Search results for: Acute Inflammatory Demyelinating Polyneuropathy

Authors: Patompong Satapornpong, Therdpong Tempark, Pawinee Rerknimitr, Jettanong Klaewsongkram, Chonlaphat Sukasem

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Dapsone (4, 4’-diaminodiphenyl sulfone, DDS) is broadly used for the treatment of inflammatory diseases and infections such as; leprosy, Pneumocystis jiroveci pneumonia in patients with HIV infection, neutrophilic dermatoses, dermatitis herpetiformis and autoimmune bullous disease. The severe cutaneous adverse drug reactions (SCARs) including, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) are rare but severe life-threatening adverse drug reactions. Dapsone is one of many culprit drugs induced SJS, TEN and DRESS. Notwithstanding, to our knowledge, there are no studies of the association of HLA class I alleles and dapsone-induced SCARs in non-leprosy Thai patients. This investigation was a prospective cohort study, which performed in a total of 45 non-leprosy patients. Fifteen patients of dapsone-induced SCARs were classified as following the RegiSCAR criteria, and 30 dapsone-tolerant controls were exposed to dapsone more than 6 months without any evidence of cutaneous reactions. The genotyping of HLA-A, -B and –C were performed using sequence-specific oligonucleotides (PCR-SSOs). The Ethics Committee of Ramathibodi hospital, Mahidol University, approved this study. Among all HLA class I alleles, HLA-A*24:07, HLA-B*13:01, HLA-B*15:02, HLA-C*03:04 and HLA-C*03:09 were significantly associated with dapsone-induced SCARs (OR = 10.55, 95% CI = 1.06 – 105.04, p = 0.0360; OR = 56.00, 95% CI = 8.27 – 379.22, p = 0.0001; OR = 7.00, 95% CI = 1.17 – 42.00, p = 0.0322; OR = 6.00, 95% CI = 1.24 – 29.07, p = 0.0425 and OR = 17.08, 95% CI = 0.82 – 355.45, p = 0.0321, respectively). Furthermore, HLA-B*13:01 allele had strong association with dapsone-induced SJS-TEN and DRESS when compared with dapsone-tolerant controls (OR = 42.00, 95% CI = 2.88 – 612.31, p = 0.0064 and OR = 63.00, 95% CI = 7.72 – 513.94 and p = 0.0001, respectively). Consequently, HLA-B*13:01 might serve as a pharmacogenetic marker for screening before initiating the therapy with dapsone for prevention of dapsone-induced SCARs.

Keywords: dapsone-induced SCARs, HLA-B*13:01, HLA class I alleles, severe cutaneous adverse reactions, Thai

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Authors: Suraj Muke, Vikas Mankumare, Sadhana Sathaye

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Osteoporosis is the most common metabolic bone disease which affects an estimated 25 million people worldwide, leading to 1 million fractures, 40,000 annual deaths and health costs of billions of dollars. It is estimated that about 80% of total osteoporosis patients are women, amongst which majority are above the age of 45 years. Postmenopausal osteoporosis is associated with lack of intestinal calcium absorption, increasing pro-oxidant and inflammatory mediators. Lawsonia inermis is a biennial dicotyledonous herbaceous shrub is reported to possess a high flavonoid, high phenolic and Inhibitors of osteoclastogenesis like Daphneside and Daphnorin. The present study aimed to screen osteoprotective effect of methanolic extract of Lawsonia inermis (LIM) in rat model along with its antioxidant activity. LIM shows phenolic content 146.3Milligrams of Gallic acid equivalent present per gram of extract and 19.8 Milligrams of rutin per gram of extract of Total flavonoid content with IC50 value 42.99μg/ml. bilateral ovariectomized rat model in which Healthy female wistar rats were used for screening. Treatment with LIM was carried out using graded doses of 25mg/kg, 50mg/kg and 100mg/kg for period of 28 days. The negative control group comprised of ovariectomized rats along with saline treatment for four weeks whereas sham operated rats were used as positive control.LIM showed a decrease in bone turnover by preventing loss of urinary calcium and phosphorous moreover it decreased the alkaline phosphatase levels and loss of bone density is prevented by LIM suggesting decrease in osteoclast activity.

Keywords: antioxidant, osteoclast, osteoporosis, ovariectomized

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Authors: Nalan Kaya, Elif Erdem, Mehmet Ali Kisacam, Gonca Ozan, Enver Ozan

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Tobacco smokers continuously inhale thousands of carcinogens and free radicals. It is estimated that about 1017 oxidant molecules are present in each puff of tobacco smoke. It is known that smoking has adverse effects on the structure and functions of the liver. Ellagic acid (EA) has antioxidant, antiapoptotic, anticarcinogenic, antibacterial and antiinflammatory effects. The aim of our study was to investigate the possible protective effect of ellagic acid against tobacco smoke-mediated oxidative stress in the rat liver. 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, and liver tissues were removed. Histological and biochemical analyzes were performed. Sinusoidal dilatation, inflammatory cell infiltration in portal area, increased Kuppfer cells were examined in tobacco smoke group and tobacco smoke+ corn oil groups. The results, observed in tobacco smoke and tobacco smoke+corn oil groups, were found significantly decreased in tobacco smoke+EA group. Group-II and group-III MDA levels were significantly higher, and GSH activities were not different than group-I. Compared to group-II, group-IV MDA level was decreased, and GSH activities was increased significantly. The results indicate that ellagic acid could protect the liver tissue from the tobacco smoke harmful effects.

Keywords: ellagic acid, liver, rat, tobacco smoke

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Authors: G. A. Ravishankar, A. Ramakrishna

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Melatonin (MEL) and Serotonin (SER), also known as [5-Hydroxytryptamine (5-HT)] are reported to be in a range of plant types which are edible. Their occurrence in plants species appears to be ubiquitous. Their presence in high quantities in plants assumes significance owing to their physiological effects upon consumption by human beings. MEL is a well known animal hormone mainly released by the pineal gland known to influence circadian rhythm, sleep, apart from immune enhancement. Similarly, SER is a neurotransmitter that regulates mood, sleep and anxiety in mammals. It is implicated in memory, behavioral changes, scavenging reactive oxygen species, antipsychotic, etc. Similarly Role of SER and MEL in plant morphogenesis, and various physiological processes through intense research is beginning to unfold. These molecules are in common foods viz banana, pineapple, plum, nuts, milk, grape wine. N- Feruloyl serotonin and p-coumaroyl serotonin found in certain seeds are found to possess antioxidant, anti-inflammatory, antitumor, antibacterial, and anti-stress potential apart from reducing depression and anxiety. MEL is found in Mediterranean diets, nuts, cherries, tomato berries, and olive products. Consumption of foods rich in MEL is known to increase blood MEL levels which have been implicated in protective effect against cardiovascular damage, cancer initiation and growth. MEL is also found in wines, green tea, beer, olive oil etc. Moreover, presence of SER and MEL in Coffee beans (green and roasted beans) and decoction has been reported us. In this communication we report the occurrence of indole amines in edible plants and their implications in human health.

