A comprehensive meta-analysis and systematic review of breath analysis in detection of COVID-19 through Volatile organic compounds.

BACKGROUND: The COVID-19 pandemic had profound global impacts on daily lives, economic stability, and healthcare systems. Diagnosis of COVID-19 infection via RT-PCR was crucial in reducing spread of disease and informing treatment management. While RT-PCR is a key diagnostic test, there is room for improvement in the development of diagnostic criteria. Identification of volatile organic compounds (VOCs) in exhaled breath provides a fast, reliable, and economically favorable alternative for disease detection. METHODS: This meta-analysis analyzed the diagnostic performance of VOC-based breath analysis in detection of COVID-19 infection. A systematic review of twenty-nine papers using the grading criteria from Newcastle-Ottawa Scale (NOS) and PRISMA guidelines was conducted. RESULTS: The cumulative results showed a sensitivity of 0.92 (95 % CI, 90 %-95 %) and a specificity of 0.90 (95 % CI 87 %-93 %). Subgroup analysis by variant demonstrated strong sensitivity to the original strain compared to the Omicron and Delta variant in detection of SARS-CoV-2 infection. An additional subgroup analysis of detection methods showed eNose technology had the highest sensitivity when compared to GC-MS, GC-IMS, and high sensitivity-MS. CONCLUSION: Overall, these results support the use of breath analysis as a new detection method of COVID-19 infection.

Characterization of Microbotryum lychnidis-dioicae Secreted Effector Proteins, Their Potential Host Targets, and Localization in a Heterologous Host Plant.

Microbotryum lychnidis-dioicae is an obligate fungal species colonizing the plant host, Silene latifolia. The fungus synthesizes and secretes effector proteins into the plant host during infection to manipulate the host for completion of the fungal lifecycle. The goal of this study was to continue functional characterization of such M. lychnidis-dioicae effectors. Here, we identified three putative effectors and their putative host-plant target proteins. MVLG_02245 is highly upregulated in M. lychnidis-dioicae during infection; yeast two-hybrid analysis suggests it targets a tubulin α-1 chain protein ortholog in the host, Silene latifolia. A potential plant protein interacting with MVLG_06175 was identified as CASP-like protein 2C1 (CASPL2C1), which facilitates the polymerization of the Casparian strip at the endodermal cells. Proteins interacting with MVLG_05122 were identified as CSN5a or 5b, involved in protein turnover. Fluorescently labelled MVLG_06175 and MVLG_05122 were expressed in the heterologous plant, Arabidopsis thaliana. MVLG_06175 formed clustered granules at the tips of trichomes on leaves and in root caps, while MVLG_05122 formed a band structure at the base of leaf trichomes. Plants expressing MVLG_05122 alone were more resistant to infection with Fusarium oxysporum. These results indicate that the fungus might affect the formation of the Casparian strip in the roots and the development of trichomes during infection as well as alter plant innate immunity.

A feasibility study on exhaled breath analysis using UV spectroscopy to detect COVID-19.

A 23-subject feasibility study is reported to assess how UV absorbance measurements on exhaled breath samples collected from silicon microreactors can be used to detect COVID-19. The silicon microreactor technology chemoselectively preconcentrates exhaled carbonyl volatile organic compounds and subsequent methanol elution provides samples for analysis. The underlying scientific rationale that viral infection will induce an increase in exhaled carbonyls appears to be supported by the results of the feasibility study. The data indicate statistically significant differences in measured UV absorbance values between healthy and symptomatic COVID-19 positive subjects in the wavelength range from 235 nm to 305 nm. Factors such as subject age were noted as potential confounding variables.

Mesenchymal Stem Cell-Conditioned Medium Reduces Disease Severity and Immune Responses in Inflammatory Arthritis.

We evaluated the therapeutic potential of mesenchymal stem cell-conditioned medium (CM-MSC) as an alternative to cell therapy in an antigen-induced model of arthritis (AIA). Disease severity and cartilage loss were evaluated by histopathological analysis of arthritic knee joints and immunostaining of aggrecan neoepitopes. Cell proliferation was assessed for activated and naïve CD4+ T cells from healthy mice following culture with CM-MSC or co-culture with MSCs. T cell polarization was analysed in CD4+ T cells isolated from spleens and lymph nodes of arthritic mice treated with CM-MSC or MSCs. CM-MSC treatment significantly reduced knee-joint swelling, histopathological signs of AIA, cartilage loss and suppressed TNFα induction. Proliferation of CD4+ cells from spleens of healthy mice was not affected by CM-MSC but reduced when cells were co-cultured with MSCs. In the presence of CM-MSC or MSCs, increases in IL-10 concentration were observed in culture medium. Finally, CD4+ T cells from arthritic mice treated with CM-MSC showed increases in FOXP3 and IL-4 expression and positively affected the Treg:Th17 balance in the tissue. CM-MSC treatment reduces cartilage damage and suppresses immune responses by reducing aggrecan cleavage, enhancing Treg function and adjusting the Treg:Th17 ratio. CM-MSC may provide an effective cell-free therapy for inflammatory arthritis.

Evaluation of canned therapeutic diets for the management of cats with naturally occurring chronic diarrhea.

