Translating Health Information Effectively for Latino Populations

California is the state with the most Latinos, constituting over one third of California’s population. The majority of Latinos, the fastest growing minority group in the United States, does not speak English at home. With lower levels of education, English-language proficiency, and health literacy, Latino people need health information they can understand. Literal translations of materials from English to Spanish without tailoring are common and often result in products containing egregious inaccuracies and awkward language usage that can also be out of context. In a medical setting, these errors can compromise health and be life-threatening. This commentary and tool provides examples of “translations gone wrong” and tips to follow to help make Spanish-language products and interpretation services more culturally and linguistically appropriate

hsp70 genes in the human genome: Conservation and differentiation patterns predict a wide array of overlapping and specialized functions

<p>Abstract</p> <p>Background</p> <p>Hsp70 chaperones are required for key cellular processes and response to environmental changes and survival but they have not been fully characterized yet. The human <it>hsp70</it>-gene family has an unknown number of members (eleven counted over ten years ago); some have been described but the information is incomplete and inconsistent. A coherent body of knowledge encompassing all family components that would facilitate their study individually and as a group is lacking. Nowadays, the study of chaperone genes benefits from the availability of genome sequences and a new protocol, chaperonomics, which we applied to elucidate the human <it>hsp70 </it>family.</p> <p>Results</p> <p>We identified 47 hsp70 sequences, 17 genes and 30 pseudogenes. The genes distributed into seven evolutionarily distinct groups with distinguishable subgroups according to phylogenetic and other data, such as exon-intron and protein features. The N-terminal ATP-binding domain (ABD) was conserved at least partially in the majority of the proteins but the C-terminal substrate-binding domain (SBD) was not. Nine proteins were typical Hsp70s (65–80 kDa) with ABD and SBD, two were lighter lacking partly or totally the SBD, and six were heavier (>80 kDa) with divergent C-terminal domains. We also analyzed exon-intron features, transcriptional variants and protein structure and isoforms, and modality and patterns of expression in various tissues and developmental stages. Evolutionary analyses, including human <it>hsp70 </it>genes and pseudogenes, and other eukaryotic <it>hsp70 </it>genes, showed that six human genes encoding cytosolic Hsp70s and 27 pseudogenes originated from retro-transposition of HSPA8, a gene highly expressed in most tissues and developmental stages.</p> <p>Conclusion</p> <p>The human <it>hsp70</it>-gene family is characterized by a remarkable evolutionary diversity that mainly resulted from multiple duplications and retrotranspositions of a highly expressed gene, HSPA8. Human Hsp70 proteins are clustered into seven evolutionary Groups, with divergent C-terminal domains likely defining their distinctive functions. These functions may also be further defined by the observed differences in the N-terminal domain.</p

Chaperonin genes on the rise: new divergent classes and intense duplication in human and other vertebrate genomes

<p>Abstract</p> <p>Background</p> <p>Chaperonin proteins are well known for the critical role they play in protein folding and in disease. However, the recent identification of three diverged chaperonin paralogs associated with the human Bardet-Biedl and McKusick-Kaufman Syndromes (BBS and MKKS, respectively) indicates that the eukaryotic chaperonin-gene family is larger and more differentiated than previously thought. The availability of complete genome sequences makes possible a definitive characterization of the complete set of chaperonin sequences in human and other species.</p> <p>Results</p> <p>We identified fifty-four chaperonin-like sequences in the human genome and similar numbers in the genomes of the model organisms mouse and rat. In mammal genomes we identified, besides the well-known CCT chaperonin genes and the three genes associated with the MKKS and BBS pathological conditions, a newly-defined class of chaperonin genes named CCT8L, represented in human by the two sequences CCT8L1 and CCT8L2. Comparative analyses from several vertebrate genomes established the monophyletic origin of chaperonin-like MKKS and BBS genes from the CCT8 lineage. The CCT8L gene originated from a later duplication also in the CCT8 lineage at the onset of mammal evolution and duplicated in primate genomes. The functionality of CCT8L genes in different species was confirmed by evolutionary analyses and in human by expression data. Detailed sequence analysis and structural predictions of MKKS, BBS and CCT8L proteins strongly suggested that they conserve a typical chaperonin-like core structure but that they are unlikely to form a CCT-like oligomeric complex. The characterization of many newly-discovered chaperonin pseudogenes uncovered the intense duplication activity of eukaryotic chaperonin genes.</p> <p>Conclusions</p> <p>In vertebrates, chaperonin genes, driven by intense duplication processes, have diversified into multiple classes and functionalities that extend beyond their well-known protein-folding role as part of the typical oligomeric chaperonin complex, emphasizing previous observations on the involvement of individual CCT monomers in microtubule elongation. The functional characterization of newly identified chaperonin genes will be a challenge for future experimental analyses.</p

