Mononuclear phagocyte morphological response to chemoattractants is dependent on geranylgeranyl pyrophosphate.

Statins are used to treat hypercholesterolemia and function by inhibiting the production of the rate-limiting metabolite mevalonate. As such, statin treatment not only inhibits de novo synthesis of cholesterol but also isoprenoids that are involved in prenylation, the posttranslational lipid modification of proteins. The immunomodulatory effects of statins are broad and often conflicting. Previous work demonstrated that statins increased survival and inhibited myeloid cell trafficking in a murine model of sepsis, but the exact mechanisms underlying this phenomenon were unclear. Herein, we investigated the role of prenylation in chemoattractant responses. We found that simvastatin treatment abolished chemoattractant responses induced by stimulation by C5a and FMLP. The inhibitory effect of simvastatin treatment was unaffected by the addition of either farnesyl pyrophosphate (FPP) or squalene but was reversed by restoring geranylgeranyl pyrophosphate (GGPP). Treatment with prenyltransferase inhibitors showed that the chemoattractant response to both chemoattractants was dependent on geranylgeranylation. Proteomic analysis of C15AlkOPP-prenylated proteins identified several geranylgeranylated proteins involved in chemoattractant responses, including RHOA, RAC1, CDC42, and GNG2. Chemoattractant responses in THP-1 human macrophages were also geranylgeranylation dependent. These studies provide data that help clarify paradoxical findings on the immunomodulatory effects of statins. Furthermore, they establish the role of geranylgeranylation in mediating the morphological response to chemoattractant C5a.NEW & NOTEWORTHY The immunomodulatory effect of prenylation is ill-defined. We investigated the role of prenylation on the chemoattractant response to C5a. Simvastatin treatment inhibits the cytoskeletal remodeling associated with a chemotactic response. We showed that the chemoattractant response to C5a was dependent on geranylgeranylation, and proteomic analysis identified several geranylgeranylated proteins that are involved in C5a receptor signaling and cytoskeletal remodeling. Furthermore, they establish the role of geranylgeranylation in mediating the response to chemoattractant C5a.

Dietary Cholesterol Causes Inflammatory Imbalance and Exacerbates Morbidity in Mice Infected with Influenza A Virus.

Influenza is a common cause of pneumonia-induced hospitalization and death, but how host factors function to influence disease susceptibility or severity has not been fully elucidated. Cellular cholesterol levels may affect the pathogenesis of influenza infection, as cholesterol is crucial for viral entry and replication, as well as immune cell proliferation and function. However, there is still conflicting evidence on the extent to which dietary cholesterol influences cholesterol metabolism. In this study, we examined the effects of a high-cholesterol diet in modulating the immune response to influenza A virus (IAV) infection in mice. Mice were fed a standard or a high-cholesterol diet for 5 wk before inoculation with mouse-adapted human IAV (Puerto Rico/8/1934), and tissues were collected at days 0, 4, 8, and 16 postinfection. Cholesterol-fed mice exhibited dyslipidemia characterized by increased levels of total serum cholesterol prior to infection and decreased triglycerides postinfection. Cholesterol-fed mice also displayed increased morbidity compared with control-fed mice, which was neither a result of immunosuppression nor changes in viral load. Instead, transcriptomic analysis of the lungs revealed that dietary cholesterol caused upregulation of genes involved in viral-response pathways and leukocyte trafficking, which coincided with increased numbers of cytokine-producing CD4+ and CD8+ T cells and infiltrating dendritic cells. Morbidity as determined by percent weight loss was highly correlated with numbers of cytokine-producing CD4+ and CD8+ T cells as well as granulocytes. Taken together, dietary cholesterol promoted IAV morbidity via exaggerated cellular immune responses that were independent of viral load.

Public perceptions of air pollution and its impacts on fertility desire: a nationwide study in China.

