Strain-dependent induction of primary bile acid 7-dehydroxylation by cholic acid.

BACKGROUND: Bile acids (BAs) are steroid-derived molecules with important roles in digestion, the maintenance of host metabolism, and immunomodulation. Primary BAs are synthesized by the host, while secondary BAs are produced by the gut microbiome through transformation of the former. The regulation of microbial production of secondary BAs is not well understood, particularly the production of 7-dehydroxylated BAs, which are the most potent agonists for host BA receptors. The 7-dehydroxylation of cholic acid (CA) is well established and is linked to the expression of a bile acid-inducible (bai) operon responsible for this process. However, little to no 7-dehydroxylation has been reported for other host-derived BAs (e.g., chenodeoxycholic acid, CDCA or ursodeoxycholic acid, UDCA). RESULTS: Here, we demonstrate that the 7-dehydroxylation of CDCA and UDCA by the human isolate Clostridium scindens is induced when CA is present, suggesting that CA-dependent transcriptional regulation is required for substantial 7-dehydroxylation of these primary BAs. This is supported by the finding that UDCA alone does not promote expression of bai genes. CDCA upregulates expression of the bai genes but the expression is greater when CA is present. In contrast, the murine isolate Extibacter muris exhibits a distinct response; CA did not induce significant 7-dehydroxylation of primary BAs, whereas BA 7-dehydroxylation was promoted upon addition of germ-free mouse cecal content in vitro. However, E. muris was found to 7-dehydroxylate in vivo. CONCLUSIONS: The distinct expression responses amongst strains indicate that bai genes are regulated differently. CA promoted bai operon gene expression and the 7-dehydroxylating activity in C. scindens strains. Conversely, the in vitro activity of E. muris was promoted only after the addition of cecal content and the isolate did not alter bai gene expression in response to CA. The accessory gene baiJ was only upregulated in the C. scindens ATCC 35704 strain, implying mechanistic differences amongst isolates. Interestingly, the human-derived C. scindens strains were also capable of 7-dehydroxylating murine bile acids (muricholic acids) to a limited extent. This study shows novel 7-dehydroxylation activity in vitro resulting from the presence of CA and suggests distinct bai gene expression across bacterial species.

Microbial assisted multifaceted amelioration processes of heavy-metal remediation: a clean perspective toward sustainable and greener future.

Rapidly increasing heavy metal waste has adversely affected the environment and the Earth's health. The lack of appropriate remediation technologies has worsened the issue globally, especially in developing countries. Heavy-metals contaminants have severely impacted the environment and led to devastating conditions owing to their abundance and reactivity. As they are nondegradable, the potential risk increases even at a low concentration. However, heavy-metal remediation has increased with the up-gradation of technologies and integration of new approaches. Also, of all the treatment methodologies, microbial-assisted multifaceted approach for ameliorating heavy metals is a promising strategy for propagating the idea of a green and sustainable environment with minimal waste aggregation. Microbial remediation combined with different biotechniques could aid in unraveling new methods for eradicating heavy metals. Thus, the present review focuses on various microbial remediation approaches and their affecting factors, enabling recapitulation of the interplay between heavy-metals ions and microorganisms. Additionally, heavy-metals remediation mechanisms adapted by microorganisms, the role of genetically modified (GM) microorganisms, life cycle assessment (LCA), techno-economic assessment (TEA) limitations, and prospects of microbial-assisted amelioration of heavy-metals have been elaborated in the current review with focus toward "sustainable and greener future."

Proteomic analysis of aqueous humor reveals novel regulators of diabetic macular edema.

Diabetic macular edema (DME) is the most common cause of blindness in patients with diabetic retinopathy. To investigate the proteomic profiles of the aqueous humor (AH) of individuals with diabetic macular edema (DME), AH samples were collected from patients with non-diabetes mellitus (NDM), DM, nonproliferative diabetic retinopathy (NPDR), and DME. We performed comparative proteomic analyses using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and bioinformatics analyses. We identified 425 proteins in these AH samples, of which 113 showed changes in expression in DME compared with NDM, 95 showed changes in expression in DME vs. DM, and 84 showed changes in expression in DME compared with NPDR. The bioinformatics analysis suggested that DME is closely associated with platelet degranulation, oxidative stress-related pathway, and vascular-related pathways. Upregulation of haptoglobin (HP) and downregulation of fibrillin 1 (FBN1) were validated by ELISA. Receiver operating characteristic (ROC) analysis showed that HP and FBN1 could distinguish DME from NPDR with areas under the curve of 0.987 (p = 0.00608) and 0.791 (p = 0.00629), respectively. The findings provide potential clues for further analysis of the molecular mechanisms and the development of new treatments for DME. HP and FBN1 may be potential key proteins and therapeutic targets in human DME. The proteomics dataset generated has been deposited to the ProteomeXchange/iProX Consortium with Identifier: PXD033404/IPX0004353001.

