Natural Diet Research Articles

Development of <i>Acomys cahirinus</i> in the laboratory conditions

The Cairo spiny mouse (Acomys cahirinus) is a unique animal model for studying ontogenesis and regeneration. At the same time, the features of its biology, in particular, the small number of pups in the litter, significantly complicate research work. The aim of the article was to study the behavior and reproduction of the Cairo spiny mice and to create the reproductive nucleus of the colony in our laboratory. This article describes the husbandry of Cairo spiny mice, and techniques of working with them, such as optimizing the diet and housing conditions, handling and marking for individual identification, and also some reproductive parameters of the colony. We have optimized the animal diet by adding dry arthropods, an important component of the spiny mice natural diet, as well as enriched the environment by placing to each cage the running wheels, tunnels and houses. As a result, an increase in the number of animals was obtained by more than 50% over 9 months; the overall survival rate of the offspring was 98%.

Considerations on amino acid patterns in the natural felid diet: a review

Considerations on amino acid patterns in the natural felid diet: a review

Parasitism by Aleiodes ceres Shimbori, 2023 (Hymenoptera: Braconidae) of three species of Spodoptera Guenée, 1852: effects of preferential instar and host diet

AbstractA recently discovered koinobiont parasitoid species, Aleiodes ceres Shimbori, 2023, proved to be a promising biological control agent for larvae of Spodoptera cosmioides (Walker, 1858), S. eridania (Stoll, 1782), and S. frugiperda (J.E. Smith, 1797), all well-known pests that cause critical damage to soybean and corn crops. This study investigated the potential of parasitism by A. ceres in these three species, including different instars (1st, 2nd, 3rd, and 4th instar) and diets (artificial and natural). Parasitism was highest when it occurs in the second instar for all three host species. The egg-to-pupa period of A. ceres was shorter in the second and third instars in relation to the first instar. Parasitism was substantially enhanced by the use of natural diets (soybean and corn leaves) compared with the artificial diet in all three species of the Spodoptera complex, suggesting a possible allelochemical interaction. Based on the results from the three host species, the potential for control of Spodoptera spp. by A. ceres was evident.

Histochemical Characterisation of the Turquoise-Fronted Parrot (Amazona aestiva) Digestive Tract.

Amazona aestiva, a member of the Psittacidae family, belongs to the genus Amazona. These animals are endowed with adaptations in their digestive systems that allow a natural diet composed of seeds and fruits, with anatomical characteristics that facilitate the acquisition and use of nutrients from these food groups. Although it is an important species, no previous information is available regarding the histology and histochemistry of its digestive tract. This study aimed to describe the morphological and histochemical characteristics of the digestive tract of this species. Fragments of the tongue, oesophagus, crop, proventriculus, ventriculus, small intestine, large intestine, liver and pancreas were collected from seven specimens without any clinical alterations in the digestive tract. A. aestiva's digestive tract observed the presence of an extremely developed tongue, a proventriculus with more delicate walls and a ventricle with less-developed musculature. Here, we present a detailed morphological and histochemical description of the Turquoise-fronted Parrot's digestive tract.

Tolerance and efficient metabolization of extremely high ethanol concentrations by a social wasp

Ethanol, a natural by-product of sugar fermentation, can be found in various fruits and nectar. Although many animals routinely consume ethanol in low concentrations as part of their natural diets, its inherent toxicity can cause severe damage. Even species particularly well adapted to ethanol consumption face detrimental effects when exposed to concentrations above 4%. Here, we investigated the metabolism of ethanol and its impact on survival and behavior in the Oriental hornet (Vespa orientalis), a social wasp that naturally consumes ethanol. We show that chronic ethanol consumption, even at concentrations as high as 80%, had no impact on hornet mortality, construction behavior, or agonistic behavior. Using 13C1 labeled ethanol, we show that hornets efficiently metabolized ingested ethanol and at a much higher rate than honey bees. The presence of multiple copies of the alcohol dehydrogenase (NADP+) gene in the Vespa genera suggests a potential mechanism for ethanol tolerance. These findings support the hypothesis that the mutualistic relationship between ethanol-producing organisms and vespid hosts may be at the origin of their remarkable capacity to utilize and metabolize ethanol.

From wild to captive: Understanding the main nutritional diseases of sharks in public aquariums.

