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Blood biochemistry represents a minimally invasive tool for monitoring sea turtle health, assessing injured sea turtles and supporting conservation strategies. In Grenada, West Indies, plasma biochemical variables were examined in 33 nesting leatherback (Dermochelys coriacea), 49 foraging green (Chelonia mydas), 49 foraging hawksbill (Eretmochelys imbricata) and 12 nesting hawksbill sea turtles sampled between 2017 and 2022. Plasma biochemistry reference intervals are described herein except for nesting hawksbills, which are represented by descriptive statistics due to the low sample size. Select analyte concentrations were positively correlated with curved carapace length in leatherbacks (chloride), green turtles (total protein, albumin and globulin) and foraging hawksbills (total protein, albumin and phosphorus). Cholesterol (7.8 mmol/l ± 1.6 SD) and triglyceride (6.9 mmol/l ± 1.9 SD) concentrations were significantly higher in leatherbacks compared to foraging green turtles, foraging hawksbills and nesting hawksbills (P < 0.001 for all). Cholesterol was significantly higher in nesting hawksbills compared to foraging green turtles (P = 0.050) and foraging hawksbills (P = 0.050). Foraging hawksbills demonstrated significantly higher aspartate transaminase activities than leatherbacks (P = 0.002), green turtles (P = 0.009) and nesting hawksbills (P < 0.001). Biochemical results provide baseline population health data and support guidance for treatments during clinical sea turtle rehabilitation efforts. They also provide insight into species-specific physiologic differences and preludes further studies to better characterize the impacts of life-stage class on biochemistry reference intervals to better support wild sea turtle populations in Grenada.

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The severity of the 2019 coronavirus disease (COVID-19) and its effects remain unpredictable. Certain factors, such as obesity, hypertension, and type 2 diabetes mellitus, may increase the severity of the disease. Rheumatology experts suggest that patients with active autoimmune conditions and controlled autoimmune diseases on immunosuppressive therapy may be at higher risk of developing severe COVID-19. In this retrospective observational study, we aimed to examine the patterns of COVID-19 in patients with underlying rheumatological diseases and their association with disease severity and hospital outcomes. A total of 34 patients with underlying rheumatological diseases who tested positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) by polymerase chain reaction (PCR) were included between March 2020 and April 2021 at King Fahd Hospital of the University. The study population consisted of 76.47% female and 23.53% male patients, with a mean age ranging from 20 to 40 years. Female gender (p=0.0001) and younger age (p=0.004) were associated with milder disease. The most frequent rheumatological disease was systemic lupus erythematosus (SLE) (38.24%), which was associated with a milder infection (p=0.045). Patients treated with mycophenolate mofetil (MMF) had a milder disease course (p=0.0037). Hypertension was significantly associated with severe COVID-19 disease (p=0.037). There was no significant relationship between SLE and the need for ICU admission. Patients on hydroxychloroquine and MMF tended to develop milder disease, and there was no association between the severity of the infection and the treatment with steroids.

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The most prevalent conditions among ocular surgery and COVID-19 patients are fungal eye infections, which may cause inflammation and dry eye, and may cause ocular morbidity. Amphotericin-B eye drops are commonly used in the treatment of ocular fungal infections. Lactoferrin is an iron-binding glycoprotein with broad-spectrum antimicrobial activity and is used for the treatment of dry eye, conjunctivitis, and ocular inflammation. However, poor aqueous stability and excessive nasolacrimal duct draining impede these agens' efficiency. The aim of this study was to examine the effect of Amphotericin-B, as an antifungal against Candida albicans, Fusarium, and Aspergillus flavus, and Lactoferrin, as an anti-inflammatory and anti-dry eye, when co-loaded in triblock polymers PLGA-PEG-PEI nanoparticles embedded in P188-P407 ophthalmic thermosensitive gel. The nanoparticles were prepared by a double emulsion solvent evaporation method. The optimized formula showed particle size (177.0 ± 0.3 nm), poly-dispersity index (0.011 ± 0.01), zeta-potential (31.9 ± 0.3 mV), and entrapment% (90.9 ± 0.5) with improved ex-vivo pharmacokinetic parameters and ex-vivo trans-corneal penetrability, compared with drug solution. Confocal laser scanning revealed valuable penetration of fluoro-labeled nanoparticles. Irritation tests (Draize Test), Atomic force microscopy, cell culture and animal tests including histopathological analysis revealed superiority of the nanoparticles in reducing signs of inflammation and eradication of fungal infection in rabbits, without causing any damage to rabbit eyeballs. The nanoparticles exhibited favorable pharmacodynamic features with sustained release profile, and is neither cytotoxic nor irritating in-vitro or in-vivo. The developed formulation might provide a new and safe nanotechnology for treating eye problems, like inflammation and fungal infections.

