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Pimelea is one of the highly toxic plants in Australia, particularly affecting cattle. It contains simplexin, a potent toxin that can cause Pimelea poisoning (St. George Disease) in livestock. A survey was conducted to assess the current impact of Pimelea on livestock production, pasture systems, and financial losses among agricultural producers. In addition, information was also sought about the environmental conditions that facilitate its growth and the effectiveness of existing management strategies. The survey responses were obtained from producers affected by Pimelea across nine different Local Government Areas, through three States, viz., Queensland, New South Wales, and South Australia. Pimelea was reported to significantly affect animal production, with 97% of producers surveyed acknowledging its detrimental effects. Among livestock, cattle were the most severely affected (94%), when compared to sheep (13%), goats (3%), and horses (3%). The presence of Pimelea was mostly observed in spring (65%) and winter (48%), although 29% of respondents indicated that it could be present all year-round under favorable rainfall conditions. Germination was associated with light to moderate rainfall (52%), while only 24% linked it to heavy rainfall. Pimelea simplex F. Muell. was the most frequently encountered species (71%), followed by Pimelea trichostachya Lindl. (26%). Infestations were reported to occur annually by 47% of producers, with 41% noting occurrences every 2 to 5 years. Financially, producers estimated average annual losses of AUD 67,000, with 50% reporting an average of 26 cattle deaths per year, reaching up to 105 deaths in severe years. Some producers were spending up to AUD 2100 per annum to manage Pimelea. While chemical and physical controls were commonly employed, integrating competitive pastures and alternative livestock, such as sheep and goats, was considered as a potential management strategy. This study reiterates the need for further research on sustainable pasture management practices to reduce Pimelea-related risks to livestock and agricultural production systems. Full article

Background and Clinical Significance: Brugada syndrome (BrS) is a rare inherited cardiac channelopathy, often associated with SCN5A loss-of-function mutations. Clinical presentations range from asymptomatic to malignant arrhythmias and sudden cardiac death. Physiological and pharmacological stressors affecting sodium channel function—such as pyrexia, certain medications, and possibly pregnancy—may unmask or exacerbate arrhythmic risk. However, there is limited information regarding pregnancy and obstetric outcomes. Obstetric management remains largely informed by isolated case reports and small case series. A literature review was conducted using OVID Medline and Embase, identifying case reports, case series, and one retrospective cohort study reporting clinical presentation, obstetric management, and outcomes in maternal BrS. A case is presented detailing coordinated multidisciplinary input, antenatal surveillance, and intrapartum and postpartum care to contribute to the growing evidence base guiding obstetric care in this complex setting. Case Presentation: A 30-year-old G2P0 woman with asymptomatic BrS (SCN5A-positive) was referred at 31 + 5 weeks’ gestation for multidisciplinary antenatal care. Regular review and collaborative planning involving cardiology, anaesthetics, maternal–fetal medicine, and obstetrics guided a plan for vaginal delivery with continuous cardiac and fetal monitoring. At 38 + 0 weeks, the woman presented with spontaneous rupture of membranes and underwent induction of labour. A normal vaginal delivery was achieved without arrhythmic events. Epidural block with ropivacaine and local anaesthesia with lignocaine were well tolerated, and 24 h postpartum monitoring revealed no abnormalities. Conclusions: This case adds to the limited but growing literature suggesting that with individualised planning and multidisciplinary care, pregnancies in women with BrS can proceed safely and without complication. Ongoing case reporting is essential to inform future guidelines and optimise maternal and fetal outcomes. Full article

Hurricane Helene made landfall near Perry (Latitude 30.1 N) in the Big Bend area of Florida with a central pressure of 939 hPa. It moved northwards creating devastating damage and loss of life; however, the greatest damage and number of fatalities occurred well to the north around the City of Ashville (Latitude 35.6 N) where extreme rainfall fell and some of the strongest wind gusts were reported. This paper describes the change in the hurricane’s structure as it tracked northwards, how it gathered tropical moisture from the Atlantic and a turning wind profile between the 850 hPa and 500 hPa elevations, which led to such extreme rainfall. This turning wind profile is shown to be associated with extreme rainfall and loss of life from drowning and landslides around the globe. The area around Ashville suffered 157 fatalities, which is a considerable proportion of the 250 fatalities so far recorded in the whole United Stares from Helene. This is of extreme concern and should be investigated in detail as the public expect the greatest impact from hurricanes to be confined to coastal areas near the landfall site. It is another example of increased death tolls from tropical cyclones moving inland and generating heavy rainfall. As the global population increases and inland centres become more urbanised, run off from such rainfall events increases, which causes greater devastation. Full article