The establishment of a well-adapted and accurate feeding regimen is a fundamental determining factor in the maintenance of shark species in captivity. Replicating the natural diet in captivity is commonly accepted and recommended. Given the diverse nutritional composition of prey, supplementation may become necessary. The captive environment poses unique challenges, making sharks susceptible to an array of health issues, including numerous diseases. Mitigating these risks demands detailed husbandry practices, an appropriate physical environment and a balanced diet. Supplementation, encompassing vitamins and minerals, becomes imperative for the provision of essential nutrients. This complexity has rendered the formulation of an adapted feeding plan for aquarists exceptionally challenging. The scarcity of information in these species adds to the issue, mandating extrapolation from various shark groups and to species with analogous characteristics. This literature review concentrates predominantly on benthic and pelagic shark species prevalent in contemporary aquariums. The central argument posits that dietary choices in captivity rely on factors such as availability, quality and consistency of supply. The advocated approach highlights the importance of a balanced, diverse feeding that closely mirrors natural diets. It is then crucial to emphasize that these are general guidelines, and the specific dietary requisites may diverge between shark species. Collaborating with experts in marine biology, shark husbandry and veterinary care is imperative for the formulation and perpetuation of an adapted diet for captive sharks.

Effects of artificial diets on lipid and glucose metabolism, antioxidative capacity, and inflammation in the liver of mandarin fish (Siniperca chuatsi)

The mandarin fish (Siniperca chuatsi) is a typical carnivorous fish, which has been able to consume artificial diets after domestication in recent years. However, the potential health consequences of artificial diets in mandarin fish remain unclear. This study aimed to elucidate the molecular mechanisms underlying these concerns. Fish (initial weight: 25.1 ± 0.1 g) were fed with natural (CON group) or artificial diets (AF group) for 8 weeks. Each diet was randomly distributed to sextuplicate circular tanks (300 L) with 40 fish in each tank. The transcriptome analysis revealed significant changes in metabolism-related pathways, particularly those involved in lipid and carbohydrate metabolism. Further investigation confirmed that the artificial diets significantly increased hepatic triglyceride content and fatty acid synthase activity. The artificial diets also significantly increased hepatic glycogen and glucose-6-phosphatase activity. Furthermore, the artificial diets significantly increased hepatic malondialdehyde levels, indicating increased oxidative stress. Antioxidant defense enzyme activities and the expression of antioxidant stress-related genes were significantly decreased. Additionally, the artificial diets significantly increased the expression of proinflammatory genes, including interleukin 1 beta and interferon-gamma. These findings collectively demonstrated that the artificial diets disrupted hepatic lipid and glucose metabolism, leading to oxidative stress and inflammation, thus affecting the health status of mandarin fish.

Comparative Study of Fatty Acid Composition of Muscles of Atlantic Cod (Gadus morhua Linnaeus, 1758) with Natural Diet and Feeding near Salmon Farms

Coastal aquaculture and local fisheries interact in shared marine environments, influencing each other synergistically and/or antagonistically. Salmon farming, notably with open-net sea cages along the Norwegian coast, attracts wild fish due to increased food availability from uneaten feed, but it also exposes wild fish to farm emissions like waste and toxic chemicals (de-lice treatments, antifouling and medical agents). The attraction behaviour of wild fish can impact fatty acid composition in fish tissues, influenced by the high terrestrial fat content in salmon aquafeed. We study how the Atlantic cod, aggregating around salmon farms in a subarctic fjord in Northern Norway, can be affected, potentially altering their natural diet and fatty acid profiles. Our study compares the muscle-tissue fatty acid compositions of cod caught near aquaculture facilities (impact) versus fish caught in neighbouring fjords (control), and we hypothesise decreased omega-3 fatty acids near farms. The analysis revealed no significant differences in the fatty acid concentrations or categories between the impacted and control fish, challenging our initial expectations. However, differences were found for C18:1(n9)t (elaidic acid), with a higher value in the impacted fish. These findings suggest that salmon farming’s influence on cod’s fatty acid profiles in the flesh (i.e., relevant for the nutritional quality of the fillets that consumers eat) may be limited or minimal despite their aggregative behaviours around farms. The threshold levels of salmon feed consumed by wild cod before it affects the quality and survival of, e.g., sperm or other life stages, are not known and require new investigations. This study underscores the complexity of interactions between aquaculture and wild fisheries, impacting both ecological dynamics and consumer perspectives on seafood quality and health benefits.

