Functional analysis, diversity, and distribution of the ean cluster responsible for 17ß-estradiol degradation in sphingomonads.

17ß-estradiol (E2) is a natural endocrine disruptor that is frequently detected in surface and groundwater sources, thereby threatening ecosystems and human health. The newly isolated E2-degrading strain Sphingomonas colocasiae C3-2 can degrade E2 through both the 4,5-seco pathway and the 9,10-seco pathway; the former is the primary pathway supporting the growth of this strain and the latter is a branching pathway. The novel gene cluster ean was found to be responsible for E2 degradation through the 4,5-seco pathway, where E2 is converted to estrone (E1) by EanA, which belongs to the short-chain dehydrogenases/reductases (SDR) superfamily. A three-component oxygenase system (including the P450 monooxygenase EanB1, the small iron-sulfur protein ferredoxin EanB2, and the ferredoxin reductase EanB3) was responsible for hydroxylating E1 to 4-hydroxyestrone (4-OH-E1). The enzymatic assay showed that the proportion of the three components is critical for its function. The dioxygenase EanC catalyzes ring A cleavage of 4-OH-E1, and the oxidoreductase EanD is responsible for the decarboxylation of the ring A-cleavage product of 4-OH-E1. EanR, a TetR family transcriptional regulator, acts as a transcriptional repressor of the ean cluster. The ean cluster was also found in other reported E2-degrading sphingomonads. In addition, the novel two-component monooxygenase EanE1E2 can open ring B of 4-OH-E1 via the 9,10-seco pathway, but its encoding genes are not located within the ean cluster. These results refine research on genes involved in E2 degradation and enrich the understanding of the cleavages of ring A and ring B of E2.IMPORTANCESteroid estrogens have been detected in diverse environments, ranging from oceans and rivers to soils and groundwater, posing serious risks to both human health and ecological safety. The United States National Toxicology Program and the World Health Organization have both classified estrogens as Group 1 carcinogens. Several model organisms (proteobacteria) have established the 4,5-seco pathway for estrogen degradation. In this study, the newly isolated Sphingomonas colocasiae C3-2 could degrade E2 through both the 4,5-seco pathway and the 9,10-seco pathway. The novel gene cluster ean (including eanA, eanB1, eanC, and eanD) responsible for E2 degradation by the 4,5-seco pathway was identified; the novel two-component monooxygenase EanE1E2 can open ring B of 4-OH-E1 through the 9,10-seco pathway. The TetR family transcriptional regulator EanR acts as a transcriptional repressor of the ean cluster. The cluster ean was also found to be present in other reported E2-degrading sphingomonads, indicating the ubiquity of the E2 metabolism in the environment.

The Impact of the Measure Used to Calculate the Distance between Exchange Rate Time Series on the Topological Structure of the Currency Network.

Structural properties of the currency market were examined with the use of topological networks. Relationships between currencies were analyzed by constructing minimal spanning trees (MSTs). The dissimilarities between time series of currency returns were measured in various ways: by applying Euclidean distance, Pearson's linear correlation coefficient, Spearman's rank correlation coefficient, Kendall's coefficient, partial correlation, dynamic time warping measure, and Kullback-Leibler relative entropy. For the constructed MSTs, their topological characteristics were analyzed and conclusions were drawn regarding the influence of the dissimilarity measure used. It turned out that the strength of most types of correlations was highly dependent on the choice of the numeraire currency, while partial correlations were invariant in this respect. It can be stated that a network built on the basis of partial correlations provides a more adequate illustration of pairwise relationships in the foreign exchange market. The data for quotations of 37 of the most important world currencies and four precious metals in the period from 1 January 2019 to 31 December 2022 were used. The outbreak of the COVID-19 pandemic in 2020 and Russia's invasion of Ukraine in 2022 triggered changes in the topology of the currency network. As a result of these crises, the average distances between tree nodes decreased and the centralization of graphs increased. Our results confirm that currencies are often pegged to other currencies due to countries' geographic locations and economic ties. The detected structures can be useful in descriptions of the currency market, can help in constructing a stable portfolio of the foreign exchange rates, and can be a valuable tool in searching for economic factors influencing specific groups of countries.

An empirical investigation of time-varying cost-effectiveness across the product life cycle.

