Post-development Research Articles

Myclobutanil induces cardiotoxicity in developing zebrafish larvae by initiating oxidative stress and apoptosis: The protective role of curcumin

Myclobutanil (MYC) is a common triazole fungicide widely applied in agriculture. MYC extensively exists in the natural environment and can be detected in organisms. However, little is known about MYC-induced embryonic developmental damage. This study aimed to unravel the cardiotoxicity of MYC and the underlying mechanisms, as well as the cardioprotective effect of curcumin (CUR, an antioxidant polyphenol) using the zebrafish model. Here, zebrafish embryos were exposed to MYC at concentrations of 0, 0.5, 1 and 2 mg/L from 4 to 96 h post fertilization (hpf) and cardiac development was assessed. As results, MYC reduced the survival and hatching rate, body length and heart rate, but increased the malformation rate and spontaneous movement. MYC caused abnormal cardiac morphology and function in myl7:egfp transgenic zebrafish, and downregulated cardiac developmental genes. MYC promoted oxidative stress through excessive reactive oxygen species (ROS) accumulation and suppressed the activities of antioxidant enzymes, triggering cardiomyocytic apoptosis via upregulated expression of apoptosis-related genes. These adverse toxicities could be significantly ameliorated by the antioxidant properties of CUR, indicating that CUR rescued MYC-induced cardiotoxicity by inhibiting oxidative stress and apoptosis. Overall, our study revealed the potential mechanisms of oxidative stress and apoptosis in MYC-induced cardiotoxicity in zebrafish and identified the cardioprotection of CUR in this pathological process.

Influence of abiotic factors on diapause termination and temperature requirements for postdiapause development in the European red mite, Panonychus ulmi (Acari: Tetranychidae).

The European red mite Panonychus ulmi (Koch) is widely distributed and it can severely affect pome fruit crops, particularly apple. Pest outbreaks are related to an overuse of non-selective pesticide treatments that lead to the development of resistance and the absence of natural enemies in the orchard. A key aspect to optimize the use of pesticide treatments in the context of IPM is to increase the knowledge on the biology and ecology of the pest to better predict population dynamics and outbreaks. For the European red mite, knowledge on the conditions that lead to diapause breaking by winter eggs is essential to model population dynamics. To increase this knowledge, winter eggs were collected during field surveys in northen Spain during three years and egg hatching was monitored under controlled temperature and photoperiod conditions in the laboratory. The "number of days exposed to cold temperatures" was the most significant factor that positively affected hatching of overwintering eggs. The time required for 50% of the egg population to hatch (T50%) was also negatively modulated by the duration of exposure to cold temperature. The temperature threshold for postdiapause eggs development collected from the field was estimated between 5 and 6 ºC in 2005 and 2007, respectively. Moreover, the degree-days required for post diapause development were estimated between 263.2 and 270.3, depending on the year of collection. Collectively, we provide additional information on the diapause termination and postdiapause development of the European red mite that may effectively contribute to optimize pest population models.

Distinction within the ‘global north’? A Bourdieusian approach for analysing development discourse: The case of U.S. and E.U. relations with the Colombian state (2016–2022): A comparative analysis

The paper conducts a comparative analysis of EU (91 texts) and US (93 texts) discourses concerning post-peace accord Colombia (late 2016 to mid-2022). Employing a Bourdieu-influenced methodology, our proposal aims to reconcile Post-Development theories with International Relations research. This innovative and multidimensional approach illuminates both discursive continuities within Global North while concurrently providing a framework that allows to identify and interpret internal political divergences. Our findings highlight a shared commitment to a liberal conception of peacebuilding, alongside internal distinction strategies employed to legitimize respective policies towards Colombia.

