Determining the prevalence of people's knowledge that third-hand smoke is harmful to health: A meta-analysis study.

INTRODUCTION: Although the health effects of first-hand smoke and second-hand smoke are well known, third-hand smoke (THS) is a relatively new concept. We estimated the prevalence of people's knowledge that THS is harmful to health, including for some subgroups, in a meta-analysis. METHODS: We searched PubMed, Web of Science, Scopus, EBSCO Host, ProQuest, and YOKTEZ databases for the prevalence of people's knowledge that THS is harmful to health using specified search words. A total of 12 publications (n = 8549 people) were included in the meta-analysis. The random effect model was used for meta-analysis, and Cochran's Q test and I2 values were used to determine heterogeneity. Subgroup analyzes and meta-regression were also performed. RESULTS: The prevalence of people's knowledge that THS is harmful was 80.1%. The prevalence of people's knowledge that THS is harmful for children was 82%, and the prevalence of people's knowledge that THS is harmful for adults was 70.4%. For health professionals, the prevalence of people's knowledge that THS is harmful for children was 89.8%, the highest prevalence value calculated in this meta-analysis. Cochran's Q test and I2 values indicated that the included studies were heterogeneous. CONCLUSIONS: In this meta-analysis, the overall prevalence of people's knowledge that THS is harmful was 80.1%, but large variations were found between samples.

Two-Dimensional MXene as a Promising Adsorbent for Trihalomethanes Removal: A Density-Functional Theory Study.

This groundbreaking research delves into the intricate molecular interactions between MXene and trihalomethanes (THs) through a comprehensive theoretical study employing density-functional theory (DFT). Trihalomethanes are common carcinogenic chlorination byproducts found in water sanitation systems. This study focuses on a pristine MXene [Mn+1·Xn] monolayer and its various terminal [Tx] functional groups [Mn+1·XnTx], strategically placed on the surface for enhanced performance. Our investigation involves a detailed analysis of the adsorption energies of THs on different MXene types, with the MXene-Cl layer emerging as the most compatible variant. This specific MXene-Cl layer exhibits remarkable properties, including a total dipole moment (TDM) of 12.443 Debye and a bandgap of 0.570 eV, achieved through meticulous geometry optimization and computational techniques. Notably, THs such as trichloromethane (CHCl3), bromide-chloromethane (CHBrCl2), and dibromochloromethane (CHBr2Cl) demonstrate the highest TDM values, indicating substantial changes in electronic and optical parameters, with TDM values of 16.363, 15.998, and 16.017 Debye, respectively. These findings highlight the potential of the MXene-Cl layer as an effective adsorbent and detector for CHF3, CHClF2, CHCl3, CHBrCl2, and CHBr2Cl. Additionally, we observe a proportional increase in the TDM and bandgap energy, indicative of conductivity, for various termination atom combinations, such as Mxene-O-OH, Mxene-O-F, Mxene-O-Cl, Mxene-OH-F, Mxene-F-Cl, and Mxene-OH-Cl, with bandgap energies measured at 0.734, 0.940, 1.120, 0.835, and 0.927 eV, respectively. Utilizing DFT, we elucidate the adsorption energies of THs on different MXene surfaces. Our results conclusively demonstrate the significant influence of the termination atom nature and quantity on MXene's primitive TDM value. This research contributes to our understanding of MXene-THs interactions, offering promising avenues for the development of efficient adsorbents and detectors for THs. Ultimately, these advancements hold the potential to revolutionize water sanitation practices and enhance environmental safety.

Thirdhand tobacco smoke exposure increases the genetic background-dependent risk of pan-tumor development in Collaborative Cross mice.

Increasing evidence has shown that thirdhand smoke (THS) exposure is likely to induce adverse health effects. An important knowledge gap remains in our understanding of THS exposure related to cancer risk in the human population. Population-based animal models are useful and powerful in investigating the interplay between host genetics and THS exposure on cancer risk. Here, we used the Collaborative Cross (CC) mouse population-based model system, which recapitulates the genetic and phenotypic diversity observed in the human population, to assess cancer risk after a short period of exposure, between 4 and 9 weeks of age. Eight CC strains (CC001, CC019, CC026, CC036, CC037, CC041, CC042 and CC051) were included in our study. We quantified pan-tumor incidence, tumor burden per mouse, organ tumor spectrum and tumor-free survival until 18 months of age. At the population level, we observed a significantly increased pan-tumor incidence and tumor burden per mouse in THS-treated mice as compared to the control (p = 3.04E-06). Lung and liver tissues exhibited the largest risk of undergoing tumorigenesis after THS exposure. Tumor-free survival was significantly reduced in THS-treated mice compared to control (p = 0.044). At the individual strain level, we observed a large variation in tumor incidence across the 8 CC strains. CC036 and CC041 exhibited a significant increase in pan-tumor incidence (p = 0.0084 and p = 0.000066, respectively) after THS exposure compared to control. We conclude that early-life THS exposure increases tumor development in CC mice and that host genetic background plays an important role in individual susceptibility to THS-induced tumorigenesis. Genetic background is an important factor that should be taken into account when determining human cancer risk of THS exposure.

