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.

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.

UNASSIGNED: IgG4-related disease is a rare and emerging pathology, characterized by the appearance of pseudotumors. Due to the ability to mimic other pathologies, it is essential to consider it as a differential diagnosis in multisystemic processes. The diagnosis is challenging, requiring a multidisciplinary approach, to minimize the associated morbidity and mortality.
UNASSIGNED: IgG4-related disease (IgG4-RD) is a rare, emerging, systemic and chronic pathology, characterized by the appearance of pseudotumors resulting from tissue infiltration by IgG4-positive plasma cells that promote eosinophilic inflammation of the tissue with subsequent fibrosis. We present the case of a male, 45-year-old patient, with marked weight loss and skin pallor detected by his family doctor during a child health consultation of his daughter. When questioned, the patient referred complaints of postprandial discomfort in the left hypochondrium with a feeling of fullness, weight loss, chronic fatigue and hyperhidrosis that had lasted for a month. On physical examination, he was pale, and had pain at palpation of the left hypochondrium. Laboratory data showed increased inflammation markers, abdominal ultrasound and CT demonstrated numerous enlarged lymph nodes in the upper quadrants, raising concern for a malignant lymphoproliferative process. Serological, imaging, clinical and laparoscopic excisional biopsy revealed features of IgG4-related disease and excluded malignant lymphoproliferative disease. The immediate response to treatment with oral prednisolone 30 mg/day also contributed for diagnosis confirmation. Due to refractory disease after gradual prednisolone reduction, second-line therapy with rituximab was initiated. Over the 6 years of follow-up, the patient presented multiple exacerbations characterized by the emergence of systemic symptoms, being maintained under close clinical and imaging follow-up by reumathology, infectious diseases, and family medicine specialists.

PV-10 is a 10% formulation of rose bengal sodium that has potent immunotherapeutic and anti-cancer activity against various tumors, including metastatic melanoma and refractory neuroblastoma. Currently, PV-10 is undergoing clinical testing for refractory metastatic neuroendocrine cancer and melanomas. However, preclinical investigation of PV-10 activity and its mechanisms against phenotypically and molecularly diverse adult solid tumors had not been conducted. In a panel of human cell lines derived from breast, colorectal, head and neck, and testicular cancers, we demonstrated that PV-10 induces cytotoxicity by apoptotic and autophagic pathways involving caspase-mediated PARP cleavage, downregulation of SQSTM1/p62, and upregulation of beclin-1. Treatment with PV-10 also consistently reduced phosphorylation of WNK1, which has been implicated in cancer cell migration and autophagy inhibition. By wound healing assay, PV-10 treatment inhibited the migration of cancer cells. Finally, significant inhibition of tumor growth was also noted in tumor-bearing mice treated with PV-10 by intralesional or systemic administration. In addition to known PV-10-mediated tumor-specific cytotoxic effects, we identified the mechanisms of PV-10 and provide new insights into its effect on autophagy and metastasis. Our data provide essential mechanism-based evidence and biomarkers of activity to formulate clinical studies of PV-10 in the future.