Hasil untuk "Other systems of medicine"

J. Brahmer, C. Lacchetti, B. Schneider et al.

Purpose To increase awareness, outline strategies, and offer guidance on the recommended management of immune-related adverse events in patients treated with immune checkpoint inhibitor (ICPi) therapy. Methods A multidisciplinary, multi-organizational panel of experts in medical oncology, dermatology, gastroenterology, rheumatology, pulmonology, endocrinology, urology, neurology, hematology, emergency medicine, nursing, trialist, and advocacy was convened to develop the clinical practice guideline. Guideline development involved a systematic review of the literature and an informal consensus process. The systematic review focused on guidelines, systematic reviews and meta-analyses, randomized controlled trials, and case series published from 2000 through 2017. Results The systematic review identified 204 eligible publications. Much of the evidence consisted of systematic reviews of observational data, consensus guidelines, case series, and case reports. Due to the paucity of high-quality evidence on management of immune-related adverse events, recommendations are based on expert consensus. Recommendations Recommendations for specific organ system-based toxicity diagnosis and management are presented. While management varies according to organ system affected, in general, ICPi therapy should be continued with close monitoring for grade 1 toxicities, with the exception of some neurologic, hematologic, and cardiac toxicities. ICPi therapy may be suspended for most grade 2 toxicities, with consideration of resuming when symptoms revert to grade 1 or less. Corticosteroids may be administered. Grade 3 toxicities generally warrant suspension of ICPis and the initiation of high-dose corticosteroids (prednisone 1 to 2 mg/kg/d or methylprednisolone 1 to 2 mg/kg/d). Corticosteroids should be tapered over the course of at least 4 to 6 weeks. Some refractory cases may require infliximab or other immunosuppressive therapy. In general, permanent discontinuation of ICPis is recommended with grade 4 toxicities, with the exception of endocrinopathies that have been controlled by hormone replacement. Additional information is available at www.asco.org/supportive-care-guidelines and www.asco.org/guidelineswiki .

Li Yang, Kui-Shan Wen, Xiao Ruan et al.

Plant secondary metabolites (SMs) are not only a useful array of natural products but also an important part of plant defense system against pathogenic attacks and environmental stresses. With remarkable biological activities, plant SMs are increasingly used as medicine ingredients and food additives for therapeutic, aromatic and culinary purposes. Various genetic, ontogenic, morphogenetic and environmental factors can influence the biosynthesis and accumulation of SMs. According to the literature reports, for example, SMs accumulation is strongly dependent on a variety of environmental factors such as light, temperature, soil water, soil fertility and salinity, and for most plants, a change in an individual factor may alter the content of SMs even if other factors remain constant. Here, we review with emphasis how each of single factors to affect the accumulation of plant secondary metabolites, and conduct a comparative analysis of relevant natural products in the stressed and unstressed plants. Expectantly, this documentary review will outline a general picture of environmental factors responsible for fluctuation in plant SMs, provide a practical way to obtain consistent quality and high quantity of bioactive compounds in vegetation, and present some suggestions for future research and development.

B. Stockwell, J. Angeli, H. Bayır et al.

Ferroptosis is a form of regulated cell death characterized by the iron-dependent accumulation of lipid hydroperoxides to lethal levels. Emerging evidence suggests that ferroptosis represents an ancient vulnerability caused by the incorporation of polyunsaturated fatty acids into cellular membranes, and cells have developed complex systems that exploit and defend against this vulnerability in different contexts. The sensitivity to ferroptosis is tightly linked to numerous biological processes, including amino acid, iron, and polyunsaturated fatty acid metabolism, and the biosynthesis of glutathione, phospholipids, NADPH, and coenzyme Q10. Ferroptosis has been implicated in the pathological cell death associated with degenerative diseases (i.e., Alzheimer's, Huntington's, and Parkinson's diseases), carcinogenesis, stroke, intracerebral hemorrhage, traumatic brain injury, ischemia-reperfusion injury, and kidney degeneration in mammals and is also implicated in heat stress in plants. Ferroptosis may also have a tumor-suppressor function that could be harnessed for cancer therapy. This Primer reviews the mechanisms underlying ferroptosis, highlights connections to other areas of biology and medicine, and recommends tools and guidelines for studying this emerging form of regulated cell death.

