Attraction of entomopathogenic nematodes to black truffle and its volatile organic compounds: A new approach for truffle beetle biocontrol.

The European truffle beetle, Leiodes cinnamomeus, is the most important pest in black truffle (Tuber melanosporum) plantations. Entomopathogenic nematodes (EPNs) are a promising biological control agents against L. cinnamomeus. EPNs may employ multiple sensory cues while seeking for hosts, such as volatile organic compounds (VOCs) and CO2 gradients. We report for the first time the attraction of EPNs to truffle fruitbodies, and identified some VOCs potentially playing a key role in this interaction. We conducted olfactometer assays to investigate the attraction behavior of Steinernema feltiae and Steinernema carpocapsae towards both T. melanosporum fruitbodies and larvae of L. cinnamomeus. Subsequently, a chemotaxis assay using agar plates was performed to determine which of the 14 of the main VOCs emitted by the fruitbodies attracted S. feltiae at low (0.1 %) and high (mg/100 g truffle) concentrations. Both EPN species were attracted to mature fruitbodies of T. melanosporum, which may enhance the likelihood of encountering L. cinnamomeus during field applications. L. cinnamomeus larvae in the presence of truffles did not significantly affect the behavior of EPNs 24 h after application, underscoring the importance of the chemical compounds emitted by truffles themselves. Chemotaxis assays showed that four long-chain alcohol compounds emitted by T. melanosporum fruitbodies attracted S. feltiae, especially at low concentration, providing a first hint in the chemical ecology of a little-studied ecological system of great economical value. Further studies should be conducted to gain a finer understanding of the tritrophic interactions between T. melanosporum, EPNs, and L. cinnamomeus, as this knowledge may have practical implications for the efficacy of EPNs in the biological control of this pest.

Hepatotoxicity due to dietary supplements: state-of-the-art, gaps and perspectives.

Food supplements are products intended to complement the normal diet and consist of concentrated sources of nutrients or other substances with a nutritional or physiological effect. Although they are generally considered safe if the manufacturer's recommendations are followed, many of them have shown hepatotoxic properties. This can cause many diseases (e.g. steatohepatitis and cirrhosis) characterized by progressive damage and malfunction of the liver that in the long term can lead to death. A review of the literature was carried out to elucidate which dietary supplements have been associated with cases of hepatotoxicity in recent years, with emphasis on those relevant to the consumer and the new trends (e.g. cannabidiol). It has been reported that the supplements described as hepatotoxic are mainly of botanical origin (e.g. green tea or turmeric) and those used in sports (mainly anabolic androgenic steroids). There is a great variability of compounds described as causing liver damage, although sometimes it is not possible to identify them, because they are contaminants or adulterants of the products. In addition, the prevalence of toxic effects after the administration of supplements is difficult to define due to underreporting and the lack of specific studies. Globally regarding hepatotoxicity of dietary supplements, there is a paucity of well-conducted clinical trials on the efficacy of these compounds and the frequency of related liver damage, as the use of these products is largely uncontrolled.

In vivo evidences of the health-promoting properties of bioactive compounds obtained from olive by-products and their use as food ingredient.

Olea europaea L. is the source of virgin olive oil (VOO). During its extraction, a high amount of by-products (pomace, mill wastewaters, leaves, stones, and seeds) is originated, which possess an environmental problem. If the generation of waste cannot be prevented, its economic value must be recovered and its effects on the environment and climate change must be avoided or minimized. The bioactive compounds (e.g., phenols, pectins, peptides) of these by-product fractions are being investigated as nutraceutical due to the beneficial properties it might have. In this review, the aim is to summarize the in vivo studies carried out in animals and humans with bioactive compounds exclusively obtained from olive by-products, aiming to demonstrate the potential health benefits these products can exert, as well as to describe its use in the food industry as bioactive ingredient. Several food matrices have been fortified with olive by-products fractions, leading to an improvement of properties. Animal and human studies suggest the benefits of ingesting olive-derived products to promote health. However, the investigation until now is scarce and consequently, well-designed human studies are required in order to fully address and confirm the safety and health-promoting properties of olive oil by-products.

Natural occurrence of entomopathogenic nematodes (Steinernema and Heterorhabditis) and Pristionchus nematodes in black truffle soils from Spain.

