Search results for: chronic toxicity

Authors: Shao-Cyuan Yewang, Yu-Wen Chen

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Background: Exercise training is well known to alleviate chronic pain syndromes improve of chronic pain. This study investigated the effect of swimming exercise training on thoracotomy and rib retraction-induced allodynia. Methods: Male Sprague Dawley rats that received animal model of persistent postthoracotomy pain. All rats were divided into three groups: sham operations group (Sham), thoracotomy and rib retraction group (TRR), and TRR with swimming exercise training for 90min/day, 7 days a week for 4 weeks (TRR-SEW). The sham group did not receive retraction of the ribs. Thus, they received a pleural incision. The levels of mechanical and cold allodynia were measured by von Frey and acetone test. Results: In von Frey test, the level of mechanical allodynia in the TRR group was significantly higher than the sham group. The level of mechanical allodynia in the TRR-SEW group was significantly lower than the TRR group. In acetone test, the level of cold allodynia in the TRR group was significantly higher than the sham group. The level of cold allodynia in the TRR-SEW group was significantly lower than the TRR group. Conclusions: These results suggest that swimming exercise training decreases persistent postthoracotomy pain caused by TRR surgery. It may provide one of the new therapeutic effects of swimming exercise training could alleviate persistent postthoracotomy pain.

Keywords: chronic pain, thoracotomy pain, swimming, von Frey test, acetone test

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Authors: Martina Santobuono, Wing Sze Chan, Elettra D'Amico, Henriette Selck

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Chemicals in modern society are fundamental in many different aspects of daily human life. We use a wide range of substances, including polychlorinated compounds, pesticides, plasticizers, and pharmaceuticals, to name a few. These compounds are excessively produced, and this has led to their introduction to the environment and food resources. Municipal and industrial effluents, landfills, and agricultural runoffs are a few examples of sources of chemical pollution. Many of these compounds, such as pharmaceuticals, have been proven to mimic or alter the performance of the hormone system, thus disrupting its normal function and altering the behavior and reproductive capability of non-target organisms. Antidepressants are pharmaceuticals commonly detected in the environment, usually in the range of ng L⁻¹ and µg L⁻¹. Since they are designed to have a biological effect at low concentrations, they might pose a risk to the native species, especially if exposure lasts for long periods. Hydrophobic antidepressants, like the selective serotonin reuptake inhibitor (SSRI) Sertraline, can sorb to the particles in the water column and eventually accumulate in the sediment compartment. Thus, deposit-feeding organisms may be at particular risk of exposure. The polychaete Capitella teleta is widespread in estuarine organically enriched sediments, being a key deposit-feeder involved in geochemistry processes happening in sediments. Since antidepressants are neurotoxic chemicals and endocrine disruptors, the aim of this work was to test if sediment-associated Sertraline impacts burrowing- and feeding behavior as well as reproduction capability in Capitella teleta in a chronic exposure set-up, which could better mimic what happens in the environment. 7 days old juveniles were selected and exposed to different concentrations of Sertraline for an entire generation until the mature stage was reached. This work was able to show that some concentrations of Sertraline altered growth and the time of first reproduction in Capitella teleta juveniles, potentially disrupting the population’s capability of survival. Acknowledgments: This Ph.D. position is part of the CHRONIC project “Chronic exposure scenarios driving environmental risks of Chemicals”, which is an Innovative Training Network (ITN) funded by the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie Actions (MSCA).

