Increased Milk Yield and Reduced Enteric Methane Concentration on a Commercial Dairy Farm Associated with Dietary Inclusion of Sugarcane Extract (Saccharum officinarum).

(1) Background: The purpose of this study was to assess the influence of a natural sugarcane extract (Polygain™) on milk production, milk composition and methane emissions on a commercial dairy farm. (2) Methods: A three-week baseline was established for lactating Holstein × Friesian animals. Following this baseline period, these animals were fed Polygain™ at 0.25% of their estimated dry matter intake for 3 weeks. Methane concentration in the feed bin was determined at each milking using the Gascard NG Infrared Sensor (Edinburgh Sensors LTD). (3) Results: During the intervention phase milk yield increased significantly from 26.43 kg to 28.54 kg per cow per day, whilst methane emissions and bulk tank somatic cell counts decreased significantly in the intervention phase. For methane concentration, an average of 246 ppm during the baseline periods reduced to an average of 161.09 ppm during the intervention phase. For the bulk tank somatic cell counts, the average was observed at 283,200 during the baseline and reduced to an average value of 151,100 during the intervention phase. (4) Conclusions: The natural sugarcane extract was shown to have the potential to mitigate enteric methane emissions while also increasing production and animal wellbeing outcomes in a commercial dairy setting.

Using 17th century medication for modern diabetes management: Doctors' perceptions of self-medication practices - A qualitative study.

Purpose: This study was conducted to explore doctors' perceptions and understanding of the self-medication practices of people living with type 2 diabetes. Methods: A qualitative research design incorporating 20 semi-structured, face-to-face interviews were conducted with doctors treating people with type 2 diabetes in Mysuru, India, between July 2019 and January 2020. All the interviews were conducted in doctors' clinics, audio-recorded and thematically analyzed. Results: Three themes were identified from these interviews- i) Doctors' beliefs towards their patients' use of traditional medicine and environmental factors influencing prescription practices, ii) Doctors reported little faith in traditional medicines, iii) Limited strategies implemented by doctors to overcome barriers to self-medications. Doctors reported greater belief in western medications over traditional medications and expressed concern that their patients favored traditional medications over western. Multiple factors such as social media, accessibility of healthcare facilities and pill burden influenced adherence to western medications. Also, lack of knowledge about traditional medications and trust in western medications available under government schemes have influenced prescription practices among doctors. It appears that doctors implemented strategies such as educating patients on the detrimental effects of self-medication and insisting on patients to take only western medications to achieve desired blood glucose levels when managing self-medication practices among people with diabetes. Conclusion: These results suggest that doctors have limited strategies to implement to prevent self-medication practices among people with diabetes. Increasing knowledge amongst doctors about JAS medication effectiveness and thereby garnering greater trust in generic medications. In addition, efforts should be made to identify the best ways to integrate traditional and western medicine into patient-centered care delivery. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-022-01154-5.

Use of a sensitive multisugar test for measuring segmental intestinal permeability in critically ill, mechanically ventilated adults: A pilot study.

BACKGROUND: Increased intestinal permeability (IP) is associated with sepsis in the intensive care unit (ICU). This study aimed to pilot a sensitive multisugar test to measure IP in the nonfasted state. METHODS: Critically ill, mechanically ventilated adults were recruited from 2 ICUs in Australia. Measurements were completed within 3 days of admission using a multisugar test measuring gastroduodenal (sucrose recovery), small-bowel (lactulose-rhamnose [L-R] and lactulose-mannitol [L-M] ratios), and whole-gut permeability (sucralose-erythritol ratio) in 24-hour urine samples. Urinary sugar concentrations were compared at baseline and after sugar ingestion, and IP sugar recoveries and ratios were explored in relation to known confounders, including renal function. RESULTS: Twenty-one critically ill patients (12 males; median, 57 years) participated. Group median concentrations of all sugars were higher following sugar administration; however, sucrose and mannitol increases were not statistically significant. Within individual patients, sucrose and mannitol concentrations were higher in baseline than after sugar ingestion in 9 (43%) and 4 (19%) patients, respectively. Patients with impaired (n = 9) vs normal (n = 12) renal function had a higher L-R ratio (median, 0.130 vs 0.047; P = .003), lower rhamnose recovery (median, 15% vs 24%; P = .007), and no difference in lactulose recovery. CONCLUSION: Small-bowel and whole-gut permeability measurements are possible to complete in the nonfasted state, whereas gastroduodenal permeability could not be measured reliably. For small-bowel IP measurements, the L-R ratio is preferred over the L-M ratio. Alterations in renal function may reduce the reliability of the multisugar IP test, warranting further exploration.