Keywords: serotonin, melatonin, edible plants, neurotransmitters, physiological effects

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Authors: Mohammad Akbar Paiman, Yasmin Nadeem Parpio, Naureen Akbarali, Khwaja Mir Islam Saeed, Murad Moosa Khan

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Background: Gender-based violence (GBV) is widely considered a significant public health problem that is associated with acute morbidity and mortality. GBV is commonly understood as a physical, sexual, and mental assault from intimate partners, sexual violence by non-partners, sexual assault of girls, and acts like trafficking women for sex. Objective: This study aimed to determine the factors associated with injuries and trauma among victims of GBV in Afghanistan. Method: We conducted a record-based analysis of the data collected by the Gender Department of the Family Protection Centre nationally between November 2013 and October 2019. Cross-tabulation between different variables such as age, sex, marital status, and type of violence and associations between different types of violence, age, gender, and geographical location was determined using the logistic regression model. Results: During the study period, there were a total of 58,160 GBV in Afghanistan. Most of the victims were women 98% with over three-quarters being adults 78%. Most of the victims were married 76%, followed by single 14%, widowed 5%, and engaged 5%. Over three-quarters of the violence, 73% was observed in the victim’s house while nearly one-quarter of the violence 24 % occurred in the perpetrator’s house. Conclusions: GBV is a significant public health problem in Afghanistan that needs to be addressed at multiple levels including policy, state, and community as well as by raising public awareness and education and a strong code of conduct against GBV by all stakeholders.

Keywords: gender-based violence, physical and psychological violence, injuries, Afghanistan

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Authors: Chengbin Wang, Li Lu, Luodan Suo, Qinghai Wang, Fan Yang, Xu Wang, Mona Marin

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Background: Two-dose varicella vaccination has been recommended in Beijing since November 2012. We investigated a varicella outbreak in a highly vaccinated elementary school population to examine transmission patterns and risk factors for vaccine failure. Methods: A varicella case was defined as an acute generalized maculopapulovesicular rash without other apparent cause in a student attending the school from March 28 to May 17, 2015. Breakthrough varicella was defined as varicella >42 days after last vaccine dose. Vaccination information was collected from immunization records. Information on prior disease and clinical presentation was collected via survey of students’ parents. Results: Of the 1056 school students, 1028 (97.3%) reported no varicella history, of whom 364 (35.4%) had received 1-dose and 650 (63.2%) had received 2-dose varicella vaccine, for 98.6% school-wide vaccination coverage with ≥ 1 dose before the outbreak. A total of 20 cases were identified for an overall attack rate of 1.9%. The index case was in a 2-dose vaccinated student who was not isolated. The majority of cases were breakthrough (19/20, 95%) with attack rates of 7.1% (1/14), 1.6% (6/364) and 2.0% (13/650) among unvaccinated, 1-dose, and 2-dose students, respectively. Most cases had < 50 lesions (18/20, 90%). No difference was found between 1-dose and 2-dose breakthrough cases in disease severity or sociodemographic factors. Conclusion: Moderate 2-dose varicella vaccine coverage was insufficient to prevent a varicella outbreak. Two-dose breakthrough varicella is still contagious. High 2-dose varicella vaccine coverage and timely isolation of ill persons might be needed for varicella outbreak control in the 2-dose era.

Keywords: varicella, outbreak, breakthrough varicella, vaccination

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Authors: Mohammad Bagher Heidari, Hefzollah Mohammadian

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TETRA (Terrestrial Trunked Radio) is a digital radio communication standard, which has been implemented in several different parts of the gas refinery ninth (phase 12th) by South Pars Gas Complex. Studies on possible impacts on the users' health considering different exposure conditions are missing. Objectives: To investigate possible acute effects of electromagnetic fields (EMF) of two different levels of TETRA hand-held transmitter signals on cognitive function and well-being in healthy young males. Methods: In the present double-blind cross-over study possible effects of short-term (2.5 h) EMF exposure of handset-like signals of TETRA (450 - 470 MHz) were studied in 30 healthy male participants (mean ± SD: 25.4 ±2.6 years). Individuals were tested on nine study days, on which they were exposed to three different exposure conditions (Sham, TETRA 1.5 W/kg and TETRA 10.0 W/kg) in a randomly assigned and balanced order. Participants were tested in the afternoon at a fixed timeframe. Results: Attention remained unchanged in two out of three tasks. In the working memory, significant changes were observed in two out of four subtasks. Significant results were found in 5 out of 35 tested parameters, four of them led to an improvement in performance. Mood, well-being and subjective somatic complaints were not affected by TETRA exposure. Conclusions: The results of the present study do not indicate a negative impact of a short-term EMF- effect of TETRA on cognitive function and well-being in healthy young men.

Keywords: TETRA (terrestrial trunked radio), electromagnetic fields (EMF), mobile telecommunication health research (MTHR), antenna

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Authors: Addisu Tadesse Sahile, Tennyson Mgutshini

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Background: Periodontal disease is a common, complex, inflammatory disease characterized by the destruction of tooth-supporting soft and hard tissues of the periodontium and a major public health problem across developed and developing countries. Objectives: The study was aimed at assessing the prevalence of periodontal disease and associated factors among diabetes patients in Addis Ababa, Ethiopia, 2018. Methods: Institutional based cross-sectional study was conducted on 388 diabetes patients selected by systematic random sampling method from March to May 2018. The study was conducted at two conveniently selected public hospitals in Addis Ababa. Data were collected with pre-tested, structured and translated questionnaire then entered to SPSS version 23 software for analysis. Descriptive statistics as a summary, in line with chi-square and binary logistics regression to identify factors associated with periodontal disease, were applied. A 95% CI with a p-value less than 5% was used as a level of significance. Results: Ninety-one percent (n=353) of participants had periodontal disease while oral examination was done in six regions. While only 9% (n=35) of participants were free of periodontal disease. The number of tooth brushings per day, correct techniques of brushing, malocclusion, and fillings that are defective were associated with periodontal disease at p < 0.05. Conclusion and recommendation: A higher prevalence of periodontal disease among diabetes patient was observed. The frequency of tooth brushing, correct techniques of brushing, malocclusion and defective fillings were associated with periodontal disease. Emphasis has to be given to oral health of diabetes patients by every concerned body so as to control the current higher burden of periodontal disease in diabetes.

