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Background Trustworthy educational information for patients is critical for increasing their knowledge base and preparing them for shared decision making with clinicians. As the internet has become an important source of health information for many patients, the purpose of this study was to assess the quality and content of websites with educational content about immune checkpoint inhibitors. Methods We performed an environmental scan of the currently available websites providing educational information for patients about immune checkpoint inhibitors. We used three search engines: Google, Bing, and Yahoo! (9/20/2021). Two independent investigators selected relevant uniform resource locators (URLs), appraised the quality of the websites, and collected their characteristics. We evaluated the accuracy, completeness, technical elements, design and aesthetics, readability, usability, and accessibility of the websites. The user experience was also evaluated. Results We identified 37 websites for analysis. In 10 websites (27%), it was not possible to know the source of the information provided. Thirty-three (89%) provided a definition with a simple explanation of cancer and treatment and 30 (81%) on complications of immune checkpoint inhibitors; only seven (19%) provided information about the balance between risks and benefits. Thirty-five (95%) provided a statement of purpose. Regarding the design, all 37 (100%) had appropriate visual aspects, typography, and grammar. Thirty-six (97%) were well organized. For most of the websites (n = 35, 95%) the content was easy to find. Only two websites had a readability score of 6, while the others had higher scores. Regarding the user experience, the overall quality of websites was rated as excellent in 16 (43%), good in 14 (38%), and fair in 7 (19%). Conclusions Our findings reveal that websites with information about immune checkpoint inhibitors mostly have general information about cancer, the treatments, and adverse events. Few websites provide information about the balance between harms and benefits of treatment, costs, the source of the information, or the hierarchy of evidence. These findings identify the gap in the quality and content of websites for patients treated with immune checkpoint inhibitors and can help website creators and developers.

Objective Smoking rates among patients with rheumatoid arthritis (RA) exceed those in the general population. This study identified smoking cessation strategies used in patients with RA and synthesized data on their effects. Methods We conducted a systematic review of studies that reported effects of interventions for smoking cessation in patients with RA. We searched 5 electronic databases until March 2022. Screening, quality appraisal, and data collection were done independently by 2 reviewers. Results We included 18 studies reporting interventions for patients or providers: 14 evaluated strategies for patients (5 education on cardiovascular risk factors including smoking, 3 educational interventions on smoking cessation alone, 3 education with nicotine replacement and counseling, and 1 study each: education with nicotine replacement, counseling sessions alone, and a social marketing campaign). Smoking cessation rates ranged from 4% (95% CI: 2%-6%, 24 to 48 weeks) for cardiovascular risk education to 43% (95% CI: 21%-67%, 104 weeks) for counseling sessions alone. The pooled cessation rate for all interventions was 22% (95% CI: 8%-41%, 4 weeks to 104 weeks; 9 studies). Four interventions trained providers to ascertain smoking status and provide referrals for smoking cessation. The pooled rates of referrals to quit services increased from 5% in pre-implementation populations to 70% in post-implementation populations. Conclusion Studies varied in patient characteristics, the interventions used, and their implementation structure. Only 3 studies were controlled clinical trials. Additional controlled studies are needed to determine best practices for smoking cessation for patients with RA.