B. Ali, N. Al-Wabel, S. Shams et al.

Nowadays, use of alternative and complementary therapies with mainstream medicine has gained the momentum. Aromatherapy is one of the complementary therapies which use essential oils as the major therapeutic agents to treat several diseases. The essential or volatile oils are extracted from the flowers, barks, stem, leaves, roots, fruits and other parts of the plant by various methods. It came into existence after the scientists deciphered the antiseptic and skin permeability properties of essential oils. Inhalation, local application and baths are the major methods used in aromatherapy that utilize these oils to penetrate the human skin surface with marked aura. Once the oils are in the system, they remodulate themselves and work in a friendly manner at the site of malfunction or at the affected area. This type of therapy utilizes various permutation and combinations to get relief from numerous ailments like depression, indigestion, headache, insomnia, muscular pain, respiratory problems, skin ailments, swollen joints, urine associated complications etc. The essential oils are found to be more beneficial when other aspects of life and diet are given due consideration. This review explores the information available in the literature regarding therapeutic, medical, cosmetic, psychological, olfactory, massage aromatherapy, safety issues and different plants used in aromatherapy. All the available information was compiled from electronic databases such as Academic Journals, Ethnobotany, Google Scholar, PubMed, Science Direct, Web of Science, and library search.

B. Schuettengruber, H. Bourbon, L. D. Croce et al.

Dhrisya Chenthamara, Sadhasivam Subramaniam, S. Ramakrishnan et al.

In modern-day medicine, nanotechnology and nanoparticles are some of the indispensable tools in disease monitoring and therapy. The term “nanomaterials” describes materials with nanoscale dimensions (< 100 nm) and are broadly classified into natural and synthetic nanomaterials. However, “engineered” nanomaterials have received significant attention due to their versatility. Although enormous strides have been made in research and development in the field of nanotechnology, it is often confusing for beginners to make an informed choice regarding the nanocarrier system and its potential applications. Hence, in this review, we have endeavored to briefly explain the most commonly used nanomaterials, their core properties and how surface functionalization would facilitate competent delivery of drugs or therapeutic molecules. Similarly, the suitability of carbon-based nanomaterials like CNT and QD has been discussed for targeted drug delivery and siRNA therapy. One of the biggest challenges in the formulation of drug delivery systems is fulfilling targeted/specific drug delivery, controlling drug release and preventing opsonization. Thus, a different mechanism of drug targeting, the role of suitable drug-laden nanocarrier fabrication and methods to augment drug solubility and bioavailability are discussed. Additionally, different routes of nanocarrier administration are discussed to provide greater understanding of the biological and other barriers and their impact on drug transport. The overall aim of this article is to facilitate straightforward perception of nanocarrier design, routes of various nanoparticle administration and the challenges associated with each drug delivery method.

T. Roenneberg, M. Merrow

Dietram A. Scheufele, Nicole M. Krause

Concerns about public misinformation in the United States—ranging from politics to science—are growing. Here, we provide an overview of how and why citizens become (and sometimes remain) misinformed about science. Our discussion focuses specifically on misinformation among individual citizens. However, it is impossible to understand individual information processing and acceptance without taking into account social networks, information ecologies, and other macro-level variables that provide important social context. Specifically, we show how being misinformed is a function of a person’s ability and motivation to spot falsehoods, but also of other group-level and societal factors that increase the chances of citizens to be exposed to correct(ive) information. We conclude by discussing a number of research areas—some of which echo themes of the 2017 National Academies of Sciences, Engineering, and Medicine’s Communicating Science Effectively report—that will be particularly important for our future understanding of misinformation, specifically a systems approach to the problem of misinformation, the need for more systematic analyses of science communication in new media environments, and a (re)focusing on traditionally underserved audiences.

