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Background: Patients who have recovered from COVID-19 suffer from lasting symptoms such as numerous physical and mental disorders. It seems that these conditions can disturb the activities of daily living. Therefore, the aim of this study was to compare fatigue, quality of life and pulmonary function in recovered COVID-19 patients and healthy individuals. Materials and Methods: This experimental study was conducted on 25 recovered COVID-19 patients, discharged from Qom hospitals, Iran, in 2022, and 25 healthy people. The inclusion criteria for healthy people were a negative PCR test result and the age range of 35 to 59 years, and for recovered COVID-19 patients were at least one week of hospitalization due to COVID-19. Fatigue severity was assessed using the Fatigue Severity Questionnaire (FSS), quality of life through 36-question questionnaire (Sf-36) and pulmonary function through spirometry. The comparison of the mean data of the two groups was done using Mann-Whitney U test and independent t-test by SPSS-27 software. Results: Factors including fatigue (P0.001), physical health (P

Abstract Purpose Diabetes is the leading cause of kidney disease. Up to 40% of the population with diabetes experience diabetic kidney disease (DKD). The correlation of DKD with insulin resistance (IR) indices has been shown in previous studies. In this study, the objective was to evaluate surrogate IR indices, including the Triglyceride-Glucose (TyG) index, Visceral Adiposity Index (VAI), Lipid Accumulation Product (LAP), and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) to find the most valuable index for the correlation between albuminuria and IR in the type 2 diabetes (T2D) population. Albuminuria is defined as urine albumin excretion of > 30 mg/day. Methods In this cross-sectional study, 2934 participants were enrolled and evaluated for urinary albumin excretion, and albuminuria was detected in 526 of the entries. The logistic regression models and Receiver Operating Characteristic (ROC) curve analysis were performed to assess the relationship of TyG index, VAI, LAP, and HOMA-IR's with albuminuria in patients with T2D. Results The TyG index had the highest association (OR 1.67) with the presence of albuminuria in patients with T2D, followed by HOMA-IR (OR 1.127), VAI (OR 1.028), and LAP (OR 1.004). These four indices remained independent after adjustment for multiple confounders. Based on the ROC curve, TyG revealed the best area under the curve (AUC) for revealing albuminuria with sufficient accuracy (AUC: 0.62) in comparison with other measured indices. The calculated TyG index cut-off point for the presence of albuminuria was 9.39. Conclusion Among the indices, TyG index had the most significant correlation with albuminuria in patients with T2D.

Abstract Two common features of dietary polyphenols have hampered our mechanistic understanding of their beneficial effects for decades: targeting multiple organs and extremely low bioavailability. We show here that resveratrol intervention (REV-I) in high-fat diet (HFD)-challenged male mice inhibits chylomicron secretion, associated with reduced expression of jejunal but not hepatic scavenger receptor class B type 1 (SR-B1). Intestinal mucosa-specific SR-B1-/- mice on HFD-challenge exhibit improved lipid homeostasis but show virtually no further response to REV-I. SR-B1 expression in Caco-2 cells cannot be repressed by pure resveratrol compound while fecal-microbiota transplantation from mice on REV-I suppresses jejunal SR-B1 in recipient mice. REV-I reduces fecal levels of bile acids and activity of fecal bile-salt hydrolase. In Caco-2 cells, chenodeoxycholic acid treatment stimulates both FXR and SR-B1. We conclude that gut microbiome is the primary target of REV-I, and REV-I improves lipid homeostasis at least partially via attenuating FXR-stimulated gut SR-B1 elevation.

Abstract The demand for industrial genetically modified host cells were increased with the growth of the biopharmaceutical market. Numerous studies on improving host cell productivity have shown that altering host cell growth and viability through genetic engineering can increase recombinant protein production. During the last decades, it was demonstrated that overexpression or downregulation of some microRNAs in Chinese Hamster Ovary (CHO) cells as the host cell in biopharmaceutical manufacturing, can improve their productivity. The selection of microRNA targets has been based on their previously identified role in human cancers. MicroRNA-32 (miR-32), which is conserved between humans and hamsters (Crisetulus griseus), was shown to play a role in the regulation of cell proliferation and apoptosis in some human cancers. In this study, we investigated the effect of miR-32 overexpression on the productivity of CHO-VEGF-trap cells. Our results indicated that stable overexpression of miR-32 could dramatically increase the productivity of CHO cells by 1.8-fold. It also significantly increases cell viability, batch culture longevity, and cell growth. To achieve these results, following the construction of a single clone producing an Fc-fusion protein, we transfected cells with a pLexJRed-miR-32 plasmid to stably produce the microRNA and evaluate the impact of mir-32 overexpression on cell productivity, growth and viability in compare with scrambled control. Our findings highlight the application of miRNAs as engineering tools and indicated that miR-32 could be a target for engineering CHO cells to increase cell productivity.