BackgroundOnline health information, if evidence-based and unbiased, can improve patients' and caregivers' health knowledge and assist them in disease management and health care decision-making.ObjectiveTo identify standards for the development of health information resources on the internet for patients.MethodsWe searched in MEDLINE, CINAHL, Scopus, Web of Science, and Google Scholar for publications describing evaluation instruments for websites providing health information. Eligible instruments were identified by three independent reviewers and disagreements resolved by consensus. Items reported were extracted and categorized into seven domains (accuracy, completeness and comprehensiveness, technical elements, design and aesthetics, usability, accessibility, and readability) that were previously thought to be a minimum requirement for websites.ResultsOne hundred eleven articles met inclusion criteria, reporting 92 evaluation instruments (1609 items). We found 74 unique items that we grouped into the seven domains. For the accuracy domain, one item evaluated information provided in concordance with current guidelines. For completeness and comprehensiveness, 18 items described the disease with respect to various topics such as etiology or therapy, among others. For technical elements, 27 items evaluated disclosure of authorship, sponsorship, affiliation, editorial process, feedback process, privacy, and data protection. For design and aesthetics, 10 items evaluated consistent layout and relevant graphics and images. For usability, 10 items evaluated ease of navigation and functionality of internal search engines. For accessibility, five items evaluated the availability of websites to people with audiovisual disabilities. For readability, three items evaluated conversational writing style and use of a readability tool to determine the reading level of the text.ConclusionWe identified standards for the development of online patient health information. This proposed instrument can serve as a guideline to develop and improve how health information is presented on the internet.

Background Patients with low bone density or osteoporosis need information for effective prevention or disease management, respectively. However, patients may not be getting enough information from their primary care providers or other sources. Inadequate disease information leaves patients ill-informed and creates misconceptions and unnecessary concerns about the disease. Objective We systematically reviewed and synthesized the available literature to determine patient knowledge, beliefs, and concerns about osteoporosis and identify potential gaps in knowledge. Methods A systematic search was conducted for full-text qualitative studies addressing understanding, literacy, and/or perceptions about osteoporosis and its management, using Medline, EMBASE, Web of Science, Cochrane Library, CINAHL, ERIC, PsychINFO, Psyc Behav Sci Collec, and PubMed, from inception through September 2016. Studies were selected by two reviewers, assessed for quality, and themes extracted using the Joanna Briggs Institute data extraction tool. Thematic analysis was used to identify themes and subthemes. Results Twenty-five studies with a total of 757 participants (including 105 men) were selected for analysis out of 1031 unique citations. Selected studies were from Australia, Canada, Denmark, Norway, the United Kingdom, and the United States. Four main themes emerged: inadequate knowledge, beliefs and misconceptions, concerns about osteoporosis, and lack of information from health care providers. Participants had inadequate knowledge about osteoporosis and were particularly uninformed about risk factors, causes, treatment, and prevention. Areas of concern for participants included diagnosis, medication side effects, and inadequate information from primary care providers. Conclusion Although there was general awareness of osteoporosis, many misconceptions and concerns were evident. Education on bone health needs to reinforce areas of knowledge and address deficits, misconceptions, and concerns.

Background Three checkpoint inhibitor drugs have been approved by the US Food and Drug Administration for use in specific types of cancers. While the results are promising, severe immunotherapy-related adverse events (irAEs) have been reported. Objectives To conduct a systematic review of case reports describing the occurrence of irAEs in patients with cancer following checkpoint blockade therapy, primarily to identify potentially unrecognized or unusual clinical findings and toxicity. Data Sources We searched Medline, EMBASE, Web of Science, PubMed ePubs, and Cochrane CENTRAL with no restriction through August 2015. Study Selection Studies reporting cases of cancer develop irAEs following treatment with anti CTLA-4 (ipilimumab) or anti PD-1 (nivolumab or pembrolizumab) antibodies were included. Data Extraction We extracted data on patient characteristics, irAEs characteristics, how irAEs were managed, and their outcomes. Data Synthesis 191 publications met inclusion criteria, reporting on 251 cases. Most patients had metastatic melanoma (95.6%), and the majority were treated with ipilimumab (93.2%). Autoimmune colitis, hepatitis, endocrinopathies, and cutaneous irAEs were the most frequently reported irAEs in ipilimumab treated patients. A broad spectrum of toxicities were reported for almost every body system. Moreover, well-defined diseases such as sarcoidosis, polyarthritis, polymyalgia rheumatica/arteritis, lupus, celiac disease, dermatomyositis, and Vogt-Koyanagi-like syndrome were reported. The most frequent irAEs reported with anti-PD1 agents were dermatitis for pembrolizumab, and thyroid disease and pneumonitis for nivolumab. Complete resolution of adverse events occurred in most cases. However, persistent irAEs and death were reported, mainly in patients treated with ipilimumab. Limitations Our study is limited by information available in the original reports. Conclusions Evidence from case reports shows that cancer patients develop irAEs following checkpoint blockade therapy, and can occasionally develop clearly defined autoimmune systemic diseases. While discontinuation of therapy and/or treatment can result in resolution of irAEs, long-term sequelae and death have been reported.