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Background: Multiple acyl-coenzyme A dehydrogenase deficiency (MADD) is a rare metabolic disorder affecting fatty acid oxidation. Incidence at birth is estimated at 1:250 000, but type III presents in adults. It is characterized by nonspecific symptoms but if undiagnosed may cause ketoacidosis and rhabdomyolysis. A review of 350 patients found less than one third presented with metabolic crises. Our objective is to describe an adult with weakness after carbohydrate restriction that developed a pulmonary embolism and ketoacidosis, and was diagnosed with MADD type III. Case Report: A 27-year-old woman with obesity presented to the hospital with fatigue and weakness worsening over months causing falls and decreased intake. She presented earlier to clinic with milder symptoms starting months after initiating a low carbohydrate diet. Testing revealed mild hypothyroidism and she started Levothyroxine for presumed hypothyroid myopathy but progressed. Muscle biopsy suggested a lipid storage myopathy. Genetic testing revealed a mutation in the ETFDH (electron transfer flavoprotein dehydrogenase) gene likely pathogenic for MADD; however, before this was available she developed severe ketoacidosis and rhabdomyolysis. She empirically started a low-fat diet, carnitine, cyanocobalamin, and coenzyme Q10 supplementation with improvement. Over months her energy and strength normalized. Discussion: MADD may cause ketoacidosis and rhabdomyolysis but this is rare in adults. Diagnosis requires clinical suspicion followed by biochemical and genetic testing. It should be considered when patients present with weakness or fasting intolerance. Treatment includes high carbohydrate, low-fat diets, supplementation, and avoiding fasting. Conclusion: There should be greater awareness to consider MADD in adults presenting with neuromuscular symptoms, if untreated it may cause severe metabolic derangements.

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Eosinophilic myocarditis (EM) is a cardiac manifestation of hypereosinophilic syndrome with a high mortality rate. EM shares imaging features similar to other restrictive cardiopathies, and include patchy intramural late gadolinium enhancement on cardiac magnetic resonance with or without presence of biventricular thrombus. Diagnosis is confirmed on histopathology, and is the current gold standard. Here we report clinical presentation and imaging findings of EM in a 70-year-old woman who presented with fever and chills.

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Background: Moringa stenopetala (Baker f.) Cudof. and Mentha spicata L. are widely used in the traditional system of medicine for the treatment of diabetes, hypertension, digestive problems and various disorders. The leaves formulation of M. stenopetala and M. spicata herbal tea showed better antidiabetic and antihypertensive effects in rodent models. However, its long-term safety profile has not been investigated yet. Thus, this study investigated the subchronic (90 days) oral toxicity of the leaves formulation of M. stenopetala and M. spicata herbal tea in Wistar albino rats. Methods: Four groups of rats (n = 10, with 5/sex/group) were randomly assigned into a control (vehicle) group and three test groups (559.36, 1118.72 and 2237.44 mg/kg, respectively). The three test groups received the herbal tea of M. stenopetala and M. spicata leaves blend daily for 90 days. The control group received distilled water. During the treatment period, clinical signs were observed daily, and food consumption and body weight changes of the rats were measured weekly. At the end of the experiment, macro-pathological, hematological and biochemical parameters were evaluated. Furthermore, histopathology of liver, kidney, heart, stomach and pancreas were examined. Results: Subchronic oral administration of the herbal tea of M. stenopetala and M. spicata leaves blend did not result in death or significant toxicity signs in the treated group rats. Moreover, the herbal tea caused no significant changes on body weight, food intake, organ weight, hematological and biochemical parameters in either sex. However, the serum AST, CK and LDH levels were significantly elevated in rats treated with 2237.44 mg/kg of herbal tea in both sexes. There was no significant alteration in the histology of organs, only minor lesions in the liver, kidney and pancreas were observed. Conclusion: The study results indicate that the herbal tea of M. stenopetala and M. spicata leaves blend is relatively safe/low toxic to rats in subchronic exposure. However, further preclinical (chronic, teratogenic, reproductive and developmental toxicity) studies in animals are required in order to have sufficient safety and toxicity profiles for its use in humans.

