Silica-coated LiYF4:Yb3+, Tm3+ upconverting nanoparticles are non-toxic and activate minor stress responses in mammalian cells.

Lanthanide-doped upconverting nanoparticles (UCNPs) are ideal candidates for use in biomedicine. The interaction of nanomaterials with biological systems determines whether they are suitable for use in living cells. In-depth knowledge of the nano-bio interactions is therefore a pre-requisite for the development of biomedical applications. The current study evaluates fundamental aspects of the NP-cell interface for square bipyramidal UCNPs containing a LiYF4:Yb3+, Tm3+ core and two different silica surface coatings. Given their importance for mammalian physiology, fibroblast and renal proximal tubule epithelial cells were selected as cellular model systems. We have assessed the toxicity of the UCNPs and measured their impact on the homeostasis of living non-malignant cells. Rigorous analyses were conducted to identify possible toxic and sub-lethal effects of the UCNPs. To this end, we examined biomarkers that reveal if UCNPs induce cell killing or stress. Quantitative measurements demonstrate that short-term exposure to the UCNPs had no profound effects on cell viability, cell size or morphology. Indicators of oxidative, endoplasmic reticulum, or nucleolar stress, and the production of molecular chaperones varied with the surface modification of the UCNPs and the cell type analyzed. These differences emphasize the importance of evaluating cells of diverse origin that are relevant to the intended use of the nanomaterials. Taken together, we established that short-term, our square bipyramidal UCNPs are not toxic to non-malignant fibroblast and proximal renal epithelial cells. Compared with established inducers of cellular stress, these UCNPs have minor effects on cellular homeostasis. Our results build the foundation to explore square bipyramidal UCNPs for future in vivo applications.

RABL2 promotes the outward transition zone passage of signaling proteins in cilia via ARL3.

Certain transmembrane and membrane-tethered signaling proteins export from cilia as BBSome cargoes via the outward BBSome transition zone (TZ) diffusion pathway, indispensable for maintaining their ciliary dynamics to enable cells to sense and transduce extracellular stimuli inside the cell. Murine Rab-like 2 (Rabl2) GTPase resembles Chlamydomonas Arf-like 3 (ARL3) GTPase in promoting outward TZ passage of the signaling protein cargo-laden BBSome. During this process, ARL3 binds to and recruits the retrograde IFT train-dissociated BBSome as its effector to diffuse through the TZ for ciliary retrieval, while how RABL2 and ARL3 cross talk in this event remains uncertain. Here, we report that Chlamydomonas RABL2 in a GTP-bound form (RABL2GTP) cycles through cilia via IFT as an IFT-B1 cargo, dissociates from retrograde IFT trains at a ciliary region right above the TZ, and converts to RABL2GDP for activating ARL3GDP as an ARL3 guanine nucleotide exchange factor. This confers ARL3GTP to detach from the ciliary membrane and become available for binding and recruiting the phospholipase D (PLD)-laden BBSome, autonomous of retrograde IFT association, to diffuse through the TZ for ciliary retrieval. Afterward, RABL2GDP exits cilia by being bound to the ARL3GTP/BBSome entity as a BBSome cargo. Our data identify ciliary signaling proteins exported from cilia via the RABL2-ARL3 cascade-mediated outward BBSome TZ diffusion pathway. According to this model, hedgehog signaling defect-induced Bardet-Biedl syndrome caused by RABL2 mutations in humans could be well explained in a mutation-specific manner, providing us with a mechanistic understanding behind the outward BBSome TZ passage required for proper ciliary signaling.

Association of zoonotic protozoan parasites with microplastics in seawater and implications for human and wildlife health.

Plastics are widely recognized as a pervasive marine pollutant. Microplastics have been garnering increasing attention due to reports documenting their ingestion by animals, including those intended for human consumption. Their accumulation in the marine food chain may also pose a threat to wildlife that consume species that can accumulate microplastic particles. Microplastic contamination in marine ecosystems has thus raised concerns for both human and wildlife health. Our study addresses an unexplored area of research targeting the interaction between plastic and pathogen pollution of coastal waters. We investigated the association of the zoonotic protozoan parasites Toxoplasma gondii, Cryptosporidium parvum, and Giardia enterica with polyethylene microbeads and polyester microfibers. These pathogens were chosen because they have been recognized by the World Health Organization as underestimated causes of illness from shellfish consumption, and due to their persistence in the marine environment. We show that pathogens are capable of associating with microplastics in contaminated seawater, with more parasites adhering to microfiber surfaces as compared with microbeads. Given the global presence of microplastics in fish and shellfish, this study demonstrates a novel pathway by which anthropogenic pollutants may be mediating pathogen transmission in the marine environment, with important ramifications for wildlife and human health.