Metabolic and behavioral effects of olanzapine and fluoxetine on the model organism Caenorhabditis elegans.

The use of many psychotropic drugs (PDs) is associated with increased caloric intake, significant weight gain, and metabolic disorders. The nematode Caenorhabditis elegans (C. elegans) has been used to study the effects of PDs on food intake. However, little is known about PDs effects on the body fat of C. elegans. In C. elegans, feeding behavior and fat metabolism are regulated through independent mechanisms. This study aims to evaluate the body fat and food intake of C. elegans in response to treatment olanzapine and fluoxetine. Here we report that, with careful consideration to the dosage used, administration of fluoxetine and olanzapine increases body fat and food intake in C. elegans.

Early Exposure is Necessary for the Lifespan Extension Effects of Cocoa in C. elegans.

BACKGROUND: We previously showed that cocoa, a rich source of polyphenols improved the age-associated health and extended the lifespan in C. elegans when supplemented starting from L1 stage. AIM: In this study, we aimed to find out the effects of timing of cocoa exposure on longevity improving effects and the mechanisms and pathways involved in lifespan extension in C. elegans. METHODS: The standard E. coli OP50 diet of wild type C. elegans was supplemented with cocoa powder starting from different larval stages (L1, L2, L3, and L4) till the death, from L1 to adult day 1 and from adult day 1 till the death. For mechanistic studies, different mutant strains of C. elegans were supplemented with cocoa starting from L1 stage till the death. Survival curves were plotted, and mean lifespan was reported. RESULTS: Cocoa exposure starting from L1 stage till the death and till adult day 1 significantly extended the lifespan of worms. However, cocoa supplementation at other larval stages as well as at adulthood could not extend the lifespan, instead the lifespan was significantly reduced. Cocoa could not extend the lifespan of daf-16, daf-2, sir-2.1, and clk-1 mutants. CONCLUSION: Early-start supplementation is essential for cocoa-mediated lifespan extension which is dependent on insulin/IGF-1 signaling pathway and mitochondrial respiration.

Inhibition of the Renin-Angiotensin System Reduces Gene Expression of Inflammatory Mediators in Adipose Tissue Independent of Energy Balance.

Obesity is a growing health problem worldwide. The renin-angiotensin system (RAS) is present in adipose tissue, and evidence suggests that it is involved in both diet-induced obesity and the inflammation associated with obesity. The present experiments determined the effect of (1) different angiotensin-converting enzyme (ACE) inhibitors (captopril, perindopril, enalapril) and angiotensin receptor blockers (ARBs: telmisartan, losartan) on adiposity of mice fed a high-fat diet for 28 days (2); acute treatment with the ACE-inhibitor captopril on gene expression of inflammatory markers in mice fed a high-fat diet (HFD); and (3) short-term (2 days) and chronic (28 days) treatment of ACE-inhibition on energy expenditure (EE) and energy balance in mice fed HFD ad libitum (AL), as well as receiving HFD limited to the amount of calories eaten by controls (pair-fed (PF) group). Body weight, food intake, adiposity and plasma leptin were lower in ACE inhibitor or ARB-treated groups over 28 days compared with HFD untreated mice. Short-term treatment with captopril led to increased EE relative to the level in the PF group. After 28 days, EE was lower in both captopril-treated and PF mice compared with AL, but the effect was greater in the captopril-treated group. Adiponectin was elevated in captopril-treated mice, but not in PF mice, after both 2 and 28 days. Additionally, acute RAS blockade in HFD-fed mice reduced mRNA expression for MCP-1, IL-6, TLR4, and leptin in adipose tissue relative to values in untreated groups. These data demonstrate that ACE inhibition and angiotensin receptor blockade reduce food intake to produce weight loss and suggest that the anti-inflammatory effects of ACE inhibition may be independent of weight loss.

Oral administration of bovine milk-derived extracellular vesicles induces senescence in the primary tumor but accelerates cancer metastasis.

