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Societal Impact Statement Biological samples and their associated information are an essential resource used by scientists, governments, policymakers, practitioners and communities to ensure that biodiversity can be appropriately protected and sustainably used. Yet, considering the enormous task of documenting the vast numbers of as‐yet‐unknown plant and fungal species, greater international coordination for biological collecting and recording is necessary, built on equitable collecting practices and standards. Here, we propose five commitments to accelerate and enhance scientific knowledge of plant and fungal diversity, while increasing collaboration, benefit sharing and efficiency. Summary Almost all life depends on plants and fungi, making knowledge of their diversity and distribution—primarily derived from biological collections—fundamental to national and international conservation, restoration and sustainable use commitments. However, it is estimated that some 15% of all plant species and over 90% of all fungal species have not yet been scientifically described, hampering our ability to assess and demonstrate the impact of efforts to halt biodiversity loss. In addition, organisations and researchers around the world lack a concerted strategy for increasing complementarity and avoiding overlap in botanical and mycological research, particularly in relation to the collection of specimens. We here present the 2030 Declaration on Scientific Plant and Fungal Collecting, summarising a commitment towards such a necessary strategy. Its components were identified from discussions during and after a series of four workshops and plenary discussions at the 2023 State of the World's Plants and Fungi symposium convened by the Royal Botanic Gardens, Kew, and were then consolidated into the present form by the authors. The Declaration was subsequently opened up for endorsement by signatories. Collectively, we agree on a set of five commitments for cataloguing the world's flora and funga, designed to maximise efficiency, facilitate knowledge exchange and promote equitable collaborations: (1) use evidence‐based collection strategies; (2) strengthen local capacity; (3) collaborate across taxa and disciplines; (4) collect for the future; and (5) share the benefits. This Declaration is a first step towards increased global and regional coordination of scientific collecting efforts.

Abstract Snap‐frozen biopsies serve as a valuable clinical resource of archival material for disease research, as they enable a comprehensive array of downstream analyses to be performed, including extraction and sequencing of nucleic acids. Obtaining three‐dimensional (3D) structural information before multi‐omics is more challenging but can potentially allow for better characterization of tissues and targeting of clinically relevant cells. Conventional histological techniques are limited in this regard due to their destructive nature and the reconstruction artifacts produced by sectioning, dehydration, and chemical processing. These limitations are particularly notable in soft tissues such as the heart. In this study, the feasibility of using synchrotron‐based cryo‐X‐ray phase contrast imaging (cryo‐X‐PCI) of snap‐frozen myocardial biopsies is assessed and 3D structure tensor analysis of aggregated myocytes, followed by nucleic acid (DNA and RNA) extraction and analysis. It is shown that optimal sample preparation is the key driver for successful structural and nucleic acid preservation which is unaffected by the process of cryo‐X‐PCI. It is proposed that cryo‐X‐PCI has clinical value for 3D tissue analysis of cardiac and potentially non‐cardiac soft tissue biopsies before nucleic acid investigation.