Keywords: periodontal disease, risk factors, diabetes mellitus, Addis Ababa

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Authors: Krishna Pal Singh, Shailendra Kumar Gupta, Olaf Wolkenhauer

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Background: Our study aimed to identify common genes and potential targets across the four diseases, which include rheumatoid arthritis, melanoma metastasis, ulcerative colitis, and Crohn’s disease. We used a network and systems biology approach to identify the hub gene, which can act as a potential target for all four disease conditions. The regulatory network was extracted from the PPI using the MCODE module present in Cytoscape. Our objective was to investigate the significance of hub genes in these diseases using gene ontology and KEGG pathway enrichment analysis. Methods: Our methodology involved collecting disease gene-related information from DisGeNET databases and performing protein-protein interaction (PPI) network and core genes screening. We then conducted gene ontology and KEGG pathway enrichment analysis. Results: We found that IL6 plays a critical role in all disease conditions and in different pathways that can be associated with the development of all four diseases. Conclusions: The theoretical importance of our research is that we employed various systems and structural biology techniques to identify a crucial protein that could serve as a promising target for treating multiple diseases. Our data collection and analysis procedures involved rigorous scrutiny, ensuring high-quality results. Our conclusion is that IL6 plays a significant role in all four diseases, and it can act as a potential target for treating them. Our findings may have important implications for the development of novel therapeutic interventions for these diseases.

Keywords: melanoma metastasis, rheumatoid arthritis, inflammatory bowel diseases, integrated bioinformatics analysis

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Authors: Surbhi Aggarwal, Jaishree Paul

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Background: Role of GABA has been implicated in autoimmune diseases like multiple sclerosis, type1 diabetes and rheumatoid arthritis where they modulate the immune response but role in gut inflammation has not been defined. Ulcerative colitis (UC) and diarrhoeal predominant irritable bowel syndrome (IBS-D) both involve inflammation of gastrointestinal tract. UC is a chronic, relapsing and idiopathic inflammation of gut. IBS is a common functional gastrointestinal disorder characterised by abdominal pain, discomfort and alternating bowel habits. Mild inflammation is known to occur in IBS-D. Aim: Aim of this study was to investigate the role of GABA in UC as well as in IBS-D. Materials and methods: Blood and biopsy samples from UC, IBS-D and controls were collected. ELISA was used for measuring level of GABA in serum of UC, IBS-D and controls. RT-PCR analysis was done to determine GABAergic signal system in colon biopsy of UC, IBS-D and controls. RT-PCR was done to check the expression of proinflammatory cytokines. CurveExpert 1.4, Graphpad prism-6 software were used for data analysis. Statistical analysis was done by unpaired, two-way student`s t-test. All sets of data were represented as mean± SEM. A probability level of p < 0.05 was considered statistically significant. Results and conclusion: Significantly decreased level of GABA and altered GABAergic signal system was detected in UC and IBS-D as compared to controls. Significantly increased expression of proinflammatory cytokines was also determined in UC and IBS-D as compared to controls. Hence we conclude that insufficient level of GABA in UC and IBS-D leads to overproduction of proinflammatory cytokines which further contributes to inflammation. GABA may be used as a promising therapeutic target for treatment of gut inflammation or other inflammatory diseases.

Keywords: diarrheal predominant irritable bowel syndrome, γ-aminobutyric acid (GABA), inflammation, ulcerative colitis

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Authors: Mohadese Hashemi, Elham Akhoundi Kharanaghi, Fatemeh Haghiralsadat, Mojgan Yazdani, Omid Javani, Mahboobe Sharafodini, Davood Rajabi

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Niosomes are non-ionic surfactant vesicles in aqueous media resulting in closed bilayer structures that can be used as carriers of hydrophilic and hydrophobic compounds. The use of niosomes for encapsulation of essential oils (EOs) is an attractive new approach to overcome their physicochemical stability concerns include sensibility to oxygen, light, temperature, and volatility, and their reduced bioavailability which is due to low solubility in water. EOs are unstable and fragile volatile compounds which have strong interest in pharmaceutical due to their medicinal properties such as antiviral, anti-inflammatory, antifungal, and antioxidant activities without side effects. Trachyspermum copticum (ajwain) is an annual aromatic plant with important medicinal properties that grows widely around Mediterranean region and south-west Asian countries. The major components of the ajwain oil were reported as thymol, γ-terpinene, p-cymene, and carvacrol which provide antimicrobial and antioxidant activity. The aim of this work was to formulate ajwain essential oil-loaded niosomes to improve water solubility of natural product and evaluate its physico-chemical features and stability. Ajwain oil was obtained through steam distillation using a clevenger-type apparatus and GC/MS was applied to identify the main components of the essential oil. Niosomes were prepared by using thin film hydration method and nanoparticles were characterized for particle size, dispersity index, zeta potential, encapsulation efficiency, in vitro release, and morphology.

Keywords: trachyspermum copticum, ajwain, niosome, essential oil, encapsulation

Procedia PDF Downloads 481

Authors: Azizollah Khodakaram- Tafti, Ali Mohammadi, Ghasem Farjanikish

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Bovine viral diarrhea virus (BVDV) is one of the most important viral pathogens of cattle worldwide caused by Pestivirus genus, Flaviviridae family.The aim of the present study was to comparison several diagnostic methods and determine the prevalence of BVDV infection for the first time in dairy herds of Fars province, Iran. For initial screening, a total of 400 blood samples were randomly collected from 12 industrial dairy herds and analyzed using reverse transcription (RT)-PCR on the buffy coat. In the second step, blood samples and also ear notch biopsies were collected from 100 cattle of infected farms and tested by antigen capture ELISA (ACE), RT-PCR and immunohistochemistry (IHC). The results of nested RT-PCR (outer primers 0I100/1400R and inner primers BD1/BD2) was successful in 16 out of 400 buffy coat samples (4%) as acute infection in initial screening. Also, 8 out of 100 samples (2%) were positive as persistent infection (PI) by all of the diagnostic tests similarly including RT-PCR, ACE and IHC on buffy coat, serum and skin samples, respectively. Immunoreactivity for bovine BVDV antigen as brown, coarsely to finely granular was observed within the cytoplasm of epithelial cells of epidermis and hair follicles and also subcutaneous stromal cells. These findings confirm the importance of monitoring BVDV infection in cattle of this region and suggest detection and elimination of PI calves for controlling and eradication of this disease.

