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Introduction The uncinate process (UP) is the most important and constant landmark in the ostiomeatal complex and the middle meatus.

Purpose The present study aimed to determine the serum level of asprosin, a novel glucogenic and orexigenic hormone, in NAFLD and hypothyroidism patients.Methods This is a case–control study that included three groups of age and sex-matched subjects: hypothyroid patients with NAFLD (n = 26), hypothyroid patients without NAFLD (n = 25) and normal control subjects (n = 27). A detailed clinical history was obtained, and an examination was performed. Laboratory tests included fasting plasma glucose and insulin, lipid profile, TSH, free T4, AST, ALT, albumin, and asprosin. The homeostatic model assessment of insulin resistance (HOMA-IR) score was calculated. Abdominal ultrasonography was performed to calculate the hepatorenal index and define participants with NAFLD. The data were statistically analyzed.Results There was a statistically significant difference between the three groups regarding serum asprosin concentration (p

Abstract Deep eutectic electrolytes (DEEs) show promise for future electrochemical systems due to their adjustable buffer capacities. This study utilizes machine learning algorithms to analyse the carbon dioxide reduction reaction (CO2RR) in DEEs with a buffer capacity of approximately 10.21 mol/pH. The objective is to minimize undesired hydrogen evolution reactions (HER) and render CO2RR dominant in a membrane cell. The CO2RR process was found to be non-adiabatic, as the time of nuclear motion for CO3 2− in K2CO3 product, through CO2 ●− trapping, is 0.368 femtoseconds shorter than the 1.856 × 10−3s charge transfer relaxation time. Microkinetic analysis reveals that the rate of CO2RR to CO2 ●− is 2.14 × 103 mol/cm2/s2 with a rate constant of 2.1 × 1010 cm/s. Our findings demonstrate that ensemble and k-Nearest Neighbours algorithms learn the CO2RR dataset, achieving a prediction accuracy of over 99%. The models were verified visually and quantitatively by overlaying predicted and experimental dataset. Diagnostic and SHAP analyses highlighted the gradient boost ensemble algorithm, predicting asymptotic current densities of -4.114 mA/cm2 or -13.340 mA/cm2, with high turnover frequencies (TOF) of 3.79 × 1010 h-1 or 12.30 × 1010 h-1 for CO2 ●− or K2CO3 generation on silver electrodes, respectively. These results consider both accuracy and robustness against overfitting, providing an opportunity to optimize future non-aqueous electrolytes for convenient TOF measurements at industrially relevant current densities.

Abstract Background Epigenome‐wide association studies have identified multiple DNA methylation sites (CpGs) associated with alcohol consumption, an important lifestyle risk factor for cardiovascular diseases. This study aimed to test the hypothesis that an alcohol consumption epigenetic risk score (ERS) is associated with blood pressure (BP) traits. Results We implemented an ERS based on a previously reported epigenetic signature of 144 alcohol-associated CpGs in meta-analysis of participants of European ancestry. We found a one-unit increment of ERS was associated with eleven drinks of alcohol consumed per day, on average, across several cohorts (p

Abstract This article investigates the behavior of hybrid FRP Concrete-Steel columns with an elliptical cross section. The investigation was carried out by gathering information through literature and conducting a parametric study, which resulted in 116 data points. Moreover, multiple machine learning predictive models were developed to accurately estimate the confined ultimate strain and the ultimate load of confined concrete at the rupture of FRP tube. Decision Tree (DT), Random Forest (RF), Adaptive Boosting (ADAB), Categorical Boosting (CATB), and eXtreme Gradient Boosting (XGB) machine learning techniques were utilized for the proposed models. Finally, these models were visually and quantitatively verified and evaluated. It was concluded that the CATB and XGB are standout models, offering high accuracy and strong generalization capabilities. The CATB model is slightly superior due to its consistently lower error rates during testing, indicating it is the best model for this dataset when considering both accuracy and robustness against overfitting.

Inflammatory fibroid polyps (IFPs) are rare submucosal lesions that usually arise in the stomach. It represents 0.1% of all gastric polypoid lesions and are frequently asymptomatic. It’s usually revealed by an abdominal pain. Gastrointestinal bleeding can occur when the polyp is ulcerated. We report a case of a 72-year-old female with an IFP of the prepyloric region. The head of the polyp was thirty-five millimeters in diameter. It was revealed by an upper gastrointestinal bleeding and epigastric pain. An endoscopic resection was performed.

Abstract Concrete compressive strength (CS) is a crucial performance parameter in concrete structure design. Reliable strength prediction reduces costs and time in design and prevents material waste from extensive mixture trials. Machine learning techniques solve structural engineering challenges such as CS prediction. This study used Machine Learning (ML) models to enhance the prediction of CS, analyzing 1030 experimental CS data ranging from 2.33 to 82.60 MPa from previous research databases. The ML models included both non-ensemble and ensemble types. The non-ensemble models were regression-based, evolutionary, neural network, and fuzzy-inference-system. Meanwhile, the ensemble models consisted of adaptive boosting, random forest, and gradient boosting. There were eight input parameters: cement, blast-furnace-slag, aggregates (coarse and fine), fly ash, water, superplasticizer, and curing days, with the CS as the output. Comprehensive performance evaluations include visual and quantitative methods and k-fold cross-validation to assess the study’s reliability and accuracy. A sensitivity analysis using Shapley-Additive-exPlanations (SHAP) was conducted to understand better how each input variable affects CS. The findings showed that the Categorical-Gradient-Boosting (CatBoost) model was the most accurate prediction during the testing stage. It had the highest determination-coefficient (R2) of 0.966 and the lowest Root-Mean-Square-Error (RMSE) of 3.06 MPa. The SHAP analysis showed that the age of the concrete was the most critical factor in the predictive accuracy. Finally, a Graphical User Interface (GUI) was offered for designers to predict concrete CS quickly and economically instead of costly computational or experimental tests.

Abstract Colisepticaemia caused by avian pathogenic Escherichia coli (APEC) is a challenging disease due to its high economic importance in poultry, dubious pathogenesis and potential link with zoonosis and food safety. The existing in vitro studies can’t define hallmark traits of APEC isolates, suggesting a paradigm shift towards host response to understand pathogenesis. This study investigated the comprehensive pathological and microbial progression of colisepticaemia, and transmission of E. coli into eggs using novel tools. In total 48 hens were allocated into three groups and were inoculated intratracheally with ilux2-E. coli PA14/17480/5­/ovary (bioluminescent strain), E. coli PA14/17480/5­/ovary or phosphate buffered saline. Infection with both strains led to typical clinical signs and lesions of colibacillosis as in field outbreaks. Based on lung histopathology, colisepticaemia progression was divided into four disease stages as: stage I (1–3 days post infection (dpi)), stage II (6 dpi), stage III (9 dpi) and stage IV (16 dpi) that were histologically characterized by predominance of heterophils, mixed cells, pyogranuloma, and convalescence, respectively. As disease progressed, bacterial colonization in host organs also decreased, revealed by the quantification of bacterial bioluminescence, bacteriology, and quantitative immunohistochemistry. Furthermore, immunofluorescence, immunohistochemistry, and bacteria re-isolation showed that E. coli colonized the reproductive tract of infected hens and reached to egg yolk and albumen. In conclusion, the study provides novel insights into the pathogenesis of colisepticemia by characterizing microbial and pathological changes at different disease stages, and of the bacteria transmission to table eggs, which have serious consequences on poultry health and food safety.