Keywords: antidepressants, Capitella teleta, chronic exposure, endocrine disruption, sublethal endpoints, neurotoxicity

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Authors: David Tanujaya Kurniawan

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Background: Liver injury caused by paracetamol is marked by increased serum transaminase levels. Turmeric is a local herb that is available in large quantities and inexpensive in contradiction to its substantial benefits, including its potency to increase glutathione production and regenerate hepatocyte into normal condition. Aim: The aim of this study was to analyze the potencial treatment effect of turmeric rhizome extract to reduce serum transaminase level on paracetamol induced liver toxicity in rats. Methods: This study was a laboratory experimental research with post-test only controlled group design. A group of 24 Wistar white male rats was induced with paracetamol 360 mg/kg body weight for 10 days. The group was then separated into four groups: the first and the second was treated with 100 mg/kg body weight and 150 mg/kg body weight of turmeric rhizome extract, subsequently, the third as positive control was given 27 mg/kg body weight of lesichol, while the fourth as negative control was given CMC-Na 1%. Each of this treatment was given for seven days. At the end of the study, the blood samples were taken to measure SGOT and SGPT levels. The one-way Anova test revealed significant difference in mean of SGPT level (p=0,001). The LSD test showed significant differences of SGPT levels in both treatment groups and negative control group. However, there was no sgnificant difference between positive control and both treatment groups. Conclusion: Curcuma domestica Val. rhizome extract could not reduce SGOT level, but it reduced SGPT level significantly.

Keywords: Curcuma domestica val., SGOT, SGPT, paracetamol, liver toxicity

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Authors: Kadry M. Sadek, Tarek K. Abouzed, Mousa A. Ayoub

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The presence of endocrine-disrupting compounds, such as bisphenol A (BPA), in the environment can cause serious health problems. However, there are controversial opinions. This study investigated the reproductive, metabolic, oxidative and immunologic-disrupting effects of bisphenol A in male rabbits. Rabbits were divided into five groups. The first four rabbit groups were administered oral BPA (1, 10, 50, or 100 mg/kg/day) for ten weeks. The fifth group was administered corn oil as the vehicle. BPA significantly decreased serum testosterone, estradiol and the free androgen index (FAI) and significantly increased sex hormone binding globulin (SHBG) compared with the placebo group. The higher doses of BPA showed a significant decrease in follicular stimulating hormone (FSH) and luteinizing hormone (LH). A significant increase in blood glucose levels was identified in the BPA groups. The non-significant difference in insulin levels is a novel finding. The cumulative testicular toxicity of BPA was clearly demonstrated by the dose-dependent decrease in absolute testes weight, primary measures of semen quality and a significant increase in testicular malonaldehyde (MDA). Moreover, BPA significantly decreased total antioxidant capacity (TAC) and significantly increased immunoglobulin G (IgG) at the highest concentration. Our results suggest that BPA, especially at higher doses, is associated with many adverse effects on metabolism, oxidative stress, immunity, sperm quality and markers of androgenic action. These results may reflect the estrogenic effects of BPA, which we hypothesize could be related, in part, to an inhibitory effect on testicular steroidogenesis. The induction of oxidative stress by BPA may play an additional role in testicular toxicity. These results suggest that BPA poses a threat to endocrine and reproductive functions.

Keywords: bisphenol A, oxidative stress, rabbits, semen quality, steroidogenesis

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Authors: N. Szczepanska, B. Kudlak, G. Yotova, S. Tsakovski, J. Namiesnik