AbstractIntroduction: Ilmenite is considered the most important source of titanium and its oxide and is usually processed by sulfate, chloride, and smelting processes. In all these processes, incomplete removal of iron combined with titanium is the main problem. In order to improve iron removal, pre-processing of ilmenite by carbothermic reduction processes is a solution used in the industry. Considering the technical and environmental problems of carbothermic, replacing coke by hydrogen, is a new method that brings significant advantages in the subsequent separation processes.Methods: In this research, Kahnuj ilmenite concentrate is first characterized through physical, chemical, and structural analysis techniques. Gas reduction of the ilmenite pellets using pure hydrogen gas was performed, and then reduction products subjected to further characterization. The reduction degree was calculated based on the weight loss after the reduction process. Samples were characterized using optical microscopy, electron microscopy, X-ray diffraction analysis, and energy-dispersive X-ray spectroscopy.Findings: The Kahnuj ilmenite concentrate is composed of the FeTiO3 as the main phase, hematite, and a partial sphene phase within the ilmenite grains. Mn and Mg found in the chemical analysis of the concentrate led to incomplete separation of iron oxides in ilmenite.In this research, a maximum reduction degree of 76% is achievable at a reduction temperature of 1100 °C. With an increase in the reduction temperature, metallic iron diffused out the ilmenite structure and accumulated around the particles. With an increase in the reduction time, the aggregation of the pseudobrookite phase, occurred in the center of the ilmenite particles.

Exogenous causes, such as alcohol use, and endogenous factors, such as temperament and sex, can modulate developmental trajectories of adolescent neurofunctional maturation. We examined how these factors affect sexual dimorphism in brain functional networks in youth drinking below diagnostic threshold for alcohol use disorder (AUD). Based on the 3-year, annually acquired, longitudinal resting-state functional magnetic resonance imaging (MRI) data of 526 adolescents (12-21 years at baseline) from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) cohort, developmental trajectories of 23 intrinsic functional networks (IFNs) were analyzed for (1) sexual dimorphism in 259 participants who were no-to-low drinkers throughout this period; (2) sex-alcohol interactions in two age- and sex-matched NCANDA subgroups (N = 76 each), half no-to-low, and half moderate-to-heavy drinkers; and (3) moderating effects of gender-specific alcohol dose effects and a multifactorial impulsivity measure on IFN connectivity in all NCANDA participants. Results showed that sex differences in no-to-low drinkers diminished with age in the inferior-occipital network, yet girls had weaker within-network connectivity than boys in six other networks. Effects of adolescent alcohol use were more pronounced in girls than boys in three IFNs. In particular, girls showed greater within-network connectivity in two motor networks with more alcohol consumption, and these effects were mediated by sensation-seeking only in girls. Our results implied that drinking might attenuate the naturally diminishing sexual differences by disrupting the maturation of network efficiency more severely in girls. The sex-alcohol-dose effect might explain why women are at higher risk of alcohol-related health and psychosocial consequences than men.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

BackgroundCisplatin, a chemotherapy used to treat solid tumors, causes acute kidney injury (AKI), a known risk factor for chronic kidney disease and mortality. AKI diagnosis relies on biomarkers which are only measurable after kidney damage has occurred and functional impairment is apparent; this prevents timely AKI diagnosis and treatment. Metabolomics seeks to identify metabolite patterns involved in cell tissue metabolism related to disease or patient factors. The A Canadian study of Cisplatin mEtabolomics and NephroToxicity (ACCENT) team was established to harness the power of metabolomics to identify novel biomarkers that predict risk and discriminate for presence of cisplatin nephrotoxicity, so that early intervention strategies to mitigate onset and severity of AKI can be implemented.ObjectiveDescribe the design and methods of the ACCENT study which aims to identify and validate metabolomic profiles in urine and serum associated with risk for cisplatin-mediated nephrotoxicity in children and adults.DesignObservational prospective cohort study.SettingSix Canadian oncology centers (3 pediatric, 1 adult and 2 both).PatientsThree hundred adults and 300 children planned to receive cisplatin therapy.MeasurementsDuring two cisplatin infusion cycles, serum and urine will be measured for creatinine and electrolytes to ascertain AKI. Many patient and disease variables will be collected prospectively at baseline and throughout therapy. Metabolomic analyses of serum and urine will be done using mass spectrometry. An untargeted metabolomics approach will be used to analyze serum and urine samples before and after cisplatin infusions to identify candidate biomarkers of cisplatin AKI. Candidate metabolites will be validated using an independent cohort.MethodsPatients will be recruited before their first cycle of cisplatin. Blood and urine will be collected at specified time points before and after cisplatin during the first infusion and an infusion later during cancer treatment. The primary outcome is AKI, defined using a traditional serum creatinine-based definition and an electrolyte abnormality-based definition. Chart review 3 months after cisplatin therapy end will be conducted to document kidney health and survival.LimitationsIt may not be possible to adjust for all measured and unmeasured confounders when evaluating prediction of AKI using metabolite profiles. Collection of data across multiple sites will be a challenge.ConclusionsACCENT is the largest study of children and adults treated with cisplatin and aims to reimagine the current model for AKI diagnoses using metabolomics. The identification of biomarkers predicting and detecting AKI in children and adults treated with cisplatin can greatly inform future clinical investigations and practices.

