Search results for: Acute Inflammatory Demyelinating Polyneuropathy

Authors: Ying-Jung Hsieh, Angela S. Huang, Chu-Ming Chiu, Yu-Min Chou, Chin-Hui Yang

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Background and Objectives: Hepatitis A is primarily acquired by the fecal-oral route through person-to-person contact or ingestion of contaminated food or water. During 2010 to 2014, an average of 83 cases of locally-acquired disease was reported to Taiwan’s notifiable disease system. Taiwan Centers for Disease Control (TCDC) identified an outbreak of acute hepatitis A which began in June 2015. Of the 126 cases reported in 2015, 103 (82%) cases were reported during June–December and 95 cases (92%) of them were male. The average age of all male cases was 31 years (median, 29 years; range, 15–76 years). Among the 95 male cases, 49 (52%) were also infected with HIV, and all reported to have had sex with other men. To control this outbreak, TCDC launched a free hepatitis A vaccination program in January 2016 for close contacts of confirmed hepatitis A cases, including family members, sexual partners, and household contacts. Effect of the vaccination program was evaluated. Methods: All cases of hepatitis A reported to the National Notifiable Disease Surveillance System were included. A case of hepatitis A was defined as a locally-acquired disease in a person who had acute clinical symptoms include fever, malaise, loss of appetite, nausea or abdominal discomfort compatible with hepatitis, and tested positive for anti-HAV IgM during June 2015 to June 2016 in Taiwan. The rate of case accumulation was calculated using a simple regression model. Results: During January–June 2016, there were 466 cases of hepatitis A reported; of the 243 (52%) who were also infected with HIV, 232 (95%) had a history of having sex with men. Of the 346 cases that were followed up, 259 (75%) provided information on contacts but only 14 (5%) of them provided the name of their sexual partners. Among the 602 contacts reported, 349 (58%) were family members, 14 (2%) were sexual partners, and 239 (40%) were other household contacts. Among the 602 contacts eligible for free hepatitis A vaccination, 440 (73%) received the vaccine. There were 87 (25%) cases that refused to disclose their close contacts. The average case accumulation rate during January–June 2016 was 21.7 cases per month, which was 6.8 times compared to the average case accumulation rate during June–December 2015 of 3.2 cases per month. Conclusions: Despite vaccination program aimed to provide free hepatitis A vaccine to close contacts of hepatitis A patients, the outbreak continued and even gained momentum in transmission. Refusal by hepatitis A patients to provide names of their close contacts and rejection of contacts to take the hepatitis A vaccine may have contributed to the poor effect of the program. Targeted vaccination efforts of all MSM may be needed to control the outbreak among this population in the short term. In the long term, universal vaccination program is needed to prevent the infection of hepatitis A.

Keywords: hepatitis A, HIV, men who have sex with men, vaccination

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Authors: Ching-Yi Huang, Pi-Fen Cheng, Hui-Zhu Chen, Shi Ting Huang, Heng-Hua Wang

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This is a case of oral cancer after extensive resection and modified right lateral neck lymph node dissection followed by reconstruction with a skin flap. The nursing period lasted From September 25 to October 3, 2017, through observation, interview, physical assessment, and medical record review, the author identified the following nursing problems: acute pain, impaired oral mucous membrane, and body image change. During the nursing period, the author provided individual and overall nursing care and established mutual trust through the use of empathy. Author listened and eased the patient's physical indisposition, such as wound pain, we use medications and acupuncture massage to relieve pain. However, for oral mucosa change caused by surgery, provide continuous and complete oral care and oral exercise training to improve oral mucosal healing and restore swallowing function. In the body-image changes, guided him to express his feeling after the body-image change, and enhanced support and from the family, and encouraged him to attend head and neck cancer survivor alliance which allowed the patient to accept the altered body image and reaffirm self-worth. Hopefully, through sharing this nursing experience will help to the nursing care quality of nursing care for oral cancer patients after extensive resection and modified right lateral neck lymph node dissection followed by reconstruction with a skin flap.

Keywords: oral cancer, acute pain, impaired oral mucous membrane, body image change

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Authors: Sandeep Goyal, Sandeep Saluja

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Natural antioxidants have major role in maintenance of health. Green tea extract principally contains epigallocatechin-3-gallate (EGCG), as its abundant antioxidant constituent. Green tea is consumed daily worldwide as antioxidant to combat CNS diseases and has traditional importance also. EGCG has neuroprotective potential in various animal models of Parkinson disease, Alzheimer’s disease etc. but its exact mechanism has not been ruled out. The present study has been designed to investigate the anti-inflammatory, antioxidant and mitochondrial modulating mechanism of neuroprotective effect of epigallocatechin-3-gallate against rodent model of rotenone induced Parkinson’s disease (PD). The behavioural alterations were assessed by using open field test apparatus, Chatilon’s grip strength test apparatus and elevated plus maze for determining the locomotor activity, grip strength and cognition respectively. Biochemically, various parameters to assess oxidative stress, neuroinflammation and neurochemical estimations were performed on rat brain homogenates. A histological examination of rat brain striatum was done to check the neurodegeneration. Epigallocatechin-3-gallate (EGCG) at 10 & 20 mg/kg, were investigated for their neuroprotective potential along with levodopa as a standard agent. Minocycline, a microglial activation inhibitor, was administered alone and in combination with EGCG. EGCG and minocycline produced ameliorative effect against rotenone induced PD like symptoms by significantly reduced behavioral, biochemical and histological alterations. Results of our study reveal the neuroprotective effect of EGCG and minocycline against rotenone induced PD. Results of our study indicate that EGCG exerted neuroprotective effect against rotenone induced PD via its antioxidant, anti-inflammatory and mitochondrial modulating mechanisms and substantiate its previously reported and traditional claims for its use in CNS diseases.

Keywords: antioxidants, neurotoxicity, rotenone, EGCG

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Authors: Ahlam Ali, Katrina Lappin, Jaine Blayney, Ken Mills

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Leukaemia is the most frequently (30%) occurring type of paediatric cancer. Of these, approximately 80% are acute lymphoblastic leukaemia (ALL) with acute myeloid leukaemia (AML) cases making up the remaining 20% alongside other leukaemias. Unfortunately, children with AML do not have promising prognosis with only 60% surviving 5 years or longer. It has been highlighted recently the need for age-specific therapies for AML patients, with paediatric AML cases having a different mutational landscape compared with AML diagnosed in adult patients. Drug Repurposing is a recognized strategy in drug discovery and development where an already approved drug is used for diseases other than originally indicated. We aim to identify novel combination therapies with the promise of providing alternative more effective and less toxic induction therapy options. Our in-silico analysis highlighted ‘cell death and survival’ as an aberrant, potentially targetable pathway in paediatric AML patients. On this basis, 83 apoptotic inducing compounds were screened. A preliminary single agent screen was also performed to eliminate potentially toxic chemicals, then drugs were constructed into a pooled library with 10 drugs per well over 160 wells, with 45 possible pairs and 120 triples in each well. Seven cell lines were used during this study to represent the clonality of AML in paediatric patients (Kasumi-1, CMK, CMS, MV11-14, PL21, THP1, MOLM-13). Cytotoxicity was assessed up to 72 hours using CellTox™ Green reagent. Fluorescence readings were normalized to a DMSO control. Z-Score was assigned to each well based on the mean and standard deviation of all the data. Combinations with a Z-Score <2 were eliminated and the remaining wells were taken forward for further analysis. A well was considered ‘successful’ if each drug individually demonstrated a Z-Score <2, while the combination exhibited a Z-Score >2. Each of the ten compounds in one well (155) had minimal or no effect as single agents on cell viability however, a combination of two or more of the compounds resulted in a substantial increase in cell death, therefore the ten compounds were de-convoluted to identify a possible synergistic pair/triple combinations. The screen identified two possible ‘novel’ drug pairing, with BCL2 inhibitor ABT-737, combined with either a CDK inhibitor Purvalanol A, or AKT/ PI3K inhibitor LY294002. (ABT-737- 100 nM+ Purvalanol A- 1 µM) (ABT-737- 100 nM+ LY294002- 2 µM). Three possible triple combinations were identified (LY2409881+Akti-1/2+Purvalanol A, SU9516+Akti-1/2+Purvalanol A, and ABT-737+LY2409881+Purvalanol A), which will be taken forward for examining their efficacy at varying concentrations and dosing schedules, across multiple paediatric AML cell lines for optimisation of maximum synergy. We believe that our combination screening approach has potential for future use with a larger cohort of drugs including FDA approved compounds and patient material.

