Immunotherapeutic targets in non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is one of the most common types of cancer in the world and has a 5-year survival rate of ~20%. Immunotherapies have shown promising results leading to durable responses, however, they are only effective for a subset of patients. To determine the best therapeutic approach, a thorough and in-depth profiling of the tumour microenvironment (TME) is required. The TME is a complex network of cell types that form an interconnected network, promoting tumour cell initiation, growth and dissemination. The stroma, immune cells and endothelial cells that comprise the TME generate a plethora of cytotoxic or cytoprotective signalling pathways. In this review, we discuss immunotherapeutic targets in NSCLC tumours and how the TME may influence patients' response to immunotherapy.     

The major bioactive components of seaweeds and their mosquitocidal potential

Seaweeds are one of the most widely studied natural resources for their biological activities. Novel seaweed compounds with unique chemical structures have been reported for their pharmacological properties. The urge to search for novel insecticidal compound with a new mode of action for development of botanical insecticides supports the relevant scientific research on discovering the bioactive compounds in seaweeds. The mosquitocidal potential of seaweed extracts and their isolated compounds are documented in this review paper, along with the discussion on bioactivities of the major components of seaweeds such as polysaccharides, phenolics, proteins, terpenes, lipids, and halogenated compounds. The effects of seaweed extracts and compounds toward different life stages of mosquito (egg, larva, pupa, and adult), its growth, development, and reproduction are elaborated. The structure-activity relationships of mosquitocidal compounds are discussed to extrapolate the possible chemical characteristics of seaweed compounds responsible for insecticidal properties. Furthermore, the possible target sites and mode of actions of the mosquitocidal seaweed compounds are included in this paper. The potential synergistic effects between seaweeds and commercial insecticides as well as the toxic effects of seaweed extracts and compounds toward other insects and non-target organisms in the same habitat are also described. On top of that, various factors that influence the mosquitocidal potential of seaweeds, such as abiotic and biotic variables, sample preparation, test procedures, and considerations for a precise experimental design are discussed. The potential of active seaweed extracts and compounds in the development of effective bioinsecticide are also discussed.     

Evaluating sustainable development policies in rural coastal economies

Sustainable development (SD) policies targeting marine economic sectors, designed to alleviate poverty and conserve marine ecosystems, have proliferated in recent years. Many developing countries are providing poor fishing households with new fishing boats (fishing capital) that can be used further offshore as a means to improve incomes and relieve fishing pressure on nearshore fish stocks. These kinds of policies are a marine variant of traditional SD policies focused on agriculture. Here, we evaluate ex ante economic and environmental impacts of provisions of fishing and agricultural capital, with and without enforcement of fishing regulations that prohibit the use of larger vessels in nearshore habitats. Combining methods from development economics, natural resource economics, and marine ecology, we use a unique dataset and modeling framework to account for linkages between households, business sectors, markets, and local fish stocks. We show that the policies investing capital in local marine fisheries or agricultural sectors achieve income gains for targeted households, but knock-on effects lead to increased harvest of nearshore fish, making them unlikely to achieve conservation objectives in rural coastal economies. However, pairing an agriculture stimulus with increasing enforcement of existing fisheries’ regulations may lead to a win–win situation. While marine-based policies could be an important tool to achieve two of the United Nations Sustainable Development Goals (alleviate poverty and protect vulnerable marine resources), their success is by no means assured and requires consideration of land and marine socioeconomic linkages inherent in rural economies.