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In the scientific literature related to the widely understood issue of packaging materials designed to have contact with food (food contact materials), there is much information on raw materials used for their production, as well as their physiochemical properties, types, and parameters. However, not much attention is given to the issues concerning migration of toxic substances from packaging and its actual influence on the health of the final consumer, even though health protection and food safety are the priority tasks. The goal of this study was to estimate the impact of particular foodstuff packaging type, food production, and storage conditions on the degree of leaching of potentially toxic compounds and endocrine disruptors to foodstuffs using the acute toxicity test Microtox and XenoScreen YES YAS assay. The selected foodstuff packaging materials were metal cans used for fish storage and tetrapak. Five stimulants respectful to specific kinds of food were chosen in order to assess global migration: distilled water for aqueous foods with a pH above 4.5; acetic acid at 3% in distilled water for acidic aqueous food with pH below 4.5; ethanol at 5% for any food that may contain alcohol; dimethyl sulfoxide (DMSO) and artificial saliva were used in regard to the possibility of using it as an simulation medium. For each packaging three independent variables (temperature and contact time) factorial design simulant was performed. Xenobiotics migration from epoxy resins was studied at three different temperatures (25°C, 65°C, and 121°C) and extraction time of 12h, 48h and 2 weeks. Such experimental design leads to 9 experiments for each food simulant as conditions for each experiment are obtained by combination of temperature and contact time levels. Each experiment was run in triplicate for acute toxicity and in duplicate for estrogen disruption potential determination. Multi-factor analysis of variation (MANOVA) was used to evaluate the effects of the three main factors solvent, temperature (temperature regime for cup), contact time and their interactions on the respected dependent variable (acute toxicity or estrogen disruption potential). From all stimulants studied the most toxic were can and tetrapak lining acetic acid extracts that are indication for significant migration of toxic compounds. This migration increased with increase of contact time and temperature and justified the hypothesis that food products with low pH values cause significant damage internal resin filling. Can lining extracts of all simulation medias excluding distilled water and artificial saliva proved to contain androgen agonists even at 25°C and extraction time of 12h. For tetrapak extracts significant endocrine potential for acetic acid, DMSO and saliva were detected.

Keywords: food packaging, extraction, migration, toxicity, biotest

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Authors: Hafiz Husnain Nawaz

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Anthracnose disease in olive, caused by the fungal pathogen Colletotrichum acutatum, is considered one of the most critical issues in olive orchards in Pakistan. This disease poses a significant threat as it results in infections that can lead to the complete damage of olive plants, affecting leaves, stems, and fruits in the field. Controlling this disease is particularly challenging due to the absence of an effective fungicide that does not pose risks to farmer health and the environment. To address this challenge, our study aimed to evaluate the antagonistic activity of a biosurfactant produced by the Bacillus subtilis PE-07 strain against the anthracnose-causing agent in olive plants. This strain was selected after screening sixty rhizobacteria strains. Additionally, we assessed the heat stability, pH range, and toxicity of the biosurfactant produced by strain PE-07. Our results revealed that the biosurfactant exhibited maximum antifungal activity against C. acutatum. In vitro studies indicated that the biosurfactant could reduce fungal activity by inhibiting the spore germination of C. acutatum. Furthermore, the biosurfactant demonstrated a wide pH and temperature range, displaying antifungal activity at pH levels ranging from 5 to 10 and a temperature range from room temperature to 110°C. To evaluate the biosurfactant's safety, we conducted toxicity tests on zebra fish (Danio rerio). The results showed that the biosurfactant had minimal harmful effects, even at maximum concentrations. In conclusion, our study confirmed that the biosurfactant produced by B. subtilis exhibited high pH and heat stability with minimal harmful effects. Therefore, it presents a promising alternative to chemical pesticides for effectively controlling olive anthracnose in Pakistan.

Keywords: biological control, heat stability and PH range, toxicity, Danio rerio

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Authors: Samy S. Eleawa, Mahmoud A. Alkhateeb, Fahaid H. Alhashem, Ismaeel bin-Jaliah, Hussein F. Sakr, Hesham M. Elrefaey, Abbas O. Elkarib, Mohammad A. Haidara, Abdullah S. Shatoor, Mohammad A. Khalil