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Cardiovascular disease is the most common disease in the world and the first among the causes of human death. Its morbidity and mortality increase annually, but no effective treatment is available. Therefore, new drugs should be developed to treat cardiovascular disease. Gentianella acuta (Michx.) Hulten (G. acuta) is an important Mongolian medicine in China and elicits protective effects on cardiovascular health. In this study, liquid chromatography-mass spectrometry (LC-MS) combined with network pharmacology was used to screen the main active ingredients and confirm that bellidifolin was one of the main components for the treatment of ischemic heart disease. Then, rat myocardial (H9c2) cells injury model induced by hydrogen peroxide (H2O2) in vitro was established to verify the effect of bellidifolin on oxidative stress stimulation, including determination of antioxidant enzyme activity and apoptosis. Transcriptome sequencing, qRT-PCR, and western blot were performed to further verify the antioxidant stress mechanism of bellidifolin. Results showed that bellidifolin pretreatment decreased the rate of apoptosis and the levels of lactate dehydrogenase (LDH), creatine kinase (CK), and alanine aminotransferase (ALT). Conversely, it increased the contents of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in a dose-dependent manner, indicating that bellidifolin caused a protective effect on cardiomyocyte injury. Bellidifolin minimized the H2O2-induced cell injury by activating the PI3K-Akt signal pathway and downregulating glycogen synthase kinase-3ß (GSK-3ß) and p-Akt1/Akt1. Therefore, this work revealed that G. acuta has a good development prospect as an edible medicinal plant in cardiovascular disease. Its bellidifolin component is a potential therapeutic agent for cardiovascular disease induced by oxidative stress damage.

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Objective: To assess the outcomes of emergency revascularization with endovascular fenestration/stenting followed by delayed open aortic repair in patients with acute type A aortic dissection with lower extremity (LE) malperfusion syndrome (MPS); that is, necrosis and dysfunction of the lower extremity. Methods: From 1996 to 2019, among 760 consecutive acute type A aortic dissection patients 512 patients had no malperfusion syndrome (Non-MPS), whereas 26 patients had LE-MPS with/without renal MPS and underwent endovascular fenestration/stenting, open aortic repair, or both. Patients with coronary, cerebral, mesenteric, and celiac MPS, or managed with thoracic endovascular aortic repair, were excluded (n = 222). All patients with LE-MPS underwent upfront endovascular fenestration/stenting except 1 patient (with signs of rupture) who initially underwent emergency open aortic repair. Results: Among the LE-MPS patients, 17 (65%) had LE pain, 15 (58%) had abnormal motor function with 8 (31%) having paralysis, 10 (38%) had LE pallor, 17 (65%) had LE paresthesia, and 20 (77%) had LE pulselessness. Of the 25 patients undergoing upfront endovascular fenestration/stenting, 16 went on to open aortic repair, 3 survived to discharge without aortic repair, and 6 died before aortic repair (3-aortic rupture and 3-organ failure). In-hospital mortality among all patients was significantly higher in the LE-MPS group (31% vs 6.3%; P = .0003). Among those undergoing open aortic repair, postoperative outcomes were similar between groups, including operative mortality (18% vs 6.5%; P = .10). LE-MPS was a significant risk factor for in-hospital mortality (odds ratio, 6.0 [1.9, 19]; P = .002). Conclusions: In acute type A aortic dissection, LE-MPS was associated with high in-hospital mortality. Emergency revascularization with endovascular fenestration/stenting followed by delayed open aortic repair may be a reasonable approach.

