Organ Systems Research Articles

Calendula Flowers (Calendulae officinalis flos): Methods to Obtain Fractions of Biologically Active Substances

INTRODUCTION. The pharmaceutical industry aims at developing sustainable resource-saving technologies for manufacturing medicines. Approaches to the effective use of herbal drugs include applying technologies yielding compounds with various pharmacological effects in one production cycle. To date, no standardised herbal drug processing technology has been designed to produce calendula flower-based medicinal products with various pharmacological effects. The Member States of the Eurasian Economic Union (EAEU) process calendula flowers by extraction methods yielding one fraction of biologically active substances per cycle (either only flavonoids or only carotenoids).AIM. This article aimed to investigate the possibility of stepwise processing of calendula flowers to obtain biologically active substances with different polarities (carotenoids, flavonoids, and polysaccharides) per cycle.MATERIALS AND METHODS. The authors extracted carotenoids using hexane. The study included additional thermal pretreatment of the herbal drug. Carotenoids and flavonoids were quantified by spectrophotometry, and polysaccharides were quantified by gravimetric analysis. After hexane removal, the dry oily residue was dissolved in oil with mechanical stirring to obtain the oil extract. The study included a three-step processing method that comprised hexane extraction (extraction of carotenoids with a low-polarity organic solvent), extraction with a water–organic solvent system (extraction of flavonoids), and aqueous extraction (precipitation of polysaccharides).RESULTS. The lipophilic extracts obtained by single hexane extraction or by single hexane extraction and heat treatment had the maximum carotenoid content (~4%), which was 10 times the carotenoid content in the extracts obtained using a water– organic solvent system. Oil extracts were prepared from the dry residue left after removing hexane by distillation at its boiling point. The content of biologically active substances in the oil extracts was comparable to that in the intact herbal drug. Water–organic solvent extraction yielded 68.5% more flavonoids from the herbal drug extracted with hexane than from the intact herbal drug. In contrast, aqueous extraction applied to the intact herbal drug yielded 1.7 times the amount of flavonoids obtained by aqueous extraction preceded by hexane extraction. The water-soluble polysaccharide fraction extracted from the intact herbal drug had 10 times the flavonoid content observed in the fraction extracted from the processed herbal drug. Each subsequent processing step decreased the total polysaccharide content and the content of individual polysaccharide fractions and increased their purity. The ratio of polysaccharide fractions remained unchanged across all processing methods tested.CONCLUSIONS. Stepwise processing of calendula flowers ensured that one processing cycle provided three fractions containing increased amounts of carotenoids, flavonoids, and polysaccharides. Relative to the intact herbal drug, there was a 3.3-fold increase in the yield of carotenoids, and the yields of flavonoids and polysaccharides increased by 44.8 and 41.3%, respectively. The resulting product had a higher degree of purity than the products obtained by pretreatment and double hexane extraction or by using the intact herbal drug. The stepwise processing method is advisable for the production of medicines that are enriched with a specific group of biologically active substances or contain smaller amounts of impurities.

Management of Giant Type II Arteriovenous Malformation of the Neck With Heart Failure in a Pediatric Patient With Coil and NLE Embolization: A Case Report.

Although arteriovenous malformations (AVMs) are typically benign lesions, massive ones can lead to severe complications, including heart failure. Notably, there is no standardized treatment for AVMs. Moreover, management of AVMs can be challenging when these lesions involve vital organ systems, such as the head and neck. In this report, we describe embolization of a massive cervical AVM in a pediatric patient with heart failure. A 10-year-old boy presented with severe heart failure secondary to a massive AVM in the neck (right side). Despite 3 unsuccessful arterial embolization procedures, venous embolization of the dominant outflow vein using a coil and n-butyl-2-cyanoacrylate, lipiodol, and ethanol proved effective, and symptoms, cerebral natriuretic peptide level (568-29 pg/mL), and echocardiography were significantly improved. Although residual AVM persisted in the right upper extremity for 6 months after surgery, his cardiac function remained preserved, and his activities of daily living have improved. Venous embolization is a valuable treatment modality for type II AVMs with a dominant outflow vein. However, considering the patient burden associated with large AVMs, multiple therapeutic interventions at appropriate intervals and long-term follow-up are important. We present a pediatric patient with a type II massive arteriovenous malformation (AVM) in the neck and severe heart failure. Despite undergoing 3 arterial embolization procedures, his condition remained unchanged. However, venous embolization of the dominant outflow vein resulted in a significant improvement in symptoms. This case emphasizes the importance of considering multiple and appropriately timed therapeutic interventions, particularly for massive AVMs, to optimize patient outcomes while minimizing treatment burden.