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This effect of Resveratrol (RES) against CdCl2- induced toxicity in the rat testes was investigated. Seven experimental groups of adult male rats were formulated as follows: A) Controls + NS, B) Control+ vehicle (saline solution of hydroxypropyl cyclodextrin), C) RES treated, D) CdCl2 +NS, E) CdCl2+ vehicle, F) RES followed by CdCl2 and M) CdCl2 followed by RES. At the end of the protocol, serum levels of FSH, LH, and testosterone were measured in all groups. Testicular levels of TBARS and Super Oxide Dismutase (SOD) activity were also measured. Epidydidimal semen analysis was performed and testicular expression of Bcl-2, p53 and Bax were assessed by RT-PCR. Also, histopathological changes of testes were examined microscopically and described. Pre and Post administration of RES in cadmium chloride-intoxicated rats improved semen parameters including count, motility, daily sperm production and morphology, increased serum concentrations of gonadotropins and testosterone, decreased testicular lipid peroxidation and increased SOD activity. Not only RES attenuated cadmium chloride induced testicular histopathology but was also able to protect against the onset of cadmium chloride testicular toxicity. Cadmium chloride downregulated the anti-apoptotic gene Bcl2 and upregulated the expression of both pro-apoptotic genes p53 and Bax. Resveratrol protected from and partially reversed cadmium chloride testicular via upregulation of Bcl2 and down regulation of p53 and Bax gene expression. Antioxidant activity of RES protects against cadmium chloride testicular toxicity and partially reverses its effect via upregulation of BCl2 and downregulation of p53 and Bax expression. These findings have far reaching implications on subfertility and impotency frequently seen in hypertensive as well as metabolic syndrome patients.

Keywords: resveratrol, cadmium, infertility, sperm, testis, metabolic syndrome

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Authors: Nandini Nalika, Suhel Parvez

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Nanotechnology has emerged to play a vital role in developing all through the industrial world with an immense production of nanomaterials including nanoparticles (NPs). Many toxicological studies have confirmed that due to unique small size and physico-chemical properties of NPs (1-100nm), they can be potentially hazardous. Metallic NPs of small size have been shown to induce higher levels of cellular oxidative stress and can easily pass through the Blood Brain Barrier (BBB) and significantly accumulate in brain. With the wide applications of titanium dioxide nanoparticles (TNPs) in day-to-day life in form of cosmetics, paints, sterilisation and so on, there is growing concern regarding the deleterious effects of TNPs on central nervous system and mitochondria appear to be important cellular organelles targeted to the pro-oxidative effects of NPs and an important source that contribute significantly for the production of reactive oxygen species after some toxicity or an injury. The aim of our study was to elucidate the effect of TNPs in anatase form with different concentrations (5-50 µg/ml) following with various oxidative stress markers in isolated brain mitochondria as an in vitro model. Oxidative stress was determined by measuring the different oxidative stress markers like lipid peroxidation as well as the protein carbonyl content which was found to be significantly increased. Reduced glutathione content and major glutathione metabolizing enzymes were also modulated signifying the role of glutathione redox cycle in the pathophysiology of TNPs. The study also includes the mitochondrial enzymes (Complex 1, Complex II, complex IV, Complex V ) and the enzymes showed toxicity in a relatively short time due to the effect of TNPs. The study provide a range of concentration that were toxic to the neuronal cells and data pointing to a general toxicity in brain mitochondria by TNPs, therefore, it is in need to consider the proper utilization of NPs in the environment.

Keywords: mitochondria, nanoparticles, brain, in vitro

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Authors: Arielle Ferdinand

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A plant-based diet focuses on foods from plant sources, limiting or altogether omitting animal products. Some of the most common chronic illnesses seen in primary care are hypertension, hyperlipidemia, and diabetes type II. These common chronic illnesses can often be debilitating, costly, time-consuming, and, when left untreated, can lead to an early death. Treatment and maintenance of care are also labor intensive for the patient. They are often required to have at least four blood pressure checks yearly and a hemoglobin A1C checked quarterly. Though preventative interventions and prevention education should be included in patient visits in the primary care setting, education about dietary interventions, such as a plant-based diet, also yields positive outcomes for patients who already have hypertension, hyperlipidemia, and diabetes mellitus type 2. Evidence will show that incorporating a plant-based diet results in decreased blood pressure, as well as decreased levels of LDL-C, improved post-prandial glucose levels, and a reduction in HbA1C. It is cost-effective for the patient by generally lower grocery costs, and it can either reduce or prevent the need to pay for more office visits and pharmacotherapy. Incorporating this method of dietary changes is an easy intervention during a primary care office visit that would greatly benefit the patient in many ways.