Nitro fatty acids: A comprehensive review on analytical methods and levels in health and disease.

Nitro fatty acids (NO2-FAs) are biologically active compounds produced from the reaction of unsaturated fatty acids with reactive nitrogen species (RNS). Due to their electrophilic nature, these endogenously produced metabolites can react with nucleophilic targets, producing a spectrum of modulatory and protective effects. Determination of NO2-FAs in biological samples is challenging due to their low nanomolar to picomolar endogenous concentrations, indistinct metabolism, and distribution in many tissues and biofluids. Several attempts have been made to develop precise, standardized, and efficient methodologies for assessing physiological and pathophysiological processes to overcome the difficulties associated with their measurement. This review discusses those approaches utilizing liquid chromatography tandem mass spectrometry (LC‒MS/MS) and gas chromatography tandem mass spectrometry (GC‒MS/MS) for the quantification of NO2-FAs, in addition to a summary of their laboratory synthesis and extraction from biological samples. Clinical associations with different pathological conditions, including hyperlipidaemia, cardiac ischemia and herpes simplex type 2 viral infection (HSV-2), are also discussed.

Quantitative label-free proteomic analysis of excretory-secretory proteins in different developmental stages of Trichinella spiralis.

Trichinella spiralis (T. spiralis) is a zoonotic parasitic nematode with a unique life cycle, as all developmental stages are contained within a single host. Excretory-secretory (ES) proteins are the main targets of the interactions between T. spiralis and the host at different stages of development and are essential for parasite survival. However, the ES protein profiles of T. spiralis at different developmental stages have not been characterized. The proteomes of ES proteins from different developmental stages, namely, muscle larvae (ML), intestinal infective larvae (IIL), preadult (PA) 6 h, PA 30 h, adult (Ad) 3 days post-infection (dpi) and Ad 6 dpi, were characterized via label-free mass spectrometry analysis in combination with bioinformatics. A total of 1217 proteins were identified from 9341 unique peptides in all developmental stages, 590 of which were quantified and differentially expressed. GO classification and KEGG pathway analysis revealed that these proteins were important for the growth of the larvae and involved in energy metabolism. Moreover, the heat shock cognate 71 kDa protein was the centre of protein interactions at different developmental stages. The results of this study provide comprehensive proteomic data on ES proteins and reveal that these ES proteins were differentially expressed at different developmental stages. Differential proteins are associated with parasite survival and the host immune response and may be potential early diagnostic antigen or antiparasitic vaccine candidates.

Utilizing social determinants of health to identify most vulnerable neighborhoods-Latent class analysis and GIS map.