Keywords: AML, drug repurposing, ABT-737, apoptosis

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Authors: Dwi Endarti, Susi a Kristina, Rizki Noorizzati, Akbar E Nugraha, Fera Maharani, Kika a Putri, Asninda H Azizah, Sausanzahra Angganisaputri, Yunisa Yustikarini

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Cost utility analysis is the most recommended pharmacoeconomic method since it allows widely comparison of cost-effectiveness results from different interventions. The method uses outcome of quality-adjusted life year (QALY) or disability-adjusted life year (DALY). Measurement of QALY requires the data of utility dan life years gained. Utility is measured with the instrument for quality of life measurement such as EQ-5D. Recently, the EQ-5D is available in two versions which are EQ-5D-3L and EQ-5D-5L. This study aimed to compare the EQ-5D-3L and EQ-5D-5L to examine the most suitable version for Indonesian population. This study was an observational study employing cross sectional approach. Data of quality of life measured with EQ-5D-3L and EQ-5D-5L were collected from several groups of population which were respondent with chronic diseases, respondent with acute diseases, and respondent from general population (without illness) in Yogyakarta Municipality, Indonesia. Convenience samples of hypertension patients (83), diabetes mellitus patients (80), and osteoarthritis patients (47), acute respiratory tract infection (81), cephalgia (43), dyspepsia (42), and respondent from general population (293) were recruited in this study. Responses on the 3L and 5L versions of EQ-5D were compared by examining the psychometric properties including agreement, internal consistency, ceiling effect, and convergent validity. Based on psychometric properties tests of EQ-5D-3L dan EQ-5D-5L, EQ-5D-5L tended to have better psychometric properties compared to EQ-5D-3L. Future studies for health related quality of life (HRQOL) measurements for pharmacoeconomic studies in Indonesia should apply EQ-5D-5L.

Keywords: EQ-5D, Health Related Quality of Life, Indonesian Population, Psychometric Properties

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Authors: Antonia Stergiou

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Background: Due to the developmental trajectory of executive function in preschool age, the majority of existing studies investigating the association between acute physical activity and cognitive control have focused on adolescents and adult population. Aim- The aim of this study was to investigate the possible effects of physical activity on the inhibitory control of pre-school children. Methods: This is a prospectively designed study that was conducted in a primary school in Bristol in June 2015. The total number of subjects was n=61 and 20 trials of a modified Eriksen Flanker Task were completed before and after a 30-minutes session of moderate exercise (including both 5 minutes of warm up and cool down). For each test a pre- and post-test assessment took place that included both congruent and incongruent trials. The congruent trials were considered as the control condition and the incongruent trials as those that measure inhibitory control (experimental condition). At the end of the assessment, the participants were instructed to choose the face that described their current feelings between three options (happy, neutral, sad). Results: There was a trend for increased accuracy following moderate exercise, but there was statistical significance (p > .05). However, there was statistically significant improvement in the reaction time following the same type of exercise (p = .005). Face board assessment revealed positive emotions after 30 minutes of moderate exercise. Conclusions: The current study supports findings from previous studies related to the benefits of physical activity on the children’s inhibitory control and provides evidence of those benefits in even younger ages. Further research should take place considering each child individually. Implementation of those findings could result in an improved curriculum in schools with additional time spent on physical education courses.

Keywords: cognitive control, inhibition, physical activity, pre-school children

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Authors: Sudha Puhal, Dr Rajmala Jaiswal

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Retropharyngeal abscess occurs most commonly in children following acute upper respiratory tract and ear infection. Airway management in retropharyngeal abscess is an anesthetic challenge due to distortion of airway anatomy and the possibility of spontaneous rupture of abscess leading to aspiration or stridor due to laryngeal edema.. In this report we present a case of retropharyngeal abscess in a child, which was drained under general anaesthesia successfully without any complications.

Keywords: abscess, airway, difficult, retropharyngeal

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Authors: Nalan Kaya, D. Ozlem Dabak, Gonca Ozan, Elif Erdem, Enver Ozan

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One of the common causes of cardiovascular disease (CVD) is smoking. Moreover, tobacco smoke decreases the amount of oxygen that the blood can carry and increases the tendency for blood clots. Ellagic acid is a powerful antioxidant found especially in red fruits. It was shown to block atherosclerotic process suppressing oxidative stress and inflammation. The aim of this study was to examine the protective effects of ellagic acid against oxidative damage on heart tissues of rats induced by tobacco smoke. Twenty-four male adult (8 weeks old) Spraque-Dawley rats were divided randomly into 4 equal groups: group I (Control), group II (Tobacco smoke), group III (Tobacco smoke + corn oil) and group IV (Tobacco smoke + ellagic acid). The rats in group II, III and IV, were exposed to tobacco smoke 1 hour twice a day for 12 weeks. In addition to tobacco smoke exposure, 12 mg/kg ellagic acid (dissolved in corn oil), was applied to the rats in group IV by oral gavage. An equal amount of corn oil used in solving ellagic acid was applied to the rats by oral gavage in group III. At the end of the experimental period, rats were decapitated. Heart tissues and blood samples were taken. Histological and biochemical analyzes were performed. Vascular congestion, hyperemic areas, inflammatory cell infiltration and increased connective tissue in the perivascular area were observed in tobacco smoke and tobacco smoke + corn oil groups. Increased connective tissue in the perivascular area, hemorrhage and inflammatory cell infiltration were decreased in tobacco smoke + EA group. Group-II GSH level was not changed (significantly), CAT, SOD, GPx activities were significantly higher than group-I. Compared to group-II, group-IV GSH, SOD, CAT, GPx activities were increased, and MDA level was decreased significantly. Group-II and Group-III levels were similar. The results indicate that ellagic acid could protect the heart tissue from the tobacco smoke harmful effects.

