Elevated Levels of Cytotoxicity, Cytokines, and Anti-SARS-CoV-2 Antibodies in Mild Cases of COVID-19.

Current evidence shows higher production of cytokines and antibodies against severe acute respiratory coronavirus 2 (SARS-CoV-2) in severe and critical cases of Coronavirus Disease 2019 (COVID-19) in comparison with patients with moderate or mild disease. A recent hypothesis proposes an important role of genotoxicity and cytotoxicity in the induction of the cytokine storm observed in some patients at later stages of the disease. Interestingly, in this study, we report significantly higher levels of interleukin (IL)-1ß, IL-6, MCP-1, and IL-4 cytokines in mild COVID-19 patients versus severe cases, as well as a high frequency of karyorrhexis (median [Me] = 364 vs. 20 cells) and karyolysis (Me = 266 vs. 52 cells) in the mucosal epithelial cells of both groups of patients compared with uninfected individuals. Although we observed higher levels of anti-SARS-CoV-2 IgM and IgG antibodies in COVID-19 patients, IgM antibodies were significantly higher only in mild cases, for the N and the S viral antigens. High levels of IgG antibodies were observed in both mild and severe cases. Our results showed elevated concentrations of proinflammatory and anti-inflammatory cytokines in mild cases, which may reflect an active innate immune response and could be related to the higher IgM and IgG antibody levels found in those patients. In addition, we found that SARS-CoV-2 infection induces cytotoxic damage in the oral mucosa, highlighting the importance of studying the genotoxic and cytotoxic events induced by infection and its role in the pathophysiology of COVID-19.

Community Forums as Amplifiers of Communities' Voices: Isolated Communities in Puerto Rico.

Social determinants of health contribute to health disparities and inequities. We conducted a community forum on the topic of isolation with the objectives of (1) identifying and prioritizing key health-related issues needing attention in isolated communities in Puerto Rico; (2) developing strategies in terms of Policies, Programs, and Practices to address the community priorities we identified. We used the triangulation method for qualitative data, integrating the Colorado State University's Tri-ethnic Center Model and the Delphi Technique for a better understanding of community health needs and priorities. The five community health-related priorities identified in the community forum were: (1) access to health services (physical and mental); (2) older adults; (3) access to basic services; (4) preparedness for future disasters/emergencies; and (5) COVID-19 and access to vaccination. The Alliance Leaders and Advisory Boards understand that we will work with the priorities of preparedness for future natural disasters/emergencies and COVID-19 and access to vaccination. Fifteen strategies were developed for these priorities and were grouped into five areas that require more attention in order to reduce health disparities. Isolated communities in Puerto Rico present an intersectionality of factors that affect a wide range of health-related risks and outcomes.

Contaminación microbiana durante la atención odontológica por la producción de aerosoles y salpicaduras / Microbial contamination during dental care due to aerosol and splash production

RESUMEN Objetivo: Analizar la contaminación microbiana durante la atención odontológica por la producción de aerosoles y salpicaduras. Metodología: De tipo documental, bibliográfica. La búsqueda se realizó a través de las bases de datos PubMed y Scopus. Considerando los lineamientos de la declaración PRISMA obteniendo un total de 221 artículos. Posteriormente se aplicaron los criterios de exclusión como de inclusión, obteniendo un total de 25 artículos. Resultados: La carga microbiana presente en el ambiente odontológico ha sido analizada de manera cuantitativa a través de las Unidades Formadoras de Colonias (UFC) en diferentes espacios y superficies de las clínicas dentales. En conclusión: La contaminación microbiológica asociada con la generación de aerosoles es una problemática que se experimenta en la consulta diaria, relacionándose principalmente con procedimientos asociados con equipos como las piezas de mano de alta velocidad, el equipo ultrasónico y la jeringa triple.

