Search results for: chronic liver disease

Authors: Howaida I. Abd-Alla, Nagwa M. M. Shalaby

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The fruit rind of Fortunella margarita (Nagami Kumkuat) was investigated for its chemical constituents. Thirteen metabolites were obtained and classified into, a sterol; β-sitosterol (1) and twelve phenolic compounds, three coumarins; xanthotoxin (2), isopimpinellin (3), umbelliferone (4), nine flavonoids of O-glycosides of flavone; apigenin-7-O-β-D-glucopyranoside (5), apigenin-7-O-rhamnoglucoside (rhoifolin) (6), C-glycosides; vitexin (7), vicenin II (8), and the methoxylated; 6-methoxyapigenin-7-methyl ether (9) and tangeretin (10) as well as flavanones class; naringenin (11), liquiritigenin (12), hesperdin (hesperetin-7-rhamnoglucoside) (13). All compounds were identified for the first time in F. margarita except compound (8). The major glycosides 5, 6, and 13 and total crude extract showed potential antiviral activity against live Newcastle disease virus vaccine strains (Komarov and LaSota) and live infectious bursitis viruses vaccine strain D78 replication in VERO cell cultures and on specific pathogen-free embryonated chicken eggs. Antiviral inhibitory concentration fifty (IC50), cytotoxic concentration fifty (CC50), and therapeutic index (TI) were calculated. In addition, the extract and compounds 7 and 13 showed marked antimicrobial activity against different strains of fungi, Gram-positive and negative bacteria, including some foodborne pathogens of animal origin, caused human disease. These results suggested that the extract of F. margarita may be considered potentially useful as a source of natural antiviral and antimicrobial agents. It can be used as an ingredient for functional food and/or pharmaceuticals.

Keywords: antimicrobial, antiviral, Fortunella margarita, Nagami Kumkuat, phenolic secondary metabolites

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Authors: Chao Li, Lei Zhou, Ruiqi Ren, Dan Li, Yali Wang, Daxin Ni, Zijian Feng, Qun Li

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Background: In 2016, yellow fever had been first ever discovered in China, soon after the yellow fever epidemic occurred in Angola. After the discovery, China had promptly made the national protocol of control and prevention and strengthened the surveillance on passenger and vector. In this study, a descriptive analysis was conducted to summarize China’s experiences of response towards this import epidemic, in the hope of providing experiences on prevention and control of yellow fever and other similar imported infectious diseases in the future. Methods: The imported cases were discovered and reported by General Administration of Quality Supervision, Inspection and Quarantine (AQSIQ) and several hospitals. Each clinically diagnosed yellow fever case was confirmed by real-time reverse transcriptase polymerase chain reaction (RT–PCR). The data of the imported yellow fever cases were collected by local Centers for Disease Control and Prevention (CDC) through field investigations soon after they received the reports. Results: A total of 11 imported cases from Angola were reported in China, during Angola’s yellow fever outbreak. Six cases were discovered by the AQSIQ, among which two with mild symptom were initiative declarations at the time of entry. Except for one death, the remaining 10 cases all had recovered after timely and proper treatment. All cases are Chinese, and lived in Luanda, the capital of Angola. 73% were retailers (8/11) from Fuqing city in Fujian province, and the other three were labors send by companies. 10 cases had experiences of medical treatment in Luanda after onset, among which 8 cases visited the same local Chinese medicine hospital (China Railway four Bureau Hospital). Among the 11 cases, only one case had an effective vaccination. The result of emergency surveillance for mosquito density showed that only 14 containers of water were found positive around places of three cases, and the Breteau Index is 15. Conclusions: Effective response was taken to control and prevent the outbreak of yellow fever in China after discovering the imported cases. However, though the similar origin of Chinese in Angola has provided an easy access for disease detection, information sharing, health education and vaccination on yellow fever; these conveniences were overlooked during previous disease prevention methods. Besides, only one case having effective vaccination revealed the inadequate capacity of immunization service in China. These findings will provide suggestions to improve China’s capacity to deal with not only yellow fever but also other similar imported diseases in China.

Keywords: yellow fever, first import, China, suggestion

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Authors: Samia A. El-Fiky, F. A. Abou-Zaid, Ibrahim M. Farag, Naira M. Efiky

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Clomipramine hydrochloride is one of the most used tricyclic antidepressant drug in Egypt. This drug contains in its chemical structure on two benzene rings. Benzene is considered to be toxic and clastogenic agent. So, the present study was designed to assess the genotoxic effect of Clomipramine hydrochloride on somatic and germ cells in mice. Three dose levels 0.195 (Low), 0.26 (Medium), and 0.65 (High) mg/kg.b.wt. were used. Seven groups of male mice were utilized in this work. The first group was employed as a control. In the remaining six groups, each of the above doses was orally administrated for two groups, one of them was treated for 5 days and the other group was given the same dose for 30 days. At the end of experiments, the animals were sacrificed for cytogenetic and sperm examination as well as histopathological investigations by using hematoxylin and eosin stains (H and E stains) and electron microscope. Concerning the sperm studies, these studies were confined to 5 days treatment with different dose levels. Moreover, the ultrastructural investigation by electron microscope was restricted to 30 days treatment with drug doses. The results of the dose dependent effect of Clomipramine showed that the treatment with three different doses induced increases of frequencies of chromosome aberrations in bone marrow and spermatocyte cells as compared to control. In addition, mitotic and meiotic activities of somatic and germ cells were declined. The treatments with medium or high doses were more effective for inducing significant increases of chromosome aberrations and significant decreases of cell divisions than treatment with low dose. The effect of high dose was more pronounced for causing such genetic deleterious in respect to effect of medium dose. Moreover, the results of the time dependent effect of Clomipramine observed that the treatment with different dose levels for 30 days led to significant increases of genetic aberrations than treatment for 5 days. Sperm examinations revealed that the treatment with Clomipramine at different dose levels caused significant increase of sperm shape abnormalities and significant decrease in sperm count as compared to control. The adverse effects on sperm shape and count were more obviousness by using the treatments with medium or high doses than those found in treatment with low dose. The group of mice treated with high dose had the highest rate of sperm shape abnormalities and the lowest proportion of sperm count as compared to mice received medium dose. In histopathological investigation, hematoxylin and eosin stains showed that, the using of low dose of Clomipramine for 5 or 30 days caused a little pathological changes in liver tissue. However, using medium and high doses for 5 or 30 days induced severe damages than that observed in mice treated with low dose. The treatment with high dose for 30 days gave the worst results of pathological changes in hepatic cells. Moreover, ultrastructure examination revealed, the mice treated with low dose of Clomipramine had little differences in liver histological architecture as compared to control group. These differences were confined to cytoplasmic inclusions. Whereas, prominent pathological changes in nuclei as well as dilated of rough Endoplasmic Reticulum (rER) were observed in mice treated with medium or high doses of Clomipramine drug. In conclusion, the present study adds evidence that treatments with medium or high doses of Clomipramine have genotoxic effects on somatic and germ cells of mice, as unwanted side effects. However, the using of low dose (especially for short time, 5 days) can be utilized as a therapeutic dose, where it caused relatively similar proportions of genetic, sperm, and histopathological changes as those found in normal control.