Keywords: antigen capture ELISA, bovine viral diarrhea virus, immunohistochemistry, RT-PCR, cattle

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Authors: Emmanuel Ademola Anigilaje, Ibraheem Ishola

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Background: Childhood steroid-sensitive idiopathic nephrotic syndrome (SSINS) is plagued with relapses that contribute to its morbidity and the cost of treatment. Materials and Methods: This is a retrospective review of relapses among children with SSINS at the University of Abuja Teaching Hospital from January 2016 to July 2020. Triggers related to relapse incidents were noted. Chi-square test was deployed for predictors (factors at the first clinical presentations that associate with subsequent relapses) of relapses. Predictors with p-values of less than 0.05 were considered significant and 95% confidence intervals (CI) and odd ratio (OR) were described. Results: Sixty SSINS comprising 52 males (86.7%), aged 23 months to 18 years, with a mean age of 7.04±4.16 years were studied. Thirty-eight (63.3%) subjects had 126 relapses including infrequent relapses in 30 (78.9%) and frequent relapses in 8 (21.1%). The commonest triggers were acute upper respiratory tract infections (68, 53.9%) and urinary tract infections (UTIs) in 25 (19.8%) relapses. In 4 (3.2%) relapses, no trigger was identified. The time-to-first relapse ranged 14 days to 365 days with a median time of 60 days. The significant predictors were hypertension (OR=3.4, 95% CI; 1.04-11.09, p=0.038), UTIs (OR=9.9, 95% CI; 1.16-80.71, p= 0.014), malaria fever (OR=8.0, 95% CI; 2.45-26.38, p˂0.001), micro-haematuria (OR=4.9, 95% CI; 11.58-15.16, p=0.004), elevated serum creatinine (OR=12.3, 95%CI; 1.48-101.20, p=0.005) and hypercholesterolaemia (OR=4.1, 95%CI; 1.35-12.63, p=0.011). Conclusion: While the pathogenesis of relapses remains unknown, it is prudent to consider relapse-specific preventive strategies against triggers and predictors of relapses in our setting.

Keywords: Patterns, triggers, predictors, steroid-sensitive idiopathic nephrotic syndrome, relapses, Nigeria

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Authors: Abhilasha Dadhich, Manisha Mathur, Sanjay Kumar, Hemant Dadhich

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The camel (Camelus dromedarius) is an important animal component of the fragile desert eco-system of India. Apart from others, impaired milk and meat production decrease in performance and even death are some of the major consequences of parasitic disease like coccidiosis in camel. Coccidiosis which is an acute invasion and destruction of intestinal mucosa by protozoa of the genera Eimeria or isospora spp. Post-Mortem examinations of 5 carcasses of dromedary of different age groups aged from 2 to 5 years were conducted. The history indicated that the camels were suffering from diarrhoea, dysentery, pyrexia, inappetence, weight loss, and emaciation. Post mortem examinations showed macroscopic and microscopic alterations in the small intestine, particularly in jejunum and ileum regions. The mucosae were congested, and haemorrhagic on which there were numerous whitish-grey nodular foci were observed. The affected intestinal tissue specimens were preserved in 10% formal saline and processed mechanically for paraffin embedding by acetone and benzene technique. The sections were stained with haematoxylin and eosin method of staining for histopathological examinations. Histologically, typical lesions such as congestion and haemorrhages were present. The intestinal villi were oedematous; mucosa degenerated and desquamated, along with infiltration of eosinophils and macrophages. Crypts of lieberkuhn were obliterated due to presence of schizonts in lamina propria. Older camels served as the source of spread of coccidial infection and were also predisposed to secondary infections.

Keywords: camel, coccidiosis, Eimeria, histopathology

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Authors: A. Erragh, K. Amanzoui, M. Elharit, H. Salem, M. Ababneh, K. Elfakhr, S. Kalouch, A. Chlilek

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Guillain-Barre syndrome (GBS) is the most common form of acute polyradiculoneuritis (PRNA). It is a medical emergency in pediatrics that requires rapid diagnosis and immediate assessment of the severity criteria for the implementation of appropriate treatment. Retrospective, descriptive study in 24 patients under the age of 18 who presented with GBS between September 2017 and July 2021 and were hospitalized in the multipurpose pediatric intensive care unit of the Abderrahim EL Harouchi children's hospital in Casablanca. The average age was 7.91 years, with extremes ranging from 18 months and 14 years and a male predominance of 75%. After a prodromal event, most often infectious (80%) and a free interval of 12 days on average, 2 types of motor disorders begin either hypo or arereflectic flaccid paralysis of the lower limbs (45.8%) or flaccid quadriplegia hypo or arereflectic (54.2%). During GBS, the most formidable complication is respiratory distress, which can occur at any time. In our study, respiratory impairment was observed in 70.8% of cases. In addition, other signs of severity, such as swallowing disorders (75%) and dysautonomic disorders (8.33%), were also observed, which justified care in the intensive care unit for all of our patients. The use of invasive ventilation was necessary in 76.5% of cases, and specific treatments based on immunoglobulins were administered in all our patients. Despite everything, the death rate remains high (25%) and is mainly due to complications related to hospitalization. Guillain Barré syndrome is, therefore, a pediatric emergency that requires rapid diagnosis and immediate assessment of severity criteria for the implementation of appropriate treatment.