ABSTRACT Objective: To analyze microbial contamination during dental care due to the production of aerosols and splashes. Methodology: Documentary, bibliographic type. The search was carried out through the Pubmed and SCOPUS databases. Considering the guidelines of the PRISMA declaration, a total of 221 articles were obtained. Subsequently, the exclusion and inclusion criteria were applied, obtaining a total of 25 articles. Results: The microbial load present in the dental environment has been analyzed quantitatively through Colony Forming Units (CFU) in different spaces and surfaces of dental clinics. In conclusion: Microbiological contamination associated with the generation of aerosols is a problem that is experienced in the daily dental practice, mainly related to procedures associated with equipment such as high-speed handpieces, ultrasonic equipment and triple syringe.

Correction: Identification of drug resistance mutations among Mycobacterium bovis lineages in the Americas.

[This corrects the article DOI: 10.1371/journal.pntd.0009145.].

The Effects of Pictorial Health Warning Label on Waterpipe (Low- and High-Frequency) Smokers' Experiences, Toxicant Exposures, and Puffing Behavior.

BACKGROUND: Pictorial health warning label (PHWL) is an effective risk communication measure among cigarette smokers. However, there is a lack of knowledge regarding the effect of PHWL on low- and high-frequency waterpipe (WP) smokers. This study examined the effects of PHWL on puffing behavior, subjective experiences, and toxicant exposures among low- and high-frequency WP smokers in the United States (US). METHODS: Sixty current (past-month) WP smokers (low-frequency; n = 30 and high-frequency; n = 30) completed two 45-min ad libitum WP smoking sessions in a cross-over design study (WP with no-PHWL vs. WP with PHWL). We compared the mean differences of puff topography, expired carbon monoxide (eCO), plasma nicotine concentration, and subjective experiences between the two smoking groups. RESULTS: Mean age of low-frequency smokers was 21.5 years and high-frequency smokers was 21.3 years. Compared to high-frequency, low-frequency smokers had significant reduction in average total smoking time [mean difference (SD) = -7.6 (10.2) min vs. -2.6 (6.7) min, p = 0.03] and number of puffs [mean difference (SD) = -33.37 (70.7) vs. -0.70 (29.2), p = 0.02] following exposure to PHWL compared to no-PHWL condition. Post-session subjective experiences were lower among high-frequency smokers compared to low-frequency smokers following smoking WP with PHWL compared to the no-PHWL session (puff liking -1.2 vs. -0.5; puff satisfaction -1.0 vs. -0.3; craving reduction -0.5 vs. 1.2) (p < 0.05 for all). CONCLUSION: Our findings indicate that placing PHWL on the WP device may be a promising strategy with differential effectiveness among WP smokers: low-frequency (reduce puffing behaviors) and high-frequency (reduce smoking experience).

Characterization of Inflammatory Breast Cancer in Hispanic Women from Puerto Rico.

Background: Breast cancer (BC) is the most diagnosed cancer and the leading cause of cancer death among women in Puerto Rico (PR). Inflammatory breast cancer (IBC) is considered the most aggressive BC subtype. This study characterized the IBC population of Hispanic women living in Puerto Rico and aimed to estimate the IBC survival rate using data from the Puerto Rico Central Cancer Registry (PRCCR). Methods: This is a retrospective, population-based study using the PRCCR database and the Health Insurance Linkage Database (PRCCR-HILD). We analyzed data from patients that were diagnosed with IBC from January 1, 2008 to December 31, 2018. Patients were identified using the International Classification of Diseases for Oncology, 3rd edition (ICD-O-3) site codes C50.0-C50.9 and histology code 8530. Variables such as age at diagnosis, marital status, health insurance, geographic area of residence, staging variables, tumor receptor subtypes, treatment received, and overall survival (OS) were studied. Statistical analysis methods were employed to describe the population, estimate survival curves and examine the risk of dying. Results: The data of 51 patients were included. The mean age at diagnosis of IBC in the current study was 59 years old. A total of 62.8% of patients had no metastases at diagnosis and 64.7% were diagnosed with stage III disease. Most tumors presented with ER+/PR+/Her2- (21.6%), or a triple negative (ER-/PR-/Her2-, 15.7%) tumor concordance. The OS during the first year was 66% (90% CI: 0.54-0.76), whereas 36 months post-diagnosis was at a low 39% (90% CI: 0.27-0.59). The triple-negative subtype had the worst survival at 36 months (36% [90% CI: 0.11-0.62]). This study revealed through Cox regression analysis that women with stage IV disease and those with ER-/PR- tumor subtype have a higher risk of dying (HR 4.99; [90% CI: 2.30-10.83] and HR 4.74; [90% CI: 1.88-11.95]), respectively. Conclusions: Our results suggest that the Puerto Rican IBC patient population presents unique characteristics. This is the first research to describe the patient profile and characteristics of women diagnosed with IBC in PR. This research increases awareness about this lethal disease in PR.

