Search

The gut microbiome plays a key role in the pathogenesis and disease activity of inflammatory bowel disease (IBD). While research has focused on the bacterial microbiome, recent studies have shifted towards host genetics and host-fungal interactions. The mycobiota is a vital component of the gastrointestinal microbial community and plays a significant role in immune regulation. Among fungi, Candida species, particularly Candida albicans ( C. albicans ), have been extensively studied due to their dual role as gut commensals and invasive pathogens. Recent findings indicate that various strains of C. albicans exhibit considerable differences in virulence factors, impacting IBD's pathophysiology. Intestinal fungal dysbiosis and antifungal mucosal immunity may be associated to IBD, especially Crohn's disease (CD). This article discusses intestinal fungal dysbiosis and antifungal immunity in healthy individuals and CD patients. It discusses factors influencing the mycobiome's role in IBD pathogenesis and highlights significant contributions from the scientific community aimed at enhancing understanding of the mycobiome and encouraging further research and targeted intervention studies on specific fungal populations. Our article also provided insights into a recent study by Wu et al in the World Journal of Gastroenterology regarding the role of the gut microbiota in the pathogenesis of CD., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest relevant to the content of this manuscript., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Hyperuricemia (HUA) is a condition associated with a high concentration of uric acid (UA) in the bloodstream and can cause gout and chronic kidney disease. The gut microbiota of patients with gout and HUA is significantly altered compared to that of healthy people. This article focused on the complex interconnection between alterations in the gut microbiota and the development of this disorder. Some studies have suggested that changes in the composition, diversity, and activity of microbes play a key role in establishing and progressing HUA and gout pathogenesis. Therefore, we discussed how the gut microbiota contributes to HUA through purine metabolism, UA excretion, and intestinal inflammatory responses. We examined specific changes in the composition of the gut microbiota associated with gout and HUA, highlighting key bacterial taxa and the metabolic pathways involved. Additionally, we discussed the effect of conventional gout treatments on the gut microbiota composition, along with emerging therapeutic approaches that target the gut microbiome, such as the use of probiotics and prebiotics. We also provided insights into a study regarding the gut microbiota as a possible novel therapeutic intervention for gout treatment and dysbiosis-related diagnosis., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Alzheimer's disease (AD) is marked by the gradual and age-related deterioration of nerve cells in the central nervous system. The histopathological features observed in the brain affected by AD are the aberrant buildup of extracellular and intracellular amyloid-β and the formation of neurofibrillary tangles consisting of hyperphosphorylated tau protein. Axonal transport is a fundamental process for cargo movement along axons and relies on molecular motors like kinesins and dyneins. Kinesin's responsibility for transporting crucial cargo within neurons implicates its dysfunction in the impaired axonal transport observed in AD. Impaired axonal transport and dysfunction of molecular motor proteins, along with dysregulated signaling pathways, contribute significantly to synaptic impairment and cognitive decline in AD. Dysregulation in tau, a microtubule-associated protein, emerges as a central player, destabilizing microtubules and disrupting the transport of kinesin-1. Kinesin-1 superfamily members, including kinesin family members 5A, 5B, and 5C, and the kinesin light chain, are intricately linked to AD pathology. However, inconsistencies in the abundance of kinesin family members in AD patients underline the necessity for further exploration into the mechanistic impact of these motor proteins on neurodegeneration and axonal transport disruptions across a spectrum of neurological conditions. This review underscores the significance of kinesin-1's anterograde transport in AD. It emphasizes the need for investigations into the underlying mechanisms of the impact of motor protein across various neurological conditions. Despite current limitations in scientific literature, our study advocates for targeting kinesin and autophagy dysfunctions as promising avenues for novel therapeutic interventions and diagnostics in AD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Durairajan, Selvarasu, Singh, Patnaik, Iyaswamy, Jaiswal, Williams and Huang.)

The zelkovamycin family is a class of cyclic octapeptides with potent antibacterial and antiviral activity. Due to their unique chemical structures and excellent bioactivity, zelkovamycins have consistently attracted the interest of synthetic chemists. However, only the total synthesis of zelkovamycin and zelkovamycin G has been reported until now. The current work presents, for the first time, the synthesis of zelkovamycin analogues, along with their anticancer activity assessment. Firstly, the corresponding chain peptide based on the amino acid sequence of zelkovamycin H was synthesized using the Fmoc solid-phase peptide strategy. This was followed by cyclization under high dilution conditions to obtain compound 21 , and its structure was elucidated by NMR analysis. The results confirm that compound 21 is not the natural product of zelkovamycin H. We deduced that during the synthesis of peptide 12 , the D-Abu residue epimerized to the L-Abu form, leading to the formation of peptide 20 , which blocked our efforts during the synthesis of zelkovamycin H. Two more analogues, 22 and 23, were synthesized by changing the structure of amino acid residues using the same strategy. The anticancer activity of analogues 21 - 23 against Huh-7 cells was evaluated in vitro; however, their IC 50 values were >50 μM.

Various extracts are tested for anti-allergic or anti-inflammatory properties on in vitro models. RBL-2H3 cells are widely used in allergic or immunological studies. FCεRI and its downstream signaling cascades, such as MAPK, NF-κB, and JAK/STAT signaling pathways, are important allergic or inflammatory signaling mechanisms in mast and basophil cells. This systematic review aims to study common signaling pathways of the anti-allergic or anti-inflammatory compounds on RBL-2H3 cells. We selected the relevant research articles published after 2015 from the PubMed, Scopus, Science Direct and Web of Science databases. The risk of bias of the studies was assessed based on the modified CONSORT checklist for in vitro studies. The cell lines, treatments, assay, primary findings, and signaling pathways on RBL-2H3 cells were extracted to synthesize the results. Thirty-eight articles were included, and FCεRI and its downstream pathways, such as Lyn, Sky, PLCγ, and MAPK, were commonly studied. Moreover, the JAK/STAT pathway was a potential signaling mechanism in RBL-2H3 cells. However, the findings based on RBL-2H3 cells needed to be tested along with human mast cells to confirm its relevance to human health. In conclusion, a single plant extract may act as an anti-inflammatory reagent in RBL-2H3 cells via multiple signaling pathways besides the MAPK signaling pathway.