Keywords: plant-based, nutrition, diabetes, hyperlipidemia

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Authors: Iva Blazkova, Amitava Moulick, Vedran Milosavljevic, Pavel Kopel, Marketa Vaculovicova, Vojtech Adam, Rene Kizek

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Doxorubicin is one of the most commonly used and the most effective chemotherapeutic drugs. This antracycline drug isolated from the bacteria Streptomyces peuceticus var. caesius is sold under the trade name Adriamycin (hydroxydaunomycin, hydroxydaunorubicin). Doxorubicin is used in single therapy to treat hematological malignancies (blood cancers, leukaemia, lymphoma), many types of carcinoma (solid tumors) and soft tissue sarcomas. It has many serious side effects like nausea and vomiting, hair lost, myelosupression, oral mucositis, skin reactions and redness, but the most serious one is the cardiotoxicity. Because of the risk of heart attack and congestive heart failure, the total dose administered to patients has to be accurately monitored. With the aim to lower the side effects and to targeted delivery of doxorubicin into the tumor tissue, the different nanoparticles are studied. The drug can be bound on a surface of nanoparticle, encapsulated in the inner cavity, or incorporated into the structure of nanoparticle. Among others, carbon nanoparticles (graphene, carbon nanotubes, fullerenes) are highly studied. Besides the number of inorganic nanoparticles, a great potential exhibit also organic ones mainly lipid-based and polymeric nanoparticle. The aim of this work was to perform a toxicity study of free doxorubicin compared to doxorubicin conjugated with various nanotransporters. The effect of liposomes, fullerenes, graphene, and carbon nanotubes on the toxicity was analyzed. As a first step, the binding efficacy of between doxorubicin and the nanotransporter was determined. The highest efficacy was detected in case of liposomes (85% of applied drug was encapsulated) followed by graphene, carbon nanotubes and fullerenes. For the toxicological studies, the chicken embryos incubated under controlled conditions (37.5 °C, 45% rH, rotation every 2 hours) were used. In 7th developmental day of chicken embryos doxorubicin or doxorubicin-nanotransporter complex was applied on the chorioallantoic membrane of the eggs and the viability was analyzed every day till the 17th developmental day. Then the embryos were extracted from the shell and the distribution of doxorubicin in the body was analyzed by measurement of organs extracts using laser induce fluorescence detection. The chicken embryo mortality caused by free doxorubicin (30%) was significantly lowered by using the conjugation with nanomaterials. The highest accumulation of doxorubicin and doxorubicin nanotransporter complexes was observed in the liver tissue

Keywords: doxorubicin, chicken embryos, nanotransporters, toxicity

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Authors: Rohit Sane, Snehal Dongre, Pravin Ghadigaonkar, Rahul Mandole

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The present study was designed to evaluate efficacy of heart failure reversal therapy (HFRT) that uses herbal procedure (panchakarma) and allied therapies, in chronic heart failure (CHF) patients with low ejection fraction. Methods: This efficacy study was conducted in CHF patients (aged: 25-65 years, ejection fraction (EF) < 30%) wherein HFRT (60-75 minutes) consisting of snehana (external oleation), swedana (passive heat therapy), hrudaydhara(concoction dripping treatment) and basti(enema) was administered twice daily for 7 days. During this therapy and next 30 days, patients followed the study dinarcharya and were prescribed ARJ kadha in addition to their conventional treatment. The primary endpoint of this study was evaluation of maximum aerobic capacity uptake (MAC) as assessed by 6-minute walk distance (6MWD) using Cahalins equation from baseline, at end of 7 day treatment, follow-up after 30 days and 90 days. EF was assessed by 2D Echo at baseline and after 30 days of follow-up. Results: CHF patients with < 30% EF (N=52, mean [SD] age: 58.8 [10.8], 85% men) were enrolled in the study. There was a 100% compliance to study therapy. A significant improvement was observed in MAC levels (7.11%, p =0.029), at end of 7 day therapy as compared to baseline. This improvement was maintained at two follow-up visits. Moreover, ejection fraction was observed to be increased by 6.38%, p=0,012 as compared to baseline at day 7 of the therapy. Conclusions: This 90 day follow up study highlights benefit of HFRT, as a part of maintenance treatment for CHF patients with reduced ejection fraction.