The European truffle beetle Leiodes cinnamomeus is the most important pest in black truffle (Tuber melanosporum) plantations. Current control methods against it are inefficient, so entomopathogenic nematodes (EPNs) could play an important role in their population regulation due to their efficacy against many soil-dwelling insect pests. A survey of EPNs and Pristionchus nematodes was conducted in truffle soils of Spain, considering environmental and physical-chemical soil factors. A total of 164 soil samples were collected from forests, productive plantations and null-low productive plantations, representing three distinct black truffle-growing habitat types. EPNs were isolated from seven soil samples (4.3%); four nematodes were identified as Steinernema feltiae and three as Heterorhabditis bacteriophora. Both species were sampled in three types of soil texture (loam, sandy loam or sandy clay loam), characterized by alkaline pH (7.5 to 8.5) and high organic matter (2.1-11.04%). The presence of these EPNs was influenced by habitat type and organic matter content. Pristionchus nematodes were isolated from truffle soil, around truffle fruit bodies and under the elytra of L. cinnamomeus, with Pristionchus maupasi being the most commonly identified species. No significant associations were found between environmental and soil factors and the occurrence of Pristionchus nematodes. These nematodes were found in alkaline soils (pH 7.75 to 8.7), across all seven sampled soil textures, with variable organic matter content (0.73%-5.92%). The ecological trends and the presence of Pristionchus may affect the occurrence of EPNs and their prospective use as biological control agents against L. cinnamomeus in black truffle plantations.

'Business can't stop.' Women engaged in prostitution during the COVID-19 pandemic in southern Spain: A qualitative study.

A detailed analysis was made of the experience of women engaged in prostitution during the state of emergency due to the COVID-19 virus through a phenomenological study. Eleven telephone interviews were conducted with women engaged in prostitution. It was found that confinement had increased the vulnerability of these women. Business has not stopped and they continue to work fearful of being infected and with increased abuse from the 'clients'. Economic necessity and pressures from the organisations that exploit them are the main reasons for engaging in prostitution during the pandemic.

Evaluation of serological diagnostic tests of human brucellosis for prevention and control in Mexico.

Brucellosis is a zoonosis mainly present in developing countries. The WHO reports 500,000 new cases every year. From 2012 to 2016, 13,677 cases were reported in Mexico, with 2.00 to 2.64 rate per 100,000 inhabitants. To analyze the diagnostic algorithm of brucellosis in Mexico, we compared the commercial laboratory tests ELISA, Brucellacapt®, and lateral flow test (LFT) in a study of 473 individuals from two endemic Mexican populations. All patients were treated in first-level medical units for presenting brucellosis compatible symptoms and without a history of the disease. Clinical-epidemiological information was gathered and initial serum samples were obtained to react with anti-Brucella antibodies; subsequent samples were collected at follow-up treatment visits. Using the Rose Bengal screening, we found 165 negative samples and 308 positive reactive samples, of which 222 cases were confirmed and 234 were positive on at least one marker (IgG or IgM) or LFT. When Brucellacapt® was used, similar results to those observed with the conventional algorithm were found as judged by the Cohen's kappa coefficient (κ) (0.813, 95% CI 0.7788-0.8472). Similar κ indices between conventional algorithm and ELISA pair were found, 0.7038 (95% CI 0.6555-0.7521), representing high similarity between both groups of diagnosis. We conclude that conventional serodiagnoses, Brucellacapt® and LFT, presented inconclusive results and poor correlation between them. By contrast, ELISA test pair (IgG + IgM) presented high correlation with the conventional algorithm and greater capacity for correct positive and negative classification.

[ALFA-1 antitrypsin deficiency, a commonly missed cause of chronic liver disease in theadult: presentation of 9 cases with review of current literature]. / Déficit de Alfa-1 antitripsina, una causa de hepatopatía crónica comúnmente insospechada en el adulto: presentación de 9 casos con revisión de literature.