A surge in the number of anthropogenic pollutants has been caused by increasing industrial activities. Nanoplastics are spotlighted as a new aquatic pollutant that are a threat to microbes and larger organisms. Our previous study showed that the subinhibitory concentrations of aquatic pollutants such as phenol and formalin act as signaling molecules and modulate global gene expression and metabolism. In this study, we aimed to investigate the impact of a new type of anthropogenic contaminant, polystyrene (PS) nanoplastics, on the expression of key virulence factors in zoonotic pathogen Edwardsiella piscicida and the assessment of potential changes in the susceptibility of zebrafish as a model host. The TEM data indicated a noticeable change in the cell membrane indicating that PS particles were possibly entering the bacterial cells. Transcriptome analyses performed to identify the differentially expressed genes upon PS exposure revealed that the genes involved in major virulence factor type VI secretion system (T6SS) were down-regulated. However, the expression of T6SS-related genes was recovered from the PS adapted E. piscicida when nanoplastics are free. This demonstrated the hypervirulence of pathogen in infection assays with both cell lines and in vivo zebrafish model. Therefore, this study provides experimental evidence elucidating the direct regulatory impact of nanoplastics influx into aquatic ecosystems on fish pathogenic bacteria, notably influencing the expression of virulence factors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The symbiotic community of microorganisms in the gut plays an important role in the health of the host. While many previous studies have been performed on the interactions between the gut microbiome and the host in mammals, studies in fish are still lacking. In this study, we investigated changes in the intestinal microbiome and pathogen susceptibility of zebrafish ( Danio rerio ) following chronic antibiotics exposure. The chronic antibiotics exposure assay was performed on zebrafish for 30 days using oxytetracycline (Otc), sulfamethoxazole/trimethoprim (Smx/Tmp), or erythromycin (Ery), which are antibiotics widely used in the aquaculture industry. The microbiome analysis indicated that Fusobacteria, Proteobacteria, Firmicutes, and Bacteroidetes were the dominant phyla in the gut microbiome of the zebrafish used in this study. However, in Smx/Tmp-treated zebrafish, the compositions of Fusobacteria and Proteobacteria were changed significantly, and in Ery-treated zebrafish, the compositions of Proteobacteria and Firmicutes were altered significantly. Although alpha diversity analysis showed that there was no significant difference in the richness, beta diversity analysis revealed a community imbalance in the gut microbiome of all chronically antibiotics-exposed zebrafish. Intriguingly, in zebrafish with dysbiosis in the gut microbiome, the pathogen susceptibility to Edwardsiella piscicida , a representative Gram-negative fish pathogen, was reduced. Gut microbiome imbalance resulted in a higher count of goblet cells in intestinal tissue and an upregulation of genes related to the intestinal mucosal barrier. In addition, as innate immunity was enhanced by the increased mucosal barrier, immune and stress-related gene expression in the intestinal tissue was downregulated. In this study, we provide new insight into the effect of gut microbiome dysbiosis on pathogen susceptibility.

Natively unfolded tau has a low propensity to form aggregates, but in tauopathies, such as Alzheimer's disease (AD), tau aggregates into paired helical filaments (PHFs) and neurofibrillary tangles (NFTs). Multiple intracellular transport pathways utilize kinesin-1, a plus-end-directed microtubule-based motor. Kinesin-1 is crucial in various neurodegenerative diseases as it transports multiple cargoes along the microtubules (MT). Kinesin-1 proteins cannot progress along MTs due to an accumulation of tau on their surfaces. Although kinesin-1-mediated neuronal transport dysfunction is well-documented in other neurodegenerative diseases, its role in AD has received less attention. Very recently, we have shown that knocking down and knocking out of kinesin-1 heavy chain (KIF5B KO) expression significantly reduced the level and stability of tau in cells and tau transgenic mice, respectively. Here, we report that tau interacts with the motor domain of KIF5B in vivo and in vitro, possibly through its microtubule-binding repeat domain. This interaction leads to the inhibition of the ATPase activity of the motor domain. In addition, the KIF5B KO results in autophagy initiation, which subsequently assists in tau degradation. The mechanisms behind KIF5B KO-mediated tau degradation seem to involve its interaction with tau, promoting the trafficking of tau through retrograde transport into autophagosomes for subsequent lysosomal degradation of tau. Our results suggest how KIF5B removal facilitates the movement of autophagosomes toward lysosomes for efficient tau degradation. This mechanism can be enabled through the downregulation of kinesin-1 or the disruption of the association between kinesin-1 and tau, particularly in cases when neurons perceive disturbances in intercellular axonal transport.

We present the first evidence that sub-anesthetic ketamine infusions for treatment resistant depression (TRD) may facilitate deprescription of long-term benzodiazepine/z-drugs (BZDRs). Long-term BZDR prescriptions are potentially harmful yet common, partly because of challenging withdrawal symptoms. Few pharmacological interventions have evidence for facilitating BZDR discontinuation, and none in patients actively suffering from TRD. In this ambi-directional cohort study, discontinuation of long-term (>6 month) BZDRs was attempted in 22 patients with severe unipolar or bipolar TRD receiving a course of six subanesthetic ketamine infusions over four weeks. We investigated the rates of successful BZDRs deprescription, trajectories of acute psychological withdrawal symptoms, and subsequent BZDRs abstinence during a mean follow-up of 1 year (primary outcome). Clinically significant deteriorations in depression, anxiety, sleep, and/or suicidality during the acute BZDR discontinuation phase were measured by repeated standardized scales and analyzed by latent growth curve models and percent correct classification analysis. Of the 22 eligible patients, all enrolled in this study and 91% (20/22) successfully discontinued all BZDRs by the end of the 4-week intervention, confirmed by urinary analyses. Less than 25% of discontinuers experienced any significant worsening of anxiety, depression, sleep difficulties, or suicidality during treatment. During follow-up (mean [range] duration, 12 [3-24] months), 64% (14/22) of patients remained abstinent from any BZDRs. These preliminary results suggest that ketamine infusions for TRD may facilitate the deprescription of BZDRs, even in patients with active depressive symptoms and significant comorbidity. Further investigation is warranted into this potential novel application of ketamine., (© 2023. The Author(s).)

Spray-dried plasma (SDP) contain a variety of functional proteins that play an immunomodulatory role. To evaluate the potential of SDP to stimulate the immune system, day-old Ross 708 male broiler chicks (200) were allocated randomly to five dietary treatments. Treatment 1 (CX) comprised chicks fed basal unmedicated corn-soybean meal (SBM) without the addition of SDP. Treatment 2 (MX) includes chicks fed unmedicated corn-SBM basal containing Bacitracin methylene disalicylate (BMD) at 0.055 g/kg diet. Treatments 3 (SDP1), 4 (SDP2), and 5 (SDP3) contained chicks given unmedicated corn-SBM basal, into which SDP was included at 10, 20, and 30 g/kg diet, respectively. On d 7, 14, and 21, chicks' body weight and FCR were calculated. Additionally, leucocyte counts, oxidative status, and IgY concentrations were determined in blood. On d 23, fecal populations of selected indicator bacteria species were determined. Results showed that FCR for SP3 was superior ( p < 0.05) to other treatments. Likewise, heterophil numbers decreased in MX and SDP treatments compared to CX. Circulating IgY concentration was higher for SDP dietary treatments ( p < 0.05) compared to MX. In conclusion, dietary SDP at 30 g/kg enhanced immune surveillance by increasing circulating IgY levels, maintaining a normal oxidative state, and increasing gut Bifidobacteria, thereby improving chick growth performance.