Coastal and island nations are adopting “blue growth” sustainable development (SD) policies to alleviate poverty and conserve vulnerable ocean resources. Generally speaking, SD policies manage resources and direct investments in order to meet current and future human needs and aspirations, without endangering the natural systems (1). The feasibility and potential of SD has been the focus of decades of academic research; many regard the consideration of economic, social, environmental, and institutional needs and linkages as fundamental to successful policy design and implementation (2–6). Given their novelty, what constitutes a blue growth policy is not universal (7), but like traditional SD policies that focus on land-based sectors such as agriculture, manufacturing, and energy sectors (8, 9), blue growth policies seek to achieve social, economic, and environmental goals simultaneously (10). Blue growth policies attempt to achieve these goals by supporting marine-based industries such as offshore fishing, aquaculture, shipping, and tourism (11, 12). The marine focus has reinvigorated SD efforts of international organizations (including the Global Environmental Facility, United Nations Food and Agriculture Organization, the European Union, and The World Bank) that have collectively invested hundreds of millions of dollars into the development and monitoring of blue growth programs (12–16).While small-scale artisanal fishers consider a variety of factors when making fishing decisions (17), evidence suggests allocation of time is, in part, based on relative returns to labor (18–21). Thus, some blue growth policies attempt to alter returns to fishing relative to alternative income-generating activities as a way to achieve both poverty alleviation and conservation objectives. For example, if poor fishing households are incentivized to participate in offshore fishing, it may lead to increased household incomes and reduced fishing pressure on overexploited nearshore fish stocks (22, 23). Policies enforcing and increasing the regulation of fishing activities are also considered important to achieving blue growth objectives (10, 24).Many SD policies are designed to reduce upfront costs of switching to more sustainable livelihoods. Historically, large-scale fisheries receive the majority of subsidy benefits (25), arguably to the detriment of small-scale fisheries who are often outcompeted by industrialized operations (26). Recently, however, developing countries including Kenya, the Philippines, India, Tanzania, Vietnam, and Indonesia have been investing in programs that bolster the fishing capacity of small-scale and artisanal fishermen (27–33). These programs are designed to help small-scale fishers access larger or better vessels and gear, allowing them to reach more plentiful fishing grounds, compete with commercial vessels, and relieve pressure on vulnerable nearshore fisheries.Despite the recent surge in popularity, we lack evidence that these marine-based SD policies will achieve both poverty reduction and conservation objectives when implemented in rural economies. The complexity of coupled natural–human systems makes it difficult to measure the ex post performance of SD policies, especially in marine environments (34, 35). Additionally, local market failures due to high transportation costs and poorly developed marketing infrastructure (36) can lead to locally defined prices that fluctuate with changes in local supply and demand; local prices may distort household responses to policies, leading to unintended environmental consequences (37–40). Because local market failures are more common in rural economies in developing countries, methods and lessons learned from studies of industrialized fisheries in developed countries may not be relevant. Rather, management of fisheries in rural coastal economies may be more successful if market imperfections, alternative livelihood options, and ecological feedback are considered (20, 41–47).Recent studies explore the causal impacts of land-based SD policy instruments in developing countries (48–56). A key finding of these studies is that community heterogeneity is an important factor in policy performance. However, findings from forestry research do not necessarily carry over to marine settings because fish resources are mobile and regenerate relatively quickly, and, typically, access rights to fisheries are not well defined. This study begins to address the need for research examining responses to SD policy in rural coastal economies.We use a coupled natural–human modeling framework to estimate the ex ante impacts of common SD policies. Our ex ante mechanistic approach that includes a general equilibrium local economy model captures important dynamic feedback between the economy and health of the fish stocks. Indeed, other researchers have studied the correlations between markets and ecosystems in coastal communities in developing countries (44, 57–59). However, the theoretical structure of our analysis approach allows us to examine the causal mechanisms between policy and its outcomes. Our model captures the feedback between economic sectors and households within the economy (Fig. 1, details in SI Appendix). This broad scope is necessary to estimate the extent to which policies targeting poor households in a community also impact nontargeted households (knock-on effects). For example, a policy supporting a subset of fishing households could be detrimental to other households that harvest from the same fish stocks and compete in the same input and output markets.Open in a separate windowFig. 1.A conceptual framework for the bioeconomic local general equilibrium model. Households are represented by four representative groups and may produce goods and services (e.g., agricultural, offshore and nearshore fish, retail, and restaurants) available in local, and possibly global, markets. The simulated policies provide different types of capital to poor households and may also restrict use of fishing capital.Here, we estimate the impacts of two common marine fisheries policies (provision of offshore fishing vessels and increased enforcement of fishing regulations) and an alternative agricultural policy (provision of agricultural capital) in a rural coastal economy. To estimate the impacts of these SD policies in coastal economies, we use a modeling approach that has been developed using theory from development economics, natural resource economics, and marine ecology (37, 60). Introducing new features to the framework, we develop a model of a rural economy capable of disentangling fisher participation in two distinct fishing activities and household consumption of two fish goods. We use microeconomic data collected from household and business surveys to parameterize and calibrate our model, allowing us to realistically estimate policy impacts. An inherent strength to our methodology is the ability to adjust the structure of the model to represent alternative economies. We demonstrate how the model can be used to predict policy outcomes for a typology of rural coastal economies.Although combining policies that simultaneously target marine and agricultural sectors is currently not part of the dialogue on the adoption of blue SD policies around the world (e.g., see The World Bank’s strategy document for its Blue Economy Program and PROBLUE (13)), we find that pairing policy instruments that target both sectors—increased enforcement of vessel regulations and capital investments in the agricultural sector—is better able to achieve both conservation and poverty reduction goals.Why is an agricultural policy combined with enforcement capabilities of marine fishing regulations able to achieve a win–win while marine-focused SD policies are not? Our coupled natural–human modeling framework highlights the mechanisms leading to this counterintuitive outcome. That is, investing in the agricultural sector increases the returns to agricultural labor, which in turn creates upward pressure on wages and encourages a reduction in labor allocated to nearshore fishing. At the same time, the increased wealth in the local economy due to greater agricultural productivity drives up demand for nearshore fish. Although higher prices of fish draw some labor back into the fishery, increased enforcement of vessel regulations prevents fishers from illegally using larger boats in the nearshore habitat as a means to increase harvests. Without coupling increased enforcement and agricultural subsidy, the higher demand for fish would lead to increased harvests in the nearshore environment and lower fish stocks over time.     