Cost-effectiveness is traditionally treated as a static estimate driven by clinical trial efficacy and drug price at launch. Prior studies suggest that cost-effectiveness varies over the drug's lifetime. We examined the impact of "learning by doing," one of the least studied drivers of changes in cost-effectiveness across the product life cycle. We combined time-series trends in effectiveness over time by cancer regimen using the Surveillance, Epidemiology, and End Results-Medicare database. We estimated the time-varying effects of treatments in colorectal and pancreatic cancer over their life cycle, including FOLFOX (leucovorin, 5-fluorouracil, and oxaliplatin) and gemcitabine, on survival of patients. Mean prices over time by strength and dosage form were calculated using historical wholesale acquisition costs. We found consistent downward trends in the mortality hazard ratios, which suggest that effectiveness improves over time. In the case of first-line FOLFOX for colorectal cancer, the implied incremental cost-effectiveness ratio based on the observational data fell from $610,000 per life year gained in 2004 to $27,000 per life year gained in 2011. Cost-effectiveness estimated at launch is unlikely to be representative of cost-effectiveness over the drug's lifetime. In the drugs studied, the impact of time-varying clinical effectiveness dominated the impact of changing prices overtime.

Early-onset of symptoms and clinical course of Pompe disease associated with the c.-32-13 T > G variant.

BACKGROUND: Individuals with late-onset Pompe disease (LOPD) and the common c.-32-13 T > G variant are widely thought to have milder, adult-onset disease. This belief, and the consequent low suspicion of clinical involvement in children, has led to delays in diagnosis and treatment initiation in patients with early onset of symptoms. Previous reports of LOPD in children do not include description of the early-onset phenotype. This description of signs and symptoms, some of which are subtle and less known, is important to facilitate prompt identification and appropriate treatment in symptomatic children. METHODS: Retrospective chart review of a cohort of 84 LOPD patients with the c.-32-13 T > G variant was conducted to identify patients diagnosed clinically (as opposed to through newborn screening) who had clinically documented symptom-onset within the first two years of life. RESULTS: Four patients had early onset of symptoms, with age at onset ranging from 10 days to 20 months. Initial symptoms included delay in achievement of gross motor milestones, signs of proximal muscle weakness, swallow and feeding difficulties, and sleep apnea. Early and characteristic alterations in posture and movement were identified in all patients. Age at diagnosis ranged from 10 months to 26 months. Median age at enzyme replacement therapy (ERT) initiation was 23.5 months. Despite ERT, progression of musculoskeletal involvement and residual muscle weakness was evident in all patients, as evidenced by ptosis, myopathic facies, scoliosis, lumbar lordosis, scapular winging, and trunk and lower extremity weakness. Standardized functional assessments showed gross motor function below age level as measured by the Alberta Infant Motor Scales, the Peabody Developmental Motor Scales-2, the Bruininks-Oseretsky Test of Motor Proficiency, Second Edition, and the six-minute walk test. CONCLUSIONS: Onset of symptoms including delay in achievement of gross motor milestones, signs of proximal muscle weakness, swallow and feeding difficulties, and sleep apnea in the first two years of life is not uncommon in individuals with LOPD and the c.-32-13 T > G variant. Patients with early-onset disease appear to have a more, rapid and severe progression of disease with persistent residual muscle deficits which partially improve with higher doses of ERT. Careful evaluation for specific and characteristic patterns of posture and movement in patients with this variant is necessary to identify those who have early onset of disease. Increased awareness of the early-onset signs and symptoms may also enable early identification of disease onset in children who are diagnosed through newborn screening.

Fetal Serum Metabolites Are Independently Associated with Gestational Diabetes Mellitus.

BACKGROUND/AIMS: Gestational diabetes (GDM) might be associated with alterations in the metabolomic profile of affected mothers and their offspring. Until now, there is a paucity of studies that investigated both, the maternal and the fetal serum metabolome in the setting of GDM. Mounting evidence suggests that the fetus is not just passively affected by gestational disease but might play an active role in it. Metabolomic studies performed in maternal blood and fetal cord blood could help to better discern distinct fetal from maternal disease interactions. METHODS: At the time of birth, serum samples from mothers and newborns (cord blood samples) were collected and screened for 163 metabolites utilizing tandem mass spectrometry. The cohort consisted of 412 mother/child pairs, including 31 cases of maternal GDM. RESULTS: An initial non-adjusted analysis showed that eight metabolites in the maternal blood and 54 metabolites in the cord blood were associated with GDM. After Benjamini-Hochberg (BH) procedure and adjustment for confounding factors for GDM, fetal phosphatidylcholine acyl-alkyl C 32: 1 and proline still showed an independent association with GDM. CONCLUSIONS: This study found metabolites in cord blood which were associated with GDM, even after adjustment for established risk factors of GDM. To the best of our knowledge, this is the first study demonstrating an independent association between fetal serum metabolites and maternal GDM. Our findings might suggest a potential effect of the fetal metabolome on maternal GDM.