Contrastive learning explains the emergence and function of visual category-selective regions.

Modular and distributed coding theories of category selectivity along the human ventral visual stream have long existed in tension. Here, we present a reconciling framework-contrastive coding-based on a series of analyses relating category selectivity within biological and artificial neural networks. We discover that, in models trained with contrastive self-supervised objectives over a rich natural image diet, category-selective tuning naturally emerges for faces, bodies, scenes, and words. Further, lesions of these model units lead to selective, dissociable recognition deficits, highlighting their distinct functional roles in information processing. Finally, these pre-identified units can predict neural responses in all corresponding face-, scene-, body-, and word-selective regions of human visual cortex, under a highly constrained sparse positive encoding procedure. The success of this single model indicates that brain-like functional specialization can emerge without category-specific learning pressures, as the system learns to untangle rich image content. Contrastive coding, therefore, provides a unifying account of object category emergence and representation in the human brain.

502 Cat and mouse: The effect of consuming four different diet formants (intact mice, raw, canned wet and kibble) on energy expended to consume a meal and immediately post-prandial in domestic cats

Abstract Cats are obligate carnivores; however, we feed them a variety of different diet formats without a clear understanding of feeding behavior and metabolism among diet formats. Whole-prey or raw diets may mimic a more natural diet and require more energy to consume. However, there is currently a dearth of literature examining feline energy expenditure (EE) during the consumption of and immediate post-prandial period when fed different diet formats. The present study aimed to investigate differences in the energetics of adult cats consuming four different diet formats in isocaloric offerings: raw intact mice, commercial raw, canned wet, and kibble diets. Adult neutered male cats [n = 12; body weight (BW) = 4.82 ± 0.164 kg) were used in a 4 x 4 replicated Latin square design and adapted to consuming each diet format before the initiation of the study. Following a 2-d adaptation period, cats were fed 25% of their daily caloric requirement (50.77 ± 1.549 kcal) in indirect calorimetry chambers in which VO2 and VCO2 exchange were measured. Energy expenditure (kcal/BW0.67 kg) was calculated for the consumption period, 15 min immediately post-prandial and 2 h post-prandial. Respiratory gases were measured for one fasted reading, followed by the first feeding. During each feeding, measurements were taken during the consumption period and 15 min post-prandial. For the following 2 h, respiratory gases were measured every 25 min for an additional 4 measures of respiratory gases. All data were analyzed using a generalized linear mixed model considering the effects of treatment, time and their interaction as fixed, and the effects of cat and period as random. A spatial power covariance structure was used to model repeated measures. Significance was considered at P < 0.05 and Tukey’s post-hoc test was performed to separate means. Energy expenditure during consumption and 15 min post-prandial was similar among treatments, and EE for 15 min post-prandial was greater than EE during consumption (P < 0.001). During the 2 h post-prandial, EE for the mice diet was greater than the kibble and canned wet diets (P < 0.001), while EE for the raw diet was only greater than the kibble diet (P < 0.001). Energy expenditure was similar between the kibble and canned wet diets (P = 0.919) and between the mice and raw diets (P = 0.598). Among all treatments and time periods, the mouse diet had the greatest mean EE. An increase in EE during the feeding period and post-prandial could benefit sedentary indoor cats who may be in positive energy balance. Feeding cats a naturalistic diet, such as intact mice or a raw diet, may increase activity levels and EE, but the longer-term effects of these feeding formats on energy balance need to be explored.

291 Isoenergetic reduction of dietary macronutrients changes body composition and physical activity in cats, regardless of body condition, when fed to maintenance