Over the past few years, there has been a significant focus on air pollution due to its various detrimental effects on human health. However, its influence on people's tendency to have children remains uncertain, as only a few studies have examined the correlation between public perception of air pollution and the desire to start a family. This article introduces a theoretical framework utilizing a two-stage interval iteration model to explore the connection between children's relative utility and the perception of air pollution. Data for this study were gathered from the "Chinese General Social Survey" (CGSS 2013). The CGSS 2013 project employed a four-stage stratified random sampling technique and conducted household interviews using questionnaires. The sample covered 28 provincial-level cities across China. The hypothesis was tested using a Probit regression model. The findings indicate that individuals considering air pollution a significant issue are 8.62% less likely to have more than one child. The variation in fertility desire sensitivity to air pollution points to heterogeneity among residents, such as registered residents and those living in various residential areas, as well as individuals with different characteristics like education levels. The study concludes that air quality significantly influences human fertility desire, highlighting the urgent necessity to raise awareness of environmental protection issues among both the public and authorities. In particular, there are two key steps to address this issue. Firstly, the government should establish clear air pollution control objectives and refine policies to enhance governance efficiency. Secondly, there is a need to encourage environmentally friendly behaviours among the public, promote more significant involvement in public environmental matters, and ensure effective oversight of the government's responsibilities in managing air pollution.

Comparison of the efficacy of Diclofenac 0.1% and Nepafenac 0.1% on anterior chamber cells in patients undergoing cataract surgery: A prospective clinical practice trial.

Objectives: To compare the efficacy of topical Nepafenac 0.1 % and Diclofenac 0.1% eye drops in reducing the aqueous cells in the anterior chamber in an un-eventful post cataract surgery. Methods: This prospective, clinical trial was conducted at an Eye OPD of Qazi Hussain Ahmad Medical Complex, Nowshera from January till December 2021. Ophthalmic assessment included Visual acuity (VA), slit-lamp examination, Intraocular pressure (IOP), Central macular thickness (CMT) by Optical coherence tomography (OCT) and anterior chamber-aqueous cells measurement pre-operatively and at day 1st, 2nd, 4th and 8th week post-operatively. Patients were randomly allocated to topical diclofenac 0.1% (TD) four times a day and nepafenac 0.1% (TN) three times a day for four weeks each along with topical steroids and antibiotics. Results: Seventy patients (70) were randomly distributed into two treatment arms of 35 each. In both the arms VA improved which achieved a level of statistical significance post-operatively, however statistically insignificant difference was observed between the groups at 8th week follow up visit (p= 0.62). However, IOP and CMT values didn't achieve statistical significance between the arms pre and post operatively. In TN arm, level of AC-cells at 2nd and 4th week post-operatively were significantly lower (10.54 ± 4.05 and 08.20 ± 4.44) than TD arm (11.28 ± 5.04 and 09. 66 ± 5.50) with statistically significant difference (p < 0.05). Conclusions: Topical Nepafenac 0.1% was more effective in suppressing the anterior chamber inflammation as compared to diclofenac during the early few post-operative weeks.

Applications of machine learning and artificial intelligence for Covid-19 (SARS-CoV-2) pandemic: A review.

BACKGROUND AND OBJECTIVE: During the recent global urgency, scientists, clinicians, and healthcare experts around the globe keep on searching for a new technology to support in tackling the Covid-19 pandemic. The evidence of Machine Learning (ML) and Artificial Intelligence (AI) application on the previous epidemic encourage researchers by giving a new angle to fight against the novel Coronavirus outbreak. This paper aims to comprehensively review the role of AI and ML as one significant method in the arena of screening, predicting, forecasting, contact tracing, and drug development for SARS-CoV-2 and its related epidemic. METHOD: A selective assessment of information on the research article was executed on the databases related to the application of ML and AI technology on Covid-19. Rapid and critical analysis of the three crucial parameters, i.e., abstract, methodology, and the conclusion was done to relate to the model's possibilities for tackling the SARS-CoV-2 epidemic. RESULT: This paper addresses on recent studies that apply ML and AI technology towards augmenting the researchers on multiple angles. It also addresses a few errors and challenges while using such algorithms in real-world problems. The paper also discusses suggestions conveying researchers on model design, medical experts, and policymakers in the current situation while tackling the Covid-19 pandemic and ahead. CONCLUSION: The ongoing development in AI and ML has significantly improved treatment, medication, screening, prediction, forecasting, contact tracing, and drug/vaccine development process for the Covid-19 pandemic and reduce the human intervention in medical practice. However, most of the models are not deployed enough to show their real-world operation, but they are still up to the mark to tackle the SARS-CoV-2 epidemic.