Nano-fertilizers are a new tool that can be used to address plant production challenges, and it addresses such nutrient deficiencies through smart agriculture approaches. Iron (Fe) is a vital element for several metabolic and physiological processes; however, Fe deficiency is common in poorly fertile soils (sand soil) and in arid areas. Therefore, additional research is required to select the most efficient form of iron absorbance. This research was implemented on broad bean plants ( Vicia faba L. var. major Harz) to examine the impact of three iron sources: nano-iron (FeNPs, T1), iron sulfate (T2), and chelated iron (T3) as a foliar spray on the morphological properties, physiological attributes, and nutritional status of these plants compared to the untreated plants (control). The obtained results showed that foliar spraying with FeNPs, chelated iron and sulphate iron fertilizers increased plant height by 35.01%, 26.2, and 20.4%; leaf area by 38.8%, 18.3%, and 8.1%; the fresh weight of the plant by 47%, 32.8%, and 7.3%; the dry weight of the plant by 52.9%, 37.3%, and 11.2%; and the number of branches by 47%, 31.3%, and 25.6 %, respectively, compared to the control treatment (CT). Furthermore, the application of FeNPs, chelated iron, and sulphate iron fertilizers improved the number of pods by 47.9%, 24.8%, and 6.1%; the number of seeds by 32.8%, 7.9%, and 2.8%; and seed weight by 20.8%, 9.1%, and 5.4%, compared to control treatment (CT). Additionally, foliar application of FeNPs showed the highest values of photosynthesis rate ( Pn ), water-use efficiency (WUE), total chlorophyll, and phytohormones (IAA, GA3) compared to all the other treatments. The anatomical structure revealed an enhancement of leaf size and thickness (epidermis cells and mesophyll tissue) affected by FeNPs treatment compared to other treatments. Foliar application of FeNPs also improved the total content of carbohydrates, crude protein, element content (N, P, K, Ca, Na, Fe, Zn, Mn, and Cu), and some amino acids such as lysine, arginine, phenylalanine, isoleucine, and tyrosine in the seeds of broad beans. Based on the above results, the maximum values of all tested measurements were observed when FeNPs were used as the foliar spraying followed by chelated and sulphate iron fertilizers. Therefore, these findings suggest that using FeNPs, as a foliar treatment, could be a promising strategy for reducing the Fe deficiency in sandy soil and enhancing plant growth, pod yield, and pod quality of broad bean plants in addition to being environmentally favored in arid areas.

Background: Toxoplasma gondii ( T. gondii ) is a ubiquitous obligatory intracellular parasite which infects over 40 million Americans and causes toxoplasmosis. Inside the human body, T. gondii can damage tissues and invade vital organs., Methods: This study evaluated the association of T. gondii infection and liver disease using data from the National Health and Nutrition Examination Survey (NHANES) 2009-2010, with a sample size of 3371 participants (age 20-80 years). Toxoplasma infection was determined by the level of T. gondii IgG antibody in serum samples. Liver disease was assessed by liver injury biomarkers and the Fatty Liver Index (US-FLI). The evaluation of the association between T. gondii infection and liver disease included the calculation of the Mantel-Haenszel risk ratio (RRMH), Rho-Scott chi-square bivariate analyses, design-based t-tests, and linear and logistic regression models which were adjusted for demographic and anthropometric covariates., Results: Mean levels of aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were significantly more elevated in the T. gondii IgG-positive (IgG+) participants as compared to T. gondii -negative (IgG-) participants, p = 0.0435 and 0.0310, respectively. In linear regression analysis, exposure to T. gondii IgG+ had statistically significant positive associations with AST ( p = 0.0211), alanine aminotransferase (ALT) ( p = 0.0221), and gamma-glutamyl transferase (GGT) ( p = 0.0258) after adjusting for BMI, age, gender, and race. T. gondii exposure was associated with an elevated relative risk of chronic liver disease (CLD) (RRMH = 1.26, 95% CI: 1.05-1.51). This association was more pronounced in certain occupations, such as construction, agriculture, forestry, and fishing, where Toxoplasma infection is more common ( p = 0.0477). Moreover, Toxoplasma infection increased the odds of nonalcoholic fatty liver disease (NAFLD) (OR = 6.99, 95% CI = 1.85-26.32, p = 0.0237)., Conclusion: T. gondii IgG+ antibody was significantly associated with liver injury biomarkers (ALT, AST, GGT, and ALP) and an increased risk of CLD and NAFLD. Moreover, the association of Toxoplasma with CLD was more evident in specific occupations where the prevalence of Toxoplasma was high. The findings of this study provide insight into utilizing liver biomarkers and US-FLI to assess the health complications of Toxoplasma when imaging tests are not accessible.

Food safety is a critical problem that impacts everyone worldwide. Many countries around the world are becoming increasingly reliant on the availability and safety of their food supply. Despite growing public consciousness about food-related dangers, the growth in food poisoning cases implies that individuals continue to make food consumption, food storage, and food preparation decisions that are less than optimal from a health and safety standpoint. The aim of this study was to assess Saudi Arabia's households' knowledge and practices of food safety. A cross-sectional study was conducted to assess knowledge of food safety and practices among a group of households in Saudi Arabia. An online questionnaire using social media (Facebook, Twitter, Instagram, and WhatsApp), and emails communications were distributed. A total of 309 adults (age range 18-59 years) participated in the study. In general, there were no differences between regions regarding the knowledge of food safety. Additionally, most of the participants had good practices of food safety. The findings of our study show that the gender, age, and educational level are factors that have an impact on the knowledge of food safety among respondents. Regarding food safety practices, in general, the results show that the participants had good practices. Therefore, organizations should focus on educational programs, training, holding workshops and activities in public places such as malls, schools, and home visit to improve and increases food safety knowledge and practices.

The World Health Organization declared coronavirus disease 2019 (COVID-19) a pandemic in March 2020. Global efforts have been made to prevent the disease from spreading through political decisions and personal behaviors, all of which rely on public awareness. The aim of our study was to examine the effect of dietary habits on weight and physical activity (PA) during the COVID-19 stay-at-home order in Jeddah, Saudi Arabia. An online questionnaire was distributed using social media (Facebook, Twitter, Instagram, and WhatsApp) and email communication. A total of 472 adults (age range, 18-59 years), over half of the study population (68.0%) being females, 55.5% being between 19 and 29 years old, 15.0%-between 30 and 39 years old, and 11.2%-older than 50 years old, participated in the study. Our results indicated that the overall body weight was slightly increased among the 50+ age group (47.2%, p > 0.05), but it highly increased among the 30-39-years-old age group (32.4%, p > 0.05) as compared to before the pandemic lockdown period. Therefore, our results show that a significant difference ( p < 0.05) was found for all the assessments: weight status, physical activity patterns, hours spent on screen time, homemade meals, and changes in dietary habits before and during the full COVID-19 curfew period. This study demonstrated that changes in eating habits were commonly reported among the participants who represented the full COVID-19 curfew period and that changes in eating habits and decreased physical activity led to weight gain.