OBJECTIVES: Public Health officials are often challenged to effectively allocate limited resources. Social determinants of health (SDOH) may cluster in areas to cause unique profiles related to various adverse life events. The authors use the framework of unintended teen pregnancies to illustrate how to identify the most vulnerable neighborhoods. METHODS: This study used data from the U.S. American Community Survey, Princeton Eviction Lab, and Connecticut Office of Vital Records. Census tracts are small statistical subdivisions of a county. Latent class analysis (LCA) was employed to separate the 832 Connecticut census tracts into four distinct latent classes based on SDOH, and GIS mapping was utilized to visualize the distribution of the most vulnerable neighborhoods. GEE Poisson regression model was used to assess whether latent classes were related to the outcome. Data were analyzed in May 2021. RESULTS: LCA's results showed that class 1 (non-minority non-disadvantaged tracts) had the least diversity and lowest poverty of the four classes. Compared to class 1, class 2 (minority non-disadvantaged tracts) had more households with no health insurance and with single parents; and class 3 (non-minority disadvantaged tracts) had more households with no vehicle available, that had moved from another place in the past year, were low income, and living in renter-occupied housing. Class 4 (minority disadvantaged tracts) had the lowest socioeconomic characteristics. CONCLUSIONS: LCA can identify unique profiles for neighborhoods vulnerable to adverse events, setting up the potential for differential intervention strategies for communities with varying risk profiles. Our approach may be generalizable to other areas or other programs. KEY MESSAGES: What is already known on this topic Public health practitioners struggle to develop interventions that are universally effective. The teen birth rates vary tremendously by race and ethnicity. Unplanned teen pregnancy rates are related to multiple social determinants and behaviors. Latent class analysis has been applied successfully to address public health problems. What this study adds While it is the pregnancy that is not planned rather than the birth, access to pregnancy intention data is not available resulting in a dependency on teen birth data for developing public health strategies. Using teen birth rates to identify at-risk neighborhoods will not directly represent the teens at risk for pregnancy but rather those who delivered a live birth. Since teen birth rates often fluctuate due to small numbers, especially for small neighborhoods, LCA may avoid some of the limitations associated with direct rate comparisons. The authors illustrate how practitioners can use publicly available SDOH from the Census Bureau to identify distinct SDOH profiles for teen births at the census tract level. How this study might affect research, practice or policy These profiles of classes that are at heightened risk potentially can be used to tailor intervention plans for reducing unintended teen pregnancy. The approach may be adapted to other programs and other states to prioritize the allocation of limited resources.

Validating nutrient selection for product-group-specific nutrient indices for use as functional units in life cycle assessment of foods.

The ability to provide adequate nutrition is considered a key factor in evaluating the sustainability of foods and diets. Nutrient indices are used as functional units (FU) in life cycle assessment of foods to include nutritional performance in the environmental assessment of a product. Several general and food-group-specific nutrient indices exist but many lack validation, particularly when used as FU. In addition, the nutrient selection strategies and reference units for nutrient intake can vary considerably among studies. To validate intake-based product-group-specific nutrient indices previously developed for protein (NR-FIprot) and carbohydrate (NR-FIcarb) foods and for fruits and vegetables (NR-FIveg), we applied principal component analysis to investigate correlations between nutrients in foods and dishes representing a typical Finnish diet. The reference amounts for meal components were based on a plate model that reflected Finnish dietary recommendations. The portion sizes for the different food groups were anchored at 100 g, 135 g and 350 g for proteins, carbohydrates and fruits/vegetables, respectively. Statistical modelling largely validated the NR-FI indices, highlighting protein foods as sources of niacin, vitamin B12 and Se, carbohydrate foods as sources of Mg, Fe and phosphorous, and fruits/vegetables as sources of potassium, vitamin K, vitamin C, fibre and thiamine. However, in contrast to the intake-based approach applied in NR-FIprot, the dietary recommendation-based validation process suggested that fruits and vegetables should be favoured as sources of riboflavin and vitamin B6.

Latent Class Analysis of Online Platforms for Partner-Seeking and Sexual Behaviors Among Men Who Have Sex with Men from Central Kentucky.

Little is known whether engagement in sexual behaviors associated with potential HIV risks differs by subgroups of men who have sex with men (MSM), who are distinct regarding patterns of use of online tools for partner-seeking. Using latent class analysis, we revealed four classes of app-using MSM (n = 181, 18-34 y.o., 82.4% identified as White and non-Hispanic) residing in Central Kentucky: the Grindr/Tinder class; the Poly App Use class of MSM-oriented apps; the General Social Media class, and the Bumble class. Unadjusted penalized logistic regressions showed associations of the Poly App Use class with increased numbers of receptive anal sex partners and reporting condomless receptive anal sex. Adjusting for other covariates, poly app users versus others were more likely to be older (25-34 vs. 18-24, AOR = 3.81, 95%CI = 1.70-9.03), to report past six-month illicit drug use (AOR = 2.93, 95%CI = 1.25-7.43) and to have ever used pre-exposure prophylaxis (AOR = 2.79, 95%CI = 1.10-7.12). Poly app users had behavior profiles associated with an elevated HIV risk and also reported HIV-related protective behaviors likely indicating increased risk awareness among this class. Our findings warrant differentiation of behavior profiles by patterns of app use and suggest not to generalize sexual behaviors associated with potential HIV risks to all app-using MSM.