Dietary therapy plays an important role in the management of most gastrointestinal disorders. This study was designed to test the efficacy of a new therapeutic diet for cats with diarrhea, compared to the top selling brand. Sixteen adult cats with chronic diarrhea were grouped and assigned to diet X (Hill's Prescription Diet i/d Feline) or diet Y (Purina Veterinary Diets EN Gastroenteric Feline Formula). Following baseline evaluations, cats were fed their assigned test diet for 4 weeks. Fecal scores (FS; 7=very watery; 1=extremely dry and firm) were recorded daily during the last week on each diet. Each cat was then switched to the alternate test diet and the procedure was repeated. Fifteen cats completed the study. Both therapeutic diets resulted in a significant improvement in average FS and diet Y also resulted in significantly better results compared with diet X. Average FS improved at least one unit in 40% of the cats while fed diet X and in 67% of the cats while fed diet Y, resulting in normal stools (average FS≤3) in 13.3% of cats fed diet X and 46.7% of cats fed diet Y. This study confirms the value of dietary change in the management of chronic diarrhea in cats.

Evaluation of dietary energy intake and physical activity in dogs undergoing a controlled weight-loss program.

OBJECTIVE: To quantify physical activity and dietary energy intake in dogs enrolled in a controlled weight-loss program and assess relationships between energy intake and physical activity, sex, age, body weight, and body condition score (BCS). DESIGN: Prospective clinical study. ANIMALS: 35 client-owned obese dogs (BCS > 7/9). PROCEDURES: Dogs were fed a therapeutic diet with energy intake restrictions to maintain weight loss of approximately 2%/wk. Collar-mounted pedometers were used to record the number of steps taken daily as a measure of activity. Body weight and BCS were assessed at the beginning of the weight-loss program and every 2 weeks thereafter throughout the study. Relationships between energy intake and sex, age, activity, BCS, and body weight at the end of the study were assessed via multivariable linear regression. Variables were compared among dogs stratified post hoc into inactive and active groups on the basis of mean number of steps taken (< or > 7,250 steps/d, respectively). RESULTS: Mean ± SD daily energy intake per unit of metabolic body weight (kg(0.75)) of active dogs was significantly greater than that of inactive dogs (53.6 ± 15.2 kcal/kg(0.75) vs 42.2 ± 9.7 kcal/kg(0.75), respectively) while maintaining weight-loss goals. In regression analysis, only the number of steps per day was significantly associated with energy intake. CONCLUSIONS AND CLINICAL RELEVANCE: Increased physical activity was associated with higher energy intake while maintaining weight-loss goals. Each 1,000-step interval was associated with a 1 kcal/kg(0.75) increase in energy intake.

The effects of weight loss on adipokines and markers of inflammation in dogs.

Evidence suggests that adipose tissue-derived adipokines induce mild inflammation and may play a role in insulin resistance associated with diabetes. The present study was designed to examine a series of adipokines and markers of inflammation in dogs before and after a successful weight loss. The study included fasting serum samples from twenty-five dogs before and after a weight-loss programme. Serum C-reactive protein (CRP) and monocyte chemoattractant protein-1 (MCP-1) were measured as indicators of chronic inflammation, while serum adipokines including total adiponectin, high-molecular-weight (HMW) adiponectin, resistin and leptin were also examined. Medians for CRP (before, 10.0 (interquartile range 5.4-15.0) µg/ml; after, 5.6 (interquartile range 3.8-7.0) µg/ml) and MCP-1 (before, 212 (interquartile range 157-288) ng/ml; after, 185 (interquartile range 143-215) ng/ml) decreased significantly after weight loss. Medians for resistin showed a mild, yet significant reduction (before, 67.1 (interquartile range 44.4-88.5) pg/ml; after, 60.5 (interquartile range 32.3-67.1) pg/ml), while leptin showed a dramatic decrease after weight loss (before, 18.9 (interquartile range 10.8-35.4) ng/ml; after, 6.6 (interquartile range 3.9-10.2) ng/ml). Serum total adiponectin and HMW adiponectin were unchanged on all analyses performed. These data suggest that weight loss can decrease chronic inflammation; however, the clinical implications of this decrease are not well elucidated in dogs. Surprisingly, there was no increase in total or HMW serum adiponectin after weight loss, as observed previously in human subjects. The lack of change in total and HMW adiponectin might explain why insulin resistance and type 2 diabetes are less prevalent in obese dogs when compared with humans and cats.

Effects of dietary sodium chloride on health parameters in mature cats.

High sodium diets have been shown to enhance water intake and urine output, a potential benefit in the management of lower urinary tract diseases. However, one study suggested that high salt (sodium chloride) diets might have adverse effects on the kidneys [Kirk CA, Jewell DE, Lowry SR. Effects of sodium chloride on selected parameters in cats. Vet Ther 2006; 7: 333-46]. Therefore, the objective of this controlled, prospective study was to evaluate the effects of diets with different salt content (1.11% sodium and 1.78% chloride versus 0.55% sodium and 1.02% chloride, dry matter (dm)) when fed to mature cats (mean age 7.0 years; 12 cats per group) over a 6-month period. Food intake, body weight, bone mineral content, total body hydration status, blood pressure, and markers of renal function were unaffected by salt intake, and no adverse effects were observed. When a subset of cats (n=9) with an initial serum creatinine > or =1.6mg/dl was evaluated separately, there remained no evidence of adverse effects associated with increased salt intake. These results are consistent with the majority of other studies evaluating sodium intake in cats, as well as with the National Research Council's assessment, all of which indicate that sodium at 1.5% of the diet dm is not harmful to healthy cats.

Evaluation of two diets in the nutritional management of cats with naturally occurring chronic diarrhea.

Feeding either a highly digestible, moderate-carbohydrate diet or a highly digestible, high-protein, low-carbohydrate diet resulted in significant (P < .05) improvements in fecal scores in 71% of cats with chronic, nonspecific diarrhea. Approximately 58% of the cats improved on either diet, with no significant differences between the two diets regarding the percentage of cats responding or the degree of response. These results suggest that dietary management may be helpful in cats with chronic diarrhea. If cats do not respond within 1 month, an alternative diet should be considered.