Effect of menthol/mint-flavored pods on young JUUL E-cigarette users' subjective experience, puffing behavior, and nicotine exposure: A pilot study.

BACKGROUND: Recent regulations have banned all flavors except menthol/mint and classic tobacco from pod-based e-cigarette devices such as JUUL. However, menthol/mint flavor can present a potential risk given its increasing popularity among young people in the US and its puffing and nicotine-enhancing properties. This study examines the impact of menthol/mint flavor manipulation on users' puffing behavior, subjective experience, and nicotine exposure among young people. METHODS: JUUL users (n = 33, 18-24 years) attended two 60-min ad libitum e-cigarette use sessions (menthol/mint flavor vs. classic tobacco flavor) in a cross-over design. Puff topography and plasma nicotine concentration were measured, and participants completed subjective experience questionnaires. RESULTS: Following the use of the menthol/mint-flavored pod, increases were observed in measures of satisfaction, pleasurable/interest to use, willingness to use again, enjoyment, urge to vape, product appeal, taste, and concentration (p < .05 for all). For example, compared to the classic tobacco flavor, participants experienced significantly more satisfaction of the product (4.24 vs. 3.09; p = .001) and sensation enjoyment of the product (3.55 vs. 2.48; p = .002) when using the menthol/mint flavor. While means of the plasma nicotine boost and puff parameters were lower in the classic tobacco condition compared to the menthol/mint flavor condition, no statistical significance was observed between the two conditions (p > .05 for all). CONCLUSIONS: Results of this pilot study suggest that menthol/mint-flavor increases e-cigarette users' subjective experience significantly. Regulating menthol/mint flavor is a potentially promising strategy to curb e-cigarette use among young people.

Intra-host genetic population diversity: Role in emergence and persistence of drug resistance among Mycobacterium tuberculosis complex minor variants.

Drug resistant tuberculosis (DR-TB) is an important public health issue in different parts of the world. Mycobacterium tuberculosis complex variants (MTBC vars) preferentially infect certain hosts, limiting their distribution to different ecosystems. However, MTBC vars can infect other hosts beyond their preferred target potentially contributing to persistence of drug resistance (DR) in other niches. Here, we performed a comprehensive intra-host genetic analysis for the identification of DR-related mutations among all MTBC minor vars whole genome sequences (8,095 strains) publicly available worldwide. High confidence drug-resistance mutations in katG (isoniazid), rpsL (streptomycin), pncA (pyrazinamide), rpoB (rifampicin) and gyrA (fluoroquinolones) genes were identified among intrahost minor sub-populations in 197 different strains (2.43%) belonging to vars africanum, bovis, caprae, microti, orygis and pinnipedii. In addition, a three-dimensional structure modeling analysis to assess the role of novel mutations was also performed. Our findings highlight the importance of detecting discrete intra-host populations carrying DR mutations.

The Effect of Graphic Health Warning Labels Placed on the ENDS Device on Young Adult Users' Experience, Exposure and Intention to Use: A Pilot Study.