RESUMEN: Poco se sabe si la participación en comportamientos sexuales asociados con riesgos potenciales de VIH difiere según distintos subgrupos de hombres que tienen sexo con hombres (HSH) en base a patrones en el uso de herramientas online para la búsqueda de pareja. Mediante el análisis de clases latentes, identificamos cuatro clases de HSH que usan aplicaciones (n = 181, 18­34 años, 82.4% identificados como Blancos y no-Hispanos) y residen en Kentucky Central: la clase Grindr/Tinder, la clase Poly App Use de aplicaciones orientadas a HSH, la clase General Social Media y la clase Bumble. Las regresiones logísticas penalizadas no ajustadas mostraron asociaciones de la clase Poly App Use con un alza en el número de parejas receptivas en relaciones sexuales anales y con reportes de sexo anal receptivo sin condón. Al ajustar por otras covariables, los miembros de la clase Poly App Use, con respecto a las otras clases, tuvieron más probabilidades de ser mayores (25­34 vs. 18­24, ORA = 3,81; IC95%=1,70 − 9,03), de informar el uso de drogas ilícitas en los últimos 6 meses (ORA = 2,93; IC95%=1,25 − 7,43) y haber utilizado alguna vez profilaxis-preexposición (ORA = 2,79; IC95%=1,10 − 7,12). Así mismo, los miembros de esta clase tuvieron perfiles de comportamiento asociado con el riesgo elevado de VIH y también informaron comportamientos de protección relacionados con el VIH que probablemente indican una mayor conciencia del riesgo entre ellos. Nuestros hallazgos justifican la diferenciación de perfiles de comportamiento en base a patrones de uso de aplicaciones y sugieren no generalizar los comportamientos sexuales asociados con riesgos potenciales de VIH a todos los HSH que las usan.

Combining Fleetwide AviTeam Aviation Emission Modeling with LCA Perspectives for an Alternative Fuel Impact Assessment.

Reducing aviation emissions is important as they contribute to air pollution and climate change. Several alternative aviation fuels that may reduce life cycle emissions have been proposed. Comparative life cycle assessments (LCAs) of fuels are useful for inspecting individual fuels, but systemwide analysis remains difficult. Thus, systematic properties like fleet composition, performance, or emissions and changes to them under alternative fuels can only be partially addressed in LCAs. By integrating the geospatial fuel and emission model, AviTeam, with LCA, we can assess the mitigation potential of a fleetwide use of alternative aviation fuels on 210 000 shorter haul flights. In an optimistic case, liquid hydrogen (LH2) and power-to-liquid fuels, when produced with renewable electricity, may reduce emissions by about 950 GgCO2eq when assessed with the GWP100 metric and including non-CO2 impacts for all flights considered. Mitigation potentials range from 44% on shorter flights to 56% on longer flights. Alternative aviation fuels' mitigation potential is limited because of short-lived climate forcings and additional fuel demand to accommodate LH2 fuel. Our results highlight the importance of integrating system models into LCAs and are of value to researchers and decision-makers engaged in climate change mitigation in the aviation and transport sectors.

Characterizing the Opportunity Space for Sustainable Hydrothermal Valorization of Wet Organic Wastes.

Resource recovery from wet organic wastes can support circular economies by creating financial incentives to produce renewable energy and return nutrients to agriculture. In this study, we characterize the potential for hydrothermal liquefaction (HTL)-based resource recovery systems to advance the economic and environmental sustainability of wastewater sludge, FOG (fats, oils, and grease), food waste, green waste, and animal manure management through the production of liquid biofuels (naphtha, diesel), fertilizers (struvite, ammonium sulfate), and power (heat, electricity). From the waste management perspective, median costs range from -193 $·tonne-1 (FOG) to 251 $·tonne-1 (green waste), and median carbon intensities range from 367 kg CO2 eq·tonne-1 (wastewater sludge) to 769 kg CO2 eq·tonne-1 (green waste). From the fuel production perspective, the minimum selling price of renewable diesel blendstocks are within the commercial diesel price range (2.37 to 5.81 $·gal-1) and have a lower carbon intensity than petroleum diesel (101 kg CO2 eq·MMBTU-1). Finally, through uncertainty analysis and Monte Carlo filtering, we set specific targets (i.e., achieve wastewater sludge-to-biocrude yield >0.440) for the future development of hydrothermal waste management system components. Overall, our work demonstrates the potential of HTL-based resource recovery systems to reduce the costs and carbon intensity of resource-rich organic wastes.

