Systems thinking has been recognized as valuable to public health policy, research and practice. Commentators and reviews have highlighted that there is still much to be done to embrace its potential. Here, we highlight that much of the discourse about systems thinking in, and for, public health supports the pursuit of a narrow path and is limited with respect to the lineages of Systems that are embraced. We invite readers to see the potential of systems thinking in pursuing a broader path which is motivated by a concern for alleviating health inequalities. This does not replace the narrow path but encompasses it. It prompts different considerations with respect to the nature of the transformation, partnership working and legitimacy. It also invites a different way of engaging with systems thinking and different ways of conceptualizing and managing change. The broad path both requires, and helps enhance, new ways of doing, relating, organizing, knowing and framing which are vital for the future of public health as a global concern.

UNASSIGNED: Antinuclear antibody-negative full-house lupus nephritis though previously reported, is fairly uncommon. Some patients go on to develop antibodies later in the disease course. The presence of RO-52 antibody in this case suggests an underlying immunological cause. Swift management based on strong clinical suspicion can be life-saving to the patient.
UNASSIGNED: Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE) and is more likely to progress to end-stage renal disease (ESRD). With the recent EULAR/ACR criteria mandating antinuclear antibody (ANA) positivity as an entry criterion, clinicians are faced with a diagnostic dilemma in diagnosing cases of seronegative SLE. We present the case of a 25-year-old female who presented with photosensitive malar rash, hair loss, oral ulcers, menorrhagia, and kidney dysfunction, suggestive of SLE. Her ANA tests were negative, raising doubts about the diagnosis. Biopsy was delayed owing to anemia and thrombocytopenia, and clinical judgment led to the patient being diagnosed with LN, with prompt treatment resulting in significant improvement. Renal biopsy subsequently confirmed the case as diffuse class IV LN with full-house nephropathy. This case highlights the limitations of relying solely on ANA positivity in diagnosing LN and underscores the need for a comprehensive diagnostic approach for SLE that incorporates clinical features, immunological markers, and patient demographics. ANA-negative SLE patients demand heightened clinical suspicion, especially when other diagnostic parameters align with the disease. Swift intervention with immunosuppressive therapy, as seen in this case, can be life-saving.

Tuberculous paradoxical reaction presents as clinical deterioration during appropriate tuberculosis therapy and is a separate entity from treatment failure and drug resistance. We describe a case of central nervous system paradoxical reaction following tuberculous meningoencephalitis treatment in an immunocompromised patient with systemic lupus erythematosus.

BACKGROUND: Atopic dermatitis (AD) substantially burdens individuals, families, and healthcare systems. We aimed to document the treatment journey of pediatric patients with moderate-to-severe AD in a referral center based in our country.
METHODS: This retrospective study reviewed patients aged 1-18 years diagnosed with AD, seeking systemic treatment recommendations from the \"pediatric allergy and dermatology multidisciplinary team meeting\".
RESULTS: Over the 14-month study period, 30 (12.5%) of 240 AD patients were evaluated in the pediatric dermato-allergy team meetings. The median age of the patients was 13.66 years (Q1-Q3: 7.94-17.27), of whom 60% were male. The median annual healthcare visits for AD were 4 (Q1-Q3: 1.00-8.75). Among the study group, 70% were sensitized to aeroallergens, and admission markers included total IgE (median: 1980 IU/mL, Q1-Q3: 794.50-5446), and eosinophil counts (median: 650, Q1-Q3: 275-1275). All patients utilized intermittent and/or continuous topical corticosteroids (CS), with 56.6% employing short-term/long-term topical tacrolimus. Over the past two years, systemic CSs were utilized in 93.3% of the patients, whereas 57.1% received more than one course. Approximately 43.3% of the patients agreed to receive systemic cyclosporine treatment, with only 30.8% benefiting and 3.3% reporting adverse effects (hypertrichosis and cellulitis). Three patients self-funded dupilumab, all benefiting without adverse effects. Omalizumab, mycophenolate mofetil and narrow-band  ultraviolet (UV) treatments were used in one patient each, with limited benefit observed. Health insurance did not grant approval for a Janus kinase inhibitor for one patient.
CONCLUSIONS: Managing moderate to severe AD is complex and costly, considering disease heterogeneity, comorbidities, care pathways, and health system challenges. Addressing the unmet needs should be a priority in Türkiye\'s healthcare systems.