Chemical and in vitro toxicological comparison of emissions from a heated tobacco product and the 1R6F reference cigarette.

It has previously been found that, compared with cigarette smoke, the aerosols generated by heated tobacco products contain fewer and lower harmful and potentially harmful constituents (HPHCs) and elicit lower biological activity in in vitro models and lower smoking-related exposure biomarker levels in clinical studies. It is important to accumulate such scientific evidences for heated tobacco products with a novel heating system, because different heating system may affect the quantitative aspect of the amount of HPHCs and the qualitative aspect of the biological activity of the aerosol generated. Here, the chemical properties of, and toxicological responses to aerosols emitted by DT3.0a, a new heated tobacco product with a novel heating system, and cigarette smoke (CS) were compared, using chemical analyses, in vitro battery (standardized genotoxicity and cytotoxicity) assays, and mechanistic (ToxTracker and two-dimensional cell culture) assays. Regular- and menthol-flavored DT3.0a and standard 1R6F reference cigarettes were tested. Selected HPHC yields were lower in DT3.0a aerosol than 1R6F CS. The genotoxicity-related assays indicated that DT3.0a aerosol was not genotoxic, regardless of metabolic activation. The other biological assays indicated that less cytotoxicity induction and oxidative stress response were elicited by DT3.0a aerosol compared with 1R6F CS. Similar results were found for both regular and menthol DT3.0a. Like previous reports for heated tobacco products with other heating systems, the results of this study indicated that DT3.0a aerosols have chemical and biological properties less likely to be harmful than 1R6F CS.

A case report on recurrent alternating Tolosa-Hunt syndrome due to bacterial sphenoid sinusitis: rediscussing the diagnostic terminology and classification.

BACKGROUND: Tolosa-Hunt syndrome (THS) is characterized by painful ophthalmoplegia caused by idiopathic granulomatous inflammation involving the cavernous sinus region. Patients respond well to steroid therapy. THS is included in the differential diagnosis of cavernous sinus syndrome, so it is important to fully exclude other lesions in this area before treatment, otherwise steroid treatment may lead to fatal outcomes. Here we describe a patient who initially presented with symptoms that simulated THS symptoms and developed recurrent alternating painful ophthalmoplegia during follow-up, and the patient was finally diagnosed with cavernous sinusitis caused by bacterial sphenoid sinusitis. CASE PRESENTATION: A 34-year-old woman presented with left painful ophthalmoplegia. Magnetic resonance imaging (MRI) revealed abnormal signals in the left cavernous sinus area, and these abnormal signals were suspected to be THS. After steroid treatment, the patient obtained pain relief and had complete recovery of her ophthalmoplegia. However, right painful ophthalmoplegia appeared during the follow-up period. MRI showed obvious inflammatory signals in the right cavernous sinus and right sphenoid sinus. Then nasal sinus puncture and aspiration culture were performed, and the results showed a coagulase-negative staphylococcus infection. After antibiotic treatment with vancomycin, the painful ophthalmoplegia completely resolved, and the neurological examination and MRI returned to normal. CONCLUSION: Some other causes of painful ophthalmoplegia also fulfill the diagnostic criteria for THS in the International Classification of Headache Disorders third edition (ICHD-3) and respond well to steroid therapy. Early diagnosis of THS may be harmful to patients, and clinicians should exercise great caution when dealing with similar cases without a biopsy. Using "cavernous sinus syndrome" instead of "Tolosa-Hunt syndrome" as a diagnostic category may provide a better clinical thinking for etiological diagnosis.

Color stability of resin-based composites exposed to smoke. A systematic review.