Maternal diet supplementation with pro- and prebiotics is associated with decreased incidence of diarrhea and greater piglet performance. This study investigated the impact adding whole ground oat as a prebiotic, alone or in combination with a probiotic, yeast culture (YC) ( Saccharomyces cerevisiae ), to sow gestation and lactation rations had on milk protein composition, piglet growth, and incidence of post-weaning diarrhea (PWD). Diets: control (CON), CON + yeast culture (YC) [5 g/kg], CON + oat (15% inclusion rate) (Oat) or CON+ YC [5 g/kg] + Oat (15%) were fed the last 30 days of gestation and throughout lactation (18-21 days). Shotgun proteome analysis of day 4 and 7 postpartum milk found 36 differentially abundant proteins (P-adj < 0.1) in both Oat and YC supplemented sows relative to CON. Notable was the increased expression of antimicrobial proteins, lactoferrin and chitinase in milk of Oat and YC sows compared to CON. The levels of IgA, IgM (within colostrum and milk) and IgG (within milk) were similar across treatments. However, colostral IgG levels in Oat-supplemented sows were significantly lower ( p < 0.05) than that of the control sows, IgG from Oat-supplemented sows displayed greater reactivity to E. coli -antigens compared with CON and YC. Piglets from sows that consumed Oat alone or in combination weighed significantly more ( p < 0.05) at birth compared to CON and YC. However, piglets in the Oat + YC group weighed less at weaning and had the lowest weight gain ( p < 0.05) postweaning, compared with CON. Taken together with the observation that piglets of either YC- or Oat-fed sows had less PWD compared to CON and YC+ Oat suggests that Oat or YC supplementation positively impacts piglets through expression of certain milk-associated immune and antimicrobial proteins.

Background: Kava is an important neuroactive medicinal plant. While kava has a large global consumer footprint for its clinical and recreational use, factors related to its use lack standardization and the tissue-specific metabolite profile of its neuroactive constituents is not well understood., Results: Here we characterized the metabolomic profile and spatio-temporal characteristics of tissues from the roots and stems using cross-platform metabolomics and a 3D imaging approach. Gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry revealed the highest content of kavalactones in crown root peels and lateral roots. Infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) imaging revealed a unique tissue-specific presence of each target kavalactone. X-ray micro-computed tomography analysis demonstrated that lateral roots have morphological characteristics suitable for synthesis of the highest content of kavalactones., Conclusions: These results provide mechanistic insights into the social and clinical practice of the use of only peeled roots by linking specific tissue characteristics to concentrations of neuroactive compounds., (© The Author(s) 2020. Published by Oxford University Press GigaScience.)

Objective: Symptom accommodation is an important interpersonal construct associated with more severe symptoms, lower levels of functioning, and worse treatment outcomes across various mental health conditions, including social anxiety. Research on this phenomenon is surprisingly absent in Chinese culture, where interpersonal relationships are highly emphasized. This may be due to the absence of a valid Chinese symptom accommodation measure for individuals with social anxiety symptoms. The current study aimed to examine the factor structure and psychometric properties of the Family Accommodation Scale Anxiety-Adult Report (FASA-AR) in Chinese adults., Methods: Three hundred and seventy-five Chinese undergraduate students with social anxiety symptoms completed a battery of self-report measures assessing symptom accommodation in relation to social anxiety symptoms and related impairments, as well as overall symptoms of anxiety and depression., Results: Confirmatory factor analysis supported a two-factor model of symptom accommodation, with factors named Participation in symptom-related behaviors and Modification of functioning. The multiple indicators multiple causes model indicated the indicators of the FASA-AR, mainly the participation in symptom-related behaviors subscale, were not invariant across gender. Internal consistency for the FASA-AR total score and subscale scores was good. Convergent validity of the FASA-AR was evidenced by significant positive association with ratings of social anxiety symptoms, social anxiety related impairments, and anxiety symptoms. Divergent validity was supported by non-significant relation with depression symptoms. Nearly all participants (94.7%) endorsed being accommodated to some extent in the past month., Conclusion: Symptom accommodation is an important construct and is related to social anxiety symptoms among Chinese adults. The FASA-AR demonstrated a clear two-factor latent structure and possessed good psychometric properties that can validly and reliably assess symptom accommodation of social anxiety among Chinese adults., (Copyright © 2020 Lou, Zhou, Lebowitz, Williams and Storch.)

Polypores are cosmopolitan mushrooms, widely investigated for their beneficial properties in combatting multidrug resistant pathogens. The present study focuses on the need for new, naturally sourced antimicrobial and antioxidant compounds from mushrooms. The antioxidant and antibacterial activity of the phenolic extract of strains of Trametes polyzona (Pers.) Justo, were investigated. Strains of T. polyzona were analyzed for total phenolic content, Trolox antioxidant equivalent, DPPH radical scavenging and antibacterial activities. The amplification of the ribosomal DNA-ITS fragments from DNA of selected mushrooms was carried out using ITS1 and ITS4 primers. The antibacterial activity of phenolic extracts of T. polyzona was comparable to the antibiotics, ceftazidime and erythromycin. T. polyzona extracts inhibited the growth of the different strains of K. pneumoniae , E. coli , S. aureus , and S. enterica tested in this study. The results of the study demonstrate that, T. polyzona can be a potential source of antimicrobial and antioxidant compounds., Competing Interests: Conflict of interestAll authors declare that they have no conflict of interest., (© The Korean Society of Food Science and Technology 2019.)

Exposure to hog barn organic dust contributes to occupational lung diseases, which are mediated by inflammatory and oxidative stress pathways. Isoprostanes-a family of eicosanoids produced by oxidation of phospholipids by oxygen radicals-are biomarkers of pulmonary oxidative stress. Importantly, 8-isoprostane has been implicated as a key biomarker and mediator of oxidative stress because it is a potent pulmonary vasoconstrictor. Antioxidants found in fruits and vegetables hold promise for preventing or reducing effects of oxidative stress-related diseases including chronic bronchitis and chronic obstructive pulmonary disease (COPD). Here, we investigated 8-isoP and oxidant production by organic dust-exposed airway epithelial cells and the inhibitory effects of an extract from calyces of the sorrel plant, Hibiscus sabdariffa , on oxidant-producing pathways. Confluent cultures of normal human tracheobronchial epithelial cells were pretreated or not with 1% sorrel extract prior to 5% dust extract (DE) exposure. Following DE treatments, live cells, cell-free supernatants, or cell extracts were evaluated for the presence of 8-isoprostane, superoxide, hydrogen peroxide, nitric oxide, hydroxyl radical, peroxynitrite, and catalase activity to evaluate sorrel's inhibitory effect on oxidative stress. The well-known radical scavenging antioxidant, N-acetyl cysteine (NAC), was used for comparisons with sorrel. DE exposure augmented the production of all radicals measured including 8-isoprostane ( p value < 0.001), which could be inhibited by NAC or sorrel. Among reactive oxygen and nitrogen species generated in response to DE exposure, sorrel had no effect on H 2 O 2 production and NAC had no significant effect on NO · production. The observations reported here suggest a possible role for sorrel in preventing 8-isoprostane and oxidant-mediated stress responses in bronchial epithelial cells exposed to hog barn dust. These findings suggest a potential role for oxidative stress pathways in mediating occupational lung diseases and antioxidants within sorrel and NAC in reducing dust-mediated oxidative stress within the airways of exposed workers., Competing Interests: The authors declare that there is no conflict of interest.

