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.

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.

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.

Thirdhand smoke associations with the gut microbiomes of infants admitted to a neonatal intensive care unit: An observational study.

INTRODUCTION: Microbiome differences have been found in adults who smoke cigarettes compared to non-smoking adults, but the impact of thirdhand smoke (THS; post-combustion tobacco residue) on hospitalized infants' rapidly developing gut microbiomes is unexplored. Our aim was to explore gut microbiome differences in infants admitted to a neonatal ICU (NICU) with varying THS-related exposure. METHODS: Forty-three mother-infant dyads (household member[s] smoke cigarettes, n = 32; no household smoking, n = 11) consented to a carbon monoxide-breath sample, bedside furniture nicotine wipes, infant-urine samples (for cotinine [nicotine's primary metabolite] assays), and stool collection (for 16S rRNA V4 gene sequencing). Negative binomial regression modeled relative abundances of 8 bacterial genera with THS exposure-related variables (i.e., household cigarette use, surface nicotine, and infant urine cotinine), controlling for gestational age, postnatal age, antibiotic use, and breastmilk feeding. Microbiome-diversity outcomes were modeled similarly. Bayesian posterior probabilities (PP) ≥75.0% were considered meaningful. RESULTS: A majority of infants (78%) were born pre-term. Infants from non-smoking homes and/or with lower NICU-furniture surface nicotine had greater microbiome alpha-diversity compared to infants from smoking households (PP ≥ 75.0%). Associations (with PP ≥ 75.0%) of selected bacterial genera with urine cotinine, surface nicotine, and/or household cigarette use were evidenced for 7 (of 8) modeled genera. For example, lower Bifidobacterium relative abundance associated with greater furniture nicotine (IRR<0.01 [<0.01, 64.02]; PP = 87.1%), urine cotinine (IRR = 0.08 [<0.01,2.84]; PP = 86.9%), and household smoking (IRR<0.01 [<0.01, 7.38]; PP = 96.0%; FDR p < 0.05). CONCLUSIONS: THS-related exposure was associated with microbiome differences in NICU-admitted infants. Additional research on effects of tobacco-related exposures on healthy infant gut-microbiome development is warranted.

The Cdc48-20S proteasome degrades a class of endogenous proteins in a ubiquitin-independent manner.

The 26S proteasome is the major degradation machinery for soluble proteins in eukaryotes. Recent evidence reveals the existence of an alternative ATP-powered protein degradation complex, the Cdc48-20S proteasome complex, and we have identified yeast Sod1, a copper-zinc superoxide dismutase, as an endogenous substrate protein. Here, we identified yeast Ths1, an essential threonyl tRNA synthetase, as another endogenous substrate protein of the Cdc48-20S proteasome. In order to analyze the degradation mechanism in more details, we established an in vitro degradation system reconstituted using purified yeast components. Recombinant Sod1 and Ths1 directly interacted with Cdc48, and were degraded in a Cdc48-20S proteasome-dependent manner. Because the substrate proteins were purified from E. coli cells, no eukaryotic modifications including ubiquitination and phosphorylation exist. Therefore, although the 26S proteasome requires ubiquitination for specific recognition of the substrate proteins, the Cdc48-20S proteasome can degrade a class of substrate proteins without any modifications.

A Halogen Bonding Perspective on Iodothyronine Deiodinase Activity.

Iodothyronine deiodinases (Dios) are involved in the regioselective removal of iodine from thyroid hormones (THs). Deiodination is essential to maintain TH homeostasis, and disruption can have detrimental effects. Halogen bonding (XB) to the selenium of the selenocysteine (Sec) residue in the Dio active site has been proposed to contribute to the mechanism for iodine removal. Polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) are known disruptors of various pathways of the endocrine system. Experimental evidence shows PBDEs and their hydroxylated metabolites (OH-BDEs) can inhibit Dio, while data regarding PCB inhibition are limited. These xenobiotics could inhibit Dio activity by competitively binding to the active site Sec through XB to prevent deiodination. XB interactions calculated using density functional theory (DFT) of THs, PBDEs, and PCBs to a methyl selenolate (MeSe-) arrange XB strengths in the order THs > PBDEs > PCBs in agreement with known XB trends. THs have the lowest energy C-X*-type unoccupied orbitals and overlap with the Se lp donor leads to high donor-acceptor energies and the greatest activation of the C-X bond. The higher energy C-Br* and C-Cl* orbitals similarly result in weaker donor-acceptor complexes and less activation of the C-X bond. Comparison of the I···Se interactions for the TH group suggest that a threshold XB strength may be required for dehalogenation. Only highly brominated PBDEs have binding energies in the same range as THs, suggesting that these compounds may inhibit Dio and undergo debromination. While these small models provide insight on the I···Se XB interaction itself, interactions with other active site residues are governed by regioselective preferences observed in Dios.