UNASSIGNED: Uveitis, a notable cause of severe visual impairment, is frequently characterized as infectious or noninfectious autoimmune uveitis (AU), the latter of which is commonly associated with younger individuals and systemic diseases. Despite the condition\'s widespread impact, there are substantial gaps in the comprehension of its pathogenesis, clinical presentation, and therapeutic response, particularly concerning systemic disease-associated uveitis.
UNASSIGNED: The current study aims to bridge these gaps through an extensive examination of demographic and clinical features in AU patients, thereby informing future research, and therapeutic strategies, and improving patient outcomes.
UNASSIGNED: This retrospective observational study analyzed 261 patients with systemic disease-associated uveitis from January 2018 to December 2022 in Damascus, Syria. With diagnoses made using the Standardization of Uveitis Nomenclature Working Group Criteria, the study evaluated tailored treatment efficacy at the 24-month post-treatment mark, alongside comprehensive ophthalmic examinations, laboratory evaluations, and radiographic assessments.
UNASSIGNED: In our study, included 87 patients with Systemic Disease-Associated Autoimmune Uveitis (SDA-AU). Women represented 64.36% of this group, and the mean age at diagnosis was 39.8±17.9 years (range 7-71) for men and 43.8±15.4 years (range 11-69). The most reported symptom was a painful red eye (52.87%). The onset of symptoms was sudden for 32.18% of patients, while 67.81% reported gradual development. Complications occurred in 33.33% of patients, including cataracts (41.37% of those with complications) and glaucoma (17.24%). Laboratory evaluations showed elevated inflammation markers in 66.66% of patients. Upon the 24-month assessment, 48.27% of patients achieved complete remission, 37.93% showed significant improvement, while disease worsened in 13.79% of cases.
UNASSIGNED: Our findings demonstrated that the presentation of AU in this cohort frequently precedes the diagnosis of systemic diseases, affirming the vital role of an early and accurate diagnosis of uveitis for the detection of underlying systemic conditions. In conclusion, our study underlines the significance of a comprehensive and multidisciplinary approach in the management of SD-AU, leading to improved prognosis and quality of life for patients.

This study examines the relationship between cyber violence and cyber sex crimes, specifically focusing on these crimes as systemic issues among adolescents. The research highlights the severe impact of cyber sex crimes, characterized by the non-consensual sharing of sexually explicit content. It examines various factors that may contribute to witnessing cyber sex crimes, including exposure to violent online content, personal experiences of cyber violence (either as a victim or perpetrator), and the role of parental and teacher interventions. Utilizing data from a nationwide survey conducted by the Korea Communications Commission, the study analyzes responses from 9016 adolescents in 2021 and 9693 in 2022. This analysis reveals significant predictors of witnessing cyber sex crimes and examines how perceptions of cyber violence and interventions of authoritative figures may influence adolescents\' perception of cyber sex crimes as either systemic or individual issues. With females disproportionately affected, the findings underscore a gendered aspect of cyber violence. Furthermore, these insights suggest that perceiving cyber violence as a serious issue leads to viewing cyber sex crimes as systemic problems necessitating societal intervention. The study advocates for enhanced digital literacy education and systemic changes to protect adolescents from the widespread threats of cyber violence and sex crimes.

UNASSIGNED: People with systemic sclerosis (SSc) face barriers to physical activity. Few studies have described physical activity in SSc, and none have explored physical activity longitudinally during COVID-19. We evaluated physical activity from April 2020 to March 2022 among people with SSc.
UNASSIGNED: The Scleroderma Patient-centred Intervention Network (SPIN) COVID-19 Cohort was launched in April 2020 and included participants from the ongoing SPIN Cohort plus external enrolees. Participants completed measures bi-weekly through July 2020, then every 4 weeks afterwards (28 assessments). Physical activity was assessed via the self-reported International Physical Activity Questionnaire-Elderly. Analyses included estimated means with 95% confidence intervals for physical activity across assessments. Missing data were imputed for main analyses. Sensitivity analyses included evaluating only participants who completed >90% of items for >21 of 28 possible assessments (\'completers\') and stratified analyses by sex, age, country and SSc subtype.
UNASSIGNED: A total of 800 people with SSc enrolled. Mean age was 55.6 (standard deviation (SD) = 12.6) years. Physical activity significantly decreased from April 2020 to March 2021 (standardized mean difference (SMD) = -0.17, 95% confidence interval (CI) = -0.26 to -0.07) and was stable from March 2021 to March 2022 (SMD = -0.05, 95% CI = -0.15 to 0.05). Results were similar for completers and subgroups. The proportion of participants who met World Health Organization minimum physical activity recommendations of at least 150 min of moderate-to-vigorous activity per week ranged from 63% to 82% across assessments.
UNASSIGNED: Physical activity decreased by a relatively small amount, on average, across the pandemic. Most participants met recommended physical activity levels.