Incidence of post open appendectomy incisional hernia in Erbil City

Background: since acute appendicitis is the most common presenting diseases in the surgical emergency departments, Appendectomy regarded as a common emergency surgical procedure that is done by the surgeons in the general surgery specialty. The complication of an incisional hernia development after open appendectomy is rare, found in about 0.12% of the appendectomy operations; interstitial type of incisional hernia complication following open appendectomy surgery is extremely rare condition, small number of reports found to deal with the incisional hernia development at the site of appendectomy in a range of (0.4-0.7%).
 Objective: To assess the incidence of incisional hernia following open appendectomy in Erbil province – Kurdistan region- Iraq.
 Patients and Methods: This retrospective study involved 598 cases between the period of first of July 2015 to 30th of April 2020, the cases presented with features of acute appendicitis, after admission and complete history taking, surgical intervention (open appendectomy) has been done for all of them, follow up for the diagnosis of the post appendectomy incisional hernia development done throughout revising the files and ID s of the patients and contacting them or their close relatives via personal mobile numbers, others re-consulted us for any operation site discomforts, any patient with suspicion of operation site problems asked to return to the outpatient surgical room for follow up and excluding or confirmation of operation site incisional hernia. The patients followed up for about 2-3 years after the operation days and contacting period with the patients or their close relatives to exclude incisional hernia development at open appendectomy site took about 6 months.
 Results: Out of 598 cases included in this retrospective study, 286 cases were male and 312 cases were female, the ages ranged between 5 and 91 years old with a mean and Standard Deviation (SD) 24.13, the age group of up to 10 years old included 13 cases, 2nd decade age group included 258 cases, while the third age group (21 – 30 years old) was included 167 cases. Risk factors for development of incisional hernia assessed among all cases, 56.85% of all cases had at least one of the risk factors and the remaining 43.15% devoid of any risk factors, the risk factors distributed among constipation (19.4%), pregnancy among female patients (18.9%), followed by diabetes mellitus, chronic cough and heavy working occupations (4.85% ,4.52% and 3.34% respectively), and BPH and anemia with other immunocompromised risk factors made only about 5.8%, only three patients (0.5%) developed incisional hernia after open appendectomy.
 Conclusion: Post open appendectomy incisional hernia is rare in patients without risk factors of wound dehiscence, with minimizing the risk factors of incisional hernia and wound dehiscence, the incidence of open appendectomy wound incisional hernia can be minimized to lowest rate.

Vision on India’s hunger rate index with special reference to the mission of sustainable development reform

Hunger is the one of the biggest challenges in independent India. To tackle this challenge sustainable development goals were adopted with the target year of 2023. This instigates the researchers to compare the pre and post sustainable development reform of zero hunger indicators to analyse the India’s performance towards the vision of zero hunger. The result of the disclosed that India has made a progress towards the mission of sustainable development reform by reducing child stunting and undernourishment.

MTOR hypoactivity leads to trophectoderm cell failure by enhancing lysosomal activation and disrupting the cytoskeleton in preimplantation embryo

BackgroundMetabolic homeostasis is closely related to early impairment of cell fate determination and embryo development. The protein kinase mechanistic target of rapamycin (mTOR) is a key regulator of cellular metabolism in the body. Inhibition of mTOR signaling in early embryo causes postimplantation development failure, yet the mechanisms are still poorly understood.MethodsPregnancy mice and preimplantation mouse embryo were treated with mTOR inhibitor in vivo and in vitro respectively, and subsequently examined the blastocyst formation, implantation, and post-implantation development. We used immunofluorescence staining, RNA-Seq smart2, and genome-wide bisulfite sequencing technologies to investigate the impact of mTOR inhibitors on the quality, cell fate determination, and molecular alterations in developing embryos.ResultsWe showed mTOR suppression during preimplantation decreases the rate of blastocyst formation and the competency of implantation, impairs the post implantation embryonic development. We discovered that blocking mTOR signaling negatively affected the transformation of 8-cell embryos into blastocysts and caused various deficiencies in blastocyst quality. These included problems with compromised trophectoderm cell differentiation, as well as disruptions in cell fate specification. mTOR suppression significantly affected the transcription and DNA methylation of embryos. Treatment with mTOR inhibitors increase lysosomal activation and disrupts the organization and dynamics of the actin cytoskeleton in blastocysts.ConclusionsThese results demonstrate that mTOR plays a crucial role in 8-cell to blastocyst transition and safeguards embryo quality during early embryo development.