This proof-of-concept study aims to evaluate the effect of placing graphic health warning labels (GHWLs) on the ENDS device on users' experience, puffing patterns, harm perception, nicotine exposure, and intention to quit or use in the future. JUUL users (n = 26, age 18-24 years; 69% male; 85% Hispanic) were recruited to complete two 60 minutes ad libitum sessions that differed by GHWL on the device (GHWL vs. no-GHWL control) in an experimental clinical lab study. Compared to the control session, using JUUL with GHWL on the device was significantly associated with reduced positive experiences such as pleasure, product liking, and user satisfaction (p-value < 0.05 for all). Also, after exposure to GHWL, participants were less interested in using the same product again (p-value = 0.007), even if it was the only product available on the market compared to control (p-value = 0.03). Trends toward reduced puffing behavior and nicotine boost were also noted during the GHWL, compared to control sessions. This pilot study shows that placing GHWL on the ENDS device may be an effective and promising strategy to reduce ENDS use among young people.

COVID-19, las enfermedades no transmisibles y el envejecimiento saludable en México / COVID-19, Noncommunicable Diseases and Healthy Aging in Mexico

Resumen Introducción. La pandemia de COVID-19 ha visibilizado la situación actual de los sistemas y las condiciones de salud de la población en todo el mundo. Objetivo. Analizar las condiciones de salud de la población en México, sobre todo en el grupo de 45 a 59 años, y cómo las enfermedades no transmisibles y la edad son factores de mal pronóstico para COVID-19, a fin de mostrar al envejecimiento saludable como una alternativa para replantear las políticas públicas. Argumentos para la discusión. Se requiere que el grupo etario de 45 a 59 años sea considerado como objetivo dentro de la cobertura del Paquete Garantizado de Servicios de Salud, cuyas acciones se aplican en todo el sector a manera de medicina preventiva; esto, porque actualmente está incluido en un grupo etario más amplio y se debe tomar en cuenta el incremento de la mortalidad asociada con la edad y la comorbilidad ocurrida por la pandemia. Conclusiones. México demanda un replanteamiento sobre la política pública de envejecimiento saludable, mediante la implementación de estrategias y acciones en todo el curso de vida, pero de forma urgente durante la segunda mitad, después de los 45 años, con medidas de prevención secundaria de enfermedades no transmisibles, ya que es a partir de esta edad y hasta los 79 años donde se han presentado la mayor cantidad de defunciones por COVID-19; de tal modo, se busca enfrentar con mejores condiciones de salud de la población las siguientes pandemias que se presenten.

Abstract Introduction. The COVID-19 pandemic has unleashed the current situation of health systems and the health conditions of the population throughout the world. Objective. Analyze the health conditions of the population in Mexico, especially in the 45 to 59 age group, and how non-communicable diseases and age are poor prognostic factors for COVID-19, showing healthy aging as an alternative to rethink public policies. Arguments for discussion. The age group from 45 to 59 years is required to be considered as a target group for the coverage of the Guaranteed Package of Health Services, whose actions are applied throughout the sector as preventive medicine actions, since it is currently included in a broader age group, taking into account the increase in mortality associated with age and comorbidity caused by the pandemic. Conclusions. Mexico requires a rethinking of the public policy of healthy aging, with the application of strategies and actions throughout the life course, seeking to apply urgent measures from the second half of life, starting at age 45, with secondary prevention actions of non-communicable diseases, since it is from this age and up to 79 years where the highest number of deaths has occurred in Mexico due to COVID-19, thus seeking to face the following pandemics with better health conditions of the population they come forward.

Identification of drug resistance mutations among Mycobacterium bovis lineages in the Americas.