Sexual Sadism Disorder and Coercive Paraphilic Disorder: A Scoping Review.

BACKGROUND: Valid and reliable diagnostic criteria are essential in forensic psychiatry and sexual medicine due to the severe implications of potential misdiagnoses. One challenge in this field is the poor operationalization of sexual sadism disorder (SSD) and coercive paraphilic disorder (CP+) definitions. AIM: The aim of this scoping literature review is to provide a comprehensive overview of the key conceptual differences between SSD and CP+, as well as consider pragmatic and clinically useful approaches to their diagnostic formulation. METHODS: Arksey and O'Malley's methodological framework was followed. A literature search of Medline, PsychInfo, Web of Science, and Cumulative Index to Nursing and Allied Health Literature electronic databases was conducted. Publications in English describing the construct and/or operational definition of SSD or CP+ were included. Full-text studies were reviewed by 2 authors and data was charted and synthesized qualitatively. RESULTS: The initial search provided 1,271 records, after which 120 full-text papers were considered for eligibility and 48 studies were ultimately included. The most common sources of definitions for SSD and CP+ were the Diagnostic and Statistical Manual of Mental Disorders (n = 53) and the International Classification of Disease (n = 12). There was more variation of terms used for CP+ than SSD. Both CP+ and SSD are critiqued by reviewed literature for having low validity, reliability, and consistency, as well as being conflated with sexual crime. SSD is better described due to having diagnostic criteria and validated diagnostic tools. CLINICAL IMPLICATIONS: Currently, clinicians rely mostly on the DSM to diagnose SSD or CP+. As applications of SSD and CP+ definitions vary, interpretations may not be generalizable between clinicians. Furthermore, specific diagnoses may be practically unhelpful and unreliable. It may therefore be beneficial for treatment to be determined by risk of harm. In addition to these concerns, the stigma associated with SSD and CP+ may also impact treatment. STRENGTHS & LIMITATIONS: Strengths of this study include duplicate review and charting to increase methodological rigor, transparent reporting to minimize publication bias, and encompassing a comprehensive scope. Limitations include the weaknesses of low strength of reviewed literature and risk of publication bias. CONCLUSION: Despite their significant implications, the definitions of SSD and CP+ are inconsistent and lack reliability. Future research is necessary to develop stronger diagnostic criteria and tools. Liu A, Zhang E, Leroux EJ et al. Sexual Sadism Disorder and Coercive Paraphilic Disorder: A Scoping Review. J Sex Med 2022;000:1-11.

Assessment of the risk posed to Singapore by the emergence of artemisinin-resistant malaria in the Greater Mekong Subregion.

OBJECTIVE: To assess the public health risk to Singapore posed by the emergence of artemisinin-resistant (ART-R) malaria in the Greater Mekong Subregion (GMS). METHODS: We assessed the likelihood of importation of drug-resistant malaria into Singapore and the impact on public health of its subsequent secondary spread in Singapore. Literature on the epidemiology and contextual factors associated with ART-R malaria was reviewed. The epidemiology of malaria cases in Singapore was analysed. The vulnerability and receptivity of Singapore were examined, including the connectivity with countries reporting ART-R malaria, as well as the preparedness of Singaporean health authorities. Sources of information include international journals, World Health Organization guidelines, data from the Singapore Ministry of Health and National Public Health Laboratory of the National Centre for Infectious Diseases, and the International Air Transport Association. RESULTS: The importation of ART-R malaria into Singapore is possible given the close proximity and significant travel volume between Singapore and the GMS countries reporting artemisinin resistance. Singapore's vulnerability is further enhanced by the presence of foreign workers from neighbouring endemic countries. Nonetheless, the overall likelihood of such an event is low based on the rarity and decreasing trend of imported malaria incidence.​: With the presence of Anopheles vectors in Singapore, imported cases of drug-resistant malaria could cause secondary transmission. Nevertheless, the risk of sustained spread is likely to be mitigated by the comprehensive surveillance and control system in place for both infected vectors and human cases. DISCUSSION: This risk assessment highlights the need for a continued high degree of vigilance of ART-R malaria locally and globally to minimize the risk and public health impact of drug-resistant malaria in Singapore.