Abstract Commercial extruded cat foods deviate noticeably from the natural diet of wild cats and contain greater carbohydrate and less protein. This alteration in macronutrient distribution is postulated as a potential factor in feline obesity, yet the precise role of carbohydrates in either predisposing to, or treating, obesity in cats remains inconclusive. This study explored the effects of diets differing in protein, fat, and carbohydrates (NFE) on physical activity and body composition when fed to adult male cats to maintain body weight (BW). Three extruded diets were formulated for adult maintenance according to AAFCO in an isoenergetic approach using the same ingredients in varying proportions: low-protein (LP; protein 28% of metabolizable energy [ME], fat 40% ME, NFE 32% ME), low-fat (LF; protein 42% ME, fat 30% ME, NFE 30% ME), or low-carbohydrate (LC; protein 36% ME, fat 41%ME, NFE 23% ME). Lean (n = 9) and obese (n = 9) adult male neutered cats were fed each diet for 4-wk in a 3 x 3 Latin square design. Physical activity was measured via actigraphy on d 15 to 21 of each period. On d 23 total tissue mass (TTM), body fat mass (BFM), lean soft tissue mass (LSTM), and bone mineral content (BMC) were assessed by dual energy x-ray absorptiometry. Daily food intake and weekly BW were recorded. Data were statistically analyzed in SAS Studio via the GLIMMIX procedure with diet and body condition (bc) as fixed effects and cat as subject. A Tukey post-hoc analysis was performed to assess multiple comparisons when significant (P < 0.05). Body weight (Pbc < 0.0001), TTM (Pbc < 0.0001), BFM (Pbc < 0.0001), LSTM (Pbc < 0.0001), and BMC (Pbc = 0.004) were greater in obese compared with lean cats. Regardless of body condition, LSTM was greater in cats consuming the LF diet (P = 0.010). Daily physical activity was similar between lean and obese cats; however, activity as a ratio of light:dark activity was greater for lean cats compared with obese (Pbc = 0.027). Additionally, cats were more active during dark hours when fed LC and LF (Pdiet = 0.016), though no difference was observed for activity during light hours (P = 0.452). These findings support previous observations regarding body composition disparities between lean and obese cats. Contrary to previous reports, no discernible distinctions in voluntary physical activity were noted between lean and obese cats. In previous studies, both high-carbohydrate and high-fat diets reduced voluntary physical activity when fed to maintain BW which was attributed to a potential alteration in mood and energy levels seen in other species. An increase in physical activity in cats consuming the LF diet could suggest a similar pattern. Future research should explore the metabolic implications of varied macronutrient distributions to expand upon the physiological insights presented herein. Funding for this study was provided by Champion Petfoods, Mitacs Accelerate, and the Natural Sciences and Engineering Council of Canada.

The natural diet of Prolatilus jugularis inhabiting Lessonia trabeculata kelp forests of south-central Chile

Kelp forests support species-rich food webs that predator-prey interactions may sustain. Here, we analyze prey availability and stomach contents of the predatory fish Prolatilus jugularis in an unexplored subtidal kelp forest of Lessonia trabeculata in south-central Chile. In the kelp forest, 42 invertebrate taxa and 1016 individuals were observed. In the diet of P. jugularis, 21 taxa and 130 individuals were identified. Crustacea, particularly amphipods, were the dominant and more frequent taxa in the kelp forest and stomach contents. Annelida and Mollusca were also present in the kelp forest and diets but were less abundant. We did not find a statistically significant correlation between kelp forest and stomach-content prey abundances and frequencies. Also, dominance structure significantly differed between kelps and stomach contents. Our results indicate that P. jugularis could feed in other habitats outside the survey area. Seven predatory fish were sampled in the kelp forest. Pinguipes chilensis was the dominant fish, with 65% of the total fish biomass, followed by P. jugularis with 20%.

Comprehensive review of toxicological risks in wild game consumption

The consumption of wild game meat, rooted in cultural traditions and increasingly favored as a natural food source, presents both nutritional benefits and toxicological challenges. While wild game offers a rich source of protein and essential nutrients, it also carries unique risks associated with environmental contaminants, naturally occurring toxins, and zoonotic diseases. This review provides a comprehensive analysis of these toxicological hazards, drawing from a wide range of scientific literature. It examines the origins of toxins in wild game, including heavy metals, pesticides, and other environmental pollutants, as well as the risks posed by animals' natural diets and traditional hunting methods. Additionally, the review addresses the public health implications of consuming contaminated wild game and offers strategies for mitigating these risks. By exploring the complex interplay between wild game consumption and toxicology, this review aims to inform both consumers and public health professionals, emphasizing the importance of safe practices in the handling and preparation of wild game meat to minimize potential health hazards.