Molecular characterization and expression analysis of complement component 3 in dojo loach (Misgurnus anguillicaudatus).

The complement component 3 (C3) is a central component of complement system. All three pathways converge at formation of C3 convertases and share the terminal pathways of membrane attack complex (MAC) formation. In this study, three isoforms of C3 were discovered in Misgurnus anguillicaudatus, named "C3-1", "C3-2" and "C3-3", respectively. The full-length of C3-1 cDNA sequence was firstly identified and analyzed from dojo loach (Misgurnus anguillicaudatus). The Ma-C3-1 cDNA sequence comprised of 4509 bp encoding 1454 amino acids with a putative signal peptide of 20 amino acid residues. The deduced amino acid sequence showed that Ma-C3-1 has conserved residues and domain, which are known to be crucial for C3 function. Interestingly, an amino acid substitution of the highly conserved GCGEQ was discovered in Ma-C3-1. Phylogenetic analysis showed that Ma-C3-1 was closely related to Cyprinidae. The mRNA expression levels of three isoforms of C3 were detected in kidney, eye, spleen, gonad, heart, fin ray, gut, muscle, brain, gill, skin, blood and liver. The expression of Ma-C3-1 and Ma-C3-3 were mainly detected in liver, followed by spleen, gonad. However, the high expression of Ma-C3-2 was found in kidney, followed by blood and gonad. The morphological changes of gill and skin, and the expression pattern of these three isoforms C3 molecular following the infection with Aeromonas hydrophila were investigated. The mRNA expression levels of three C3 isoforms were up-regulated in the gill, skin, liver and spleen after infection with A.hydrophila. Similarly, challenge experiments resulted in significant up-regulated expression of other complement-relevant genes in gill, liver and skin, such as C4, C5, C8b, especially at 24 h and 36 h. These results suggest that complement system might play an important role not only in liver, but also in the mucosal tissues as gill and skin of teleost fish.

Insight into the phenotype of infants with Pompe disease identified by newborn screening with the common c.-32-13T>G "late-onset" GAA variant.

OBJECTIVE: Newborn screening (NBS) has led to early diagnosis and early initiation of treatment for infantile onset Pompe Disease (IOPD). However, guidelines for management of late onset Pompe disease (LOPD) via NBS, especially with the IVS c.-32-13T>G are not clear. This IVS variant is noted in 68-90% cases with LOPD and has been presumed to result in "adult" disease in compound heterozygosity, with a few cases with earlier onset and a mild to no phenotype in homozygosity. Our study evaluates newborns with LOPD having IVS variant with a diligent multidisciplinary approach to determine if they have an early presentation. METHODS: Seven children with LOPD identified by NBS with IVS variant (3 compound heterozygous, and 4 homozygous) were evaluated with clinical, biochemical (CK, AST, ALT, and urinary Glc4), cardiac evaluation, physical therapy (PT), occupational, and speech/language therapy. RESULTS: All seven patients demonstrated motor involvement by age 6months; the three patients with c.-32-13 T>G variant in compound heterozygosity had symptoms as neonates. Patients with c.-32-13 T>G variant in compound heterozygosity had more involvement with persistent hyperCKemia, elevated AST and ALT, swallowing difficulties, limb-girdle weakness, delayed motor milestones, and were initiated on ERT. The patients with c.-32-13T>G variant in homozygosity had normal laboratory parameters, and presented with very subtle yet LOPD specific signs, identified only by meticulous assessments. CONCLUSION: This patient cohort represents the first carefully phenotyped cohort of infants with LOPD with the "late-onset" GAA variant c.-32-13T>G detected by NBS in the USA. It emphasizes not only the opportunity for early detection of skeletal and other muscle involvement in infants with c.-32-13T>G variant but also a high probability of overlooking or underestimating the significance of clinically present and detectable features. It can thus serve as a valuable contribution in the development of evaluation and treatment algorithms for infants with LOPD.