Globalization, institutions, and environmental quality in Middle East and North African countries.

Sustainable development has received significant attention due to rapidly rising environmental issues, and finding solutions to these issues caused by various indicators are the subject of research nowadays. To this end, the increasing globalization and institutional quality to address environmental challenges have become hot subject and need better attention. Accordingly, this study enhances the literature by examining the role of political stability, the rule of law, control of corruption, and globalization on the environment for 14 Middle Eastern and North African (MENA) countries between 1996 & 2018, applying cross-sectional augmented autoregressive distributed lags (CS-ARDL) approach. The short and long-run estimates obtained from CS-ARDL confirm that globalization, the rule of law, political stability, and corruption control significantly reduce carbon emissions (CO2e). Contrarily, energy production, financial development, and economic growth have significant positive effects, suggesting they raise CO2e. The study also estimates a robustness analysis with the Driscoll-Kraay estimator, confirming results on signs and magnitude identical to those with CS-ARDL. These results drive the MENA countries to adhere to environmental standards to reduce CO2e strictly. Environmental-friendly industrial techniques should be employed, mainly while producing. The governments of these countries should facilitate the governance process through the globalization of environmental products to ensure long-term environmental sustainability.

Determinants of the CO2 emissions, economic growth, and ecological footprint in Pakistan: asymmetric and symmetric role of agricultural and financial inclusion.

In this study, the effects of financial inclusion (FI), agricultural innovation (AI), trade (TR), and forest rent (FR) on carbon dioxide emissions (CO2), economic growth (Y), and ecological footprint (EFP) for Pakistan from 1970 to 2017 are examined using symmetric and asymmetric cointegration approaches. These links are investigated using linear and non-linear autoregressive distributive lag (NARDL) techniques. In contrast to the asymmetry results, the symmetric results revealed no cointegration among the variables over the long run. Moreover, asymmetry results from the Y-model indicated that a positive shock in AI significantly affects Y over the long run while raising it over the short term. Furthermore, CO2 rises in the wake of positive shocks like AI, Y, and FR but falls in the wake of adverse shocks. A negative shock to FI raises CO2 temporarily, whereas a negative shock to FR causes CO2 emissions to fall over time. According to the EFP-model, long-term EFP is decreased by both positive shocks to AI and adverse shocks to FR with one-period lags. On the other hand, positive shocks to FI and FR cause the short-term EFP to rise. In addition to a bidirectional causal relationship between Y, EFP, and FI, we found a one-way causative relationship between Y, FR, AI, CO2, and EFP. The FMOLS estimator also supports NARDL estimations. The key recommendations to help Pakistan keep its environment and economy are to enhance green mechanization in agriculture, allocate adequate research and development funds, and initiate integrated environmental and economic growth policies by relevant institutions.

Prophylactic simvastatin increased survival during endotoxemia and inhibited granulocyte trafficking in a cell-intrinsic manner.

Cross sectional studies have shown that statin-users have improved odds of surviving severe sepsis. Meanwhile controlled clinical trials failed to demonstrate improved sepsis survival with acute statin administration following hospitalization. Here, a lethal murine peritoneal lipopolysaccharide (LPS) endotoxemia model was used to assess the efficacy of chronic versus acute simvastatin on survival. Mirroring clinical observations, chronic but not acute treatment with simvastatin significantly increased survival. At a pre-mortality time point in LPS-treated mice, chronic simvastatin suppressed granulocyte trafficking in to the lungs and peritoneum without otherwise suppressing emergency myelopoiesis, myeloid cells in circulation, or inflammatory cytokines. Chronic simvastatin treatment significantly downregulated inflammatory chemokine gene signature in the lungs of LPS-treated mice. Thus, it was unclear if simvastatin was inhibiting granulocyte chemotaxis in a cell intrinsic or extrinsic manner. Adoptive transfer of fluorescently labeled granulocytes from statin and vehicle treated mice into LPS-treated mice showed that simvastatin inhibited lung-granulocyte trafficking in a cell intrinsic manner. Congruent with this, chemotaxis experiments using in vitro macrophages and ex vivo granulocytes demonstrated that simvastatin inhibited chemotaxis in a cell-intrinsic manner. Collectively, chronic but not acute simvastatin treatment improved survival in murine endotoxemia, and this was associated with cell-intrinsic inhibition of granulocyte chemotaxis.