Keywords: ellagic acid, heart, rat, tobacco smoke

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Authors: Soumaya Mrabet, Imen Akkari, Amira Atig, Elhem Ben Jazia

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Introduction: Celiac disease (CD) is a chronic autoimmune inflammatory enteropathy caused by gluten. The clinical presentation is very variable. Malabsorption in the MC is responsible for an alteration of the bone metabolism. Our purpose is to study the osteoarticular manifestations related to this condition. Material and methods: It is a retrospective study of 41 cases of CD diagnosed on clinical, immunological, endoscopic and histological arguments, in the Internal Medicine and Gastroenterology Department of Farhat Hached Hospital between September 2005 and January 2016. Results: Osteoarticular manifestations were found in 9 patients (22%) among 41 patients presenting CD. These were 7 women and 2 men with an average age of 35.7 years (25 to 67 years). These manifestations were revelatory of CD in 3 cases. Abdominal pain and diarrhea were present in 6 cases. Inflammatory polyarthralgia of wrists and knees has been reported in 7 patients. Mechanical mono arthralgia was noted in 2 patients. Biological tests revealed microcytic anemia by iron deficiency in 7 cases, hypocalcemia in 5 cases, Hypophosphatemia in 3 cases and elevated alkaline phosphatases in 3 cases. Upper gastrointestinal endoscopy with duodenal biopsy found villous atrophy in all cases. In immunology, Anti-transglutaminase antibodies were positive in all patients, Anti-endomysium in 7 cases. Measurement of bone mineral density (BMD) by biphotonic X-ray absorptiometer with evaluation of the T-score and the Z-score was performed in Twenty patients (48.8%). It was normal in 7 cases (33%) and showed osteopenia in 5 patients (25%) and osteoporosis in 2 patients (10%). All patients were treated with a Gluten-free diet associated with vitamin D and calcium substitution in 5 cases. The evolution was favorable in all cases with reduction of bone pain and normalization of the phosphocalcic balance. Conclusion: The bone impact of CD is frequent but often asymptomatic. Patients with CD should be evaluated by the measurement of bone mineral density and monitored for calcium and vitamin D deficiencies.

Keywords: bone mineral density, celiac disease, osteoarticular manifestations, vitamin D and calcium

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Authors: Anca Maria Cimpean, Serban Comsa

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Chick embryo chorioallantoic membrane (CAM) is a well vascularised in vivo experimental model used as a platform for testing the behavior of different implants inserted on it from tumor fragments to therapeutic agents or various biomaterials. Five types of collagen-based biomaterials with 2D and 3D structure (MotifMesh, Optimaix2D, Optimaix3D, Dual Layer Collagen and Xenoderm) were implanted on CAM and continuously evaluated by stereomicroscope for up to 5 days post-implant with an emphasis of their ability to requisite and develop new blood vessels (BVs) followed by microscopic analysis. MotifMEsh did not induce any angiogenic response lacking to be invaded by BVs from the CAM, but it induced intense inflammatory response necrosis and fibroblastic reaction around the implant. Optimaix2D has good adherence. CAM with minimal or no inflammatory reaction, a good integration of the CAM between the collagen mesh’s fibers, consistent adhesion of the cells to the collagen fibers,and a good ability to form pseudo-vascular channels filled with cells. Optimaix3D induced the highest angiogenic effects on CAM. The material shows good integration on CAM. The collagen fibers of the material show the ability to organize themselves into linear and tubular structures. It is possible to see blood elements, especially at the periphery of the implant. Dual-layer collagen behaves similar to Optimaix 3D, while Xenoderm induced a moderate angiogenic effect on CAM. Based on these data, we may conclude that collagen-based materials have variable ability to requisite and develop new blood vessels. A proper selection of collagen-based biomaterial scaffolds may crucially influence the acquisition and development of blood vessels during angiogenesis assays.

Keywords: chick embryo chorioallantoic membrane, collagen scaffolds, blood vessels, vascular microenvironment

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Authors: Asma Naseer Cheema, Attya Bhatti, Jabar Ali, John Peter

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Background: High cholesterol levels, endothelial dysfunction, inefficient coagulation cascade and hyper inflammatory response all are the basis of coronary artery disease (CAD). Several studies are carried out to see the genetic influence of these factors on disease outcome. Objective: The objective of our study was to see the association of 10 putative loci with coronary artery disease in our population. Materials & Methods: We screened our population for 10 putative loci of CAD showing significant association (p < 5x10-8) with candidate genes (regulating the cholesterol metabolism, endothelial function, coagulation cascade and inflammatory response of body). Hardy-Weinberg equilibrium and linkage disequilibrium in cases and controls s were estimated separately. Approximately 5-10 ng of dried DNA in 384 well plate format was used to genotype each sample on the Sequenom iPLEX assay at University of Pittsburgh Genomics and Proteomics Core Laboratories. It was built on single-base primer extension with the MALDI-TOF MS detection possessing high sensitivity and specificity. The SNPs were genotyped through Taqman assay. Hardy Weinberg test was applied. The 10 SNPs were selected as genetic markers for this study (rs579459, rs1561198, rs2954029, rs1122608, rs17114036, rs9515203, rs10947789, rs7173743, rs2895811, rs2075650). Results: Mean age of the patient was 52 ± 11 years. Blood pressure and positive family history was found a significant risk factor for CAD. None of the selected SNPs showed significant association with coronary artery disease in our population (p>0.05). Conclusion: rs579459, rs1561198, rs2954029, rs1122608, rs17114036, rs9515203, rs10947789, rs7173743, rs2895811, rs2075650 are not significant genetic markers for CAD in our population.

Keywords: CAD, genetic markers, loci, risk factors

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Authors: Majid Mardaniyan Ghahfarokhi, Abdolhamid Habibi, Majid Mohammad Shahi

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The combination of exercise and diet as the most important strategy to reduce weight and control obesity-related factors, including Irisin, Insulin, and Glucose was raised. The aim of this study was to investigate the effect of aerobic exercise combined with four different diets on serum levels of Irisin, Insulin, and Glucose in overweight men. Methods: In this quasi-experimental study, 8 overweight men (BMI 29.23±0.47) with average age of (23±1.6) voluntarily participated in 4 sessions by one-week interval. The study was done in exercise physiology lab. In each session, subjects performed a 30 minutes treadmill test with 60-70% of maximum heart rate, after consuming a high carbohydrate, high-fat, high-protein and normal diet. For biochemical measurement, three blood samples were taken in fasting state, two hours after meals and after exercise Results: Statistical analysis of data showed that the serum levels of Irisin after consumption all four diets had been reduced which this reduce as a result of high-fat diet that were significantly (p ≤ 0/038). Serum concentration of Insulin and Glucose increased after consuming four diets. However, increase in serum Insulin and Glucose was significant only after consuming high-carbohydrate diet (Respectively p ≤ 0/001, p ≤ 0/042). In addition, during exercise after consuming all four regular diet, high carbohydrate, high-protein and high-fat, Irisin significant increased significantly (Respectively p ≤ 0/021, p ≤ 0/049, p ≤ 0/001, P ≤ 0/003), Insulin decreased significantly (Respectively p ≤ 0/002, p ≤ 0/001, p ≤ 0/001, p ≤ 0/002) and Glucose were significantly reduced (Respectively p ≤ 0/001, p ≤ 0/001, P ≤ 0/001, p ≤ 0/002). After aerobic activity following the consumption of a high protein diet the highest increase in irisin levels, and after aerobic exercise following consumption of high carbohydrate diet the greatest decrease in insulin and glucose levels were observed. Conclusion: It seems that diet alone and exercises following different consumption diets can have a significant effect on Irisin, Insulin, and Glucose serum levels in overweight young men.