Keywords: guillain barre syndrome, emergency, children, medical

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Authors: Tella Toluwani, Adegbegi Ademuyiwa, Musei Chiedu, Adekunle Odola, Ayangbenro Ayansina, Adaramoye Oluwatosin

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Dithiocarbamates are very useful biological agents with antioxidant properties. Diclofenac (DIC) is a non-steroidal analgesic, anti-inflammatory, and antipyretic agent. The use of diclofenac has been linked with reproductive toxicity/damage. The purpose of this study is (i) To investigate the therapeutic potential of diisopropyldithiocarbamate sodium salt (Na(i-Pr₂dtc)) and vitamin E (VIT E) against diclofenac induced toxicity in the testes of male Wistar rats. (ii) To investigate the effect of (Na(i-Pr₂dtc)) and vitamin E on ameliorating damage done to the testes through histological analysis of the testes. Thirty-six (36) male Wistar rats were used for the experiment, they were divided into six (6) groups, the animals in group 1 served as control, animals in groups 2, 3, 4, 5 and 6 received DIC only, DIC and (Na(i-Pr₂dtc)), DIC and VIT E, (Na(i-Pr₂dtc) only and VIT E only respectively. A single dose of 100 mg/kg body weight of DIC was administered to male Wistar rats, while 30 mg/kg body weight of (Na(i-Pr₂dtc)) was used to treat both normal and DIC treated animals, control animals were treated with the vehicle, after 24 hrs of treatment the animals were euthanized and the testes were removed for analysis. The treatment of rats with Na(i-Pr₂dtc) significantly restored catalase (CAT) activity depressed by diclofenac. (Na(i-Pr₂dtc)) also restored glutathione levels reduced by DIC treatment and this was also accompanied by reduced lipid peroxidation (LPO) level. VIT E significantly restored superoxide dismutase (SOD) activity when compared with DIC only treated animals. Photomicrographs of testes from (Na(i-Pr₂dtc)) treated rats showed seminiferous epithelium with no lesions. We conclude that (Na(i-Pr₂dtc)) has an antioxidant effect, which might be related to the dose and duration of administration.

Keywords: diisopropyldithiocarbamate sodium salt, diclofenac, vitamin E, testes

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Authors: Treder Natalia, Siemiński Mariusz

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Takotsubo cardiomyopathy (TC) is a recently defined clinical entity. First described by Japanese researchers, today is diagnosed worldwide in 1-2% of patients admitted with the preliminary diagnosis of Acute Coronary Syndrome. The etiology of takotsubo cardiomyopathy remains still largely unknown. Currently, the most likely cause of takotsubo is direct cytotoxicity caused by catecholamine surge triggered by emotional stress. There is a strong relation between recent severe emotional stress and TC. The aim of this study was to analysis the role of stress and personality as a risk factor of TT. The presented research involves 35 people who are diagnosed TC. All patients were women, mean age 60 years. The methods used in the research are popular psychological tests: Perceived Stress Scale, DS14 scale to measure type D personality, The Neo-Five Factor Inventory of Personality and psychological interview. The obtained results prove that stress events may directly precede or even release TC. The stressful events occurred directly before the symptoms in 75% examined. 65% assessed their family life as very stressful. Examiners have also a high level of experienced stress. Only 25% of the TC were classified as having type D personality but they have a high level of negative affectivity. The subjects had a high level of extraversion, openness to experiences and an average level of neuroticism. The results suggested that such a type of personality profile may predispose to the development of takotsubo cardiomyopathy. Patients with TT are the individuals who reveal joint tendency to the experience of negative emotions and very stressful family life.

Keywords: stress, personality trails, familiar problems, Takotsubo cardiomyopathy

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Authors: Saul Emilio Rivero Mejia, Estefanya Marin Tabares, Carlos Andres Rodriguez Toro, Katherine Bolano Restrepo, Sarita Santa Cortes

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Medellin is the Colombian city with the best public transportation system in the country, which is composed of two subway lines, five metro cables, two Bus Rapid Transit lines, and a streetcar. But despite the above, the Aburra Valley, the area in which the city is located, comparatively speaking, has a lower number of urban roads per inhabitant built, compared to the national average. In addition, since there is approximately one vehicle for every three inhabitants in Medellin, the problems of congestion and environmental pollution have become more acute over the years, and it has even been necessary to implement restrictive measures to the use of private vehicles on a permanent basis. In that sense, due to the limitations of physical space, the low public investment in road infrastructure, it is necessary to opt for mobility alternatives according to the above. Within the options for the city, there is what is known as micromobility. Micromobility is understood as those small and light means of transport used to travel short distances, which use electrical energy, such as skateboards and bicycles. These transport alternatives have a high potential for use by the city's young population, but this requires an adequate infrastructure and also state regulation. Taking into account the above, this paper will analyze the current state and future of micro mobility in the city of Medellin, making a prospective analysis, supported by a PEST (political, economic, social and technological) analysis. Based on the above, it is expected to identify the growth of demand for these alternative means and its impact on the mobility of the city in the medium and short term.

Keywords: electric, micromobility, transport, sustainable

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Authors: Yi-Hui Lai, Chih-Hsiang Yang, Li-Chung Hsu

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The inflammasome is a protein complex that modulates caspase-1 activity, resulting in proteolytic cleavage of proinflammatory cytokines such as IL-1β and IL-18, into their bioactive forms. It has been shown that the inflammasomes play a crucial role in the clearance of pathogenic infection and tissue repair. However, dysregulated inflammasome activation contributes to a wide range of human diseases such as cancers and auto-inflammatory diseases. Yet, regulation of NLRP3 inflammasome activation remains largely unknown. We discovered a novel DEAD box protein, whose biological function has not been reported, not only negatively regulates NLRP3 inflammasome activation by interfering NLRP3 inflammasome assembly and cellular localization but also mitigate pyroptosis upon pathogen evasion. The DEAD-box protein is the first DEAD-box protein gets involved in modulation of the inflammasome activation. In our study, we found that caspase-1 activation and mature IL-1β production were largely enhanced upon LPS challenge in the DEAD box-containing protein- deleted THP-1 macrophages and bone marrow-derived macrophages (BMDMs). In addition, this DEAD box-containing protein migrates from the nucleus to the cytoplasm upon LPS stimulation, which is required for its inhibitory role in NLRP3 inflammasome activation. The DEAD box-containing protein specifically interacted with the LRR motif of NLRP3 via its DEAD domain. Furthermore, due to the crucial role of the NLRP3 LRR domain in the recruitment of NLRP3 to mitochondria and binding to its adaptor ASC, we found that the interaction of NLRP3 and ASC was downregulated in the presence of the DEAD box-containing protein. In addition to the mechanical study, we also found that this DEAD box protein protects host cells from inflammasome-triggered cell death in response to broad-ranging pathogens such as Candida albicans, Streptococcus pneumoniae, etc., involved in nosocomial infections and severe fever shock. Collectively, our results suggest that this novel DEAD box molecule might be a key therapeutic strategy for various infectious diseases.