Evaluation of five multisteroid LC‒MS/MS methods used for routine clinical analysis: comparable performance was obtained for nine analytes.

OBJECTIVES: A mass spectrometry (LC‒MS/MS)-based interlaboratory comparison study was performed for nine steroid analytes with five participating laboratories. The sample set contained 40 pooled samples of human serum generated from preanalyzed leftovers. To obtain a well-balanced distribution across reference intervals of each steroid, the leftovers first underwent a targeted mixing step. METHODS: All participants measured a sample set once using their own multianalyte protocols and calibrators. Four participants used in-house developed measurement platforms, including IVD-CE certified calibrators, which were used by three participants; the 5th lab used the whole LC‒MS kit from an IVD manufacturer. All labs reported results for 17-hydroxyprogesterone, androstenedione, cortisol, and testosterone, and four labs reported results for 11-deoxycortisol, corticosterone, cortisone, dehydroepiandrosterone sulfate (DHEAS), and progesterone. RESULTS: Good or acceptable overall comparability was found in Bland‒Altman and Passing‒Bablok analyses. Mean bias against the overall mean remained less than ±10 % except for DHEAS, androstenedione, and progesterone at one site and for cortisol and corticosterone at two sites (max. -18.9 % for androstenedione). The main analytical problems unraveled by this study included a bias not previously identified in proficiency testing, operator errors, non-supported matrix types and higher inaccuracy and imprecision at lower ends of measuring intervals. CONCLUSIONS: This study shows that intermethod comparison is essential for monitoring the validity of an assay and should serve as an example of how external quality assessment could work in addition to organized proficiency testing schemes.

Development of a corn flour certified reference material for the accurate determination of zearalenone.

A certified reference material (CRM, KRISS 108-01-002) for zearalenone in corn flour was developed to assure reliable and accurate measurements in testing laboratories. Commercially available corn flour underwent freeze-drying, pulverization, sieving, and homogenization. The final product was packed in amber bottles, approximately 14 g per unit, and preserved at -70 °C. 13C18-Zearalenone was used as an internal standard (IS) for the certification of zearalenone by isotope-dilution liquid chromatography-tandem mass spectrometry (ID-LC‒MS/MS) and for the analysis of α-zearalenol, ß-zearalenol, and zearalanone by LC‒MS/MS. The prepared CRM was sufficiently homogeneous, as the among-unit relative standard deviation for each mycotoxin ranged from 2.2 to 5.7 %. Additionally, the stability of the mycotoxins in the CRM was evaluated under different temperature conditions and scheduled test periods, including storage at -70°C, -20°C, and 4°C and room temperature for up to 12 months, 6 months, and 1 month, respectively. The content of each target mycotoxin in the CRM remained stable throughout the monitoring period at each temperature. Zearalenone content (153.6 ± 8.0 µg/kg) was assigned as the certified value. Meanwhile, the contents of α-zearalenol (1.30 ± 0.17 µg/kg), ß-zearalenol (4.75 ± 0.33 µg/kg), and zearalanone (2.09 ± 0.16 µg/kg) were provided as informative values.

The in vitro gastrointestinal digestion-associated protein corona of polystyrene nano- and microplastics increases their uptake by human THP-1-derived macrophages.