In a study using a randomized crossover approach, cyclists ( n = 20, overnight fasted) engaged in three 75 km time trials while ingesting water (WAT) or carbohydrate (0.2 g/kg every 15 min) from bananas (BAN) or a 6% sugar beverage (SUG). Blood samples were collected pre-exercise and 0 h, 1.5 h, and 21 h post-exercise and analyzed for natural killer (NK) cytotoxicity activity (NKCA) using pure NK cell populations. The two carbohydrate trials (BAN, SUG) compared to WAT were associated with higher post-exercise glucose and lower cortisol, total blood leukocyte, neutrophil, and NK cell counts (interaction effects, p < 0.001). The immediate post-exercise increase in NK cell counts was higher in WAT (78%) compared to BAN (32%) and SUG (15%) trials ( p ≤ 0.017). The 1.5 h post-exercise decrease in NK cell counts did not differ after WAT (-46%), BAN (-46%), and SUG (-51%) trials. The pattern of change in post-exercise NKCA differed between trials ( p < 0.001). The 1.5 h post-exercise decreases in NKCA were 23%, 29%, and 33% in the WAT, BAN, and SUG trials, respectively, but trial contrasts did not differ significantly. Carbohydrate ingestion from BAN or SUG attenuated immediate post-exercise increases in leukocyte, neutrophil, and NK cell counts, but did not counter the 1.5 h decreases in NK cell counts and NKCA.

Human norovirus (NoV) is the leading cause of foodborne illnesses in the United States. Norovirus is shed in high numbers in the feces and vomitous of infected individuals. Contact surfaces contaminated with bodily fluids harboring infectious virus particles serve as vehicles for pathogen transmission. Environmental stability of NoV and its resistance to many conventional disinfectants necessitate effective inactivation strategies to control the spread of virus. We investigated the efficacy of two commercial disinfectants, hydrogen peroxide (7.5%) and a chlorine dioxide (0.2%)-surfactant-based product using a fogging delivery system against human NoV GI.6 and GII.4 Sydney strains as well as the cultivable surrogate, feline calicivirus (FCV) dried on stainless steel coupons. Log 10 reductions in human NoV and FCV were calculated utilizing RNase RT-qPCR and infectivity (plaque) assay, respectively. An improved antiviral activity of hydrogen peroxide as a function of disinfectant formulation concentration in the atmosphere was observed against both GII.4 and FCV. At 12.4 ml/m 3 , hydrogen peroxide achieved a respective 2.5 ± 0.1 and 2.7 ± 0.3 log 10 reduction in GI.6 and GII.4 NoV genome copies, and a 4.3 ± 0.1 log 10 reduction in infectious FCV within 5 min. At the same disinfectant formulation concentration, chlorine dioxide-surfactant-based product resulted in a respective 1.7 ± 0.2, 0.6 ± 0.0, and 2.4 ± 0.2 log 10 reduction in GI.6, GII.4, and FCV within 10 min; however, increasing the disinfectant formulation concentration to 15.9 ml/m 3 negatively impacted its efficacy. Fogging uniformly delivered the disinfectants throughout the room, and effectively decontaminated viruses on hard-to-reach surfaces. Hydrogen peroxide delivered by fog showed promising virucidal activity against FCV by meeting the United States EPA 4-log 10 reduction criteria for an anti-noroviral disinfectant; however, fogged chlorine dioxide-surfactant-based product did not achieve a 4-log 10 inactivation. Future investigation aimed at optimizing decontamination practices is warranted.

A broad suite of 87 contaminants of emerging concern (CECs), including 26 polybrominated diphenyl ethers (PBDEs), 23 non-PBDEs halogenated FRs (NPHFRs), 16 organophosphate esters (OPEs), 4 perfluorinated sulfonates (PFSAs), 13 perfluorinated carboxylic acids (PFCAs) and 5 emerging perfluoroalkyl acids (PFAAs) or precursors, were determined in 30 individual Caspian tern (listed as a threatened species in the U.S. State of Michigan) eggs collected in 2013 and 2014 from Michigan nesting sites on Two Tree Island (St, Mary's River), Charity Reef (Saginaw Bay) and Channel-Shelter Island (a Confined Disposal Facility (CDF) in Saginaw Bay). The same CEC suite was determined in 10 herring gull eggs on the Pipe Island Twins in the lower St. Mary's River. In tern eggs, the order of concentrations were ΣPFSA (mean: 793 ng/g wet weight (ww); range: 116-4690 ng/g ww) > ΣPFCAs (131; 30.4-506 ng/g ww) ≈ ΣPBDEs (86.7; 32.4-189 ng/g ww) » ΣNPHFRs (0.67; ND-4.3 ng/g ww) ≈ ΣOPEs (0.46; ND-2.89 ng/g ww). Compared to gull eggs collected from the same area, tern egg exposure contained significantly lower concentrations of ΣPBDE, but with up to 10 times greater mean concentrations of ΣPFSAs and ΣPFCAs. This study highlights the importance of consistent monitoring in eggs of different Great Lakes birds of PBDEs, perfluorooctane sulfonate (PFOS) and perfluoro-4-ethylcyclohexane sulfonate (PFEtCHxS) given that: 1) PBDE concentrations in all analyzed avian eggs exceeded or approached a concentration of 29 ng/g ww, which for birds is the current Canadian FEQG (Federal Environmental Quality Guideline); 2) ΣPBDE concentrations were comparable to lowest observed effect concentration (LOEC) values reported in the literature; 3) PFOS concentrations in Caspian tern eggs were extremely high with many eggs across sites exceeding 1 ppm, and with the greatest being up to 4.7 ppm; and 4) PFEtCHxS, a potentially persistent and bioaccumulative substance, showed a detection frequency of 100% in 40 of the analyzed eggs., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Proanthocyanidins are oligomeric flavonoids found in plant sources, most notably in apples, cinnamon, grape skin and cocoa beans. They have been also found in substantial amounts in cranberry, black currant, green tea, black tea and peanut skins. These compounds have been recently investigated for their health benefits. Proanthocyanidins have been demonstrated to have positive effects on various metabolic disorders such as inflammation, obesity, diabetes and insulin resistance. Another upcoming area of research that has gained widespread interest is microRNA (miRNA)-based anticancer therapies. MicroRNAs are short non-coding RNA segments, which plays a crucial role in RNA silencing and post-transcriptional regulation of gene expression. Currently, miRNA based anticancer therapies are being investigated either alone or in combination with current treatment methods. In this review, we summarize the current knowledge and investigate the potential of naturally occurring proanthocyanidins in modulating miRNA expression. We will also assess the strategies and challenges of using this approach as potential cancer therapeutics.

Ayurveda is considered as one of the oldest of the traditional systems of medicine (TSMs) accepted worldwide. The ancient wisdom in this traditional system of medicine is still not exhaustively explored. The junction of the rich knowledge from different traditional systems of medicine can lead to new avenues in herbal drug discovery process. The lack of the understanding of the differences and similarities between the theoretical doctrines of these systems is the major hurdle towards their convergence apart from the other impediments in the discovery of plant based medicines. This review aims to bring into limelight the age old history and the basic principles of Ayurveda. This would help the budding scholars, researchers and practitioners gain deeper perspicuity of traditional systems of medicine, facilitate strengthening of the commonalities and overcome the challenges towards their global acceptance and harmonization of such medicinal systems.