HPB P39 Pre-operative Cardiopulmonary Exercise test as a Predictive tool for post pancreaticoduodenectomy intra-abdominal collection development. A Retrospective study

Abstract Background Cardiopulmonary Exercise Test (CPET) provides a non-invasive assessment tool for physiological fitness and peri-operative mortality in major abdominal surgery including Pancreaticoduodenectomy (PD). Post-operative complications including intra-abdominal collection could potentially delay adjuvant chemotherapy following PD. There is minimal evidence in the literature to link CPET derived variables to post PD complications. The aim of this study is to evaluate the role of CPET in predicting post operative intra-abdominal collection. Methods A retrospective single centre analysis of a prospectively maintained database from 2016 to 2021 for all patients who had PD was performed. Patient demographics, co-morbidities, and CPET variables were collected. Post-operative adverse events including Clavien-Dindo (CD) grade III intraabdominal collection, length of hospital stay and Readmission within 1 year were looked at. P value ≤ 0.05 was considered statistically significant. Results 143 patients had PD during the study period. CPET was performed in 30 patients (21%). The patients’ age was 67 ±9 (Mean±SD). Forty patients (28.2%) had developed Intra-abdominal collection CDIII. In the CPET subgroup, Anaerobic Threshold (AT) ≤ 14 on CPET was a risk factor to develop intra-abdominal collection CDIII in univariate analysis (60% Vs 9%, Chi2, p 0.02) and multivariate analysis (HR 3.5, 95% CI 1.6-657, p 0.02). Another significant risk factor was a post-operative pancreatic leak (POPF) (40% Vs 22%, Chi2, p 0.04). Conclusions Patients who have Anaerobic Threshold ≤ 14 on CPET, are more likely to develop intra-abdominal collection requiring drainage after Pancreaticoduodenectomy. This group of patients will be less likely to start chemotherapy early.

The MidPIC study: Midwives’ knowledge, perspectives and learning needs regarding preconception and interconception care

Preconception and interconception care improves health outcomes of women and communities. Little is known about how prepared and willing Australian midwives are to provide preconception and interconception care. The aim of this study was to explore midwives’ knowledge, perspectives and learning needs, and barriers and enablers to delivering preconception and interconception care. We conducted a cross-sectional exploratory study of midwives working in any Australian maternity setting. An online survey measured midwives’ self-rated knowledge; education needs and preferences; attitudes towards pre and interconception care; and views on barriers, enablers; and, future service and workforce planning. Quantitative data were analysed descriptively and demographic characteristics (e.g., years of experience, model of care) associated with knowledge and attitudes regarding pre- and interconception care were examined using univariate logistic regression analysis. Qualitative data were captured through open-ended questions and analysed using inductive content analysis. We collected responses from (n = 338) midwives working across all models of care (full survey completion rate 96%). Most participants (n = 290; 85%) rated their overall knowledge about pre and interconception health as excellent, above average or average. Participants with over 11 years of experience were more likely to report above average to excellent knowledge (OR 3.11; 95% CI 1.09, 8.85). Online e-learning was the most preferred format for education on this topic (n = 244; 72%). Most (n = 257; 76%) reported interest in providing pre and interconception care more regularly and that this is within the midwifery scope of practice (n = 292; 87%). Low prioritisation in service planning was the most frequently selected barrier to providing preconception and interconception care, whereas continuity models and hybrid child health settings were reported as enablers of pre and interconception care provision. Findings revealed that midwives are prepared and willing to provide preconception and interconception care. Pre and post registration professional development; service and funding reform; and policy development are critical to enable Australian midwives’ provision of pre and interconception care.

SAT631 EPAS1 Mutations In Three Adjacent Nucleotides Resulting In Different Phenotypes