Lending to Parents and Insuring Children: Is There a Role for Microcredit in Complementing Health Insurance in Rural China?

This paper assesses the causal impact on child health of borrowing formal microcredit for Chinese rural households by exploiting a panel dataset (2000 and 2004) in a poor northwest province. Endogenous borrowing is controlled for in a dynamic regression-discontinuity design creating a quasi-experimental environment for causal inferences. There is causal relationship running from formal microcredit to improved child health in the short term, while past borrowing behaviour has no protracted impact on subsequent child health outcomes. Moreover, formal microcredit appears to be a complement to health insurance in improving child health through two mechanisms-it enhances affordability for out-of-pocket health care expenditure and helps buffer consumption against adverse health shocks and financial risk incurred by current health insurance arrangements. Government efforts in expanding health insurance for rural households would be more likely to achieve its optimal goals of improving child health outcomes if combined with sufficient access to formal microcredit.

The impact of government failure on tourism in the Philippines.

While the Philippines aspires to be one of the top tourist destinations in Southeast Asia, self-inflicted wounds like the failure of the government to comply with international aviation safety standards may derail the country from achieving its goals. This article estimates the short- and long-term impact of the US FAA downgrade of the Philippine civil aviation system in 2008 and the EU ban of Philippine carriers in 2010 on tourist expenditures, arrivals, and length of stay using monthly time series data. The econometric model, consisting of three equations due to the endogeneity of the tourist arrivals and length of stay variables in the tourist expenditures equation, is estimated simultaneously using the generalized method of moments. The results indicate that the US FAA downgrade and the EU ban impact monthly tourist receipts negatively in the short term while the downgrade also impacts tourist expenditures in the long term. Moreover, the ban impacts length of stay negatively in the short and long term while the downgrade impacts length of stay negatively only in the long term. The substantial decline in tourism receipts from 2008 to 2010 despite an increasing trend in tourist arrivals is due to the shorter stay of tourists, indicating that high-spending tourists have not returned following the downgrade and ban.

Functional proteomics approaches for the identification of transnitrosylase and denitrosylase targets.

Protein S-nitrosylation is a dynamic post-translational modification (PTM) of specific cysteines within a target protein. Both proteins and small molecules are known to regulate the attachment and removal of this PTM, and proteins exhibiting such a function are transnitrosylase or denitrosylase candidates. With the advent of the biotin switch technique coupled to high-throughput proteomics workflows, the identification and quantification of large numbers of S-nitrosylated proteins and peptides is now possible. Proper analysis and interpretation of high throughout and quantitative proteomics data will help identify specific transnitrosylase and denitrosylase target peptide sequences and contribute to an understanding of the function and regulation of specific S-nitrosylation events. Here we describe the application of a quantitative proteomics approach using isotope-coded affinity tags (ICAT) in the biotin switch approach for the identification of transnitrosylation and denitrosylation targets of thioredoxin 1, an enigmatic protein with both reported transnitrosylase and denitrosylase activities.

The impact of containment measures and monetary and fiscal responses on US financial markets during the COVID-19 pandemic.

This paper analyses the effects of containment measures and monetary and fiscal responses on US financial markets during the Covid-19 pandemic. More specifically, it applies fractional integration methods to analyse their impact on the daily S&P500, the US Treasury Bond Index (USTB), the S&P Green Bond Index (GREEN) and the Dow Jones (DJ) Islamic World Market Index (ISLAM) over the period 1/01/2020-10/03/2021. The results suggest that all four indices are highly persistent and exhibit orders of integration close to 1. A small degree of mean reversion is observed only for the S&P500 under the assumption of white noise errors and USTB with autocorrelated errors; therefore, market efficiency appears to hold in most cases. The mortality rate, surprisingly, seems to have affected stock and bond prices positively with autocorrelated errors. As for the policy responses, both the containment and fiscal measures had a rather limited impact, whilst there were significant announcement effects which lifted markets, especially in the case of monetary announcements. There is also evidence of a significant, positive response to changes in the effective Federal funds rate, which suggests that the financial industry, mainly benefiting from interest rises, plays a dominant role.