The concept that extracellular vesicles (EVs) from the diet can be absorbed by the intestinal tract of the consuming organism, be bioavailable in various organs, and in-turn exert phenotypic changes is highly debatable. Here, we isolate EVs from both raw and commercial bovine milk and characterize them by electron microscopy, nanoparticle tracking analysis, western blotting, quantitative proteomics and small RNA sequencing analysis. Orally administered bovine milk-derived EVs survive the harsh degrading conditions of the gut, in mice, and is subsequently detected in multiple organs. Milk-derived EVs orally administered to mice implanted with colorectal and breast cancer cells reduce the primary tumor burden. Intriguingly, despite the reduction in primary tumor growth, milk-derived EVs accelerate metastasis in breast and pancreatic cancer mouse models. Proteomic and biochemical analysis reveal the induction of senescence and epithelial-to-mesenchymal transition in cancer cells upon treatment with milk-derived EVs. Timing of EV administration is critical as oral administration after resection of the primary tumor reverses the pro-metastatic effects of milk-derived EVs in breast cancer models. Taken together, our study provides context-based and opposing roles of milk-derived EVs as metastasis inducers and suppressors.

Potential contributions of the methodology to the variability of glycaemic index of foods.

Glycaemic index (GI) testing provides a useful point of comparison between carbohydrate sources. For this comparison to be meaningful, the methods used to determine GI values need to be rigorous and consistent between testing events. This requirement has led to increasing standardization of the GI methodology, with an international standard developed in joint consultation with FAO/WHO (ISO 26642:2010) currently the most up to date document. The purpose of this review is to compare the international standard to methods of published studies claiming to have performed a GI test. This analysis revealed that the international standard permits a wide range of choices for researchers when designing a GI testing plan, rather than a single standardized protocol. It has also been revealed that the literature contains significant variation, both between studies and from the international standard for critical aspects of GI testing methodology. The primary areas of variation include; what glucose specification is used, which reference food is used, how much reference food is given, what drink is given during testing, the blood sampling site chosen and what assay and equipment is used to measure blood glucose concentration. For each of these aspects we have explored some of the methodological and physiological implications of these variations. These insights suggest that whilst the international standard has assisted with framing the general parameters of GI testing, further stan-dardization to testing procedures is still required to ensure the continued relevance of the GI to clinical nutrition.

The Effect of Mianserin on Lifespan of Caenorhabditis elegan is Abolished by Glucose.

BACKGROUND: The antidepressant Mianserin has been shown to extend the lifespan of Caenorhabditis elegan (C. elegan), a well-established model organism used in ageing research. The extension of lifespan in C. elegan was shown to be dependent on increased expression of the scaffolding protein (ANK3/unc-44). In contrast, antidepressant use in humans is associated with an increased risk of death. The C. elegan elegan in the laboratory are fed Escherichia coli (E. coli), a diet high in protein and low in carbohydrate, whereas a typical human diet is high in carbohydrates. We hypothesized that dietary carbohydrates might mitigate the lifespan-extension effect of mianserin. OBJECTIVE: To investigate the effect of glucose added to the diet of C. elegan on the lifespan-extension effect of mianserin. METHODS: Wild-type Bristol N2 and ANK3/unc-44 inactivating mutants were cultured on agar plates containing nematode growth medium and fed E. coli. Treatment groups included (C) control, (M50) 50 µM mianserin, (G) 73 mM glucose, and (M50G) 50 µM mianserin and 73 mM glucose. Lifespan was determined by monitoring the worms until they died. Statistical analysis was performed using the Kaplan-Meier version of the log-rank test. RESULTS: Mianserin treatment resulted in a 12% increase in lifespan (P<0.05) of wild-type Bristol N2 worms but reduced lifespan by 6% in ANK3/unc-44 mutants, consistent with previous research. The addition of glucose to the diet reduced the lifespan of both strains of worms and abolished the lifespan-extension by mianserin. CONCLUSION: The addition of glucose to the diet of C. elegan abolishes the lifespan-extension effects of mianserin.

Factors affecting self-medication practices among people living with type 2 diabetes in India- A systematic review.