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Objective: To characterize the utility of an existing electrocardiogram (ECG)-artificial intelligence (AI) algorithm of left ventricular dysfunction (LVD) in immune-mediated necrotizing myopathy (IMNM). Patients and Methods: A retrospective cohort observational study was conducted within our tertiary-care neuromuscular clinic for patients with IMNM meeting European Neuromuscular Centre diagnostic criteria (January 1, 2000, to December 31, 2020). A validated AI algorithm using 12-lead standard ECGs to detect LVD was applied. The output was presented as a percent probability of LVD. Electrocardiograms before and while on immunotherapy were reviewed. The LVD-predicted probability scores were compared with echocardiograms, immunotherapy treatment response, and mortality. Results: The ECG-AI algorithm had acceptable accuracy in LVD prediction in 74% (68 of 89) of patients with IMNM with available echocardiograms (discrimination threshold, 0.74; 95% CI, 0.6-0.87). This translates into a sensitivity of 80.0% and specificity of 62.8% to detect LVD. Best cutoff probability prediction was 7 times more likely to have LVD (odds ratio, 6.75; 95% CI, 2.11-21.51; P=.001). Early detection occurred in 18% (16 of 89) of patients who initially had normal echocardiograms and were without cardiorespiratory symptoms, of which 6 subsequently advanced to LVD cardiorespiratory failure. The LVD probability scores improved for patients on immunotherapy (median slope, -3.96; R = -0.12; P=.002). Mortality risk was 7 times greater with abnormal LVD probability scores (hazard ratio, 7.33; 95% CI, 1.63-32.88; P=.009). Conclusion: In IMNM, an AI-ECG algorithm assists detection of LVD, enhancing the decision to advance to echocardiogram testing, while also informing on mortality risk, which is important in the decision of immunotherapy escalation and monitoring.

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Background: Ischemia reperfusion (I/R) play an imperative role in the expansion of cardiovascular disease. Sinomenine (SM) has been exhibited to possess antioxidant, anticancer, anti-inflammatory, antiviral and anticarcinogenic properties. The aim of the study was scrutinized the cardioprotective effect of SM against I/R injury in rat. Methods: Rat were randomly divided into normal control (NC), I/R control and I/R + SM (5, 10 and 20 mg/kg), respectively. Ventricular arrhythmias, body weight and heart weight were estimated. Antioxidant, inflammatory cytokines, inflammatory mediators and plasmin system indicator were accessed. Results: Pre-treated SM group rats exhibited the reduction in the duration and incidence of ventricular fibrillation, ventricular ectopic beat (VEB) and ventricular tachycardia along with suppression of arrhythmia score during the ischemia (30 and 120 min). SM treated rats significantly (P < 0.001) altered the level of antioxidant parameters. SM treatment significantly (P < 0.001) repressed the level of creatine kinase MB (CK-MB), creatine kinase (CK) and troponin I (Tnl). SM treated rats significantly (P < 0.001) repressed the tissue factor (TF), thromboxane B2 (TXB2), plasminogen activator inhibitor 1 (PAI-1) and plasma fibrinogen (Fbg) and inflammatory cytokines and inflammatory mediators. Conclusion: Our result clearly indicated that SM plays anti-arrhythmia effect in I/R injury in the rats via alteration of oxidative stress and inflammatory reaction.

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S-Adenosylhomocysteine (SAH) hydrolase deficiency is an autosomal recessive disorder in methionine metabolism caused by pathogenic variants in the gene AHCY. To date, only 15 patients with this disorder have been reported, including several patients treated with dietary management. In this study, we report a new case with SAH hydrolase deficiency and conduct a literature review with a focus on the biochemical profiles and the efficacy of dietary management. The biochemical markers associated with SAH hydrolase deficiency includes elevated levels of methionine, creatine kinase (CK), SAH, and S-Adenosylmethionine (SAM). However, half of the cases (6/12) had normal methionine levels at the initial evaluation. In contrary, SAM and SAH were markedly elevated in all reported patients at the initial evaluation (SAM: range 1.7× -53×, median 21.5×; SAH: range 4.9× -193.8×, median 98.1×). Nine patients were treated with methionine-restricted diet, which markedly reduced SAM and SAH in all patients but the levels did not normalize. CK and liver function did not show significant improvement with dietary treatment. The majority of patients (5/8) demonstrated clinical improvements with dietary management, such as increase in muscle strength; but all patients continued to experience developmental delay and two deaths were reported from cardiopulmonary arrest. This study suggests that methionine is not a reliable diagnostic biochemical marker for SAH hydrolase deficiency and SAM/SAH levels should be considered in the workup in neonates with unexplained hypotonia, liver dysfunction, or elevated CK. Dietary restriction of methionine demonstrates clinical benefits in some affected patients and should be trialed in patients with SAH hydrolase deficiency.