OBJECTIVE: To conduct a systematic review on color stability of dental resin-based composites (RBC) exposed to conventional and electronic cigarettes. MATERIALS AND METHODS: In vitro studies reporting on the color stability of RBC exposed to conventional cigarettes or to e-cigarettes: both Tobacco Heating Systems (THS) and Electronic Nicotine Delivery Systems (ENDS). The quality of the included studies was assessed with the QUIN tool (risk-of-bias tool for assessing in vitro studies conducted in dentistry). A systematic search, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was performed on four (n = 4) databases (Embase, Medline, Scopus, Web of Science) for articles published until March 28th, 2022. RESULTS: Of the 365 screened articles, 13 were included in this review. All the included articles analyzed conventional cigarette smoke (CS), four analyzed Electronic Nicotine Delivery Systems (ENDS) and two Tobacco Heating Systems (THS). In terms of study design, smoke exposure time, smoke flow, type and number of cigarettes a high variability was reported. CONCLUSIONS: The available evidence suggests that CS smoke significantly affects color stability. Electronic cigarettes show less color change that seems to be easily recovered under clinical acceptability thresholds, although evidence is scarce. CLINICAL SIGNIFICANCE: Clinicians should be aware, and should therefore warn their patients, that RBCs are subjected to irreversible color change if exposed to smoke. Electronic cigarettes (both ENDS and THS) induce less color change that can be recovered with repolishing or whitening procedures.

Disseminated tuberculosis masquerading as Tolosa-Hunt syndrome in initial presentation: A case report with literature review.

Tolosa-Hunt syndrome (THS) is a painful ophthalmoplegia due to non-specific granulomatous inflammation in the cavernous sinus region. It is diagnosed by the International Classification of Headache Disorders (ICHD)-3 criteria. We report the case of a young lady who presented with a right-sided headache for 2 weeks, followed by right-sided diplopia for 4 days. Clinical examination revealed right trochlear nerve palsy. Magnetic resonance imaging (MRI) of her brain showed abnormal thickening and postcontrast enhancement of the right orbital apex and superior orbital fissure, suggesting THS. Examination of cerebrospinal fluid (CSF) ruled out intracranial infection. The initial presentation satisfied the ICHD-3 criteria. Further imaging revealed cervical, axillary, and intra-abdominal lymphadenopathy with granulomatous lesions in the spleen and right kidney. Ultrasound (US)-guided axillary lymph node biopsy was positive for Mycobacterium tuberculosis. QuantiFERON TB gold plus test from serum was positive. Based on radiological and histopathological findings, a diagnosis of disseminated tuberculosis involving lymph nodes, kidneys, spleen, and lungs was made. THS is a diagnosis of exclusion. This case signifies that patients diagnosed with THS based on ICHD-3 criteria should be extensively evaluated to rule out granulomatous infections such as tuberculosis. Typical THS symptoms with granulomatous inflammation can give false reassurance to clinicians and prevent investigation for more dangerous etiologies. As painful ophthalmoplegia can arise secondary to a myriad of pathologies, diagnostic workups for all possibilities should be exhausted before arriving at a diagnosis of THS. Regardless of MRI findings, workups for tuberculosis and fungal infections should be completed.

Opposite Effect of Thyroid Hormones on Oxidative Stress and on Mitochondrial Respiration in COVID-19 Patients.

BACKGROUND: Thyroid hormones (TH)s are master regulators of mitochondrial activity and biogenesis. Nonthyroidal illness syndrome (NTIS) is generally considered an adaptative response to reduced energy that is secondary to critical illness, including COVID-19. COVID-19 has been associated with profound changes in the cell energy metabolism, especially in the cells of the immune system, with a central role played by the mitochondria, considered the power units of every cell. Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects and alters mitochondrial functions, both to influence its intracellular survival and to evade host immunity. AIM OF THE STUDY: This study was undertaken to analyze the oxidative balance and mitochondrial respiration in COVID-19 patients with and without NTIS to elucidate the role that thyroid hormones (TH)s play in this context. METHODS: In our cohort of 54 COVID-19 patients, admitted to our University Hospital during the COVID-19 pandemic, we evaluated the generation of reactive oxygen species (ROS) by measuring the serum levels of derivatives of reactive oxygen metabolites (dROMs), and we analyzed the antioxidant capacity by measuring the serum biological antioxidant potential (BAP). We then analyzed the mitochondrial respiration in peripheral blood mononuclear cells (PBMC)s of 28 of our COVID-19 patients, using the seahorse instrument (Agilent). Results were correlated with the serum levels of THs and, in particular, of FT3. In addition, the role of T3 on bioelectrical impedance analysis (BIA) and mitochondrial respiration parameters was directly evaluated in two COVID-19 patients with NTIS, in which treatment with synthetic liothyronine (LT3) was given both in vivo and in vitro. RESULTS: In our COVID-19 patients with NTIS, the dROMs values were significantly lower and the BAP values were significantly higher. Consequently, the oxidative stress index (OSi), measured as BAP/dROMs ratio was reduced compared to that observed in COVID-19 patients without NTIS, indicating a protective role exerted by NTIS on oxidative stress. In our COVID-19 patients, the mitochondrial respiration, measured in PBMCs, was reduced compared to healthy controls. Those with NTIS showed a reduced maximal respiratory capacity and a reduced proton leak, compared to those with normal FT3 serum values. Such lowered mitochondrial respiratory capacity makes the cells more vulnerable to bioenergetic exhaustion. In a pilot study involving two COVID-19 patients with NTIS, we could reinforce our previous observation regarding the role of T3 in the maintenance of adequate peripheral hydroelectrolytic balance. In addition, in these two patients, we demonstrated that by treating their PBMCs with LT3, both in vitro and in vivo, all mitochondrial respiration parameters significantly increased. CONCLUSIONS: Our results regarding the reduction in the serum levels of the reactive oxygen species (ROS) of COVID-19 patients with NTIS support the hypothesis that NTIS could represent an adaptative response to severe COVID-19. However, beside this beneficial effect, we demonstrate that, in the presence of an acute reduction of FT3 serum levels, the mitochondrial respiration is greatly impaired, with a consequent establishment of a hypoenergetic state of the immune cells that may hamper their capacity to react to massive viral infection.