Keywords: acute aerobic exercise, diet, irisin, overweight

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Authors: B. T. Naveen Kumar, Anuj Tyagi, Niraj Kumar Singh, Visanu Boonyawiwat, A. H. Shanthanagouda, Orawan Boodde, K. M. Shankar, Prakash Patil, Shubhkaramjeet Kaur

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Early mortality syndrome (EMS)/Acute Hepatopancreatic Necrosis Disease (AHPND) has emerged as a major obstacle for the shrimp farming around the world. It is caused by a strain of Vibrio parahaemolyticus. The possible preventive and control measure is, early and rapid detection of the pathogen in the broodstock, post-larvae and monitoring the shrimp during the culture period. Polymerase chain reaction (PCR) based early detection methods are good, but they are costly, time taking and requires a sophisticated laboratory. The present study was conducted to develop a simple, sensitive and rapid diagnostic farmer level kit for the reliable detection of AHPND in shrimp. A panel of monoclonal antibodies (MAbs) were raised against the recombinant Pir B protein (rPirB). First, an immunodot was developed by using MAbs G3B8 and Mab G3H2 which showed specific reactivity to purified r-PirB protein with no cross-reactivity to other shrimp bacterial pathogens (AHPND free Vibrio parahaemolyticus (Indian strains), V. anguillarum, WSSV, Aeromonas hydrophila, and Aphanomyces invadans). Immunodot developed using Mab G3B8 is more sensitive than that with the Mab G3H2. However, immunodot takes almost 2.5 hours to complete with several hands-on steps. Therefore, the flow-through assay (FTA) was developed by using a plastic cassette containing the nitrocellulose membrane with absorbing pads below. The sample was dotted in the test zone on the nitrocellulose membrane followed by continuos addition of five solutions in the order of i) blocking buffer (BSA) ii) primary antibody (MAb) iii) washing Solution iv) secondary antibody and v) chromogen substrate (TMB) clear purple dots against a white background were considered as positive reactions. The FTA developed using MAbG3B8 is more sensitive than that with MAb G3H2. In FTA the two MAbs showed specific reactivity to purified r-PirB protein and not to other shrimp bacterial pathogens. The FTA is simple to farmer/field level, sensitive and rapid requiring only 8-10 min for completion. Tests can be developed to kits, which will be ideal for use in biosecurity, for the first line of screening (at the port or pond site) and during monitoring and surveillance programmes overall for the good management practices to reduce the risk of the disease.

Keywords: acute hepatopancreatic necrosis disease, AHPND, flow-through assay, FTA, farmer level, immunodot, pond site, shrimp

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Authors: Yahia Massinissa, Henhouda Affaf, Yahia Mouloud

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The aim of this study was to investigate the toxicity; analgesic and anti-pyretic properties of standardized HA methanolic extract (HAMeOH) in vivo. The acute toxicity study was performed on rats while adopting the OECD-420 Guidelines (fixed dose procedure). Assessment of analgesic activity was performed in rats with two analgesic models. One was acetic acid induced writhing response and the other formalin-induced paw licking. The anti-pyretic effect was tested by brewer’s yeast induced fever in rats. For the acute toxicity test, the higher dose administration of 2000 mg/kg bw. of Hyoscyamus albus did not produce any toxic signs or deaths in rats. There were no significant differences (p>0.05) in the body and organ weights between control and treated groups. The (LD50) of Hyoscyamus albus was higher than 2000 g/kg bw. In subacute toxicity study, no mortality and toxic signs were observed with the doses of 100 and 200 mg/kg bw. of extracts of for 28 consecutive days. These analgesic experimental results indicated that HAMeOH (100 mg/kg and 200 mg/kg) decreased the acetic acid-induced writhing responses and HAMeOH (100 mg/kg and 200 mg/kg) decreased the licking time in the second phase of the formalin test. Moreover, in the model of yeast induced elevation of the body temperature HAMeOH showed dose-dependent lowering of the body temperature up to 3h at both the doses these results obtained, were comparable to that of paracetamol. The present findings indicate that the leaves of Hyoscyamus albus L. possess potent analgesic and antipyretic activity.

Keywords: Hyoscyamus albus, methanolic extract, toxicity, analgesic activity, antipyretic activity, formalin test

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Authors: S. Moustafa El Shanawany, I. Labib Salem, F. Mohamed Magdy Badr El Dine, H. Tag El Deen Abd Allah

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Thermal injuries remain a global health problem and a common issue encountered in forensic pathology. They are a devastating cause of morbidity and mortality in children and adults especially in developing countries, causing permanent disfigurement, scarring and grievous hurt. Burns have always been a matter of legal concern in cases of suicidal burns, self-inflicted burns for false accusation and homicidal attempts. Assessment of burn injuries as well as rating permanent disabilities and disfigurement following thermal injuries for the benefit of compensation claims represents a challenging problem. This necessitates the development of reliable scoring systems to yield an expected likelihood of permanent disability or fatal outcome following burn injuries. The study was designed to identify the risk factors of mortality in acute burn patients and to evaluate the applicability of FLAMES (Fatality by Longevity, APACHE II score, Measured Extent of burn, and Sex) and BOBI (Belgian Outcome in Burn Injury) model scores in predicting the outcome. The study was conducted on 100 adult patients with acute burn injuries admitted to the Burn Unit of Alexandria Main University Hospital, Egypt from October 2014 to October 2015. Victims were examined after obtaining informed consent and the data were collected in specially designed sheets including demographic data, burn details and any associated inhalation injury. Each burn patient was assessed using both BOBI and FLAMES scoring systems. The results of the study show the mean age of patients was 35.54±12.32 years. Males outnumbered females (55% and 45%, respectively). Most patients were accidently burnt (95%), whereas suicidal burns accounted for the remaining 5%. Flame burn was recorded in 82% of cases. As well, 8% of patients sustained more than 60% of total burn surface area (TBSA) burns, 19% of patients needed mechanical ventilation, and 19% of burnt patients died either from wound sepsis, multi-organ failure or pulmonary embolism. The mean length of hospital stay was 24.91±25.08 days. The mean BOBI score was 1.07±1.27 and that of the FLAMES score was -4.76±2.92. The FLAMES score demonstrated an area under the receiver operating characteristic (ROC) curve of 0.95 which was significantly higher than that of the BOBI score (0.883). A statistically significant association was revealed between both predictive models and the outcome. The study concluded that both scoring systems were beneficial in predicting mortality in acutely burnt patients. However, the FLAMES score could be applied with a higher level of accuracy.

Keywords: BOBI, burns, FLAMES, scoring systems, outcome

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Authors: Camelia Porey, Binaya Kumar Jaiswal

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BACKGROUND: Antiphospholipid antibody (APLA) syndrome is an autoimmune disorder predisposing to thrombotic complications affecting CNS either by arterial vasooclusion or venous thrombosis. Cerebral venous sinus thrombosis (CVST) secondarily causes raised intracranial pressure (ICP). However, intracranial hypertension without evidence of CVST is a rare entity. Here we present two cases of elevated ICP with absence of identifiable CVST. CASE SUMMARY: Case 1, 28-year female had a 2 months history of holocranial headache followed by bilateral painless vision loss reaching lack of light perception over 20 days. CSF opening pressure was elevated. Fundoscopy showed bilateral grade 4 papilledema. MRI revealed a partially empty sella with bilateral optic nerve tortuosity. Idiopathic intracranial hypertension (IIH) was diagnosed. With acetazolamide, there was complete resolution of the clinical and radiological abnormalities. 5 months later she presented with acute onset right-sided hemiparesis. MRI was suggestive of acute left MCA infarct.MR venogram was normal. APLA came positive with high titres of Anticardiolipin and Beta 2 glycoprotein both IgG and IgM. Case 2, 23-year female, presented with headache and diplopia of 2 months duration. CSF pressure was elevated and Grade 3 papilledema was seen. MRI showed bilateral optic nerve hyperintensities with nerve head protrusion with normal MRV. APLA profile showed elevated beta 2 glycoprotein IgG and IgA. CONCLUSION: This is an important non thrombotic complication of APLA syndrome and requires further large-scale study for insight into the pathogenesis and early recognition to avoid future complications.