J. Grover, S. Yadav, V. Vats

G. Eysenbach

In an ongoing effort of this Journal to develop and further the theories, models, and best practices around eHealth research, this paper argues for the need for a “science of attrition”, that is, a need to develop models for discontinuation of eHealth applications and the related phenomenon of participants dropping out of eHealth trials. What I call “law of attrition” here is the observation that in any eHealth trial a substantial proportion of users drop out before completion or stop using the appplication. This feature of eHealth trials is a distinct characteristic compared to, for example, drug trials. The traditional clinical trial and evidence-based medicine paradigm stipulates that high dropout rates make trials less believable. Consequently eHealth researchers tend to gloss over high dropout rates, or not to publish their study results at all, as they see their studies as failures. However, for many eHealth trials, in particular those conducted on the Internet and in particular with self-help applications, high dropout rates may be a natural and typical feature. Usage metrics and determinants of attrition should be highlighted, measured, analyzed, and discussed. This also includes analyzing and reporting the characteristics of the subpopulation for which the application eventually “works”, ie, those who stay in the trial and use it. For the question of what works and what does not, such attrition measures are as important to report as pure efficacy measures from intention-to-treat (ITT) analyses. In cases of high dropout rates efficacy measures underestimate the impact of an application on a population which continues to use it. Methods of analyzing attrition curves can be drawn from survival analysis methods, eg, the Kaplan-Meier analysis and proportional hazards regression analysis (Cox model). Measures to be reported include the relative risk of dropping out or of stopping the use of an application, as well as a “usage half-life”, and models reporting demographic and other factors predicting usage discontinuation in a population. Differential dropout or usage rates between two interventions could be a standard metric for the “usability efficacy” of a system. A “run-in and withdrawal” trial design is suggested as a methodological innovation for Internet-based trials with a high number of initial dropouts/nonusers and a stable group of hardcore users.

C. Lipscomb

Tarun Sahu, Y. K. Ratre, S. Chauhan et al.

Abstract Nanotechnology or Nano medicine has been identified as the dominant and most commercially invented technology that aims to improve the quality of health care strategies. Although nanotechnology has some limitations, many pharmaceutical and medical equipment companies have already adhered to medical nanotechnology. In some cases, drugs with high toxic potential, such as chemotherapeutic cancer drugs, can be administered with a better safety profile using nanotechnology. It is important to note that Living cells are tiny virtual machines involved in all biological activities, including cell signalling, metabolism, energy generation and nutrient transport. Therefore it can be considered a major candidate technology to deal with biology and medicine for therapeutic purposes. In this review, we discuss the importance of nanoscience with different nanotechnology platforms being used in other aspects of medicine. Besides, we are also addressing the future opportunities of nanotechnology in human health.

Melody D. Fulton, Wided Najahi-Missaoui

Since their first discovery in the 1960s by Alec Bangham, liposomes have been shown to be effective drug delivery systems for treating various cancers. Several liposome-based formulations received approval by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA), with many others in clinical trials. Liposomes have several advantages, including improved pharmacokinetic properties of the encapsulated drug, reduced systemic toxicity, extended circulation time, and targeted disposition in tumor sites due to the enhanced permeability and retention (EPR) mechanism. However, it is worth noting that despite their efficacy in treating various cancers, liposomes still have some potential toxicity and lack specific targeting and disposition. This explains, in part, why their translation into the clinic has progressed only incrementally, which poses the need for more research to focus on addressing such translational limitations. This review summarizes the main properties of liposomes, their current status in cancer therapy, and their limitations and challenges to achieving maximal therapeutic efficacy.

W. Pedrycz, F. Gomide

Salvi S. Shah, Shraddha J. Diwan

Abstract Background and purpose Physical fitness (PF) and physical activity (PA) appear to be a proposed way to improve global health, cognition, Executive functions and Academic Achievement (AA) in children and adolescents. Hence, the present study was undertaken to explore the relationship of Physical fitness with academic achievement among school children of Surat City. Results Within physical fitness components, a statistically significant negligible to weak positive correlation (“rho” value ranged from 0.04 to 0.26) was found for body composition, Muscular strength and endurance, flexibility and cardiorespiratory endurance with academic achievement. A statistically significant weak negative correlation (“rho” value ranged from 0.1 to 0.14) was found between agility and academic achievement. All correlations remain significant in Spearman’s partial correlations analysis model adjusted for age and socio-economic status except the correlation of flexibility with academic achievement in girls. Conclusion and clinical implications The findings of the study suggest that in schoolchildren, academic achievement is significantly influenced by different components of physical fitness. More opportunities need to be made to help parents, educators, and teachers to see the importance of PF in addition to education in this competitive society.

Saleh Alrajhi, Ayman Afify Konswa, Nisreen Alhamdi et al.