Tofacitinib for child-onset systemic lupus erythematosus

BackgroundSystemic lupus erythematosus (SLE) is a chronic autoimmune disease that can cause diverse clinical manifestations in multiple organ systems. Child-onset SLE (cSLE) is associated with significantly higher morbidity and mortality than adult-onset SLE. The traditional treatments for SLE (glucocorticoids, antimalarials, conventional and biological disease-modifying antirheumatic drugs) often have significant adverse effects and may not fully control disease activity. Tofacitinib is an oral Janus kinase (JAK) inhibitor that inhibits the JAK-STAT pathway and has the potential to reduce SLE severity.MethodscSLE patients who received tofacitinib and had at least one follow-up visit were retrospectively examined. Case histories, laboratory test results, and treatment regimens were analyzed at disease onset, initiation of tofacitinib treatment, and 1, 3, 6, 9, 12, 18, and 24 months after starting tofacitinib.ResultsWe examined 9 patients with refractory cSLE. All patients were female and the average age at diagnosis was 10.67 years. At initiation of tofacitinib, the average age was 13.28 years and the average disease duration was 2.62 years. Four patients experienced alleviation of symptoms and reduced their daily prednisone dosages; one of them also discontinued cyclosporine A and two of them also discontinued belimumab. The other 5 patients experienced no apparent benefit.ConclusionTofacitinib may provide clinical benefits for some patients with refractory cSLE, and can also allow reduction in the glucocorticoid dosage. Tofacitinib has the potential as an adjunctive treatment for some patients with cSLE.

Importance of risk adjusting central line-associated bloodstream infection rates in children.

Central line-associated bloodstream infection (CLABSI) is one of the most prevalent pediatric healthcare-associated infections and is used to benchmark hospital performance. Pediatric patients have increased in acuity and complexity over time. Existing approaches to risk adjustment do not control for individual patient characteristics, which are strong predictors of CLABSI risk and vary over time. Our objective was to develop a risk adjustment model for CLABSI in hospitalized children and compare observed to expected rates over time. We conducted a prospective cohort study using electronic health record data at a quaternary Children's Hospital. We included hospitalized children with central catheters. Risk factors identified from published literature were considered for inclusion in multivariable modeling based on association with CLABSI risk in bivariable analysis and expert input. We calculated observed and expected (risk model-adjusted) annual CLABSI rates. Among 16,411 patients with 520,209 line days, 633 patients experienced 796 CLABSIs. The final model included age, behavioral health condition, non-English speaking, oncology service, port catheter type, catheter dwell time, lymphatic condition, total parenteral nutrition, and number of organ systems requiring ICU level care. For every organ system receiving ICU level care the odds ratio for CLABSI was 1.24 (95% CI 1.12-1.37). Although not statistically different, observed rates were lower than expected rates for later years. Failure to adjust for patient factors, particularly acuity and complexity of disease, may miss clinically significant differences in CLABSI rates, and may lead to inaccurate interpretation of the impact of quality improvement efforts.

Zinc Chemistries of Hybrid Electrolytes in Zinc Metal Batteries: From Solvent Structure to Interfaces.

Along with the booming research on zinc metal batteries (ZMBs) in recent years, operational issues originated from inferior interfacial reversibility have become inevitable. Presently, single-component electrolytes represented by aqueous solution, "water-in-salt," solid, eutectic, ionic liquids, hydrogel, or organic solvent system are hard to undertake independently the task of guiding the practical application of ZMBs due to their specific limitations. The hybrid electrolytes modulate microscopic interaction mode between Zn2+ and other ions/molecules, integrating vantage of respective electrolyte systems. They even demonstrate original Zn2+ mobility pattern or interfacial chemistries mechanism distinct from single-component electrolytes, providing considerable opportunities for solving electromigration and interfacial problems in ZMBs. Therefore, it is urgent to comprehensively summarize the zinc chemistries principles, characteristics, and applications of various hybrid electrolytes employed in ZMBs. This review begins with elucidating the chemical bonding mode of Zn2+ and interfacial physicochemical theory, and then systematically elaborates the microscopic solvent structure, Zn2+ migration forms, physicochemical properties, and the zinc chemistries mechanisms at the anode/cathode interfaces in each type of hybrid electrolytes. Among of which, the scotoma and amelioration strategies for the current hybrid electrolytes are actively exposited, expecting to provide referenceable insights for further progress of future high-quality ZMBs.