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OBJECTVIES: This study is aimed at establishing reference intervals (RIs) of 40 chemistry and immunochemistry analytes for Ghanaian adults based on internationally harmonized protocol by IFCC Committee on Reference Intervals and Decision Limits (C-RIDL). METHODS: A total of 501 healthy volunteers aged ≥18 years were recruited from the northern and southern regions of Ghana. Blood samples were analyzed with Beckman-Coulter AU480 and Centaur-XP/Siemen auto-analyzers. Sources of variations of reference values (RVs) were evaluated by multiple regression analysis (MRA). The need for partitioning RVs by sex and age was guided by the SD ratio (SDR). The RI for each analyte was derived using parametric method with application of the latent abnormal values exclusion (LAVE) method. RESULTS: Using SDR≥0.4 as threshold, RVs were partitioned by sex for most enzymes, creatinine, uric acid (UA), bilirubin, immunoglobulin-M. MRA revealed age and body mass index (BMI) as major source of variations of many analytes. LAVE lowered the upper limits of RIs for alanine/aspartate aminotransferase, γ-glutamyl transaminase and lipids. Exclusion of individuals with BMI≥30 further lowered the RIs for lipids and CRP. After standardization based on value-assigned serum panel provided by C-RIDL, Ghanaian RIs were found higher for creatine kinase, amylase, and lower for albumin and urea compared to other collaborating countries. CONCLUSIONS: The LAVE effect on many clinical chemistry RIs supports the need for the secondary exclusion for reliable derivation of RIs. The differences in Ghanaian RIs compared to other countries underscore the importance of country specific-RIs for improved clinical decision making.

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This study aimed to investigate the nonclinical safety of lincomycin and spectinomycin hydrochloride (LC-SPH) intramuscular (i.m) doses on target animals (chickens) to provide guidelines for dose level design and side effect monitoring in clinical trials. A total of 80 healthy Arbor Acres plus broiler chicks were completely randomized and blindly divided into four treatment groups (control, one-time dose, three-time dose, and five-time dose) of 20 chicks each (20 chickens per group). At the age of day 15, all chickens (except the control group) were administered LC-SPH intramuscularly (chest muscles) at different doses of 20 mg/kg.bw, 60 mg/kg.bw, and 100 mg/kg.bw respectively for 9 consecutive days recommended by veterinary international cooperation on harmonization (VICH) guidelines. The chickens had ad libitum access to antibiotic-free feed and water. Feeding chickens were observed twice a day throughout the study. The drug safety was evaluated by complete blood count, biochemical parameters, histopathological, clinical signs, body weight gain, and feed conversion ratio (FCR). Hence, considering the minor toxicity of 60 mg/kg, our results reveal that intramuscular injection of at least 20 mg/kg body weight has no effects on growth performance, clinical blood parameters, organ coefficient, and histopathological parameters. Thus, a combination of LC-SPH 20 mg/kg body weight i.m injection investigated safe followed daily administration for nine consecutive days in healthy chickens. It is concluded that the experimental results support the safety of 20 mg/kg body weight in combination for the further clinical research study.

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Enzyme replacement therapy (ERT) with recombinant human acid alpha-glucosidase (rhGAA) in late-onset Pompe disease (LOPD) shows beneficial effects in the first years often followed by a decline. We aimed to examine long-term ERT effects in an elderly LOPD cohort. Patients with age at diagnosis/start of ERT >50 years and ERT duration > seven years were included. Outcome parameters were MRC sum-score, 6 Minute Walk Test 6MWT, Quick Motor Function Test QMFT, forced vital capacity FVC sitting/supine, CK levels and rhGAA IgG antibody titers. We retrospectively analysed six patients with a median age at diagnosis/start of ERT of 63 years (range 52-69), and a median ERT duration of eight years (range 7-12). 6MWT improved in 4/6, and 2/6 each showed an improvement or stabilization in muscle strength and FVC supine. In contrast, FVC showed a decline in all patients in a sitting position, and QMFT worsened in 5/6. CK levels decreased in all patients. Antibody titers were not associated with treatment effects. Highest titers were present in best responders who were female, still ambulatory and without ventilatory support at follow-up. ERT effects were very heterogeneous and showed best results in 6MWT, followed by muscle strength in manual testing and FVC supine.

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A 79-year-old man with chest pain and dyspnea underwent emergency percutaneous coronary intervention for acute myocardial infarction. However, he died 17 days later due to refractory heart failure. An autopsy revealed cardiac strangulation caused by herniation of the apical heart through a pericardial defect due to partial absence of the pericardium. (Level of Difficulty: Advanced.).