The differences between gonadal and extra-gonadal malignant teratomas in both genders and the effects of chemotherapy.

BACKGROUND: A tumor comprising of different types of tissues (such as hair, muscle, bone, etc.) is known as a teratoma. It is a type of germ cell (cells that make sperm or eggs) tumor. When these germ cells have rapid cancerous growth, then such a teratoma is called a malignant teratoma. We have studied the differences between gonadal and extra-gonadal malignant teratomas and the effects of chemotherapy in both genders. METHODS: The samples of 3799 male and 1832 female patients with malignant teratoma samples, between the ages of 1 and 85+ years, were selected from the years 1973 to 2014. Trends in incidence, estimated prevalence, incidence rates, and frequency were calculated in gonadal and extra-gonadal tumors with age adjustment. The five-year observed, expected, and relative survival rates were analyzed to study the prognosis. RESULTS: The gonadal took over a majority percentage of malignant teratomas compared with the extra-gonadal (90% vs. 10% in male; 83% vs. 17% in female). For the male, the total of the gonadal and the extra-gonadal were all significantly decreased from 1973 to 2014 (p < 0.05). For the female, there were no significant trends. As for prevalence, incidence, and frequency, there were two separate peaks of malignant teratomas. One peak was at under 1 year old, which was composed of the extra-gonadal tumor; the other peak was at 20-24 for male and 10-34 for female, which was composed of the gonadal tumor. This separation of the gonadal and extra-gonadal showed a significant difference (p < 0.05). As for the prognosis, the extra-gonadal tumor showed significantly lower survival rates than the gonadal (p < 0.05). In the short term, the survival rate of the chemotherapy group was higher than the supportive care group. However, in the long term, the survival rate of the chemotherapy group was lower than the supportive care group. CONCLUSION: The gonadal and extra-gonadal malignant teratomas show lots of differences. Chemotherapy might not help improve survival rates.

Structural Determinants of Health among Im/Migrants in the Indoor Sex Industry: Experiences of Workers and Managers/Owners in Metropolitan Vancouver.

BACKGROUND: Globally, im/migrant women are overrepresented in the sex industry and experience disproportionate health inequities. Despite evidence that the health impacts of migration may vary according to the timing and stage of migration (e.g., early arrival vs. long-term migration), limited evidence exists regarding social and structural determinants of health across different stages of migration, especially among im/migrants engaged in sex work. Our aim was to describe and analyze the evolving social and structural determinants of health and safety across the arrival and settlement process for im/migrants in the indoor sex industry. METHODS: We analyzed qualitative interviews conducted with 44 im/migrant sex workers and managers/owners working in indoor sex establishments (e.g., massage parlours, micro-brothels) in Metropolitan Vancouver, Canada in 2011; quantitative data from AESHA, a larger community-based cohort, were used to describe socio-demographic and social and structural characteristics of im/migrant sex workers. RESULTS: Based on quantitative data among 198 im/migrant workers in AESHA, 78.3% were Chinese-born, the median duration in Canada was 6 years, and most (86.4%) serviced clients in formal indoor establishments. Qualitative narratives revealed diverse pathways into sex work upon arrival to Canada, including language barriers to conventional labour markets and the higher pay and relative flexibility of sex work. Once engaged in sex work, fear associated with police raids (e.g., immigration concerns, sex work disclosure) and language barriers to sexual negotiation and health, social and legal supports posed pervasive challenges to health, safety and human rights during long-term settlement in Canada. CONCLUSIONS: Findings highlight the critical influences of criminalization, language barriers, and stigma and discrimination related to sex work and im/migrant status in shaping occupational health and safety for im/migrants engaged in sex work. Interventions and policy reforms that emphasize human rights and occupational health are needed to promote health and wellbeing across the arrival and settlement process.

Assessment of the risk posed to Singapore by the 2015 Middle East respiratory syndrome outbreak in the Republic of Korea.