Imaging data in COVID-19 patients: focused on echocardiographic findings

To assess imaging data in COVID-19 patients and its association with clinical course and survival and 86 consecutive patients (52 males, 34 females, mean age?=?58.8 year) with documented COVID-19 infection were included. Seventy-eight patients (91%) were in severe stage of the disease. All patients underwent transthoracic echocardiography. Mean LVEF was 48.1% and mean estimated systolic pulmonary artery pressure (sPAP) was 27.9 mmHg. LV diastolic dysfunction was mildly abnormal in 49 patients (57.6%) and moderately abnormal in 7 cases (8.2%). Pericardial effusion was present in 5/86 (minimal in size in 3 cases and mild- moderate in 2). In 32/86 cases (37.2%), the severity of infection progressed from “severe” to “critical”. Eleven patients (12.8%) died. sPAP and computed tomography score were associated with disease progression (P value?=?0.002, 0.002 respectively). Tricuspid annular plane systolic excursion (TAPSE) was significantly higher in patients with no disease progression compared with those who deteriorated (P value?=?0.005). Pericardial effusion (minimal, mild or moderate) was detected more often in progressive disease (P?=?0.03). sPAP was significantly lower among survivors (P value?=?0.007). Echocardiographic findings (including systolic PAP, TAPSE and pericardial effusion), total CT score may have prognostic and therapeutic implication in COVID-19 patients.

     

Healthy ranges of serum alanine aminotransferase levels in Iranian blood donors

AIM: The healthy ranges for serum alanine aminotransferase (ALT) levels are less well studied. The aim of this study was to define the upper limit of normal (ULN) for serum ALT levels, and to assess factors associated with serum ALT activity in apparently healthy blood donors. METHODS: A total of 1,939 blood donors were included. ALT measurements were performed for all cases using the same laboratory method. Healthy ranges for ALT levels were computed from the population at the lowest risk for liver disease. Univariate and multivariate analyses were performed to evaluate associations between clinical factors and ALT levels. RESULTS: Serum ALT activity was independently associated with body mass index (BMI) and male gender, but not associated with age. Association of ALT with BMI was more prominent in males than in females. Upper limit of normal for non-overweight women (BMI of less than 25) was 34 U/L, and for non-overweight men was 40 U/L. CONCLUSION: Serum ALT is strongly associated with sex and BMI. The normal range of ALT should be defined for male and female separately.     

Healthy ranges of serum alanine aminotransferase levels in Tranian blood donors

AIM:The healthy ranges for serum alanine aminotransferase (ALT) levels are less well studied. The aim of this study was to define the upper limit of normal (ULN) for serum ALT levels, and to assess factors associated with serum ALT activity in apparently healthy blood donors.METHODS: A total of 1 939 blood donors were included.ALT measurements were performed for all cases using the same laboratory method. Healthy ranges for ALT levels were computed from the population at the lowest risk for liver disease. Univariate and multivariate analyses were performed to evaluate associations between clinical factors and ALT levels.RESULTS: Serum ALT activity was independently associated with body mass index (BMI) and male gender, but not associated with age. Association of ALT with BMI was more prominent in males than in females. Upper limit of normal for non-overweight women (BMI of less than 25) was 34 U/L,and for non-overweight men was 40 U/L.CONCLUSION: Serum ALT is strongly associated with sex and BMI. The normal range of ALT should be defined for male and female separately.     

The effect of spraying different disinfectants on condensational silicone impressions; an in vitro study

Background:

Dentistry equipment are exposed to different types of pathogenic microorganisms. The aim of this study was to investigate the effect of spraying three different types of disinfectants on condensational silicones after 5 and 10 min.

Materials and Methods:

Totally, 66 circular samples of condensational silicone impression materials of 1 cm diameter and 2 mm thickness were contaminated by Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans fungus. Except for control samples, all of them were disinfected with sodium hypochlorite (NaOCl) 0.525%, Deconex and Epimax by spraying method. Afterward, they kept in plastic bags with humid rolled cotton for 5 and 10 min. In order to isolate microbiotas, the samples were immersed in 2% trypsin for 1 h and diluted with normal saline in a portion of 1, 1/2, and 1/4. The trypsin suspensions were transferred to culture plates for incubation and colony-forming unit assay. The data were analyzed by Mann–Whitney test and SPSS software version 16 at a significant level of 0.05.

Results:

There was a meaningful difference between disinfection effects of Epimax-Deconex for all mentioned microorganisms after 5 min (P = 0.034), and between disinfection effects of NaOCl 0.525%-Epimax for S. aureus (P = 0.043) and P. aeruginosa (P = 0.046) after 5 min. Furthermore, there was a meaningful difference between disinfection effects of Epimax-Deconex (P = 0.034) and NaOCl 0.525%-Epimax (P = 0.034) for P. aeruginosa after 10 min.

Conclusion:

Condensational silicone can be effectively disinfected by spraying tested three disinfecting agents. More specifically, Deconex showed the best results compared to the other agents.Key Words: Condensational silicone, disinfection, impression materials, spray