Histopathology of Skeletal Muscle in a Distal Motor Neuropathy Associated with a Mutant CCT5 Subunit: Clues for Future Developments to Improve Differential Diagnosis and Personalized Therapy

Genetic chaperonopathies are rare but, because of misdiagnosis, there are probably more cases than those that are recorded in the literature and databases. This occurs because practitioners are generally unaware of the existence and/or the symptoms and signs of chaperonopathies. It is necessary to educate the medical community about these diseases and, with research, to unveil their mechanisms. The structure and functions of various chaperones in vitro have been studied, but information on the impact of mutant chaperones in humans, in vivo, is scarce. Here, we present a succinct review of the most salient abnormalities of skeletal muscle, based on our earlier report of a patient who carried a mutation in the chaperonin CCT5 subunit and suffered from a distal motor neuropathy of early onset. We discuss our results in relation to the very few other published pertinent reports we were able to find. A complex picture of multiple muscle-tissue abnormalities was evident, with signs of atrophy, apoptosis, and abnormally low levels and atypical distribution patterns of some components of muscle and the chaperone system. In-silico analysis predicts that the mutation affects CCT5 in a way that could interfere with the recognition and handling of substrate. Thus, it is possible that some of the abnormalities are the direct consequence of defective chaperoning, but others may be indirectly related to defective chaperoning or caused by other different pathogenic pathways. Biochemical, and molecular biologic and genetic analyses should now help in understanding the mechanisms underpinning the histologic abnormalities and, thus, provide clues to facilitate diagnosis and guide the development of therapeutic tools

HSPD1 (Heat Shock 60kDa Protein 1)

The HSPD1 gene encodes a protein known as HSP60 or Hsp60, also commonly referred to as Cpn60. This protein is a molecular chaperone typically localized inside mitochondria where it forms a chaperoning machine with HSP10 (encoded by the HSPE1 gene), also called Cpn10, to assist protein folding inside the organelle. Hsp60 also occurs in the cytosol, plasma-cell membrane, intercellular space, and blood. Its functions in all these extramitochondrial locations are poorly understood. While the canonical functions of Hsp60 are considered to be cytoprotective, anti-stress and maintenance of protein homeostasis, other roles are currently being investigated. For example, Hsp60 participates in the pathogenesis of diseases in various ways in certain types of cancer, and chronic inflammatory and autoimmune pathological conditions. These are considered chaperonopathies by mistake, in which a normal chaperone (normal at least as far as it can be determined by current methods to study the structure of a molecule available only at extremely low concentrations and quantities) turns against the organism instead of protecting it, favouring the growth and dissemination of cancer cells, or the initiation-progression of inflammation, for instance. In addition, Hsp60 mutations cause at least two types of severe genetic chaperonopathies. All this knowledge is expanding nowadays clearly pointing to Hsp60 as a potential target for chaperonotherapy by replacement when it is defective or by inhibition when it is pathogenic

Developing a Bilingual Fotonovela to Encourage Human Papillomavirus Preteen Immunization in California: A Case Study

Background. Cervical cancer affects Latinas disproportionately in the United States, especially in California. Fotonovelas are an entertaining educational medium within the Latino community. Purpose. The California Department of Public Health, Immunization Branch partnered with a fotonovela production company to develop a bilingual fotonovela to motivate Latina mothers of preteens to get their children vaccinated against human papillomavirus (HPV). This paper reviews the process of and lessons learned from creating and pilot testing the HPV fotonovela. Methods. We convened a 10-member advisory committee to guide the development of the fotonovela and field-tested the medium with three focus groups of Latina mothers of preteens (n=22). The focus group participants completed a pre- and post-survey to assess knowledge gain after reading the fotonovela on their own. After participants completed the post-survey, the moderator facilitated a discussion. Results. The advisory committee identified barriers and myths around HPV vaccination and suggested culturally appropriate messaging for the fotonovela. The pre-/post-survey showed statistically significant knowledge gain on the HPV vaccine among focus group participants. Conclusion. We found that the fotonovela is a well-accepted educational vehicle for Latinas. An intervention/control study to test the effectiveness of a fotonovela and/or webnovela in bringing about measurable behavior change is needed