Keywords: APLA syndrome, idiopathic intracranial hypertension, MR venogram, papilledema

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Authors: Mohammad Karam, Abdulmalik Alsaif, Abdulrahman Al-Naseem, Amrit Hayre, Abdurrahman Al Jabbouri, Ahmad Aldubaikhi, Narvair Kahlar, Salem Al-Mutairi

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Purpose: To compare the outcomes of mycophenolate mofetil (MMF) versus methotrexate (MTX) in non-infectious ocular inflammatory disease (NIOID). Methods: A systematic review and meta-analysis were performed as per the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) Guidelines and an electronic search was conducted to identify all comparative studies of MMF versus MTX in NIOID. Treatment results and side effects were primary outcome measures. Secondary outcome measures included visual acuity and resolution of macular oedema. Fixed and random-effects models were used for the analysis. Results: Four studies enrolling 905 patients were identified. There was no significant difference between MMF and MTX groups in overall treatment success (Odds Ratio [OR] = 0.97, P = 0.96) and failure (OR = 0.86, P = 0.85) of NIOID. Although treatment success of uveitis showed no significant difference for anterior and intermediate uveitis cases (OR = 2.33, P = 0.14), MTX showed a significantly improved effect in cases involving posterior uveitis and panuveitis (OR = 0.41, P = 0.003). However, the median dose required for treatment success was lower for MTX whereas MMF was associated with a faster median time to treatment success. Further to this, MMF showed a reduced rate of side effects when compared to MTX, but MTX failed to reach statistical significance, most notably for liver enzyme elevation (OR = 0.65, P = 0.16), fatigue (OR = 0.84, P = 0.49) and headache (OR = 0.81, P = 0.37). For secondary outcomes, no significant difference was noted in visual acuity and resolution of macular edema. Conclusions: MMF is comparable to MTX in the treatment of NIOID as there was no significant difference in the outcome of treatment success and side effect profiles.

Keywords: Mycophenolate mofetil, methotrexate, non-infectious ocular inflammation, uveitis, scleritis

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Authors: Che Hsiu Chen, Kuo Wei Tseng, Zih Jian Huang, Hon Wen Cheng

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A typical warm-up contains both stretching exercises and jogging. The static stretching prior to training or competition may cause detrimental effects to athletic performance. However, it is unclear whether different types of dynamic stretching exercises had different acute effects on knee flexors stiffness, flexibility, and strength. The purpose of this study was to analyze the knee flexors stiffness, flexibility, and strength gains after dynamic straight leg raise (DSLR) and dynamic modified toe-touch (MTT) stretching. Sixteen healthy university active men (height 176.27 ± 4.03 cm; weight 72.27 ± 8.90 kg; age 22.09 ± 2.31 years). After 5 minutes (8km/h) of running subjects performed 2 randomly ordered stretching protocols: DSLR and MTT stretching protocols. There were a total of six, 30 seconds bouts of dynamic stretching (15 repetitions) with 30seconds rest between bouts. The outcome measures were maximal voluntary isokinetic concentric hamstring strength (60°/s), muscle flexibility test by passive straight leg raise (PSLR), active straight leg raise (ASLR), and muscle stiffness using ultrasound Acoustic Radiation Forced Impulse (ARFI) elastography before and immediately after stretching. The muscle stiffness and concentric strength decreased significantly (p < .05), the flexibility no significant change after DSLR protocol (p > .05). The concentric strength decreased significantly (p < .05), the flexibility and muscle stiffness no significant change after MTT protocol (p > .05), whereas no significant differences were found for the DSLR and MTT. Our findings suggest that dynamic stretching (30s x 6 bouts) resulted in change in muscle stiffness or may be induced slack in the musculotendinous unit thereby, reducing force production. Therefore, 30s x 6 bouts of dynamic stretching adversely affects efforts of hamstring muscle maximal concentric strength.

Keywords: sport injury, ultrasound, eccentric exercise, performance

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Authors: Enrico Gugliandolo, Salvatore Cuzzocrea, Rosalia Crupi

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Osteoarthritis (OA) is one of the most common chronic pain conditions in dogs and cats. OA pain is currently viewed as a mixed phenomenon involving both inflammatory and neuropathic mechanisms at the peripheral (joint) and central (spinal and supraspinal) levels. Oxidative stress has been implicated in OA pain. Although nonsteroidal anti-inflammatory drugs are commonly prescribed for OA pain, they should be used with caution in pets because of adverse effects in the long term and controversial efficacy on neuropathic pain. An unmet need remains for safe and effective long-term treatments for OA pain. Palmitoyl-glucosamine (PGA) is an analogue of the ALIAamide palmitoylethanolamide, i.e., a body’s own endocannabinoid-like compound playing a sentinel role in nociception. PGA, especially in the micronized formulation, was shown safe and effective in OA pain. The aim of this study was to investigate the effect of a co-micronized formulation of PGA with the natural antioxidant curcumin (PGA-cur) on OA pain. Ten Sprague-Dawley male rats were used for each treatment group. The University of Messina Review Board for the care and use of animals authorized the study. On day 0, rats were anesthetized (5.0% isoflurane in 100% O2) and received intra-articular injection of MIA (3 mg in 25 μl saline) in the right knee joint, with the left being injected an equal volume of saline. Starting the third day after MIA injection, treatments were administered orally three times per week for 21 days, at the following doses: PGA 20 mg/kg, curcumin 10 mg/kg, PGA-cur (2:1 ratio) 30 mg/kg. On day 0 and 3, 7, 14 and 21 days post-injection, mechanical allodynia was measured using a dynamic plantar Von Frey hair aesthesiometer and expressed as paw withdrawal threshold (PWT) and latency (PWL). Motor functional recovery of the rear limb was evaluated on the same time points by walking track analysis using the sciatic functional index. On day 21 post-MIA injection, the concentration of the following inflammatory and nociceptive mediators was measured in serum using commercial ELISA kits: tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), nerve growth factor (NGF) and matrix metalloproteinase-1-3-9 (MMP-1, MMP-3, MMP-9). The results were analyzed by ANOVA followed by Bonferroni post-hoc test for multiple comparisons. Micronized PGA reduced neuropathic pain, as shown by the significant higher PWT and PWL values compared to vehicle group (p < 0.0001 for all the evaluated time points). The effect of PGA-cur was superior at all time points (p < 0.005). PGA-cur restored motor function already on day 14 (p < 0.005), while micronized PGA was effective a week later (D21). MIA-induced increase in the serum levels of all the investigated mediators was inhibited by PGA-cur (p < 0.01). PGA was also effective, except on IL-1 and MMP-3. Curcumin alone was inactive in all the experiments at any time point. The encouraging results suggest that PGA-cur may represent a valuable option in OA pain management and warrant further confirmation in well-powered clinical trials.

Keywords: ALIAmides, curcumin, osteoarthritis, palmitoyl-glucosamine

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Authors: Brian M. Mehling, Louis Quartararo, Marine Manvelyan, Paul Wang, Dong-Cheng Wu

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Numerous investigations suggest that Mesenchymal Stem Cells (MSCs) in general represent a valuable tool for therapy of symptoms related to chronic inflammatory diseases. Blue Horizon Stem Cell Therapy Program is a leading provider of adult and children’s stem cell therapies. Uniquely we have safely and efficiently treated more than 600 patients with documenting each procedure. The purpose of our study is primarily to monitor the immune response in order to validate the safety of intravenous infusion of human umbilical cord blood derived MSCs (UC-MSCs), and secondly, to evaluate effects on biomarkers associated with chronic inflammation. Nine patients were treated for conditions associated with chronic inflammation and for the purpose of anti-aging. They have been given one intravenous infusion of UC-MSCs. Our study of blood test markers of 9 patients with chronic inflammation before and within three months after MSCs treatment demonstrates that there is no significant changes and MSCs treatment was safe for the patients. Analysis of different indicators of chronic inflammation and aging included in initial, 24-hours, two weeks and three months protocols showed that stem cell treatment was safe for the patients; there were no adverse reactions. Moreover data from follow up protocols demonstrates significant improvement in energy level, hair, nails growth and skin conditions. Intravenously administered UC-MSCs were safe and effective in the improvement of symptoms related to chronic inflammation. Further close monitoring and inclusion of more patients are necessary to fully characterize the advantages of UC-MSCs application in treatment of symptoms related to chronic inflammation.