Advancing Abalone Nutrition: The Science and Benefits of Formulated Feeds

The aquaculture industry has increasingly turned to formulated feeds to enhance the growth and health of abalone, a valuable marine species. This paper reviews the current state of research on abalone nutrition, focusing on the development and benefits of formulated feeds. The nutritional requirements of abalone are examined, highlighting the essential macro- and micro-nutrients needed for optimal growth. Various ingredients and additives used in feed formulations are discussed, along with the effectiveness of different feed types. The performance of formulated feeds is compared to natural diets, considering factors such as growth rates, health indicators, and environmental impact. Challenges in digestibility, palatability, and cost-effectiveness are addressed, and recent innovations in feed formulation techniques are explored. The review identifies gaps in current research and suggests directions for future studies to further advance abalone nutrition. Overall, formulated feeds are shown to offer significant benefits in terms of growth performance and sustainability, making them a promising solution for the future of abalone aquaculture.

Short-Term Chronic Toxicity of Copper to Hyalella azteca: Contrast in Terms of Equilibrating Diet, Diet Type, and Organic Matter Source.

The most up-to-date regulatory guidelines for establishing acute and chronic numeric limits for copper in freshwaters are based on a biotic ligand model for various species, but the model for Cu lacks data on dietary uptake. In addition, some common macroinvertebrate toxicity assay parameters are less representative of the ecosystem. We investigated the effects of diet and its type in the experimental setup and as an exposure pathway to an established amphipod (crustacean) Hyalella azteca (H. azteca) for Cu toxicity assays. We also investigated another overlooked aspect, the organic matter (OM) source. Our experiments compared the toxicity of pre-equilibrated and unequilibrated natural diets and a laboratory-favored diet in effluent and stormwater sources of organic matter adjusted to standard water characteristics. The experiments indicated a more toxic effect of the pre-equilibrated diet and natural dietary sources, and less toxic effects in the presence of effluent OM compared with stormwater OM, shifting LC50 or EC20 values by as much as 67% compared with the controls. The use of a pre-equilibrated natural diet in toxicity assays provides the advantage of producing toxicity data more representative of field conditions. Considering organic matter type, especially in dietary exposures, will better predict toxicity, accounting for copper complexation with OM from different sources and partitioning to the food supply. Adapting these ecologically relevant parameters in whole effluent toxicity testing or other assays will also provide safer regulatory oversite of discharges to surface waters.

The analysis of natural forage of blue smimming crab (Portunus pelagicus Linnaeus, 1758) on the east coast of Pangandaran, West Java

Continuous use of blue swimming crab (Portunus pelagicus) without any control can cause population decline which leads to damage to the stability of the marine ecosystem, especially in East Coast Pangandaran, therefore cultivation is needed. In aquaculture, it is necessary to provide the right feed by knowing its natural diet. This study aimed to determine the natural diet of blue swimming crabs. The method used was descriptive analysis. The parameters observed were carapace width, gastric weight, the composition of natural diet. The relationship between the carapace width and gastric weight was analyzed by simple regression while the main type of natural diet was known by calculating the percentage of food composition. The relationship between carapace width and gastric weight was positive. Based on the composition found in crab gastric, there were 5 types of natural foods consisting of crustaceans (28.35%), meat (25.37%), mollusk (18.65%), fish (15.67%), and undefined material (UM) (4.47%). It is revealed that crabs are carnivores and scavengers, pose significant relationship between their size and gut content weight. It was also found that the composition of female crab feed was generally higher than that of males.

Growth and Color Brightness of Glofish Fed Natural and Artificial Diets In Cianjur District, West Java Province

It is known that natural feed, in addition to being preferred because it moves, also has dyes that make the color of ornamental fish more contrasting than artificial feed. The purpose of this study is to find out which type of natural feed (Silk Worm (Tubifex sp.), Daphnia sp., Frozen Blood Worm) and artificial feed, which is more effective against the growth and brightness of the color of Glofish Starfire Red, which will be carried out in August 2024-October 2024 in Cianjur Regency, West Java Province. The study was conducted using an experimental method using a Complete Random Design (RAL) with 4 treatments and 3 replicates. The treatment given is as follows: A (Research using natural feed Daphnia sp, B (Research using natural feed Bloodwarm/Chironomidae, C (Research using natural feed Tubifex sp), D (Research using artificial feed). The parameters observed were Absolute Length Growth, Absolute Weight Growth, Specific Growth Rate and Color Brightness, to analyze the color brightness of Starfire Red fish using https://redketchup.io color comparison.