Keywords: chronic heart failure, functional capacity, heart failure reversal therapy, oxygen uptake, panchakarma

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Authors: Mahnaz Zarein, Hamed Shoorei

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Background: Malathion is one of the most toxic agents widely used in agriculture throughout the world. This agent has adverse effects on the functions of multiple organs such as the reproductive system in both male and female genders. On the one hand, daily use of antioxidant supplementations such as hesperidin is capable to neutralize the deleterious impacts of malathion. Therefore, in this experimental study, the protective effects of hesperidin against ovarian toxicity induced by malathion were investigated. Material & Methods: Balb/c adult mice (n=32) were randomly divided into 4 groups including 1) the control group, treated with normal saline, 2) the Mal group, treated with 30mg/kg malathion, daily for 1 month, 3) Mal + Hes group, treated with 20 mg/kg malathion and 20 mg/kg hesperidin, daily for 1 month, and 5) Hes group, treated with 20 mg/kg hesperidin. At the end of the experimental period, mice were anesthetized and their drops of blood were collected to the assessment of some hormones such as LH, FSH, E2, and P4. Also, the right ovaries were used to H&E staining, and the left ovaries were used for IHC staining (PCNA and FSHR). Results: Histopathological assessments showed that the number of follicles, i.e. primordial, primary, and secondary, significantly decreased, while the atretic follicle counts remarkably increased compared to the control group (p<0.05). Hormonal levels revealed that the production of all mentioned hormones decreased in the Mal group in comparison with the control group (p<0.05). The expression of PCNA, as a proliferative marker, and FHSR, as a marker showing maturation, decreased when mice received malathion compared to the control group (p<0.05). Interestingly, treatment with hesperidin significantly neutralized the adverse effects of malathion on all mentioned parameters. Conclusion: Daily use of antioxidant supplementations such as hesperidin could alleviate the ovarian toxicity induced by malathion.

Keywords: malathion, ovary, antioxidant hesperidin, FSHR PCNA, ovary

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Authors: Jiangang Shen

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Olfactory dysfunction is a common symptom companied by anxiety- and depressive-like behaviors in depressive patients. Chronic stress triggers hormone responses and inhibits the proliferation and differentiation of neural stem cells (NSCs) in the hippocampus and subventricular zone (SVZ)-olfactory bulb (OB), contributing to depressive behaviors and olfactory dysfunction. However, the cellular signaling molecules to regulate chronic stress mediated olfactory dysfunction are largely unclear. Adaptor proteins containing the pleckstrin homology domain, phosphotyrosine binding domain, and leucine zipper motif (APPLs) are multifunctional adaptor proteins. Herein, we tested the hypothesis that APPL2 could inhibit hippocampal neurogenesis by affecting glucocorticoid receptor (GR) signaling, subsequently contributing to depressive and anxiety behaviors as well as olfactory dysfunctions. The major discoveries are included: (1) APPL2 Tg mice had enhanced GR phosphorylation under basic conditions but had no different plasma corticosterone (CORT) level and GR phosphorylation under stress stimulation. (2) APPL2 Tg mice had impaired hippocampal neurogenesis and revealed depressive and anxiety behaviors. (3) GR antagonist RU486 reversed the impaired hippocampal neurogenesis in the APPL2 Tg mice. (4) APPL2 Tg mice displayed higher GR activity and less capacity for neurogenesis at the olfactory system with lesser olfactory sensitivity than WT mice. (5) APPL2 negatively regulates olfactory functions by switching fate commitments of NSCs in adult olfactory bulbs via interaction with Notch1 signaling. Furthermore, baicalin, a natural medicinal compound, was found to be a promising agent targeting APPL2/GR signaling and promoting adult neurogenesis in APPL2 Tg mice and chronic corticosterone-induced depression mouse models. Behavioral tests revealed that baicalin had antidepressant and olfactory-improving effects. Taken together, APPL2 is a critical therapeutic target for antidepressant treatment.

