Synergetic Effect of Physical Activity and Fruit-vegetable Intake on the Decreasing of Cognitive Decline in Older Taiwanese

Factors which are associated with cognitive decline among elders include physical activity and the intake of fruit and vegetable, however, long-term effects and the concurrence of physical activity and fruit-vegetable intake are unknown. The present study explores this potential synergy for the mitigation of cognitive decline among a cohort of older Taiwanese in a 16-year longitudinal study. Five population-based surveys from the Taiwan Longitudinal Survey on Aging (1995–2015) involving 4,440 respondents over 53 years old in 1999 were studied. Trends in decrease of cognitive decline were observed for 16 years. Cognitive function was assessed using the Short Portable Mental Status Questionnaire (SPMSQ). Adjustments made on regression analysis included demographic, socioeconomic, health behavioral, and disease status covariates. The risk of cognitive decline decreased 63% when high physical activity group and high intake of fruit-vegetable group were combined (OR :0.37, 95% CI: 0.23–0.59). More physical activity was combined with greater fruit-vegetable intake, cognitive decline among older Taiwanese was mitigated. This indicates that there may be a synergistic effect of physical activity and fruit-vegetable intake on mitigating cognitive decline. Synergistic personal behavior is a safe, effective, and economical approach to health in later life.

Evaluating mono and combination therapy of meropenem and amikacin against Pseudomonas aeruginosa bacteremia in the Hollow-Fiber Infection Model

Debate continues as to the role of combination antibiotic therapy for the management of Pseudomonas aeruginosa infections. We studied extent of bacterial killing and resistance emergence of meropenem and amikacin as monotherapy and as a combination therapy against susceptible and resistant P. aeruginosa isolates from bacteremic patients using the dynamic in vitro hollow-fiber infection model. Three P. aeruginosa isolates (meropenem MICs 0.125, 0.25 & 64 mg/L) were used simulating bacteremia with an initial inoculum ~ 1×105 CFU/mL and the expected pharmacokinetics of meropenem and amikacin in critically ill patients. For isolates susceptible to amikacin and meropenem (isolates 1 and 2), the rate of bacterial killing was increased with the combination regimen when compared with monotherapy of either antibiotic. Both the combination and meropenem monotherapy were able to sustain bacterial killing throughout the seven-day treatment course, whereas regrowth of bacteria occurred with amikacin monotherapy after 12 hours. For the meropenem-resistant P. aeruginosa isolate (isolate 3), only the combination regimen demonstrated bacterial killing. Given that tailored antibiotic regimens can maximize potential synergy against some isolates, future studies should explore the benefit of combination therapy against resistant P. aeruginosa.

Thermochemical and Catalytic Conversion Technologies for the Development of Brazilian Biomass Utilization

The social, economic, and environmental impacts of climate change have been shown to affect poorer populations throughout the world disproportionally, and the COVID-19 pandemic of 2020–2021 has only exacerbated the use of less sustainable energy, fuel, and chemical sources. The period of economic and social recovery following the pandemic presents an unprecedented opportunity to invest in biorefineries based on the pyrolysis of agricultural residues. These produce a plethora of sustainable resources while also contributing to the economic valorization of first-sector local economies. However, biomass-derived pyrolysis liquid is highly oxygenated, which hinders its long-term stability and usability. Catalytic hydrogenation is a proposed upgrading method to reduce this hindrance, while recent studies on the use of nickel and niobium as low-cost catalysts, both abundant in Brazil, reinforce the potential synergy between different economic sectors within the country. This review gathers state-of-the-art applications of these technologies with the intent to guide the scientific community and lawmakers alike on yet another alternative for energy and commodities production within an environmentally sustainable paradigm.

Metabolic Pathways and Targets in Chondrosarcoma

Chondrosarcomas are the second most common primary bone malignancy. Chondrosarcomas are characterized by the production of cartilaginous matrix and are generally resistant to radiation and chemotherapy and the outcomes are overall poor. Hence, there is strong interest in determining mechanisms of cancer aggressiveness and therapeutic resistance in chondrosarcomas. There are metabolic alterations in chondrosarcoma that are linked to the epigenetic state and tumor microenvironment that drive treatment resistance. This review focuses on metabolic changes in chondrosarcoma, and the relationship between signaling via isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2), hedgehog, PI3K-mTOR-AKT, and SRC, as well as histone acetylation and angiogenesis. Also, potential treatment strategies targeting metabolism will be discussed including potential synergy with immunotherapies.