Keywords: inflammasome, inflammation, innate immunity, pyroptosis

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Authors: Pia Berner Hansson, Robert Murison Anders Lund, Hammar Åsa

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Major Depressive Disorder (MDD) is often associated with high levels of stress and disturbances in the Hypothalamic Pituitary Adrenal (HPA) system, yielding high levels of cortisol, in addition to cognitive dysfunction. Previous studies in this patient group have shown a relationship between cortisol profile and cognitive functioning in the acute phase of MDD and that the patients had significantly less suppression after dexamethasone administration. However, few studies have investigated this relationship over time and in phases of symptom reduction. The aim of the present study was to examine the relationships between cortisol levels after the Dexamethasone Suppression Test (DST) and cognitive function in a long term perspective in MDD patients. Patients meeting the DSM-IV criteria for a MDD were included in the study and tested in symptom reduction. A control group was included. Cortisol was measured in saliva collected with Salivette sampling devices. Saliva samples were collected 4 times during a 24 hours period over two consecutive days: at awakening, after 45 minutes, after 7 hours and at 11 pm. Dexamethasone (1.0 mg) was given on Day 1 at 11 pm. The neuropsychological test battery consisted of standardized tests measuring memory and Executive Functioning (EF). Cortisol levels did not differ significantly between patients and controls on Day 1 or Day 2. Both groups showed significant suppression after Dexamethasone. There were no correlations between cortisol levels or suppression after Dexamethasone and cognitive measures. The results indicate that the HPA-axis functioning normalizes in phases of symptom reduction in MDD patients and that there no relation between cortisol profile and cognitive functioning in memory or EF.

Keywords: depression, MDD, cortisol, suppression, cognitive functioning

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Authors: Senthil Rajan Dharmalingam, Shamala Nadaraju, Srinivasan Ramamurthy

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Doxorubicin is the most widely used anticancer drugs in chemotherapy treatment. However, problems related to the development of multidrug resistance (MDR) and acute cardiotoxicity have led researchers to investigate alternative forms of administering doxorubicin for cancer therapy. Several methods have been attempted to overcome MDR, including the co-administration of a chemosensitizer inhibiting the efflux caused by ATP binding cassette transporters with anticancer drugs, and the bypass of the efflux mechanism. Co encapsulation of doxorubicin (Dox) and cyclosporine A (CSA) into poly (DL-lactide-co-glycolide) nanoparticles was emulsification-solvent evaporation method using polyvinyl alcohol as emulsion stabilizers. The Dox-CSA loaded nanoparticles were evaluated for particle size, zeta potential and PDI by light scattering analysis and thermal characterizations by differential scanning calorimetry (DSC). Loading efficiency (LE %) and in-vitro dissolution samples were evaluated by developed and validated HPLC method. The optimum particle size obtained is 298.6.8±39.4 nm and polydispersity index (PDI) is 0.098±0.092. Zeta potential is found to be -29.9±4.23. Optimum pH to increase Dox LE% was found 7.1 which gave 42.5% and 58.9% increase of LE% for pH 6.6 and pH 8.6 compared respectively. LE% achieved for Dox is 0.07±0.01 % and CSA is 0.09±0.03%. Increased volume of PVA and weight of PLGA shows increase in size of nanoparticles. DSC thermograms showed shift in the melting peak for the nanoparticles compared to Dox and CSA indicating encapsulation of drugs. In conclusion, these preliminary studies showed the feasibility of PLGA nanoparticles to entrap Dox and CSA and require future in-vivo studies to be performed to establish its potential.

Keywords: doxorubicin, cyclosporine, PLGA, nanoparticles

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Authors: Swati Bhasin, Ali Ahmed, Valence Xavier, Ben Liu

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Aims: Diarrhea is a problem that is a frequent clinic referral to the gastroenterology and surgical team from the General practitioner. To establish a diagnosis, these patients undergo colonoscopy. The current practice at our district general hospital is to perform random left and right colonic biopsies. National guidelines issued by the British Society of Gastroenterology advise all patients presenting with chronic diarrhea should have an Ileoscopy as an indicator for colonoscopy completion. Our primary aim was to check if Terminal ileum (TI) biopsy is required to establish a diagnosis of inflammatory bowel disease (IBD). Methods: Data was collected retrospectively from November 2018 to November 2019. The target population were patients who underwent colonoscopies for diarrhea. Demographic data, endoscopic and histology findings of TI were assessed and analyzed. Results: 140 patients with a mean age of 57 years (19-84) underwent a colonoscopy (M: F; 1:2.3). 92 patients had random colonic biopsies taken and based on the histological results of these, 15 patients (16%) were diagnosed with IBD. The TI was successfully intubated in 40 patients, of which 32 patients had colonic biopsies taken as well. 8 patients did not have a colonic biopsy taken. Macroscopic abnormality in the TI was detected in 5 patients, all of whom were biopsied. Based on histological results of the biopsy, 3 patients (12%) were diagnosed with IBD. These 3 patients (100%) also had colonic biopsies taken simultaneously and showed inflammation. None of the patients had a diagnosis of IBD confirmed on TI intubation alone (where colonic biopsies were not done). None of the patients has a diagnosis of IBD confirmed on TI intubation alone (where colonic biopsies were negative). Conclusion: TI intubation is a highly-skilled, time-consuming procedure with a higher risk of perforation, which as per our study, has little additional diagnostic value in finding IBD for symptoms of diarrhea if colonic biopsies are taken. We propose that diarrhea is a colonic symptom; therefore, colonic biopsies are positive for inflammation if the diarrhea is secondary to IBD. We conclude that all of the IBDs can be diagnosed simply with colonic biopsies.

Keywords: biopsy, colon, IBD, terminal ileum

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Authors: Fariha Qureshi, Mohammad Tahir

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Epidemiological evidences indicated that arsenic contamination in drinking water increased the incidence of spontaneous abortion, stillbirth and premature babies in pregnant women. This study was designed to investigate the protective role of vitamin C&E against sodium arsenate induced fetal toxicity in albino mice. Twenty-four pregnant albino mice of BALB/c strain were randomly divided into 4 groups having 6 animals in each. Group A1 served as control and was injected with 0.1ml/kg/day distilled water I/P for 18 days. Groups A2,A3 & A4 received single I/P injection of sodium arsenate 35mg/kg on 8th gestational day, whereas groups A3 and A4 were also given Vitamin C and E by I/P injection, 9 mg/kg/day and 15 mg/kg/day respectively, starting from 8th GD and continued for the rest of the pregnancy period. The early implantation sites, fetal resorptions, weight of live fetuses and crown rump length were recorded. Gross morphological examination was carried out for malformations. Fetal kidneys were extracted for histological and micrometric analysis. Group A2 exhibited an increased incidence of abortion, fetal resorptions, significant decrease in number of litter and fetal weight; the difference of means was statistically significant among the groups (p<0.000). In group A2 fetal kidneys presented glomerulonephritis with acute tubular necrotic changes and interstitial fibrosis. Groups A3&A4 showed statistically significant improvement in these parameters. The results revealed the antioxidant potential of Vitamin C and E in protecting against arsenic induced fetal toxicity in mice.