BACKGROUND: Micro- and nanoplastics (MNPs) represent one of the most widespread environmental pollutants of the twenty-first century to which all humans are orally exposed. Upon ingestion, MNPs pass harsh biochemical conditions within the gastrointestinal tract, causing a unique protein corona on the MNP surface. Little is known about the digestion-associated protein corona and its impact on the cellular uptake of MNPs. Here, we systematically studied the influence of gastrointestinal digestion on the cellular uptake of neutral and charged polystyrene MNPs using THP-1-derived macrophages. RESULTS: The protein corona composition was quantified using LC‒MS-MS-based proteomics, and the cellular uptake of MNPs was determined using flow cytometry and confocal microscopy. Gastrointestinal digestion resulted in a distinct protein corona on MNPs that was retained in serum-containing cell culture medium. Digestion increased the uptake of uncharged MNPs below 500 nm by 4.0-6.1-fold but did not affect the uptake of larger sized or charged MNPs. Forty proteins showed a good correlation between protein abundance and MNP uptake, including coagulation factors, apolipoproteins and vitronectin. CONCLUSION: This study provides quantitative data on the presence of gastrointestinal proteins on MNPs and relates this to cellular uptake, underpinning the need to include the protein corona in hazard assessment of MNPs.

Clinical and genetic studies for a cohort of patients with Leber congenital amaurosis.

PURPOSE: Leber congenital amaurosis (LCA) is a group of early-onset retinal degenerative disorders, resulting in blindness in children. This study aimed to describe the clinical and genetic characteristics of a cohort of patients with LCA and to investigate the retinal vascular characteristics in LCA patients. METHODS: Fifty-two children with LCA were included in the study. All patients underwent detailed ocular examinations. Electroretinography (ERG) was used to evaluate the retinal function. Optical coherence tomography (OCT) was used to assess the structure change of the retina for those patients who were able to cooperate very well. Panel-based next-generation sequencing was performed to identify pathogenic variants in genes associated with LCA. Diameters of the retinal vessels were measured using the EVision AI screening system with an artificial intelligence (AI) technique. An ultrasound Doppler was used to evaluate hemodynamic parameters, including peak systolic velocity (PSV), resistive index (RI), and pulsatility index (PI), in the ophthalmic, central retinal, posterior ciliary, carotid, and internal carotid as well as external carotid arteries in 12 patients aged from 3 to 14 years. RESULTS: We detected 75 pathogenic variants from ten genes of RPGRIP1, CEP290, GUCY2D, LCA5, AIPL1, CRB1, RPE65, CRX, RDH12, and TULP1, including 29 novel and 36 previously reported variants in 52 affected children with LCA, with the highest detective rate in RPGRIP1 (26.9%). Fundus appearance is diverse in patients with LCA, ranging from normal to severe peripheral or central retinopathy. Retinal vasculature was evaluated in 12 patients with different gene variants, showing narrowed arteries with an average diameter of 43.6 ± 3.8 µm compared to that of 51.7 ± 2.6 µm in the normal controls (P < 0.001, n = 12). Meanwhile, their hemodynamic parameters were changed as well in the ophthalmic artery (OA), with a decreased PSV (P = 0.0132, n = 12) and slightly increased PI (P = 0.0488, n = 12) compared to the normal controls. However, the hemodynamic parameters did not change significantly in the other vessels. CONCLUSIONS: Blood supply to the eyeball is predicted to be reduced in patients with LCA, presumably due to photoreceptor cell degeneration. The novel identified variants will expand the spectrum of variants in LCA-related genes and be useful for studying the molecular mechanisms of LCA.

Environmental impact of Norwegian self-selected diets: comparing current intake with national dietary guidelines and EAT-Lancet targets.

OBJECTIVES: Dietary environmental impact in a Norwegian adult population was estimated for six environmental impact categories. Moreover, environmental benefits of scenario diets complying with the Norwegian Food-Based Dietary Guidelines (FBDG) and the EAT-Lancet reference diet were assessed. DESIGN: The current diet of Norwegian adults was estimated according to 24-h dietary recall data from a national dietary surveillance survey (Norkost 3). Scenario diets were modelled to represent the Norwegian FBDG and the EAT-Lancet healthy reference diet. Dietary environmental impact in terms of global warming potential, freshwater and marine eutrophication, terrestrial acidification, water use and transformation and use of land was estimated for the current and scenario diets using environmental impact data representative of the Norwegian market. Significant associations between impact and gender/educational attainment were assessed at P < 0·05. SETTING: Norway. PARTICIPANTS: Adults (n=1787) aged 18-70 years who participated in the Norkost 3 survey (2010-2011). RESULTS: Environmental impact varied significantly by gender and educational attainment. The food groups contributing most to environmental impact of Norwegian diets were meat, dairy, beverages, grains and composite dishes. Compared with the current Norwegian diet, the FBDG scenario reduced impacts from 2 % (freshwater eutrophication) to 32 % (water use), while the EAT-Lancet scenario reduced impacts from 7 % (marine eutrophication) to 61 % (land use). The EAT-Lancet scenario resulted in 3-48 % larger reductions in impact than the FBDG scenario. CONCLUSIONS: The Norwegian FBDG, while not as environmentally friendly as the EAT-Lancet reference diet, can still be an important tool in lessening environmental burden of Norwegian diets.