β-Dystroglycan Restoration and Pathology Progression in the Dystrophic mdx Mouse: Outcome and Implication of a Clinically Oriented Study with a Novel Oral Dasatinib Formulation

ROS-activated cSrc tyrosine kinase (TK) promotes the degradation of β-dystroglycan (β-DG), a dystrophin-glycoprotein complex component, which may reinforce damaging signals in Duchenne muscular dystrophy (DMD). Therefore, cSrc-TK represents a promising therapeutic target. In mdx mice, a 4-week subcutaneous treatment with dasatinib (DAS), a pan-Src-TKs inhibitor approved as anti-leukemic agent, increased muscle β-DG, with minimal amelioration of morphofunctional indices. To address possible dose/pharmacokinetic (PK) issues, a new oral DAS/hydroxypropyl(HP)-β-cyclodextrin(CD) complex was developed and chronically administered to mdx mice. The aim was to better assess the role of β-DG in pathology progression, meanwhile confirming DAS mechanism of action over the long-term, along with its efficacy and tolerability. The 4-week old mdx mice underwent a 12-week treatment with DAS/HP-β-CD10% dissolved in drinking water, at 10 or 20 mg/kg/day. The outcome was evaluated via in vivo/ex vivo disease-relevant readouts. Oral DAS/HP-β-CD efficiently distributed in mdx mice plasma and tissues in a dose-related fashion. The new DAS formulation confirmed its main upstream mechanism of action, by reducing β-DG phosphorylation and restoring its levels dose-dependently in both diaphragm and gastrocnemius muscle. However, it modestly improved in vivo neuromuscular function, ex vivo muscle force, and histopathology, although the partial recovery of muscle elasticity and the decrease of CK and LDH plasma levels suggest an increased sarcolemmal stability of dystrophic muscles. Our clinically oriented study supports the interest in this new, pediatric-suitable DAS formulation for proper exposure and safety and for enhancing β-DG expression. This latter mechanism is, however, not sufficient by itself to impact on pathology progression. In-depth analyses will be dedicated to elucidating the mechanism limiting DAS effectiveness in dystrophic settings, meanwhile assessing its potential synergy with dystrophin-based molecular therapies.

Co-culturing Hyphomicrobium nitrativorans strain NL23 and Methylophaga nitratireducenticrescens strain JAM1 allows sustainable denitrifying activities under marine conditions

Background Hyphomicrobium nitrativorans strain NL23 and Methylophaga nitratireducenticrescens strain JAM1 are the principal bacteria involved in the denitrifying activities of a methanol-fed, fluidized-bed marine denitrification system. Strain NL23 possesses the complete denitrification pathway, but cannot grow under marine conditions in pure cultures. Strain JAM1 is a marine bacterium that lacks genes encoding a dissimilatory nitrite (NO2−) reductase and therefore cannot reduce NO2−. Here, we report the characterization of some of their physiological traits that could influence their co-habitation. We also perform co-cultures to assess the potential synergy between the two strains under marine and denitrifying conditions. Methodology Anoxic planktonic pure cultures of both strains were grown with different concentrations of nitrate (NO3−). Anoxic planktonic co-cultures could only be cultured on low NaCl concentrations for strain NL23 to grow. Biofilm co-cultures were achieved in a 500-mL bioreactor, and operated under denitrifying conditions with increasing concentrations of NaCl. NO3− and NO2− concentrations and the protein content were measured to derive the denitrification rates. The concentrations of both strains in co-cultures were determined by quantitative PCR (qPCR). Ectoine concentration was measured by mass spectrometry in the biofilm co-culture. The biofilm was visualized by fluorescence in situ hybridization. Reverse-transcription-qPCR and RNA-seq approaches were used to assess changes in the expression profiles of genes involved in the nitrogen pathways in the biofilm cultures. Results Planktonic pure cultures of strain JAM1 had a readiness to reduce NO3− with no lag phase for growth in contrast to pure cultures of strain NL23, which had a 2-3 days lag phase before NO3− starts to be consumed and growth to occur. Compared to strain NL23, strain JAM1 has a higher µmax for growth and higher specific NO3− reduction rates. Denitrification rates were twice higher in the planktonic co-cultures than those measured in strain NL23 pure cultures. The biofilm co-cultures showed sustained denitrifying activities and surface colonization by both strains under marine conditions. Increase in ectoine concentrations was observed in the biofilm co-culture with the increase of NaCl concentrations. Changes in the relative transcript levels were observed in the biofilm culture with genes encoding NapA and NapGH in strain NL23. The type of medium had a great impact on the expression of genes involved in the N-assimilation pathways in both strains. Conclusions These results illustrate the capacity of both strains to act together in performing sustainable denitrifying activities under marine conditions. Although strain JAM1 did not contribute in better specific denitrifying activities in the biofilm co-cultures, its presence helped strain NL23 to acclimate to medium with NaCl concentrations >1.0%.