Keywords: fetal toxicity, fetal resorptions, interstitial fibrosis, tocopherol

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Authors: Meltem Koray, Arda Ozgon, Duygu Ofluoglu, Mehmet Yaltirik

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Oral ulcerations can be seen as a side effect of different drugs. These ulcers usually appear within a few weeks following drug treatment. In most of cases, these ulcers resist to conventional treatments, such as anesthetics, antiseptics, anti-inflammatory agents, cauterization, topical tetracycline and corticosteroid treatment. The diagnosis is usually difficult, especially in patients receiving multiple drug therapies. Hyaluronan or hyaluronic acid (HA) is a biomaterial that has been introduced as an alternative approach to enhance wound healing and also used for oral ulcer treatment. The aim of this report is to present the treatment of drug-induced oral ulceration on maxillary mucosa with HA gel. 60-year-old male patient was referred to Department of Oral and Maxillofacial Surgery complaining of oral ulcerations during few weeks. He had received chemotherapy and radiotherapy in 2014 with the diagnosis of nasopharyngeal carcinoma, and he has accompanying systemic diseases such as; cardiological, neurological diseases and gout. He is medicated with Escitalopram (Cipralex® 20mg), Quetiapine (Seroquel® 100mg), Mirtazapine (Zestat® 15mg), Acetylsalicylic acid (Coraspin® 100mg), Ramipril-hydrochlorothiazide (Delix® 2.5mg), Theophylline anhydrous (Teokap Sr® 200mg), Colchicine (Colchicum Dispert® 0.5mg), Spironolactone (Aldactone® 100mg), Levothyroxine sodium (Levotiron® 50mg). He had painful oral ulceration on the right side of maxillary mucosa. The diagnosis was 'drug-induced oral ulceration' and HA oral gel (Aftamed® Oral gel) was prescribed 3 times a day for 2 weeks. Complete healing was achieved within 3 weeks without any side effect and discomfort. We suggest that HA oral gel is a potentially useful local drug which can be an alternative for management of drug-induced oral ulcerations.

Keywords: drug-induced, hyaluronic acid, oral ulceration, maxillary mucosa

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Authors: Tanveer Hussain, Misbah Hussain, Masroor Ellahi Babar, Muhammad Traiq Pervez, Fiaz Hussain, Sana Zahoor, Rashid Saif

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Interleukin 2 (IL-2) is a cytokine which is produced by activated T cells, play important role in immune response against antigen. It act in both autocrine and paracrine manner. It can stimulate B cells and various other phagocytic cells like monocytes, lymphokine-activated killer cells and natural killer cells. Acting in autocrine fashion, IL-2 protein plays a crucial role in proliferation of T cells. IL-2 triggers the release of pro and anti- inflammatory cytokines by activating several pathways. In present study, exon 1 of IL-2 gene of four local Pakistani breeds (Dera Din Panah, Beetal, Nachi and Kamori) from two provinces was amplified by using reported Ovine IL-2 primers, yielding PCR product of 501 bp. The sequencing of all samples was done to identify the polymorphisms in amplified region of IL-2 gene. Analysis of sequencing data resulted in identification of one novel nucleotide substitution (T→A) in amplified non-coding region of IL-2 gene. Comparison of IL-2 gene sequence of all four breeds with other goat breeds showed high similarity in sequence. While phylogenetic analysis of our local breeds with other mammals showed that IL-2 is a variable gene which has undergone many substitutions. This high substitution rate can be due to the decreased or increased changed selective pressure. These rapid changes can also lead to the change in function of immune system. This pioneering study of Pakistani goat breeds urge for further studies on immune system of each targeted breed for fully understanding the functional role of IL-2 in goat immunity.

Keywords: interleukin 2, mutational analysis, phylogeny, goat breeds, Pakistan

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Authors: Ankit Patil, Tushar D. Deshpande, Yogesh M. Nimdeo

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Pickering emulsions (PE) were developed in response to increased demand for organic, eco-friendly, and biocompatible products. These emulsions are usually stabilized by solid particles. In this research, we created chitosan-based sunflower oil-in-water (O/W) PE without the need for a surfactant. In our work, we employed chitosan, a biopolymer derived from chitin, as a stabilizer. This decision was influenced by chitosan's biocompatibility and biodegradability, as well as its anti-inflammatory and antibacterial capabilities. It also has other functional properties, such as antioxidant activity, a probiotic delivery mechanism, and the ability to encapsulate bioactive compounds. The purpose of this study was to govern key parameters that can be changed to obtain stable PE, such as the concentration of chitosan (0.3-0.5 wt.%), the concentration of oil (0.8-1 vol%), the pH of the emulsion (3-7) manipulated by the addition of 1M HCl/ 4M NaOH, and the amount of electrolyte (NaCl-0-300mM) added to increase or decrease ionic strength. A careful combination of these properties resulted in the production of the most stable and optimal PE. Particle size study found that emulsions with pH 6, 0.4% chitosan, and 300 mM salts were exceptionally stable, with droplet size 886 nm, PI of 0.1702, and zeta potential of 32.753.83 mV. It is fair to infer that when ionic strength rises, particle size, zeta potential, and PI value decrease. A lower PI value suggests that emulsion nanoparticles are more homogeneous. The addition of sodium chloride increases the ionic strength of the emulsion, facilitating the formation of more compact and ordered particle layers. These findings provide light on the creation of stimulus-responsive chitosan-based PE capable of encapsulating bioactive materials, functioning as antioxidants, and serving as food-grade emulsifiers.

