, such that calcitonin would retain its therapeutic efficacy. Therefore, prompted by recent experimental data generated with a model of rheumatoid arthritis, where calcitonin displayed synergistic effect when given as a cotreatment with prednisolone, as well as by clinical data showing efficacy of this hormone in osteoarthritis, we here propose a revamped use for calcitonin, as a cotreatment for different forms of arthritides. [ABSTRACT FROM AUTHOR]

In our previous reports, aspirin, an antipyretic analgesic, suppressed the genotoxicity of mitomycin C (MMC) in a somatic mutation and recombination test (SMART) in Drosophila melanoga s te r. In order to reveal the mechanism of the anti-genotoxicity of aspirin, we evaluated the suppressing ability of each aspirin metabolite, such as salicylic acid (SA), salicyluric acid (SUA), gentisic acid (GA), gentisuric acid (GUA), and 2,3-dihydroxybenzoic acid (DHBA), in SMART in Drosophila melanogaster using the cotreatment protocol in this report. SUA, GA, GUA, and DHBA reduced the number of the three types of spot induced by MMC without decrease of survival. These aspirin metabolites decreased the genotoxicity frequency of MMC for total spots in a dose-dependent manner. Furthermore, each metabolite decreased the genotoxicity frequency of MMC by approximately 80% at a dose of 40 mg/bottle, respectively. It is suggested that these metabolites are the main substances of anti-genotoxicity in the aspirin metabolic pathway. [ABSTRACT FROM AUTHOR]

A patient who complained of mistaking objects in his peripheral visual field for a dog was diagnosed with Generalized Anxiety Disorder (GAD) and Post-Traumatic Stress Disorder (PTSD). He also had poor nutrition, sleep problems, somatic features, drank a considerable amount of alcohol, and exercised little. As patients with these difficulties often benefit from psychological as well as medical intervention strategies, a physician and a psychologist interviewed the patient together and developed a coordinated treatment plan. The psychologist was to work with the patient on behavioral aspects of these difficulties, although the physician treated the patient with medication. Both professionals evaluated the patient’s response to medical as well as psychological treatment strategies and reinforced the other professional’s therapeutic activities. The patient improved significantly from the combined treatment program. Although it cannot be determined, it is likely that he would not have improved as much if his treatment program had not involved both the psychologist and the physician. [ABSTRACT FROM PUBLISHER]

Addition of landfill leachate to a domestic wastewater treatment system may have negative impacts since leachate is a highly concentrated wastewater both in terms of inorganic and organic pollutants. The aim of this study was to investigate the effluent quality in the cotreatment of sanitary landfill leachate and domestic wastewater and the improving effect of powdered activated carbon (PAC). The volumetric ratio of leachate was varied from 5 to 25% (v/v). Batch activated sludge (AS) reactors were fed with leachate and domestic wastewater. Parallel AS + PAC reactors also contained PAC, which was added at the dose of 100-3,500 mg L-1. The nonbiodegradable soluble COD (SCOD) in leachate was decreased to very low levels by this addition. Experiments were also conducted in Semi-Continuously Fed Batch (SCFB) and Continuous-Flow (CF) activated sludges with recycle. In both types of operations, effluent COD and ammonium nitrogen concentrations increased when the leachate input increased. In all cases, the positive effect of PAC addition became more apparent at high leachate inputs. The study revealed that the negative impact of leachate on a municipal wastewater treatment system could be prevented by the addition of PAC. Particularly, if the leachate contribution in a publicly owned treatment work (POTW) exceeds 10%, or in the case of shock leachate loadings, the effluent quality may be considerably improved with PAC addition. [ABSTRACT FROM AUTHOR]

Summary: Purpose: Topiramate (TPM) is widely used as add-on therapy for epilepsy. TPM inhibits carbonic anhydrase, which may result in metabolic acidosis from decreased serum bicarbonate. The ketogenic diet (KGD) predisposes patients to metabolic acidosis, especially during induction. In children with refractory epilepsy, cotreatment with TPM and KGD may be considered, but special attention should be paid to the combined risks for metabolic acidosis and nephrolithiasis. We report our experience in 14 children cotreated with TPM and the KGD. Methods: Medical records of 14 children cotreated with the KGD and TPM for medically refractory epilepsy were reviewed retrospectively. Bicarbonate levels were analyzed and correlated with clinical profiles, including duration of cotreatment, TPM dose, KGD ratio, and seizure control. Results: Nine children had a <20% decrease in bicarbonate levels, from 5.3 to 12.3 mEq/L (mean, 7.6 mEq/L). Cotreatment was continued in all patients for duration of 33 to 544 days (seven had remained on cotreatment at the end of the study period), although two children required bicarbonate supplements to continue the KGD. No patient had nephrolithiasis. Conclusions: Although a large decrease in bicarbonate level occurred in the majority of children, the decrease appeared mostly at the time of KGD induction when added to prior TPM therapy. Bicarbonate levels should be monitored carefully with TPM and KGD cotreatment, and bicarbonate supplements given when symptomatic. [ABSTRACT FROM AUTHOR]