INTRODUCTION: Alfa 1-antitrypsin deficiency is one of the most prevalent genetic diseases in the human being, sadly it is not a commonly suspected clinical entity. With more than 100 known mutations, those associated with hepatic disease are the Z homocygote allele mutations in the gene a1AT which occur in every 2000-3500 births. Opposing to the pulmonary disease, in which de sequelae are caused by the deficit of this protein which in turn fastens the enzymatic destruction of the airway microstructure, the hepatic compromise is secondary to the intracellular accumulation of the aberrant misfolded protein. This accumulation causes cellular damage, hepatitis, fibrosis, cirrhosis and hepatocellular carcinoma through activation of a series of mechanisms which culminate in hepatocitary apoptosis, regeneration and chronic cellular injury. MATERIALS AND METHODS: 9 cases of confirmed a1AT deficiency are presented, from different ages ranging from adolescence through elderly patients. RESULTS: Each of one of them with different clinical presentation going from asymptomatic liver enzyme elevations to transplanted cirrhosis in which the diagnosis was post procedural. CONCLUSION: We comment about the management of the chronic liver disease and the evolution of these patients through time in the liver clinic.

Infectivity of Steinernema carpocapsae and S. feltiae to Larvae and Adults of the Hazelnut Weevil, Curculio nucum: Differential Virulence and Entry Routes.

We investigated the existing susceptibility differences of the hazelnut weevil, Curculio nucum L. (Coleoptera:, Curculionidae) to entomopathogenic nematodes by assessing the main route of entry of the nematodes, Steinernema carpocapsae strain B14 and S. feltiae strain D114, into larvae and adult insects, as well as host immune response. Our results suggested that S. carpocapsae B14 and S. feltiae D114 primarily entered adult insects and larvae through the anus. Larvae were more susceptible to S. feltiae D114 than S. carpocapsae B14 and adults were highly susceptible to S. carpocapsae B14 but displayed low susceptibility to S. feltiae D114. Penetration rate correlated with nematode virulence. We observed little evidence that hazelnut weevils mounted any cellular immune response toward S. carpocapsae B14 or S. feltiae D114. We conclude the differential susceptibility of hazelnut weevil larvae and adults to S. carpocapsae B14 and S. feltiae D114 primarily reflected differences in the ability of these two nematodes to penetrate the host.

Access to the Health Care System of Undocumented Moroccan Migrant Slum Dwellers in Southern Spain: A Qualitative Study.

Spain has grown economically due to the recent boosts in the industrial sector, the agricultural sector, construction and services. Those who carry out agricultural tasks are mainly undocumented immigrants living in marginal neighborhoods. OBJECTIVES: to know the perception of undocumented Moroccan migrants living in marginal neighborhoods regarding access to the Public Health System. METHODS: A qualitative method with a phenomenological approach was used to get closer to the experience of the participants in the study. In this work, 24 semi-structured interviews were conducted following a guide with a set of open questions to facilitate an in-depth discussion of the topics of interest. The participants were given an informed consent form, which guaranteed anonymity and confidentiality regarding the information obtained. For this, codes were used to identify them. The data were stored, managed, classified, and organized with the ATLAS-ti 9 software. RESULTS: access and use of health services by the immigrants in the study was difficult due to communication problems related to language and culture, the discriminatory attitude and lack of cultural competence of health personnel, and the location of the neighborhoods (which were marginal far from urban centers), as well as the lack of transportation to health centers. CONCLUSIONS: it is an ethical imperative of the Health System to offer greater attention to the population in situations of extreme vulnerability, implement intercultural mediators and train health professionals in cultural competence.

Anxiety and Depression after Spinal Cord Injury: A Cross-Sectional Study.

Spinal cord injury (SCI) is a life-changing event that often results in chronic physical damage and challenges in maintaining a good quality of life as it affects every aspect of life. These situations require adjustment, increasing vulnerability to psychological disorders. The objective of this study was to evaluate the impact of SCI on psychological morbidity in individuals with subacute and chronic SCI. The present investigation was designed to determine the presence and extent of psychological complications following SCI. We used two reliable questionnaires and validated psychological assessments to study depression (BDI) and anxiety (STAI), a broad range of factors derived from SCI that may be predictors of certain psychological problems. The psychological assessment revealed alterations in depression and anxiety, although the data do not exceed those of previous investigations. No clear predisposing factors leading to certain psychological pathologies were found. In addition, individuals in the subacute and chronic stages differed in their scores. In individuals with SCI, identifying predictors of psychological problems is difficult, but premature assessment of mental state is essential. This early diagnosis of possible problems or changes at the mental level is fundamental and necessary to avoid possible alterations at the cognitive level and, of course, more serious mental complications.