Developing Therapeutic Splice-Correcting Antisense Oligomers for Adult-Onset Pompe Disease with c.-32-13T>G Mutation.

The mutation c.-32-13T>G in the GAA gene impacts normal exon 2 splicing and is found in two-thirds of late-onset Pompe disease cases. We have explored a therapeutic strategy using splice modulating phosphorodiamidate morpholino oligomers to enhance GAA exon 2 inclusion in the mature mRNA of patients carrying this common mutation. We performed in silico analysis of the GAA gene transcript for potential splicing silencers and designed oligomers targeting motifs predicted to enhance exon 2 retention in the mature mRNA. Two patient-derived fibroblasts were obtained from Coriell Institute for Medical Research, and seven fibroblast strains from unrelated patients were supplied by Westmead Hospital in Sydney, Australia. Both fibroblasts and forced-myogenic cells were treated with optimized phosphorodiamidate morpholino oligomers supplied by Sarepta Therapeutics. Total RNA and protein were extracted from the cells after incubation with phosphorodiamidate morpholino oligomers, and RT-PCR and RT-qPCR were performed to confirm exon 2 inclusion is enhanced. Acid α-glucosidase activity and expression levels were also assessed to confirm therapeutic potential.

Elucidation of the Potential Hair Growth-Promoting Effect of Botryococcus terribilis, Its Novel Compound Methylated-Meijicoccene, and C32 Botryococcene on Cultured Hair Follicle Dermal Papilla Cells Using DNA Microarray Gene Expression Analysis.

A person's quality of life can be adversely affected by hair loss. Microalgae are widely recognized for their abundance and rich functional components. Here, we evaluated the hair growth effect of a green alga, Botryococcus terribilis (B. terribilis), in vitro using hair follicle dermal papilla cells (HFDPCs). We isolated two types of cells from B. terribilis-green and orange cells, obtained from two different culture conditions. Microarray and real time-PCR results revealed that both cell types stimulated the expression of several pathways and genes associated with different aspect of the hair follicle cycle. Additionally, we demonstrated B. terribilis' effect on collagen and keratin synthesis and inflammation reduction. We successfully isolated a novel compound, methylated-meijicoccene (me-meijicoccene), and C32 botryococcene from B. terribilis to validate their promising effects. Our study revealed that treatment with the two compounds had no cytotoxic effect on HFDPCs and significantly enhanced the gene expression levels of hair growth markers at low concentrations. Our study provides the first evidence of the underlying hair growth promoting effect of B. terribilis and its novel compound, me-meijicoccene, and C32 botryococcene.

Hospitalization risk in pediatric patients with bipolar disorder treated with lurasidone vs. other oral atypical antipsychotics: a real-world retrospective claims database study.

BACKGROUND: Real-world evidence on atypical antipsychotic (AAP) use in pediatric bipolar disorder is limited. OBJECTIVE: To assess the risk of all-cause and psychiatric hospitalization among pediatric patients with bipolar disorder when treated with lurasidone versus other atypical antipsychotics (AAPs). METHODS: This retrospective cohort study used commercial claims data (January 1, 2011 to June 30, 2017) to identify pediatric patients (age ≤17 years) with bipolar disorder treated with oral atypical antipsychotics (N = 16,201). The date of the first claim for an AAP defined the index date, with pre- and post-index periods of 180 days. Each month of the post-index period was categorized as monotherapy treatment with lurasidone, aripiprazole, olanzapine, quetiapine, or risperidone, no/minimal treatment, or other. The risk of all-cause and psychiatric hospitalizations (defined by a psychiatric diagnosis on the facility claim) was analyzed based on treatment in the current month, time-varying covariates (prior treatment-month classification, hospitalization in the prior month, emergency room visit in the prior month), and fixed covariates (age, gender, pervasive development disorder/mental retardation, disruptive behavior/conduct disorder, attention deficit hyperactivity disorder, depression, anxiety, adjustment disorder, obesity, diabetes, antidepressants, anxiolytics, other co-medication) using a marginal structural model. RESULTS: Treatment with aripiprazole (OR = 1.60, 95% CI: 1.08-2.36) and olanzapine (OR = 1.68, CI: 1.03-2.71) was associated with significantly higher odds of all-cause hospitalizations compared to lurasidone, but treatment with quetiapine (OR = 1.03, CI: 0.69-1.54) or risperidone (OR = 1.02, CI: 0.68-1.53) was not. Similarly, treatment with aripiprazole (OR = 1.61, 95% CI: 1.08-2.38) and olanzapine (OR = 1.73, CI: 1.06-2.80) was associated with significantly higher odds of psychiatric hospitalizations compared to lurasidone, but treatment with quetiapine (OR = 1.02, CI: 0.68-1.54) or risperidone (OR = 1.01, CI: 0.67-1.51) was not. CONCLUSION: In usual clinical care, pediatric patients with bipolar disorder treated with lurasidone had a significantly lower risk of all-cause and psychiatric hospitalizations when compared to aripiprazole and olanzapine, but not quetiapine or risperidone.