BACKGROUND AND OBJECTIVES: We sought to determine clinical significance of neuronal septin autoimmunity and evaluate for potential IgG effects. METHODS: Septin-IgGs were detected by indirect immunofluorescence assays (IFAs; mouse tissue and cell based) or Western blot. IgG binding to (and internalization of) extracellular septin epitopes were evaluated for by live rat hippocampal neuron assay. The impact of purified patient IgGs on murine cortical neuron function was determined by recording extracellular field potentials in a multielectrode array platform. RESULTS: Septin-IgGs were identified in 23 patients. All 8 patients with septin-5-IgG detected had cerebellar ataxia, and 7 had prominent eye movement disorders. One of 2 patients with co-existing septin-7-IgG had additional psychiatric phenotype (apathy, emotional blunting, and poor insight). Fifteen patients had septin-7 autoimmunity, without septin-5-IgG detected. Disorders included encephalopathy (11; 2 patients with accompanying myelopathy, and 2 were relapsing), myelopathy (3), and episodic ataxia (1). Psychiatric symptoms (≥1 of agitation, apathy, catatonia, disorganized thinking, and paranoia) were prominent in 6 of 11 patients with encephalopathic symptoms. Eight of 10 patients with data available (from 23 total) improved after immunotherapy, and a further 2 patients improved spontaneously. Staining of plasma membranes of live hippocampal neurons produced by patient IgGs (subclasses 1 and 2) colocalized with pre- and post-synaptic markers. Decreased spiking and bursting behavior in mixed cultures of murine glutamatergic and GABAergic cortical neurons produced by patient IgGs were attributable to neither antigenic crosslinking and internalization nor complement activation. INTERPRETATION: Septin-IgGs are predictive of distinct treatment-responsive autoimmune central nervous system (CNS) disorders. Live neuron binding and induced electrophysiologic effects by patient IgGs may support septin-specific pathophysiology. ANN NEUROL 2022;92:1090-1101.

Abstract Phenotypic and functional changes in vascular smooth muscle cells (VSMCs) contribute significantly to cardiovascular diseases (CVD) but factors driving early adverse vascular changes are poorly understood. We report on novel and important roles for the Brn-3b/POU4F2 (Brn-3b) transcription factor (TF) in controlling VSMC integrity and function. Brn-3b protein is expressed in mouse aorta with localisation to VSMCs. Male Brn-3b knock-out (KO) aortas displayed extensive remodelling with increased extracellular matrix (ECM) deposition, elastin fibre disruption and small but consistent narrowing/coarctation in the descending aortas. RNA sequencing analysis showed that these effects were linked to deregulation of genes required for calcium (Ca2+) signalling, vascular contractility, sarco-endoplasmic reticulum (S/ER) stress responses and immune function in Brn-3b KO aortas and validation studies confirmed changes in Ca2+ signalling genes linked to increased intracellular Ca2+ and S/ER Ca2+ depletion [e.g. increased, Cacna1d Ca2+ channels; ryanodine receptor 2, (RyR2) and phospholamban (PLN) but reduced ATP2a1, encoding SERCA1 pump] and chaperone proteins, Hspb1, HspA8, DnaJa1 linked to increased S/ER stress, which also contributes to contractile dysfunction. Accordingly, vascular rings from Brn-3b KO aortas displayed attenuated contractility in response to KCl or phenylephrine (PE) while Brn-3b KO-derived VSMC displayed abnormal Ca2+ signalling following ATP stimulation. This data suggests that Brn-3b target genes are necessary to maintain vascular integrity /contractile function and deregulation upon loss of Brn-3b will contribute to contractile dysfunction linked to CVD.

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a recently emerging autoimmune disease of the central nervous system (CNS); GFAP astrocytopathy is characterized by optic neuritis and meningoencephalomyelitis. We report the case of a 55-year-old man, otherwise healthy, who presented with isolated headaches for three months, without other features of meningoencephalitis or myelitis. His neurological examination and fundoscopy were unremarkable. Gadolinium-enhanced brain MRI demonstrated increased T2 hyperintensity within the right sub-lenticular basal ganglia, with additional leptomeningeal enhancement along the bilateral perisylvian regions and mesial temporal lobes. Cerebrospinal fluid (CSF) analysis showed lymphocytic pleocytosis, elevated protein, matching oligoclonal bands, and a negative infectious and cytological workup. Cell-based assays for anti-aquaporin-4, anti-myelin oligodendrocyte glycoprotein, autoimmune encephalitis panel, and vasculitis workup were all negative, except for CSF positivity for GFAP α antibody. Oncological screening, including CT of the chest, abdomen, pelvis, and scrotal US, was unremarkable. Immunotherapy with high-dose intravenous steroids for five days and subsequent single four-weekly doses resulted in the resolution of both clinical and radiographic features, with a maintained status 24 months after onset. This case highlights isolated headache and basal ganglia, mesial temporal lobe involvement as a rare presentation of autoimmune GFAP astrocytopathy.