Keywords: APPL2, hippocampal neurogenesis, depressive behaviors and olfactory dysfunction, stress

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Authors: S. Nurdiana, A. S. Nor Haziqah, M. K. Nur Ezwa Khairunnisa, S. Nurul Izzati, Y. Siti Amna M. J. Norashirene, I. Nur Hilwani

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Azadirachta excelsa or locally known as sentang are frequently used as a traditional medicine by diabetes patients in Malaysia. However, less attention has been given to their toxicity effect. Thus, the study is an attempt to examine the protective effect of A. excelsa on the pancreas and to determine possible toxicity mediated by the extract. Diabetes was induced experimentally in rats by high-fat-diet for 16 weeks followed by intraperitoneal injection of streptozotocin at dosage of 35 mg/kg of body weight. Declination of the fasting blood glucose level was observed after continuous administration of A. excelsa for 14 days twice daily. This is due to the refining structure of the pancreas. However, surprisingly, the plant extract reduced the leukocytes, erythrocytes, hemoglobin, MCHC and lymphocytes. In addition, the rat treated with the plant extract exhibited increment in AST and eosinocytes level. Overall, the finding shows that A. excelsa possesses antidiabetic activity by improving the structure of pancreatic islet of Langerhans but involved in ameliorating of hematology and biochemical parameters.

Keywords: Azadirachta excelsa, diabetes, pancreas, hemato-biochemical parameters

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Authors: Jeanne Leblond, Warren Viricel, Amira Mbarek

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Although several products have reached the market, gene therapeutics are still in their first stages and require optimization. It is possible to improve their lacking efficiency by the use of carefully engineered vectors, able to carry the genetic material through each of the biological barriers they need to cross. In particular, getting inside the cell is a major challenge, because these hydrophilic nucleic acids have to cross the lipid-rich plasmatic and/or endosomal membrane, before being degraded into lysosomes. It takes less than one hour for newly endocytosed liposomes to reach highly acidic lysosomes, meaning that the degradation of the carried gene occurs rapidly, thus limiting the transfection efficiency. We propose to use a new pH-sensitive lipid able to change its conformation upon protonation at endosomal pH values, leading to the disruption of the lipidic bilayer and thus to the fast release of the nucleic acids into the cytosol. It is expected that this new pH-sensitive mechanism promote endosomal escape of the gene, thereby its transfection efficiency. The main challenge of this work was to design a preparation presenting fast-responding lipidic bilayer destabilization properties at endosomal pH 5 while remaining stable at blood pH value and during storage. A series of pH-sensitive lipids able to perform a conformational switch upon acidification were designed and synthesized. Liposomes containing these switchable lipids, as well as co-lipids were prepared and characterized. The liposomes were stable at 4°C and pH 7.4 for several months. Incubation with siRNA led to the full entrapment of nucleic acids as soon as the positive/negative charge ratio was superior to 2. The best liposomal formulation demonstrated a silencing efficiency up to 10% on HeLa cells, very similar to a commercial agent, with a lowest toxicity than the commercial agent. Using flow cytometry and microscopy assays, we demonstrated that drop of pH was required for the transfection efficiency, since bafilomycin blocked the transfection efficiency. Additional evidence was brought by the synthesis of a negative control lipid, which was unable to switch its conformation, and consequently exhibited no transfection ability. Mechanistic studies revealed that the uptake was mediated through endocytosis, by clathrin and caveolae pathways, as reported for previous lipid nanoparticle systems. This potent system was used for the treatment of hypercholesterolemia. The switchable lipids were able to knockdown PCSK9 expression on human hepatocytes (Huh-7). Its efficiency is currently evaluated on in vivo mice model of PCSK9 KO mice. In summary, we designed and optimized a new cationic pH-sensitive lipid for gene delivery. Its transfection efficiency is similar to the best available commercial agent, without the usually associated toxicity. The promising results lead to its use for the treatment of hypercholesterolemia on a mice model. Anticancer applications and pulmonary chronic disease are also currently investigated.