7157 Unveiling PROP1 protein complex: NFIB as a key candidate in pituitary development

Abstract Disclosure: L.C. Iglesias García: None. M.F. Mercogliano: None. C. Schuster: None. L. Cheung: None. F. Brunello: None. V. Michan: None. M. Waldman: None. L. Defelipe: None. M. Martí: None. S.A. Camper: None. M.I. Perez-Millan: None. The transcription factor PROP1 is essential for pituitary development, and mutations in the gene are the most common cause of hypopituitarism in children. To understand PROP1 function, it is essential to identify the protein components of the PROP1 transcription complex. Rapid immunoprecipitation and mass spectrometry (RIME) experiments in GHFT1 cells, genetically engineered to express biotin-tagged PROP1, have revealed the association of PROP1 with 43 transcription factors (including β-CATENIN and the Nuclear Factor I/B). In silico analysis showed association between the armadillo domains of β-CATENIN and a predicted nuclear localization signal motif of PROP1. This interaction between PROP1 and β-CATENIN was confirmed in pituitary GHFT1 cells, where over-expression of PROP1 induces the translocation of β-CATENIN from the membrane and cytoplasm to the nucleus. Moreover, in pituitaries from Prop1df/df mutant embryos at e12.5, β-CATENIN was predominantly membrane-bound compared to wild-type embryos. These findings suggest that PROP1 is necessary for translocation of β-CATENIN to the nucleus during pituitary development.The association of PROP1 with NFIB is intriguing because PROP1 is necessary for the epithelial to mesenchymal-like transition of stem cells in pituitary development, and NFIB is associated with induction of EMT in several cancer models. We used immunohistochemistry to show that NFIB is expressed in embryonic pituitary glands from e12.5 to e16.5, and it co-localizes with the stem cell marker SOX2. To determine whether PROP1 and NFIB have common downstream targets, we performed CUT&RUN experiments for NFIB in GHFT-1 cells and compared the results with those from PROP1 ChIP-seq. Both PROP1 and NFIB bind to three sites in the NFIB gene, suggesting that NFIB is a downstream target of PROP1 and subject to autoregulation. Consistent with this idea, NFIB is reduced in pituitaries from Prop1df/df embryos at both e12.5 and e14.5 relative to normal littermates. Integration of the results from PROP1 ChIP-seq and RNA-seq (GHFT1 vs PROP1-GHFT1 cells) with NFIB CUT&RUN generated a list of 190 potential target genes. These genes are associated with cell migration, emphasizing their correlation with the EMT-like process orchestrated by PROP1 during pituitary development. In sum, we have identified an interesting set of PROP1 interacting proteins, including the transcription factor NFIB, which plays an important role in regulating stem cell differentiation in several organ systems. We have also cataloged the genome-wide set of binding sites for PROP1 and NFIB, which overlap at many genes regulating cell migration, a process that is important for pituitary stem cells to leave the niche and initiate differentiation. Presentation: 6/3/2024

8183 An Unusual Cause of Fluctuating Thyroid Hormone Levels

Abstract Disclosure: V. Taqi: None. W. Akhter: None. J.L. Gilden: None. Background: Thyroid disease, especially congenital hypothyroidism is a common endocrine problem with an estimated global prevalence of 4.25%. Since every organ system is affected by thyroid hormones, untreated hypothyroidism can lead to profound adverse outcomes. Many drugs, hormones, and dietary supplements have been noted to affect the efficacy of thyroid hormones, yet there was always concern about the effect of the excessive growth of intestinal flora in the small intestine on thyroid supplement absorption. Drugs, malabsorption, celiac disease and increased excretion are common causes of fluctuating thyroid hormones. In this case, we present a young male patient with congenital hypothyroidism, who required fluctuating doses of levothyroxine due to abnormal thyroid hormone levels, despite compliance with proper administration, and dramatic improvement of thyroid hormone levels after starting probiotic therapy. Case : An 18-year-old Caucasian male with congenital hypothyroidism had been treated with varying doses of thyroid hormone replacement by a Pediatric Endocrine Center. Due to his recall that TSH=4.13 mIU/L and he was “tired of taking medication”, he stopped taking 125 mcg of levothyroxine. Four months later, TSH was > 200 mIU/L (nl=0.48-4.17). Levothyroxine 137 mcg was then started. However, 11 months later, TSH=14.2 mIU/L, Free T4=1.6 ng/dL (nl=1.03-1.64). He was then referred to our Endocrine Clinic. He denied symptoms of hypo or hyperthyroidism or other medical issues. His grandfather was known to have hypothyroidism and diabetes mellitus (details unknown). On exam: Wt. was 149 Ib, Ht= 67 Inch. VS: BP 98/46, P 69, R:16,temp: 97.9F, Physical exam showed normal findings without thyromegaly, but there was a delay in tendon reflexes. Laboratory-unremarkable CBC, CMP panels with normal thyroid antibodies, and Celiac titers. TSH initially improved from 14.2 to 8.4 mIU/L after increasing the thyroxine dosage from 137 to 150 mcg for 2 weeks, then to 175 mcg after 4 weeks, but TSH increased to 12.1 mIu/L, despite being compliant with medication and ensuring proper way of administration. He continued to deny symptoms of hypo or hyperthyroidism, or any other medical issues, including lactose intolerance or malabsorption. However, probiotics were then added to his regimen, and continuation of the current dose resulted in a suppressed TSH=0.15 mIU/L. The levothyroxine was then decreased to 150 mcg with continuation of probiotics. One month later, TSH was 1.31 mIU/L with Free T4 of 1.5 ng/dL. Conclusion : Common causes for fluctuating thyroid hormone levels include intestinal malabsorption, celiac disease, nephrotic syndrome, drugs, and food interaction. This case demonstrates that despite proper administration, fluctuating thyroid hormone levels can result from some uncommon causes, such as lactose intolerance, which can be unmasked by co-administration of probiotics. Presentation: 6/2/2024