In the Laurentian Great Lakes basin of North America, an increasing number of chemicals of emerging concern (CECs) are being investigated, including legacy and replacement flame retardants (FRs). In the present study, 14 polybrominated diphenyl ethers (PBDEs), 23 non-PBDEs halogenated FRs (NPHFRs) and 16 organophosphate ester FRs (OPE-FRs) were analyzed in 100 individual eggs collected in 2012 and 2013 and in 15 egg pools of herring gulls collected in 2012 from 20 colonies across the entire Laurentian Great Lakes basin. For CEC-FRs in eggs from all colonies, 14 PBDEs, 12 NPHFRs and 9 OPE-FRs were quantifiable in at least one of the 115 analyzed samples. The mean sum PBDE (Σ14PBDE) concentrations ranged from 244 to 657 ng/g wet weight (ww), and on average were 1-2 orders of magnitude greater than the Σ12NPHFR concentrations (13.8-35.6 ng/g ww), and 2-3 orders of magnitude greater than Σ9OPE-FR concentrations (0.31-2.14 ng/g ww). Mean Σ14PBDE and sum of syn- and anti-Dechlorane Plus isomer (Σ2DDC-CO) concentrations in eggs from colonies within Laurentian Great Lakes Areas of Concern (AOCs) were in most cases greater than in eggs from nearby colonies outside of AOCs. Comparing CEC-FR concentrations in eggs collected in 2012-2013 to those previously measured in eggs collected approximately 7 years earlier (2006 and 2008) showed that Σ7PBDE (BDE-28, -47, -100, -99, -154,-153 and -183) mean concentrations in eggs from 6 colonies were approximately 30% less than they were in eggs from the same colonies from the earlier time period, whereas 3 current-use FR (BDE-209, HBCDD and Σ2DDC-CO) concentrations were significantly greater (p<0.05) than previously measured. Between 2006 and 2013 there were significant changes in individual PBDE patterns for BDE-71, -138, -153, -203, -206 and -207. Among all of the examined CEC-FRs, concentrations of Σ4PBDE (BDE-47, -99, -100 and -153) and HBCDD in gull eggs from all colonies were greater than or comparable to their lowest observed effect concentrations (LOECs) based on in ovo egg injection studies. Overall, the current profiles of a broad suite of FRs in Laurentian Great Lakes herring gull eggs highlights the need to better understand e.g., exposure-effect implications and metabolism of FRs, i.e. OPE-FRs, and emphasizes the importance of continued monitoring of CEC-FRs whose concentrations appear to be increasing, including BDE-209, HBCDD and DDC-COs., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Craving is a core feature of tobacco use disorder as well as a significant predictor of smoking relapse. Studies have shown that appetitive smoking-related stimuli (e.g., someone smoking) trigger significant cravings in smokers impede their self-control capacities and promote drug seeking behavior. In this review, we begin by an overview of functional magnetic resonance imaging (fMRI) studies investigating the neural correlates of smokers to appetitive smoking cues. The literature reveals a complex and vastly distributed neuronal network underlying smokers' craving response that recruits regions involved in self-referential processing, planning/regulatory processes, emotional responding, attentional biases, and automatic conducts. We then selectively review important factors contributing to the heterogeneity of results that significantly limit the implications of these findings, namely between- (abstinence, smoking expectancies, and self-regulation) and within-studies factors (severity of smoking dependence, sex-differences, motivation to quit, and genetic factors). Remarkably, we found that little to no attention has been devoted to examine the influence of personality traits on the neural correlates of cigarette cravings in fMRI studies. Impulsivity has been linked with craving and relapse in substance and tobacco use, which prompted our research team to examine the influence of impulsivity on cigarette cravings in an fMRI study. We found that the influence of impulsivity on cigarette cravings was mediated by fronto-cingulate mechanisms. Given the high prevalence of cigarette smoking in several psychiatric disorders that are characterized by significant levels of impulsivity, we conclude by identifying psychiatric patients as a target population whose tobacco-smoking habits deserve further behavioral and neuro-imaging investigation.

Peanut skin is a rich source of polyphenols, such as proanthocyanidins. Peanut skin proanthocyanidins mainly consist of a subgroup called procyanidins. Peanut-based procyanidins contain oligomers of both type A and type B procyanidins. Recent studies have shown that peanut skin extracts exert protection against hepatic steatosis induced on rats fed with a high-fat diet. Studies have shown that proanthocyanidins protect against cardiovascular diseases (CVDs). The mechanism of CVD protection and hypolipidemic effect of peanut skin procyanidins has been gradually revealed in recent years. Due to the high molecular weight of procyanidins, they are not readily absorbed through the gut barrier. It is hypothesized that procyanidins exert their effect by inhibiting the absorption of dietary lipid and chylomicron secretion by enterocytes. In this review, we aim to highlight the hypolipidemic effects of peanut skin polyphenols and discuss the various molecular mechanisms, with which the polyphenols may exert the lipid-lowering function observed by weighing the absorption characteristics as well as gene expression mechanism responsible for lipid homeostasis.

Metformin is an oral biguanide used for type II diabetes. Epidemiologic studies suggest a link between metformin use and reduced risk of breast and other types of cancers. ErbB2-expressing breast cancer is a subgroup of tumors with poor prognosis. Previous studies demonstrated that metformin is a potent inhibitor of ErbB2-overexpressing breast cancer cells; metformin treatment extends the life span and impedes mammary tumor development in ErbB2 transgenic mice in vivo. However, the mechanisms of metformin associated antitumor activity, especially in prevention models, remain unclear. We report here for the first time that systemic administration of metformin selectively inhibits CD61(high)/CD49f(high) subpopulation, a group of tumor-initiating cells (TIC) of mouse mammary tumor virus (MMTV)-ErbB2 mammary tumors, in preneoplastic mammary glands. Metformin also inhibited CD61(high)/CD49f(high) subpopulation in MMTV-ErbB2 tumor-derived cells, which was correlated with their compromised tumor initiation/development in a syngeneic tumor graft model. Molecular analysis indicated that metformin induced downregulation of ErbB2 and EGFR expression and inhibited the phosphorylation of ErbB family members, insulin-like growth factor-1R, AKT, mTOR, and STAT3 in vivo. In vitro data indicate that low doses of metformin inhibited the self-renewal/proliferation of cancer stem cells (CSC)/TICs in ErbB2-overexpressing breast cancer cells. We further demonstrated that the expression and activation of ErbB2 were preferentially increased in CSC/TIC-enriched tumorsphere cells, which promoted their self-renewal/proliferation and rendered them more sensitive to metformin. Our results, especially the in vivo data, provide fundamental support for developing metformin-mediated preventive strategies targeting ErbB2-associated carcinogenesis.