Cost-effectiveness of nivolumab monotherapy in the third-line treatment of small cell lung cancer.

AIMS: Present cost-effectiveness analysis of nivolumab monotherapy vs. commonly prescribed third-line (3 L+) treatment in small cell lung cancer (SCLC). MATERIALS AND METHODS: A three health states partitioned survival model (progression-free, progressed disease, and death; US payer perspective) was developed. The systematic literature review identified no randomized controlled or single-arm trials with separate outcomes for 3 L + SCLC patients. Topotecan was chosen as a comparator because it is frequently prescribed in real-world practice for 3 L SCLC. Clinical inputs for topotecan were derived from the Flatiron database with inclusion/exclusion criteria matched to patients treated with 3 L + nivolumab in CheckMate 032. Intravenous (IV) and oral topotecan clinical efficacy were assumed equivalent. Base-case analysis used a 20-year lifetime horizon. An annual discount rate of 3.0% for costs and outcomes was applied. Uncertainty was assessed using sensitivity analyses adjusted for key parameters. RESULTS: Incremental cost per quality-adjusted life-year (QALY) gained with nivolumab was US$153,312 vs. IV topotecan and US$123,003 vs. oral topotecan, respectively. When results were disaggregated, nivolumab-related costs were mainly driven by drug acquisition costs, and topotecan-related costs were primarily due to adverse event treatment. Mean overall survival (OS) was 21.69 months with nivolumab and 5.80 months with IV or oral topotecan. More favorable outcomes were found by the landmark response analyses. Deterministic sensitivity analyses showed that changes to the discount rate for costs and outcomes and body weight had the greatest impacts on results. LIMITATIONS: Included use of real-world data for OS outcomes associated with 3 L topotecan, use of second-line topotecan data for progression-free survival, and no indirect costs. CONCLUSIONS: Based on the literature on willingness-to-pay for a QALY in metastatic cancer, nivolumab monotherapy might represent a cost-effective option for 3 L + treatment of SCLC compared with IV and oral topotecan. Sensitivity analysis using response-based methods yielded further favorable cost-effectiveness estimates.

A Matrix-Variate t Model for Networks.

Networks represent a useful tool to describe relationships among financial firms and network analysis has been extensively used in recent years to study financial connectedness. An aspect, which is often neglected, is that network observations come with errors from different sources, such as estimation and measurement errors, thus a proper statistical treatment of the data is needed before network analysis can be performed. We show that node centrality measures can be heavily affected by random errors and propose a flexible model based on the matrix-variate t distribution and a Bayesian inference procedure to de-noise the data. We provide an application to a network among European financial institutions.

Supramolecular organization and biological interaction of squalenoyl siRNA nanoparticles.

Small interfering RNAs (siRNA) are attractive and powerful tools to inhibit the expression of a targeted gene. However, their extreme hydrophilicities combined with a negative charge and short plasma half-life counteract their use as therapeutics. Previously, we chemically linked siRNA to squalene (SQ) which self-assembled as nanoparticles (NPs) with pharmacological efficiency in cancers and recently in a hereditary neuropathy. In order to understand the siRNA-SQ NP assembly and fate once intravenously injected, the present study detailed characterization of siRNA-SQ NP structure and its interaction with serum components. From SAXS and SANS analysis, we propose that the siRNA-SQ bioconjugate self-assembled as 11-nm diameter supramolecular assemblies, which are connected one to another to form spherical nanoparticles of around 130-nm diameter. The siRNA-SQ NPs were stable in biological media and interacted with serum components, notably with albumin and LDL. The high specificity of siRNA to decrease or normalize gene expression and the high colloidal stability when encapsulated into squalene nanoparticles offer promising targeted therapy with wide applications for pathologies with gene expression dysregulation.