Background and importanceLifestyle choices and practices are often the primary contributors to most preventable chronic diseases encountered in both outpatient and inpatient settings worldwide. Lifestyle medicine (LM) therapeutic interventions have consistently been shown through numerous scientific studies to improve and, in many cases, reverse chronic diseases. Globally, there is widespread acceptance of the 15 core competencies, 6 pillars, and the overarching definition of Lifestyle Medicine (LM) established by the American College of Lifestyle Medicine and its partners. While these 6 pillars provide a robust framework, they may not fully address the diverse needs of individuals and populations across various cultures, countries, and communities. The implementation of LM is inherently context-sensitive, influenced by factors such as local legislation, culinary traditions, food availability, economic conditions, agricultural development, whole-food retail accessibility, healthcare infrastructure, training opportunities, community resources, and faith or religious practices at both the individual and community levels. Furthermore, the MENA region, in particular, experiences a disproportionately high prevalence of lifestyle-related non-communicable diseases (NCDs) such as obesity, impaired glucose tolerance (IGT), type 2 diabetes mellitus (T2DM), hypertension (HTN), coronary artery disease (CAD), polycystic ovary syndrome (PCOS), and various forms of cancer, along with other related syndromes and co-morbid conditions. Addressing these challenges requires careful consideration of the local context—a complex interplay of culture, traditions, beliefs, and behaviors—that significantly shapes lifestyle choices, resource availability, and their subsequent impact on health and wellness outcomes. Significantly, the Hail Lifestyle Medicine International Conferences held in 2022 and 2023 have emphasized the strategic importance of Lifestyle Medicine in the MENA region, particularly in Saudi Arabia. These conferences underscored the need to define the scope of practice for Lifestyle Medicine in alignment with the ongoing Saudi healthcare transformation, the region's unique societal features, available local resources, and the specific needs of the population. Furthermore, these conferences served as pivotal platforms for convening experts, facilitating knowledge exchange, and fostering collaborations to tackle the distinct health challenges prevalent in the region. To provide a more comprehensive understanding, information regarding the establishment of the technical working group for the MENA region—critical to conceptualizing and adapting the LM pillars—should be included in the background or methods section earlier in the paper. This addition would offer readers insights into the foundational steps and collaborative efforts that initially shaped the initiative.Establishment of the technical working group for the MENA regionIn response to the rising prevalence of non-communicable diseases (NCDs) and the pressing need for a tailored approach to Lifestyle Medicine (LM) in the MENA region, a Technical Working Group (TWG) was established. The initiative sought to adapt the six pillars of LM to align with the region's unique cultural, economic, and social contexts. The TWG comprised experts from various disciplines, including family medicine, preventive medicine, public health, nutrition, and related fields, ensuring diverse perspectives and expertise in primary care and lifestyle interventions. The concept of adopting expanded LM pillars was initially formulated during a series of international and regional conferences, notably the Hail Lifestyle Medicine International Conferences held in 2022 and 2023. These conferences highlighted the urgent need for a region-specific approach to mitigate the high prevalence of lifestyle-related NCDs in the MENA region. The TWG was tasked with conducting a comprehensive review of the existing LM pillars while taking into account critical factors such as local legislation, culinary traditions, food resources, economic conditions, and health systems infrastructure. To achieve expert consensus on the adapted LM pillars, the Delphi process was employed. This structured communication method involved several rounds of anonymous questionnaires, enabling experts to provide their input and refine their responses based on collective feedback. The process ensured a balanced, inclusive approach that minimized potential power imbalances and produced LM pillars tailored to the MENA region's specific needs.MethodsA survey was distributed to professional group panels representing multiple healthcare specialties, as well as to researchers and healthcare academic leaders of Lifestyle Medicine (LM) across Saudi Arabia and the broader Middle East. A Strength, Weakness, Opportunity, and Threat (SWOT) analysis was conducted, and the Delphi method was employed for structured communication and opinion formation. Using the nominal polling technique, formal responses were collected to develop an official written consensus position statement. The survey questions were validated and approved by an expert panel before being disseminated to the national Lifestyle Medicine group via WhatsApp for voting. Participants were asked to select one of three options: retain the American LM pillars, expand to the newly validated Saudi Arabian (MENA) LM pillars, or abstain from voting (neutral).Conclusions and relevanceOut of 815 members in the national Lifestyle Medicine (LM) group, 136 responses were received, while 679 members abstained from voting, indicating neutrality. Among the 136 votes, 36 supported retaining the LM pillars developed by the American College of Lifestyle Medicine AMCL and its partners without modifications. In contrast, 118 voted in favor of the newly developed MENA/Saudi Arabian pillars, acknowledging the need to address local healthcare needs that extend beyond traditional or classical medicine. The new pillars incorporated motor vehicle driving disturbances as a leading modifiable lifestyle factor contributing to death and disability in the region. Additionally, the impact of smart technology, particularly mobile phones and other devices, was recognized as a key contributor to motor vehicle accidents (MVAs), which significantly increase mortality and disability rates. Further, the new pillars emphasized emotional and mental health, spirituality, and sexuality, driven by the growing demand for comprehensive mental and emotional healthcare combined with faith-based and spiritual empowerment. Finaly, the inclusion of sexuality as a pillar was prompted by rapid societal changes, the rising prevalence of risky sexual behaviors, and the increased incidence of sexually transmitted infections (STIs). These challenges, coupled with the ambiguity surrounding who should manage such patients and the need for timely access to care, highlighted amajor gap in addressing this critical aspect of human health and quality of life. This addition ensures that LM physicians can provide appropriate care to close the gap in services related to sexual health.