Establishment of a human embryonic stem cell-based liver differentiation model for hepatotoxicity evaluations.

The liver is one of the major targets of hormones, including thyroid hormones (THs), and many industrial chemicals, such as endocrine-disrupting chemicals. Those compounds may permeate the placenta barrier and pose a risk for embryonic development. Therefore, it is necessary to assess the toxic effects of those kind of industrial chemicals during liver development. In this study, to mimic liver specification in vitro, we differentiated human embryonic stem cells (ESCs) into functional hepatocyte-like cells. We performed this differentiation process in presence of two THs, triiodothyronine (T3) and thyroxine (T4), with the purpose of identifying biomarkers for toxicity screening. TH exposure (3, 30 and 300 nM) yielded to hepatocytes with impaired glycogen storage ability and abnormal lipid droplets' accumulation. Global gene expression analysis by RNA-seq identified a number of genes responsible for hepatic differentiation and function which were affected by 30 nM T3 and T4. Those differentially expressed genes were used to assess the potential developmental liver toxicity of two famous environmental pollutants, 2, 2, 4, 4-tetrabromodiphenyl ether (BDE-47) and decabromodiphenyl ether (BDE-209), at 10 nM to 1 µM treatments. Our findings demonstrate that BDE-47 and BDE-209, dysregulated pathways such as "chemical carcinogenesis", "steroid hormone biosynthesis" and "drug metabolism-cytochrome P450". Moreover, we were able to identify a set of 17 biomarkers, very useful to predict the potential developmental hepatotoxicity of industrial chemicals.

Nicotine pharmacokinetic profiles of the Tobacco Heating System 2.2, cigarettes and nicotine gum in Japanese smokers.

Two open-label randomized cross-over studies in Japanese smokers investigated the single-use nicotine pharmacokinetic profile of the Tobacco Heating System (THS) 2.2, cigarettes (CC) and nicotine replacement therapy (Gum). In each study, one on the regular and one on the menthol variants of the THS and CC, both using Gum as reference, 62 subjects were randomized to four sequences: Sequence 1: THS - CC (n = 22); Sequence 2: CC - THS (n = 22); Sequence 3: THS - Gum (n = 9); Sequence 4: Gum - THS (n = 9). Plasma nicotine concentrations were measured in 16 blood samples collected over 24 h after single use. Maximal nicotine concentration (Cmax) and area under the curve from start of product use to time of last quantifiable concentration (AUC0-last) were similar between THS and CC in both studies, with ratios varying from 88 to 104% for Cmax and from 96 to 98% for AUC0-last. Urge-to-smoke total scores were comparable between THS and CC. The THS nicotine pharmacokinetic profile was close to CC, with similar levels of urge-to-smoke. This suggests that THS can satisfy smokers and be a viable alternative to cigarettes for adult smokers who want to continue using tobacco.

Comparative assessment of HPHC yields in the Tobacco Heating System THS2.2 and commercial cigarettes.

There has been a sustained effort in recent years to develop products with the potential to present less risk compared with continued smoking as an alternative for adult smokers who would otherwise continue to smoke cigarettes. During the non-clinical assessment phase of such products, the chemical composition and toxicity of their aerosols are frequently compared to the chemical composition and toxicity of the smoke from a standard research cigarette - the 3R4F reference cigarette. In the present study, it is demonstrated that results of these analytical comparisons are similar when considering commercially available cigarette products worldwide. A market mean reduction of about 90% is observed on average across a broad range of harmful and potentially harmful constituents (HPHC) measured in the aerosol of a candidate modified risk tobacco product, the Tobacco Heating System 2.2 (THS2.2), compared against the levels of HPHC of cigarettes representative of selected markets; this mean reduction is well in line with the reduction observed against 3R4F smoke constituents in previous studies.