Key Clinical Message Graves's disease must be treated promptly to avoid serious sequelae such as cardiomyopathy, liver injury, and pancytopenia. Early initiation of antithyroid medications and beta blockers could not be overrated even in the presence of these complications. Abstract Graves' disease causes a large spectrum of clinical manifestations. Delayed diagnosis and management of Graves' disease could lead to serious systemic sequelae. We describe a case of a young man who presented with progressive cough, increased abdominal girth and ankle swelling for a few months. On examination, he had jaundice, bilateral exophthalmos, diffuse goiter, ascites, and significant lower limb edema. Laboratory investigations showed increased Thyroxin level with a suppressed thyroid stimulating hormone and positive anti‐thyrotropin receptor antibodies. Also, the patient had pancytopenia, coagulopathy and cholestatic pattern of elevated liver enzymes. Echocardiography demonstrated mildly reduced left ventricular function with diastolic dysfunction, but electrocardiogram did not show atrial fibrillation. Despite the concerns about using antithyroid medications in patients with impaired liver function tests and pancytopenia, the patient improved dramatically without worsening of his hematological or biochemical parameters. Early initiation of antithyroid medications and beta blockers is essential for patients who are newly diagnosed with hyperthyroidism.

Background. Multiple sclerosis (MS) is a common neurological disorder between adults. Magnetic resonance imaging (MRI) is the imaging modality of choice, new MRI techniques helped in more accurate assessment of the disease extent, activity and severity. In dynamic susceptibility contrast (DSC), the perfusion of the lesions as well as normally appearing white and gray matter of the brain have been assessed. Objective. To highlight the role of MRI perfusion of the deep gray matter in multiple sclerosis patients and its relation to their clinical disability and cognitive impairment. Methods. 40 patients with MS were enrolled in this study, they were divided into two groups (group A with mild clinical disease and preserved cognitive functions, and group B with marked clinical disease and cognitive functions impairment) they were divided according to their clinical disability and cognitive impairment assessed by experienced neurologist. Additional 20 healthy controls were included. Perfusion parameters including cerebral blood volume(CBV), cerebral blood flow (CBF) and mean transit time (MTT) of the deep gray matter were compared for healthy controls and for the study groups. Results. The perfusion values of the thalamus, putamen and caudate were significantly changed in group B that shows marked decrease in CBV and CBF and increased MTT compared with group A and the controls, With respect to group (A), there was no significant difference between the patients and controls. Conclusion. The decrease of perfusion of the deep gray matter in patients with MS is associated with the severity of the disease and cognitive impairment.

Abstract Researchers are constantly searching for drugs to combat the coronavirus pandemic caused by SARS-CoV-2, which has lasted for over two years. Natural compounds such as phenolic acids are being tested against Mpro and AAK1, which are key players in the SARS-CoV-2 life cycle. This research work aims to study the ability of a panel of natural phenolic acids to inhibit the virus's multiplication directly through Mpro and indirectly by affecting the adaptor-associated protein kinase-1 (AAK1). Pharmacophore mapping, molecular docking, and dynamic studies were conducted over 50 ns and 100 ns on a panel of 39 natural phenolic acids. Rosmarinic acid (16) on the Mpro receptor (− 16.33 kcal/mol) and tannic acid (17) on the AAK1 receptor (− 17.15 kcal/mol) exhibited the best docking energy against both receptors. These favourable docking score values were found to be superior to those of the co-crystallized ligands. Preclinical and clinical research is required before using them simultaneously to halt the COVID-19 life cycle in a synergistic manner.

Abstract Background Granulosa tumor is a rare tumor that arises from the mesenchyme and the sexual cord of the ovary. The prognosis is generally excellent, and treatment is mainly based on surgery, followed by chemotherapy depending on the extension of the disease. However, “the obstetrical prognosis” is compromised. Case presentation We report the case of a 32-year-old Caucasian patient who was diagnosed during a primary infertility assessment with an ultrasound image of a 39 mm organic left ovarian cyst confirmed on pelvic magnetic resonance imaging with infiltration of the uterosacral space. Tumor markers, including cancer antigen 125, alpha fetoprotein, and β-human chorionic gonadotropin, were normal. Histological study of biopsies of the ovarian lesion taken during exploratory laparoscopy confirmed the diagnosis of adult granulosa tumor. After a normal extension assessment including a thoracoabdominopelvic computed tomography scan and a positron emission tomography scan, the patient underwent complete conservative surgery and the disease was classified as stage Ic. Three cycles of adjuvant chemotherapy according to the “BEP” protocol combining bleomycin, etoposide, and cisplatin were performed after oocyte cryopreservation. After a 5-year follow-up period, the patient had no sign of tumor progression and had two spontaneous pregnancies, the first occurring 3 months after the end of chemotherapy and the second 14 months later. Conclusion Granulosa cell tumor remains a rare tumor whose management considerably compromises fertility and reduces the chances of having a spontaneous pregnancy. The particularity of our observation is that the diagnosis of the granulosa tumor was made following a primary infertility assessment and that the patient had two spontaneous pregnancies 3 months after the end of a medico-surgical treatment known to be very gonadotoxic.

Abstract Non-alcoholic steatohepatitis (NASH) is the clinically aggressive variant of non-alcoholic fatty liver disease. Hippo pathway dysregulation can contribute to NASH development and progression. The use of probiotics is effective in NASH management. Our aim is to investigate the efficacy of kefir Milk in NASH management via modulation of hepatic mRNA-miRNA based panel linked to NAFLD/NASH Hippo signaling and gut microbita regulated genes which was identified using bioinformatics tools. Firstly, we analyzed mRNAs (SOX11, SMAD4 and AMOTL2), and their epigenetic regulator (miR-6807) followed by validation of target effector proteins (TGFB1, IL6 and HepPar1). Molecular, biochemical, and histopathological, analyses were used to evaluate the effects of kefir on high sucrose high fat (HSHF) diet -induced NASH in rats. We found that administration of Kefir proved to prevent steatosis and development of the inflammatory component of NASH. Moreover, Kefir improved liver function and lipid panel. At the molecular level, kefir down-regulated the expression of miR 6807-5p with subsequent increase in the expression of SOX 11, AMOTL2 associated with downregulated SMAD4, resulting in reduction in the expression of the inflammatory and fibrotic markers, IL6 and TGF-β1 in the treated and prophylactic groups compared to the untreated rats. In conclusion, Kefir suppressed NASH progression and improved both fibrosis and hepatic inflammation. The produced effect was correlated with modulation of SOX11, SMAD4 and AMOTL2 mRNAs) – (miR-6807-5p) – (TGFB, IL6 and, HepPar1) expression.