6724 A Broken Heart Due to Excess Thyroid

Abstract Disclosure: R. Subramani: None. R. Subramani: None. V. Zeykan: None. Introduction: Tachycardia-induced cardiomyopathy related to thyrotoxicosis is an uncommon yet serious complication affecting fewer than 1% of individuals with hyperthyroidism. Restoring a euthyroid state can potentially reverse the abnormal cardiac structure and function. Here we report a case of tachycardia-induced cardiomyopathy secondary to thyrotoxicosis Case Summary: A 52-year-old woman with a history of hypertension presented with recent-onset exertional dyspnea, a nonproductive cough, and paroxysmal nocturnal dyspnea. On examination, she exhibited tachycardia (heart rate: 150/min), tachypnea, hypertension, and was afebrile. Physical findings included a mildly enlarged, firm, non-tender thyroid gland bilaterally, without exophthalmos or tremors. Auscultation revealed bilateral crackles in the left lower lung fields. Laboratory analysis revealed undetectable TSH (<0.02 uIU/mL), elevated free T4 (5.3 ng/dL), free T3 (16.30 pg/mL), thyroid stimulating immunoglobulin (TSI) at 216%, and NT proBNP at 8528 pg/mL. Neck ultrasound and CT confirmed diffuse enlargement of the thyroid gland. Transthoracic echocardiography (TTE) displayed severely depressed left ventricular systolic function, estimating an ejection fraction (EF) of 25-30%. Initial management involved intravenous beta-blockers for heart rate control, IV Lasix, and IV hydrocortisone. Subsequently, the patient received propylthiouracil, propranolol, and prednisone, resulting in symptomatic improvement. A follow-up TTE after 6 months revealed an improved EF of 50%. Discussion: The pathophysiologic mechanisms underlying thyrotoxic cardiomyopathy encompass several factors, including tachycardia-induced cardiomyopathy, direct myopathic effects induced by the T3 hormone, and concurrent autoimmune myocarditis associated with Graves' disease. Thyroid hormone exerts a comprehensive impact on nearly all tissue and organ systems, heightening basal metabolic rate and subsequently increasing preload, myocardial contractility, and cardiac output. While thyrotoxicosis-related congestive heart failure (CHF) is relatively uncommon among patients hospitalized for acute CHF, addressing hyperthyroidism and CHF through definitive treatment yields a more favorable prognosis compared to cases of acute CHF stemming from other etiologies. The intricate interplay of these mechanisms highlights the importance of a comprehensive approach in managing thyrotoxic cardiomyopathy, emphasizing the need for targeted interventions to address both the underlying thyroid dysfunction and associated cardiac manifestations. Presentation: 6/3/2024

Assessing pesticide residue occurrence and risks in the environment across Europe and Argentina.