Comparison of the impact of the Tobacco Heating System 2.2 and a cigarette on indoor air quality.

The impact of the Tobacco Heating System 2.2 (THS 2.2) on indoor air quality was evaluated in an environmentally controlled room using ventilation conditions recommended for simulating "Office", "Residential" and "Hospitality" environments and was compared with smoking a lit-end cigarette (Marlboro Gold) under identical experimental conditions. The concentrations of eighteen indoor air constituents (respirable suspended particles (RSP) < 2.5 µm in diameter), ultraviolet particulate matter (UVPM), fluorescent particulate matter (FPM), solanesol, 3-ethenylpyridine, nicotine, 1,3-butadiene, acrylonitrile, benzene, isoprene, toluene, acetaldehyde, acrolein, crotonaldehyde, formaldehyde, carbon monoxide, nitrogen oxide, and combined oxides of nitrogen) were measured. In simulations evaluating THS 2.2, the concentrations of most studied analytes did not exceed the background concentrations determined when non-smoking panelists were present in the environmentally controlled room under equivalent conditions. Only acetaldehyde and nicotine concentrations were increased above background concentrations in the "Office" (3.65 and 1.10 µg/m(3)), "Residential" (5.09 and 1.81 µg/m(3)) and "Hospitality" (1.40 and 0.66 µg/m(3)) simulations, respectively. Smoking Marlboro Gold resulted in greater increases in the concentrations of acetaldehyde (58.8, 83.8 and 33.1 µg/m(3)) and nicotine (34.7, 29.1 and 34.6 µg/m(3)) as well as all other measured indoor air constituents in the "Office", "Residential" and "Hospitality" simulations, respectively.

Evaluation of the Tobacco Heating System 2.2. Part 2: Chemical composition, genotoxicity, cytotoxicity, and physical properties of the aerosol.

The chemical composition, in vitro genotoxicity, and cytotoxicity of the mainstream aerosol from the Tobacco Heating System 2.2 (THS2.2) were compared with those of the mainstream smoke from the 3R4F reference cigarette. In contrast to the 3R4F, the tobacco plug in the THS2.2 is not burnt. The low operating temperature of THS2.2 caused distinct shifts in the aerosol composition compared with 3R4F. This resulted in a reduction of more than 90% for the majority of the analyzed harmful and potentially harmful constituents (HPHCs), while the mass median aerodynamic diameter of the aerosol remained similar. A reduction of about 90% was also observed when comparing the cytotoxicity determined by the neutral red uptake assay and the mutagenic potency in the mouse lymphoma assay. The THS2.2 aerosol was not mutagenic in the Ames assay. The chemical composition of the THS2.2 aerosol was also evaluated under extreme climatic and puffing conditions. When generating the THS2.2 aerosol under "desert" or "tropical" conditions, the generation of HPHCs was not significantly modified. When using puffing regimens that were more intense than the standard Health Canada Intense (HCI) machine-smoking conditions, the HPHC yields remained lower than when smoking the 3R4F reference cigarette with the HCI regimen.

Evaluation of the Tobacco Heating System 2.2. Part 3: Influence of the tobacco blend on the formation of harmful and potentially harmful constituents of the Tobacco Heating System 2.2 aerosol.

The Tobacco Heating System (THS2.2), which uses "heat-not-burn" technology, generates an aerosol from tobacco heated to a lower temperature than occurs when smoking a combustible cigarette. The concentrations of harmful and potentially harmful constituents (HPHCs) are significantly lower in THS2.2 mainstream aerosol than in smoke produced by combustible cigarettes. Different tobacco types and 43 tobacco blends were investigated to determine how the blend impacted the overall reductions of HPHCs in the THS2.2 mainstream aerosol. The blend composition had minimal effects on the yields of most HPHCs in the aerosol. Blends containing high proportions of nitrogen-rich tobacco, e.g., air-cured, and some Oriental tobaccos, produced higher acetamide, acrylamide, ammonia, and nitrogen oxide yields than did other blends. Most HPHCs were found to be released mainly through the distillation of HPHCs present in the tobacco plug or after being produced in simple thermal reactions. HPHC concentrations in the THS2.2 aerosol may therefore be further minimized by limiting the use of flue- and fire-cured tobaccos which may be contaminated by HPHCs during the curing process and carefully selecting nitrogen rich tobaccos with low concentrations of endogenous HPHCs for use in the tobacco plug blend.