Objective: To explore if the oral lesions in coronavirus disease-2019 patients are caused by the drugs used in the treatment or by the virus itself. Method: The cross-sectional study was conducted from September 2020 to September 2021 at the Kafrelsheikh University Hospital, Egypt, and comprised coronavirus disease-2019 patients of either gender aged 20-60 years having severe pneumonia and breathing difficulties who had no comorbidities. Based on the level of interleukin-6 and procalcitonin, the patients were classified into high group I receiving tocilizumab and methylprednisolone, medium group II receiving methylprednisolone alone, and low group III receiving antiviral drugs. The oral manifestations were recorded at the time of admission before treatment and at 2 weeks after the respective treatment. Data was analysed using SPSS 20. Results: Of the 90 patients, 30(33.3%) were in group I; 16(%) males and 14(%) females with mean age 44.82±6.10 years. Group II had 27(%) patients; 14(%) males and 13(%) females with mean age 43.74±4.87 years. Group III had 33(%) patients; 9(%) males and 14(%) females with mean age 42.66±2.51 years (p>0.05). There was no significant difference among the groups at baseline and after 2 weeks of treatment regarding oral manifestations. Intragroup comparison demonstrated a significant difference in the two values in all the three groups (p

Objective: To evaluate the effect of interleukin-6 and procalcitonin levels in plasma on the development of oral manifestation in patients of coronavirus disease-2019. Methods: The case-control study was conducted from January to September 2021 at Kafrelsheikh University Hospital, Egypt, and comprised severe coronavirus disease. One hundred patients of either gender aged 30-60 years were included. The patients were divided into two equal groups, with group I having patients with oral manifestations, and group II had those without any oral symptoms. Plasma samples from both the groups were used to determine serum interleukin-6 and procalcitonin levels using electrochemiluminescence immunoassay. Data was analysed using SPSS 20. Result: Of the 100 patients, 50(50%) were in each of the two groups. Group I had 29(58%) males and 21(42%) females with overall mean age 44.83±6.12 years. Group II had 26(52%) males and 24(48%) females with overall mean age of 43.68±4.62 years. Interleukin 6 was significantly high in group I than in group II (p0.05). Conclusion: Interleukin-6 level could play an important role in the development of oral manifestation in coronavirus disease-2019 patients. Keyword: Interleukin, Procalcitonin, Ageusia, COVID-19, Gingivitis, Candidiasis, Mucous membrane, Immunoassay.

Objective: To investigate the possible advantage of topical lidocaine and intravenous midazolam in preventing spasm and pain related to the radial artery. Methods: The prospective, comparative study was conducted at the catheterization laboratory of the cardiology department Kafrelsheikh University Hospital, Egypt, from January 2021 to January 2022, and comprised adult patients of either gender who were due to undergo coronary angiography and/or percutaneous coronary intervention for different indications. The patients were randomised control group I which was administered a cocktail of nitroglycerine, verapamil and heparin, intervention group II which was administered the control cocktail plus topical lidocaine, group III which was administered the control cocktail plus midazolam intravenously, and group IV which was administered the control cocktail plus topical lidocaine and intravenous midazolam. The groups were compared for frequency of radial artery spasm, access site cross-over and the difference in occurrence as well as procedure events, including the puncture number, time and complications. Data was analysed using SPSS 25. Results: Of the 120 patients, there were 30(25%) in each of the 4 groups. Overall, there were 72(60%) males and 48(40%) females. Gender and mean age were not significantly different among the groups (p>0.05). Spasm of the radial artery occurred in 22(18.3%) patients, with higher incidence in the group I 12(40%). The median visual analogue scale score was higher in patients with radial artery spasm patients (p0.05), while they showed a significant difference in puncture time (p

Abstract Numerous emotional and cognitive processes mediated by the hippocampus present differences between sexes and can be markedly influenced by hormonal status in males and females of several species. In rodents, the dorsal hippocampus (dHPC) is known to contribute to the rapid antidepressant actions of the NMDA receptor antagonist ketamine. We and others have demonstrated a greater sensitivity to the fast-acting antidepressant ketamine in female versus male rats that is estrogen- and progesterone-dependent. However, the underlying mechanisms remain unclear. Using an acute low dose (2.5 mg/kg) of ketamine that is behaviorally effective in female but not male rats, a label-free phosphoproteomics approach was employed to identify ketamine-induced changes in signaling pathway activation and phosphoprotein abundance within the dHPC of intact adult male rats and female rats in either diestrus or proestrus. At baseline, males and females showed striking dissimilarities in the dHPC proteome and phosphoproteome related to synaptic signaling and mitochondrial function—differences also strongly influenced by cycle stage in female rats. Notably, phosphoproteins enriched in PKA signaling emerged as being both significantly sex-dependent at baseline and also the primary target of ketamine-induced protein phosphorylation selectively in female rats, regardless of cycle stage. Reduced phosphoprotein abundance within this pathway was observed in males, suggesting bi-directional effects of low-dose ketamine between sexes. These findings present biological sex and hormonal milieu as critical modulators of ketamine’s rapid actions within this brain region and provide greater insight into potential translational and post-translational processes underlying sex- and hormone-dependent modulation of ketamine’s therapeutic effects.

Abstract Hydatid disease is a real public health problem in developing countries. Cerebral localization is rare; it does not exceed 2%. It is more frequent in children and adolescents. It is often primary in children. In adults, it is less frequent and generally associated with other localizations. We report the case of a 60‐year‐old Tunisian patient with pulmonary, hepatic and cerebral hydatid cyst, revealed by neurological symptoms with an expansive intracranial process on brain imaging.

Drug repurposing is the finding new activity of the existing drug. Recently, Albendazole’s well-known antihelmintic has got the attention of an anticancer drug. Plausible evidence of the interaction of Albendazole with one of the types of tyrosine kinase protein receptor, vascular endothelial growth factor receptor-2 (VEGFR-2) is still not well understood. Inhibition of the VEGFR-2 receptor can prevent tumor growth. The current study investigated the interaction of Albendazole with VEGFR-2.It was found that the said interaction exhibited potent binding energy ΔG = -7.12 kcal/mol, inhibitory concentration (Ki) = 6.04 μM, and as positive control comparison with standard drug (42Q1170A) showed ΔG = -12.35 kcal/mol and Ki = 881 μM. The key residue Asp1046 was formed involved hydrogen bonding with Albendazole. The molecular dynamics simulation study revealed the stable trajectory of the VEGFR-2 receptor with Albendazole bound complex having significant high free energy of binding as calculated from Molecular Mechanics Generalized Born and Surface Area study ΔG = -42.07±2.4 kcal/mol. The binding energy is significantly high for greater stability of the complex. Principal component analysis of molecular docking trajectories exhibited ordered motion at higher modes, implying a high degree of VEGFR-2 and Albendazole complex stability as seen with the standard drug 42Q. Therefore, the current work suggests the role of Albendazole as a potent angiogenesis inhibitor as ascertained by its potential interaction with VEGFR-2. The findings of research will aid in the future development of Albendazole in anticancer therapy.

Abstract Oncocytic carcinomas of the salivary glands are rare. The submandibular gland is a rare location. It is usually associated with a poor prognosis and recurrence after treatment. We report a case of a 52‐year‐old man with a lymph node and brain metastasis recurrence of an oncocytic carcinoma of the submandibular gland.

Aim: Colonic tuberculosis is rare. It accounts for 2–3% of abdominal tuberculosis. Clinical, radiological and endoscopic features are nonspecific. The diagnosis must be considered in front of chronic abdominal pain, vesperal fever and weight loss with on colonoscopy the presence of nodules or ulcers. The diagnosis is made on pathological findings. Case report: We report a case of an 82-year-old female patient with the diagnosis of colonic tuberculosis. The diagnosis were suspected on clinical presentation: chronic abdominal pain, fever and weight loss. The colonoscopy showed a nodular aspect of the left and sigmoid colonic mucosa and the pathology examination of the multiple biopsy specimens showed an epithelioid and gigantocellular granulomas with caseous necrosis. Conclusion: In front of a nonspecific clinical and endoscopic aspects, multiples colonic biopsies are mandatory to rule out differential diagnosis and confirm colonic tuberculosis.