Keywords: clomipramine, mice, chromosome aberrations, sperm abnormalities, histopathology

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Authors: Gianluca Castelnuovo, Gian Mauro Manzoni, Giada Pietrabissa, Stefania Corti, Emanuele Giusti, Roberto Cattivelli, Enrico Molinari, Susan Simpson

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Obesity is currently an important public health problem of epidemic proportions (globesity). Moreover Binge Eating Disorder (BED) is typically connected with obesity, even if not occurring exclusively in conjunction with overweight conditions. Typically obesity with BED requires a longer term treatment in comparison with simple obesity. Rehabilitation interventions that aim at improving weight-loss, reducing obesity-related complications and changing dysfunctional behaviors, should ideally be carried out in a multidisciplinary context with a clinical team composed of psychologists, dieticians, psychiatrists, endocrinologists, nutritionists, physiotherapists, etc. Long-term outpatient multidisciplinary treatments are likely to constitute an essential aspect of rehabilitation, due to the growing costs of a limited inpatient approach. Internet-based technologies can improve long-term obesity rehabilitation within a collaborative approach. The new m health (m-health, mobile health) paradigm, defined as clinical practices supported by up to date mobile communication devices, could increase compliance- engagement and contribute to a significant cost reduction in BED and obesity rehabilitation. Five psychological components need to be considered for successful m Health-based obesity rehabilitation in order to facilitate weight-loss.1) Self-monitoring. Portable body monitors, pedometers and smartphones are mobile and, therefore, can be easily used, resulting in continuous self-monitoring. 2) Counselor feedback and communication. A functional approach is to provide online weight-loss interventions with brief weekly or monthly counselor or psychologist visits. 3) Social support. A group treatment format is typically preferred for behavioral weight-loss interventions. 4) Structured program. Technology-based weight-loss programs incorporate principles of behavior therapy and change with structured weekly protocolos including nutrition, exercise, stimulus control, self-regulation strategies, goal-setting. 5) Individually tailored program. Interventions specifically designed around individual’s goals typically record higher rates of adherence and weight loss. Opportunities and limitations of m health approach in clinical psychology for obesity and BED are discussed, taking into account future research directions in this promising area.

Keywords: obesity, rehabilitation, out-patient, new technologies, tele medicine, tele care, m health, clinical psychology, psychotherapy, chronic care management

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Authors: Kornanong Yuenyongchaiwat, Duangnate Pepatsitipong, Panthip Sangprasert

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High blood pressure and diabetes have been suggested as being non-communicable disease (NCDs), and there is one of the components of the definition of metabolic syndrome. Therefore, the purpose of this study was to evaluate the effect of a 12-week pedometer based community walking intervention on change in resting blood pressure and blood glucose in participants with overweight in the community setting. Method: Participants were recruited both males and females who had a sedentary lifestyle aged 35-59 years (mean aged 49.67 years). A longitudinal quasi-experimental study was designed with 35 overweight participants who had body mass index ≥ 25 kg/m2. These volunteers were assigned to the 12-week pedometer-based walking program (an accumulated at least 10,000 steps a day). Blood pressure and blood glucose were measured initially before and after 12-week intervention. Results: Systolic blood pressure and heart rate were significantly lower in 30 individuals who had accumulated 10,000 steps d-1 in the intervention group at 12 week follow-up (-13.74 mmHg and 5.3 bpm, respectively). In addition, reduction in blood glucose (-14.89 mmol) in the intervention participants was statistically significant (p < .001). A regression analysis indicated that reductions in systolic blood pressure were significantly related to the increase in steps per day. Conclusion: The accumulation of least 10,000 steps d-1 resulted in decreased resting systolic blood pressure and blood glucose in overweight participants. This has also shown that an increase in physical activity in overweight participants with sedentary lifestyle by accumulating at least 10,000 steps a day can reduce the risk of cardiovascular disease (e.g., hypertension and diabetes).

Keywords: blood glucose, blood pressure, diabetes, hypertension, physical activity, walking

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Authors: Mustafa Metin Donma

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Metabolic syndrome (MetS) is characterized by a series of biochemical, physiological and anthropometric indicators and is a life-threatening health problem due to its close association with chronic diseases such as diabetes mellitus, hypertension, cancer and cardiovascular diseases. The syndrome deserves great interest both in adults and children. Central obesity is the indispensable component of MetS. Particularly, children, who are morbidly obese have a great tendency to develop the disease, because they are under the threat in their future lives. Preventive measures at this stage should be considered. For this, investigators seek for an informative scale or an index for the purpose. So far, several, but not many suggestions come into the stage. However, the diagnostic decision is not so easy and may not be complete particularly in the pediatric population. The aim of the study was to develop a MetS index capable of predicting MetS, while children are at the morbid obesity stage. This study was performed on morbid obese (MO) children, which were divided into two groups. Morbid obese children, who do not possess MetS criteria comprised the first group (n=44). The second group was composed of children (n=42) with MetS diagnosis. Parents were informed about the signed consent forms, which are required for the participation of their children in the study. The approval of the study protocol was taken from the institutional ethics committee of Tekirdag Namik Kemal University. Helsinki Declaration was accepted prior to and during the study. Anthropometric measurements including weight, height, waist circumference (WC), hip C, head C, neck C, biochemical tests including fasting blood glucose (FBG), insulin (INS), triglycerides (TRG), high density lipoprotein cholesterol (HDL-C) and blood pressure measurements (systolic (SBP) and diastolic (DBP)) were performed. Body fat percentage (BFP) values were determined by TANITA’s Bioelectrical Impedance Analysis technology. Body mass index and MetS indices were calculated. The equations for MetS index (MetSI) and advanced Donma MetS index (ADMI) were [(INS/FBG)/(HDL-C/TRG)]*100 and MetSI*[(SBP+DBP/Height)], respectively. Descriptive statistics including median values, compare means tests, correlation-regression analysis were performed within the scope of data evaluation using the statistical package program, SPSS. Statistically significant mean differences were determined by a p value smaller than 0.05. Median values for MetSI and ADMI in MO (MetS-) and MO (MetS+) groups were calculated as (25.9 and 36.5) and (74.0 and 106.1), respectively. Corresponding mean±SD values for BFPs were 35.9±7.1 and 38.2±7.7 in groups. Correlation analysis of these two indices with corresponding general BFP values exhibited significant association with ADMI, close to significance with MetSI in MO group. Any significant correlation was found with neither of the indices in MetS group. In conclusion, important associations observed with MetS indices in MO group were quite meaningful. The presence of these associations in MO group was important for showing the tendency towards the development of MetS in MO (MetS-) participants. The other index, ADMI, was more helpful for predictive purpose.