After the first release of synthalin B (dodecamethylenbiguanide) in 1928 and its later retraction in the 1940s in Germany, the retraction of phenformin (N-Phenethylbiguanide) and of Buformin in the USA (but not outside) because of the lethal complication of acidosis seemed to have put an end to the era of the biguanides as oral antidiabetics. The strongly hygroscopic metformin (1-1-dimethylbiguanide), first synthesized 1922 and resuscitated as an oral antidiabetic (type 2 of the elderly) compound first released in 1959 in France and in other European countries, was used in the first large multicenter prospective long-term trial in England in the UKPDS (1977–1997). It was then released in the USA after a short-term prospective trial in healthy overweight “young” type 2 diabetics (mean age 53 years) in 1995 for oral treatment of type 2 diabetes. It was, however, prescribed to mostly multimorbid older patients (above 60–65 years of age). Metformin is now the most used oral drug for type 2 diabetes worldwide. While intravenous administration of biguanides does not have any glucose-lowering effect, their oral administration leads to enormous increase in their intestinal concentration (up to 300-fold compared to that measured in the blood), to reduced absorption of glucose from the diet, to increased excretion of glucose through the stool, and to decrease in insulin serum level through increased hepatic uptake and decreased production. Intravenously injected F18-labeled glucose in metformin-treated type 2 diabetics accumulates in the small and even more in the large intestine. The densitometry picture observed in metformin-treated overweight diabetics is like that observed in patients after bowel-cleansing or chronically taking different types of laxatives, where the accumulated radioactivity can even reach values observed in colon cancer. The glucose-lowering mechanism of action of metformin is therefore not only due to inhibition of glucose uptake in the small intestine but also to “attraction” of glucose from the hepatocyte into the intestine, possibly through the insulin-mediated uptake in the hepatocyte and its secretion into the bile. Furthermore, these compounds have also a diuretic effect (loss of sodium and water in the urine) Acute gastrointestinal side effects accompanied by fluid loss often lead to the drugs’ dose reduction and strongly limit adherence to therapy. Main long-term consequences are “chronic” dehydration, deficiency of vitamin B12 and of iron, and, as observed for all the biguanides, to “chronic” increase in fasting and postprandial lactate plasma level as a laboratory marker of a clinical condition characterized by hypotension, oliguria, adynamia, and evident lactic acidosis. Metformin is not different from the other biguanides: synthalin B, buformin, and phenformin. The mechanism of action of the biguanides as antihyperglycemic substances and their side effects are comparable if not even stronger (abdominal pain, nausea, vomiting, diarrhea, fluid loss) to those of laxatives. Full article

Hemorrhage is the leading cause of preventable death in trauma care, requiring rapid and accurate detection to guide effective interventions. Hemorrhagic shock can be masked by underlying compensatory mechanisms, which may lead to delayed decision-making that can compromise casualty care. In this proof-of-concept study, we aimed to develop and evaluate machine learning models to predict Percent Estimated Blood Loss from a photoplethysmography waveform, offering non-invasive, field deployable solutions. Different model types were tuned and optimized using data captured during a hemorrhage and resuscitation swine study. Through this optimization process, we evaluated different time-lengths of prediction windows, machine learning model architectures, and data normalization approaches. Models were successful at predicting Percent Estimated Blood Loss in blind swine subjects with coefficient of determination values exceeding 0.8. This provides evidence that Percent Estimated Blood Loss can be accurately derived from non-invasive signals, improving its utility for trauma care and casualty triage in the pre-hospital and emergency medicine environment. Full article

To explore the potential seed compounds from natural products as anticancer agents against small-cell lung cancer (SCLC), the underground parts of Agapanthus africanus, a plant commonly used for ornamental purposes, were investigated. Three spirostan-type steroidal glycosides (1–3) were isolated and identified by nuclear magnetic resonance spectral analysis. Compounds 1–3 exhibited cytotoxicity against SBC-3 human SCLC cells, with IC₅₀ values of 0.56, 1.4, and 7.4 µM, respectively. Compound 1, also known an agapanthussaponin A, demonstrated the most potent cytotoxicity among the isolated compounds and was evaluated for its apoptosis- and ferroptosis-inducing activities. Compound 1 arrested the cell cycle of SBC-3 cells in the G₂/M phase and induced apoptosis primarily via the mitochondrial pathway, characterized by caspases-3 and -9 activation, loss of mitochondrial membrane potential, and overproduction of reactive oxygen species. Additionally, 1 triggered ferroptosis via a dual mechanism consisting of enhanced cellular iron uptake through upregulation of transferrin and transferrin receptor 1 expression and impaired glutathione synthesis via downregulation of both xCT and glutathione peroxidase 4 expression. Compound 1 induces cell death via the apoptosis and ferroptosis pathways, suggesting its promise as a seed compound for the development of anticancer therapeutics against SCLC. Full article