Abstract Penile's melanoma is a rare situation, often associated with late diagnosis and high morbidity and mortality. We report the case of a 70‐year‐old man. He represented progressive skin lesions of the penile gland. A surgical biopsy with histopathological and immunohistochemical studies established the diagnosis of malignant melanoma of the penis in the metastatic stage. This case was managed by palliative immunotherapy and is currently under treatment by Pembrolizumab. Malignant melanoma of the penis represents an exceptional situation, in which only rapid diagnosis at an early stage allows treatment with optimal therapeutic results.

Abstract This study intends to give qualitative results toward the understanding of different slip mechanisms impact on the natural heat transfer performance of nanofluids. The slip mechanisms considered in this study are Brownian diffusion, thermophoretic diffusion, and sedimentation. This study compares three different Eulerian nanofluid models; Single-phase, two-phase, and a third model that consists of incorporating the three slip mechanisms in a two-phase drift-flux. These slip mechanisms are found to have different impacts depending on the nanoparticle concentration, where this effect ranges from negligible to dominant. It has been reported experimentally in the literature that, with high nanoparticle volume fraction the heat transfer deteriorates. Admittingly, classical nanofluid models are known to underpredict this impairment. To address this discrepancy, this study focuses on the effect of thermophoretic diffusion and sedimentation outcome as these two mechanisms turn out to be influencing players in the resulting heat transfer rate using the two-phase model. In particular, the necessity to account for the sedimentation contribution toward qualitative modeling of the heat transfer is highlighted. To this end, correlations relating the thermophoretic and sedimentation coefficients to the nanofluid concentration and Rayleigh number are proposed in this study. Numerical experiments are presented to show the effectiveness of the proposed two-phase model in approaching the experimental data, for the full range of Rayleigh number in the laminar flow regime and for nanoparticles concentration of (0% to 3%), with great satisfaction.

Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive muscle weakness. Skeletal muscle is a prime source for biomarker discovery since it is one of the earliest sites to manifest disease pathology. From a prior RNA sequencing project, we identified FGF23 as a potential muscle biomarker in ALS. Here, we validate this finding with a large collection of ALS muscle samples and found a 13-fold increase over normal controls. FGF23 was also increased in the SOD1G93A mouse, beginning at a very early stage and well before the onset of clinical symptoms. FGF23 levels progressively increased through end-stage in the mouse. Immunohistochemistry of ALS muscle showed prominent FGF23 immunoreactivity in the endomysial connective tissue and along the muscle membrane and was significantly higher around grouped atrophic fibers compared to non-atrophic fibers. ELISA of plasma samples from the SOD1G93A mouse showed an increase in FGF23 at end-stage whereas no increase was detected in a large cohort of ALS patients. In conclusion, FGF23 is a novel muscle biomarker in ALS and joins a molecular signature that emerges in very early preclinical stages. The early appearance of FGF23 and its progressive increase with disease progression offers a new direction for exploring the molecular basis and response to the underlying pathology of ALS.

Objective(s): The present study determines the chemical constituents of Persea americana using gas chromatography-mass spectrometry (GC-MS) and its different activities. Materials and Methods: Air-dried powdered leaves of Persea americana were extracted by 95% methanol and fractionated consecutively with petroleum ether, chloroform, and ethyl acetate. The saponifiable matter, EtOAc and aqueous fractions were subjected to GC-MS. The analgesic, anti-inflammatory, antipyretic, and antihyperglycemic properties of extracts, different fractions, and crude polysaccharide were determined by hot plate, carrageenan-induced paw edema, yeast-induced pyrexia, and alloxan-induced hyperglycemia methods, respectively. Results: Fourteen fatty acid methyl esters were identified in GC-MS-based profiling of the saponifiable matter. Alongside, 13 compounds were determined from EtOAc fraction and 6 compounds from the aqueous fraction of P. americana leaves. The ethyl acetate fraction and total stem extract displayed high anti-inflammatory potential with percentage of paw edema reduction by 48.99 and 47.54 %, respectively, compared with that of indomethacin (42.90 %). The ethyl acetate fraction and total stem extract revealed the highest analgesic activity with 137.95 and 137.12 % percent of protection against external stimulus, respectively. Investigation of antipyretic efficiency showed the total stem extract and crude polysaccharides attained normal temperature after 3 hr, which was very close to that of acetylsalicylic acid. The total leaf and stem extracts displayed significant antihyperglycemic activity with significant reduction in the level of blood glucose by 76.67 and 59.05 %, respectively.Conclusion: P. americana had analgesic, anti-inflammatory, antipyretic, and antihyperglycemic properties, which refer to its bioactive metabolites.

Herein, we present a case of ischemic heart failure that occurred immediately after birth in a neonate due to coronary artery fistula (CAF) from the left main coronary artery to the left atrial appendage associated with high pulmonary artery pressure. Ischemic heart failure in a neonate with a structurally normal heart is rare. Furthermore, CAF resulting in ischemic heart failure is very rare in neonates. We believe that the small CAF caused symptoms during the first few days of life due to moderate pulmonary hypertension which resulted in a low cardiac output. The coronary perfusion improved after the normalization of the pulmonary blood pressure and improvement of the cardiac output. Echocardiography is helpful when a CAF is suspected and can be confirmed using a cardiac computed tomography scan. Small CAFs are unlikely to cause symptoms in infants, provided there are no other factors affecting the cardiac output status.

Abstract Malnutrition impacts approximately 50 million children worldwide and is linked to 45% of global mortality in children below the age of five. Severe acute malnutrition (SAM) is associated with intestinal barrier breakdown and epithelial atrophy. Extracellular vesicles including exosomes (EVs; 30–150 nm) can travel to distant target cells through biofluids including milk. Since milk-derived EVs are known to induce intestinal stem cell proliferation, this study aimed to examine their potential efficacy in improving malnutrition-induced atrophy of intestinal mucosa and barrier dysfunction. Mice were fed either a control (18%) or a low protein (1%) diet for 14 days to induce malnutrition. From day 10 to 14, they received either bovine milk EVs or control gavage and were sacrificed on day 15, 4 h after a Fluorescein Isothiocyanate (FITC) dose. Tissue and blood were collected for histological and epithelial barrier function analyses. Mice fed low protein diet developed intestinal villus atrophy and barrier dysfunction. Despite continued low protein diet feeding, milk EV treatment improved intestinal permeability, intestinal architecture and cellular proliferation. Our results suggest that EVs enriched from milk should be further explored as a valuable adjuvant therapy to standard clinical management of malnourished children with high risk of morbidity and mortality.

Cardiovascular disease is the leading cause of death of dialyzed patients. Aortic stiffness, evaluated by the carotid-femoral pulse wave velocity (cfPWV), is now considered as a prognostic factor for cardiovascular mortality in patients with chronic kidney diseases. The peritoneal dialysis (PD) patients had significantly stiffer arteries. cfPWV was 9.12 ± 2.7 m/s in PD patients without significant correlation compared to hemodialysis (HD) patients (8.97 ± 2.52 m/s). In the univariate study, we found a statistically significant correlation between PWV and age (P = 0), between the pulse wave velocity and phosphorus (P = 0.46), between the VOP and PTH (P = 0.013) and between PWV and dyslipidemia (P = 0.014). Other variables such as phospho-calcic product, hemoglobin, total cholesterol, and KT/V were not significant. To identify the risk factors independently linked to the event, we conducted a multi-varied analysis. A correlation was found between VOP and dyslipidemia (P = 0.008). The other variables were insignificant.