Keywords: body fat percentage, child, index, metabolic syndrome, obesity

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Authors: Aziz Rezapour, Abdosaleh Jafari, Marziye Hadian, Elaheh Mazaheri

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Introduction: Cardiac rehabilitation is an accurate educational and sporting program designed to help heart patients to increase their physical activities and reduce the risk factors that make their health worse and help to a healthier lifestyle so that they can return to their families and society with a better spirit. The aim of this study was to examine the cost-effectiveness and cost-utility of cardiac rehabilitation programs for patients with cardiovascular diseases. Methods: In the present review study, published articles related to cost-effectiveness and cost-utility of cardiac rehabilitation programs for patients with cardiovascular diseases within the time interval between 2004 and 2019 were searched using electronic databases. The methodological quality of the structure of articles was examined by Drummond’s standard checklist. Results: The results of reviewing studies showed that most of the studies related to the economic evaluation of cardiac rehabilitation programs in patients with cardiovascular disease were flawed in Drummond’s criteria, and only one study adhered to Drummond’s criteria. The results of the present study indicated use of cardiac rehabilitation programs in patients with cardiovascular disease was cost-effective. Conclusion: The results of this review study showed that although the results of the studies were different in terms of a number of aspects, such as the study perspective, the time horizons, and the costs of rehabilitation programs, they achieved a similar conclusion, they concluded that the use of cardiac rehabilitation programs in patients with cardiovascular diseases, leading to higher quality-adjusted life years (QALYs) and lower costs.

Keywords: economic evaluation, systematic review, cardiac rehabilitation, Drummond’s checklist

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Authors: Uwizera Egide

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Introduction: Dermatological conditions are one of the most burdensome diseases in our health system. Global studies suggest that around 1 in 3 people gets a skin disease at a certain point in their life, though this does not necessarily guarantee the urge to consult. For a high-ranking disease, it is surprising how there is not enough data to support its effect on the economy and the general health system impact. It is for that reason that this study’s aim is to identify the burden of dermatological conditions in Rwanda so as to have a general picture of what our population is going through in regards to dermatological conditions. Methods: We used a cross sectional retrospective study. Data were obtained from patient’s information recorded in an open clinic at CHUB in a period of six months from July to December of the year 2021. Results: The study had a total of 4600 patients who attended dermatology service in a period of six months from July to December of the year 2021. We found a list of 102 dermatological diseases that presented at variable rates. The most prevalent disease was atopic dermatitis, at a rate of 23%. About 90% of presented conditions had only one choice of treatment from the hospital pharmacy. Most patients who presented were between 18-35 years old and with a predominance of the female gender; the level of education was either secondary or University Degree in our study, 65.4% of patients who presented were female; the majority, around 45% were between 18-35 years old, mostly being single 56%. The majority came from Southern province as it is the location of the hospital. The insurance mostly used was community-based health insurance with 63.8%, followed by RSSB with 18.5%, MS/UR, and other private insurances. The frequency of group drugs prescribed among all dermatological medications, steroids were the most commonly given medications at a rate of 39%, followed by emollients, antibiotics, and antifungal. The drugs prescribed were mostly available in the pharmacy of CHUB, with 60% and 40% being found in pharmacies outside the hospital. Conclusion: Dermatological conditions are prevalent in all age groups and distributed through all socioeconomic classes. About 9.2% of patient who consulted CHUB in 2021 presented one Dermatological condition of which 40 % of prescribed medications is never found in Hospital urging a need to buy medication in private pharmacies with more expenses and a risk of not complying on prescribed medication if in case they can’t afford paying them outside the CHUB. This finding urges a need to avail all essential dermatological drugs in hospital pharmacies to allow our patients to get them for the proper compliance of prescribed drugs in the management of skin diseases.

Keywords: atopic dermatitis, CHUB (centre hopitalier univerisitaire de butare), dermatological condition, fungal infections

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Authors: Samawi Zepure, Beck Christine, Gallagher Peg

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This community immersion employs the NLN Excellence Model which challenges nursing programs to create student-centered, interactive, and innovative experiences to prepare students for roles in providing high quality care, effective teaching, and leadership in the delivery of nursing services to individuals, families, and communities (NLN, 2006). Senior nursing students collaborate with ethnically and linguistically diverse participants at community-based sites and develop leadership roles of coordination of care linkage within the larger healthcare system, adherence, and self-care management. The immersion encourages students to develop competencies of the NLN Nursing Education Competencies Model (NLN, 2012), proposed to address fast changes in health care delivery, which include values of caring, diversity, and holism; and integrating concepts of context and environment, relationship, and teamwork. Students engage in critical thinking and leadership as they: 1) assess health/illness beliefs, values, attitudes, and practices, explore community resources, interview key informants, and collaborate with community participants to identify learning goals, 2) develop and implement appropriate holistic health promotion and disease prevention teaching interventions promoting continuity, sustainability, and innovation, 3) evaluate interventions through participant feedback and focus groups and, 4) reflect on the immersion experience and future professional role as advocate and citizen.

Keywords: quality of care, health of communities, students as leaders, health promotion

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Authors: Kalimullah Khan, Samina Roohi, Mohammad Rafi, Rizwana Zahoor

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Labeling of 5-Aminolevulinic acid (5-ALA) with 99 mTc was achieved by using tin chloride dihydrate (Sncl2.2H2O) as reducing agent. Radiochemical purity and labeling efficiency was determined by Whattman paper No.3 and instant thin layer chromatographic strips impregnated with silica gel (ITLC/SG). Labeling efficiency was dependent on many parameters such as amount of ligand, reducing agent, pH, and incubation time. Therefore, optimum conditions for maximum labeling were selected. Stability of 99 mTc- 5-ALA was also checked in fresh human serum. Tissue bio-distribution of 99 mTc-5-ALA was evaluated in Spargue Dawley rats. 5-ALA was 98% labeled with 99 mTc under optimum conditions, i.e. 100µg of 5-ALA, pH: 4, 10µg of Sncl2.2H2O and 30 minutes incubation at room temperature. 99 mTc labelled 5- ALA remained stable for 24 hours in human serum. Bio-distribution study (%ID/gm) in rats revealed that maximum accumulation of 99 mTc-5-ALA was in liver, spleen, stomach and intestine after half hour, 4 hours, and 24 hours. Significant activity in bladder and urine indicated urinary mode of excretion.

Keywords: 99mTc-ALA, aminolevulinic acid, quality control, radiopharmaceuticals

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Authors: Tita Nofianti, Tresna Lestari, Ade Y. Aprillia, Lilis Tuslinah, Ruswanto Ruswanto

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Nanoparticle technology gives a chance for drugs, especially natural based product, to give better activities than in its macromolecule form. The ginger torch is known to have activities as an antioxidant, antimicrobial, anticancer, etc. In this research, ginger torch flower extract was nanoparticlized using poloxamer 1, 3, and 5%. Nanoparticle was charaterized for its particle size, polydispersity index, zeta potential, entrapment efficiency, and morphological form by SEM (scanning electron microscope). The result shows that nanoparticle formulations have particle size 134.7-193.1 nm, polydispersity index is less than 0.5 for all formulations, zeta potential is -41.0 to (-24.3) mV, and entrapment efficiency is 89.93 to 97.99 against flavonoid content with a soft surface and spherical form of particles. Methanolic extract of ginger torch flower could enhance superoxide dismutase activity by 1,3183 U/mL in male rats. Nanoparticle formulation of ginger torch extract is expected to increase the capability of drug to enhance superoxide dismutase activity.