Abstract Disclosure: M. Alswailem: None. B. Alghamdi: None. L.A. Alobaid: None. H. Al-Hindi: None. M. Aldawish: None. O. Alsagheir: None. A.S. Alzahrani: None. EPAS1 (HIF2a) mutations have been described in patients (pts) with paragangliomas (PGL) in association with cyanotic congenital heart disease (CHD), polycythemia and some additional tumors. Here, we present 3 cases of PGL with closely located EPAS1 mutations. Despite the common gene location, their manifestations are different. 1. A 14-year-old girl found at age 9 years (yrs) to have polycythemia (Hb 177-195 g/l) and hypertension. At age 14 years, she was diagnosed to have multiple mid abdomenal and the urinary bladder PGLs. U. noremetanephrine was 35.8 umol/day (0-3.43). No evidence of somatostatinoma so far. Family hx is negative for PGL and WES revealed no germline mutations in PGL-associated genes. Tumor testing revealed a novel heterozygous EPAS1 variant (c.1589C>T, p.A530V). 2. A 32-yr-old woman has a complex cyanotic CHD diagnosed since birth. She underwent five cardiac surgeries between 1993 and 2015. In 2011, she was diagnosed with two abdominal PGLs. She underwent surgery and remained free of disease until 2019 when she developed recurrence with metastases (mets) to the liver and spine. She received external beam radiotherapy to the spine. Currently PGL mets remained stable. WES was negative for any germline mutation but tumor testing revealed a heterozygous EPAS1 mutation (c.1591C>T, p.P531S). 3. A 55-yr-old man diagnosed to have an upper abdominal PGL with lung and bone metastases at the age of 9 yrs. Biopsy from a right femoral met confirmed the diagnosis of bone mets. He underwent four abdominal surgeries between 1978-2008 and received MIBG Tx 6 times with a cumulative dose is 586 mCi. His last surgery in 2008 revealed PGLs but also a non-functioning Pancreatic neuroendocrine tumor (pNET). PGL mets remained stable over the last 15 yrs. WES revealed no germline mutation in any of the known PGL genes but tumor testing revealed an EPAS1 mutation (c.1592C>A, p.P531H). Discussion:EPAS1 mutations are very rare. In this series, we present 3 pts with EPAS1 mutations in 3 adjacent nucleotides (c.1589, 1591, 1592) in 2 adjacent codons (p.530-531). These mutations are located in a domain that is important for recognition by propyl hydroxylases that normally lead to inactivation and proteasomal degradation of HIF2a (EPAS1). Despite the common location, the manifestations are quite different. Although all of them developed PGL at a young age, Pt # 1 had severe polycythemia, Pt#2 had complex CHD, and pt#3 had pNET. The first two patients had extensive mets but these mets have a smoldering course, especially in pt#3 who has been living with these mets for 44 yrs! Since EPAS1 mutations are usually postzygotic, as suggested by its involvement of more than one organ, it is possible that the variable presentations of these same domain adjacently located mutations is related to the timing of their post zygotic development. Another possibility is that the variable expression of the mutated EPAS1 in different tissues Presentation: Saturday, June 17, 2023

Emergency department pathology order support tool (ED POST): a protocol using qualitative inquiry to inform design and development of a prototype to reduce low value care

Laboratory tests have an important role in informing diagnosis and aiding in the determination of appropriate courses of management and/or treatment in the Emergency Department setting. Over-ordering of laboratory tests can lead to increased costs and/or unnecessary patient procedures, whilst under-ordering can lead to patient safety concerns and/or diagnostic error. Reducing over/under ordering through appropriate use of pathology has the potential to improve patient safety and/or reduce healthcare costs. As a dynamic electronic decision support tool, the Emergency Department Pathology Order Support Tool (ED POST) aims to facilitate effective ordering of pathology tests. This protocol details the methodological approach to be undertaken during the design and development of ED POST, commencing from the outset of the initial development of a prototype design. The research will undertake qualitative methods (interviews, focus group, and think-aloud observations) to develop business process models through collaboration with Emergency Department clinicians. The pre-development research will constitute stage 1 of the approach, with stage 2 focussed on evaluating the utility, usability and business process impact of the prototype to refine the prototype’s design. The collaborative and qualitative multi-method approach aims to elucidate an in-depth understanding of existing laboratory test ordering and decision-making processes in the Emergency Department, serving to inform the development of a relevant and practicable solution. Health researchers and digital health developers can draw on this approach to inform research planning activities for health information technology intervention design projects and can follow the developmental journey of ED POST as its outcomes are reported in the literature.

Blastulation time measured with time-lapse system can predict in vitro viability of bovine blastocysts.