The widespread and extensive use of pesticides in European crop production to reduce losses from weeds, diseases, and insects may have serious consequences on the ecosystem and human health. This study aimed to identify 20 active substances of high health risk, based on their detection frequency within and across the environmental matrices (soil, crop, water, and sediment) and to identify their associated hazardous effects. A sampling campaign was conducted across 10 case study sites in Europe and 1 in Argentina and included conventional and organic farming systems. In 31% of cases, the detected substances were found at a higher concentration in the soil than in the corresponding crops, 93% of the compounds were fungicides, and the remainder were insecticides. 43% of the substances, 57% of which were insecticides, were detected only in soil. There was a clear relationship between soils and crops in terms of contamination, but not between water and sediment. Portuguese soil (wine grapes) had the highest number of substances (12) with average concentrations (AC) varying between 1 and 162 μg/kg, followed by French (11 substances in wine grapes) (1≤AC≤64 μg/kg) and Spanish soils (9 substances in vegetables) (3≤AC≤59 μg/kg). The crops corresponding to these soils contained a relatively high number of detected substances and several in high average concentrations (AC). The risk quotient was consistently higher for conventional farms than for organic farms. For the soils from conventional farms, 5 active substances (chlorpyrifos, glyphosate, boscalid, difenoconazole, lambda-cyhalothrin, and one metabolite: AMPA) were considered high risk. For water samples, 2 substances (dieldrin and terbuthylazine) found were high risk, and for sediment, there were 3 substances (metalaxyl-M, spiroxamine, and lambda-cyhalothrin). There were 6 substances detected in crops that are suspected to cause human health effects. Uncontaminated soil is a prerequisite for the adoption of sustainable alternatives to pesticides. Efforts are needed to elucidate the unknown effects of mixtures, including biocides and banned compounds in addition to the substances used in agriculture.

Titanium oxide hydrates as versatile polymer crosslinkers and molecular‐hybrid formers

AbstractMolecular hybrid materials based on widely available polymers crosslinked with an inorganic species have received increasing interest for their unique property sets outside of the usual range of commodity plastics and/or nanocomposites. Here, we provide a mini‐review on molecular hybrids based on metal oxide hydrates—compounds that readily react with, for example, hydroxylated polymers to form inorganic:organic materials systems with many desirable features and properties. Focusing on titanium oxide hydrates, we discuss here that such molecular hybrids can exhibit a broad refractive index range in addition to an increased glass transition temperature, mechanical stiffness and swelling resistance in comparison to the neat polymer, which illustrates that such hybrid systems offer a new, low‐cost, robust and versatile functional materials platform with great promise for, for example, solution‐processed photonics, catalysts and antimicrobial coatings. Generally, our mini‐review seeks to provide a concise and accessible overview of titanium oxide hydrate:polymer hybrid systems, focusing on their unique properties and processability as well as their broad and largely untapped potential as functional materials. © 2024 The Author(s). Polymer International published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

7783 Pheochromocytoma Unusually Presenting As Intestinal Pseudo-Obstruction: A Case Report

Abstract Disclosure: J.V. Chua: None. E.C. Cunanan: None. J.G. Sazon: None. J.L. Reyes: None. Introduction: Pheochromocytoma is a rare neuroendocrine tumor that arises from the adrenal medulla. It may present with a variety of symptoms that can resemble other diseases as a result of the effects of catecholamine overproduction on the different organ systems of the body, occasionally making diagnosis difficult and delaying appropriate treatment.Intestinal pseudo-obstruction is an unusual presentation of pheochromocytoma from the effects of excessive catecholamines on the gastrointestinal system, resulting in decreased peristalsis with constriction of the sphincter muscles, consequently prolonging intestinal transit time. Currently, there is no available data on its incidence or prevalence rate. Clinical Case: This is a case of a 50-year-old Filipino male initially presenting with abdominal pain and enlargement with inability to pass stool and flatus, not relieved by laxatives, enemas, and nasogastric and rectal tube decompression. Abdominal radiograph revealed segmental ileus versus partial large bowel obstruction, while abdominal CT scan showed fecal impaction and an incidental finding of an enhancing adrenal mass on the left adrenal gland. Colonoscopy findings were unremarkable. Laboratory workup demonstrated elevated 24-hour urine metanephrine levels with a value of 44.62 mg/24 hours (normal value: 0-1.0 mg/24 hours). The patient was initially managed conservatively, but no improvement in symptoms was noted. Pre-operative preparation was done with terazosin and intravenous saline infusion, and the patient then underwent left open adrenalectomy with bowel decompression, which provided resolution of symptoms and resumption of regular bowel movement post-operatively. The final result of the histopathologic examination confirmed the diagnosis of pheochromocytoma. Conclusion: Gastrointestinal symptoms such as ileus and pseudo-intestinal obstruction are uncommon presentations of pheochromocytoma. A high index of suspicion is necessary among patients presenting with these symptoms, and pheochromocytoma should be considered as part of the differential diagnosis. Presentation: 6/1/2024

Mutations in fibronectin dysregulate chondrogenesis in skeletal dysplasia.