Testing the role of oil production in the environmental Kuznets curve of oil producing countries: New insights from Method of Moments Quantile Regression.

The global economic growth has triggered the continual increase in oil demand for transportation and petrochemical sectors which offshoots environmental pollution. Though there exists literature on environmental Kuznets curve, however, very few examine the scope in the light of fossil fuel energy production. This paper investigated the dynamic effect of oil production on carbon emissions in 15 oil-producing countries by accounting for the role of electricity production, economic growth, democracy, and trade over the period 1980-2010. Using the novel Method of Moments Quantile Regression (MMQR) with fixed effects, the results found an inverted U-shape relationship between economic growth and CO2 emissions only at median and higher emission countries, thus, validating the environmental Kuznets curve hypothesis. Oil production increases CO2 emissions significantly from the first to sixth quantiles with greater effect at the lowest quantile and weaker effect at the highest quantile. Electricity production was found to increase CO2 emissions while trade condenses CO2 emissions across all the quantiles thereby confirming the pollution halo hypothesis for oil-producing countries. The effect of democracy was positive across all the quantiles but only significant in countries with average CO2 emissions. The findings provide insight for policymakers to mitigate CO2 emissions in oil-producing countries through diversification and clean energy technologies such as carbon capture and storage.

Households Health Expenditure in Interannual Correlation With Public Health Expenditure in Greece.

The aim of this article is to investigate the relationship between the public and the private health expenditure (macroeconomic and microeconomic approach) over time and within the recession and austerity period in Greece, in order to find out whether the strict Memorandum health policies pass, influence, or go along with the health expenditure to the final consumer, i.e., the health services user. In this context, by using econometric tools, such as multiple regression and cointegration analysis on the raw microdata of Household Budget Surveys from 1987/88 up to 2018, as well as by using data of public expenditure of Organization for Economic Co-operation and Development-Health Statistics 2019 in the Stata version 13, the study compares the variation of household and public health expenditures before and after the financial crisis in Greece and also examines the correlation between the two variables. The analysis demonstrated that the Greek household health expenditure (HHE) was rapidly increasing during the period 1988-2008, and afterward, it started decreasing. Moreover, the total private and the total public health expenditures seem to have a bidirectional long-run relationship and significant cointegration. The same was observed regarding the public expenditure and household medical services expenditure, as well as pharmaceuticals. Furthermore, the results indicate that over the years of recession, the monthly HHE decreases, due to the confiscation of middle-class income, which led to consumerism restrictions. However, as households are now spending a bigger portion of their shrunken income for health (as health is an inelastic commodity), HHE, as a proportion of total private expenditure, has eventually risen.

A Newborn Screening, Presymptomatically Identified Infant With Late-Onset Pompe Disease: Case Report, Parental Experience, and Recommendations.

Pompe disease is an inherited lysosomal storage disorder caused by acid alpha-glucosidase (GAA) enzyme deficiency, resulting in muscle and neuron intralysosomal glycogen storage. Clinical symptoms vary from the severe, infantile-onset form with hypertrophic cardiomyopathy, gross motor delay, and early death from respiratory insufficiency; to a late-onset form with variable onset of proximal muscle weakness and progressive respiratory insufficiency. Newborn screening programs have been instituted to presymptomatically identify neonates with infantile-onset Pompe disease for early initiation of treatment. However, infants with late-onset Pompe disease are also identified, leaving families and physicians in a state of uncertainty regarding prognosis, necessity, and timing of treatment initiation. This report presents a 31 5/7 weeks' gestational age premature infant flagged positive for Pompe disease with low dried blood spot GAA activity; sequencing identified biparental c.-32-13T>G/c.29delA GAA variants predicting late-onset Pompe disease. The infant's parents' initial reactions to the positive newborn screen, subsequent experience during confirmatory testing, and post-confirmation reflections are also reported. While uncertainties regarding natural history and prognosis of presymptomatically-identified late-onset Pompe disease infants will be elucidated with additional experience, suggestions for education of first-line providers are provided to accurately communicate results and compassionately counsel families regarding anxiety-provoking positive newborn screen results.