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerular disease. The main challenge in this disease is the evaluation of prognostic factors for end-stage renal disease (ESRD). The aim of our study was to assess the clinical and prognostic implications of C4d staining in primary IgAN. This was a retrospective study, including adults with primary IgAN. The study was conducted over a period of 10 years. Renal biopsies were scored according to the Oxford classification. C4d immunohistochemical staining was performed. We included 44 patients with a sex ratio of 2.6. The average age was 35.1 ± 11 years. Twenty-two patients (57%) had hypertension (HTN). The median proteinuria was 1.92 g/day. The median of the glomerular filtration rate was 47.66 mL/min/1.73 m2. According to the Oxford classification, mesangial proliferation, endocapillary proliferation, glomerulosclerosis, interstitial fibrosis and/or tubular atrophy and crescents were present in 41%, 36%, 86%, 34%, and 25 % of cases, respectively. We found positive glomerular C4d staining in 25 renal biopsies (57%). Age at diagnosis, mean arterial pressure, HTN, and baseline glomerular filtration rate were not correlated with C4d staining. On the other hand, proteinuria was significantly higher in patients with C4d-positive renal biopsy. The median follow-up duration was 30.5 months. Ten patients (23%) reached ESRD. At univariate analysis, positive C4d staining in more than 25% of glomeruli in patients without C1q deposition in the immunofluorescent study was associated with ESRD. Our study confirms the prognostic value of C4d staining in primary IgAN.

Chronic kidney disease (CKD) treated by hemodialysis (HD) is a worldwide major public health problem. Its incidence is getting higher and higher, leading to an alarming social and economic impact. The survival of these patients is significantly low, especially during the first year of treatment. The purpose of our study was to identify the epidemiological and clinico-biological characteristics of patients at the HD initiation and to reveal the predictive factors of mortality at three months and one year of HD. This is a prospective, analytical, and descriptive study dealing with 229 patients with an end-stage renal disease (ESRD), followed up in the Nephrology Department of Charles Nicolle Hospital and La Rabta Hospital in Tunisia, that was started HD between January and June 2017. A multivariate logistic regression analysis allowed us to identify the independent predictors of mortality at three months and one year. The average age was 60.2 ± 15.3 years, with a gender ratio of 1.41. Seventy-eight percent of patients had more than two comorbidities, 59% had diabetes, and 88% had hypertension. Diabetic nephropathy was the leading etiology of kidney disease (48.9%), while 11% of nephropathies were of unknown etiology. Only 58% were early referred to a nephrologist. The average glomerular filtration rate at HD initiation was 6.06 ± 2.33 mL/min/1.73 m2. Hypocalcemia and hyperphosphatemia were noted, respectively, in 60.8% and 84.9% of cases. Anemia was objectified in 98.6% of cases. HD was started in an emergency in 56.8% of cases. One of the most urgent indications was acute pulmonary edema (APE) for 43.8% of patients. Only 10.5% of patients had functional arteriovenous fistula at the dialysis initiation. Patients were hemodialyzed one, two, or three sessions per week, respectively, in 23.2%, 26.6%, and 50.2% of cases. The crude mortality rate was 25% and 13% in, respectively, one year and three months of HD. On multivariate analysis, we identified heart failure and insufficient dialysis dose per week as predictive factors of mortality at the 1st year of HD. C-reactive protein more than 21 mg/L, insufficient dialysis per week, modified Charlson Comorbidity Index less than 6, and APE at the dialysis initiation were identified as predictive factors of three-month mortality. Despite the short period of study, this work revealed the alarming conditions of patients at HD initiation. This critical situation is due to the delay in CKD diagnosis, the late nephrologist referral, and the lack of preparation before HD initiation.

Carotid-femoral pulse wave velocity (cf-PWV) is the noninvasive gold standard technique for measuring aortic stiffness. Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic renal disease in adults. It is associated with a high risk of cardiovascular complications. We aimed to assess the prevalence of increased arterial stiffness and its predicting factors in a population of ADPKD patients. Sixty-two patients with ADPKD underwent noninvasive measurement of cf-PWV using a COMPLIOR Analyse device. Recruitment period was 17 months and we used the cut-off of 10 m/s to define a high cf-PWV. Mean age was 51 ± 12.7 years. Gender ratio male/female was 0.63. Smoking, hypertension (HTN), and dyslipidemia were reported in 14%, 66%, and 27% of the cases, respectively. Mean glomerular filtration rate (GFR) was 47.7 ± 44 mL/min/1.73 m2. Among our patients, 39% had chronic kidney disease stages 1 or 2 and 45% stage 5 (40% stage 5D). Mean cf-PWV was 9 ± 2.4 m/s, and 31% of the patients had a high cf-PWV. In univariate analysis of all our patients, cf- PWV correlated with age (r = 0.565; P

Abstract Skeletal muscle and the neuromuscular junction are the earliest sites to manifest pathological changes in amyotrophic lateral sclerosis (ALS). Based on prior studies, we have identified a molecular signature in muscle that develops early in ALS and parallels disease progression. This signature represents an intersection of signaling pathways including Smads, TGF-β, and vitamin D. Here, we show that the Wnt antagonist, Frizzled Related Protein (FRZB), was increased in ALS muscle samples and to a variable extent other denervating disease but only minimally in acquired myopathies. In the SOD1G93A mouse, FRZB was upregulated in the early stages of disease (between 40 and 60 days) until end-stage. By immunohistochemistry, FRZB was predominantly localized to endomysial connective tissue and to a lesser extent muscle membrane. There was a significant increase in immunoreactivity surrounding atrophied myofibers. Because FRZB is a Wnt antagonist, we assessed β-catenin, the canonical transducer of Wnt signaling, and found increased levels mainly at the muscle membrane. In summary, we show that FRZB is part of a molecular signature of muscle denervation that may reflect disease progression in ALS. Our findings open up avenues for future investigation as to what roles FRZB and Wnt signaling might be playing in muscle denervation/reinnervation.

Abstract We present the case of a 23‐year‐old female with multiple diffuse and nodular masses of different sizes involving predominantly the posterior wall of the uterus, omentum, and peritoneum which were histopathologically confirmed to be disseminated peritoneal leiomyomatosis. Meticulous investigation and accurate diagnosis are of utmost importance for the establishment of the correct diagnosis. Additionally, proper management of the patient while considering choice of the patients including close follow‐up of the patients is mandatory for the reason of ensuring early detection of recurrence.