Fibronectin (FN) is an extracellular matrix glycoprotein essential for the development and function of major vertebrate organ systems. Mutations in FN result in an autosomal dominant skeletal dysplasia termed corner fracture-type spondylometaphyseal dysplasia (SMDCF). The precise pathomechanisms through which mutant FN induces impaired skeletal development remain elusive. Here, we have generated patient-derived induced pluripotent stem cells as a cell culture model for SMDCF to investigate the consequences of FN mutations on mesenchymal stem cells (MSCs) and their differentiation into cartilage-producing chondrocytes. In line with our previous data, FN mutations disrupted protein secretion from MSCs, causing a notable increase in intracellular FN and a significant decrease in extracellular FN levels. Analyses of plasma samples from SMDCF patients also showed reduced FN in circulation. FN and endoplasmic reticulum (ER) protein folding chaperones (BIP, HSP47) accumulated in MSCs within ribosome-covered cytosolic vesicles that emerged from the ER. Massive amounts of these vesicles were not cleared from the cytosol, and a smaller subset showed the presence of lysosomal markers. The accumulation of intracellular FN and ER proteins elevated cellular stress markers and altered mitochondrial structure. Bulk RNA sequencing revealed a specific transcriptomic dysregulation of the patient-derived cells relative to controls. Analysis of MSC differentiation into chondrocytes showed impaired mesenchymal condensation, reduced chondrogenic markers, and compromised cell proliferation in mutant cells. Moreover, FN mutant cells exhibited significantly lower transforming growth factor beta-1 (TGFβ1) expression, crucial for mesenchymal condensation. Exogenous FN or TGFβ1 supplementation effectively improved the MSC condensation and promoted chondrogenesis in FN mutant cells. These findings demonstrate the cellular consequences of FN mutations in SMDCF and explain the molecular pathways involved in the associated altered chondrogenesis.

7165 A Case of Severe Myxedema Coma with Levothyroxine Allergy

Abstract Disclosure: A. Rothstein Costris: None. A. Yaseen: None. S. Levy: None. Introduction: Myxedema coma is a life threatening condition with a mortality rate of 25-60%. Untreated, it can lead to fatal physiological changes. The treatment is thyroid hormone replacement therapy, alongside supportive care for complications. Clinical Case: A 65-year-old woman, who has been dealing with untreated hypothyroidism since 2012 and reported allergies to various levothyroxine brands, presented with falls, weakness, and exacerbated leg numbness. During the examination, she exhibited periorbital edema, non-pitting edema in the lower extremities, bradycardia, and hypothermia. The blood work revealed an elevation in TSH levels at 301 uIU/L (0.45-5.33 uIU/mL). The patient was administered IV Synthroid (200 mcg), Atropine, and Hydrocortisone due to concerns about myxedema coma. After four hours, the patient experienced angioedema and hypotension, necessitating intubation. This situation was complicated by a pulseless electrical activity (PEA) arrest. Following cardiopulmonary resuscitation and the administration of epinephrine, the patient achieved return of spontaneous circulation. The allergy team assessed the patient for potential anaphylactic shock from IV Synthroid. Subsequently, the patient was initiated onIV Liothyronine and Hydrocortisone, leading to improvement in mental status over a period of a few weeks, and no adverse effects were reported. Thyroid labs improved to TSH of 53 (0.45-5.33 uIU/mL), FT3 of 3.3 (2.5-4.4 pg/mL) and total T3 of 133 (87-178 ng/dl). Upon discharge, the patient was prescribed Liothyronine, with plans to perform a Levothyroxine desensitization test in the outpatient setting. Conclusion: Myxedema coma is an endocrine emergency. Patients usually present with deteriorating mental status, hypothermia, and multiple organ system abnormalities. The diagnosis relies more on the clinical presentation and physical examination than on laboratory results. Thyroid replacement therapy serves as the cornerstone of treatment, with a preference for T4 due to its greater availability and lower likelihood of adverse events compared to Liothyronine, which may increase the risk of mortality at higher doses. Despite associated risks, incorporating low doses of Liothyronine is still considered in treatment plans, driven by concerns about reduced T4 to T3 conversion in myxedema patients. Hypersensitivity reactions to Levothyroxine are uncommon but may manifest as widespread hives, swelling, eczema-like skin rashes, elevated body temperature, and compromised liver function, with only one case reporting an anaphylactic reaction to Levothyroxine. In summary, the potential for experiencing an anaphylactic reaction to Levothyroxine exists, highlighting the need to contemplate alternative treatments, such as Liothyronine. Desensitization methods can be considered once the patient's condition is stable. Presentation: 6/2/2024

Toxicity of Cancer Immunotherapies in Older Patients: Does Age Make a Difference?