Among traditional hazardous waste sources, pharmaceutical-containing wastewater and acidic mine drainage need treatment to preserve the expected water supply quality. A nano zero-valent iron (nZVI)-enriched treatment of these two streams is evaluated for simultaneous removal of various heavy metal ions, organic pollutants, sulfates, the efficiency of the treatment system, and separation of reaction products in the fluidized-bed reactor. The reactor packed with silica sand was inoculated with sludge from an anaerobic digester, then 1–3 g/L of nZVI slurry added to cotreat a hospital feed and acid mine wastewater at 5:2 v/v. The biotreatment process is monitored through an oxidation–reduction potential (Eh) for 90 days. The removal pathway for the nZVI used co-precipitation, sorption, and reduction. The removal load for Zn and Mn was approximately 198 mg Zn/g Fe and 207 mg Mn/g Fe, correspondingly; achieving sulfate (removal efficiency of 94% and organic matter i.e., chemical oxygen demand (COD), biological oxygen demand (BOD), dissolved organic carbon (DOC), total dissolved nitrogen (TDN) reduced significantly, but ibuprofen and naproxen achieved 31% and 27% removal, respectively. This enriched cotreatment system exhibited a high reducing condition in the reactor, as confirmed by Eh; hence, the nZVI was dosed only a few times in biotreatment duration, demonstrating a cost-effective system. [ABSTRACT FROM AUTHOR]

Lead-zinc smelting slag (LZSS) is regarded as a hazardous waste containing heavy metals that poses a significant threat to the environment. LZSS is rich in aluminosilicate, which has the potential to prepare alkali-activated materials and solidify hazardous waste, realizing hazardous waste cotreatment. In this study, the experiment included two parts; i.e., the preparation of alkali-activated LZSS (pure smelting slag) and chromite ore processing residue (COPR) solidification/stabilization. Single-factor and orthogonal experiments were carried out that aimed to explore the effects of various parameters (alkali solid content, water glass modulus, liquid-solid ratio, and initial curing temperature) for alkali-activated LZSS. Additionally, compressive strength and leaching toxicity were the indexes used to evaluate the performance of the solidified bodies containing COPR. As a result, the highest compressive strength of alkali-activated LZSS reached 84.49 MPa, and when 40% COPR was added, the strength decreased to 1.42 MPa. However, the leaching concentrations of Zn and Cr from all the solidified bodies were far below the critical limits (US EPA Method 1311 and China GB5085.3-2007). Heavy-metal ions in LZSS and COPR were immobilized successfully by chemical and physical means, which was detected by analyses including environmental scanning electron microscopy with energy-dispersive spectrometry, Fourier transform infrared spectrometry, and X-ray diffraction.

Mechanical disruption of lignocellulose during fermentation, cotreatment, is a nascent approach to increase biologically-mediated carbohydrate solubilization without exposure to high temperatures or chemicals. However, ability to tolerate the presence of milling at intensities sufficient to allow high lignocellulose solubilization yields has to date only been evaluated for Clostridium thermocellum and Saccharomyces cerevisiae , and demonstration of high carbohydrate solubilization has only been reported for switchgrass at the time of submission. Continuous ball milling during fermentation by C. thermocellum was found to be sufficient to allow high (>85%) total carbohydrate solubilization of corn stover and poplar as well as switchgrass. Under the conditions tested, ball milling had no apparent effect on soluble sugar fermentation by Escherichia coli and Thermoanaerobacterium saccharolyticum but completely inhibited carbohydrate fermentation by Zymomonas mobilis and Bacillus subtilis. Our results are consistent with the stress of milling being sufficient to overwhelm the inefficient fermentative metabolism of Z. mobilis and B. subtilis , but not to the other microorganisms tested in this work for which fermentation is more efficient and robust. • Cotreatment was tested on three lignocellulosic feedstocks and four microorganisms. • Carbohydrate solubilization is improved with cotreatment on all feedstocks tested. • Solubilization was found to be high for both woody and herbaceous angiosperms. • Growth of some microorganisms is affected by milling but for others it is not. [ABSTRACT FROM AUTHOR]