The objective of this study was to evaluate the time of blastulation monitored by time-lapse technology to predict in vitro viability of bovine blastocysts. This technology can be a powerful tool for bovine embryos selection with higher implantation capacity and competence. Also, in humans an early blastulation is associated with higher quality and pregnancy rate. Cumulus oocyte complexes (COCs) were matured for 20 to 22 h and then fertilized by co-incubation of COCs and spermatozoa (10,000 sperm per oocyte) for 18 h. Presumptive zygotes were placed individually in microwells, in droplets of commercial culture medium. The Primo Vision TL system (EVO+; Vitrolife) captured digital images of developing embryos every 15 minutes. The time frame from IVF to the start of blastulation (tSB) and to blastocyst development (tB) was recorded. After day 7.5, the blastocysts were in vitro culture for 48 h until day 9.5 after IVF to evaluate post hatching development. In vitro viability was evaluated at day 9.5: those with a diameter greater than 200 μm and a total cell count greater than 180 were classified as viable (value 1), while the rest were classified as non in vitro viable (value 0). The area under the ROC curve (AUC) was estimated to determine the predictive power of in vitro viability through blastulation time. In addition, binary logistic regression analysis was used to generate a mathematical model with morphokinetic variables that allow the best prediction of in vitro viability. In 13 sessions, the blastocyst production rate was 46.2% (96/208). The cut-off time to discriminate early or late blastulation was 149.8 h. The post-hatching development of the embryos with early blastulation was 63.3% (31/49), being statistically superior (p = 0.001) than the late blastulation group 14.9% (7/47). Likewise, the time of blastulation showed an accuracy of 90.8% (p < 0.001) in predicting in vitro viability of bovine blastocysts. In conclusion, the selection of blastocysts based on blastulation time (< 155 h) and blastocyst diameter measured on day 7.5 after IVF (> 180 μm) maximizes the in vitro viability.

Post-development Thesis and African Intercultural Theory of Development

The aim of the paper is to address the question: is the end of development possible? Post-development theorists declare the end of development. They insist that the problematisation of poverty by development theory is one of the key defects of development. The irony in this problematisation is that development practice as an offshoot of development theory does not actually alleviate poverty, particularly in colonial spaces. Rather, the agents of development have perpetuated underdevelopment at the fringes of the colonial metropolis. Given this perpetuation of underdevelopment, post-development theorists argue, the idea of development has run its course and is no longer efficient; it should be put to an end. We assess this declaration of post-development theory from the perspective of Agbakoba’s intercultural philosophy of development. Using the philosophical methods of analysis and critique, we argue that Agbakoba’s intercultural proposal for a transition to development in Africa holds more prospects and is more feasible in addressing the concerns of post-development scholars. This is because, Agbakoba’s intercultural philosophy of development does not insist on the end of development, but on hybridity as the end of development.

Ayurveda Approach for Adhd Through ‘Medhya, Hridya &amp; Rasayana (a Case Study)

According to the centres for disease control and prevention statistics (CDC) reports that ADHD among 3-17 years of age represent to 9.8% population reaching up to 16% at higher scale of its progression. Children from 0-3 years group of post natal growth and development is also important for the prevention of syndrome where much improvments are suggesting to the present therapeutic protocols been followed in above traditonal systems of health and wellness. Based on the given literature in Sanskrit in Ayurveda is an attempt made to bring down the symptoms of agrression and irritability with poor orientation in contrast to the normal brain body image at chronoogical age to biological. The therapeutics above are connecting from physiological heart (Hridya) at centre being pleased with qualities of nourishment through live blood assessments indirectly through the sensory functions, skin colour and complexion and visual acuqity etc, for the effect over Brain (Medhya) through the process known under rejuvenation or renovation (Rasayana) the same sequence is followed for this case study preventing further progression of the condition is discussed

Social media as a catalyst to improve (personal) health.

Social media as a catalyst to improve (personal) health.

We just gotta do meta! Notes on disciplinary anxieties in Geography in India

AbstractA hundred years since its inception in college curriculum in India, geography as a discipline appears to be marked by a lack of self confidence. The persistently unenthusiastic response of Indian departments of geography to the present global health crisis over the past three years suggests that this is not a momentary loss of heart. We suggest that this is rather the result of the discipline's intertwining with post independence development policy in addition to the failure to integrate the sub disciplines of geography well with each other. As a way forward, we argue that the greatest promise in fact lies not in the universities but in networks across departments and independent research centres where geography can truly claim its place in the sun as a discipline that offers the relational approach that few other disciplines offer.