Globalization, industrialization, and urbanization in Belt and Road Initiative countries: implications for environmental sustainability and energy demand.

This study investigates the influence of globalization, industrialization, urbanization, and financial development on energy demand and environmental quality. The current study uses annual data from 92 Belt and Road Initiative countries over the sample period 1995 to 2018. After the confirmation of cross-sectional dependency and cointegration among the variables, we applied System Generalized Method of Moment, Driscoll and Karry approach, and Dumitrescu and Hurlin causality test to check the long-run relationship and direction of causality, respectively. The results reveal that globalization, financial development, industrialization, urbanization, and economic growth significantly increase the energy demand and CO2 emissions over the sample period. In addition, the granger causality test confirms a one-way causal relationship between financial development and CO2 emissions, GDP per capita and CO2 emissions, and globalization and energy demand. Moreover, there is a two-way causal relationship between urbanization and energy demand and financial development and GDP per capita. Based on these findings, number of suitable policy recommendations presented in the prospective of Belt and Road Initiative countries.

Energy poverty assessment in the Belt and Road Initiative countries: based on entropy weight-TOPSIS approach.

The Belt and Road Initiative (BRI) countries are mainly developing countries with severe energy poverty. This study combines the entropy weight and the Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) method to measure energy poverty at the household, enterprise, and national levels in 82 BRI countries. This study aims to investigate and discuss how to encourage BRI countries to develop effective decision-making mechanisms for developing more targeted supply-side solutions to domestic energy poverty. A geographic information system (GIS) is also used to construct spatial distribution maps to assess energy poverty. The findings show that countries in South Asia, Southeast Asia, and North Africa have the highest levels of energy poverty, while countries in West Asia and Europe have the lowest. East Timor, Tonga, and Equatorial Guinea are of the most extremely lowest. The assessment methodology used in this paper focuses not only on the energy poverty faced by households, but also on the overall energy supply and service situation at the enterprise and national levels. These perspectives are likely to influence policy making and help the governments in addressing domestic energy poverty more effectively from the supply side.

Transcatheter closure of recurrent aortic pseudoaneurysm previously treated by Amplatzer occluder device.

Thoracic pseudoaneurysms are a rare variety of aortic disorders that are potentially fatal. Traditionally, these are treated surgically. False aneurysms are usually a late complication of a previous surgical procedure. Surgical management is often complicated by poor outcomes with high morbidity and mortality. We report a patient with recurrence of an aortic pseudoaneurysm after closure with an Amplatzer (AGA Medical Corp, Plymouth, NH) septal occluder that was successfully treated with a second Amplatzer device.

The empirical relationship between environmental degradation, economic growth, and social well-being in Belt and Road Initiative countries.

This study used principal component analysis (PCA) to develop composite indexes for economic growth, environmental degradation, and social well-being. The mutual relationship between these indexes was empirically tested using a panel vector autoregressive model based on a generalized method of moment approach (PVAR-GMM), and robustness was determined with Driscoll and Kraay regression. To this end, we gathered the data for 36 Belt and Road Initiative (BRI) countries over the period 1995-2016. Using a multivariate framework, the empirical results showed that environmental degradation and social well-being have a significant positive impact on the economic growth index. The social well-being index and economic growth are contributors to environmental degradation. Similarly, economic growth, in the long run, improves social well-being. The results confirm bidirectional causality between economic growth and environmental degradation. Another bidirectional causal relationship was found between economic growth and social well-being. Further, causality exists from social well-being to environmental degradation, but not vice versa. The analysis of the impulse response function exhibited the presence of the environmental Kuznets curve phenomenon in BRI countries. Moreover, the results of variance decomposition suggested that a shock in one index spills over to other indexes simultaneously. The study suggests that policymakers should consider social well-being and environmental degradation in economic activity to achieve sustainable development goals.