Carotid atherosclerotic plaque rupture and its sequelae are among the leading causes of acute ischemic stroke. The risk of rupture and subsequent thrombosis is, among others, determined by vulnerable plaque characteristics and linked to activation of the immune system, in which neutrophil extracellular traps (NETs) potentially play a role. The aim of this study was to investigate how plaque vulnerability is associated with NETs levels. We included 182 patients from the Plaque At RISK (PARISK) study in whom carotid imaging was performed to measure plaque ulceration, fibrous cap integrity, intraplaque hemorrhage, lipid-rich necrotic core, calcifications and plaque volume. Principal component analysis generated a 'vulnerability index' comprising all plaque characteristics. Levels of the NETs marker myeloperoxidase-DNA complex were measured in patient plasma. The association between the vulnerability index and low or high NETs levels (dependent variable) was assessed by logistic regression. No significant association between the vulnerability index and NETs levels was detected in the total population (odds ratio 1.28, 95% confidence interval 0.90-1.83, p = 0.18). However, in the subgroup of patients naive to statins or antithrombotic medication prior to the index event, this association was statistically significant (odds ratio 2.08, 95% confidence interval 1.04-4.17, p = 0.04). Further analyses revealed that this positive association was mainly driven by intraplaque hemorrhage, lipid-rich necrotic core and ulceration. In conclusion, plaque vulnerability is positively associated with plasma levels of NETs, but only in patients naive to statins or antithrombotic medication prior to the index event.

BackgroundObesity is significantly associated with renal cell carcinoma. Surgery is the preferred treatment for demarcated lesions of renal cell carcinoma; however, obesity increases the complexity of surgical outcomes. Minimally invasive surgical techniques are preferred over open partial nephrectomy (OPN), but controversy remains regarding the most efficacious technique in patients with obesity. ObjectiveThis study aims to determine whether minimally invasive partial nephrectomy (MIPN) or OPN better preserves renal function and investigate short- and long-term renal outcomes in patients with obesity undergoing a partial nephrectomy. MethodsWe conducted a retrospective chart review of 242 adult patients aged ≥18 years who underwent MIPN or OPN between January 1, 2005, and December 31, 2016, at the University of Arkansas for Medical Sciences. Using creatinine as a measure of kidney function, patients’ preoperative levels were compared with their postoperative levels in 2-time frames: short (3-6 months postsurgery) or long (>6 months). The primary outcome was the change in creatinine values from preoperative to >6 months postoperatively in patients with obesity. Secondary outcomes included the change in creatinine values from preoperative to 3 to 6 months postoperatively in patients with obesity who underwent MIPN versus OPN. We also analyzed the creatinine values of nonobese patients (BMI 6 months after MIPN (n=20), the odds of patients with obesity having a decrease or no change in creatinine values was 1.24 times higher than those who had OPN (n=13; OR 1.24, 95% CI 0.299-6.729; P=.80). At 3 to 6 months after MIPN (n=27), the odds were 0.62 times lower than those after OPN (n=17; OR 0.62, 95% CI 0.140-2.753; P=.56). In the nonobese group, at 3 to 6 months after undergoing minimally invasive surgery (n=18), the odds of having a decrease or no change in creatinine values was 4.86 times higher than those who had open surgery (n=21; OR 4.86, 95% CI 1.085-21.809; P=.04). At more than 6 months after MIPN (n=14), the odds were 4.13 times higher than those after OPN (n=11; OR 4.13, 95% CI 0.579-29.485; P=.16). ConclusionsWe observed a nonstatistically significant preservation of renal function in patients with obesity who underwent OPN at 3 to 6 months postoperatively. Conversely, after 6 months, the same was true for MIPN, indicating the long-term benefit of MIPN. In the nonobese group, MIPN was favored over OPN.

Abstract Intestinal infestation with Enterobius vermicularis is common, especially in the developing countries. However, its migration in the bile ducts is rare, often diagnosed after cholecystectomy. More investigations are needed to define its involvement in symptoms presented by patients and the likelihood of complications.

Amoebic keratitis and encephalitis are mainly caused by free-living amoebae of the genus Acanthamoeba, which consists of both pathogenic and nonpathogenic species. The global distribution, amphizoic properties and the severity of the disease caused by Acanthamoeba species have inspired the scientific community to put more effort into the isolation of Acanthamoeba, besides exploring the direct and indirect parameters that could signify a pathogenic potential. Therefore, this study was performed to characterize the pathogenic potential of Acanthamoeba isolated from contact lens paraphernalia and water sources in Malaysia. Various methodologies were utilized to analyze the thermotolerance and osmotolerance, the secretion level of proteases and the cytopathic effect of trophozoites on the cell monolayer. In addition, the in vitro cytopathogenicity of these isolates was assessed using the LDH-release assay. A total of 14 Acanthamoeba isolates were classified as thermo- and osmotolerant and had presence of serine proteases with a molecular weight of 45–230 kDa. Four T4 genotypes isolated from contact lens paraphernalia recorded the presence of serine-type proteases of 107 kDa and 133 kDa. In contrast, all T3 genotypes isolated from environmental samples showed the presence of a 56 kDa proteolytic enzyme. Remarkably, eight T4 and a single T3 genotype isolates demonstrated a high adhesion percentage of greater than 90%. Moreover, the use of the HeLa cell monolayer showed that four T4 isolates and one T3 isolate achieved a cytopathic effect in the range of 44.9–59.4%, indicating an intermediate-to-high cytotoxicity level. Apart from that, the LDH-release assay revealed that three T4 isolates (CL5, CL54 and CL149) and one T3 isolate (SKA5-SK35) measured an exceptional toxicity level of higher than 40% compared to other isolates. In short, the presence of Acanthamoeba T3 and T4 genotypes with significant pathogenic potential in this study reiterates the essential need to reassess the functionality of other genotypes that were previously classified as nonpathogenic isolates in past research.

BackgroundCardiovascular disease is a leading cause of death in general population and the second leading cause of mortality and morbidity in cancer survivors after recurrent malignancy in the United States. The growing awareness of cancer therapy-related cardiac dysfunction (CTRCD) has led to an emerging field of cardio-oncology; yet, there is limited knowledge on how to predict which patients will experience adverse cardiac outcomes. We aimed to perform unbiased cardiac risk stratification for cancer patients using our large-scale, institutional electronic medical records.Methods and findingsWe built a large longitudinal (up to 22 years' follow-up from March 1997 to January 2019) cardio-oncology cohort having 4,632 cancer patients in Cleveland Clinic with 5 diagnosed cardiac outcomes: atrial fibrillation, coronary artery disease, heart failure, myocardial infarction, and stroke. The entire population includes 84% white Americans and 11% black Americans, and 59% females versus 41% males, with median age of 63 (interquartile range [IQR]: 54 to 71) years old. We utilized a topology-based K-means clustering approach for unbiased patient-patient network analyses of data from general demographics, echocardiogram (over 25,000), lab testing, and cardiac factors (cardiac). We performed hazard ratio (HR) and Kaplan-Meier analyses to identify clinically actionable variables. All confounding factors were adjusted by Cox regression models. We performed random-split and time-split training-test validation for our model. We identified 4 clinically relevant subgroups that are significantly correlated with incidence of cardiac outcomes and mortality. Among the 4 subgroups, subgroup I (n = 625) has the highest risk of de novo CTRCD (28%) with an HR of 3.05 (95% confidence interval (CI) 2.51 to 3.72). Patients in subgroup IV (n = 1,250) had the worst survival probability (HR 4.32, 95% CI 3.82 to 4.88). From longitudinal patient-patient network analyses, the patients in subgroup I had a higher percentage of de novo CTRCD and a worse mortality within 5 years after the initiation of cancer therapies compared to long-time exposure (6 to 20 years). Using clinical variable network analyses, we identified that serum levels of NT-proB-type Natriuretic Peptide (NT-proBNP) and Troponin T are significantly correlated with patient's mortality (NT-proBNP > 900 pg/mL versus NT-proBNP = 0 to 125 pg/mL, HR = 2.95, 95% CI 2.28 to 3.82, p < 0.001; Troponin T > 0.05 μg/L versus Troponin T ≤ 0.01 μg/L, HR = 2.08, 95% CI 1.83 to 2.34, p < 0.001). Study limitations include lack of independent cardio-oncology cohorts from different healthcare systems to evaluate the generalizability of the models. Meanwhile, the confounding factors, such as multiple medication usages, may influence the findings.ConclusionsIn this study, we demonstrated that the patient-patient network clustering methodology is clinically intuitive, and it allows more rapid identification of cancer survivors that are at greater risk of cardiac dysfunction. We believed that this study holds great promise for identifying novel cardiac risk subgroups and clinically actionable variables for the development of precision cardio-oncology.