Interaction Processes between Health Professionals and Moroccan Immigrant Women in Reproductive Healthcare: The Disagreement in the Encounter-A Qualitative Study.

INTRODUCTION: Spain is a multicultural society and has been defined by several authors as an immigrant-receiving country. Moroccan women of childbearing age constitute 28.20% of Moroccan immigrants. OBJECTIVES: describe the interaction processes that occur between health professionals and Moroccan immigrant women in reproductive healthcare. METHODS: Qualitative descriptive study based on Grounded Theory. Thirty immigrant women from Morocco and thirty-five health professionals participated in the study. Specific dimensions of analysis were defined and used to design the interview guide and focus groups. RESULTS: In the healthcare encounter, the construction of an effective communicative space between the people involved in it is essential; however, the language barrier and the interpersonal relationships characterized by silence in the encounter make a meaningful healthcare relationship difficult for those who participate in it. CONCLUSIONS: There are communication and relationship problems that alter healthcare and the professional-patient relationship which require the use of translation programs, the incorporation of intercultural meters, and the development of cultural competence in health professionals.

Food-derived vesicles as immunomodulatory drivers: Current knowledge, gaps, and perspectives.

Extracellular vesicles (EVs) are lipid-bound membrane vesicles released from cells, containing active compounds, which can be found in different foods. In this review, the role of food-derived vesicles (FDVs) as immunomodulatory drivers is summarized, with a focus on sources, isolation techniques and yields, as well as bioavailability and potential health implications. In addition, gaps and perspectives detected in this research field have been highlighted. FDVs have been efficiently extracted from different sources, and differential ultracentrifugation seems to be the most adequate isolation technique, with yields ranging from 108 to 1014 EV particles/mL. Animal studies show promising results in how these FDVs might regulate different pathways related to inflammation. Further investigation on the production of stable components in a cost-effective way, as well as human studies demonstrating safety and health-promoting properties, since scarce information has been reported until now, in the context of modulating the immune system are needed.

Production, characterisation, and biological properties of Tenebrio molitor-derived oligopeptides.

Three protein hydrolysates from Tenebrio molitor were obtained by enzymatic hydrolysis employing two food-grade proteases (i.e. Alcalase and Flavourzyme), and a complete characterisation of their composition was done. The digestion-derived products were obtained using the INFOGEST protocol. In vitro antioxidant activity and anti-inflammatory activities were evaluated. Tenebrio molitor flour and the protein hydrolysates showed a high ability to scavenge the DPPH radical (EC50 values from 0.30 to 0.87 mg/mL). The hydrolysate obtained with a combination of the two food-grade proteases could decrease the gene expression of pro-inflammatory genes after being digested. Furthermore, the peptidome was fully determined for the first time for T. molitor hydrolysates and digests, and 40 peptides were selected based on their bioactivity to be evaluated by in silico tools, including prediction tools and molecular docking. These results provide new perspectives on the use of edible insects as sustainable and not nutritionally disadvantageous food for human consumption.

Edible insects as a source of biopeptides and their role in immunonutrition.

Many edible insect species are attracting the attention of the food industry and consumers in Western societies due to their high content and quality of protein, and consequently, the potential to be used as a more environmentally friendly dietary source could be beneficial for humans. On the other hand, prevention of inflammatory diseases using nutritional interventions is currently being proposed as a sustainable and cost-effective strategy to improve people's health. In this regard, finding bioactive compounds such as peptides with anti-inflammatory properties from sustainable sources (e.g., edible insects) is one area of particular interest, which might have a relevant role in immunonutrition. This review aims to summarize the recent literature on the discovery of immunomodulatory peptides through in vitro studies from edible insects, as well as to describe cell-based assays aiming to prove their bioactivity. On top of that, in vivo studies (i.e., animal and human), although scarce, have been mentioned in relation to the topic. In addition, the challenges and future perspectives related to edible-insect peptides and their role in immunonutrition are discussed. The amount of literature aiming to demonstrate the potential immunomodulatory activity of edible-insect peptides is scarce but promising. Different approaches have been employed, especially cell assays and animal studies employing insect meal as supplementation in the diet. Insects such as Tenebrio molitor or Gryllodes sigillatus are some of the most studied and have demonstrated to contain bioactive peptides. Further investigations, mostly with humans, are needed in order to clearly state that peptides from edible insects may contribute to the modulation of the immune system.