Diagnostic Value of Tracheal Wash Cytology for Monitoring Exercise-Induced Pulmonary Hemorrhage in Thoroughbred Racehorses.

Lower airway cytology has been proposed as a complementary diagnostic method to confirm the presence and quantifying the severity of exercise-induced pulmonary hemorrhage (EIPH). Bronchoalveolar lavage is usually preferred over tracheal wash (TW), yet the need for sedation imposes as a limitation for active sport horses in addition to be a highly invasive technique. This study aims to evaluate the diagnostic value of TW with Total Hemosiderin Score (THS) for monitoring EIPH in active Thoroughbred racehorses. A sampling of 47 randomly selected Thoroughbreds were endoscopically examined for EIPH grading 30 to 60 minutes after competing in an official race and then classified as Group 1 (EIPH-negative), Group 2 (EIPH-positive) or Group 3 (furosemide users). Tracheal wash fluids (TWFs) were collected from 24 to 30 hours later and smears were stained for differential cell count and hemosiderophage grading and counting to calculate THS. Differential cell counts were compared by the median test. Comparisons between mean THS values by EIPH grade and by group were compared by the Mann-Whitney test and ANOVA, respectively. Test performance criteria were determined with a contingency table. It was not possible to establish a THS cut-off point but statistical results showed that, at THS stand view, all groups had similar results despite their EIPH grades. Most animals showed no signs of neutrophilic inflammation, but haemosiderophages were found even on a first-time runner from Group 1. Thus, TW can detect evidence of lung bleeding even on horses with no history of EIPH. The implementation of TW analysis to diagnose EIPH in racehorses is promising, as TW is both low-cost and a less invasive tool.

Impact of photoperiod on uterine redox/inflammatory and metabolic status of golden hamster, Mesocricetus auratus.

Photoperiod modulates reproductive physiology at multiple levels in seasonally breeding animals. Golden hamsters are long-day breeders that diminish their fertility during the short days. Photoperiod is known to regulate hormonal milieu and uterus is a hormone-sensitive dynamic tissue. However, there is lack of molecular insight regarding the impact of photoperiod on uterine physiology with respect to redox and metabolic status in Mesocricetus auratus. We evaluated the impact of photoperiod on circulatory hormonal parameters (triiodothyronine [T3], thyroxin [T4], estradiol [E2], progesterone [P4], melatonin, and insulin), their receptor expressions and key markers associated with redox (SIRT-1/FOXO-1), inflammatory (NFĸB/COX-2) and metabolic (IR/GLUT4) status in uterus. Adult female golden hamsters were exposed to different photoperiodic regimes, that is, short photoperiod (SP; 8L:16D) and long photoperiod (LP; 16L:8D) for 12 weeks. SP drastically decreased peripheral hormone profiles (T3, T4, E2, and P4) and compromised uterine histoarchitecture when compared with LP-exposed hamsters. Further, SP markedly decreased thyroid hormone receptor-α (TRα), insulin receptor, and glucose uptake transporter-4 (GLUT-4) expressions in uterus. We noted enhanced uterine oxidative (increased MDA and decreased SOD/CAT levels), SIRT-1/FOXO-1 expression and inflammatory (NFĸB/COX-2) load in SP condition. Further, elevated levels of circulatory insulin, melatonin, and its receptor (MT-1) expression in uterus was noted under SP condition. Thus, we may suggest that photoperiod might regulate uterine seasonality through modulation of local hormonal and redox/metabolic homeostasis thereby may restrict offspring bearing capacity under short days.