Probable Tolosa-Hunt syndrome with a normal MRI.

BACKGROUND: We are reporting a rare case of a 60-year-old woman with a past history of end-stage renal disease and non-Hodgkin lymphoma who presented to our hospital with confusion, unilateral headache, painful ophthalmoplegia and ptosis. The patient was diagnosed clinically with Tolosa-Hunt syndrome (THS). RESULTS: THS is a diagnosis of exclusion. Other diseases were ruled out. Magnetic resonance imaging (MRI) of the brain and orbit was negative twice within a week. The patient was treated with corticosteroids with marked improvement of the orbital pain and headache and mild improvement of the cranial nerves palsy. CONCLUSION: Clinical diagnosis of THS could be supported by radiological findings. According to the International Classification of Headache Disorders (ICHD)-3 beta diagnostic criteria, the diagnosis must be confirmed with an abnormal MRI and/or pathological sample. We add to the previous findings of THS with a normal MRI. Although MRI plays a crucial role in differential diagnosis, it should not, nor should the biopsy, be a must for the diagnosis. Limitations of using MRI in some patients are another problem.

Activation of the endoplasmic reticulum stress response by the amyloid-beta 1-40 peptide in brain endothelial cells.

Neurovascular dysfunction arising from endothelial cell damage is an early pathogenic event that contributes to the neurodegenerative process occurring in Alzheimer's disease (AD). Since the mechanisms underlying endothelial dysfunction are not fully elucidated, this study was aimed to explore the hypothesis that brain endothelial cell death is induced upon the sustained activation of the endoplasmic reticulum (ER) stress response by amyloid-beta (Aß) peptide, which deposits in the cerebral vessels in many AD patients and transgenic mice. Incubation of rat brain endothelial cells (RBE4 cell line) with Aß1-40 increased the levels of several markers of ER stress-induced unfolded protein response (UPR), in a time-dependent manner, and affected the Ca(2+) homeostasis due to the release of Ca(2+) from this intracellular store. Finally, Aß1-40 was shown to activate both mitochondria-dependent and -independent apoptotic cell death pathways. Enhanced release of cytochrome c from mitochondria and activation of the downstream caspase-9 were observed in cells treated with Aß1-40 concomitantly with caspase-12 activation. Furthermore, Aß1-40 activated the apoptosis effectors' caspase-3 and promoted the translocation of apoptosis-inducing factor (AIF) to the nucleus demonstrating the involvement of caspase-dependent and -independent mechanisms during Aß-induced endothelial cell death. In conclusion, our data demonstrate that ER stress plays a significant role in Aß1-40-induced apoptotic cell death in brain endothelial cells suggesting that ER stress-targeted therapeutic strategies might be useful in AD to counteract vascular defects and ultimately neurodegeneration.

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.

Effect of a thiohydantoin salt derived from l-Arginine on Leishmania amazonensis and infected cells: Insights from biological effects to molecular docking interactions.

Leishmaniasis is a neglected tropical disease caused by parasites of the genus Leishmania and is responsible for more than 1 million new cases and 70,000 deaths annually worldwide. Treatment has high costs, toxicity, complex and long administration time, several adverse effects, and drug-resistant strains, therefore new therapies are urgently needed. Synthetic compounds have been highlighted in the medicinal chemistry field as a strong option for drug development against different diseases. Organic salts (OS) have multiple biological activities, including activity against protozoa such as Leishmania spp. This study aimed to investigate the in vitro leishmanicidal activity and death mechanisms of a thiohydantoin salt derived from l-arginine (ThS) against Leishmania amazonensis. We observed that ThS treatment inhibited promastigote proliferation, increased ROS production, phosphatidylserine exposure and plasma membrane permeabilization, loss of mitochondrial membrane potential, lipid body accumulation, autophagic vacuole formation, cell cycle alteration, and morphological and ultrastructural changes, showing parasites death. Additionally, ThS presents low cytotoxicity in murine macrophages (J774A.1), human monocytes (THP-1), and sheep erythrocytes. ThS in vitro cell treatment reduced the percentage of infected macrophages and the number of amastigotes per macrophage by increasing ROS production and reducing TNF-α levels. These results highlight the potential of ThS among thiohydantoins, mainly related to the arginine portion, as a leishmanicidal drug for future drug strategies for leishmaniasis treatment. Notably, in silico investigation of key targets from L. amazonensis, revealed that a ThS compound from the l-arginine amino acid strongly interacts with arginase (ARG) and TNF-α converting enzyme (TACE), suggesting its potential as a Leishmania inhibitor.