A Mini Review on the Antibacterial Activity of Roselle (Hibiscus sabdariffa L.) Phytochemicals

Roselle (Hibiscus sabdariffa L.) has been shown to have various bioactivities with therapeutic benefits. These bioactivities are owing to the different kinds of phytochemicals, which include anthocyanins, phenolic acids, and flavonoids. This mini review aims to summarize the reported antibacterial activity of roselle phytochemicals in the literature in the past decade (2011-2021). The results revealed that roselle extracts from various extraction methods were shown to have antibacterial activity against clinical isolates and food pathogens, including multidrug resistant bacteria. Furthermore, there is evidence that roselle extract showed potential synergy with antibiotics. Overall, phytochemicals in roselle have the potential as an antibacterial for different beneficial applications.

Triple Helix or Quadruple Helix: Which Model of Innovation to Choose for Empirical Studies?

While the Triple Helix and Quadruple Helix models are popular in innovation studies, the relations between them have not been addressed extensively in the literature. There are diverse interpretations of helix models in empirical studies that apply them, but these sometimes deviate from the original theses of the models. Such a situation can confuse newcomers to the field in terms of which helix model to apply in their empirical research. We discern that the cause of this research challenge is a lack of systematic comparison of the two models. To bridge the research gap, this paper compares the models from the perspectives of how they were introduced and discussed in the literature and improved and how useful they are in addressing the innovation processes in contemporary society. Our major findings are as follows: First, reviewing the extant literature applying the two helix models for identifying research gaps, we discover that these studies were influenced by three views on the relations between the two models that were located on a continuum between two extreme ends—namely, isolation versus integration of the two models. Second, we provide a systematic comparison of both the advantages and weaknesses of the two models, and this may help researchers choose suitable helix models as conceptual/analytical tools in their empirical innovation studies. Third, our comparison of the two models shows that they are largely supplementary to each other when analysing innovation processes in contemporary society, providing a ground for potential synergy building between the two helix models.

Potency and preclinical evidence of synergy of oral azole drugs and miltefosine in an ex vivo model of Leishmania (Viannia) panamensis infection

Failure of treatment of cutaneous leishmaniasis with antimonial drugs and miltefosine is frequent. Use of oral combination therapy represents an attractive strategy to increase efficacy of treatment and reduce the risk of drug resistance. We evaluated the potency of posaconazole, itraconazole, voriconazole and fluconazole, and the potential synergy of those demonstrating the highest potency, in combination with miltefosine (HePC), against infection with Leishmania (Viannia) panamensis . Synergistic activity was determined by isobolograms and calculation of Fractional Inhibitory Concentration Index (FICI), based on parasite quantification using an ex vivo model of human PBMCs infected with a luciferase-transfected, antimony and miltefosine sensitive line of L. panamensis . The drug combination and concentrations that displayed synergy were then evaluated for anti-leishmanial effect in 10 clinical strains of L. panamensis by qRT-PCR of Leishmania 7SLRNA. High potency was substantiated for posaconazole and itraconazole against sensitive as well as HePC and antimony resistant lines of L. panamensis , whereas fluconazole and voriconazole displayed low potency. HePC combined with posaconazole (Poz) demonstrated evidence of synergy at free drug concentrations achieved in plasma during treatment (2 μM HePC + 4 μM Poz). FICI, based on 70% and 90% reduction of infection, was 0.5 for the sensitive line. Combination of 2 μM HePC + 4 μM Poz effected significantly greater reduction of infection by clinical strains of L. panamensis than individual drugs. Orally administrable miltefosine/posaconazole combinations demonstrated synergistic anti-leishmanial capacity ex vivo against L. panamensis , supporting their potential as a novel therapeutic strategy to improve efficacy, and effectiveness of treatment.

True abscopal effect in a patient with metastatic non-small cell lung cancer

Background Systemic response to local anticancer treatment is a phenomenon called ‘abscopal effect’. The immune system is thought to play a pivotal role in its occurrence. To date, several cases have been reported, particularly in patients receiving combined local treatment and immune checkpoint inhibitors. In such cases, it is impossible to discriminate between the effects of local and systemic treatment. Only a few cases of abscopal effect have been described with radiotherapy alone. Case presentation Here, we report on the case of an 81-year-old woman with recurrent metastatic squamous cell carcinoma of the lung with mediastinal tumor bulk, lymph node and bone metastases. The patient refused to undergo systemic treatment, and palliative stereotactic radiotherapy of the mediastinal tumor was performed. At restaging with FDG-PET/CT, the patient presented with a decrease in size and FDG-avidity both of the irradiated site and of the lymph node and bone metastases (which did not receive radiotherapy). At 25 months after radiotherapy, the patient is still in remission at all sites. Conclusions This is a rare case of an abscopal effect after radiotherapy as monotherapy. It is one of the few hitherto reported for lung cancer. Several ongoing studies with a combination of radiotherapy and immunotherapy are seeking to exploit a potential synergy to induce abscopal effects.