Identification and determination of the volatile organics of third-hand smoke from different cigarettes and clothing fabrics.

Third-hand smoke (THS) is a persistent mixture generated from aged second-hand smoke (SHS) that accumulates in indoor environments and reemits into the air. This work evaluates the tobacco-derived volatile organics of cigarette THS from various clothing fabrics that were exposed to side-stream smoke of several brands of cigarettes in a controlled experimental scale. The qualitative and quantitative determination of the chemicals off-gassed was performed using solid phase micro-extraction coupled with GC/MS. Sixty-six components of side-stream smoke were identified in third-hand cigarette smoke. In this study, toluene-reference concentration (TRC) was calculated for volatile compounds and estimated based on the basic response characteristics of GC/MS. Among the identified analytes, 16 compounds were quantified presenting high toxicity and/or abundance in smoke, such as: benzene, toluene, xylene, pyridine, limonene, naphthalene, furfural and nicotine. The results showed that the total quantified volatile organics released for cotton, wool, polyester and filament fabrics were 92.37, 93.09, 87.88, and 50.22 µg/l fabric, respectively. Fabric structure significantly affects chemical off-gassing. Natural fibers were more capable of holding and emitting THS than synthetic fibers. Besides, various desorption times from 15 to 45 min after exposure to cigarette smoke in the study were evaluated. With increasing desorption time, no significant decrease in the concentration of organic compounds in THS was observed. Therefore, it is necessary to pay attention to the fact that it will be difficult to clean the pollutants from the environment contaminated with cigarette smoke and it will take more hours to reduce the concentration of organic compounds.

Thyroid Hormone Receptor Isoforms Alpha and Beta Play Convergent Roles in Muscle Physiology and Metabolic Regulation.

Skeletal muscle is a key energy-regulating organ, skilled in rapidly boosting the rate of energy production and substrate consumption following increased workload demand. The alteration of skeletal muscle metabolism is directly associated with numerous pathologies and disorders. Thyroid hormones (THs) and their receptors (TRs, namely, TRα and TRß) exert pleiotropic functions in almost all cells and tissues. Skeletal muscle is a major THs-target tissue and alterations of THs levels have multiple influences on the latter. However, the biological role of THs and TRs in orchestrating metabolic pathways in skeletal muscle has only recently started to be addressed. The purpose of this paper is to investigate the muscle metabolic response to TRs abrogation, by using two different mouse models of global TRα- and TRßKO. In line with the clinical features of resistance to THs syndromes in humans, characterized by THRs gene mutations, both animal models of TRs deficiency exhibit developmental delay and mitochondrial dysfunctions. Moreover, using transcriptomic and metabolomic approaches, we found that the TRs-THs complex regulates the Fatty Acids (FAs)-binding protein GOT2, affecting FAs oxidation and transport in skeletal muscle. In conclusion, these results underline a new metabolic role of THs in governing muscle lipids distribution and metabolism.

Development of Thyroid Hormones and Synthetic Thyromimetics in Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is the fastest-growing liver disease in the world. Despite targeted agents which are needed to provide permanent benefits for patients with NAFLD, no drugs have been approved to treat NASH. Thyroid hormone is an important signaling molecule to maintain normal metabolism, and in vivo and vitro studies have shown that regulation of the 3,5,3'-triiodothyronine (T3)/ thyroid hormone receptor (TR) axis is beneficial not only for metabolic symptoms but also for the improvement of NAFLD and even for the repair of liver injury. However, the non-selective regulation of T3 to TR subtypes (TRα/TRß) could cause unacceptable side effects represented by cardiotoxicity. To avoid deleterious effects, TRß-selective thyromimetics were developed for NASH studies in recent decades. Herein, we will review the development of thyroid hormones and synthetic thyromimetics based on TR selectivity for NAFLD, and analyze the role of TR-targeted drugs for the treatment of NAFLD in the future.

Effect of miR-21-3p on lung injury in rats with traumatic hemorrhagic shock resuscitated with sodium bicarbonate Ringer's solution.