Keywords: superoxide dismutase, ginger torch flower, nanoparticle, poloxamer

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Authors: Jonathan Turner, Julie Doyle, Laura O’Philbin, Dympna O’Sullivan

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People living with dementia should be at the centre of decision-making regarding goals for daily living. These goals include basic activities (dressing, hygiene, and mobility), advanced activities (finances, transportation, and shopping), and meaningful activities that promote well-being (pastimes and intellectual pursuits). However, there is limited involvement of people living with dementia in the design of technology to support their goals. A project is described that is co-designing intelligent computer-based support for, and with, people affected by dementia and their carers. The technology will support self-management, empower participation in shared decision-making with carers and help people living with dementia remain healthy and independent in their homes for longer. It includes information from the patient’s care plan, which documents medications, contacts, and the patient's wishes on end-of-life care. Importantly for this work, the plan can outline activities that should be maintained or worked towards, such as exercise or social contact. The authors discuss how to integrate care goal information from such a care plan with data collected from passive sensors in the patient’s home in order to deliver individualized planning and interventions for persons with dementia. A number of scientific challenges are addressed: First, to co-design with dementia patients and their carers computerized support for shared decision-making about their care while allowing the patient to share the care plan. Second, to develop a new and open monitoring framework with which to configure sensor technologies to collect data about whether goals and actions specified for a person in their care plan are being achieved. This is developed top-down by associating care quality types and metrics elicited from the co-design activities with types of data that can be collected within the home, from passive and active sensors, and from the patient’s feedback collected through a simple co-designed interface. These activities and data will be mapped to appropriate sensors and technological infrastructure with which to collect the data. Third, the application of machine learning models to analyze data collected via the sensing devices in order to investigate whether and to what extent activities outlined via the care plan are being achieved. The models will capture longitudinal data to track disease progression over time; as the disease progresses and captured data show that activities outlined in the care plan are not being achieved, the care plan may recommend alternative activities. Disease progression may also require care changes, and a data-driven approach can capture changes in a condition more quickly and allow care plans to evolve and be updated.

Keywords: care goals, decision-making, dementia, self-care, sensors

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Authors: Sushil Kumar Singh, Ashok Kumar, Ankit Ganeshpurkar, Ravi Singh, Devendra Kumar

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In spectrum of neurodegenerative diseases, Alzheimer’s disease (AD) is characterized by the presence of amyloid β plaques and neurofibrillary tangles in the brain. It results in cognitive and memory impairment due to loss of cholinergic neurons, which is considered to be one of the contributing factors. Donepezil, an acetylcholinesterase (AChE) inhibitor which also inhibits butyrylcholinesterase (BuChE) and improves the memory and brain’s cognitive functions, is the most successful and prescribed drug to treat the symptoms of AD. The present work is based on designing of the selective BuChE inhibitors using computational techniques. In this work, machine learning models were trained using classification algorithms followed by screening of diverse chemical library of compounds. The various molecular modelling and simulation techniques were used to obtain the virtual hits. The amide derivatives of 4-(phenylsulfonamido) benzoic acid were synthesized and characterized using 1H & 13C NMR, FTIR and mass spectrometry. The enzyme inhibition assays were performed on equine plasma BuChE and electric eel’s AChE by method developed by Ellman et al. Compounds 31, 34, 37, 42, 49, 52 and 54 were found to be active against equine BuChE. N-(2-chlorophenyl)-4-(phenylsulfonamido)benzamide and N-(2-bromophenyl)-4-(phenylsulfonamido)benzamide (compounds 34 and 37) displayed IC50 of 61.32 ± 7.21 and 42.64 ± 2.17 nM against equine plasma BuChE. Ortho-substituted derivatives were more active against BuChE. Further, the ortho-halogen and ortho-alkyl substituted derivatives were found to be most active among all with minimal AChE inhibition. The compounds were selective toward BuChE.

Keywords: Alzheimer disease, butyrylcholinesterase, machine learning, sulfonamides

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Authors: Juan Huang, Nanqu Huang, Jingshan Shi, Yu Qiu

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Objectives: There are pathophysiological connections between type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD), and research on drugs with hypoglycemic and beta-amyloid (Aβ)-clearing effects have great therapeutic potential for AD. Dendrobium nobile Lindl. Alkaloids (DNLA) as one of the active compounds of Dendrobium nobile Lindl. In this study, we attempted to verify the hypoglycemic effect and investigate the effects of DNLA on the amyloid precursor protein (APP) metabolic pathway of the hippocampus in db/db mice. Methods: 4-weeks-old male C57BL/KsJ mice were the control group. And the same age and sexuality db/db mice were: model, DNLA-L (20 mg/kg), DNLA-M (40 mg/kg), and DNLA-H (80 mg/kg). After, mice were treated with different concentrations of DNLA for 17 weeks. The fasting blood glucose (FBG) was detected by glucose oxidase assay every week from the 4th to last week. The protein expression of β-amyloid 1-42 (Aβ1-42), β-site amyloid precursor protein-cleaving enzyme 1 (BACE1), and APP were examined by Western blotting. Results: The concentration of FBG and the protein expression of Aβ1-42, BACE1, and APP were increased in the hippocampus of the model group. Moreover, DNLA not only significantly decreased the concentration of FBG but also reduced the protein expressions of Aβ1-42, BACE1 and APP in the hippocampus of db/db mice in a dose-dependent manner. Conclusions: DNLA can decrease the protein expressions of Aβ1-42 in the hippocampus of db/db mice, and the mechanism may be involved in the APP metabolic pathway.

Keywords: Alzheimer's disease, type 2 diabetes mellitus, β-site amyloid precursor protein-cleaving enzyme 1, traditional Chinese medicines, beta-amyloid

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Authors: Mounia El Jaouhari, Mira Goral, Samir Diouny

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Introduction: Previous research has indicated that language impairments are recognized as a feature of many neurodegenerative disorders, including non-language-led dementia subtypes such as Alzheimer´s disease (AD). In this preliminary study, the focal aim is to quantify the semantic content of naming and connected speech samples of Moroccan patients diagnosed with AD using two tasks taken from the culturally adapted and validated Moroccan version of the Boston Diagnostic Aphasia Examination. Methods: Five individuals with AD and five neurologically healthy individuals matched for age, gender, and education will participate in the study. Participants with AD will be diagnosed on the basis of the Moroccan version of the Diagnostic and Statistial Manual of Mental Disorders (DSM-4) screening test, the Moroccan version of the Mini Mental State Examination (MMSE) test scores, and neuroimaging analyses. The participants will engage in two tasks taken from the MDAE-SF: 1) Picture description and 2) Naming. Expected findings: Consistent with previous studies conducted on English speaking AD patients, we expect to find significant word production and retrieval impairments in AD patients in all measures. Moreover, we expect to find category fluency impairments that further endorse semantic breakdown accounts. In sum, not only will the findings of the current study shed more light on the locus of word retrieval impairments noted in AD, but also reflect the nature of Arabic morphology. In addition, the error patterns are expected to be similar to those found in previous AD studies in other languages.

Keywords: alzheimer's disease, anomia, connected speech, semantic impairments, moroccan arabic

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Authors: N. S. Okoro

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An experiment was conducted to determine the growth performance, blood parameters and reproductive characteristics of 8-week old male weaner rabbits fed 2% boiled pigeon pea seed meal. The study lasted for 16 weeks. Results showed that hematological parameters of the two groups of rabbit bucks were not significantly affected (p > 0.05) by the treatment, meaning that the PPSM was adequate for maintaining the blood parameters at the normal levels. The 20% boiled PPSM significantly affected (P < 0.05) serum Alanine Aminotransferase (ALT) (67.72±2.5 I.U/I) more than the ALT (57.50±2.02 I.U/I) of the control, which is an indication of liver problem. The globulin level (3.00 ± 0.23g/dl) of the 20% boiled PPSM group was significantly higher than that of the control (2.60±0.06 g/dl), indicating that the test diet did not alter protein metabolism in the rabbits. Boiled pigeon pea seed meal supported organ weight and testicular development in rabbit bucks, suggesting that boiling reduced the level of the anti-nutritional factors in pigeon pea seed meal. Thus, 20% boiled pigeon pea can be included in diets of rabbits without adverse effect on blood parameters and internal organs characteristics.