Keywords: pickering emulsion, biocompatibility, eco-friendly, chitosan

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Authors: L. José, S. Vieira, E. Melo, A. R. Pinheiro

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Objectives: This study aims to characterize the stroke profile and the health care provided for people with a stroke in Luanda, Angola. Methods: A prospective longitudinal study was conducted at two Health centers, from March to November 2023, enrolling stroke patients. Data was gathered using a survey created by the researchers and validated by a health panel of experts from Angola. The analysis focused on demographic and stroke characteristics, as well as the care provided. Ethical approval and informed consent were obtained. Results: Preliminary results of a total of 186 patients are described, 122 from a Central Acute Care Hospital, with a mean age of 51.3±14.35 years old, a BMI of 26.7±4.15 kg/m2, 41% male, and 64 patients from a Rehabilitation Center, with 55.6±11.55 years old, a BMI of 27.0±3.8 kg/m2, 53% male. Ischemic stroke was reported as the most representative type in both centers (71.3% and 70.3%, respectively), though 100% of patients had no imaging diagnosis confirmation, neither data about the subtype was given. For patients admitted to the Hospital, discharge occurred before rehabilitation, and no follow-up was possible. No rehabilitation care was delivered in the first 7 days after the stroke. In the Rehabilitation Center, patient’s rehabilitation started in the late subacute phase, after a mean of 171.8±11.5 days. Conclusions: Stroke diagnosis lacks imaging confirmation, which is decisive for proper treatment, and rehabilitation starts during the late subacute phase, which is too late considering the international guidelines and the best window of opportunity for neuroplasticity and recovery. These results highlight the urgent need for the definition of Stroke-directed Health Care Policies in Angola.

Keywords: stroke, personalized health care, functional recovery, quality of life, health policies

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Authors: Aneta Binkowska, Grzegorz Michalak, Slawomir Pilip, Lukasz Bondaruk, Daniel Celinski, Robert Slotwinski

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Post-traumatic mortality rates are still very high and show an increasing tendency. Early identification of patients at high risk of severe complications has a significant impact on treatment outcomes. The aim of the study was to better understand the early pathological inflammatory response to injury and infection and to determine the usefulness of the assessment of TNF-α and sTNFR1 concentrations in the peripheral blood as early indicators of severe post-traumatic complications. The study was carried out in a group of 51 patients after trauma treated in the ED, including 32 patients that met inclusion criteria for immunological analysis. Patients were divided into two groups using the ISS scale (group A with ISS ≥20, group B with ISS <20). Serum levels of TNF-α and sTNFR1 were determined after admission to the ED and after 3, 6, 12 and 24 hours. The highest TNF-α and sTNFR1 concentrations in both groups were recorded at admission and were significantly higher in group A compared to group B (A vs B TNF-α 2.46 pg/ml vs 1.78 pg/ml; sTNFR1 1667.5 pg/ml vs 875.2 p<0.005). The concentration of sTNFR1 in patients with severe complications was significantly higher compared to patients without complications and preceded clinical symptoms of complications ( C+ vs C- 1561.5 pg/ml vs 930.6 pg/ml). Spearman's correlation showed a statistically significant positive correlation between the baseline concentrations of IL-6 (r=0.38, p<0.043) and sTNFR1 (r=0.59, p=0.001) and the ISS scores. The high diagnostic sensitivity calculated from the ROC (receiver operating characteristic) curves was found for the concentrations of both cytokines: TNF α (AUC=0.91, p=0.004) and sTNFR1 (AUC=0.86, p=0.011). Elevated levels of sTNFR1, determined in the peripheral blood shortly after injury, is significantly associated with the occurrence of later complications, which in some patients lead to death. In contrast, high levels of TNF-α shortly after injury are associated with high mortality.

Keywords: cytokine, SIRS, MODS, trauma

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Authors: John Michael Russo

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Honeybees are important to our food system and continue to suffer from high rates of colony loss. Precision feed has brought many benefits to livestock cultivation and these should transfer to apiculture. However, apiculture has unique challenges. The objective of this research is to understand how principles of precision agriculture, applied to apiculture and feed specifically, might effectively improve state-of-the-art cultivation. The methodology surveys apicultural practice to build a model for assessment. First, a review of apicultural motivators is made. Feed method is then evaluated. Finally, precision feed methods are examined as accelerants with potential to advance the effectiveness of feed practice. Six important motivators emerge: colony loss, disease, climate change, site variance, operational costs, and competition. Feed practice itself is used to compensate for environmental variables. The research finds that the current state-of-the-art in apiculture feed focuses on critical challenges in the management of feed schedules which satisfy requirements of the bees, preserve potency, optimize environmental variables, and manage costs. Many of the challenges are most acute when feed is used to dispense medication. Technology such as RNA treatments have even more rigorous demands. Precision feed solutions focus on strategies which accommodate specific needs of individual livestock. A major component is data; they integrate precise data with methods that respond to individual needs. There is enormous opportunity for precision feed to improve apiculture through the integration of precision data with policies to translate data into optimized action in the apiary, particularly through automation.

Keywords: precision agriculture, precision feed, apiculture, honeybees

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Authors: Sachin K. Samuchiwal, Barbara Balestrieri, Amanda Paskavitz, Hannah Raff, Joshua A. Boyce

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IL-33, a recently discovered member of the IL-1 cytokine family, binds to the TLR/IL1R super family receptor ST2 and induces type 2 immune responses. IL-33 is constitutively expressed in structural cells at barrier sites such as skin, lung, and intestine, and also inducibly expressed by hematopoietic cells including macrophages. Stimulation of macrophages by Lipopolysaccharide (LPS) can induce de novo IL-33 expression, and also causes the production of prostaglandin-E2 (PGE2) via cyclooxygenase (COX)-2 and microsomal PGE2 synthase-1 (mPGES-1). Because PGE2 can regulate macrophage functions through both autocrine and paracrine mechanisms, the potential interplay of endogenous PGE2 on IL-33 production was explored. Bone-marrow derived murine macrophages (bmMF) that lack either mPGES-1 or EP2 receptor expression were stimulated with LPS in the absence or presence of exogenous PGE2 along with pharmacological agonists and antagonists. The study results demonstrate that endogenous PGE2 markedly enhances LPS-induced IL-33 production by bmMFs via EP2 receptors. Moreover, exogenous PGE2 can amplify LPS-induced IL-33 expression dominantly by EP2 and partly by EP4 receptors by a pathway involving cAMP and exchange protein activated by cAMP (EPAC), but not protein kinase A (PKA). Though both IL-33 production and PGE2 generation in response to LPS require activation of both p38 MAPK and NF-κB, PGE2 did not influence this activation. In conclusion, it is demonstrated that endogenous PGE2 signaling through EP2 and EP4 receptors is a prerequisite for LPS-induced IL-33 production in bmMFs and the underlying cAMP mediated pathway involves EPAC. Since IL-33 is a critical pro-inflammatory cytokine in various pathological disorders, this PGE2-EP2/EP4-cAMP mediated pathway can be exploited to intervene in IL-33 driven pathologies.

Keywords: bone marrow macrophages, EPAC, IL-33, PGE2

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