Background: Restricted fluid resuscitation is the most important early method for treating traumatic hemorrhagic shock (THS). This study sought to explore whether micro ribonucleic acid (miR)-21-3p affected resuscitated THS rats by regulating the glycocalyx and inflammation. Methods: MiRNAs extracted from the lung tissues were analyzed by miRNA microarray assays. A rat model of THS was induced by hemorrhage from a left femur fracture. The pathological change in the lung tissues and glycocalyx structure was observed by hematoxylin and eosin staining and a transmission electron microscope examination. The miR-21-3p expression in the lung tissues and serum was detected by real-time quantitative polymerase chain reaction (RT-qPCR). The levels of glycocalyx-related factors and inflammation-related factors were determined by enzyme linked immunosorbent assays. The expression of glycocalyx-related proteins, cell junction-related proteins, and the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/nuclear factor kappa B (NF-κB) signaling pathway-related proteins was analyzed by Western blot. Results: After RT-qPCR verification, the variation trend of miR-21-3p was in line with expected trends. The mean arterial pressure (MAP) and heart rate (HR) were decreased, and the lung injury and damage to the glycocalyx were all aggravated in the THS rats resuscitated with sodium bicarbonate Ringer's solution (BRS) or sodium lactate Ringer's solution (LRS). The expression of miR-21-3p was decreased in the THS rats resuscitated with BRS and increased in the THS rats resuscitated with LRS, and the upregulation of miR-21-3p further decreased the MAP and HR, and increased the levels of syndecan-1 (SDC-1), heparanase-1 (HPA1), interleukin (IL)-6, IL-1ß, and tumor necrosis factor alpha (TNF-α) in the serum of the THS rats resuscitated with BRS. The upregulation of miR-21-3p also increased the expression of SDC-1, HPA1, ß-catenin, matrix metallopeptidase (MMP)2, and MMP9, but decreased the expression of E-cadherin (E-cad) and activated the PI3K/Akt/NF-κB signaling pathway in the THS rats resuscitated with BRS and transfected with miR-21-3p compared to that of the THS rats resuscitated with BRS and transfected with miR-negative control (NC). Conclusions: miR-21-3p promoted inflammation and glycocalyx damage by activating the PI3K/Akt/NF-κB signaling pathway, thereby aggravating the lung injury in the THS rats resuscitated with BRS.

Concurrent production of glycyrrhetic acid 3-O-mono-ß-d-glucuronide and lignocellulolytic enzymes by solid-state fermentation of a plant endophytic Chaetomium globosum.

Glycyrrhetic acid 3-O-mono-ß-d-glucuronide (GAMG) as an important derivative of glycyrrhizin (GL) shows stronger biological activities and higher sweetness than GL. The biotransformation process is considered as an efficient strategy for GAMG production, due to its mild reaction, high production efficiency and environmentally friendly status. In this study, licorice straw was used for the first time as a medium for GAMG and lignocellulosic enzyme production via solid-state fermentation (SSF) of endophytic fungus Chaetomium globosum DX-THS3. The fermentation conditions including particle size, temperature, seed age, inoculum size, and moisture of substrate were optimized. Furthermore, additional nitrogen sources and carbon sources were screened for GAMG production by C. globosum DX-THS3 of SSF. Under optimal fermentation conditions, the percent conversion of glycyrrhizin reached 90% in 15 days, whereas the control needed 35 days to achieve the same result. The productivity of optimization (P = 2.1 mg/g/day) was 2.33-fold that of non-optimization (P = 0.9 mg/g/day). Meanwhile, high activities of filter paper enzyme (FPase) (245.80 U/g), carboxymethyl cellulase (CMCase) (33.67 U/g), xylanase (83.44 U/g), and ß-glucuronidase activity (271.42 U/g) were obtained faster than those in the control during SSF. Our study provides a novel and efficient strategy for GAMG production and indicates C. globosum DX-THS3 as a potential producer of lignocellulolytic enzymes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40643-021-00441-y.

Design and Evaluation of Synthetic RNA-Based Incoherent Feed-Forward Loop Circuits.

RNA-based regulators are promising tools for building synthetic biological systems that provide a powerful platform for achieving a complex regulation of transcription and translation. Recently, de novo-designed synthetic RNA regulators, such as the small transcriptional activating RNA (STAR), toehold switch (THS), and three-way junction (3WJ) repressor, have been utilized to construct RNA-based synthetic gene circuits in living cells. In this work, we utilized these regulators to construct type 1 incoherent feed-forward loop (IFFL) circuits in vivo and explored their dynamic behaviors. A combination of a STAR and 3WJ repressor was used to construct an RNA-only IFFL circuit. However, due to the fast kinetics of RNA-RNA interactions, there was no significant timescale difference between the direct activation and the indirect inhibition, that no pulse was observed in the experiments. These findings were confirmed with mechanistic modeling and simulation results for a wider range of conditions. To increase delay in the inhibition pathway, we introduced a protein synthesis process to the circuit and designed an RNA-protein hybrid IFFL circuit using THS and TetR protein. Simulation results indicated that pulse generation could be achieved with this RNA-protein hybrid model, and this was further verified with experimental realization in E. coli. Our findings demonstrate that while RNA-based regulators excel in speed as compared to protein-based regulators, the fast reaction kinetics of RNA-based regulators could also undermine the functionality of a circuit (e.g., lack of significant timescale difference). The agreement between experiments and simulations suggests that the mechanistic modeling can help debug issues and validate the hypothesis in designing a new circuit. Moreover, the applicability of the kinetic parameters extracted from the RNA-only circuit to the RNA-protein hybrid circuit also indicates the modularity of RNA-based regulators when used in a different context. We anticipate the findings of this work to guide the future design of gene circuits that rely heavily on the dynamics of RNA-based regulators, in terms of both modeling and experimental realization.