Keywords: hematology, internal organs, Pigeon pea, rabbits, serum biochemistry

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Authors: Vijaykumar M. Baragi, Ramtilak Gattu, Gabriela Trifan, John L. Woodard, K. Meyers, Tim S. Halstead, Eric Hipple, Ewart Mark Haacke, Randall R. Benson

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NFL players, by virtue of their exposure to repetitive head injury, are at least twice as likely to develop Alzheimer's disease (AD) and dementia as the general population. Early recognition and intervention prior to onset of clinical symptoms could potentially avert/delay the long-term consequences of these diseases. Since AD is thought to have a long preclinical incubation period, the aim of the current research was to determine whether former NFL players, referred to a depression center, showed evidence of incipient dementia in their structural imaging prior to diagnosis of dementia. Thus, to identify neuroimaging markers of AD, against which former NFL players would be compared, we conducted a comprehensive volumetric analysis using a cohort of early stage AD patients (ADNI) to produce a set of brain regions demonstrating sensitivity to early AD pathology (i.e., the “AD fingerprint”). A cohort of 46 former NFL players’ brain MRIs were then interrogated using the AD fingerprint. Brain scans were done using a T1-weighted MPRAGE sequence. The Free Surfer image analysis suite (version 6.0) was used to obtain the volumetric and cortical thickness data. A total of 55 brain regions demonstrated significant atrophy or ex vacuo dilatation bilaterally in AD patients vs. healthy controls. Of the 46 former NFL players, 19 (41%) demonstrated a greater than expected number of atrophied/dilated AD regions when compared with age-matched controls, presumably reflecting AD pathology.

Keywords: alzheimers, neuroimaging biomarkers, traumatic brain injury, free surfer, ADNI

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Authors: Ragy Raafat Gaber Attaalla

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PIP: This review, based on 2 large-scale studies, discusses the pharmacology and physiology of oral steroid contraceptives (OCs). The pharmacological distinction between synthetic and naturally occurring steroids centers on changes in biological activity dependent on compound formulation and an individual's metabolism. OC mechanism of action is explained as the main prevention of ovulation by interference with gonadotropin-releasing hormone. Since some 52 metabolic alterations have been reported in OC users, these phenomena are dealt with in 3 categories: 1) effects on the primary target organs of the female reproductive tract (ovary, myometrium, endometrium, cervix, vagina, breasts, and hypothalamus), 2) general metabolic effects (serum proteins, carbohydrate metabolism, lipid metabolism, water and electrolyte metabolism, body weight, tryptophan metabolism, and vitamins and minerals), and 3) effects on other organ systems (liver, central nervous system, skin, genitourinary, gastrointestinal tract, eye, immune phenomena, and effect on subsequent fertility). The choice of the proper OC formulation and use of OCs by adolescents are discussed. Assessment of OC safety, contraindications, and patient monitoring are provided.

Keywords: steroid oral contraceptives, ovulation, female reproductive tract, metabolic effects

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Authors: Kiran Sharma, Viktor Kunder, Zerha Rizvi, Ricardo Soubelet

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Platelet rich plasma (PRP) has been recognized as a method of treatment in medicine since the 1980s. It primarily functions by releasing cytokines and growth factors that promote wound healing; these growth promoting factors released by PRP enact new processes such as angiogenesis, collagen deposition, and tissue formation that can change wound healing outcomes. Many studies recognize that PRP aids in chronic wound healing, which is advantageous for patients who suffer from chronic diabetic foot ulcers (DFUs). This scoping review aims to examine literature to identify the efficacy of PRP use in the healing of DFUs. Following PRISMA guidelines, we searched randomized-controlled trials involving PRP use in diabetic patients with foot ulcers using PubMed, Medline, CINAHL Complete, and Cochrane Database of Systematic Reviews. We restricted the search to articles published during 2005-2022, full texts in the English language, articles involving patients aged 19 years or older, articles that used PRP on specifically DFUs, articles that included a control group, articles on human subjects. The initial search yielded 119 articles after removing duplicates. Final analysis for relevance yielded 8 articles. In all cases except one, the PRP group showed either faster healing, more complete healing, or a larger percentage of healed participants. There were no situations in the included studies where the control group had a higher rate of healing or decreased wound size as compared to a group with isolated PRP-only use. Only one study did not show conclusive evidence that PRP caused accelerated healing in DFUs, and this study did not have an isolated PRP variable group. Application styles of PRP for treatment were shown to influence the level of healing in patients, with injected PRP appearing to achieve the best results as compared to topical PRP application. However, this was not conclusive due to the involvement of several other variables. Two studies additionally found PRP to be useful in healing refractory DFUs, and one study found that PRP use in patients with additional comorbidities was still more effective in healing DFUs than the standard control groups. The findings of this review suggest that PRP is a useful tool in reducing healing times and improving rates of complete wound healing in DFUs. There is room for further research in the application styles of PRP before conclusive statements can be made on the efficacy of injected versus topical PRP healing based on the findings in this study. The results of this review provide a baseline for further research in PRP use in diabetic patients and can be used by both physicians and public health experts to guide future treatment options for DFUs.

Keywords: diabetic foot ulcer, DFU, platelet rich plasma, PRP

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Authors: Fahad Almehmadi, Abdullah Alrajhi, Bader K. Alaslab, Abdullah A. Al Qurashi, Hattan A. Hassani

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Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C) is an uncommon, inheritable cardiac disorder characterized by the progressive substitution of cardiac myocytes by fibro-fatty tissues. This pathologic substitution predisposes patients to ventricular arrhythmias and right ventricular failure. The underlying genetic defect predominantly involves genes encoding for desmosome proteins, particularly plakophilin-2 (PKP2). These aberrations lead to impaired cell adhesion, heightening the susceptibility to fibrofatty scarring under conditions of mechanical stress. Primarily, ARVD/C affects the right ventricle, but it can also compromise the left ventricle, potentially leading to biventricular heart failure. Clinical presentations can vary, spanning from asymptomatic individuals to those experiencing palpitations, syncopal episodes, and, in severe instances, sudden cardiac death. The establishment of a diagnostic criterion specifically tailored for ARVD/C significantly aids in its accurate diagnosis. Nevertheless, the task of early diagnosis is complicated by the disease's frequently asymptomatic initial stages, and the overall rarity of ARVD/C cases reported globally. In some cases, as exemplified by the adult female patient in this report, the disease may advance to terminal stages, rendering therapies like Ventricular Tachycardia (VT) ablation ineffective. This case underlines the necessity for increased awareness and understanding of ARVD/C to aid in its early detection and management. Through such efforts, we aim to decrease morbidity and mortality associated with this challenging cardiac disorder.