Pregnancy in kidney and liver transplant recipients presents unique challenges and risks for both maternal and fetal health. This article examines the management of pregnancy in kidney and liver transplant recipients, focusing on pre-pregnancy counselling, trimester-specific care, the teratogenic effects of immunosuppressive drugs, and the role of the multidisciplinary team. While South African (SA) data on this topic are limited, the Transplant Pregnancy Registry International has provided valuable insights. Despite the increased risk of maternal and fetal complications, the overall risk of graft loss during pregnancy is low. Graft survival rates are comparable between pregnant and non- pregnant transplant recipients, except for pregnancies occurring within 1 year of transplantation. By addressing the complexities of managing pregnant women with kidney or liver transplants, this article underscores the importance of tailored care and the involvement of various medical specialists. It also explores the safety of and potential complications associated with specific immunosuppressive therapies during pregnancy. Further research is needed to enhance our understanding and optimise the management of these high-risk pregnancies in SA.

IntroductionIn January 2023, our laboratory began performing serum myelin oligodendrocyte glycoprotein antibody (anti-MOG) titers by fixed cell-based assay (CBA). As a quality assurance (QA) assessment, we evaluated titer positive predictive value (PPV) as well as impact of sample collection timing on titers.MethodsAmong patients who underwent antibody titers to distinguish between low-positive (

Background: Preemptive analgesia is pain control before inciting a noxious stimulus. Upper abdominal and shoulder tip pain after laparoscopy is probably caused by gas retained in the peritoneal cavity. Pain relievers were given before the incision. Aim: The study was planned to compare the Analgesic effect of pre-operative intravenous Paracetamol versus Ketorolac in laparoscopic cholecystectomy under general anesthesia. The difference in the need for first rescue analgesia and total dose of rescue analgesics in 24 hours postoperative period in both groups was assessed. Methods: This Hospital Based Double Blinded Randomized Interventional Study was carried out in ASA I and II, aged 18 to 60 years in patients undergoing elective laparoscopic cholecystectomy under general anesthesia. Group A received an Intravenous infusion of paracetamol 1gm (100ml) and Group B received an intravenous infusion of ketorolac 30mg (1ml) diluted in 99 ml 0.9% normal saline. In both groups, analgesic was given over a period of 30 minutes, 30 min before induction of general anesthesia. The chi-square test and Student’s t-test were used for the statistical analysis. Results: The time for the demand of the first rescue analgesia was219±81.0 min in group A and 350±175.1min in group B, with a p-value < 0.001. The demand for rescue analgesics was more in Group A in contrast to Group B. Conclusion: We concluded with our study, pre-emptive analgesia with 30mg ketorolac is better than 1 gm paracetamol. The time for rescue analgesia is prolonged, the number of rescue analgesics demanded is reduced, VAS score was significantly lower when ketorolac was used.

Introduction: We report a challenging case of autoimmune encephalitis in a patient with a thymoma harboring titin and acetylcholine receptor antibodies, who experienced multiple relapses despite thymectomy and aggressive first-line immunotherapy, and for whom GABAA receptor antibodies were ultimately identified. Case presentation: This 40-year-old man presented with headaches, weakness, diplopia, hearing loss and seizures progressing to status epilepticus. Brain MRI showed multifocal cortical and subcortical T2/fluid attenuated inversion recovery hyperintense lesions without enhancement. Initial neural antibody testing identified only acetylcholine receptor and titin antibodies. He presented multiple severe relapses despite complete thymoma resection, intravenous methylprednisolone with immunoglobulins or plasmapheresis, and mycophenolate mofetil. Second-line immunotherapy with rituximab was successful to alleviate symptoms and normalize the EEG and MRI after identification of anti-GABAA receptor antibodies on more comprehensive neural antibody testing for autoimmune encephalitis. Conclusion: This case demonstrates the complexity and importance of identifying pathogenic antibodies and selecting 2nd line treatment accordingly in patients with autoimmune encephalitis when multiple antibodies coexist. Despite tumor resection, aggressive immunotherapy may be needed to prevent further deterioration in anti-GABAA receptor encephalitis.