The demographics of Tolosa-Hunt syndrome in Qatar.

BACKGROUND: Tolosa Hunt syndrome (THS) is a rare disease that manifests mainly as painful unilateral ophthalmoplegia. It is caused by an inflammatory process of unknown aetiology within the cavernous sinus with a rare intracranial extension. The International Classification of Headache Disorders (ICHD)- 3 diagnostic criteria aids in its diagnosis. There is limited literature on its varied presentations, diagnosis, and management. Steroids are used in the treatment of THS with varied success. METHODS: We conducted a single-center-retrospective-study and included all patients admitted with a diagnosis of THS from January 2015 to December 2020. Descriptive and summary statistics were used to describe the study cohort's socio-demographic parameters. RESULTS: Among 31 THS patients (predominantly Asians (18) and Arabs (9)), visual disturbance was commonest presenting complaint. Third-nerve paralysis was seen in 70.9% cases. Magnetic-resonance-imaging (MRI) was abnormal in 64.5%. 93.5% patients received steroids, with a response-rate of 70.9% and a recurrence-rate of 9.7%. A previous history of THS and female gender were associated with recurrence (p-value 0.009 and 0.018). Recurrence was seen in 66.7% fully recovered and 33.3% partially recovered cases (p-value 0.04). Among the benign and inflammatory subtypes of THS, the ICHD-3 criteria were applicable in 85% of inflammatory THS. CONCLUSIONS: THS is a rare disease with ethnic variation in presentation and response to treatment. In our cohort female gender and a previous history of THS were associated with recurrence. ICHD-3 diagnostic criteria had a higher validity in our patients compared to prior studies, especially among the inflammatory THS.

Effects of social skills training on school climate / Efeitos de um treinamento de habilidades sociais sobre o clima escolar / Efectos de la capacitación en habilidades sociales sobre el clima escolar

Studies point out that the development of social skills can interfere in the students' behavior and consequently in the environment, favoring the school climate and the acquisition of knowledge. Thus, this research aimed to identify the effects of a Social Skills Training (SST) on the school climate. 21 students from the 9th grade of Elementary School participated (11 from the Experimental group and 10 from the Control group) aged between 14 and 16 years old (MD = 14.38; SD = 1.07). The instruments used were: Inventory of Social Skills for Adolescents and the Climate Scale of the Delaware Student School. Ten sessions were held, with weekly meetings of 50 minutes. For data analysis, the following tests were used: Spearman's rô, Wilcoxon and Mann-Whitney for independent samples. There were positive correlations, from moderate to strong, between the factors of social skills and the dimensions of the climate for all participants in the intervention group. In the control group, negative and positive correlations were identified.

Estudos apontam que o desenvolvimento de habilidades sociais pode interferir no comportamento dos alunos e por consequência no ambiente, favorecendo o clima escolar e a aquisição do conhecimento. Dessa forma, esta pesquisa objetivou identificar os efeitos de um treinamento de habilidades sociais (THS) no clima escolar. Participaram 21 estudantes do nono ano do ensino fundamental (11 do grupo experimental e dez do grupo controle) com idades entre 14 e 16 anos (MD = 14,38; DP = 1,07). Os instrumentos utilizados foram: Inventário de Habilidades Sociais para Adolescentes e a Escala de Clima da Escola de Delaware-Estudante. Realizaram-se dez sessões, com encontros semanais de 50 minutos. Para análise de dados, utilizaram-se os testes rô de Spearman, Wilcoxon e Mann-Whitney para amostras independentes. Observaram-se correlações positivas de moderada a forte entre os fatores das habilidades sociais e as dimensões do clima para todos os participantes do grupo intervenção. No grupo controle, identificaram-se correlações negativas e positivas.