Investment risk and natural resource potential in "Belt & Road Initiative" countries: A multi-criteria decision-making approach.

Chinese enterprises that conduct overseas investment projects encounter diverse challenges that emerge from political, economic, social, and environmental risks in the host countries. To better assess the overseas investment risks faced by Chinese enterprises, this study introduced and assessed novel aspects and an indicator system. Moreover, the "Technique for Order Preference by Similarity to Ideal Solution" (TOPSIS) method based on entropy weight was performed to generate a comprehensive assessment of China's foreign investment risk and natural resource potential in 63 "Belt & Road Initiative" (BRI) countries. This study aims to encourage Chinese enterprises to devise suitable overseas investment decision-making strategies concerning natural resource potential in host countries. A Geographic Information System (GIS) map was also created to assess the potential risks and opportunities for Chinese enterprises when making investment decisions in host countries. The findings indicate that the majority of countries in Central and Eastern Europe and other BRI countries such as Singapore, Malaysia, Nepal, Bhutan, Russia, Armenia, and the United Arab Emirates were the most suitable choices for Chinese enterprises engaging in overseas investment. Based on these results, Chinese enterprises could manage and execute BRI projects more effectively to minimise potential risks and maximise their investment benefits.

The impression of technological innovations and natural resources in energy-growth-environment nexus: A new look into BRICS economies.

We utilize extended STIRPAT "(stochastic impact of regression on population, affluence, and technology)" model to explore the impact of technological innovations and natural resources in energy-growth-environment nexus for a panel of BRICS "(i.e., Brazil, Russia, India, China, and South Africa)" economies over 1985-2014. Using Augmented Mean Group (AMG), and Fully Modified-Least Square (FM-LS) panel algorithms, the results indicate that technical innovations can reduce CO2 emissions and help to improve economic growth in BRICS countries. Furthermore, our estimates support energy push emissions and validate the existence of the traditional "environmental Kuznets curve (EKC)" for BRICS and partially across the countries. Moreover, the empirical results indicate one-way causality from income to CO2; a two-way causal relationship is operational between income and energy use and between energy use and CO2 emissions in BRICS and individual countries. The results suggest that policymakers may consider the role of innovations as a clean source of technology to achieve energy security and a sustainable environment.

Hydrolyzed Fat Formula Increases Brain White Matter in Small for Gestational Age and Appropriate for Gestational Age Neonatal Piglets.

Background: Intrauterine growth restriction is a common cause of small for gestational age (SGA) infants worldwide. SGA infants are deficient in digestive enzymes required for fat digestion and absorption compared to appropriate for gestational age (AGA) infants, putting them at risk for impaired neurocognitive development. Objective: The objective was to determine if a hydrolyzed fat (HF) infant formula containing soy free fatty acids, 2-monoacylglycerolpalmitate, cholesterol, and soy lecithin could increase brain tissue incorporation of essential fatty acids or white matter to enhance brain development in SGA and AGA neonatal piglet models. Methods: Sex-matched, littermate pairs of SGA (0.5-0.9 kg) and AGA (1.2-1.8 kg) 2 days old piglets (N = 60) were randomly assigned to control (CON) or HF formula diets in a 2 × 2 factorial design. On day 14, 24 piglets were used for hippocampal RNA-sequencing; the rest began a spatial learning task. On days 26-29, brain structure was assessed by magnetic resonance imaging (MRI). Cerebellum and hippocampus were analyzed for fatty acid content. Results: SGA piglets grew more slowly than AGA piglets, with no effect of diet on daily weight gain or weight at MRI. HF diet did not affect brain weight. HF diet increased relative volumes of 7 brain regions and white matter (WM) volume in both SGA and AGA piglets. However, HF did not ameliorate SGA total WM integrity deficits. RNA sequencing revealed SGA piglets had increased gene expression of synapse and cell signaling pathways and decreased expression of ribosome pathways in the hippocampus compared to AGA. HF decreased expression of immune response related genes in the hippocampus of AGA and SGA piglets, but did not correct gene expression patterns in SGA piglets. Piglets learned the T-maze task at the same rate, but SGA HF, SGA CON, and AGA HF piglets had more accurate performance than AGA CON piglets on reversal day 2. HF increased arachidonic acid (ARA) percentage in the cerebellum and total ARA in the hippocampus. Conclusions: HF enhanced brain development in the neonatal piglet measured by brain volume and WM volume in specific brain regions; however, more studies are needed to assess long-term outcomes.