Angiogenesis is a process of new blood vessel generation and under pathological conditions, lead to tumor development, progression, and metastasis. Many bioactive components have been studied for its antiangiogenic properties as a preventive strategy against tumor development. This study is focused on the effects of cinnamon extract in modulating the pathway involved in angiogenesis. Human umbilical vein endothelial cells (HUVEC) were treated with cinnamon extract at a concentration of 25 μg/mL for 1, 3, or 6 h followed by treatment with phorbol ester (TPA) at a concentration of 10 nmol/L to induce mitogen-activated protein kinase (MAPK) expression. Results show that cinnamon extract inhibited TPA-induced phosphorylation of MAPK and AKT in a dose-dependent manner. Gene expression results in HUVEC showed that cinnamon extract treatment inhibited TPA induction of protein kinase C, PKCα and PKCη messenger RNA (mRNA) expression in a dose-dependent manner along with suppression of vascular endothelial growth factor receptor 1 (VEGFR1/Flt1) and vascular endothelial growth factor receptor 2 (VEGFR2/KDR/Flk1) mRNA expression. Cinnamon extract was administered to zebrafish embryos during gastrulation at 6-8 h post fertilization (hpf). The embryos were observed for changes in morphology, toxicity, and blood vessel development. The intersegmental vessels in the zebrafish embryos were attenuated and underdeveloped at an effective cinnamon extract dose of 250 μg/mL compared with the DMSO-treated control. Exposure to cinnamon extract for 36 h resulted in gross morphological deformities. The results suggest the effect of cinnamon extract on angiogenesis is mediated by PKC-dependent phosphorylation of MAPK.

Experimental as well as epidemiologic studies in human populations provide evidence that consumption of phytochemicals reduces the incidence of degenerative diseases. Green tea (GT) catechins are known for their antioxidative potential. Phytic acid (PA) also acts as a natural antioxidant and may have numerous health benefits. This experiment was designed to investigate the inhibitory effects of combinations of 1% and 2% GT, PA, and inositol (I) in reducing the incidence of azoxymethane-induced colon tumors in Fisher 344 male rats. After an acclimatization period of 1 week, nine groups of rats (15 rats per group) were initially assigned to consume AIN 93 G diet and later AIN 93 M diet after 20 weeks of age. Treatments were given in drinking water. All rats received azoxymethane injections (16 mg/kg of body weight) subcutaneously at 7 and 8 weeks of age. Rats were killed at 45 weeks of age by CO(2) euthanasia. Tumor incidence (93.76%) and the number of tumors per tumor-bearing rat ratio (2.25) were significantly (P<.05) higher in the control group compared with treatment groups. Glutathione S-transferase activity was significantly (P<.05) higher in rats fed combinations of 2% GT+PA+I and GT+PA (33.25 ± 1.23 and 29.83 ± 1.10 μmol/mL, respectively) compared with other groups. These findings suggest that the synergistic effect of the 2% level of GT, PA, and I may reduce the incidence of colon tumors and therefore have potential as a chemopreventive agent.

The use of medicinal plants as natural antimicrobial agents is gaining popularity. Sorrel (Hibiscus sabdariffa) is widely used for the treatment of diseases. The objective of this study was to investigate the antimicrobial activity of sorrel on Escherichia coli O157:H7 isolates from food, veterinary, and clinical samples. Phenolics of the calyces were extracted from 10 g of ground, freeze-dried samples using 100 mL of 80% aqueous methanol. Concentrations of 10%, 5%, and 2.5% methanol extract of sorrel were investigated for its antimicrobial activity. Inhibition zones were indicated by a lack of microbial growth due to inhibitory concentrations of sorrel diffused into semisolid culture medium beneath the sorrel-impregnated disk. The results of this experiment showed that the most potent sorrel concentration was 10%, then 5%, and finally 2.5%. The overall mean zone of inhibition for the sorrel extract was 12.66 mm for 10%, 10.75 mm for 5%, and 8.9 mm for 2.5%. The highest inhibition zones (11.16 mm) were observed in veterinary samples, and the lowest (10.57 mm) in the food samples. There were significant (P<.05) differences among mean zones of inhibition found in the food, veterinary, and clinical sources. Based on the source of samples and concentration of sorrel extract, the lowest mean inhibition was 7.00±0.04 mm from clinical samples, and the highest was 15.37±0.61 mm from a food source. These findings indicated that sorrel was effective at all levels in inhibiting E. coli O157:H7; thus it possesses antimicrobial activity and hold great promise as an antimicrobial agent.

Local health departments that investigate foodborne disease outbreaks do not have adequate guidelines for collecting data that could be used to estimate dose-response relationships, a key component of hazard characterization in quantitative microbial risk assessment. To meet this need, criteria and a questionnaire template for the collection of appropriate dose-response data in the context of outbreaks were developed and applied in the investigation of a point-source outbreak linked to Salmonella serotype Enteritidis in a salmon entrée in February 2000. In this outbreak, the attack rate and risk of hospitalization increased with the amount of salmon entrée consumed, and detailed data were obtained on illness severity measures and host susceptibility factors. Local health departments might consider broadening investigations to include the collection of additional data when investigating outbreaks that have met a specific set of conditions. These data could provide information needed by federal regulatory agencies and other organizations for quantitative microbial risk assessment. Intensive investigations of outbreaks could prevent future illnesses by providing information needed to develop approaches to minimizing risk.

Adult female rainbow trout were exposed to dietary 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at concentrations of 1.8, 18 and 90 ng TCDD/kg (ww) food for up to 300 day. At the end of the exposure fish were spawned and the reproductive outcomes were assessed. TCDD was accumulated into tissues and eggs in a dose-dependent manner with steady state being achieved after 50-100 day of exposure. Biochemical and hematological parameters were monitored at 50, 100, 150, and 200 day after the beginning of exposure. The survival of adult female trout was reduced in a dose-dependent manner by exposure to TCDD in the diet. Fish fed 1.8 ng TCDD/kg, moist weight of diet, showed significantly reduced survival compared with those fed the control diet. TCDD also affected survival of fry from females fed 1.8 ng TCDD/kg. Observed adverse effects in adult fish were as sensitive as early life-stage endpoints. Liver EROD activity was only moderately increased in all exposure groups after 250+ day of exposure. Low rates of edema and deformities were observed in fry from all treatment groups including controls. This study has demonstrated adverse effects of TCDD to both adults and fry at concentrations comparable to current environmental concentrations. This suggests that direct adult toxicity as well as reproductive endpoints need to be incorporated in the current risk assessment paradigm for these compounds.

This study was designed to determine the effect of 10% dietary long-chain inulin on the azoxymethane (AOM)-induced colonic preneoplastic aberrant crypt foci (ACF) and small intestinal and colon tumors at the initiation (I), promotion (P) and I + P stages (20 rats per treatment) in Fisher 344 male weanling rats. After an acclimatization period of 1 wk, groups of Fisher 344 male weanling rats were assigned to consume AIN 93G diet (control) or AIN 93G diet containing 10% inulin. All the rats received 16 mg/kg body AOM dissolved in saline subcutaneously at 7 wk of age followed by a second injection at 8 wk of age. An additional group of five rats received only saline and consumed the control diet. The rats received the assigned diets until asphyxiation by CO(2) at 16 wk of age for the ACF experiment and 45 wk for the end-point tumor experiment. Feed intake, weight gain, diarrheal index, cecal weight, cecal pH, ACF and tumors in the colon were determined. Rats fed inulin had diarrhea after 2 wk of feeding and recovered by approximately 4 wk. Cecal weight was greater in rats fed inulin and cecal pH was lower. The inulin group had more than 66% fewer aberrant crypts and 60% fewer ACF compared with the control group. Tumor incidences in the small intestine and colon of rats in the control, I, P and I + P groups were: 78, 31, 0 and 11% and 90, 73, 69 and 50%, respectively. The corresponding values for the distal portion of the colon were 87, 63, 45 and 33%, respectively. Colon tumors per tumor-bearing rat were 4.2, 3.09, 1.36 and 1.2 for the control, I, P and I + P groups, respectively. All groups differed, P < 0.05. The results of this study indicate that dietary long-chain inulin suppresses AOM-induced ACF formation, an early preneoplastic marker of colon tumorigenesis in rats, and colon tumors, particularly at the promotion stage.