Self-medication practices of type 2 diabetes in India include the use of both traditional and western medications. It is important to understand the factors influencing self-medication. A total of 3257 studies were screened and nine studies (six quantitative and three qualitative) were included. The Hawker tool and Joanna Briggs Institute Critical Appraisal tool were used to assess the quality of studies. The findings of the quantitative studies were descriptively analysed while thematic analysis was performed to identify key themes from the qualitative studies. The analysis indicated that participants had greater trust in traditional medications regardless of their socioeconomic and/or educational backgrounds as these were often recommended by friends and family members. Low cost, ease of availability and perceived lower side effects of traditional medications were some of the factors contributing to greater trust. It is suggested that ongoing management of type 2 diabetes requires stringent policies and regulations in the dispensing of traditional and western medications. Continual education to inform people on the use of self-medications and its possible adverse effects is also required.

Serum zonulin measured by enzyme-linked immunosorbent assay may not be a reliable marker of small intestinal permeability in healthy adults.

The association between intestinal permeability (IP) and body composition remains unclear. The gold standard differential sugar-absorption test is arduous to complete, with zonulin being increasingly used as an independent biomarker of IP. This pilot study aimed to explore the association between small IP, zonulin concentrations, and body composition in healthy adults. The urinary lactulose-rhamnose ratio was used to measure small IP. Serum zonulin, lipopolysaccharide (LPS) and high-sensitivity C-reactive protein (hs-CRP) were analyzed in serum. Body composition was measured using dual-energy X-ray absorptiometry and anthropometric measurements were collected. In total, 34 participants were included (12 males, median age 28 years, body mass index 24 kg/m2, waist circumference 77cm). No correlation was observed between the lactulose-rhamnose ratio and zonulin (r = -.016, P = .929). The lactulose-rhamnose ratio displayed a strong positive correlation with LPS (n 20, r = .536, P = .018) but did not correlate with body composition measures. Conversely, zonulin displayed a moderate positive correlation with waist circumference (r = .437, P = .042) in female participants and hs-CRP (r = .485, P = .004) in all participants. These findings raise important considerations for the measurement of small IP, warranting exploration in larger powered studies that address the limitations of the present study.

A High-throughput Assay for the Prediction of Chemical Toxicity by Automated Phenotypic Profiling of Caenorhabditis elegans.

Applying toxicity testing of chemicals in higher order organisms, such as mice or rats, is time-consuming and expensive, due to their long lifespan and maintenance issues. On the contrary, the nematode Caenorhabditis elegans (C. elegans) has advantages to make it an ideal choice for toxicity testing: a short lifespan, easy cultivation, and efficient reproduction. Here, we describe a protocol for the automatic phenotypic profiling of C. elegans in a 384-well plate. The nematode worms are cultured in a 384-well plate with liquid medium and chemical treatment, and videos are taken of each well to quantify the chemical influence on 33 worm features. Experimental results demonstrate that the quantified phenotype features can classify and predict the acute toxicity for different chemical compounds and establish a priority list for further traditional chemical toxicity assessment tests in a rodent model.

Effects of herbs and spices on blood pressure: a systematic literature review of randomised controlled trials.

: Hypertension is a major risk factor for cardiovascular disease, affecting 1 billion people worldwide. Literature suggests some herbs and spices have cardiovascular benefits, such as decreasing blood pressure; yet evidence is inconsistent. This article reviewed randomized controlled trials investigating effects of herbs and spices on blood pressure in normotensive, pre-hypertensive and hypertensive participants. Ovid Medline, Embase, Biological abstracts, CINAHL and Cochrane Collaboration were systematically searched. After inclusion and exclusion criteria were applied, nine articles were included for analysis. Overall, three of the nine studies reported statistically significant results, including one of the two studies on hypertensive participants and two of the six studies on pre-hypertensive participants. The remaining study was conducted on normotensive participants and reported no change in blood pressure. There is evidence to suggest certain herbs and spices can reduce blood pressure in a hypertensive and pre-hypertensive population and may not induce hypotension in a normotensive population.

Regulation of myostatin expression is associated with growth and muscle development in commercial broiler and DMC muscle.