Bycatch is the most common cause of death of small delphinids worldwide, including the Mediterranean Sea. The diagnosis of bycatch as cause of death in stranded cetaceans depends on the cumulative presence of multiple findings, termed bycatch criteria. In this study, we retrospectively evaluated the presence of bycatch criteria in 138 necropsied cetaceans, 136 stranded and 2 confirmed bycaught, in the Catalan Mediterranean Sea across a 13-year period. With the aim of identifying the most specific and reliable bycatch criteria, the animals’ cause of death was classified as either bycaught or other causes. Animals were necropsied according to standard procedures with complete histopathological examination and ancillary diagnostic techniques. We reviewed the necropsy reports and photographs of 138 cetaceans of seven species. Bycatch had been determined as the cause of death/stranding in 40 (29%) necropsied cetaceans. Both sexes were equally represented in the bycatch group. Bycatch was diagnosed in the Mediterranean common bottlenose dolphin (10/14; 71.4%), striped dolphin (29/108; 26.9%), and Risso’s dolphin (1/11; 9.1%). Sixty-seven out of 98 (68.3%) cetaceans that had been classified as non-bycatch had one or two bycatch criteria. Cetaceans with two and three major criteria had an overlap of causes of death, as some animals were diagnosed with bycatch and others with other causes of mortality. Animals with four criteria were invariably diagnosed as being bycaught. Recent feeding, absence of disease, good nutritional status, marks of fishing gear, multiorgan intravascular gas bubbles, hyphema and amputations or sharp incisions presumably inflicted by humans were significantly more likely to result in a diagnosis of bycatch, while loss of teeth and cranial fractures were not. None of the dolphins diagnosed as bycatch had ingested fishing gear. Our results highlight the relevance of bycatch as the cause of death of dolphins in the Mediterranean and suggest that some criteria traditionally linked to bycatch are not specific for bycatch in our region. Full article

Despite the current level of public immunity to SARS-CoV-2, the early inflammatory events associated with respiratory distress in COVID-19 patients are not fully elucidated. Syrian golden hamsters, facultative hibernators, recapitulate the phenotype of SARS-CoV-2-induced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—induced severe acute lung injury seen in patients. In this study, we describe the predominance of the innate immune response in hamsters inoculated with four different SARS-CoV-2 variants, underscoring phenotypic differences among them. Severe inflammatory lung injury was chronologically associated with acute and significant weight loss, mainly in animals inoculated with A.2 and Delta variants. Omicron-infected animals had lower overall histopathology scores compared to other variants. We highlight the central role of endothelial injury and activation in the pathogenesis of experimental SARS-CoV-2 infection in hamsters, characterised by the presence of proliferative type I and type II pneumocytes with abundant surfactant expression, thereby maintaining hyperinflated alveolar fields. Additionally, there was evidence of intrapulmonary lymphatic vessel proliferation, which was accompanied by a lack of detectable microthrombosis in the lung parenchyma. However, white microthrombi were observed in lymphatic vessels. Our findings suggest that the physiological compensatory mechanisms that maintain respiratory homeostasis in Golden Syrian hamsters prevent severe respiratory distress and death after SARS-CoV-2 infection. Full article

In October 2024, a DANA (Isolated Depression at High Levels) triggered torrential rains across the Valencian Community, causing 227 deaths, severe infrastructure damage, and economic losses estimated at €17.8 billion. In this context of crisis, startups, despite having fewer resources and less experience than large corporations, played a significant role in crisis communication, shaping public perception and operational continuity. This study explores the communication strategies adopted by startups during and after the disaster, focusing on their activity on Instagram, TikTok, and Facebook between October 2024 and January 2025. Using a mixed-methods approach, we conducted a quantitative analysis of digital discourse through the Fanpage Karma tool, assessing metrics such as engagement, reach, and posting frequency. Sentiment analysis was performed using GPT-4, an advanced natural language processing model, and in-depth interviews with startup representatives provided qualitative insights into reputational impacts. The findings reveal that startups which aligned their discourse with the social context, prioritizing transparency and emotional proximity, enhanced their visibility and credibility. These results underscore how effective crisis communication not only mitigates reputational risk but also strengthens the local entrepreneurial ecosystem through trust-building and social responsibility. Full article