Dialysis patients have higher rates of sudden cardiac death. The study of the electrocardiogram could identify patients at risk of developing rhythm disorders. The aim of this study was to evaluate the electrocardiographic findings before and after the hemodialysis (HD) session and to examine associations of clinical and serum electrolytes with electrocardiogram findings. We conducted a multicentric transversal study, including chronic HD patients during January 2018. Standard 12-lead electrocardiogram was recorded, before and after the HD session. A medical history was documented. It included age, gender, initial nephropathy, and comorbidities. Serum potassium and total serum calcium were measured before a routine HD session. Serum potassium was measured after HD session. Corrected QT for heart rate was calculated using Bazett’s formula. The study included 66 patients. Nineteen patients (28.8%) had hyperkalemia before the HD session and 44 (66.7%) patients had hypokalemia after the HD session. Seventeen patients had prolonged QTc interval (25.7%). On multiple regression analysis, only the prolonged QTc interval was significantly correlated with the serum potassium (P = 0.046).When comparing the mean values of electrocardiogram parameters before and after the HD session, we noted a significant change of heart rate (P = 0.001), R wave (P = 0.016), T wave (P = 0.001), and T/R (P = 0.001) wave. Delta K+ did not correlate with the change in T wave amplitude (r = 0.23, P = 0.59), R wave amplitude (r = –0.16, P = 0.2), T/R wave (r = 0.055, P = 0.65), or QRS duration (r = 0.023, P = 0.85). Delta QTc was correlated to ΔK+. We conclude that usual electrographic manifestations of hyperkalemia are less pronounced in HD patients. Our results confirmed the unstable status of cardiac electrophysiology during HD session.

Immunoglobulin A nephropathy is the most common primary glomerular disease. The main challenge in this disease is the evaluation of prognostic factors for end-stage renal disease. The aim of our study was to describe the characteristics of immunoglobulin A nephropathy, to evaluate the histological data according to Oxford classification, and to identify factors associated with renal survival. This was a retrospective study, including adults with primary immunoglobulin A nephropathy. The study was conducted over a period of 10 years. Renal biopsies were scored according to Oxford classification. Oxford score, based on the sum of the different histological lesions of Oxford classification, was calculated for each patient. We included 50 patients with a gender ratio (male:female) of 2.8. The average age was 35.6 ± 10.6 years. Fifty-eight percent of the patients had hypertension (HTN). The median proteinuria was 1.9 g/day. The median of the glomerular filtration rate was 47.6 mL/min/1.73 m2. According to Oxford classification, mesangial proliferation, endocapillary proliferation, glomerulosclerosis, interstitial fibrosis, and/or tubular atrophy and crescents were present in 40%, 38%, 88%, 36%, and 22% of the cases, respectively. The median Oxford score was 2. The median follow-up duration was 30 months. Ten patients (20%) reached end-stage renal disease. At univariate analysis, HTN, glomerular filtration rate, proteinuria, tubular involvement, and Oxford score >3 were associated with progression to end-stage renal disease (ESRD). Tubular involvement was an independent risk factor for ESRD. Our study confirms the prognostic value of the Oxford classification in immunoglobulin A nephropathy.

Glomerulonephritis associated with anti-neutrophil cytoplasmic antibody (ANCA) vasculitis still has a high prevalence of end-stage renal disease (ESRD), particularly in patients with advanced renal failure at presentation. This study aims to evaluate the clinical and histo- pathological features of renal involvement and investigate factors associated with ESRD. Patients with renal biopsy-proven ANCA-associated glomerulonephritis were included retrospectively over a period of nine years (June 2007 to March 2016). The renal survival, defined as time to reach ESRD, was evaluated based on clinical parameters, histopathological classification, and renal risk score. A total of 37 patients with crescentic glomerulonephritis were included in the study. The average age was 54 ± 16 years (range: 17-80) and 51.3% were female. Twenty-two patients were diagnosed with microscopic polyangiitis and 15 had granulomatosis with polyangiitis. The median glomerular filtration rate at presentation was 16.73 mL/min/1.73 m2. Thirty-five patients (94.5%) had renal failure at presentation and 23 patients (62.1%) required initial hemodialysis (HD) therapy. The pattern of glomerular injury was categorized as sclerotic in 48.6% of cases, crescentic in 24.3%, mixed in 24.3%, and focal class in 2.7%. Regarding renal risk score, we had five patients with low risk, 17 with intermediate risk and 15 with high risk. ESRD occurred in 47% of intermediate-risk group and 66% of the high risk group. During follow-up, 17 patients (45.9%) developed ESRD. Tobacco addiction (P = 0.02), alveolar hemorrhage (P = 0.04), hypertension (P = 0.04), initial HD (P = 0.04), and sclerotic class (P = 0.004) were associated with ESRD. In our patients, a sclerotic class was associated with a higher risk of ESRD, suggesting that histo- pathological classification is potentially an important parameter to predict outcomes in renal disease secondary to ANCA-associated vasculitis.

This research was designed to identify thermodynamically and kinetically stable lipidic self-emulsifying formulations through simple energy dynamics in addition to highlighting and clarifying common ambiguities in the literature in this regard. Proposing a model study, this research shows how most of the professed energetically stable systems are actually energetically unstable, subjected to indiscriminate and false characterization, leading to significant effects for their pharmaceutical applications. A self-emulsifying drug delivery system (SEDDS) was developed and then solidified (S-SEDDS) using a model drug finasteride. Physical nature of SEDDS was identified by measuring simple dynamics which showed that the developed dispersion was thermodynamically unstable. An in vivo study of albino rats showed a three-fold enhanced bioavailability of model drug with SEDDS as compared to the commercial tablets. The study concluded that measuring simple energy dynamics through inherent properties can distinguish between thermodynamically stable and unstable lipidic systems. It might lead to correct identification of a specific lipidic formulation and the application of appropriate characterization techniques accordingly. Future research strategies include improving their pharmaceutical applications and understanding the basic differences in their natures.

