ANALYSIS AND SYNTHESIS OF PRECISION RESOLVER SYSTEM

Ph.DDOCTOR OF PHILOSOPH

The Role of Social Determinants of Health in Cardiovascular Diseases: An Umbrella Review

Cardiovascular disease (CVD) is the leading cause of mortality worldwide. Addressing social determinants of health (SDoH) may be the next forefront of reducing the enormous burden of CVD. SDoH can be defined as any social, economic, or environmental factor that influences a health outcome. Comprehensive evidence of the role of SDoH in CVD is lacking, nevertheless. This umbrella review aims to give a comprehensive overview of the role of SDoH in CVD. We searched systematic reviews (with or without meta-analyses) using 8 databases and included review reference lists. Four themes (economic circumstances, social/community context, early childhood development, and neighbourhood/built environment) and health literacy in the health/health care theme were considered. Seventy reviews were eligible. Despite the quality of the included reviews being low or critically low, there was consistent evidence that factors relating to economic circumstances and early childhood development themes were associated with an increased risk of CVD and CVD mortality. We also found evidence that factors in the social/community context and neighbourhood/built environment themes, such as social isolation, fewer social roles, loneliness, discrimination, ethnicity, neighborhood socioeconomic status, violence, and environmental attributes, had a role in CVD. SDoH factors without (or with minimal) evidence synthesis for CVD were also identified. In sum, this umbrella review offers evidence that SDoH, especially economic circumstance and early childhood development, play a significant role in CVD. This calls for the strengthening of nonmedical interventions that address multiple factors simultaneously and the inclusion of SDoH in future CVD risk prediction models. Registration URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42022346994

Food allergy alters jejunal circular muscle contractility and induces local inflammatory cytokine expression in a mouse model

<p>Abstract</p> <p>Background</p> <p>We hypothesized that food allergy causes a state of non-specific jejunal dysmotility. This was tested in a mouse model.</p> <p>Methods</p> <p>Balb/c mice were epicutaneously sensitized with ovalbumin and challenged with 10 intragastric ovalbumin administrations every second day. Smooth muscle contractility of isolated circular jejunal sections was studied in organ bath with increasing concentrations of carbamylcholine chloride (carbachol). Smooth muscle layer thickness and mast cell protease-1 (MMCP-1) positive cell density were assayed histologically. Serum MMCP-1 and immunoglobulins were quantified by ELISA, and mRNA expressions of IFN-γ, IL-4, IL-6 and TGFβ-1 from jejunal and ileal tissue segments were analyzed with quantitative real-time PCR.</p> <p>Results</p> <p>Ovalbumin-specific serum IgE correlated with jejunal MMCP-1⁺cell density. In the allergic mice, higher concentrations of carbachol were required to reach submaximal muscular stimulation, particularly in preparations derived from mice with diarrhoea. Decreased sensitivity to carbachol was associated with increased expression of IL-4 and IL-6 mRNA in jejunum. Smooth muscle layer thickness, as well as mRNA of IFN-γ and TGF-β1 remained unchanged.</p> <p>Conclusion</p> <p>In this mouse model of food allergy, we demonstrated a decreased response to a muscarinic agonist, and increased levels of proinflammatory IL-6 and Th2-related IL-4, but not Th1-related IFN-γ mRNAs in jejunum. IgE levels in serum correlated with the number of jejunal MMCP-1⁺cells, and predicted diarrhoea. Overall, these changes may reflect a protective mechanism of the gut in food allergy.</p