Myostatin is a negative regulator of skeletal muscle growth. Muscle tissue is the largest tissue in the body and influences body growth. Commercial Avian broiler chickens are selected for high growth rate and muscularity. Daweishan mini chickens are a slow growing small-sized chicken breed. We investigated the relations between muscle (breast and leg) myostatin mRNA expression and body and muscle growth. Twenty chickens per breed were slaughtered at 0, 30, 60, 90, 120, and 150 days of age. Body and muscle weights were higher at all times in Avian chickens. Breast muscle myostatin expression was higher in Avian chickens than in Daweishan mini chickens at day 30. Myostatin expression peaked at day 60 in Daweishan mini chickens and expression remained higher in breast muscle. Daweishan mini chickens myostatin expression correlated positively with carcass weight, breast and leg muscle weight from day 0 to 60, and correlated negatively with body weight from day 90 to 150, while myostatin expression in Avian chickens was negatively correlated with carcass and muscle weight from day 90 to 150. The results suggest that myostatin expression is related to regulation of body growth and muscle development, with two different regulatory mechanisms that switch between days 30 and 60.

Classification and prediction of toxicity of chemicals using an automated phenotypic profiling of Caenorhabditis elegans.

BACKGROUND: Traditional toxicological studies have relied heavily on various animal models to understand the effect of various compounds in a biological context. Considering the great cost, complexity and time involved in experiments using higher order organisms. Researchers have been exploring alternative models that avoid these disadvantages. One example of such a model is the nematode Caenorhabditis elegans. There are some advantages of C. elegans, such as small size, short life cycle, well defined genome, ease of maintenance and efficient reproduction. METHODS: As these benefits allow large scale studies to be initiated with relative ease, the problem of how to efficiently capture, organize and analyze the resulting large volumes of data must be addressed. We have developed a new method for quantitative screening of chemicals using C. elegans. 33 features were identified for each chemical treatment. RESULTS: The compounds with different toxicities were shown to alter the phenotypes of C. elegans in distinct and detectable patterns. We found that phenotypic profiling revealed conserved functions to classify and predict the toxicity of different chemicals. CONCLUSIONS: Our results demonstrate the power of phenotypic profiling in C. elegans under different chemical environments.

Spatially and temporally variable urinary N loads deposited by lactating cows on a grazing system dairy farm.

Feed nitrogen (N) intakes in Australian grazing systems average 545 g cow-1 day-1, indicating that urinary N is likely to be the dominant form excreted. Grazing animals spend disproportionate amounts of time in places on dairy farms where N accumulation is likely to occur. We attached to grazing cows sensors that measure urine volume and N concentration, as well as global positioning systems sensors used to monitor the times the cows spent in different places on a farm and the location of urination events. The cows were monitored for up to 72 h in each of two seasons. More urination events and greater urine volumes per event were recorded in spring 2014 (3.1 L) compared with winter 2015 (1.4 L), most likely influenced by environmental conditions and the greater spring rainfall observed. Mean (range) N concentration (0.71%; 0.02 to 1.52%) and N load (12.8 g cow-1 event-1; 0.3 to 64.5 g cow-1 event-1) did not differ over the two monitoring periods. However, mean (range) daily N load was greater in spring (277 g cow-1 day-1; 200 to 346 g cow-1 day-1) than in winter (90 g cow-1 day-1; 44 to 116 g cow-1 day-1) due to the influence of urine volume. Relatively greater time was spent in paddocks overnight (13.3 h) than in paddocks between morning and evening milking (6.4 h), compared with the mean numbers of urinations in these places (6.4 and 3.8 respectively). The mean N load deposited overnight in paddocks (89.6 g cow-1) was more than twice that deposited in paddocks during the day (43.8 g cow-1), due to the greater N load per event overnight, and was more closely linked to the relative difference in time spent in paddocks than in the number of urination events. These data suggest that routinely holding cows in the same paddocks overnight will lead to high urinary N depositions, increasing the potential for N losses from these places. Further research using this technology is required to acquire farm and environment specific urinary data to improve N management.

Growth of Caenorhabditis elegans in Defined Media Is Dependent on Presence of Particulate Matter.

Caenorhabditis elegans are typically cultured in a monoxenic medium consisting of live bacteria. However, this introduces a secondary organism to experiments, and restricts the manipulation of the nutritional environment. Due to the intricate link between genes and environment, greater control and understanding of nutritional factors are required to push the C. elegans field into new areas. For decades, attempts to develop a chemically defined, axenic medium as an alternative for culturing C. elegans have been made. However, the mechanism by which the filter feeder C. elegans obtains nutrients from these liquid media is not known. Using a fluorescence-activated cell sorting based approach, we demonstrate growth in all past axenic C. elegans media to be dependent on the presence of previously unknown particles. This particle requirement of C. elegans led to development of liposome-based, nanoparticle culturing that allows full control of nutrients delivered to C. elegans.