Keywords: chronic inflammatory diseases, intravenous infusion, stem cell therapy, umbilical cord blood derived mesenchymal stem cells (UC-MSCs)

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Authors: Ionelia Taranu, Gina Cecilia Pistol, Mihai Alexandru Gras, Mihai Laurentiu Palade, Mariana Stancu, Veronica Sanda Chedea

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In the last decade bioactive compounds from grape waste are investigated as new therapeutic agents for the inhibition of carcinogenesis and other diseases. The objective of this study was to characterize several bioactive compounds (polyphenols and polyunsaturated fatty acids) of a dried grape pomace (GP) derived from a Romanian winery and further to evaluate their effect on inflammation and oxidative markers in liver of pig used as animal model. The total polyphenol concentration of pomace was 36.2g gallic acid equiv /100g. The pomace was rich in polyphenols from the flavonoids group, the main class being flavanols (epicatechins, catechin, epigallocatechin, procyanidins) and antocyanins (Malvidin 3-O-glucoside). The highest concentration was recorded for epicatechin (51.96g/100g) and procyanidin dimer (22.79g/100g). A high concentration of total polyunsaturated fatty acids (PUFA) especially ω-6 fatty acids (59.82 g/100g fat) was found in grape pomace. 20 crossbred TOPIG hybrid fattening pigs were randomly assigned (n = 10) to two experimental treatments: a normal diet (control group) and a diet included 5% grape pomace (GP group) for 24 days. The GP diet lowered the gene expression and protein concentration of IL-1β, IL-8, TNF-α and IFN-γ cytokines in liver suggesting an anti-inflammatory effect of GP diet. Concentration of hepatic TBARS also decreased, but the total antioxidant capacity (liver TEAC) and activity and gene expression of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) did not differ between the GP and control diet. The results showed that GP diet exerted an anti-inflammatory effect, but the 5% dietary inclusion modulated only partially the oxidative stress.

Keywords: animal model, inflammation, grape waste, immune organs

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Authors: Ahmed A. A. Fadol, Guangji Tong, Wlaa Mohamed

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This paper provides a comprehensive analysis of food insecurity in Sudan, focusing on consumption patterns and their implications, employing the Integrated Food Security Phase Classification (IPC) assessment framework. Years of conflict and economic instability have driven large segments of the population in Sudan into crisis levels of acute food insecurity according to the (IPC). A substantial number of people are estimated to currently face emergency conditions, with an additional sizeable portion categorized under less severe but still extreme hunger levels. In this study, we explore the multifaceted nature of food insecurity in Sudan, considering its historical, political, economic, and social dimensions. An analysis of consumption patterns and trends was conducted, taking into account cultural influences, dietary shifts, and demographic changes. Furthermore, we employ logistic regression and random forest analysis to identify significant independent variables influencing food security status in Sudan. Random forest clearly outperforms logistic regression in terms of area under curve (AUC), accuracy, precision and recall. Forward projections of the IPC for Sudan estimate that 15 million individuals are anticipated to face Crisis level (IPC Phase 3) or worse acute food insecurity conditions between October 2023 and February 2024. Of this, 60% are concentrated in Greater Darfur, Greater Kordofan, and Khartoum State, with Greater Darfur alone representing 29% of this total. These findings emphasize the urgent need for both short-term humanitarian aid and long-term strategies to address Sudan's deepening food insecurity crisis.

Keywords: food insecurity, consumption patterns, logistic regression, random forest analysis

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Authors: Yahia Massinissa, Afaf Benhouda, Mouloud Yahia

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Objective: The aim of this study was to investigate the toxicity; analgesic and anti-pyretic properties of standardized HA methanolic extract (HAMeOH) in vivo. Methods: The acute toxicity study was performed on rats while adopting the OECD-420 Guidelines (fixed dose procedure). Assessment of analgesic activity was performed in rats with two analgesic models. One was acetic acid induced writhing response and the other formalin-induced paw licking. The anti-pyretic effect was tested by Brewer’s yeast induced fever in rats. Results: For the acute toxicity test, the higher dose administration of 2000 mg/kg bw. of H.albus did not produce any toxic signs or deaths in rats. There were no significant differences (p>0.05) in the body and organ weights between control and treated groups. The (LD50) of 'H. albus' was higher than 2000 g/kg bw. In subacute toxicity study, no mortality and toxic signs were observed with the doses of 100 and 200 mg/kg bw. of extracts of for 28 consecutive days. These analgesic experimental results indicated that HAMeOH (100 mg/kg and 200 mg/kg) decreased the acetic acid-induced writhing responses and HAMeOH (100 mg/kg and 200 mg/kg) decreased the licking time in the second phase of the formalin test. Moreover, in the model of yeast-induced elevation of the body temperature HAMeOH showed dose-dependent lowering of the body temperature up to 3h at both the doses these results obtained, were comparable to that of paracetamol. Conclusion: The present findings indicate that the leaves of Hyoscyamus albus L. possess potent analgesic and antipyretic activity.

Keywords: Hyoscyamus albus, Umbilicus rupestris, secondary metabolites, NMR with protons, pharmacobiologic activities, methanolic extract

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Authors: Zhao Jiashen, Serene Goh, Jerry Goo, Anthony Li, Lim Woan Wui, Paul Drakeford, Chen Qing Yan

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Introduction: Emergency laparotomy (EL) is one of the most common surgeries done in Singapore to treat acute abdominal pathologies. A significant proportion of these surgeries are performed in the geriatric population (65 years and older), who tend to have the highest postoperative morbidity, mortality, and highest utilization of intensive care resources. Frailty, the state of vulnerability to adverse outcomes from an accumulation of physiological deficits, has been shown to be associated with poorer outcomes after surgery and remains a strong driver of healthcare utilization and costs. To date, there is little understanding of the impact it has on emergency laparotomy outcomes. The objective of this study is to examine the impact of frailty on postoperative morbidity, mortality, and length of stay after EL. Methods: A retrospective study was conducted in two tertiary centres in Singapore, Tan Tock Seng Hospital and Khoo Teck Puat Hospital the period from January to December 2019. Patients aged 65 years and above who underwent emergency laparotomy for intestinal obstruction, perforated viscus, bowel ischaemia, adhesiolysis, gastrointestinal bleed, or another suspected acute abdomen were included. Laparotomies performed for trauma, cholecystectomy, appendectomy, vascular surgery, and non-GI surgery were excluded. The Clinical Frailty Score (CFS) developed by the Canadian Study of Health and Aging (CSHA) was used. A score of 1 to 4 was defined as non-frail and 5 to 7 as frail. We compared the clinical outcomes of elderly patients in the frail and non-frail groups. Results: There were 233 elderly patients who underwent EL during the study period. Up to 26.2% of patients were frail. Patients who were frail (CFS 5-9) tend to be older, 79 ± 7 vs 79 ± 5 years of age, p <0.01. Gender distribution was equal in both groups. Indication for emergency laparotomies, time from diagnosis to surgery, and presence of consultant surgeons and anaesthetists in the operating theatre were comparable (p>0.05). Patients in the frail group were more likely to receive postoperative geriatric assessment than in the non-frail group, 49.2% vs. 27.9% (p<0.01). The postoperative complications were comparable (p>0.05). The length of stay in the critical care unit was longer for the frail patients, 2 (IQR 1-6.5) versus 1 (IQR 0-4) days, p<0.01. Frailty was found to be an independent predictor of 90-day mortality but not age, OR 2.9 (1.1-7.4), p=0.03. Conclusion: Up to one-fourth of the elderly who underwent EL were frail. Patients who were frail were associated with a longer length of stay in the critical care unit and a 90-day mortality rate of more than three times that of their non-frail counterparts. PPOSSUM was a better predictor of 90-day mortality in the non-frail group than in the frail group. As frailty scoring was a significant predictor of 90-day mortality, its integration into acute surgical units to facilitate shared decision-making and discharge planning should be considered.