Identifying the Mycobacterium tuberculosis resistance mutation patterns is of the utmost importance to assure proper patient's management and devising of control programs aimed to limit spread of disease. Zoonotic Mycobacterium bovis infection still represents a threat to human health, particularly in dairy production regions. Routinary, molecular characterization of M. bovis is performed primarily by spoligotyping and mycobacterial interspersed repetitive units (MIRU) while next generation sequencing (NGS) approaches are often performed by reference laboratories. However, spoligotyping and MIRU methodologies lack the resolution required for the fine characterization of tuberculosis isolates, particularly in outbreak settings. In conjunction with sophisticated bioinformatic algorithms, whole genome sequencing (WGS) analysis is becoming the method of choice for advanced genetic characterization of tuberculosis isolates. WGS provides valuable information on drug resistance and compensatory mutations that other technologies cannot assess. Here, we performed an analysis of the most frequently identified mutations associated with tuberculosis drug resistance and their genetic relationship among 2,074 Mycobacterium bovis WGS recovered primarily from non-human hosts. Full-length gene sequences harboring drug resistant associated mutations and their phylogenetic relationships were analyzed. The results showed that M. bovis isolates harbor mutations conferring resistance to both first- and second-line antibiotics. Mutations conferring resistance for isoniazid, fluoroquinolones, streptomycin, and aminoglycosides were identified among animal strains. Our findings highlight the importance of molecular surveillance to monitor the emergence of mutations associated with multi and extensive drug resistance in livestock and other non-human mammals.

Markers of oxidative stress and toxicant exposure among young waterpipe smokers in the USA.

Waterpipe (aka hookah) tobacco smokers are exposed to toxicants that can lead to oxidative DNA and RNA damage, a precursor to chronic disease formation. This study assessed toxicant exposure and biomarkers of DNA [8-oxo-7, 8-dihydro-2'-deoxyguanosine (8-oxodG)] and RNA [8-oxo-7,8-dihydroguanosine (8-oxoGuo)] oxidative damage during smoking of flavored and non-flavored waterpipe tobacco. Thirty waterpipe smokers completed two counterbalanced 2-h lab waterpipe smoking sessions (flavored vs. non-flavored waterpipe tobacco). Urinary concentrations of 8-oxodG and 8-oxoGuo and expired carbon monoxide (eCO) were measured before and after the smoking sessions. A significant increase in the urinary concentrations of 8-oxodG (from 2.12 ± 0.83 to 2.35 ± 0.91 ng/mg creatinine, p = 0.024) and 8-oxoGuo (from 2.96 ± 0.84 to 3.45 ± 0.76 ng/mg creatinine, p = 0.003) were observed after smoking the non-flavored and flavored waterpipe tobacco, respectively. Our results also showed that the mean ± SD of eCO increased significantly after smoking the flavored (from 1.3 ± 1.1 to 20.3 ± 23.6 ppm, p < 0.001) and non-flavored waterpipe tobacco (from 1.8 ± 1.2 to 24.5 ± 26.1 ppm, p < 0.001). There were no significant differences in the means of 8-oxodG (p = 0.576), 8-oxoGuo (p = 0.108), and eCO (p = 0.170) between the flavored and non-flavored tobacco sessions. Smoking non-flavored and flavored waterpipe tobacco leads to oxidative stress and toxicant exposure. Our findings add to the existing evidence about the adverse effects of waterpipe tobacco smoking (WTS) and the need for strong policies to inform and protect young people from the risks of WTS.

Effect of flavour manipulation on ENDS (JUUL) users' experiences, puffing behaviour and nicotine exposure among US college students.