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that primarily affects motor neurons, leading to loss of muscle control, and, ultimately, respiratory failure and death. Despite some advances in recent years, the underlying genetic and molecular mechanisms of ALS remain largely elusive. In this respect, a better understanding of these mechanisms is needed to identify new and biologically relevant therapeutic targets that could be developed into treatments that are truly disease-modifying, in that they address the underlying causes rather than the symptoms of ALS. In this study, we used two approaches to model multi-omics data in order to map and elucidate the genetic and molecular mechanisms involved in ALS, i.e., the molecular landscape building approach and the Patrimony platform. These two methods are complementary because they rely upon different omics data sets, analytic methods, and scoring systems to identify and rank therapeutic target candidates. The orthogonal combination of the two modeling approaches led to significant convergences, as well as some complementarity, both for validating existing therapeutic targets and identifying novel targets. As for validating existing targets, we found that, out of 217 different targets that have been or are being investigated for drug development, 10 have high scores in both the landscape and Patrimony models, suggesting that they are highly relevant for ALS. Moreover, through both models, we identified or corroborated novel putative drug targets for ALS. A notable example of such a target is MATR3, a protein that has strong genetic, molecular, and functional links with ALS pathology. In conclusion, by using two distinct and highly complementary disease modeling approaches, this study enhances our understanding of ALS pathogenesis and provides a framework for prioritizing new therapeutic targets. Moreover, our findings underscore the potential of leveraging multi-omics analyses to improve target discovery and accelerate the development of effective treatments for ALS, and potentially other related complex human diseases. Full article

In wet subtropical environments, perennial groundcovers are common in horticultural plantations to protect the soil from erosion. However, there has been little investigation into whether seeding annual cover crops into the perennial groundcovers provides additional soil services including carbon and nutrient cycling in these systems. To investigate this, farmer participatory field trials were conducted in commercial avocado, macadamia, and coffee plantations in the wet Australian subtropics. Cover crops were direct-seeded into existing inter-row groundcovers in winter (cool season cover crops), and into the same plots the following summer (warm season cover crops). Inter-row biomass was quantified at the end of winter and summer in the control (no cover crop) and cover crops treatments. Soil carbon and nutrient cycling parameters including hot water extractable carbon, water soluble carbon, autoclavable citrate-extractable protein and soil enzyme activities were quantified every two months from early spring (September) 2021 to late autumn (May) 2022. Seeded cover crops produced 500 to 800 kg ha⁻¹ more total inter-row biomass over winter at the avocado coffee sites, and 3000 kg ha⁻¹ biomass in summer at the coffee site. However, they had no effect on biomass production in either season at the macadamia site. Soil functional parameters changed with season (i.e., time of sampling), with few significant effects of cover crop treatments on soil function parameters across the three sits. Growing a highly productive annual summer cover crop at the coffee site led to suppression and death of perennial groundcovers, exposing bare soil in the inter-row by 3 weeks after termination of the summer cover crop. Annual cover crops seeded into existing perennial groundcovers in tree crop systems had few significant impacts on soil biological function over the 12-month period, and their integration needs careful management to avoid investment losses and exacerbating the risk of soil erosion on sloping lands in the wet subtropics. Full article

Background: Primary sclerosing cholangitis (PSC) accounts for 10–15% of liver transplants but is the leading cause of retransplant. This study evaluates whether PSC patients have different survival and graft outcomes when receiving grafts from donors after brain death (DBD) versus circulatory (DCD) death. Methods: Using the SRTR database (2004–2024), we compared PSC patients receiving DCD vs. DBD grafts. Demographics and outcomes including graft loss, mortality, and retransplant were analyzed using multivariable logistic and Cox regression, along with propensity-matched analysis. Results: Among 5762 PSC patients, 391 (6.8%) received DCD grafts. Patients receiving DCD grafts were older but had lower MELD scores (19 vs. 22; p < 0.001) and were less often functionally dependent (11.3% vs. 24.4%; p < 0.001). Multivariable Cox regression demonstrated that receipt of a DCD graft was independently associated with time to graft loss (HR 1.59; CI 1.10–2.31; p = 0.013. Similarly, DCD graft receipt significantly increased the likelihood of requiring retransplant (HR 3.25; CI: 1.93–5.46; p < 0.001) but did not increase the likelihood of mortality. Propensity matched analysis further supported these finding with significantly higher graft loss with DCD grafts at one and two years and higher retransplant rates at all time points including 5-years (+7.9%, CI 4.4 to 11.4%; p < 0.001). Conclusions: DCD grafts in PSC patients are linked to worse graft survival and higher retransplant rates. They may be best suited for older, lower-MELD patients, but further studies on perfusion strategies are needed. Full article