Shuqing Shi, Xiaohan Zhang, Jiayu Lv et al.

Abstract Background Atrial Fibrillation (AF) is the most common arrhythmia in clinical practice, and age is an independent risk factor for the development of AF. Qi-Po-Sheng-Mai granule (QPSM) has been used clinically to treat aging-related AF, however, its underlying mechanisms remain incompletely understood. Methods In this study, we established a D-galactose-induced aging rat model to evaluate the effects of QPSM on aging-related AF through electrocardiograms, echocardiography, and histopathological analysis. Further, we employed transcriptomics and metabolomics to uncover molecular mechanisms and targets. Finally, in vivo experiments were conducted to validate the expression of key targets in the D-Gal-induced aging rat model and the intervention effects of QPSM. Results QPSM significantly reduced the susceptibility to AF in aging rats and alleviated atrial dilation and fibrosis. The combined analysis of transcriptomics and metabolomics suggested that QPSM may inhibit the occurrence of aging-related AF by modulating Nampt expression and increasing NAD+ content in atrial tissue. Additionally, in vivo experiments confirmed that QPSM increased ATP content, reduced mitoSOX fluorescence intensity, and decreased the proportion of senescent cells. Whole-cell patch clamp results showed that QPSM could prolong the action potential duration of isolated atrial cells, increase I caL. This might be achieved by regulating the expression of Oxi-CaMKII and RyR2 ser2814, thereby alleviating calcium overload in atrial cells. Conclusions Our study demonstrates that QPSM may reduce the susceptibility to aging-related AF by regulating Nampt expression and NAD+ content, thereby mitigating calcium overload in atrial cells. This provides a direction for future research in related fields. Graphical Abstract

Marwa Khammassi, Anouar Abidi, Naoures Ochi et al.

Background: Wild fennel (Foeniculum vulgare Mill.) is a very common plant used in traditional medicine to treat several diseases. In recent years, scientific research proved its biological properties. However, the protective effect of fennel against bleomycin-induced pulmonary fibrosis (BLM-IPF) is not yet study. Purpose: Fennel essential oil (FEO) composition was characterized and its protective effect was assessed. Methods: GC–MS was employed to determine the chemical composition of fennel essential oil. The antioxidant activity was evaluated using TAC, DPPH, RAP and ABTS assays. After inducing fibrosis by bleomycin, several biological assays were used to evaluate the protective effect [proteins content, malondialdehyde MD, thiol group, superoxide dismutase (SOD) and catalase (CAT)]. Results: FEO was rich in estragole (77.55 %), fenchone (9.23 %), and limonene (9.23 %), and phenolic compounds and showed a significant antioxidant potential. The effects on BLM-IPF were revealed by disruption and alteration of oxidative stress biomarkers in lung, liver and kidney. Treatment of rats with FEO improved abnormal fluctuations in protein and thiol levels, decreased oxidative stress in terms of MDA and also restored the response of the antioxidant system, measured in terms of SOD and CAT, in lung, liver and kidney. The biological activity was recorded in a dose response manner. The potential of FEO in limiting the progress of the histopathologic effects of BLM-IPF was confirmed by microscopic histological observations, with a reduction of the fibrosis score and the inflammatory index in the FEO treated lung tissue. Conclusion: These results, proved that FEO could attenuate BLM-induced PF, thus suggesting that the latter could serve as a potential therapeutic approach for PF.