Babesia bovis, an intra-erythrocytic tick-borne apicomplexan protozoan, is one of the causative agents of bovine babesiosis. Its life cycle includes sexual reproduction within cattle fever ticks, Rhipicephalus spp. Six B. bovis 6-Cys gene superfamily members were previously identified (A, B, C, D, E, F) where their orthologues in Plasmodium parasite have been shown to encode for proteins required for the development of sexual stages. The current study identified four additional 6-Cys genes (G, H, I, J) in the B. bovis genome. These four genes are described in the context of the complete ten 6-Cys gene superfamily. The proteins expressed by this gene family are predicted to be secreted or surface membrane directed. Genetic analysis comparing the 6-Cys superfamily among five distinct B. bovis strains shows limited sequence variation. Additionally, A, B, E, H, I and J genes were transcribed in B. bovis infected tick midgut while genes A, B and E were also transcribed in the subsequent B. bovis kinete stage. Transcription of gene C was found exclusively in the kinete. In contrast, transcription of genes D, F and G in either B. bovis infected midguts or kinetes was not detected. None of the 6-Cys transcripts were detected in B. bovis blood stages. Subsequent protein analysis of 6-Cys A and B is concordant with their transcript profile. The collective data indicate as in Plasmodium parasite, certain B. bovis 6-Cys family members are uniquely expressed during sexual stages and therefore, they are likely required for parasite reproduction. Within B. bovis specifically, proteins encoded by 6-Cys genes A and B are markers for sexual stages and candidate antigens for developing novel vaccines able to interfere with the development of B. bovis within the tick vector.

Genetic manipulation is an essential technique to analyze gene function; however, limited methods are available for Babesia bovis, a causative pathogen of the globally important cattle disease, bovine babesiosis. To date, two stable transfection systems have been developed for B. bovis, using selectable markers blasticidin-S deaminase (bsd) or human dihydrofolate reductase (hdhfr). In this work, we combine these two selectable markers in a sequential transfection system. Specifically, a parent transgenic B. bovis line which episomally expresses green fluorescent protein (GFP) and human dihydrofolate reductase (hDHFR), was transfected with a plasmid encoding a fusion protein consisting of red fluorescent protein (RFP) and blasticidin-S deaminase (BSD). Selection with WR99210 and blasticidin-S resulted in the emergence of parasites double positive for GFP and RFP. We then applied this method to complement gene function in a parasite line in which thioredoxin peroxidase-1 (Bbtpx-1) gene was knocked out using hDHFR as a selectable marker. A plasmid was constructed harboring both RFP-BSD and Bbtpx-1 expression cassettes, and transfected into a Bbtpx-1 knockout (KO) parasite. Transfectants were independently obtained by two transfection methods, episomal transfection and genome integration. Complementation of Bbtpx-1 resulted in full recovery of resistance to nitrosative stress, via the nitric oxide donor sodium nitroprusside, which was impaired in the Bbtpx-1 KO parasites. In conclusion, we developed a sequential transfection method in B. bovis and subsequently applied this technique in a gene complementation study. This method will enable broader genetic manipulation of Babesia toward enhancing our understanding of the biology of this parasite., PLOS ONE, 10(5), e0125993; 2015