Background: Chronic infection by Staphylococcus aureus drives pathogenesis in important clinical settings, such as recurrent pulmonary infection in cystic fibrosis and relapsing infection in osteomyelitis. Treatment options for intracellular S. aureus infection are limited. Rifampin, a lipophilic antibiotic, readily penetrates host cell membranes, yet monotherapy is associated with rapid antibiotic resistance and development of severe adverse events. Antibiotic cotreatment can reduce this progression, yet efficacy diminishes as antibiotic resistance develops. ML141 and simvastatin inhibit S. aureus invasion through host-directed rather than bactericidal mechanisms., Objective: To determine whether cotreatment of ML141 or of simvastatin with rifampin would enhance rifampin efficacy., Methods: Assays to assess host cell invasion, host cell viability, host cell membrane permeability, and bactericidal activity were performed using the human embryonic kidney (HEK) 293-A cell line infected with S. aureus (29213) and treated with vehicle control, simvastatin, ML141, rifampin, or cotreatment of simvastatin or ML141 with rifampin., Results: We found cotreatment of ML141 with rifampin reduced intracellular infection nearly 85% when compared to the no treatment control. This decrease more than doubled the average 40% reduction in response to rifampin monotherapy. In contrast, cotreatment of simvastatin with rifampin failed to improve rifampin efficacy. Also, in contrast to ML141, simvastatin increased propidium iodide (PI) positive cells, from an average of 10% in control HEK 293-A cells to nearly 20% in simvastatin-treated cells, indicating an increase in host cell membrane permeability. The simvastatin-induced increase was reversed to control levels by cotreatment of simvastatin with rifampin., Conclusion: Taken together, rifampin efficacy is increased through host-directed inhibition of S. aureus invasion by ML141, while efficacy is not increased by simvastatin. Considerations regarding novel therapeutic approaches may be dependent on underlying differences in pharmacology., Competing Interests: The authors declare the following patents. 1. METHODS FOR TREATING BACTERIAL INFECTION Co-inventors: Susan McDowell, Larry Sklar, Mark Haynes, Robert Sammelson Patent No.: US 9,259,415 B2 Date of Patent: Feb. 16, 2016 2. METHODS FOR TREATING BACTERIAL INFECTION Co-inventors: Susan McDowell, Larry Sklar, Mark Haynes, Robert Sammelson Patent No.: US 9,763,967 B2 Date of Patent: Sep. 19, 2017 3. METHODS FOR TREATING BACTERIAL INFECTION Co-inventors: Susan McDowell, Larry Sklar, Mark Haynes, Robert Sammelson Patent No.: US 2018/0021357 A1 Date of Patent: Jan. 25, 2018., (©2020 Evans et al.)

Background: The recalcitrance of cellulosic biomass is widely recognized as a key barrier to cost-effective biological processing to fuels and chemicals, but the relative impacts of physical, chemical and genetic interventions to improve biomass processing singly and in combination have yet to be evaluated systematically. Solubilization of plant cell walls can be enhanced by non-biological augmentation including physical cotreatment and thermochemical pretreatment, the choice of biocatalyst, the choice of plant feedstock, genetic engineering of plants, and choosing feedstocks that are less recalcitrant natural variants. A two-tiered combinatoric investigation of lignocellulosic biomass deconstruction was undertaken with three biocatalysts (Clostridium thermocellum, Caldicellulosiruptor bescii, Novozymes Cellic® Ctec2 and Htec2), three transgenic switchgrass plant lines (COMT, MYB4, GAUT4) and their respective nontransgenic controls, two Populus natural variants, and augmentation of biological attack using either mechanical cotreatment or cosolvent-enhanced lignocellulosic fractionation (CELF) pretreatment. Results: In the absence of augmentation and under the conditions tested, increased total carbohydrate solubilization (TCS) was observed for 8 of the 9 combinations of switchgrass modifications and biocatalysts tested, and statistically significant for five of the combinations. Our results indicate that recalcitrance is not a trait determined by the feedstock only, but instead is coequally determined by the choice of biocatalyst. TCS with C. thermocellum was significantly higher than with the other two biocatalysts. Both CELF pretreatment and cotreatment via continuous ball milling enabled TCS in excess of 90%. Conclusion: Based on our results as well as literature studies, it appears that some form of non-biological augmentation will likely be necessary for the foreseeable future to achieve high TCS for most cellulosic feedstocks. However, our results show that this need not necessarily involve thermochemical processing, and need not necessarily occur prior to biological conversion. Under the conditions tested, the relative magnitude of TCS increase was augmentation > biocatalyst choice > plant choice > plant modification > plant natural variants. In the presence of augmentation, plant modification, plant natural variation, and plant choice exhibited a small, statistically non-significant impact on TCS. [ABSTRACT FROM AUTHOR]