IgE sensitization to the fish parasite Anisakis simplex in Norway

Anisakis simplex is a fish parasite which infects many commercially important fish species worldwide. When ingested in contaminated raw or poorly prepared seafood, this parasite may lead to infection and/or allergic reaction in humans. During the last decade, cases of this food-borne infection and allergy have increased in countries with high fish consumption, causing an emerging public health problem. Norway is one of the high fishconsuming countries, but the situation of this parasite-related problem was still unknown. Therefore, we conducted the first pilot study in Norway to investigate the prevalence of IgE sensitization to A. simplex. In this epidemiologic survey, the anonymized serum samples from newly recruited blood donors (designated as &ldquo;BDO&rdquo;) and from patients with high serum IgE antibodies level &ge; 1000 kU\l (designated as &ldquo;IGE+&rdquo;) were collected at the Haukeland University Hospital, Bergen. The sera were analyzed by the ImmunoCAP&reg; method for total IgE and IgE antibodies against A. simplex and other possible cross allergens such as house dust mite (HDM), shrimp and cod. The results showed 2.0% and 37% of IgE sensitization to A. simplex in BDO and IgE+ groups, respectively. But these prevalences might be overestimated owing to crosssensitization. Later on, we performed an extended study using larger population sizes and a recently developed more specific analysis method. This test is an enzyme-linked immunosorbent assay (ELISA) which utilizes 2 recombinant (r) major and specific allergens of A. simplex, namely rAni s 1 and rAni s 7 as target antigens. SDS-PAGE and Western immunoblotting analyses were also performed. As expected, the results of the extended study showed even lower prevalences of sensitization than that obtained in the previous study. Whereas the prevalences by the ImmunoCAP&reg; method were 0.4% and 16.2%, analyses with the more specific test showed very low incidences of 0.0% and 0.2% in the BDO and IGE+ groups, respectively. Cross-reactivity analyses also suggested that most of the ImmunoCAP&reg; positive sera were probably false-positive due to cross-sensitization to HDM and shrimp. The 0.0% prevalence in the BDO group may indicate an absence of sensitization against the fish parasite A. simplex in the healthy population. On the other hand, the frequency of 0.2% in the IGE+ group may either represent a certain degree of true sensitization in the &ldquo;allergic&rdquo; population or maybe still due to cross-sensitization. The low prevalence of A. simplex sensitization in Norway compared to other high-fish consuming countries might be partly explained by the relatively low consumption of raw or uncooked fish among the Norwegians and the low genetic susceptibility of Norwegian population to A. simplex allergens. With respect to food safety, certain regulations for storing and preparing the fish have been implemented to kill this commonly occurring nematode in fish. However, among Anisakis allergens, several heat- and pepsin-resistant proteins have been shown to remain active even after cooking or digestion. The ingestion or inhalation of or contact with A. simplex allergens has been claimed to evoke allergic symptoms in sensitized individuals. While directly contaminated fish were accounted for most allergic cases, indirect contamination of food via carry-over from contaminated feed has also been reported to be involved. For this reason, we conducted a zebrafish (Danio rerio) feeding trial to investigate the transmissibility of A. simplex allergens from feed to fish. Zebrafish was chosen as the study object owing to their rapid maturation and favorable small size affording less space and feed than edible fish such as salmon or trout. The results of feed analyses by both ELISA and immunostaining indicated that certain A. simplex allergens have been retained throughout feed processing, confirming the presence of heat and degradation-resistant proteins of this parasite as reported in other studies. The trace amounts of A. simplex peptides in the fish flesh were detected by both immunostaining and LCMSMS, thereby providing a positive proof for the transmissibility of A. simplex allergens from feed to fish. Nevertheless, considering the relatively higher effect dose of A. simplex allergens compared to other food allergens, the low amounts of Anisakis proteins transferred via contaminated feed to fish probably do not represent a major food safety problem for consumers with A. simplex allergy. In conclusion, our seroprevalence studies indicated a very low sensitization against the fish parasite A. simplex in the studied Norwegian populations as compared with other high fish-consuming countries. Our zebrafish feeding trial suggested the transmissibility of A. simplex allergens from feed to fish, but only the low amounts were detected. Given the results from our surveys, the fish parasite A. simplex is apparently not an immediate food safety and public health problem in Norway

A Rare Thermophilic Bug in Complicated Diverticular Abscess

Actinomycosis is a form of painful abscess in the gastrointestinal tract or in deep tissue caused by actinomyces species. They are one of the commensal bacteria in the oral cavity and gastrointestinal tract of humans but can opportunistically cause infection in immunosuppressive hosts through invasion of breached mucosa or necrotic tissue while mimicking malignancy, gastrointestinal tuberculosis, and inflammatory bowel disease. Actinomyces israelii is, by far, the major and most common human pathogen throughout literatures. By virtue of rarity and diagnostic confusion with masquerading malignancies, only 10% of the cases have been diagnosed preoperatively, so as to be able to verge patients from undergoing unnecessary surgical intervention. Herein, we present a rare case of complicated diverticular abscess manifested by Actinomyces meyeri after postoperative tissue diagnosis