Working together: A study of civil society partnerships between WASH (water, sanitation, and hygiene) and GESI (gender equality and social inclusion) organisations in Timor-Leste

This article reports on an empirical study conducted in Timor-Leste that explored the drivers, benefits, and challenges of partnerships and collaborations between water, sanitation, and hygiene (WASH) and gender equality and social inclusion (GESI) organisations as integral parts of the WASH system. The research design was primarily qualitative and included a data-collection workshop with 30 representatives from 16 civil society organisations (CSOs) in Dili, longitudinal research involving two rounds of semi-structured interviews over 2.5 years with five organisations, and semi-structured interviews with an additional 18 CSOs. We applied a framework of post-development theory, including critical localism and working contingently. Key drivers to form partnerships were found to be the identification of community WASH service gaps and the alignment of advocacy agendas. Key benefits reported were increased inclusion and empowerment outcomes and strengthened organisational knowledge and capacity. Challenges emerge when organisations' key staff change, strategies misalign, and financial and administrative capabilities differ. The study contributes practical insights into how civil society organisations (CSOs) partner to strengthen mutual WASH and GESI strategies and programmes and their outcomes. We recommend strengthening the partnerships between WASH and GESI organisations in ways that are cognisant of power dynamics, local priorities, and capacity needs and promote longevity and continuity through ownership of decisions at the local level. Our findings suggest that meaningful, reciprocal, and respectful engagement with WASH and GESI organisations enables WASH programmes to be in a better position to address the harmful norms that drive inequitable behaviours, thus strengthening localism, and the WASH governance system overall.

Post-endodontic restorative treatments and their mechanical behavior: A narrative review

Dental treatment after endodontic therapy is quite challenging in clinical practice. While multiple post-and-core systems emerged and disappeared in the dental field, the historical process was laborious and still requires several up to date scientific evidence. Furthermore, once considered the gold standard, rigid metallic post-and-cores might be considered a limited option. Moreover, the development of glass-fiber posts and the biomechanical principles for root preparation bring multiple advantages, but also raise concerns over guidelines and indications. This review examined the classic literature so that clinicians may understand the concepts behind post endodontic restorative treatments and the doubts that still remain in the daily practice before performing this restorative modality.

Toward a Convivial Design

Abstract This article is inspired by the work of Ivan Illich, especially Tools for Conviviality, which critiques industrialization and elaborates Illich's proposal for conviviality and is a major influence on post-development theory. In the early 1970s, Illich anticipated issues that design begins to explore only at the end of the twentieth century. This article discusses what he anticipated and develops this into practical suggestions for the evolution of design. Above all, the article provides suggestions for two intertwined design fields: design for sustainability and codesign. An analysis of Illich's work allows for the identification of three methodological movements acting toward a convivial design: (1) conduct a critique of the status quo, (2) imagine alternative proposals, and (3) carefully qualify the ethos of alternatives.

ЭФФЕКТИВНОСТЬ ПРИМЕНЕНИЯ ФИТОПРЕПАРАТА НА ОСНОВЕ ХВОИ ПРИ ВЫРАЩИВАНИИ ЦЫПЛЯТ-БРОЙЛЕРОВ

The results have been given in the paper on usage of new phytopreparation at needles base in broiler rearing. Its positive effect has been established on blood hematologic and biochemical parameters and on broiler im- munity and production. The best dose is 30 g/kg feed since third till 42th rearing days and 40 g/kg feed since 11th till 42th days. This scheme using effects positively on poultry physiologic condition and increases blood hemoglobin con- tent by 35.8%, total protein by 29.5%, albumins and globulins by 16.2 and 39.7% respectively. Phytopreparation pro- motes post vaccination antibodies development against Newcastle disease virus increasing average antibodies titer by 0.4 log2, promotes poultry body weight increasing by 8.0% and lowering feed costs per 1 kg body weight increas- ing by 7.6%.

Early Life Stress, Neuroinflammation, and Psychiatric Illness of Adulthood.

Stress exposure during early stages of life elevates the risk of developing psychopathologies and psychiatric illness in later life. The brain and immune system are not completely developed by birth and therefore continue develop after birth; this post birth development is influenced by several psychosocial factors; hence, early life stress (ELS) exposure can alter brain structural development and function. A growing number of experimental animal and observational human studies have investigated the link between ELS exposure and increased risk of psychopathology through alternations in the immune system, by evaluating inflammation biomarkers. Recent studies, including brain imaging, have also shed light on the mechanisms by which both the innate and adaptive immune systems interact with neural circuits and neurotransmitters, which affect psychopathology. Herein, we discuss the link between the experience of stress in early life and lifelong alterations in the immune system, which subsequently lead to the development of various psychiatric illnesses.