Keywords: ARVD/C, cardiology, interventional cardiology, cardiac electrophysiology

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Authors: M. Sulieman, H. Arabiyat, H. Ali, K. Potiszil, I. Abbas, R. English, P. King, I. Brown, P. Drew

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Introduction: The incidence of breast ductal Carcinoma in Situ (DCIS) has been increasing; it currently represents up 20-25% of all breast carcinomas. Some aspects of DCIS management are still controversial, mainly due to the heterogeneity of its clinical presentation and of its biological and pathological characteristics. In DCIS, histological diagnosis obtained preoperatively, carries the risk of sampling error if the presence of invasive cancer is subsequently diagnosed. The mammographic extent over than 4–5 cm and the presence of architectural distortion, focal asymmetric density or mass on mammography are proven important risk factors of preoperative histological under staging. Intracystic papillary cancer (IPC) is a rare form of breast carcinoma. Despite being previously compared to DCIS it has been shown to present histologically with invasion of the basement membrane and even metastasis. SLNB – Carries the risk of associated comorbidity that should be considered when planning surgery for DCIS and IPC. Objectives: The aim of this Audit was to better define a ‘high risk’ group of patients with pre-op diagnosis of non-invasive cancer undergoing breast conserving surgery, who would benefit from sentinel node biopsy. Method: Retrospective data collection of all patients with ductal carcinoma in situ over 5 years. 636 patients identified, and after exclusion criteria applied: 394 patients were included. High risk defined as: Extensive micro-calcification >40mm OR any mass forming DCIS. IPC: Winpath search from for the term ‘papillary carcinoma’ in any breast specimen for 5 years duration;.29 patients were included in this group. Results: DCIS: 188 deemed high risk due to >40mm calcification or a mass forming (radiological or palpable) 61% of those had a mastectomy and 32% BCS. Overall, in that high-risk group - the number with invasive disease was 38%. Of those high-risk DCIS pts 85% had a SLN - 80% at the time of surgery and 5% at a second operation. For the BCS patients - 42% had SLN at time of surgery and 13% (8 patients) at a second operation. 15 (7.9%) pts in the high-risk group had a positive SLNB, 11 having a mastectomy and 4 having BCS. IPC: The provisional diagnosis of encysted papillary carcinoma is upgraded to an invasive carcinoma on final histology in around a third of cases. This has may have implications when deciding whether to offer sentinel node removal at the time of therapeutic surgery. Conclusions: We have defined a ‘high risk’ group of pts with pre-op diagnosis of non-invasive cancer undergoing BCS, who would benefit from SLNB at the time of the surgery. In patients with high-risk features; the risk of invasive disease is up to 40% but the risk of nodal involvement is approximately 8%. The risk of morbidity from SLN is up to about 5% especially the risk of lymphedema.

Keywords: breast ductal carcinoma in Situ (DCIS), intracystic papillary carcinoma (IPC), sentinel node biopsy (SLNB), high-risk, non-invasive, cancer disease

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Authors: Joseph George, Anne Kotteswara Roa

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Skin disease is one of the most common and popular kinds of health issues faced by people nowadays. Skin cancer (SC) is one among them, and its detection relies on the skin biopsy outputs and the expertise of the doctors, but it consumes more time and some inaccurate results. At the early stage, skin cancer detection is a challenging task, and it easily spreads to the whole body and leads to an increase in the mortality rate. Skin cancer is curable when it is detected at an early stage. In order to classify correct and accurate skin cancer, the critical task is skin cancer identification and classification, and it is more based on the cancer disease features such as shape, size, color, symmetry and etc. More similar characteristics are present in many skin diseases; hence it makes it a challenging issue to select important features from a skin cancer dataset images. Hence, the skin cancer diagnostic accuracy is improved by requiring an automated skin cancer detection and classification framework; thereby, the human expert’s scarcity is handled. Recently, the deep learning techniques like Convolutional neural network (CNN), Deep belief neural network (DBN), Artificial neural network (ANN), Recurrent neural network (RNN), and Long and short term memory (LSTM) have been widely used for the identification and classification of skin cancers. This survey reviews different DL techniques for skin cancer identification and classification. The performance metrics such as precision, recall, accuracy, sensitivity, specificity, and F-measures are used to evaluate the effectiveness of SC identification using DL techniques. By using these DL techniques, the classification accuracy increases along with the mitigation of computational complexities and time consumption.

Keywords: skin cancer, deep learning, performance measures, accuracy, datasets

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Authors: Fernanda Gonçalves, Karla Alcântara, Vanessa Moura, Patrícia Nolasco, Jorge Kalil, Maristela Hernandez

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Introduction: Atherosclerosis is a chronic disease where two striking features are observed: retention of lipids and inflammation. Understanding the interaction between immune cells and lipoproteins involved in atherogenesis are urgent challenges, since cardiovascular diseases are the leading cause of death worldwide. Macrophages are critical to the development of atherosclerotic plaques and in the perpetuation of inflammation in these lesions. These cells are also directly involved in unstable plaque rupture. Recently different populations of macrophages are being identified in atherosclerotic lesions. Although the presence of M2 macrophages (macrophages activated by the alternative pathway, eg. The IL-4) has been identified, the function of these cells in atherosclerosis is not yet defined. M2 macrophages have a high endocytic capacity, they promote remodeling of tissues and to have anti-inflammatory activity. However, in atherosclerosis, especially unstable plaques, severe inflammatory reaction, accumulation of cellular debris and intense degradation of the tissue is observed. Thus, it is possible that the M2 macrophages have altered function (phenotype) in atherosclerosis. Objective: Our aim is to evaluate if the presence of oxidized LDL alters the phenotype and function of M2 macrophages in vitro. Methods: For this, we will evaluate whether the addition of lipoprotein in M2 macrophages differentiated in vitro with IL -4 induces 1) a reduction in the secretion of anti-inflammatory cytokines (CBA and ELISA), 2) secretion of inflammatory cytokines (CBA and ELISA), 3) expression of cell activation markers (Flow cytometry), 4) alteration in gene expression of molecules adhesion and extracellular matrix (Real-Time PCR) and 5) Matrix degradation (confocal microscopy). Results: In oxLDL stimulated M2 macrophages cultures we did not find any differences in the expression of the cell surface markers tested, including: HLA-DR, CD80, CD86, CD206, CD163 and CD36. Also, cultures stimulated with oxLDL had similar phagocytic capacity when compared to unstimulated cells. However, in the supernatant of these cultures an increase in the secretion of the pro-inflammatory cytokine IL-8 was detected. No significant changes where observed in IL-6, IL-10, IL-12 and IL-1b levels. The culture supernatant also induced massive extracellular matrix (produced by mouse embryo fibroblast) filaments degradation. When evaluating the expression of 84 extracellular matrix and adhesion molecules genes, we observed that the stimulation of oxLDL in M2 macrophages decreased 47% of the genes and increased the expression of only 3% of the genes. In particular we noted that oxLDL inhibit the expression of 60% of the genes constituents of extracellular matrix and collagen expressed by these cells, including fibronectin1 and collagen VI. We also observed a decrease in the expression of matrix protease inhibitors, such as TIMP 2. On the opposite, the matricellular protein thrombospondin had a 12 fold increase in gene expression. In the presence of native LDL 90% of the genes had no altered expression. Conclusion: M2 macrophages stimulated with oxLDL secrete the pro-inflammatory cytokine IL-8, have an altered extracellular matrix constituents gene expression, and promote the degradation of extracellular matrix. M2 macrophages may contribute to the perpetuation of inflammation in atherosclerosis and to plaque rupture.