Los estúdios señalan que el desarrollo de habilidades sociales puede interferir em el comportamiento de los estudiantes y consecuentemente em el entorno, favoreciendo el clima escolar y la adquisición de conocimientos. Por lo tanto, esta investigación tuvo como objetivo identificar los efectos de un Entrenamiento de habilidades sociales (EHS) en el clima escolar. Participaron 21 alumnos de 9º de primaria (11 del grupo experimental y diez del grupo control) con edades comprendidas entre 14 y 16 años (DM = 14,38; DT = 1,07). Los instrumentos utilizados fueron: Inventario de Habilidades Sociales para Adolescentes y Escala de Clima de la Escuela de Delaware-Estudiantes. Se realizaron diez sesiones, con reuniones semanales de 50 minutos. Para el análisis de los datos se utilizaron las pruebas: rô de Spearman, Wilcoxon y Mann-Whitney para muestras independientes. Hubo correlaciones positivas de moderadas a fuertes entre los factores de habilidades sociales y las dimensiones del clima para todos los participantes en el grupo de intervención. Em el grupo de control se identificaron correlaciones negativas y positivas.

Impact of 6-Month Exposure to Aerosols From Potential Modified Risk Tobacco Products Relative to Cigarette Smoke on the Rodent Gastrointestinal Tract.

Cigarette smoking causes adverse health effects that might occur shortly after smoking initiation and lead to the development of inflammation and cardiorespiratory disease. Emerging studies have demonstrated the role of the intestinal microbiome in disease pathogenesis. The intestinal microbiome is susceptible to the influence of environmental factors such as smoking, and recent studies have indicated microbiome changes in smokers. Candidate modified risk tobacco products (CMRTP) are being developed to provide substitute products to lower smoking-related health risks in smokers who are unable or unwilling to quit. In this study, the ApoE-/- mouse model was used to investigate the impact of cigarette smoke (CS) from the reference cigarette 3R4F and aerosols from two CMRTPs based on the heat-not-burn principle [carbon-heated tobacco product 1.2 (CHTP 1.2) and tobacco heating system 2.2 (THS 2.2)] on the intestinal microbiome over a 6-month period. The effect of cessation or switching to CHTP 1.2 after 3 months of CS exposure was also assessed. Next-generation sequencing was used to evaluate the impact of CMRTP aerosols in comparison to CS on microbiome composition and gene expression in the digestive tract of mice. Our analyses highlighted significant gene dysregulation in response to 3R4F exposure at 4 and 6 months. The findings showed an increase in the abundance of Akkermansiaceae upon CS exposure, which was reversed upon cessation. Cessation resulted in a significant decrease in Akkemansiaceae abundance, whereas switching to CHTP 1.2 resulted in an increase in Lactobacillaceae abundance. These microbial changes could be important for understanding the effect of CS on gut function and its relevance to disease pathogenesis via the microbiome.

Early-life exposure to tris (1,3-dichloro-2-propyl) phosphate caused multigenerational neurodevelopmental toxicity in zebrafish via altering maternal thyroid hormones transfer and epigenetic modifications.

Tris (1,3-dichloro-2-propyl) phosphate (TDCIPP), an alternative to brominated flame retardants, might pose an exposure risk to humans and wild animals during fetal development. Our recent study suggested that short-term TDCIPP exposure during early development caused sex-dependent behavioral alteration in adults. In the present study, multigenerational neurodevelopmental toxicity upon early-life exposure of parental zebrafish was evaluated, and the possible underlying mechanisms were further explored. Specifically, after embryonic exposure (0-10 days post-fertilization, dpf) to TDCIPP (0, 0.01, 0.10, and 1.00 µM), zebrafish larvae were cultured in clean water until the sexually matured to produce progeny (F1). The results confirmed neurodevelopmental toxicity in F1 larvae characterized by changes of developmental endpoints, reduced thigmotaxis, as well as altered transcription of genes including myelin basic protein a (mbpa), growth associated protein (gap43) and synapsin IIa (syn2a). Sex-specific changes in thyroid hormones (THs) indicated the relationship of abnormal THs levels with previously reported neurotoxicity in adult females after early-life exposure to TDCIPP. Similar changing profiles of TH levels (increased T3 and decreased T4) in adult females and F1 eggs, but not in F1 larvae, suggested that the TH disruptions were primarily inherited from the maternal fish. Further results demonstrated hypermethylation of global DNA and key genes related to TH transport including transthyretin (ttr) and solute carrier family 16 member 2 (slc16a2), which might affect the transport of THs to target tissues, thus at least partially contributing to the neurodevelopmental toxicity in F1 larvae. Overall, our results confirmed that early-life TDCIPP exposure of parental fish could affect the early neurodevelopment of F1 offspring. The underlying mechanism could involve altered TH levels inherited from maternal zebrafish and epigenetic modifications in F1 larvae.