BackgroundVaccine hesitancy is a complex, contested social phenomenon and existing research highlights the multifaceted role of trust in strengthening vaccine confidence. However, understanding public engagement with vaccination through the lens of (mis)trust requires more contextual evidence on trust's qualitative determinants. This includes expanding the geographic focus beyond current studies' focus on High Income Countries. Furthermore, obstacles remain in effectively integrating social science findings in the design of vaccine deployment strategies, and in ensuring that those who implement interventions and are affected by them are directly involved in producing knowledge about vaccination challenges.MethodsWe piloted a community-led ethnographic approach, training Community Health Workers (CHWs) in Kambia District, Sierra Leone, in qualitative social science methods. Methods included participant observation, participatory power mapping and rumour tracking, focus group discussions and key stakeholder interviews. CHWs, with the support of public health officials and professional social scientists, conducted research on vaccination challenges, analysed data, tested new community engagement strategies based on their findings and elicited local perspectives on these approaches.ResultsOur findings on vaccine confidence in five border communities highlighted three key themes: the impact of prior experiences with the health system on (mis)trust; relevance of livelihood strategies and power dynamics for vaccine uptake and access; and the contextual nature of knowledge around vaccines. Across these themes, we show how expressions of trust centered on social proximity, reliability and respect and the role of structural issues affecting both vaccine access and confidence. The pilot also highlighted the value and practical challenges to meaningfully co-designed research.ConclusionThere is scope for broader application of a community-led ethnographic approach will help redesign programming that is responsive to local knowledge and experience. Involving communities and low-cadre service providers in generating knowledge and solutions can strengthen relationships and sustain dialogue to bolster vaccine confidence.

Background/objectiveWeight loss is a predictor of shorter survival in amyotrophic lateral sclerosis (ALS). We performed serial measures of body composition using Dual-energy X-ray Absorptiometry (DEXA) in ALS patients to explore its utility as a biomarker of disease progression.MethodsDEXA data were obtained from participants with ALS (enrollment, at 6- and 12- months follow ups) and Parkinson's disease (enrollment and at 4-month follow up) as a comparator group. Body mass index, total lean mass index, appendicular lean mass index, total fat mass index, and percentage body fat at enrollment were compared between the ALS and PD cohorts and age-matched normative data obtained from the National Health and Nutrition Examination Survey database. Estimated monthly changes of body composition measures in the ALS cohort were compared to those of the PD cohort and were correlated with disease progression measured by the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R).ResultsThe ALS cohort (N = 20) had lower baseline total and appendicular lean mass indices compared to the PD cohort (N = 20) and general population. Loss in total and appendicular lean masses were found to be significantly associated with follow-up time. Low baseline percentage body fat (r = 0.72, p = 0.04), loss of percentage body fat (r = 0.81, p = 0.01), and total fat mass index (r = 0.73, p = 0.04) during follow up correlated significantly with monthly decline of ALSFRS-R scores in ALS cohort who had 2 or more follow-ups (N = 8).ConclusionMeasurement of body composition with DEXA might serve as a biomarker for rapid disease progression in ALS.

Takotsubo syndrome is a reversible, stress-induced transient systolic and diastolic dysfunction. It was first described as a characteristic ballooning of left ventricular apex which closely resembles a Japanese fishing pot. Here the authors present a case report of a 40-year-old female who was posted for elective tonsillectomy, that developed sudden de-saturation immediately post-intubation, examination showed bilateral extensive and ECG showed symmetrical T wave inversion in leads V1 to V6 and troponin I was positive. A diagnosis of Perioperative myocardial infarction was made and hence patient was taken for coronary angiogram which was found to be normal. The left ventricular angiogram showed a typical finding of apical ballooning. The patient was diagnosed to have- Takotsubo Syndrome. Treatment included tablet Torsemide, Ramipril and Metoprolol. She was discharged after 7 days as the vitals got normalised.

Thalidomide, which is an angiogenesis inhibitor and immunomodulator that reduces tumor necrosis factor-alpha, has regained value in the treatment of multiple myeloma. Serious pulmonary complications due to thalidomide use remain relatively uncommon. We describe a case of bronchiolitis obliterans organizing pneumonia (BOOP) due to thalidomide. A 51-year-old man with IgG lambda myeloma was treated with thalidomide and dexamethasone. Seven days after the beginning of chemotherapy, the patient presented a fever and a persistent cough. Auscultation revealed crackles in both pulmonary bases. The chest X-ray showed a diffuse bilateral alveolar–interstitial syndrome. Computed tomography scan revealed bilateral pulmonary involvement, with bilateral interstitial alveolar infiltration and ground-glass pattern consolidations. Pulmonary infection, malignant tumor, and lung involvement of multiple myeloma were excluded through various tests. Thalidomide-induced BOOP was suspected, and the drug was withdrawn and replaced by Melphalan. The patient had complete resolution of his symptoms and radiologic pulmonary involvement on discontinuation of the drug. In the absence of other etiologies, physicians should be cognizant of this potential complication in patients receiving thalidomide who present with respiratory symptoms.

Pellagra usually results from niacin deficiency and presents with the classic triad of dermatitis, diarrhea, and dementia. It is most commonly associated with malnutrition and poverty. We report a case of pellagra in a hemodialysis (HD) patient with breast neoplasia, aged 68-years, female, on HD unit for seven years. Her original nephropathy was indeterminate. The patient was followed up for homozygous beta-thalassemia and breast neoplasia with hepatic metastases on chemotherapy. The body mass index of the patient was 18.5 kg/m2. Physical examination showed a thickening of the epidermis with a scaly surface, pigmented, and atrophied areas. We noted neuropsychiatric signs (apathy, irritability, anorexia, and depression) and digestive symptomatology (diarrhea). The laboratory tests revealed hypoproteinemia at 55 g/L, hypoalbuminemia at 21 g/L, and hypocholesterolemia at 0.8 g/L. The diagnosis of pellagra disease was made. Vitamin and protein supplementation was initiated, but the patient committed suicide by puncture of her arteriovenous fistula, causing hemorrhagic shock. Pellagra is usually reported to be associated with malnutrition, chronic alcoholism, and some chemotherapeutic agents. In our patient, pellagra was caused by malnutrition and co-morbidities. Pellagra disease requires multidisciplinary care and can be frequently seen in HD patients due to the associated malnutrition.

Epstein syndrome is characterized by sensorineural hearing impairment, macro- thrombocytopenia without neutrophil inclusion bodies, and hereditary nephritis which can progress to end-stage renal disease (ESRD) in adolescence. The prognosis of Epstein’s syndrome depends on the severity of the hematological disorders and renal involvement that can lead to ESRD at an early age. Thrombocytopenia in Epstein syndrome is not an absolute contraindication for major surgical procedures like arteriovenous fistula formation or kidney transplantation. There are no set guidelines for preoperative prophylaxis in a patient with this pathology.

Tungiasis is a cutaneous parasitosis caused by an embedded female sand flea. The distribution of cases can be spatially heterogeneous even in areas with similar risk profiles. This study assesses household and remotely sensed environmental factors that contribute to the geographic distribution of tungiasis cases in a rural area along the Southern Kenyan Coast. Data on household tungiasis case status, demographic and socioeconomic information, and geographic locations were recorded during regular survey activities of the Health and Demographic Surveillance System, mainly during 2011. Data were joined with other spatial data sources using latitude/longitude coordinates. Generalized additive models were used to predict and visualize spatial risks for tungiasis. The household-level prevalence of tungiasis was 3.4% (272/7925). There was a 1.1% (461/41,135) prevalence of infection among all participants. A significant spatial variability was observed in the unadjusted model (p-value < 0.001). The number of children per household, earthen floor, organic roof, elevation, aluminum content in the soil, and distance to the nearest animal reserve attenuated the odds ratios and partially explained the spatial variation of tungiasis. Spatial heterogeneity in tungiasis risk remained even after a factor adjustment. This suggests that there are possible unmeasured factors associated with the complex ecology of sand fleas that may contribute to the disease’s uneven distribution.