Keywords: frailty elderly, emergency, laparotomy

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Authors: Jorge Martinez, Brandon Roberts, Holly Payton Toca

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Background: Therapeutic hypothermia (TH) is the international standard of care for all comatose patients after cardiac arrest, but criticism focuses on poor outcomes. We sought to develop criteria to identify American urban patients more likely to benefit from TH. Methods: Retrospective chart review of 107 consecutive adults undergoing TH in downtown New Orleans from 2010-2014 yielded records for 99 patients with all 44 survivors or families contacted up to four years. Results: 69 males and 38 females with a mean age of 60.2 showed 63 dead (58%) and 44 survivors (42%). Presenting cardiac rhythm was divided into shockable (Pulseless Ventricular Tachycardia, Ventricular Fibrillation) and non-shockable (Pulseless Electrical Activity, Asystole). Presenting in shockable rhythms with ROSC <20 minutes were 21 patients with 15 (71%) survivors (p=.001). Time >20 minutes until ROSC in shockable rhythms had 5 patients with 3 survivors (78%, p=0.001). Presenting in non-shockable rhythms with ROSC <20 minutes were 54 patients with 18 survivors (33%, p=.001). ROSC >20 minutes in non-shockable rhythms had 19 patients with 2 survivors (8%, p=.001). Survivors of shockable rhythms showed 19 (100%) living post TH. 15 survivors (79%, n=19, p=.001) had CPC score 1 or 2 with 4 survivors (21%, n=19) having a CPC score of 3. A total of 25 survived non-shockable rhythm. Acute survival of patients with non-shockable rhythm showed 18 expired <72 hours (72%, n=25) with long-term survival of 4 patients (5%, n=74) and CPC scores of 1 or 2 (p=.001). Interestingly, patients with time to ROSC <20 minutes exhibiting more than one loss of sustained ROSC showed 100% mortality (p=.001). Patients presenting with shockable >20 minutes ROSC had overall survival of 70% (p=.001), but those undergoing >3 cardiac rhythm changes had 100% mortality (p=.001). Conclusion: Patients presenting with shockable rhythms undergoing TH had overall acute survival of 70% followed by long-term survival of 100% after 4 years. In contrast, patients presenting with non-shockable rhythm had long-term survival of 5%. TH is not recommended for patients presenting with non-shockable rhythm and requiring greater than 20 minutes for restoration of ROSC.

Keywords: cardiac rhythm changes, Pulseless Electrical Activity (PEA), Therapeutic Hypothermia (TH)

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Authors: Vidia A. Nuraini, Eugene M. H. Yee, Mohan Bhadbhade, David StC. Black, Naresh Kumar

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Flavonoids are naturally occurring compounds that have been shown to exhibit a wide range of biological properties including anticancer and anti-inflammatory activities. However, flavonoids suffer from low bioavailability, which limits their overall utility for therapeutic applications. One of the methods to overcome this limitation is through structural modification of natural flavonoids. In this study, flavanone, isoflavanone, and isoflavene, were structurally modified through the introduction of additional fused-ring systems via ortho-quinone methide intermediates (o-QMs). These intermediates can readily undergo a [4+2] cycloaddition through an inverse-electron-demand Diels–Alder reaction with electron-rich dienophiles. A regioselective Mannich reaction using bis-(N,N-dimethylamino)methane was employed to generate the o-QM precursors of flavanone, isoflavanone, and isoflavene. The o-QM intermediates were subsequently generated in situ through thermal elimination of the dimethylamine functionality and reacted with a variety of dienophiles to produce novel flavonoids with fused-ring systems. A total of 21 novel flavonoid analogs were successfully synthesized. The X-ray crystal structure of cycloaddition adducts, particularly those derived from 3,4-dihydro-2H-pyran and p-methoxystyrene revealed a special case of enantiomeric disorder, where two enantiomers in equal amounts superpose with one another, with the exception for atoms that have opposite configuration. The anticancer properties of fused-ring systems derived from isoflavene were evaluated against the neuroblastoma SKN-BE(2)C, the triple negative breast cancer MDA-MB-231, and the glioblastoma U87 cancer cell lines. One of these cycloaddition adducts had displayed improved anti-proliferative activity against MDA-MB-231 and U87 cancer cell lines as compared to the parent compound. Further anticancer and anti-inflammatory activities of the flavanone and isoflavanone analogs are currently being investigated.

Keywords: Diels-Alder reaction, flavonoids, Mannich reaction, ortho-quinone methide.

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Authors: Nurul Mazni Abdullah, Saw Kian Cheah, Raha Abdul Rahman, Qurratu 'Aini Musthafa

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Purpose: Candidemia was associated with high mortality in the critically ill patients. Early candidemia prediction is imperative for preemptive antifungal treatment. This study aimed to externally validate the candidemia risk prediction scores by Jameran et al. (2021) by identifying risk factors of acute kidney injury, renal replacement therapy, parenteral nutrition, and multifocal candida colonization. Methods: This single-center, retrospective observational study included all critically ill patients admitted to the intensive care unit (ICU) in a tertiary referral center from January 2018 to December 2023. The study evaluated the candidemia risk prediction score performance by analysing the occurrence of candidemia within the study period. Patients’ demographic characteristics, comorbidities, SOFA scores, and ICU outcomes were analyzed. Patients who were diagnosed with candidemia prior to ICU admission were excluded. Results: A total of 500 patients were analyzed with 2 dropouts due to incomplete data. Validation analysis showed that the candidemia risk prediction score has a sensitivity of 75.00% (95% CI: 59.66-86.81), specificity of 65.35% (95% CI: 60.78-69.72), positive predictive value of 17.28, and negative predictive value of 96.44. The incidence of candidemia was 8.86%, with no significant differences in demographics or comorbidities except for higher SOFA scoring in the candidemia group. The candidemia group showed significantly longer ICU, hospital LOS, and higher ICU in-hospital mortality. Conclusion: This study concluded the candidemia risk prediction score by Jameran et al. (2021) had good sensitivity and a high negative prediction value. Thus, the risk prediction score was validated for candidemia prediction in critically ill patients.