The use of immunotherapy agents especially immune checkpoint inhibitors is growing, and toxicities known as immune-related adverse events affecting any organ system may develop as a consequence of the treatment. With an ageing population, a considerable number of patients who will receive these therapies will be older adults. However, older patients who have highly heterogenous clinical characteristics, age-related changes in the immune system, a higher prevalence of comorbidities and frailty have been poorly represented in clinical trials, leaving gaps in understanding the safety of immune checkpoint inhibitor agents in this subgroup. Therefore, the safety of immune checkpoint inhibitors is a primary point of consideration when treating older patients with cancer. The available evidence is conflicting, but it generally suggests that the incidence of immune-related adverse events is not necessarily higher in older patients, but it may have a different profile. It is important to also note that the management of immune-related adverse events can be a challenge in these patients, owing to the risks associated with the use of corticosteroids and a reduced physiological reserve. A comprehensive characterisation of immune ageing, potential biomarkers to predict immune-related adverse events, the use of measures for frailty, enrolling older patients with cancer to clinical trials and analysis of real-world data are necessary to improve the evidence-based decision making for immune checkpoint inhibitor treatment in a geriatric oncology population.

Barriers of adopting sustainable soil management practices for organic and conventional farming systems

There is a general consensus among stakeholders about the benefits of sustainable soil management practices for soil health, yet their implementation lags behind expectations. The aim of this paper is to analyse factors supporting or hindering the implementation of sustainable soil management practices in conventional and organic farming systems. This is achieved using a Logit model, based on penalized maximum likelihood estimation on survey data by 76 farmers from 10 federal states in Germany. Affected factors were categorized in two main groups: agricultural soil management practices, and barriers to their implementation. The measures for soil improving agricultural management included (I) structural landscape elements, (II) organic fertilization, (III) diversified crop rotation, (IV) permanent soil cover (V) conservation tillage, (VI) reduced weight pressure, and (VII) optimized timing of wheeling. Results show differences in preferences between conventional and organic farmers for key sustainable soil management practices, including conservation tillage, optimized wheeling timing, reduced weight pressure, and diversified crop rotation. Economic constraints decrease crop rotation diversification in conventional systems by 14%. Conservation tillage raises the chance of a farm being conventional by 16%, while optimizing wheeling timing reduces it by 60%, highlighting soil compaction concerns among organic farmers. Marginal effects confirm that economic factors, not knowledge, are the main barriers to sustainable soil management. Inconsistent policies, lack of support, and insufficient financial incentives from government institutions can hinder the willingness of farmers to adopt these practices, further exacerbating the barriers to adoption.

A Systematic Review of the Complications Associated with Free Fibular Flaps in Adult and Pediatric Spinal Reconstruction.

Background Free fibular flaps have been suggested as a modality of reconstruction for complex spinal deformities. However, there is limited data that describes associated post-operative outcomes. The purpose of this systematic review was to characterize outcomes after spinal reconstruction using the free fibular flap for both adults and children. Methods Thirty-nine articles among four databases were identified as having met inclusion criteria. Patient demographics, indications for spinal reconstruction as well as location and anastomosis, history of chemotherapy and radiation therapy, and post-operative outcomes including complications were identified. Major complications were defined as complications requiring reoperation, while minor complications were those that did not require reoperation. Systemic complications were defined as complications affecting sites or organ systems beyond the local donor and recipient sites. Statistical analysis was performed using Fischer's exact, Chi-squared, and t-tests. Results We identified 218 adult patients (mean age 47.7 years, 56.4% male) and 27 pediatric patients (mean age 12.7 years, 55.6% male). While there was no significant difference in the rates of bony union between the two groups (adults: 90.8%, children: 90%, p>0.9), adults had significantly higher rates of major (27% vs. 7.4%, p=0.026), minor (26.1% vs. 7.4%, p=0.032), and systemic (14.2% vs. 0%, p=0.047) complications. Conclusions Free fibular flaps are effective for spinal reconstruction for both adults and children, as evidenced by the high rates of bony union. However, adults exhibited significantly higher complication rates. Further research is required to better understand the patient and clinical risk factors associated with increased rate of complications.

Real-time visualisation of developing chick embryos cultured in transparent plastic films from the blastoderm stage until hatching

Real-time visualisation of chick embryo development occurring inside an opaque eggshell is a major goal of developmental biology. This goal was partially achieved when 3-day-old embryos recovered from fertilised shelled eggs, preincubated in a conventional incubator, hatched after the egg contents had been transferred into shell-less embryo culture systems constructed of transparent plastic film placed in a plastic cup. However, the hatchable shell-less embryo culture systems described thus far cannot be used to visualise the dynamic morphological changes associated with the emergence of major organ systems during the first 3 days of embryo development, as the blastoderm area needs to be covered with an opaque membrane. Here, we present the development of a chick embryo culture system that enables omnidirectional real-time visualisation of the developing embryo, beginning from the newly laid blastoderm stage embryo until hatching.