SIGNIFICANCE: Electronic nicotine delivery system (ENDS) use has continued to increase exponentially among young people in the USA, with unique flavours being one of the most cited reasons for use. Yet, controlled studies examining the effects of restricting flavour are lacking. This study evaluates the impact of ENDS flavour manipulation on user's puffing behaviour, subjective experience, harm perception and nicotine exposure among college-aged ENDS users. METHODS: JUUL users (n=30, age 18 to 24 years) attended two 60 min ad libitum ENDS use sessions (JUUL preferred flavour vs JUUL classic tobacco flavour) in a cross-over design. Puff topography and plasma nicotine concentration were measured, and participants completed subjective experience questionnaires. RESULTS: Increases were observed on measures of satisfaction, taste, enjoyment, urges to vape/smoke, pleasure, product appeal and increased concentration following using the preferred flavour pod (p values <0.05). Compared with preferred flavour, participants in the tobacco flavour were less motivated to use it in the future (70.9 vs 19.1 scores, p<0.001), even if it was the only product on the market (75.8 vs 30.7 scores, p<0.001). While nicotine levels significantly increased in both conditions from pre to post session (p values <0.001), no significant differences were observed in nicotine boost levels or on puff topography parameters when comparing both flavour conditions. CONCLUSIONS: This pilot study provides evidence that ENDS flavours have a substantial effect in enhancing young current ENDS users' experiences, product appeal and motivation to use the product in the future. It highlights that limiting flavours could play a potential role when designing strategic policies to reduce the appeal of ENDS use among young people.

Manejo del colapso de válvula nasal externa: revisión de la literatura / Management of external nasal valve collapse: literature review

La rinoplastia es una de las cirugías estéticas más realizadas en el mundo y entre las complicaciones más frecuentes está el colapso valvular por la excesiva resección del cartílago alar. La parálisis facial, así como el envejecimiento pueden colapsar la pared lateral en inspiración por disfunción del músculo nasal, al provocar debilitamiento del tejido fibroalveolar de la pared lateral nasal, existiendo también causas genéticas que producen colapso valvular. Actualmente se practican diversas técnicas para mejorar el colapso valvular y ninguna es cien por ciento efectiva, la mayor parte se centran en corregir la propia válvula nasal o el cartílago triangular, lo que indica que se fijan en un solo factor y no en la etiología multifactorial que la produce. Este estudio revisa la evidencia clínica que guía a un diagnóstico correcto y al manejo efectivo de la disfunción de la válvula nasal externa, mediante el uso de diversas técnicas que se emplean actualmente para perfeccionar el colapso valvular nasal.

Rhinoplasty is one of the most frequent cosmetic surgeries in the world and among the most common complications is valve collapse due to excessive resection of the alar cartilage. Facial paralysis, as well as aging, can collapse the lateral wall in inspiration due to dysfunction of the nasal muscle, causing weakening of the fibroalveolar tissue of the nasal lateral wall, and there are also genetic causes that produce valve collapse. Currently, various techniques are practiced to improve valve collapse and none are one hundred percent effective, most of them focus on correcting the nasal valve itself or the triangular cartilage, which indicates that they are fixed on a single factor and not on multifactorial etiology that produces it. This study reviews the clinical evidence that guides a correct diagnosis and effective management of external nasal valve dysfunction, using various techniques that are currently used to improve nasal valve collapse.

In Vitro Employment of Recombinant Taenia solium Calreticulin as a Novel Strategy Against Breast and Ovarian Cancer Stem-like Cells.

BACKGROUND AND AIMS: Calreticulin is a chaperone and master regulator of intracellular calcium homeostasis. Several additional functions have been discovered. Human and parasite calreticulin have been shown to suppress mammary tumor growth in vivo. Here, we explored the capacity of recombinant Taenia solium calreticulin (rTsCRT) to modulate cancer cell growth in vitro. METHODS: We used different concentrations of rTsCRT to treat cancer cell lines and analyzed viability and colony formation capacity. We also tested the combination of the IC20 or IC50 doses of rTsCRT and of the chemotherapeutic drug 5-fluorouracil on MCF7 and SKOV3 cell lines. As a control, the non-tumorigenic cell line MCF10-A was employed. The effect of the drug combinations was also assessed in cancer stem-like cells. Additionally, scavenger receptor ligands were employed to identify the role of this receptor in the rTsCRT anti-tumoral effect. RESULTS: rTsCRT has a dose-dependent in vitro anti-tumoral effect, being SKOV3 the most sensitive cell line followed by MCF7. When rTsCRT/5-fluorouracil were used, MCF7 and SKOV3 showed a 60% reduction in cell viability; colony formation capacity was also diminished. Treatment of cancer stem-like cells from MCF7 showed a higher reduction in cell viability, while those from SKOV3 were more sensitive to colony disaggregation. Finally, pharmacological inhibition of the scavenger receptor, abrogated the reduction in viability induced by rTsCRT in both the parental and stem-like cells. CONCLUSION: Our data suggest that rTsCRT alone or in combination with 5-fluorouracil inhibits the growth of breast and ovarian cancer cell lines through its interaction with scavenger receptors.