Introduction: Continuous subcutaneous insulin infusion (CSII) in type 1 diabetes has been regarded as a major diabetic ketoacidosis (DKA) risk factor. We aimed to determine secular trends in risk since CSII implementation in the 1980s. Research Design and Methods: We assessed the relationship between time-varying CSII use and DKA events from 1983 to 2017 and by each decade in the 1441 Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study participants using crude and adjusted Cox proportional hazards models. Results: Time-varying CSII exposure was associated with significantly higher DKA risk in the 1980s (adjusted hazard ratio [HR] 5.81; 95% confidence interval [CI] 3.28–10.29; P < 0.001), but in the 2010s, this risk was not significantly elevated (adjusted HR 1.24; 95% CI 0.73–2.12; P = 0.43). Conclusions: DKA risk associated with CSII in type 1 diabetes has declined substantially since the 1980s such that the remaining risk in the past decade appears to be of low magnitude. [ABSTRACT FROM AUTHOR]

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an inflammatory demyelinating disease that is distinct from multiple sclerosis. Initial manifestations of MOGAD that were reported in the literature included optic neuritis, myelitis, brainstem demyelination and encephalitis, with emphasis placed on acute disseminated encephalomyelitis (ADEM) as the primary encephalitic presentation. In 2017, however, Ogawa et al. described four patients with seizures, unilateral cortical hyperintensities on brain magnetic resonance imaging T2-fluid-attenuated inversion recovery sequences, and anti-MOG positivity, indicating a potentially novel form of encephalitis in MOGAD. In 2019, we systematically reviewed the literature to better characterize this unique syndrome, which we referred to as unilateral cortical FLAIR-hyperintense Lesions in Anti-MOG-associated Encephalitis with Seizures (FLAMES). Subsequently, anti-MOG positivity in patients with a variety of cortical and meningeal disease presentations has been reported, indicating a broader spectrum of meningo-cortical manifestations in MOGAD that we review herein.

Abstract Background A reliable expected date of delivery (EDD) is important for pregnant women in planning for a safe delivery and critical for management of obstetric emergencies. We compared the accuracy of LMP recall, an early ultrasound (EUS) and a Smartphone App in predicting the EDD in South African pregnant women. We further evaluated the rates of preterm and post-term births based on using the different measures. Methods This is a retrospective sub-study of pregnant women enrolled in a randomized controlled trial between October 2017-December 2019. EDD and gestational age (GA) at delivery were calculated from EUS, LMP and Smartphone App. Data were analysed using SPSS version 25. A Bland–Altman plot was constructed to determine the limits of agreement between LMP and EUS. Results Three hundred twenty-five pregnant women who delivered at term (≥ 37 weeks by EUS) and without pregnancy complications were included in this analysis. Women had an EUS at a mean GA of 16 weeks and 3 days). The mean difference between LMP dating and EUS is 0.8 days with the limits of agreement 31.4–30.3 days (Concordance Correlation Co-efficient 0.835; 95%CI 0.802, 0.867). The mean(SD) of the marginal time distribution of the two methods differ significantly (p = 0.00187). EDDs were 42 weeks gestation) births was 11.4% (95%CI 8.4–15.3), 1.9% (95%CI 0.9–3.9) and 3.4% (95%CI 1.9–5.9) by LMP, EUS and Smartphone respectively. Conclusions EUS and Smartphone App were the most accurate to estimate the EDD in pregnant women. LMP-based dating resulted in misclassification of a significantly greater number of preterm and post-term deliveries compared to EUS and the Smartphone App.