Investigation of serum neurofilament light chain as a biomarker in Fabry disease

Fabry disease (FD) constitutes a rare, X-linked lysosomal storage disorder affecting multiple organ systems, most notably heart, kidneys, and the central nervous system. Neurofilament light chains (NfL) have emerged as a prime candidate for a body fluid biomarker reflecting neuro-axonal injury. We aimed to evaluate its addition to the diagnostic and monitoring armamentarium in FD. Serum NfL concentrations (sNfL) were measured in 50 people with FD (PwFD) and 30 healthy control subjects (HC) using the Simoa© technology, followed by calculation of Z-scores adjusted for age and body mass index. In addition, clinical disease severity in PwFD was measured using the FOS-MSSI (Fabry outcome study – Mainz severity score index), which comprises clinical and paraclinical parameters. PwFD show elevated sNfL Z-scores compared to HC (PwFD: 1.12 [SD 1.5], HC: 0.01 [SD 1.2], p < 0.001). In PwFD, males showed higher sNfL Z-scores than females (1.75 [SD 1.5] vs. 0.73 [SD 1.4]). Importantly, sNfL Z-scores were increased in PwFD with ischemic white matter lesions of the CNS (1.5, SD 2.2 vs. 0.5, SD 2.9, p = 0.03). In our small cohort, sNfL Z-scores correlated fairly with FOS-MSSI (Kendall’s-Tau [τ] = 0.25, p = 0.01), and, interestingly with serum creatinine (τ = 0.28, p = 0.005) and estimated glomerular filtration rate (eGFR, τ =-0.28, p = 0.005). Based on these exploratory results, sNfL might provide value as a biomarker of neuroaxonal damage in FD, possibly reflecting cerebrovascular injury. Additionally, the correlation of sNfL with renal function warrants further investigation.

Transforming the feeding regime towards low-input increases the environmental impact of organic milk production on a case study farm in central germany

Abstract Purpose Despite the direct effect of the feeding regime on the environmental impacts of dairy farming systems, its level of intensity, particularly in organic systems, has rarely been investigated. This study compares the environmental impact of a high-input feeding regime with a grassland-based, low-input feeding regime scenario within an organic milk production system conducted on Gladbacherhof, the research farm of Justus Liebig University Giessen, in Central Germany. Methods An integrated Life Cycle Assessment (LCA) analysis was performed from a cradle-to-farm gate perspective to quantify five environmental impacts, namely Global Warming (GW), Non-Renewable Energy Use (NREU), Land Use (LU), Terrestrial Acidification (TA), and Freshwater Eutrophication (FE). All agronomic data of the Gladbacherhof research farm, averaged over the years 2010–2017, were included. When not directly measured on the farm, ecoinvent data were included. Results and discussion Contrary to our hypothesis, the results suggest that a grassland-based low-input system has a higher environmental impact as compared to a high-input system for each of the five impact categories when using fat and protein-corrected milk (FPCM) as the functional unit. A 50% reduction in concentrates and exclusion of maize silage from the feed ration in the modelled low-input production system lead to a 20% drop in milk yield. To balance the energy content in low-input feeding ration, longer grazing period and higher amount of hay, alfalfa, and grass silage are required. This in turn results in higher emissions from enteric fermentation, manure management, and feed production and hence in higher environmental impact, particularly for GW, TA, and FE. Conclusions This study is one of the few that directly explores the environmental impact of feeding intensity in an organic milk production system. Nevertheless, there is a lack of research on consolidated emission factors for several greenhouse gas (GHG) sources in organic livestock and cropping systems to perform more robust carbon footprint calculations that comply with the Intergovernmental Panel on Climate Change (IPCC) Tier 3 GHG reporting guidelines. To generalize the results at the regional or national scale, direct comparisons with a larger number of organic farms representative of high-input and low-input intensities are still essential.

Unlocking amplified magneto-photocurrent using multi-field manipulation in nonfullerene organic bulk heterojunction systems.

An effective manipulation of polaron pairs (PPs) for realizing amplified magneto-photocurrent (AMPC) is of critical importance toward the development of low power consumption and high-performance organic spin-optoelectronic devices, for instance magneto-photo-volatile memories. By far, it is challenging and there is a lack of method to reach AMPC. The typical magneto-photocurrent due to the light-matter interanion is primarily for unveiling the spin-dependent electron-hole dissociation in organic solar cells. Herein, we achieved an AMPC of ∼140% in nonfullerene organic bulk heterojunction systems at room temperature. We found that the amplification can be effectively triggered by a multi-field to a large number of photogenerated PPs at intermediate charge transfer states. We further postulate that, at steady state, they may experience a cyclic photophysical process due to the triplet-exciton polaron interaction. This study paves the way for the realization of AMPC in the organic spin-optoelectronic system.