Keywords: atherosclerosis, LDL, macrophages, m2

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Authors: Masoumeh Haghbin Nazarpak, Hamidreza Tolabi, Aryan Ekhlasi

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Bone defects are mentioned as one of the most challenging clinical conditions, affecting millions of people each year. A fracture, osteoporosis, tumor, or infection usually causes these defects. At present, autologous and allogeneic grafts are used to correct bone defects, but these grafts have some difficulties, such as limited access, infection, disease transmission, and immune rejection. Bone tissue engineering is considered a new strategy for repairing bone defects. However, problems with scaffolds’ design with unique structures limit their clinical applications. In addition, numerous in-vitro studies have been performed on the behavior of bone cells in two-dimensional environments. Still, cells grow in physiological situations in the human body in a three-dimensional environment. As a result, the controlled design of porous structures with high structural complexity and providing the necessary flexibility to meet specific needs in bone tissue repair is beneficial. For this purpose, a three-dimensional composite scaffold based on gelatin and sodium alginate hydrogels is used in this research. In addition, the antibacterial drug-loaded halloysite nanotubes were introduced into the hydrogel scaffold structure to provide a suitable substrate for controlled drug release. The presence of halloysite nanotubes improved hydrogel’s properties, while the drug eliminated infection and disease transmission. Finally, it can be acknowledged that the composite scaffold prepared in this study for bone tissue engineering seems promising.

Keywords: halloysite nanotubes, bone tissue engineering, composite scaffold, controlled drug release

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Authors: Anne-Margré C. Vink

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Background: Food-related allergies and intolerances are frequently occurring in dogs. Diagnosis and monitoring according to ‘Golden Standard’ of elimination efficiency are time-consuming, expensive, and requires expert clinical setting. In order to facilitate rapid and robust, quantitative testing of intolerance, and determining the individual offending foods, a serological test is implicated. Method: As we developed Medisynx IgG Human Screening Test ELISA before and the dog’s immune system is most similar to humans, we were able to develop Medisynx IgG Dog Screening Test ELISA as well. In this study, 47 dogs suffering from Canine Atopic Dermatitis (CAD) and several secondary induced reactions were included to participate in serological Medisynx IgG Dog Screening Test ELISA (within < 0,02 % SD). Results were expressed as titers relative to the standard OD readings to diagnose alimentary induced diseases and monitoring the efficacy of an individual eliminating diet in dogs. Split sample analysis was performed by independently sending 2 times 3 ml serum under two unique codes. Results: The veterinarian monitored these dogs to check dog’ results at least at 3, 7, 21, 49, 70 days and after period of 6 and 12 months on an individual negative diet and a positive challenge (retrospectively) at 6 months. Data of each dog were recorded in a screening form and reported that a complete recovery of all clinical manifestations was observed at or less than 70 days (between 50 and 70 days) in the majority of dogs(44 out of 47 dogs =93.6%). Conclusion: Challenge results showed a significant result of 100% in specificity as well as 100% positive predicted value. On the other hand, sensitivity was 95,7% and negative predictive value was 95,7%. In conclusion, an individual diet based on IgG ELISA in dogs provides a significant improvement of atopic dermatitis and pruritus including all other non-specific defined allergic skin reactions as erythema, itching, biting and gnawing at toes, as well as to several secondary manifestations like chronic diarrhoea, chronic constipation, otitis media, obesity, laziness or inactive behaviour, pain and muscular stiffness causing a movement disorders, excessive lacrimation, hyper behaviour, nervous behaviour and not possible to stay alone at home, anxiety, biting and aggressive behaviour and disobedience behaviour. Furthermore, we conclude that a relatively more severe systemic candidiasis, as shown by relatively higher titer (class 3 and 4 IgG reactions to Candida albicans), influence the duration of recovery from clinical manifestations in affected dogs. These findings are consistent with our preliminary human clinical studies.

Keywords: allergy, canine atopic dermatitis, CAD, food allergens, IgG-ELISA, food-incompatibility

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Authors: Zhou Shangcheng, Yi Sicen

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Objective: To understand the mortality patterns of Zhangwan District in 2010 and provide the basis for the development of scientific and rational health policy. Methods: Data are collected from the Sixth Census of Zhangwan District and disease surveillance system. The statistical analysis include death difference between age, gender, region and time and the related factors. Methods developed for the Global Burden of Disease (GBD) Study by the World Bank and World Health Organization (WHO) were adapted and applied to Zhangwan District population health data. DALY rate per 1,000 was calculated for varied causes of death. SPSS 16 is used by statistic analysis. Results: From the data of death population of Zhangwan District we know the crude mortality rate was 6.03 ‰. There are significant differences of mortality rate in male and female population which was respectively 7.37 ‰ and 4.68 ‰. 0 age group population life expectancy in Zhangwan District in 2010 was 78.40 years old(Male 75.93, Female 81.03). The five leading causes of YLL in descending order were: cardiovascular diseases(42.63DALY/1000), malignant neoplasm (23.73DALY/1000), unintentional injuries (5.84DALY/1000), Respiratory diseases(5.43 DALY/1000), Respiratory infections (2.44DALY/1000). In addition, there are strong relation between the marital status , educational level and mortality in some to a certain extend. Conclusion Zhangwan District, as city level, is at lower mortality levels. The mortality of the total population of Zhangwan District has a downward trend and life expectancy is rising.

Keywords: sixth census, Zhangwan district, death level differences, influencing factors, cause of death

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Authors: Samuel Munaf, Kevin Swingler, Franz Brülisauer, Anthony O’Hare, George Gunn, Aaron Reeves

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Web scraping and text mining are popular computer science methods deployed by public health researchers to augment traditional epidemiological surveillance. However, within veterinary disease surveillance, such techniques are still in the early stages of development and have not yet been fully utilised. This study presents an exploration into the utility of incorporating internet-based data to better understand the smallholder farming communities within Scotland by using online text extraction and the subsequent mining of this data. Web scraping of the livestock fora was conducted in conjunction with text mining of the data in search of common themes, words, and topics found within the text. Results from bi-grams and topic modelling uncover four main topics of interest within the data pertaining to aspects of livestock husbandry: feeding, breeding, slaughter, and disposal. These topics were found amongst both the poultry and pig sub-forums. Topic modeling appears to be a useful method of unsupervised classification regarding this form of data, as it has produced clusters that relate to biosecurity and animal welfare. Internet data can be a very effective tool in aiding traditional veterinary surveillance methods, but the requirement for human validation of said data is crucial. This opens avenues of research via the incorporation of other dynamic social media data, namely Twitter and Facebook/Meta, in addition to time series analysis to highlight temporal patterns.