Antimicrobial stewardship involves a delicate balance between the risk of undertreating individuals and the potential societal burden of overprescribing antimicrobials. This balance is especially crucial in neonatal care. In this observational study, the usefulness of biomarkers of infectious diseases (calprotectin, procalcitonin (PCT), C-reactive protein (CRP), and white blood cells (WBCs) were evaluated in 141 febrile infants aged 28–90 days presenting to an emergency department. Since our focus was on the usefulness of serum calprotectin, this biomarker was not part of clinical decision-making. A significant difference was observed in the levels of all biomarkers, related to final discharge diagnosis and disposition status. The difference in levels related to antibiotic prescription was significant for all biomarkers but WBCs. The performance of calprotectin in the detection of bacterial infections (AUC (95% CI): 0.804 (0.691, 0.916)) was comparable to the performance of both PCT (0.901 (0.823, 0.980)) and CRP (0.859 (0.764, 0.953)) and superior to the WBC count (0.684 (0.544, 0.823)). Procalcitonin and CRP demonstrated a statistically significantly higher specificity relative to calprotectin. In this cohort, antibiotic use did not always correlate to a definite diagnosis of confirmed bacterial infection. The sample size was limited due to associated challenges with recruiting febrile infants. Hence, there is a need for adequate diagnostic tools to help discriminate between various kinds of infections. This study suggests serum calprotectin, procalcitonin, and CRP may serve as valuable biomarkers to differentiate between types of infection, in addition to clinical input and decision-making.

Atopic dermatitis (AD), a chronic-relapsing inflammatory skin disorder, manifests with intense itching and eczematous lesions impairing quality of life. A heterogeneous population, and regional clinical practices for treating AD warrant the development of guidelines in Qatar. Therefore, guidelines for the management of moderate-to-severe AD in Qatar have been developed and discussed. Experts, including dermatologists and immunologists, used the Delphi technique for developing guidelines. Consensus was defined as ≥75% agreement or disagreement. AD is highly prevalent in primary and tertiary dermatology centers. AD-associated foot eczema and psoriasiform eczema are more frequent in Qatar than in Europe or USA. SCORing Atopic Dermatitis Index quantifies disease severity and itch. Dermatology Life Quality Index assesses the quality of life. Atopic Dermatitis Control Tool assesses long-term disease control. Moderate-severe AD benefits from new topicals like Janus-kinase-inhibitors or PDE4-inhibitors combined with phototherapy. Currently approved systemic agents are dupilumab, baricitinib, abrocitinib, and upadacitinib. New anti-IL-13 and anti-IL-31 therapies will soon be available. Patient education, allergy testing, and comorbidity consideration are critical in the management of AD. The expert panel established a comprehensive and pragmatic approach to managing moderate-to-severe AD, thereby assisting clinical decision-making for healthcare professionals in Qatar.