Keywords: Candidemia, intensive care, acute kidney injury, clinical prediction rule, incidence

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Authors: Skyler Kim

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An early diagnosis of leukemia has always been a challenge to doctors and hematologists. On a worldwide basis, it was reported that there were approximately 350,000 new cases in 2012, and diagnosing leukemia was time-consuming and inefficient because of an endemic shortage of flow cytometry equipment in current clinical practice. As the number of medical diagnosis tools increased and a large volume of high-quality data was produced, there was an urgent need for more advanced data analysis methods. One of these methods was the AI approach. This approach has become a major trend in recent years, and several research groups have been working on developing these diagnostic models. However, designing and implementing a leukemia diagnostic system in real clinical environments based on a deep learning approach with larger sets remains complex. Leukemia is a major hematological malignancy that results in mortality and morbidity throughout different ages. We decided to select acute lymphocytic leukemia to develop our diagnostic system since acute lymphocytic leukemia is the most common type of leukemia, accounting for 74% of all children diagnosed with leukemia. The results from this development work can be applied to all other types of leukemia. To develop our model, the Kaggle dataset was used, which consists of 15135 total images, 8491 of these are images of abnormal cells, and 5398 images are normal. In this paper, we design and implement a leukemia diagnostic system in a real clinical environment based on deep learning approaches with larger sets. The proposed diagnostic system has the function of detecting and classifying leukemia. Different from other AI approaches, we explore hybrid architectures to improve the current performance. First, we developed two independent convolutional neural network models: VGG19 and ResNet50. Then, using both VGG19 and ResNet50, we developed a hybrid deep learning architecture employing transfer learning techniques to extract features from each input image. In our approach, fusing the features from specific abstraction layers can be deemed as auxiliary features and lead to further improvement of the classification accuracy. In this approach, features extracted from the lower levels are combined into higher dimension feature maps to help improve the discriminative capability of intermediate features and also overcome the problem of network gradient vanishing or exploding. By comparing VGG19 and ResNet50 and the proposed hybrid model, we concluded that the hybrid model had a significant advantage in accuracy. The detailed results of each model’s performance and their pros and cons will be presented in the conference.

Keywords: acute lymphoblastic leukemia, hybrid model, leukemia diagnostic system, machine learning

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Authors: Michael R. Shurin, Galina Shurin, Vladimir A. Kirichenko

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Background. Visibility of hepatic malignancies is poor on non-contrast imaging for daily verification of liver malignancies prior to radiation therapy on MRI-guided Linear Accelerators (MR-Linac). Ferumoxytol® (Feraheme, AMAG Pharmaceuticals, Waltham, MA) is a SPION agent that is increasingly utilized off-label as hepatic MRI contrast. This agent has the advantage of providing a functional assessment of the liver based upon its uptake by hepatic Kupffer cells proportionate to vascular perfusion, resulting in strong T1, T2 and T2* relaxation effects and enhanced contrast of malignant tumors, which lack Kupffer cells. The latter characteristic has been recently utilized for MRI-guided radiotherapy planning with precision targeting of liver malignancies. However potential radiotoxicity of SPION has never been addressed for its safe use as an MRI-contrast agent during liver radiotherapy on MRI-Linac. This study defines the radiomodulating properties of SPIONs in vitro on human monocyte and macrophage cell lines exposed to 60Go gamma-rays within clinical radiotherapy dose range. Methods. Human monocyte and macrophages cell line in cultures were loaded with a clinically relevant concentration of Ferumoxytol (30µg/ml) for 2 and 24 h and irradiated to 3Gy, 5Gy and 10Gy. Cells were washed and cultured for additional 24 and 48 h prior to assessing their phenotypic activation by flow cytometry and function, including viability (Annexin V/PI assay), proliferation (MTT assay) and cytokine expression (Luminex assay). Results. Our results reveled that SPION affected both human monocytes and macrophages in vitro. Specifically, iron oxide nanoparticles decreased radiation-induced apoptosis and prevented radiation-induced inhibition of human monocyte proliferative activity. Furthermore, Ferumoxytol protected monocytes from radiation-induced modulation of phenotype. For instance, while irradiation decreased polarization of monocytes to CD11b+CD14+ and CD11bnegCD14neg phenotype, Ferumoxytol prevented these effects. In macrophages, Ferumoxytol counteracted the ability of radiation to up-regulate cell polarization to CD11b+CD14+ phenotype and prevented radiation-induced down-regulation of expression of HLA-DR and CD86 molecules. Finally, Ferumoxytol uptake by human monocytes down-regulated expression of pro-inflammatory chemokines MIP-1α (Macrophage inflammatory protein 1α), MIP-1β (CCL4) and RANTES (CCL5). In macrophages, Ferumoxytol reversed the expression of IL-1RA, IL-8, IP-10 (CXCL10) and TNF-α, and up-regulates expression of MCP-1 (CCL2) and MIP-1α in irradiated macrophages. Conclusion. SPION agent Ferumoxytol increases resistance of human monocytes to radiation-induced cell death in vitro and supports anti-inflammatory phenotype of human macrophages under radiation. The effect is radiation dose-dependent and depends on the duration of Feraheme uptake. This study also finds strong evidence that SPIONs reversed the effect of radiation on the expression of pro-inflammatory cytokines involved in initiation and development of radiation-induced liver damage. Correlative translational work at our institution will directly assess the cyto-protective effects of Ferumoxytol on human Kupfer cells in vitro and ex vivo analysis of explanted liver specimens in a subset of patients receiving Feraheme-enhanced MRI-guided radiotherapy to the primary liver tumors as a bridge to liver transplant.

Keywords: superparamagnetic iron oxide nanoparticles, radioprotection, magnetic resonance imaging, liver

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Authors: M. Iqbal Hossain, Azharul Islam Khan, S. M. Rafiqul Islam, Tahmeed Ahmed

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Objective: Moderate acute malnutrition (MAM) is a major cause of morbidity and mortality in under-5 children of low-income countries. Approximately 14.6% of all under-5 mortality worldwide is attributed to MAM with >3 times increased risk of death compared to well-nourished peers. Prevalence of MAM among under-5 children in Bangladesh is ~12% (~1.7 million). Providing a diet containing adequate nutrients is the mainstay of treatment of children with MAM. It is now possible to process fish into fish peptides with longer shelf-life without refrigerator, known as ‘Fish Surimi peptide’ and this could be an attractive alternative to supply fish protein in the diet of children in low-income countries like Bangladesh. We conducted this study to assess the acceptability of Fish Surimi peptide given with various foods/meals in 2-5 years old children with MAM. Design/methods: Fish Surimi peptide is broken down from white fish meat using plant-derived enzyme and the ingredient is just fish meat consisted of 20 different kinds of amino acids including nine essential amino acids. In a convenience sample of 34 children we completed the study ward of Dhaka Hospital of icddr,b in Bangladesh during November 2014 through February 2015. For each child the study was for two consecutive days: i.e. direct observation of food intake of two lunches and two suppers. In a randomly and blinded manner and cross over design an individual child received Fish Surimi peptide (5g at lunch and 5g at supper) mixed meal [e.g. 30g rice and 30g dahl (thick lentil soup) or 60g of a vegetables-lentil-rice mixed local dish known as khichuri in one day and the same meal on other day without any Fish Surimi peptide. We observed the completeness and eagerness of eating and any possible side effect (e.g. allergy, vomiting, diarrhea etc.) over these two days. Results: The mean±SD age of the enrolled children was 38.4±9.4 months, weight 11.22±1.41 kg, height 91.0±6.3 cm, and WHZ was -2.13±0.76. Their mean±SD total feeding time (minutes) for lunch was 25.4±13.6 vs. 20.6±11.1 (p=0.130) and supper was 22.3±9.7 vs. 19.7±11.2 (p=0.297), and total amount (g) of food eaten in lunch and supper was found similar 116.1±7.0 vs. 117.7±8.0 (p=3.01) in A (Fish Surimi) and B group respectively. Score in Hedonic scale by mother on test of food given to children at lunch or supper was 3.9±0.2 vs. 4.0±0.2 (p=0.317) and on overall acceptance (including the texture, smell, and appearance) of food at lunch or supper was 3.9±0.2 vs. 4.0±0.2 (p=0.317) for A and B group respectively. No adverse event was observed in any food group during the study period. Conclusions: Fish Surimi peptide may be a cost effective supplementary food, which should be tested by appropriately designed randomized community level intervention trial both in wasted children and stunted children.

Keywords: protein-energy malnutrition, moderate acute malnutrition, weight-for-height z-score, mid upper arm circumference, acceptability, fish surimi peptide, under-5 children

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