Abnormal expression of LCA and CD43 in SCLC: a rare case report and brief literature review.

BACKGROUND: To present an unusual case of abnormal LCA expression and CD43 in SCLC and to review the reported literature to avoid potential diagnostic pitfalls. CASE PRESENTATION: A 73-year-old male patient suffered from persistent back pain for more than one month. MRI revealed a compression fracture of the L1-L5 vertebra. A CT scan revealed multiple nodules and masses at the left root of the neck, lung hilum and mediastinum, and multiple areas of bony destruction of the ribs. Histology of the tumor revealed that small and round cells were arranged in nests with areas of necrosis. The tumor cells were round to ovoid with scant cytoplasm and indistinct cell borders. The nuclear chromatin was finely granular, and the nucleoli were absent or inconspicuous. Immunohistochemically, the tumor cells were positive for cytokeratin, TTF-1, POU2F3, LCA, and CD43. CONCLUSION: This report highlights a potential diagnostic pitfall in the diagnosis of SCLC, urges pathologists to exercise caution in cases of LCA and CD43 positivity and illustrates the need for further immunohistochemical studies to avoid misdiagnosis.

Nutrient deficiency patterns and all-cause and cardiovascular mortality in older adults with hypertension: a latent class analysis.

BACKGROUND: Previous researches examining the impact of dietary nutrition on mortality risk have mainly focused on individual nutrients, however the interaction of these nutrients has not been considered. The purpose of this study was to identify of nutrient deficiencies patterns and analyze their potential impact on mortality risk in older adults with hypertension. METHODS: We included participants from the National Health and Nutrition Examination Survey (NHANES) study. The latent class analysis (LCA) was applied to uncover specific malnutrition profiles within the sample. Risk of the end points across the phenogroups was compared using Kaplan-Meier analysis and Cox proportional hazard regression model. Multinomial logistic regression was used to determine the influencing factors of specific malnutrition profiles. RESULTS: A total of 6924 participants aged 60 years or older with hypertension from NHANES 2003-2014 was followed until December 31, 2019 with a median follow-up of 8.7 years. Various nutrients included vitamin A, vitamin B1, vitamin B12, vitamin C, vitamin D, vitamin E, vitamin K, fiber, folate, calcium, magnesium, zinc, copper, iron, and selenium, and LCA revealed 4 classes of malnutrition. Regarding all-cause mortality, "Nutrient Deprived" group showed the strongest hazard ratio (1.42 from 1.19 to 1.70) compared with "Adequate Nutrient" group, followed by "Inadequate Nutrient" group (1.29 from 1.10 to 1.50), and "Low Fiber, Magnesium, and Vit E" group (1.17 from 1.02 to 1.35). For cardiovascular mortality, "Nutrient Deprived" group showed the strongest hazard ratio (1.61 from 1.19 to 2.16) compared with "Adequate Nutrient" group, followed by "Low Fiber, Magnesium, and Vit E" group (1.51 from 1.04 to 2.20), and "Inadequate Nutrient" group (1.37 from 1.03 to 1.83). CONCLUSIONS: The study revealed a significant association between nutrients deficiency patterns and the risk of all-cause and cardiovascular mortality in older adults with hypertension. The findings suggested that nutrients deficiency pattern may be an important risk factor for mortality in older adults with hypertension.

Effects of physical activity patterns on myopia among children and adolescents: A latent class analysis.