The oldest-known air-breathing land animal is the millipede Pneumodesmus newmani, found in the Cowie Harbour Fish Bed at Stonehaven, Scotland. Here we report the youngest, most concordant 238U-206Pb zircon age from ash below the fish bed of 413.7±4.4 Ma (±2σ), whereas the youngest age from a tuffaceous sandstone above the fish bed is statistically indistinguishable at 414.3±7.1 Ma. The Cowie Harbour Fish Bed thus appears to be lowermost Devonian (Lochkovian), contrary to the previously accepted mid-Silurian age based on palynomorphs from adjacent exposures. This has implications for the evolutionary timetable of land colonization, as the Cowie ages overlap late Lochkovian zircon ages reported elsewhere for andesite below the nearby (~50 mi) Rhynie Chert, which has more advanced terrestrial biota. The results postdate the possible late Silurian Ludford Lane locality in Shropshire, England. Pneumodesmus newmani is thus not the earliest air-breathing land animal, unless the Ludford Lane locality is younger than presently assigned.

Babesia bovis is a tick-borne intraerythocytic protozoan responsible for acute disease in cattle which can be controlled by vaccination with attenuated B. bovis strains. Emerging B. bovis transfection technologies may increase the usefulness of these live vaccines. One use of transfected B. bovis parasites may be as a vaccine delivery platform. Previous transfection methods for B. bovis were limited by single expression sites and intracellular expression of transfected antigens. This study describes a novel transfection system in which two exogenous genes are expressed: one for selection and the other for a selected antigen designed to be delivered to the surface of the parasites. The strategy for duplicating the number of transfected genes was based on the use of the putative bidirectional promoter of the B. bovis 1.4 Kb ef-1α intergenic region. The ability of this region to regulate two independent expression sites was demonstrated using a luciferase assay on transiently transfected B. bovis parasites and then incorporated into a stable transfection plasmid to control independent expression of the selectable marker GFP-BSD and another gene of interest. A chimeric gene was synthetized using sequences from the protective B-cell epitopes of Rhipicephalus microplus tick antigen Bm86 along with sequences from the surface exposed B. bovis major surface antigen-1. This chimeric gene was then cloned into the additional expression site of the transfection plasmid. Transfection of the B. bovis Mo7 strain with this plasmid resulted in stable insertion into the ef-1α locus and simultaneous expression of both exogenous genes. Expression of the Bm86 epitopes on the surface of transfected merozoites was demonstrated using immunofluorescence analyses. The ability to independently express multiple genes by the inclusion of a bidirectional promoter and the achievement of surface expression of foreign epitopes advances the potential of transfected B. bovis as a future vaccine delivery platform.

Members of the CCp protein family have been previously described to be expressed on gametocytes of apicomplexan Plasmodium parasites. Knocking out Plasmodium CCp genes blocks the development of the parasite in the mosquito vector, making the CCp proteins potential targets for the development of a transmission-blocking vaccine. Apicomplexans Babesia bovis and Babesia bigemina are the causative agents of bovine babesiosis, and apicomplexan Theileria equi causes equine piroplasmosis. Bovine babesiosis and equine piroplasmosis are the most economically important parasite diseases that affect worldwide cattle and equine industries, respectively. The recent sequencing of the B. bovis and T. equi genomes has provided the opportunity to identify novel genes involved in parasite biology. Here we characterize three members of the CCp family, named CCp1, CCp2 and CCp3, in B. bigemina, B. bovis and T. equi. Using B. bigemina as an in vitro model, expression of all three CCp genes and proteins was demonstrated in temperature-induced sexual stages. Transcripts for all three CCp genes were found in vivo in blood stages of T. equi, and transcripts for CCp3 were detected in vivo in blood stages of B. bovis. However, no protein expression was detected in T. equi blood stages or B. bovis blood stages or B. bovis tick stages. Collectively, the data demonstrated a differential pattern of expression of three orthologous genes of the multidomain adhesion CCp family by B. bigemina, B. bovis and T. equi. The novel CCp members represent potential targets for innovative approaches to control bovine babesiosis and equine piroplasmosis.