Background: Astrocytes are not only structural cells but also play a pivotal role in neurogenesis and neuroprotection by secreting a variety of neurotrophic factors that support neuronal survival, growth, and repair. This study investigates the time-dependent responses of primary rat cortical astrocytes to oxygen–glucose deprivation (OGD) and evaluates the neuroprotective potential of astrocyte-conditioned medium (ACM). Methods: Primary rat cortical astrocytes and neurons were obtained from postnatal Sprague Dawley rat pups (P1–3) and embryos (E17–18), respectively. Astrocytes exposed to 6, 24, and 48 h of OGD (0.3% O₂) were assessed for viability, metabolic function, hypoxia-inducible factor 1 and its downstream genes expression. Results: While 6 h OGD upregulated protective genes such as Vegf, Glut1, and Pfkfb3 without cell loss, prolonged OGD, e.g., 24 or 48 h, led to significant astrocyte death and stress responses, including elevated LDH release, reduced mitochondrial activity, and increased expression of pro-apoptotic marker Bnip3. ACM from 6 h OGD-treated astrocytes significantly enhanced neuronal survival following 6 h OGD and 24 h reperfusion, preserving dendritic architecture, improving mitochondrial function, and reducing cell death. This protective effect was not observed with ACM from 24 h OGD astrocytes. Furthermore, 6 h OGD-ACM induced autophagy in neurons, as indicated by elevated LC3b-II and decreased p62 levels, suggesting autophagy as a key mechanism in ACM-mediated neuroprotection. Conclusions: These findings demonstrate that astrocytes exhibit adaptive, time-sensitive responses to ischemic stress and secrete soluble factors that can confer neuroprotection. This study highlights the therapeutic potential of targeting astrocyte-mediated signalling pathways to enhance neuronal survival following ischemic stroke. Full article

Hypertensive left ventricular hypertrophy (LVH) is an ominous cardiovascular sequel to chronic hypertension, marked by structural and functional alterations in the heart. Identified as a significant risk factor for adverse cardiovascular outcomes, LVH is typically detected through echocardiography and is characterized by pathological thickening of the left ventricular wall. This hypertrophy results from chronic pressure overload (increased afterload), leading to concentric remodelling, or from increased diastolic filling (preload), contributing to eccentric changes. Apoptosis, a regulated process of cell death, plays a critical role in the pathogenesis of LVH by contributing to cardiomyocyte loss and subsequent cardiac dysfunction. Given the substantial clinical implications of LVH for cardiovascular health, this review critically examines the role of cardiomyocyte apoptosis in its disease progression, evaluates the impact of pharmacological interventions, and highlights the necessity of a comprehensive, multifaceted treatment approach for the prevention and management of hypertensive LVH. Finally, we address the health disparities associated with LVH, with particular attention to the disproportionate burden faced by African Americans and other Black communities, as this remains a key priority in advancing equity in cardiovascular care. Full article

Objectives: This study aims to explore the experiences of bereaved family members during and after the loss of a relative in an intensive care unit (ICU) during the COVID-19 pandemic-related visitation restrictions, as well as to assess their perceptions of a nurse-led bereavement support programme. Methods: Ten participants with a relative who had died in an ICU were recruited in September 2020 during a follow-up bereavement meeting at a tertiary cardiac centre in Switzerland. Descriptive qualitative research was conducted. Face-to-face nurse-led follow-up bereavement meetings, adapted to the pandemic circumstances and conducted as semi-structured interviews, were analysed by a thematic analysis. Findings: Fifteen sub-themes and three main categories were identified. The motivation behind the family members’ participation in the meetings was to ask and learn about their experiences regarding the death of their relative during this abnormal time. The reactions to the meetings varied among the families. Many expressed that the experience of bereavement was particularly challenging and painful, and that the absence of a final farewell to their loved one, as well as the impossibility of having a formally held funeral, made the deaths harder to accept. The families appreciated the interview as it gave them clarification, information, and an awareness of the facts and the care provided, and for several of them it was also a chance to share their emotions and express any difficulties they might have encountered both during and after the patient’s death. Conclusion: The COVID-19 pandemic’s restrictions had a profound impact on families who lost a loved one in an ICU. The nurse-led bereavement support service responded to the needs of grieving families, providing valuable emotional and practical support and re-establishing a healthy relationship between the families and the caregivers that was hindered by pandemic restrictions. The study also shows that a nurse-led bereavement support service can be a valuable component of family-centred care. Full article