Genetic polymorphisms present in IL10, IL23R, NOD2, and ATG16L1 associated with susceptibility to inflammatory bowel disease in Mexican population.

OBJECTIVE: Ulcerative colitis and Crohn's disease are the two clinical forms of inflammatory bowel disease (IBD). Diverse studies have shown the association of single nucleotide polymorphism (SNP) in molecules of the immune system and the occurrence of IBD. Here, several SNPs of the immune system with controversial results for their association with UC and CD were evaluated in a Mexican population. METHODS: SNPs rs1800896, rs3024505 (IL-10); rs11209026 (IL23R); rs2066844, rs2066845 (NOD-2), and rs2241880 (ATG16L1) were assessed in 93 patients with IBD and 200 healthy controls by hybridization probes and quantitative PCR. RESULTS: The AG genotype for rs1800896 was associated with an increased risk for both UC and CD (P = 0.005 and P = 0.026, respectively); whereas the AA genotype presents a negative association (P = 0.011 for UC, and 0.0038 for CD). For this SNP, G allele was associated with risk of UC (P = 0-043) but not for CD. For the rs3024505 in IL-10, T allele was associated with UC (P = 0.011). Moreover, this allele was associated with early onset of UC (P = 0.033) and with the use of steroid treatment (P = 0.019). No significant differences for NOD2 (rs2066844T and rs2066845C), IL23R (rs11209026), and ATG16L1 (rs22411880) were found between cases and controls and the homozygous TT genotype for rs2066844 and CC for rs2066845 were not observed. CONCLUSION: Our results show both genotypic and phenotypic associations of IL-10 SNPs with IBD but not with the other immune-related SNPs studied in this Mexican cohort.

Labeling Stem Cells with a New Hybrid Bismuth/Carbon Nanotube Contrast Agent for X-Ray Imaging.

The poor retention and survival of cells after transplantation to solid tissue represent a major obstacle for the effectiveness of stem cell-based therapies. The ability to track stem cells in vivo can lead to a better understanding of the biodistribution of transplanted cells, in addition to improving the analysis of stem cell therapies' outcomes. Here, we described the use of a carbon nanotube-based contrast agent (CA) for X-ray computed tomography (CT) imaging as an intracellular CA to label bone marrow-derived mesenchymal stem cells (MSCs). Porcine MSCs were labeled without observed cytotoxicity. The CA consists of a hybrid material containing ultra-short single-walled carbon nanotubes (20-80 nm in length, US-tubes) and Bi(III) oxo-salicylate clusters which contain four Bi3+ ions per cluster (Bi4C). The CA is thus abbreviated as Bi4C@US-tubes.

Calreticulin in phagocytosis and cancer: opposite roles in immune response outcomes.