Effect of alternative natural diet on microplastic ingestion, functional responses and trophic transfer in a tri-trophic coastal pelagic food web

The patchy distribution of microplastics (MP) and their size range similar to planktonic organisms, are likely to have major ecological consequences, through MP ingestion, food dilution, and transfer across trophic levels. Our study applied a community module using tritrophic food chain with zooplankton as prey, and a planktivorous seabass fry as predator. We conducted a series of feeding experiments and recorded the direct uptake of MP under six different concentrations ranging from 25 to 800 particles L−1. We also estimated the indirect transfer of MP via trophic link. The ingestion rates for Brachionus plicatilis, Mesocyclops isabellae, and Lates calcarifer, were 3.7 ± 0.3 MP ind−1 min−1, 1.69 ± 0.1 MP ind−1 min−1, and 3.51 ± 0.52 MP ind−1 h−1, respectively. In the presence of a natural diet, rotifers and copepods ingested significantly lower number, whereas, fish fry ingested a higher number of MP, suggesting further vulnerability to the consumers of MP-contaminated fish and potential biomagnification at higher trophic levels. Overall, the MP uptake rate increased with increasing concentration, and finally leveled off, indicating a type II functional response to MP concentration. The presence of natural diet led to a lower Km value. In the indirect transfer experiment, 74 % of B. plicatilis and 78 % of M. isabellae individuals were contaminated with MP, when offered as prey. Brachionid mastax and MP particles were observed in the gut of copepods. The fish fry gut content also recorded brachionid mastax, MP-contaminated copepods, and MP particles, showing direct evidence of trophic transfer pointing to a cascading effect on higher trophic levels including humans via piscivory.

From traditional to industrial use of insects as feed: a review

Abstract Insects are part of the natural diet of fish and poultry species and to a lesser extent of pigs, dogs and cats. In traditional farming, poultry gather their food in a free roaming manner, and insects are part of the diet. Similarly, a large fraction of the diet of freshwater fish consists of aquatic insects. These features are exploited by farmers all over the world, as feed costs are high. For example, farmers lure termites to baskets filled with organic matter, and the insects are then fed to chickens. They also employ light sources above fishponds to attract insects for their fish. More sophisticated methods are, for example, attracting naturally occurring houseflies to containers filled with organic waste, e.g. manure. The captured maggots or pupae are then fed to poultry. We discuss the following insect groups as feeds for poultry, pigs, fish, dogs and cats: bees, caterpillars, cockroaches, flies, grasshoppers and termites. Feed for poultry can also consist of insect pests, which are then controlled at the same time, for example ducks to control rice pests. Moreover, leftovers from the silk industry can be used to feed chickens, pigs and fish. Insects are also commonly used as bait for fishing. The interest in a more industrial production of insects such as the black soldier fly and housefly as animal feed started in the 1970s. In the last 15 years, large-scale rearing of insects for animal feed has taken off, with the industry receiving more than 1.5 billion dollars in investment. The market is expanding, the legislation is becoming more conducive, while academic interest is increasing exponentially. The environmental, nutritional and functional benefits of insects as feed are becoming more and more recognized. Insects are poised to play an increasingly prominent role in shaping the future of animal feed production.

Behaviour of Tunisian Psammomys obesus fed high-calorie diets: biochemical disturbance and histopathological alterations

This work investigated the biochemical disturbances and histological alteration in Psammomys obesus animal model fed different high calorie diets (HCDs) during three months. Four diets were used: a low-calorie natural diet, Chenopodiaceae halophyte plant used as control (LCD), a high standard carbohydrate diet rich in protein, HCD 0, a high carbohydrate diet rich in two concentrations of fat, HCD 1 and HCD 2. All animals having received HCDs developed dyslipidemia after one month of experiment with distinction of different sub-groups developing or not obesity and diabetes. HCDs induced a remarkable increasing in blood cholesterol, LDL-cholesterol and triglyceride levels indicating a fast induction of dyslipidemia and a significant increase of aminotransaminases activities revealing a pronounced hepatotoxicity. Animal developing diabetes showed a severe hepatic injury, a degeneration of the adipose tissue and a significant reduction of retinal thickness. P. obesus seems to be an excellent animal model to investigate nutritional metabolic diseases.