Identification of the Bioavailable Peptidome of Chia Protein Hydrolysate and the In Silico Evaluation of Its Antioxidant and ACE Inhibitory Potential.

The incorporation of novel, functional, and sustainable foods in human diets is increasing because of their beneficial effects and environmental-friendly nature. Chia (Salvia hispanica L.) has proved to be a suitable source of bioactive peptides via enzymatic hydrolysis. These peptides could be responsible for modulating several physiological processes if able to reach the target organ. The bioavailable peptides contained in a hydrolysate obtained with Alcalase, as functional foods, were identified using a transwell system with Caco-2 cell culture as the absorption model. Furthermore, 20 unique peptides with a molecular weight lower than 1000 Da and the higher statistical significance of the peptide-precursor spectrum match (-10 log P) were assessed by in silico tools to suggest which peptides could be those exerting the demonstrated bioactivity. From the characterized peptides, considering the molecular features and the results obtained, the peptides AGDAHWTY, VDAHPIKAM, PNYHPNPR, and ALPPGAVHW are anticipated to be contributing to the antioxidant and/or ACE inhibitor activity of the chia protein hydrolysates.

Mediterranean Diet Combined with Regular Aerobic Exercise and Hemp Protein Supplementation Modulates Plasma Circulating Amino Acids and Improves the Health Status of Overweight Individuals.

Plant protein is considered a sustainable health-promoting strategy to prevent metabolic syndrome. Lifestyle changes (including dietary patterns and exercise) have been demonstrated to exert an effect on human health by modulating the biochemical status in humans. The objective of this study was to assess whether supplementation with hemp protein within a Mediterranean diet context together with exercise could help to ameliorate the metabolic statuses of patients prone to developing metabolic syndrome. For this study, 23 patients followed with Mediterranean diet and engaged in aerobic exercise according to the WHO's recommendations, while also being supplemented with hemp protein, for 12 weeks. A comparison of anthropometric, biochemical, and mineral data as well as amino acid values was made between the start and the end of the study, with the subjects acting as their own control group. Statistical analyses included a paired t-test, Wilcoxon paired test, Pearson correlation coefficient, and Sparse Partial Least Squares Discriminant Analysis to evaluate significant differences and correlations among parameters. There were statistically significant changes in total cholesterol, HDL-C (+52.3%), LDL-C (-54.0%), and TAG levels (-49.8%), but not in glucose plasma levels. Following the intervention, plasma concentrations of some amino acids, including α-aminoadipic acid, phosphoethanolamine, and 1-metylhistidine, increased, whereas those of asparagine and alanine declined. Different correlations between amino acids and the other parameters evaluated were reported and discussed. A Mediterranean diet combined with regular aerobic exercise, together with protein supplementation, can highly improve the metabolic parameters and anthropometric parameters of subjects with obesity and impaired glucose levels, ameliorating their health status and likely delaying the development of metabolic syndrome.

Prospective, Randomized, Double-Blind Parallel Group Nutritional Study to Evaluate the Effects of Routine Intake of Fresh vs. Pasteurized Yogurt on the Immune System in Healthy Adults.

The immune system is affected by the dietary products humans intake. Immune system regulation by nutrition has uses in the clinical context, but it can also benefit healthy populations by delaying or preventing the emergence of immune-mediated chronic illnesses. In this study, the purpose was to describe and compare the modulator effects on the immune system of the routine ingestion of fresh vs. pasteurized yogurt. A unicentral, prospective, randomized, double-blind, parallel group 8-week nutritional study was carried out comparing the ingestion of 125 g of the products in healthy adults three times a day. A complete battery of in vitro tests on the activity of the immune system, processes and phenomena was performed. Exclusive immune-modulatory effects of fresh yogurt with respect to base line were found in terms of increased systemic IgM (primary immune responses), increased synthesis of IFN-gamma upon stimulation (Th1) and increased peripheral T cells (mainly "naive" CD4s). In the three interventions, we observed an increased phagocytic activity and burst test in granulocytes, together with increased secretion of IL-6, IL-1 ß and IL-8 (pro-inflammatory) and increased CD16 expression (FcR favoring phagocytosis) in granulocytes. Overall, it is concluded that regardless of bacteria being alive or thermally inactivated, yogurt has common effects on the innate system, but the presence of live bacteria is necessary to achieve a potentiating effect on the specific immune response.