Calreticulin (CRT) is a pleiotropic and highly conserved molecule that is mainly localized in the endoplasmic reticulum. Recently, CRT has gained special interest for its functions outside the endoplasmic reticulum where it has immunomodulatory properties. CRT translocation to the cell membrane serves as an "eat me" signal and promotes efferocytosis of apoptotic cells and cancer cell removal with completely opposite outcomes. Efferocytosis results in a silenced immune response and homeostasis, while removal of dying cancer cells brought about by anthracycline treatment, ionizing-irradiation or photodynamic therapy results in immunogenic cell death with activation of the innate and adaptive immune responses. In addition, CRT impacts phagocyte activation and cytokine production. The effects of CRT on cytokine production depend on its conformation, species specificity, degree of oligomerization and/or glycosylation, as well as its cellular localization and the molecular partners involved. The controversial roles of CRT in cancer progression and the possible role of the CALR gene mutations in myeloproliferative neoplasms are also addressed. The release of CRT and its influence on the different cells involved during efferocytosis and immunogenic cell death points to additional roles of CRT besides merely acting as an "eat me" signal during apoptosis. Understanding the contribution of CRT in physiological and pathological processes could give us some insight into the potential of CRT as a therapeutic target.

Flavored Versus Nonflavored Waterpipe Tobacco: A Comparison of Toxicant Exposure, Puff Topography, Subjective Experiences, and Harm Perceptions.

INTRODUCTION: Flavored waterpipe (WP) tobacco is the main type of tobacco used by young WP smokers, and a major factor attracting youth to smoke. However, evidence regarding the effect of limiting flavor on WP smokers' experience continues to be lacking. This study aims at evaluating the effect of flavor restriction on WP smokers' toxicant exposure, smoking topography, subjective experiences and harm perception. METHODS: Thirty-two WP smokers completed two, 45-minute ad libitum smoking sessions (preferred flavor vs non-flavored tobacco) in a crossover design pilot study. Plasma nicotine concentration and exhaled carbon monoxide (eCO) were measured before and after each smoking session. Puff topography was recorded throughout the smoking session. Participants completed survey questionnaires assessing subjective smoking experiences and harm perception. RESULTS: Significant differences were observed in plasma nicotine concentration between the two WP tobacco conditions, with a higher increase in plasma nicotine concentration following the flavored tobacco session. There were no significant differences between the two WP tobacco conditions for eCO and smoking topography measures. Compared with the non-flavored WP tobacco, we documented enhanced subjective smoking measures of satisfaction, calmness, taste, puff liking and enjoyment following the preferred flavored WP tobacco session. Cigarette harm perception was significantly higher among participants after smoking their preferred flavor compared with non-flavored WP tobacco. CONCLUSIONS: Limiting tobacco flavor has a substantial effect on WP smokers' nicotine exposure, subjective experience and harm perception. Therefore, eliminating or restricting WP flavors could be an essential element of comprehensive tobacco control policies to reduce the appeal of WP tobacco products for youth. IMPLICATIONS: This study highlights the important role of flavor in shaping WP smokers' experiences and exposures and the potential impact that regulating flavored WP tobacco may have on curbing WP use among youth in the US. Such regulations may reduce the appeal and the interest in WP smoking initiation and continued use.

A New High-Performance Gadonanotube-Polymer Hybrid Material for Stem Cell Labeling and Tracking by MRI.

A gentle, rapid method has been developed to introduce a polyacrylic acid (PAA) polymer coating on the surface of gadonanotubes (GNTs) which significantly increases their dispersibility in water without the need of a surfactant. As a result, the polymer, with its many carboxylic acid groups, coats the surface of the GNTs to form a new GNT-polymer hybrid material (PAA-GNT) which can be highly dispersed in water (ca. 20 mg·mL-1) at physiological pH. When dispersed in water, the new PAA-GNT material is a powerful MRI contrast agent with an extremely short water proton spin-lattice relaxation time (T1) which results in a T1-weighted relaxivity of 150 mM-1·s-1 per Gd3+ ion at 1.5 T. Furthermore, the PAA-GNTs have been used to safely label porcine bone-marrow-derived mesenchymal stem cells for magnetic resonance imaging. The labeled cells display excellent image contrast in phantom imaging experiments, and transmission electron microscopy images of the labeled cells reveal the presence of highly dispersed PAA-GNTs within the cytoplasm with 1014 Gd3+ ions per cell.