Snap‐frozen biopsies serve as a valuable clinical resource of archival material for disease research, as they enable a comprehensive array of downstream analyses to be performed, including extraction and sequencing of nucleic acids. Obtaining three‐dimensional (3D) structural information before multi‐omics is more challenging but can potentially allow for better characterization of tissues and targeting of clinically relevant cells. Conventional histological techniques are limited in this regard due to their destructive nature and the reconstruction artifacts produced by sectioning, dehydration, and chemical processing. These limitations are particularly notable in soft tissues such as the heart. In this study, the feasibility of using synchrotron‐based cryo‐X‐ray phase contrast imaging (cryo‐X‐PCI) of snap‐frozen myocardial biopsies is assessed and 3D structure tensor analysis of aggregated myocytes, followed by nucleic acid (DNA and RNA) extraction and analysis. It is shown that optimal sample preparation is the key driver for successful structural and nucleic acid preservation which is unaffected by the process of cryo‐X‐PCI. It is proposed that cryo‐X‐PCI has clinical value for 3D tissue analysis of cardiac and potentially non‐cardiac soft tissue biopsies before nucleic acid investigation. [ABSTRACT FROM AUTHOR]

Zusammenfassung: Einleitung: Wir berichten über einen herausfordernden Fall von Autoimmunenzephalitis bei einem Patienten mit einem Thymom, das Titin- und Acetylcholinrezeptor-Antikörper enthielt. Trotz Thymektomie und aggressiver Erstlinien-Immuntherapie erlitt er mehrere Schübe. Letztendlich wurden GABAA-Rezeptor-Antikörper identifiziert. Falldarstellung: Dieser 40-jährige Mann wurde mit Kopfschmerzen, Schwäche, Diplopie, Hörverlust und Anfällen, die bis zum Status epilepticus reichten, vorstellig. Eine Magnetresonanztomografie (MRT) des Gehirns zeigte multifokale kortikale und subkortikale, in der T2/Fluid-Attenuated-Inversion-Recovery-Bildgebung hyperintensive Läsionen ohne Verbesserung. Bei anfänglichen neuronalen Antikörpertests wurden nur Acetylcholinrezeptor- und Titin-Antikörper identifiziert. Der Patient zeigte mehrere schwere Schübe trotz vollständiger Thymomresektion, intravenöser Gabe von Methylprednisolon mit Immunglobulinen oder Plasmapherese und Mycophenolat-Mofetil. Die Zweitlinien-Immuntherapie mit Rituximab linderte die Symptome und normalisierte die Elektroenzephalografie (EEG)- und MRT-Befunde nach der Identifizierung von Anti-GABAA-Rezeptor-Antikörpern durch die umfassenderen neuronalen Antikörpertests auf Autoimmunenzephalitis. [ABSTRACT FROM AUTHOR]

Emphysematous pyelonephritis (EPN) is a rare, life-threatening infection, and misdiagnosis asuncomplicated pyelonephritis is potentially fatal. Point-of-care ultrasound (POCUS) is a valuable toolfor evaluation of the kidneys in patients with septic shock and pyelonephritis. While used primarilyto assess for the complication of obstruction and hydronephrosis, POCUS may also detect signs ofEPN and prompt surgical consultation for nephrectomy. We present a case in which the emergencyphysician diagnosed EPN by POCUS in a patient with septic shock and pyelonephritis.

Phlegmasia cerulea dolens (PCD) is a rare entity that is associated with significant morbidity and mortality, including limb ischemia and pulmonary embolism. Point-of-care ultrasound (POCUS) can expedite the diagnosis, leading to earlier life- and limb-saving treatment. Although primarily used for assessing for the presence of deep venous thrombosis, in the appropriate clinical setting POCUS can also be used to diagnosis PCD as well as to distinguish between venous and arterial occlusion, which can lead to a difference in management. We present a case of phlegmasia cerulea dolens after mild trauma in a patient with an underlying hypercoagulability disorder diagnosed by an emergency physician using POCUS, which expedited treatment with catheter-directed thrombolytic therapy.