BACKGROUND: The daily physical activity (PA) patterns of children and adolescents are intricate and ambiguous, with varying effects on myopia resulting from different combinations of PA. This study aims to scrutinize the spectrum of PA patterns among children and adolescents and assess their impact on myopia. METHODS: Data sourced from the 2014 National Student Physical Fitness Survey (Tianjin segment) encompassed PA records and visual acuity measurements of participants. Latent Class Analysis and a generalized linear model were employed to investigate the relationship between PA categories and visual acuity across different educational stages. RESULTS: The study comprised 6465 primary and middle school students, among whom 50.13% were male. PA patterns were categorized into high (27.16%), medium (29.88%) and low visual acuity regulation groups (13.97%) and the nonmainstream group (28.99%). Following adjustments for sex, age, region and BMI, the medium visual acuity regulation group exhibited a lower risk of myopia (OR = 0.617, 95% CI = 0.424-0.897, p = 0.012; OR = 0.654, 95% CI = 0.438-0.976, p = 0.038) compared to the nonmainstream group among junior and senior middle school students. CONCLUSION: The efficacy of diverse PA patterns in mitigating myopia risk varies across educational stages and is influenced by sex-specific factors. It is imperative to advance myopia management strategies by emphasizing tailored PA interventions, discerning between PA patterns and delivering timely guidance and interventions tailored to distinct educational stages and sexes.

Dog ownership in infancy is protective for persistent wheeze in 17q21 asthma-risk carriers.

BACKGROUND: Asthma-associated single nucleotide polymorphisms from large genome-wide association studies only explain a fraction of genetic heritability. Likely causes of the missing heritability include broad phenotype definitions and gene-environment interactions (GxE). The mechanisms underlying GxE in asthma are poorly understood. Previous GxE studies on pet ownership showed discordant results. OBJECTIVES: We sought to study the GxE between the 17q12-21 locus and pet ownership in infancy in relation to wheeze. METHODS: Wheezing classes derived from 5 UK-based birth cohorts (latent class analysis) were used to study GxE between the 17q12-21 asthma-risk variant rs2305480 and dog and cat ownership in infancy, using multinomial logistic regression. A total of 9149 children had both pet ownership and genotype data available. Summary statistics from individual analyses were meta-analyzed. RESULTS: rs2305480 G allele was associated with increased risk of persistent wheeze (additive model odds ratio, 1.37; 95% CI, 1.25-1.51). There was no evidence of an association between dog or cat ownership and wheeze. We found significant evidence of a GxE interaction between rs2305480 and dog ownership (P = 8.3 × 10-4) on persistent wheeze; among dog owners, the G allele was no longer associated with an increased risk of persistent wheeze (additive model odds ratio, 0.95; 95% CI, 0.73-1.24). For those without pets, G allele was associated with increased risk of persistent wheeze (odds ratio, 1.61; 95% CI, 1.40-1.86). Among cat owners, no such dampening of the genetic effect was observed. CONCLUSIONS: Among dog owners, rs2305480 G was no longer associated with an increased risk of persistent wheeze (or asthma). Early-life environmental exposures may therefore attenuate likelihood of asthma in those carrying 17q12-21 risk alleles.

Four Unique Genetic Variants in Three Genes Account for 62.7% of Early-Onset Severe Retinal Dystrophy in Chile: Diagnostic and Therapeutic Consequences.

Leber congenital amaurosis (LCA)/early-onset severe retinal dystrophy (EOSRD) stand as primary causes of incurable childhood blindness. This study investigates the clinical and molecular architecture of syndromic and non-syndromic LCA/EOSRD within a Chilean cohort (67 patients/60 families). Leveraging panel sequencing, 95.5% detection was achieved, revealing 17 genes and 126 variants (32 unique). CRB1, LCA5, and RDH12 dominated (71.9%), with CRB1 being the most prevalent (43.8%). Notably, four unique variants (LCA5 p.Glu415*, CRB1 p.Ser1049Aspfs*40 and p.Cys948Tyr, RDH12 p.Leu99Ile) constituted 62.7% of all disease alleles, indicating their importance for targeted analysis in Chilean patients. This study underscores a high degree of inbreeding in Chilean families affected by pediatric retinal blindness, resulting in a limited mutation repertoire. Furthermore, it complements and reinforces earlier reports, indicating the involvement of ADAM9 and RP1 as uncommon causes of LCA/EOSRD. These data hold significant value for patient and family counseling, pharmaceutical industry endeavors in personalized medicine, and future enrolment in gene therapy-based treatments, particularly with ongoing trials (LCA5) or advancing preclinical developments (CRB1 and RDH12).