Introduction: Antipsychotic co-treatment is common in schizophrenia, despite lacking evidence for its efficacy and safety. Areas: We conducted a systematic search of PubMed/PsycInfo/CJN/WangFan/CBM without language restrictions from database inception until 05/25/2015 for randomized trials comparing antipsychotic monotherapy with antipsychotic co-treatment in ≥20 adults with schizophrenia reporting meta-analyzable adverse events (AEs) data. Meta-analyzing 67 studies (n=4,861, duration=10.3±5.2 weeks), antipsychotic co-treatment was similar to monotherapy regarding intolerability-related discontinuation (risk ratio (RR)=0.84, 95% confidence interval (CI)=0.53-1.33, p=0.455). While incidence of ≥1 AE was lower with antipsychotic co-treatment (RR=0.77, 95%CI=0.66-0.90, p=0.001), these results were solely driven by open-label and efficacy-focused studies. Adjunctive D2-antagonists lead to less nausea (RR=0.220, 95%CI=0.06-0.87, p=0.030) and insomnia (RR=0.26, 95%CI=0.08-0.86, p=0.028), but higher prolactin (SMD=2.20, 95%CI=0.43-3.96, p=0.015). Conversely, adjunctive partial D2-agonists (aripiprazole=100%) resulted in lower electrocardiogram abnormalities (RR=0.43, 95%CI=0.25-0.73, p=0.002), constipation (RR=0.45, 95%CI=0.25-0.79, p=0.006), drooling/hypersalivation (RR=0.14, 95%CI=0.07-0.29, p<0.001), prolactin (SMD=-1.77, 95%CI=-2.38, -1.15, p<0.001), total and LDL-cholesterol (SMD=-0.33, 95%CI=-0.55, -0.11, p=0.003; SMD=-0.33, 95%CI=-0.54, -0.10, p=0.004)., Expert Opinion: No double-blind evidence for altered AE burden associated with antipsychotic co-treatment was found. However, AEs were insufficiently and incompletely reported and follow-up duration was modest. Adjunctive partial D2-agonists might be beneficial for counteracting several AEs. High-quality, long-term studies that comprehensively assess AEs are needed.

Aim: To assess genotype effect on efavirenz (EFV) pharmacokinetics, treatment outcomes and provide genotype-based EFV doses recommendations during for tuberculosis (TB)-HIV-1 cotreatment., Materials & Methods: EFV concentrations from 158 HIV-TB co-infected patients treated with EFV/lamivudine/zidovidine and rifampicin were analyzed. Genotype and CD4 and viral load data were analyzed using a population PK model., Results: Simulated AUCs for 600 mg EFV dose were 1.2- and 2.4-times greater than the product label for Ugandans in general and CYP2B6*6/*6 genotypes respectively. EFV daily doses of 450 and 250 mg for Ugandans and CYP2B6*6/*6 genotypes, respectively, yielded simulated exposures comparable to the product label., Conclusions: Around 450 and 250 mg daily doses might meet EFV dosing needs of HIV-TB infected Ugandans in general and CYP2B6*6/*6 genotypes, respectively.

The synergy effect of trisodium phosphate (TSP) and ethanol against murine norovirus 1 (MNV-1), as a surrogate for human noroviruses, on fresh produces was evaluated. More than 2% (w/v) of TSP effectively inactivated MNV-1. The single treatment of 1% TSP or 30% ethanol for 30 min was not effective on MNV-1; however, cotreatment showed inactivation of MNV-1 on stainless steel and the produces of lettuce and bell pepper under 15 min. The results suggest that cotreatment of TSP and ethanol at a low concentration and a short time of exposure might be useful for the reduction of norovirus in some produce.