Percutaneous closure of aortic pseudoaneurysm by Amplatzer occluder device-case series of six patients.

Thoracic pseudoaneurysms are rare variety of aortic disorders. Although mostly asymptomatic, they represent potentially fatal conditions (Sullivan et al., Chest 1988;93:138-143; Razzouk et al., Ann Surg 1993;59:818-823) that are traditionally treated surgically. False aneurysms of aorta are usually a late complication of previous surgical procedure (Sullivan et al., 1988)-especially reconstructive surgery, trauma (Razzouk et al., 1993), and rarely infection (Sanchez-Recalde et al., J Am Coll Cardiol 2003;41:152-154). Surgical management is often complicated by poor outcomes with high morbidity and mortality (Mulder et al., Arch Surg 1998;133:45-49). Endovascular treatment is emerging as promising options for aortic diseases with fewer complications. We report a series of six cases at a single center where Amplatzer device was used to treat thoracic aortic pseudo aneurysm. To our knowledge only one series of three cases (Kanani et al., Catheter Cardiovasc Interv 2007;69:146-153) and few case reports (Bashi et al., Catheter Cardiovasc Interv 2005;65:547-551) of successful closure have been published previously. Our case series is the largest, so far, including mortality and specifically the preprocedural and postprocedural CT angiographic assessment of the pseudoaneurysms.

Does energy consumption, financial development, and investment contribute to ecological footprints in BRI regions?

This study applies augmented mean group (AMG) along with common correlated effect mean group (CCEMG) estimator and panel heterogeneous causality to examine the interrelationship between GDP, energy consumption, financial development, foreign investment, and ecological footprints for five Belt and Road initiative (BRI) regions and in aggregated panel of BRI over the time 1990-2016. Using a multivariate framework, this study examines four alternative and conceivable hypotheses, including Pollution haven hypothesis, environmental Kuznets curve hypothesis, energy push emission hypothesis, and finance push emission hypothesis. The empirical results supported all four hypotheses for the panel of BRI and partially supported the existence of these hypotheses across the regions. Moreover, a variety of causal nexuses has been discussed in the study. Based on these results, the current research has proposed policy implications to combat the ecological footprints of BRI countries and across the regions.

Viability assessment by multidetector computed tomography in Takotsubo cardiomyopathy.

Stress-induced cardiomyopathy, known as Takotsubo, is an increasingly recognized syndrome, characterized by transient apical or midventricular dysfunction, which mimics myocardial infarction in the absence of significant coronary artery disease, and is thought to be due to transient catecholamine overload. Multidetector computed tomography (MDCT) is a novel imaging approach increasingly recognized as a rapid, noninvasive diagnostic modality to assess coronary anatomy and cardiac function. Few reports have been published regarding its utility in the assessment of myocardial viability after myocardial infarction. We describe 2 patients with Takotsubo cardiomyopathy who underwent MDCT imaging. To our knowledge, this is the first report describing the utility of MDCT that shows the absence of delayed hyperenhancement in patients with Takotsubo cardiomyopathy.

Transhepatic approach to closure of patent foramen ovale: report of 2 cases in adults.

Patent foramen ovale is increasingly diagnosed in patients who are undergoing clinical study for cryptogenic stroke or migraine. In addition, patent foramen ovale is often suspected as a cause of paradoxical embolism in patients who present with arterial thromboembolism. The femoral venous approach to closure has been the mainstay. When the femoral approach is not feasible, septal occluder devices have been deployed via a transjugular approach.Herein, we describe 2 cases of patent foramen ovale in which the transhepatic approach was used for closure. To our knowledge, this is the 1st report of a transhepatic approach to patent foramen ovale closure in an adult patient. Moreover, no previous case of patent foramen ovale closure has been reported in a patient with interrupted inferior vena cava.