OBJECTIVE: To assess the public health risk to Singapore posed by the Middle East respiratory syndrome (MERS) outbreak in the Republic of Korea in 2015. METHODS: The likelihood of importation of MERS cases and the magnitude of the public health impact in Singapore were assessed to determine overall risk. Literature on the epidemiology and contextual factors associated with MERS coronavirus infection was collected and reviewed. Connectivity between the Republic of Korea and Singapore was analysed. Public health measures implemented by the two countries were reviewed. RESULTS: The epidemiology of the 2015 MERS outbreak in the Republic of Korea remained similar to the MERS outbreaks in Saudi Arabia. In addition, strong infection control and response measures were effective in controlling the outbreak. In view of the air traffic between Singapore and MERS-affected areas, importation of MERS cases into Singapore is possible. Nonetheless, the risk of a serious public health impact to Singapore in the event of an imported case of MERS would be mitigated by its strong health-care system and established infection control practices. DISCUSSION: The MERS outbreak was sparked by an exported case from the Middle East, which remains a concern as the reservoir of infection (thought to be camels) continues to exist in the Middle East, and sporadic cases in the community and outbreaks in health-care settings continue to occur there. This risk assessment highlights the need for Singapore to stay vigilant and to continue enhancing core public health capacities to detect and respond to MERS coronavirus.

Leveraging social networking sites for disease surveillance and public sensing: the case of the 2013 avian influenza A(H7N9) outbreak in China.

We conducted in-depth analysis on the use of a popular Chinese social networking and microblogging site, Sina Weibo, to monitor an avian influenza A(H7N9) outbreak in China and to assess the value of social networking sites in the surveillance of disease outbreaks that occur overseas. Two data sets were employed for our analysis: a line listing of confirmed cases obtained from conventional public health information channels and case information from Weibo posts. Our findings showed that the level of activity on Weibo corresponded with the number of new cases reported. In addition, the reporting of new cases on Weibo was significantly faster than those of conventional reporting sites and non-local news media. A qualitative review of the functions of Weibo also revealed that Weibo enabled timely monitoring of other outbreak-relevant information, provided access to additional crowd-sourced epidemiological information and was leveraged by the local government as an interactive platform for risk communication and monitoring public sentiment on the policy response. Our analysis demonstrated the potential for social networking sites to be used by public health agencies to enhance traditional communicable disease surveillance systems for the global surveillance of overseas public health threats. Social networking sites also can be used by governments for calibration of response policies and measures and for risk communication.

Leveraging social networking sites for disease surveillance and public sensing: the case of the 2013 avian influenza A(H7N9) outbreak in China

We conducted in-depth analysis on the use of a popular Chinese social networking and microblogging site, Sina Weibo, to monitor an avian influenza A(H7N9) outbreak in China and to assess the value of social networking sites in the surveillance of disease outbreaks that occur overseas. Two data sets were employed for our analysis: a line listing of confirmed cases obtained from conventional public health information channels and case information from Weibo posts. Our findings showed that the level of activity on Weibo corresponded with the number of new cases reported. In addition, the reporting of new cases on Weibo was significantly faster than those of conventional reporting sites and non-local news media. A qualitative review of the functions of Weibo also revealed that Weibo enabled timely monitoring of other outbreak-relevant information, provided access to additional crowd-sourced epidemiological information and was leveraged by the local government as an interactive platform for risk communication and monitoring public sentiment on the policy response. Our analysis demonstrated the potential for social networking sites to be used by public health agencies to enhance traditional communicable disease surveillance systems for the global surveillance of overseas public health threats. Social networking sites also can be used by governments for calibration of response policies and measures and for risk communication.

Distinct splice variants and pathway enrichment in the cell-line models of aggressive human breast cancer subtypes.