Abstract Metabolic and cardiovascular diseases are highly prevalent and chronic conditions that are closely linked by complex molecular and pathological changes. Such adverse effects often arise from changes in the expression of genes that control essential cellular functions, but the factors that drive such effects are not fully understood. Since tissue-specific transcription factors control the expression of multiple genes, which affect cell fate under different conditions, then identifying such regulators can provide valuable insight into the molecular basis of such diseases. This review explores emerging evidence that supports novel and important roles for the POU4F2/Brn-3b transcription factor (TF) in controlling cellular genes that regulate cardiometabolic function. Brn-3b is expressed in insulin-responsive metabolic tissues (e.g. skeletal muscle and adipose tissue) and is important for normal function because constitutive Brn-3b-knockout (KO) mice develop profound metabolic dysfunction (hyperglycaemia; insulin resistance). Brn-3b is highly expressed in the developing hearts, with lower levels in adult hearts. However, Brn-3b is re-expressed in adult cardiomyocytes following haemodynamic stress or injury and is necessary for adaptive cardiac responses, particularly in male hearts, because male Brn-3b KO mice develop adverse remodelling and reduced cardiac function. As a TF, Brn-3b regulates the expression of multiple target genes, including GLUT4, GSK3β, sonic hedgehog (SHH), cyclin D1 and CDK4, which have known functions in controlling metabolic processes but also participate in cardiac responses to stress or injury. Therefore, loss of Brn-3b and the resultant alterations in the expression of such genes could potentially provide the link between metabolic dysfunctions with adverse cardiovascular responses, which is seen in Brn-3b KO mutants. Since the loss of Brn-3b is associated with obesity, type II diabetes (T2DM) and altered cardiac responses to stress, this regulator may provide a new and important link for understanding how pathological changes arise in such endemic diseases.

Autoimmune myelopathies are immune-mediated disorders of the spinal cord that can cause significant neurologic disability. Discoveries of antibodies targeting aquaporin-4 (AQP4-IgG) and myelin oligodendrocyte glycoprotein (MOG-IgG) have facilitated the diagnosis of autoimmune myelopathies that were previously considered to be atypical presentations of multiple sclerosis (MS) or idiopathic, and represent major advancements in the field of autoimmune neurology. The detection of these antibodies can substantially impact patient diagnosis and management, and increasing awareness of this has led to a dramatic increase in testing for these antibodies among patients with suspected autoimmune myelopathy. In this review we discuss test methodologies used to detect these antibodies, the role of serum vs. cerebrospinal fluid testing, and the value of antibody titers when interpreting results, with the aim of helping laboratorians and clinicians navigate this testing when ordered as part of the diagnostic evaluation for suspected autoimmune myelopathy.

The therapeutical attributes of silver nanoparticles (Ag-NPs) in both conditions (in vitro and in vivo) have been investigated using different plants. This study focused on the green chemistry approach that was employed to optimize the synthesis of silver nanoparticles (AgNPs) using Cleome brachycarpa aqueous extract as a reducing and stabilizing agent. The characterization of obtained CB-AgNPs was undertaken using UV-visible spectroscopy, Atomic-force microscopy (AFM), Fourier-Transform Infrared Spectroscopy (FTIR), scanning electron microscopy (SEM), and Energy-Dispersive X-ray (EDX) analysis. Results suggest that CB-AgNPs synthesized via stirring produced small-sized particles with more even distribution. The synthesized silver nanoparticles were spherical with a 20 to 80 nm size range. In vitro studies were used to analyze antioxidant, antidiabetic, and cytotoxic potential under different conditions. The results also indicated that CB-AgNPs may have significant potential as an antidiabetic in low concentrations, but also exhibited potential antioxidant activity at different concentrations. Moreover, the anticancer activity against the breast cell line (MCF-7) with IC50 reached up to 18 μg/mL. These results suggest that green synthesized silver nanoparticles provide a promising phytomedicine for the management of diabetes and cancer therapeutics.