A Rare Thermophilic Bug in Complicated Diverticular Abscess

Actinomycosis is a form of painful abscess in the gastrointestinal tract or in deep tissue caused by actinomyces species. They are one of the commensal bacteria in the oral cavity and gastrointestinal tract of humans but can opportunistically cause infection in immunosuppressive hosts through invasion of breached mucosa or necrotic tissue while mimicking malignancy, gastrointestinal tuberculosis, and inflammatory bowel disease. Actinomyces israelii is, by far, the major and most common human pathogen throughout literatures. By virtue of rarity and diagnostic confusion with masquerading malignancies, only 10% of the cases have been diagnosed preoperatively, so as to be able to verge patients from undergoing unnecessary surgical intervention. Herein, we present a rare case of complicated diverticular abscess manifested by Actinomyces meyeri after postoperative tissue diagnosis

A Rare Thermophilic Bug In Complicated Diverticular Abscess

Actinomycosis is a form of painful abscess in the gastrointestinal tract or in deep tissue caused by actinomyces species. They are one of the commensal bacteria in the oral cavity and gastrointestinal tract of humans but can opportunistically cause infection in immunosuppressive hosts through invasion of breached mucosa or necrotic tissue while mimicking malignancy, gastrointestinal tuberculosis, and inflammatory bowel disease. Actinomyces israelii is, by far, the major and most common human pathogen throughout literatures. By virtue of rarity and diagnostic confusion with masquerading malignancies, only 10% of the cases have been diagnosed preoperatively, so as to be able to verge patients from undergoing unnecessary surgical intervention. Herein, we present a rare case of complicated diverticular abscess manifested by Actinomyces meyeri after postoperative tissue diagnosis

Fish feed as source of potentially allergenic peptides from the fish parasite Anisakis simplex (s.l.)

The carry-over of certain feed components into animal products can be of concern for human health. The safety assessment of chemical contaminants including natural toxins, agrochemicals, veterinary drugs, and environmental pollutants is a key element of the “farm-to-fork” (“One Health”) approach. The transmissibility of proteinaceous feed constituents such as enzymes, proteins from genetically engineered crops, and infectious prions in animal meal has also become of interest; but the transfer of proteins with allergic potential is little studied. In the present study, an exploratory zebrafish feeding trial using feed containing 20 percent of processed larvae of the marine fish parasite Anisakis simplex was performed as a proof-of-principle experiment. After a 2-week exposure period, anisakid peptides were detected in zebrafish tissue by high-resolution liquid-chromatography Orbitrap mass spectrometry and immunostaining using specific polyclonal antibodies or sera from patients with confirmed allergy to A. simplex. Since fishmeal produced from marine pelagic fish is an important feed component in the culture of Atlantic salmon and in the poultry industry, it should be considered as a source of potentially allergenic peptides in the final products. Furthermore, the substitution of fishmeal with plant proteins would not eliminate the potential health risk by allergen carry-over since crops of high nutritional value such as legumes also contain important food allergens. If our preliminary results from the present zebrafish feeding trial should be confirmed in necessary follow-up experiments, the question of labeling information on fish and animal food products raised on feed containing potentially allergenic ingredients could arise in order to minimize the exposure risk of allergic consumers

Exposure to diverse sarbecoviruses indicates frequent zoonotic spillover in human communities interacting with wildlife

BackgroundSarbecoviruses are a subgenus of Coronaviridae that mostly infect bats with known potential to infect humans (SARS-CoV and SARS-CoV-2). Populations in Southeast Asia, where these viruses are most likely to emerge, have been undersurveyed to date.MethodsWe surveyed communities engaged in extractive industries and bat guano harvesting from rural areas in Myanmar. Participants were screened for exposure to sarbecoviruses, and their interactions with wildlife were evaluated to determine the factors associated with exposure to sarbecoviruses.ResultsOf 693 people screened between July 2017 and February 2020, 12.1% were seropositive for sarbecoviruses. Individuals were significantly more likely to have been exposed to sarbecoviruses if their main livelihood involved working in extractive industries (logging, hunting, or harvesting of forest products; odds ratio [OR]&nbsp;=&nbsp;2.71, P&nbsp;=&nbsp;0.019) or had been hunting/slaughtering bats (OR&nbsp;=&nbsp;6.09, P&nbsp;=&nbsp;0.020). Exposure to a range of bat and pangolin sarbecoviruses was identified.ConclusionExposure to diverse sarbecoviruses among high-risk human communities provides epidemiologic and immunologic evidence that zoonotic spillover is occurring. These findings inform risk mitigation efforts needed to decrease disease transmission at the bat-human interface, as well as future surveillance efforts warranted to monitor isolated populations for viruses with pandemic potential