This study aims to investigate the relationship between currency crises and fluctuations in banking credits in Iran. Utilizing a time-varying coefficients approach spanning from 1989 to 2022, alongside economic boom and recession indicators, the analysis assesses the impact of currency crisis occurrences on banking credit cycles. The currency crisis index, based on a dummy variable, and the credit cycle index, derived from banking credit booms and busts, are examined alongside the economic cycle, gauged by production fluctuations using intermediate filters. Findings suggest that currency crises influence the occurrence of credit cycles and production facility cycles, while shocks stemming from economic cycles exacerbate currency crises and credit cycles within the banking system. Given the bidirectional relationship observed between the currency crisis index and credit cycles, policymakers are advised to exercise caution in implementing drastic measures during economic fluctuations and credit cycles. Prudent management of currency markets can mitigate the adverse effects of currency crises on economic variables. Introduction Financial crises have profound and far-reaching implications, encompassing economic, political, and social spheres. They exact a heavy toll on society, manifesting in reduced welfare, heightened unemployment, and diminished public trust. Given their extensive repercussions across various sectors, financial crises have garnered considerable attention from economic policymakers. Among the diverse forms they take, currency crises stand out as particularly significant. These crises, marked by sudden depreciation or robust intervention by monetary authorities to bolster national currency values through foreign exchange reserve sales, exert widespread influence across the economy. They precipitate pressures on consumers, producers, and central banks, disrupting market dynamics for other assets and impinging on monetary policy frameworks. Moreover, they adversely impact credit allocation within the banking system, underscoring their multifaceted ramifications. The main question investigated in this article pertains to the interplay between currency crises and credit cycles during the economic upswings and downturns in Iran. Given the nuanced nature of credit cycle delineation, coupled with the fluctuating dynamics of economic expansions and contractions, the vector autoregression (VAR) approach with time-varying coefficients has been employed to examine the evolving dynamics of this relationship spanning the period from 1989 to 2022. This methodological choice is motivated by its ability to yield more realistic findings, accounting for the temporal variability of coefficients and the dynamic interrelationships among variables. This contrasts with traditional time series models and conventional VAR frameworks, thereby enabling the formulation of more informed policy recommendations. Methods and Material In this study, credit cycles and currency crises spanning the period from 1989 to 2022 were extracted using the Cristiano and Fitzgerald filters. The relationship between these components and economic expansions and contractions was then explored. Additionally, the dynamic interplay among these variables was assessed using the vector autoregression method with time-varying coefficients (TVP-VAR). The study incorporates four primary variables: the currency crisis index, credit cycle, economic boom and recession periods, and liquidity growth. To compute the currency crisis index, a virtual variable was employed. The data utilized in this research were sourced from the Central Bank's database and statistical quarterly reports. Results and Discussion The findings from the TVP-VAR model reveal several significant dynamics. Initially, in response to a shock from the credit cycle, liquidity growth displays a positive reaction, with the impact dissipating over the long term. Conversely, the currency crisis initially reacts negatively to the credit cycle shock but eventually exhibits a positive response, indicating that the creation of the credit cycle contributes to the occurrence of currency crises. The economic cycle, when shocked by the credit cycle, responds negatively. On the other hand, when the credit cycle is shocked by the currency crisis, it initially reacts positively, followed by a subsequent negative reaction, with the long-term effect dissipating. Liquidity growth, in response to the currency crisis shock, demonstrates a positive reaction. Regarding the economic cycle, its response to the currency crisis shock is initially negative, then positive, and eventually negative again, suggesting that currency crises give rise to periods of economic expansion and contraction. In another aspect, the shock from the credit cycle prompts a positive reaction in liquidity growth, while the currency crisis variable responds negatively to the credit cycle shock. Initially, the credit cycle variable reacts positively to the credit cycle shock, but over time, it turns negative, with the impact fading in the long run. Finally, in response to the shock of liquidity growth, the currency crisis variable shows a positive reaction, the economic cycle reacts positively, and the credit cycle also responds positively, with the effect of the shock diminishing over time.. Figure 1. IRF diagram in TVP-VAR model format Conclusion The findings from this study highlight the adverse impact of currency crises on the economic cycle, leading to periods of recession. Conversely, economic downturns can exacerbate currency crises. Based on these results, it is advisable for monetary authorities and central banks to refrain from implementing contractionary policies, particularly in foreign exchange policies and credit restrictions, during economic downturns. Instead, they should expedite the process of foreign exchange allocation to economic enterprises for purchasing production inputs, thereby fostering an environment conducive to improving production and stimulating economic growth. Furthermore, during credit crises, commercial banks are encouraged to increase credit limits for commercial enterprises and streamline the loan repayment process in the micro-finance sector. These measures aim to prevent the economy from slipping into recession and promote sustainable economic development.

Background: Knee osteoarthritis is the most degenerative joint disease and can consequently cause a defect in balance control. Controlling balance is necessary to prevent physical and psychological damage. The current study investigated the effects of the Mulligan mobilization technique on static and dynamic balances in patients with moderate to severe knee osteoarthritis. Methods: In a randomized controlled clinical trial, 31 patients with moderate to severe knee osteoarthritis were selected and then randomly assigned to two groups of treatment (16 patients) and control (15 patients). Static and dynamic balances and pain score were evaluated in these patients once before and once after 10 sessions of treatment. Independent and paired t-tests were used for statistical analysis. The level of statistical significance was set at p