This study was conducted as a part of the Chromosome-Centric Human Proteome Project (C-HPP) of the Human Proteome Organization. The United States team of C-HPP is focused on characterizing the protein-coding genes in chromosome 17. Despite its small size, chromosome 17 is rich in protein-coding genes; it contains many cancer-associated genes, including BRCA1, ERBB2, (Her2/neu), and TP53. The goal of this study was to examine the splice variants expressed in three ERBB2 expressed breast cancer cell-line models of hormone-receptor-negative breast cancers by integrating RNA-Seq and proteomic mass spectrometry data. The cell lines represent distinct phenotypic variations subtype: SKBR3 (ERBB2+ (overexpression)/ER-/PR-; adenocarcinoma), SUM190 (ERBB2+ (overexpression)/ER-/PR-; inflammatory breast cancer), and SUM149 (ERBB2 (low expression) ER-/PR-; inflammatory breast cancer). We identified more than one splice variant for 1167 genes expressed in at least one of the three cancer cell lines. We found multiple variants of genes that are in the signaling pathways downstream of ERBB2 along with variants specific to one cancer cell line compared with the other two cancer cell lines and with normal mammary cells. The overall transcript profiles based on read counts indicated more similarities between SKBR3 and SUM190. The top-ranking Gene Ontology and BioCarta pathways for the cell-line specific variants pointed to distinct key mechanisms including: amino sugar metabolism, caspase activity, and endocytosis in SKBR3; different aspects of metabolism, especially of lipids in SUM190; cell-to-cell adhesion, integrin, and ERK1/ERK2 signaling; and translational control in SUM149. The analyses indicated an enrichment in the electron transport chain processes in the ERBB2 overexpressed cell line models and an association of nucleotide binding, RNA splicing, and translation processes with the IBC models, SUM190 and SUM149. Detailed experimental studies on the distinct variants identified from each of these three breast cancer cell line models that may open opportunities for drug target discovery and help unveil their specific roles in cancer progression and metastasis.

Genome wide proteomics of ERBB2 and EGFR and other oncogenic pathways in inflammatory breast cancer.

In this study we selected three breast cancer cell lines (SKBR3, SUM149 and SUM190) with different oncogene expression levels involved in ERBB2 and EGFR signaling pathways as a model system for the evaluation of selective integration of subsets of transcriptomic and proteomic data. We assessed the oncogene status with reads per kilobase per million mapped reads (RPKM) values for ERBB2 (14.4, 400, and 300 for SUM149, SUM190, and SKBR3, respectively) and for EGFR (60.1, not detected, and 1.4 for the same 3 cell lines). We then used RNA-Seq data to identify those oncogenes with significant transcript levels in these cell lines (total 31) and interrogated the corresponding proteomics data sets for proteins with significant interaction values with these oncogenes. The number of observed interactors for each oncogene showed a significant range, e.g., 4.2% (JAK1) to 27.3% (MYC). The percentage is measured as a fraction of the total protein interactions in a given data set vs total interactors for that oncogene in STRING (Search Tool for the Retrieval of Interacting Genes/Proteins, version 9.0) and I2D (Interologous Interaction Database, version 1.95). This approach allowed us to focus on 4 main oncogenes, ERBB2, EGFR, MYC, and GRB2, for pathway analysis. We used bioinformatics sites GeneGo, PathwayCommons and NCI receptor signaling networks to identify pathways that contained the four main oncogenes and had good coverage in the transcriptomic and proteomic data sets as well as a significant number of oncogene interactors. The four pathways identified were ERBB signaling, EGFR1 signaling, integrin outside-in signaling, and validated targets of C-MYC transcriptional activation. The greater dynamic range of the RNA-Seq values allowed the use of transcript ratios to correlate observed protein values with the relative levels of the ERBB2 and EGFR transcripts in each of the four pathways. This provided us with potential proteomic signatures for the SUM149 and 190 cell lines, growth factor receptor-bound protein 7 (GRB7), Crk-like protein (CRKL) and Catenin delta-1 (CTNND1) for ERBB signaling; caveolin 1 (CAV1), plectin (PLEC) for EGFR signaling; filamin A (FLNA) and actinin alpha1 (ACTN1) (associated with high levels of EGFR transcript) for integrin signalings; branched chain amino-acid transaminase 1 (BCAT1), carbamoyl-phosphate synthetase (CAD), nucleolin (NCL) (high levels of EGFR transcript); transferrin receptor (TFRC), metadherin (MTDH) (high levels of ERBB2 transcript) for MYC signaling; S100-A2 protein (S100A2), caveolin 1 (CAV1), Serpin B5 (SERPINB5), stratifin (SFN), PYD and CARD domain containing (PYCARD), and EPH receptor A2 (EPHA2) for PI3K signaling, p53 subpathway. Future studies of inflammatory breast cancer (IBC), from which the cell lines were derived, will be used to explore the significance of these observations.