Keywords: veterinary epidemiology, disease surveillance, infodemiology, infoveillance, smallholding, social media, web scraping, sentiment analysis, geolocation, text mining, NLP

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Authors: Samia A. El-Fiky, Fouad A. Abou-Zaid, Ibrahim M. Farag, Naira M. El-Fiky

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Clomipramine hydrochloride is one of the most used tricyclic antidepressant drug in Egypt. This drug contains in its chemical structure on two benzene rings. Benzene is considered to be toxic and clastogenic agent. So, the present study was designed to assess the genotoxic effect of Clomipramine hydrochloride on somatic and germ cells in mice. Three dose levels 0.195 (Low), 0.26 (Medium), and 0.65 (High) mg/kg.b.wt. were used. Seven groups of male mice were utilized in this work. The first group was employed as a control. In the remaining six groups, each of the above doses was orally administrated for two groups, one of them was treated for 5 days and the other group was given the same dose for 30 days. At the end of experiments, the animals were sacrificed for cytogenetic and sperm examination as well as histopathological investigations by using hematoxylin and eosin stains (H and E stains) and electron microscope. Concerning the sperm studies, these studies were confined to 5 days treatment with different dose levels. Moreover, the ultrastructural investigation by electron microscope was restricted to 30 days treatment with drug doses. The results of the dose dependent effect of Clomipramine showed that the treatment with three different doses induced increases of frequencies of chromosome aberrations in bone marrow and spermatocyte cells as compared to control. In addition, mitotic and meiotic activities of somatic and germ cells were declined. The treatments with medium or high doses were more effective for inducing significant increases of chromosome aberrations and significant decreases of cell divisions than treatment with low dose. The effect of high dose was more pronounced for causing such genetic deleterious in respect to effect of medium dose. Moreover, the results of the time dependent effect of Clomipramine observed that the treatment with different dose levels for 30 days led to significant increases of genetic aberrations than treatment for 5 days. Sperm examinations revealed that the treatment with Clomipramine at different dose levels caused significant increase of sperm shape abnormalities and significant decrease in sperm count as compared to control. The adverse effects on sperm shape and count were more obviousness by using the treatments with medium or high doses than those found in treatment with low dose. The group of mice treated with high dose had the highest rate of sperm shape abnormalities and the lowest proportion of sperm count as compared to mice received medium dose. In histopathological investigation, hematoxylin and eosin stains showed that, the using of low dose of Clomipramine for 5 or 30 days caused a little pathological changes in liver tissue. However, using medium and high doses for 5 or 30 days induced severe damages than that observed in mice treated with low dose. The treatment with high dose for 30 days gave the worst results of pathological changes in hepatic cells. Moreover, ultrastructure examination revealed, the mice treated with low dose of Clomipramine had little differences in liver histological architecture as compared to control group. These differences were confined to cytoplasmic inclusions. Whereas, prominent pathological changes in nuclei as well as dilated of rough Endoplasmic Reticulum (rER) were observed in mice treated with medium or high doses of Clomipramine drug. In conclusion, the present study adds evidence that treatments with medium or high doses of Clomipramine have genotoxic effects on somatic and germ cells of mice, as unwanted side effects. However, the using of low dose (especially for short time, 5 days) can be utilized as a therapeutic dose, where it caused relatively similar proportions of genetic, sperm, and histopathological changes as those found in normal control.

Keywords: chromosome aberrations, clomipramine, mice, histopathology, sperm abnormalities

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Authors: Jake Tempo, Georgina Williams, Iain Robertson, Claire Pascoe, Darren Rama, Richard Cetti

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Introduction: The twelfth rib is commonly used as a landmark for surgery; however, its variability in length has not been formally studied. The highly variable rib length provides a challenge for urologists seeking a consistent landmark for percutaneous nephrolithotomy and retroperitoneoscopic surgery. Methods and materials: We analysed CT scans of 100 adults who had imaging between 23rd March and twelfth April 2020 at an Australian Hospital. We measured the distance from the mid-sagittal line to the twelfth rib tip in the axial plane as a surrogate for true rib length. We also measured the distance from the twelfth rib tip to the kidney, spleen, and liver. Results: Length from the mid-sagittal line to the right twelfth rib tip varied from 46 (percentile 95%CI 40 to 57) to 136mm (percentile 95%CI 133 to 138). On the left, the distances varied from 55 (percentile 95%CI 50 to 64) to 134mm (percentile 95%CI 131 to 135). Twenty-three percent of people had an organ lying between the tip of the twelfth rib and the kidney on the right, and 11% of people had the same finding on the left. Conclusion: The twelfth rib is highly variable in its length. Similar variability was recorded in the distance from the tip to intra-abdominal organs. Due to the frequency of organs lying between the tip of the rib and the kidney, it should not be used as a landmark for accessing the kidney without prior knowledge of an individual patient’s anatomy, as seen on imaging.

Keywords: PCNL, rib, anatomy, nephrolithotomy

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Authors: Huan Peng, Chenye Zeng, Zhao Wang

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Alzheimer’s disease (AD) is an age-related neurodegenerative disease that is a leading cause of dementia syndromes and has become a huge burden on society and families. The main pathological features of AD involve excessive deposition of β-amyloid (Aβ) and Tau proteins in the brain, resulting in loss of neurons, expansion of neuroinflammation, and cognitive dysfunction in patients. Researchers have found effective drugs to clear the brain of error-accumulating proteins or to slow the loss of neurons, but their direct administration has key bottlenecks such as single-drug limitation, rapid blood clearance rate, impenetrable blood-brain barrier (BBB), and poor ability to target tissues and cells. Therefore, we are committed to seeking a suitable and efficient delivery system. Inspired by the possibility that exosomes may be involved in the secretion and transport mechanism of many signaling molecules or proteins in the brain, exosomes have attracted extensive attention as natural nanoscale drug carriers. We selected exosomes derived from bone marrow mesenchymal stem cells (MSC-EXO) with low immunogenicity and exosomes derived from hippocampal neurons (HT22-EXO) that may have excellent homing ability to overcome the deficiencies of oral or injectable pathways and bypass the BBB through nasal administration and evaluated their delivery ability and effect on AD. First, MSC-EXO and HT22 cells were isolated and cultured, and MSCs were identified by microimaging and flow cytometry. Then MSC-EXO and HT22-EXO were obtained by gradient centrifugation and qEV SEC separation column, and a series of physicochemical characterization were performed by transmission electron microscope, western blot, nanoparticle tracking analysis and dynamic light scattering. Next, exosomes labeled with lipophilic fluorescent dye were administered to WT mice and APP/PS1 mice to obtain fluorescence images of various organs at different times. Finally, APP/PS1 mice were administered intranasally with two exosomes 20 times over 40 days and 20 μL each time. Behavioral analysis and pathological section analysis of the hippocampus were performed after the experiment. The results showed that MSC-EXO and HT22-EXO were successfully isolated and characterized, and they had good biocompatibility. MSC-EXO showed excellent brain enrichment in APP/PS1 mice after intranasal administration, could improve the neuronal damage and reduce inflammation levels in the hippocampus of APP/PS1 mice, and the improvement effect was significantly better than HT22-EXO. However, intranasal administration of the two exosomes did not cause depression and anxious-like phenotypes in APP/PS1 mice, nor significantly improved the short-term or spatial learning and memory ability of APP/PS1 mice, and had no significant effect on the content of Aβ plaques in the hippocampus, which also meant that MSC-EXO could use their own advantages in combination with other drugs to clear Aβ plaques. The possibility of realizing highly effective non-invasive synergistic treatment for AD provides new strategies and ideas for clinical research.

Keywords: Alzheimer’s disease, exosomes derived from mesenchymal stem cell, intranasal administration, therapy-carrier dual roles

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