Identification, characterization, and molecular docking of immunomodulatory oligopeptides from bioavailable hempseed protein hydrolysates.

Promoting dietary patterns in which the content of vegetables is higher than the current consumption of them is one of the strategies to achieve a sustainable food system while promoting health in humans. Hemp (Cannabis sativa L.) protein contains bioactive peptides that can be released via enzymatic hydrolysis. These peptides must reach the target organ in order to potentially exert bioactivity and regulate specific metabolic pathways. The peptides contained in two bioavailable hempseed protein hydrolysates (bioHPHs) showing anti-inflammatory activity were identified using a transwell system employing CACO-2 cell culture as absorption model and subjected to in silico analysis to select 10 unique peptides. These sequences were chemically synthetized to verify their activity in primary human monocytes (assessing gene expression of IL-1ß, IL-6, TNF-α, IL-4, IL-10, and TLR4), in addition to evaluate the interaction with TRL4/MD2 by molecular docking. Six peptides (DDNPRRF, SRRFHLA, RNIFKGF, VREPVFSF, QADIFNPR and SAERGFLY) showed high immunomodulatory activity in in vitro and the mechanisms of interaction with TLR4/MD2 were described. Bioavailable anti-inflammatory hempseed-derived peptides were identified, and their activity verified, suggesting the health benefits that the ingestion of HPHs could exert in humans. These findings open new opportunities for developing nutritional strategies with hemp as a dietary source of biopeptides to prevent the development and progression of inflammatory-related diseases.

Sex-related differences in the susceptibility of Periplaneta americana and Capnodis tenebrionis to the entomopathogenic nematode Steinernema carpocapsae.

Entomopathogenic nematodes have a broad range of insect hosts, but efficacy varies depending on many factors including insect species and life stage of the host. In this study we examined the susceptibility of males and females of two insect species, the American cockroach Periplaneta americana and the flatheaded rootborer Capnodis tenebrionis to Steinernema carpocapsae by exposing adults to different concentrations. A separate study examined the routes of entry used by nematodes into males and females. Males of both species were more susceptible than females, with greater than 97% infection when a concentration of 50 IJs/cm(2) was applied, whereas mortalities lower than 58% were achieved against females 14 days post-infection. Infective juveniles were detected in similar number on the surface of both sexes, but when compared among internal regions the number of nematodes was significantly higher in gonads and ducts of males than of females for P. americana (5.49 in males; 0.02 in females) and C. tenebrionis (6.88 in males; 0.00 in females).

Sociocultural and linguistic boundaries influencing intercultural communication between nurses and Moroccan patients in southern Spain: a focused ethnography.

BACKGROUND: During the last 25 years, cultural diversity has increased substantially with global migration. In more recent years this has become highly evident in the south of Spain with its steadily increasing Moroccan population. The accompanying differences in ethnocultural values and traditions between the host and newcomer populations may greatly impact healthcare interactions and thus also effective provision of care. This landscape provides for excellent exploration of intercultural communication in healthcare settings and elucidation of possible ways to overcome existing barriers to provision of culturally competent care by nurses. This study aimed to ascertain how nurses perceive their intercultural communication with Moroccan patients and what barriers are evident which may be preventing effective communication and care. METHODS: A focused ethnography was conducted with semi-structured interviews of 32 nurses in three public hospitals in southern Spain. Interviews were audio-recorded and transcribed verbatim before undergoing translation and back-translation between Spanish and English. Data was managed, classified and ordered with the aid of AQUAD.6 (Günter L. Huber, Tübingen, Germany) qualitative data analysis software. RESULTS: As an important dimension of cultural competence, findings from the interviews with nurses in this study were interpreted within the framework of intercultural communication. Various barriers, for which we have termed "boundaries", seem to exist preventing effective communication between nurses and their patients. The substantial language barrier seems to negatively affect communication. Relations between the nurses and their Moroccan patients are also marked by prejudices and social stereotypes which likely compromise the provision of culturally appropriate care. CONCLUSIONS: The language barrier may compromise nursing care delivery and could be readily overcome by implementation of professional interpretation within the hospital settings. Moreover, it is essential that the nurses of southern Spain are educated in the provision of culturally appropriate and sensitive care.