David Holthaus, David Holthaus, Christoph Rogmans et al.

IntroductionCervical cancer represents one of the main causes of female, cancer-related mortality worldwide. The majority of cancers are caused by human papillomaviruses such as HPV16 and HPV18. As chemotherapeutic resistance to first-line platinum treatment is still a predominant clinical challenge in advanced cervical cancer, novel treatment options including combinatorial therapies are urgently required to overcome chemotherapeutic resistance. Inhibition of A Disintegrin And Metalloproteinase (ADAM)-family members, heavily involved in tumour progression of a vast range of solid tumours, strongly improved response to chemotherapeutic treatment in other tumour entities including ovarian cancer.MethodsWe established two- and three-dimensional models derived from three traditional cervical cancer cell lines and ectocervical cancer-derived organoids. Following characterisation, these models were used to investigate their response to cisplatin treatment in the absence and presence of ADAM inhibitors using viability assays and automated live cell imaging.ResultsThe pivotal role of the metalloprotease ADAM17 driving chemotherapy resistance was detectable in all ectocervical cultures irrespective of the model system used, whereas ADAM10 inhibition was predominantly effective only in loosely aggregated spheroids. We showed prominent differences regarding treatment responses between 2D monolayers compared to 3D spheroid and 3D organoid model systems. Particularly, the organoid system, regarded as the closest representation of primary tumours, exhibited reliably the combinatorial effect of ADAM17 inhibition and cisplatin in all three individual donors.DiscussionAs two- and three-dimensional models of the same cell lines differ in their responses to chemotherapy it is essential to validate treatment strategies in more advanced model systems representing the patient situation more realistically. Ectocervical organoids showed reliable results regarding treatment responses closely mimicking the primary tumours and could therefore serve as an important tool for personalized medicine in cervical cancer. These findings strengthen the role of ADAM17 as a potential novel target for combinatorial treatments to overcome chemoresistance in cervical cancer.

Edward Nicol, Ngcwalisa Amanda Jama, Vuyelwa Mehlomakulu et al.

Abstract Ending AIDS by 2030 would depend on how successful health systems are in linking people living with HIV (PLHIV) into care. The World Health Organization recommended the ‘Universal Test and Treat’ (UTT) strategy – initiating all individuals testing positive on antiretroviral therapy (ART) irrespective of their CD4 count and clinical staging. This study aimed to explore the enablers and barriers to linkage to HIV care among adults with a new HIV diagnosis in a high-HIV prevalent rural district in South Africa. A qualitative study was undertaken to explore patients’ perceptions of enablers and barriers of linkage-to-care, using a life-story narration and dialogue approach. In-depth interviews were conducted with 38 HIV-positive participants sampled from a cohort of 1194 HIV-positive patients recruited from December 2017 to June 2018. Participants were selected based on whether they had been linked to care or not within 3 months of positive HIV diagnosis. Interviews were thematically analysed using a general inductive approach. Of the 38 participants, 22 (58%) linked to care within three months of HIV-positive diagnosis. Factors that facilitated or inhibited linkage-to-care were found at individual, family, community, as well as health systems levels. Enablers included a positive HIV testing experience, and assistance from the fieldwork team. Support from family, and friends, as well as prior community-based education about HIV and ART were also noted. Individual factors such as acceptance of HIV status, previous exposure to PLHIV, and fear of HIV progressing, were identified. Barriers to linkage included, denial of HIV status, dislike of taking pills, and preference for alternative medicine. Negative experiences with counselling and health systems inefficiency were also noted as barriers. Perceived stigma and socio-economic factors, such as lack of food or money to visit the clinic were other barriers. Community-based and health system-level interventions would need to focus on clinic readiness in providing patients with necessary and effective health services such as proper and adequate counselling. This could increase the number of patients who link to care. Finally, interventions to improve linkage-to-care should consider a holistic approach, including training healthcare providers, community outreach and the provision of psychological, social, and financial support.