Thirdhand smoke exposure promotes gastric tumor development in mouse and human.

The pollution of indoor environments and the consequent health risks associated with thirdhand smoke (THS) are increasingly recognized in recent years. However, the carcinogenic potential of THS and its underlying mechanisms have yet to be thoroughly explored. In this study, we examined the effects of short-term THS exposure on the development of gastric cancer (GC) in vitro and in vivo. In a mouse model of spontaneous GC, CC036, we observed a significant increase in gastric tumor incidence and a decrease in tumor-free survival upon THS exposure as compared to control. RNA sequencing of primary gastric epithelial cells derived from CC036 mice showed that THS exposure increased expression of genes related to the extracellular matrix and cytoskeletal protein structure. We then identified a THS exposure-induced 91-gene expression signature in CC036 and a homologous 84-gene signature in human GC patients that predicted the prognosis, with secreted phosphoprotein 1 (SPP1) and tribbles pseudokinase 3 (TRIB3) emerging as potential targets through which THS may promote gastric carcinogenesis. We also treated human GC cell lines in vitro with media containing various concentrations of THS, which, in some exposure dose range, significantly increased their proliferation, invasion, and migration. We showed that THS exposure could activate the epithelial-mesenchymal transition (EMT) pathway at the transcript and protein level. We conclude that short-term exposure to THS is associated with an increased risk of GC and that activation of the EMT program could be one potential mechanism. Increased understanding of the cancer risk associated with THS exposure will help identify new preventive and therapeutic strategies for tobacco-related disease as well as provide scientific evidence and rationale for policy decisions related to THS pollution control to protect vulnerable subpopulations such as children.

Exposure to monocrotophos pesticide causes disruption of the hypothalamic-pituitary-thyroid axis in adult male goldfish (Carassius auratus).

The thyroid hormones (THs) 3,3',5-triiodo-l-thyronine (T3) and l-thyroxine (T4) exert a wide range of biological effects on physiological processes of fish. To elucidate the thyroid disruption effects of monocrotophos (MCP), an organophosphate pesticide, on male goldfish (Carassius auratus), thyroid follicle histology, plasma total T3 (TT3), total T4 (TT4), free T3 (FT3) and free T4 levels, and the mRNA expression of indices involved in the hypothalamic-pituitary-thyroid axis (HPT axis) were examined following 21-day exposure to 0.01, 0.10 and 1.00mg/L of a 40% MCP-based pesticide. The results showed that MCP exposure induced the hyperplasia and hypertrophy of thyroid follicular epithelium and led to decreased plasma TT3 levels and TT3-to-TT4 ratios, without effect on plasma TT4 levels. Profiles of the changes in the relative abundance of deiodinase (D1, D2 and D3) transcripts were observed in the liver, brain and kidneys, during MCP exposure. An increase in the metabolism of T3, expressed as highly elevated hepatic d1 and d3 mRNA levels, might be associated with the reduction in plasma TT3 levels in both the 0.01 and 0.10mg/L groups, while in the 1.00mg/L MCP group, inhibited hepatic d2 transcripts might have also resulted in decreased TT3 levels by preventing the activation of T4 to T3. As a compensatory response to decreased T3 levels, pituitary thyroid-stimulating hormone ß subunit mRNA transcription was up-regulated by the MCP pesticide. Decreases in plasma FT3 levels were also correlated with the modulation of hepatic transthyretin mRNA expression. Overall, the MCP pesticide exhibited thyroid-disrupting effects via interference with the HPT axis at multiple potential sites, resulting in disturbance of TH homeostasis.

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.