The author, an American, examines British Columbia's health care system as it struggles to retain equity and access as two of its implacable tenets. Some sources argue that realities fall far short of the abstract ideals. Certainly implementation and funding problems are growing as B.C.'s policy makers struggle with large-scale economic pressures and management priorities. Despite the system's shortcomings, however, U.S. readers would be wise to consider the philosophical and rhetorical impact of these normative concepts. Their presence and power encapsulates the breadth of the contrast between the Canadian and American systems.

Long-term follow-up information was obtained for 17 cats with cerebral meningiomas treated by surgical excision. Three cats died or were euthanatized in the immediate postoperative period: 2 cats, because of brain herniation and 1 cat, because of acute renal failure. In the remaining 14 cats, most clinical signs resolved within 1 week of surgery. Three cats (21.4%) had confirmed or presumed local tumor recurrence. Two of these cats developed recurrent neurologic signs, and died or were euthanatized at 3 and 9 months, respectively, after surgery. One cat was euthanatized for an unrelated problem 72 months after surgery, and on postmortem examination, had a recurrent meningioma at the surgery site. The remaining 11 cats (78.6%) did not develop evidence of local tumor recurrence within follow-up periods ranging from 18 to 47 months (median, 27 months).

Phagocytosis, a secondary function of retinal pigment epithelial (RPE) cells essential to sight, was significantly decreased, when measured with latex beads, during persistent rubella virus (RV) infection of human cultured RPE cells. A target for RV in vivo, RPE cells infected with RV (RPE/RV) ingested fewer fluorescent microspheres (26%) than did uninfected RPE cells (68%) (P < 0.001), as measured by flow cytometry. In RPE/RV cells, with characteristic RPE monolayer appearance and normal growth during subculturing over 6 months, persistent RV infection was shown by specific RV antigen immunofluorescence, by the presence of the RV genome in RPE/RV cell messenger RNA, and by recovery of cell-free RV after cocultivation with Vero cells. The adhesion of latex beads to apical cell surfaces of RPE/RV and uninfected RPE cells appeared similar, as imaged by scanning electron microscopy. Cytoskeletal actin, a component of phagocytosis in RPE, appeared altered in 60 to 75% of RPE/RV cells by antiactin immunofluorescence staining, as previously described in other RV-infected cells, but its role in the disturbed phagocytosis of latex beads was not determined. Persistently RV-infected human RPE is an additional example of RV-associated secondary cellular dysfunction in the absence of cytopathic effects.

Interleukin-2 receptor (IL-2R) is an activation molecule that, when expressed on peripheral blood lymphocyte (PBL) membranes, indicates the secretion of IL-2 and initiation of an immune system activation cascade. Comparing the average of IL-2R expression in 34 patients with retinitis pigmentosa (RP) syndrome (561 +/- 282 cells/mm3; mean +/- standard deviation) with 35 age-matched normal subjects (194 +/- 39 cells/mm3), it was found that those with RP had greater numbers of IL-2R-positive cells (P less than 0.001). The increased amounts of IL-2R on PBL of 29 RP and the homotypic self-aggregation of RP PBL by phase and scanning electron microscopy led to the study of the interaction of RP PBL with cultured human postmortem retinal pigment epithelial cells (RPE). A direct correlation was found between the amount of IL-2R expression and the numbers of RP lymphocytes adhering to RPE monolayers. However, the adherence effect was not unique to RP syndrome but appeared to be a nonspecific result of lymphocyte activation. Greater adherence to RPE than normal also was observed in PBL from disease control subjects with elevated IL-2R values and in PBL stimulated by the mitogen, concanavalin A (Con-A). In addition, RPE monolayers were destroyed by Con-A-stimulated PBL that showed 95-98% IL-2R expression. Similar, but less serious effects, occurring in RPE cells after 1 wk's cocultivation with RP PBL, suggested that activated RP lymphocytes can be cytotoxic to RPE during prolonged contact. Because macrophage-like cells and class II major histocompatibility complex expression have been found in RP-affected retinas, immune-mediated cytopathologic effects may contribute to retinal degeneration in RP.

Elevated serum ELISA IgG antibodies to rubella virus (RV) were found by three independent determinations in 41 (72%) of 57 adults with the retinal degeneration retinitis pigmentosa, while antibody responses to five other common neurotropic viruses were normal. However, these patients lacked clinical signs of active RV infection or known recent RV exposure, and 56 lacked IgM anti-RV antibody. Unusual relative percentages of IgG antibody to RV structural proteins compared with those of controls were found in patients' sera by radioimmunoprecipitation assay. For retinitis pigmentosa patients, percentage of RV envelope glycoprotein E1 antibody was similar to, of RV envelope glycoprotein E2 antibody was greater than, and of antibody to RV nucleocapsid C protein was lower than control percentages. Abnormal immunity to RV was also suggested by a lack of increased proliferation of lymphocytes to RV antigen despite elevated anti-RV antibody in patients with retinitis pigmentosa. Not associated with age or particular genetic pattern, these divergences from normal immunity suggest an unusual association between RV proteins and retinitis pigmentosa.

A previous isolation of a human cytomegalovirus (CMV) from fibroblasts derived from intact skin of a Charcot-Marie-Tooth disease patient has prompted examination of six blind-coded cultured human skin lines by CMV DNA hybridization. The detection of CMV genome equivalents in three of the lines suggests that, in some cases, intact human skin may be a site of CMV latency.

Forty-three fibroblast cell line were initiated from normal skin biopsies. One cell line from a patient with Charcot--Marie--Tooth disease (CMT) spontaneously developed c.p.e. suggestive of cytomegalovirus (CMV). Characterization of the virus showed it to be a new strain of CMV and the results suggested that skin fibroblasts from CMT patients may carry latent CMV.

Systemic infection, induced by intraocular inoculation of type 1 herpes simplex virus (HSV 1) in young rabbits, is accompanied by the appearance of autofluorescent pigments precisely in the midportion of their fur follicles. Histochemical and solubility reactions of the pigment led to its characterization as a lipofuscinlike pigment. Follicle fluorescence correlated with the severity of clinical symptoms; it was present in 100% of the follicles of rabbits that died but was found in only 30% to 50% of follicles of surviving animals. Similar fluorescence was also present in 10% to 20% of the follicles of uninfected rabbits. This autofluorescent material may be formed by the peroxidation of lipids from sebaceous gland secretions, but neither HSV 1 nor antigens could be found in the skin as possible initiators of this reaction.