The chaperone system in cancer therapies: Hsp90

: The chaperone system (CS) of an organism is composed of molecular chaperones, chaperone co-factors, co-chaperones, and chaperone receptors and interactors. It is present throughout the body but with distinctive features for each cell and tissue type. Previous studies pertaining to the CS of the salivary glands have determined the quantitative and distribution patterns for several members, the chaperones, in normal and diseased glands, focusing on tumors. Chaperones are cytoprotective, but can also be etiopathogenic agents causing diseases, the chaperonopathies. Some chaperones such as Hsp90 potentiate tumor growth, proliferation, and metastasization. Quantitative data available on this chaperone in salivary gland tissue with inflammation, and benign and malignant tumors suggest that assessing tissue Hsp90 levels and distribution patterns is useful for differential diagnosis-prognostication, and patient follow up. This, in turn, will reveal clues for developing specific treatment centered on the chaperone, for instance by inhibiting its pro-carcinogenic functions (negative chaperonotherapy). Here, we review data on the carcinogenic mechanisms of Hsp90 and their inhibitors. Hsp90 is the master regulator of the PI3K-Akt-NF-kB axis that promotes tumor cell proliferation and metastasization. We discuss pathways and interactions involving these molecular complexes in tumorigenesis and review Hsp90 inhibitors that have been tested in search of an efficacious anti-cancer agent. This targeted therapy deserves extensive investigation in view of its theoretical potential and some positive practical results and considering the need of novel treatments for tumors of the salivary glands as well as other tissues

The Role of Molecular Chaperones in Virus Infection and Implications for Understanding and Treating COVID-19

The COVID-19 pandemic made imperative the search for means to end it, which requires a knowledge of the mechanisms underpinning the multiplication and spread of its cause, the coronavirus SARS-CoV-2. Many viruses use members of the hosts' chaperoning system to infect the target cells, replicate, and spread, and here we present illustrative examples. Unfortunately, the role of chaperones in the SARS-CoV-2 cycle is still poorly understood. In this review, we examine the interactions of various coronaviruses during their infectious cycle with chaperones in search of information useful for future research on SARS-CoV-2. We also call attention to the possible role of molecular mimicry in the development of autoimmunity and its widespread pathogenic impact in COVID-19 patients. Viral proteins share highly antigenic epitopes with human chaperones, eliciting anti-viral antibodies that crossreact with the chaperones. Both, the critical functions of chaperones in the infectious cycle of viruses and the possible role of these molecules in COVID-19 autoimmune phenomena, make clear that molecular chaperones are promising candidates for the development of antiviral strategies. These could consist of inhibiting-blocking those chaperones that are necessary for the infectious viral cycle, or those that act as autoantigens in the autoimmune reactions causing generalized destructive effects on human tissues

Understanding the Support Needs of Minority Women with Heart Disease

Background. Cardiovascular disease (CVD) affects minority women disproportionately. WomenHeart: The National Coalition for Women with Heart Disease sought to determine effective ways to support non-Caucasian women with CVD. We surveyed women of color living with CVD to understand their unique CVD-related support needs. Methods. 514 non-white women (100 Hispanic, 180 African American, 104 Asian, 107 Indigenous, 23 multiracial) with CVD from 46 states responded to a 55-question survey (online/telephone, English/Spanish) 8/28/15 through 9/11/15. Results. Among respondents not currently attending support groups, 80% were interested in attending support groups. Of WomenHeart services, respondents were most interested in online message boards. Among new services, respondents were most interested in a support group with a medical expert facilitator. Women with tachycardia wanted a support group with others with the same condition. Those with cardiomyopathy preferred to meet most frequently. Respondents most preferred a monthly support group with flexible membership. Community venues were the most popular location for support groups. Indigenous populations had the lowest CVD knowledge and self-efficacy levels, were most likely to prefer a support group with women of their own race, and wished to meet with their groups most frequently. Multiracial women were most likely to have never been told about clinical trials and were least interested in support groups. Hispanics had the least social support. Conclusions. Minority women with CVD indicated interest in support groups. They may benefit from referrals to tailored support group types, including online platforms facilitated by medical experts, and to cardiac rehabilitation and clinical trials