Segmenting Microscopy Images of Multi-Well Plates Based on Image Contrast.

Image segmentation is a key process in analyzing biological images. However, it is difficult to detect the differences between foreground and background when the image is unevenly illuminated. The unambiguous segmenting of multi-well plate microscopy images with various uneven illuminations is a challenging problem. Currently, no publicly available method adequately solves these various problems in bright-field multi-well plate images. Here, we propose a new method based on contrast values which removes the need for illumination correction. The presented method is effective enough to distinguish foreground and therefore a model organism (Caenorhabditis elegans) from an unevenly illuminated microscope image. In addition, the method also can solve a variety of problems caused by different uneven illumination scenarios. By applying this methodology across a wide range of multi-well plate microscopy images, we show that our approach can consistently analyze images with uneven illuminations with unparalleled accuracy and successfully solve various problems associated with uneven illumination. It can be used to process the microscopy images captured from multi-well plates and detect experimental subjects from an unevenly illuminated background.

Bovine milk-derived exosomes from colostrum are enriched with proteins implicated in immune response and growth.

Exosomes are extracellular vesicles secreted by multiple cell types into the extracellular space. They contain cell-state specific cargos which often reflects the (patho)physiological condition of the cells/organism. Milk contains high amounts of exosomes and it is unclear whether their cargo is altered based on the lactation stage of the organism. Here, we isolated exosomes from bovine milk that were obtained at various stages of lactation and examined the content by quantitative proteomics. Exosomes were isolated by OptiPrep density gradient centrifugation from milk obtained from cow after 24, 48 and 72 h post calving. As control, exosomes were also isolated from cows during mid-lactation period which has been referred to as mature milk (MM). Biochemical and biophysical characterization of exosomes revealed the high abundance of exosomes in colostrum and MM samples. Quantitative proteomics analysis highlighted the change in the proteomic cargo of exosomes based on the lactation state of the cow. Functional enrichment analysis revealed that exosomes from colostrum are significantly enriched with proteins that can potentially regulate the immune response and growth. This study highlights the importance of exosomes in colostrum and hence opens up new avenues to exploit these vesicles in the regulation of the immune response and growth.

Quinoa Seed Lowers Serum Triglycerides in Overweight and Obese Subjects: A Dose-Response Randomized Controlled Clinical Trial.

Background: Quinoa (Chenopodium quinoa) is a pseudo-cereal originally cultivated in the Andean region. The popularity of its seeds has increased in recent years due to the claims of health benefits and superfood qualities. Studies to date on the health benefits of quinoa have been restricted to animal models, and the results provide weak to moderate evidence to support improved plasma lipid profiles. Clinical trials in humans to examine the claims of health benefits of quinoa are limited to a few prospective studies and one randomized trial carried out in postmenopausal women. To our knowledge, no studies have been conducted in the general population. Objective: The objective of this randomized clinical trial was to investigate the effect of different quinoa doses (25 and 50 g/d) on body composition, serum lipids and hormones, and nutrient intakes in overweight and obese humans. Methods: This was a dose-response randomized, controlled, single-blind trial with a parallel design (1 control and 2 treatment groups) that compared the effect of 25 and 50 g quinoa/d in 50 overweight and obese participants over a 12-wk intervention period. Results: Body composition, nutrient intake, and total, LDL, and HDL cholesterol were not significantly altered by quinoa consumption (P > 0.05). Mean serum triglyceride (TG) concentration was reduced significantly in the 50-g quinoa group from 1.14 to 0.72 mmol/L at 12 wk (P < 0.05). The prevalence of metabolic syndrome (MetS) was also reduced in this group by 70%. No significant changes in TGs were observed in the control and 25-g quinoa groups. The prevalence of MetS was reduced by 40% (from n = 7 at baseline to n = 4 at 12 wk) in the 25-g group. Conclusions: The consumption of 50 g quinoa/d lowers serum TGs in overweight and obese participants and reduces the prevalence of MetS. This trial was registered at clinicaltrials.gov as UTN U1111-1175-470.