Obesity is a complex disease associated with augmented risk of metabolic disorder development and cellular dysfunction in various species. The goal of the present study was to investigate the impacts of obesity on the metabolic health of old mares as well as test the ability of diet supplementation with either a complex blend of nutrients designed to improve equine metabolism and gastrointestinal health or L-carnitine alone to mitigate negative effects of obesity. Mares (n = 19, 17.9 ± 3.7 years) were placed into one of three group: normal-weight (NW, n = 6), obese (OB, n = 7) or obese fed a complex diet supplement for 12 weeks (OBD, n = 6). After 12 weeks and completion of sample collections, OB mares received L-carnitine alone for an additional 6 weeks. Obesity in mares was significantly associated with insulin dysregulation, reduced muscle mitochondrial function, and decreased skeletal muscle oxidative capacity with greater ROS production when compared to NW. Obese mares fed the complex diet supplement had better insulin sensivity, greater cell lipid metabolism, and higher muscle oxidative capacity with reduced ROS production than OB. L-carnitine supplementation alone did not significantly alter insulin signaling, but improved lipid metabolism and muscle oxidative capacity with reduced ROS. In conclusion, obesity is associated with insulin dysregulation and altered skeletal muscle metabolism in older mares. However, dietary interventions are an effective strategy to improve metabolic status and skeletal muscle mitochondrial function in older mares.

This paper provides a complete protocol for studying the effects of inhaled paraquat (PQ), a toxic herbicide that has negative effects systemically and on the lungs. The protocol aims to evaluate the effects of aerosolized PQ exposure on lung and systemic injury in an animal model, which will provide significant information for therapeutic interventions for PQ-induced pulmonary and systemic damage. The protocol involves the following key components: 1. Study groups: By including control, non-treated aerosolized PQ-exposed, and treated PQ-exposed animals with various agent groups in the experiment, lung and systemic injury in each group could be evaluated, and different measured parameters could be compared among groups. 2. PQ exposure: Animals in the PQ-exposed groups are subjected to PQ aerosol inhalation, simulating occupational or accidental exposure in farmers working with this herbicide. 3. Assessment measures: To determine the degree of lung and systemic injury and its physiological effects, several assessments, such as biochemical markers, histopathological analysis, and functional tests, are used. The protocol offers reliable and accurate results by using standardized methods and data collection. The effect of PQ exposure on lung and systemic injury could be evaluated by statistical analysis of the collected data, which also makes it easier to identify possible protective agents or interventions. This comprehensive evaluation protocol provides an essential basis for studying the mechanisms behind PQ-induced lung and systemic injury and assessing the effectiveness of preventative or therapeutic strategies in minimizing its adverse effects.

Tetraploidy, a condition in which a cell has four homologous sets of chromosomes, may be a natural physiological condition or pathophysiological such as in cancer cells or stress induced tetraploidisation. Its contribution to cancer development is well known. However, among the many models proposed to explain the causes, mechanisms and steps of malignant cell transformation, only few integrate tetraploidization into a systemic multistep approach of carcinogenesis. Therefore, we will i) describe the molecular and cellular characteristics of tetraploidy; ii) assess the contribution of stress-induced tetraploidy in cancer development; iii) situate tetraploidy as a metastable state leading to cancer development in a systemic cell-centered approach; iiii) consider knowledge gaps and future perspectives. The available data shows that stress-induced tetraploidisation/polyploidisation leads to p53 stabilisation, cell cycle arrest, followed by cellular senescence or apoptosis, suppressing the proliferation of tetraploid cells. However, if tetraploid cells escape the G1-tetraploidy checkpoint, it may lead to uncontrolled proliferation of tetraploid cells, micronuclei induction, aneuploidy and deploidisation. In addition, tetraploidization favors 3D-chromatin changes and epigenetic effects. The combined effects of genetic and epigenetic changes allow the expression of oncogenic gene expression and cancer progression. Moreover, since micronuclei are inducing inflammation, which in turn may induce additional tetraploidization, tetraploidy-derived genetic instability leads to a carcinogenic vicious cycle. The concept that polyploid cells are metastable intermediates between diploidy and aneuploidy is not new. Metastability denotes an intermediate energetic state within a dynamic system other than the system\'s state at least energy. Considering in parallel the genetic/epigenetic changes and the probable entropy levels induced by stress-induced tetraploidisation provides a new systemic approach to describe cancer development.