Keywords: liposomes, siRNA, pH-sensitive, molecular switch

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Authors: Min-Pei Ling

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Aflatoxin is a fungal secondary metabolite with high toxicity capable of contaminating various types of food crops. It has been identified as a Group 1 human carcinogen by the International Agency for Research on Cancer. Chronic aflatoxin exposure has caused a worldwide public food safety concern. Peanuts and peanut products are the major sources of aflatoxin exposure. Therefore, some reduction interventions have been developed to minimize contamination through the peanut production chain. The purpose of this study is to estimate the efficacy of interventions in reducing the health impact of hepatocellular carcinoma caused by aflatoxin contamination in peanuts. The estimated total disability-adjusted life-years (DALYs) was calculated using FDA-iRISK online software. Six aflatoxin reduction strategies were evaluated, including good agricultural practice (GAP), biocontrol, Purdue Improved Crop Storage packaging, basic processing, ozonolysis, and ultraviolet irradiation. The results indicated that basic processing could prevent huge public health loss of 4,079.7–21,833 total DALYs per year, which accounted for 39.6% of all decreased total DALYs. GAP and biocontrol were both effective strategies in the farm field, while the other three interventions were limited in reducing total DALYs. In conclusion, this study could help farmers, processing plants, and government policymakers to alleviate aflatoxin contamination issues in the peanut production chain.

Keywords: aflatoxin, health burden, disability-adjusted life-years, peanuts

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Authors: Ghulam Hassan Abbasi, Moazzam Jamil, Ghazala Akhtar, M.Anwar-ul-Haq

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Heavy metals are significant pollutants in environment and their toxicity is a problem for survival of living things while salicylic acid (SA) is signaling and ubiquitous bioactive molecule that regulates cellular mechanism in plants under stress condition. Therefore, exogenous application of salicylic acid (SA) under chromium stress in two chickpea varieties were investigated in hydroponic experiment with five treatments comprising of control, 5 µM Cr + 5 mM SA, 5µM Cr + 10 mM SA, 10µM Cr + 5 mM SA, and 10µM Cr + 10 mM SA. Results revealed that treatments of plants with 10 mM SA application under both 5 µM Cr and 10 µM Cr stress resulted in maximum improvement in plant morphological attributes (root and shoot length, root and shoot fresh and dry weight, membrane stability index and relative water contents) relative to 5 mM SA application in both chickpea varieties. Results regarding Cr concentration showed that Cr was more retained in roots followed by shoots and maximum reduction in Cr uptake was observed at 10 mM SA application. Chickpea variety BRC-61 showed maximum growth and least concentration of Cr in root and shoot relative to BRC-390 variety.

Keywords: chromium, Chickpea, salicylic acid, growth

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Authors: Dhananjay W. Bansod, Santosh Phad

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Non-Communicable Diseases (NCD) are major contributing factors to the disease burden in the world as well as in India. With a growing proportion of older persons in India gives rise to several challenges. With the advancement of age, elderly is exposed to various kinds of health problems more specifically NCDs. Therefore, an effort has been made to examine the prevalence of NCDs among older persons and its treatment-seeking behaviour, also it is tried to explore the association between the NCDs and its effect on the overall wellbeing of older persons. Data used from “Building Knowledge Base of Population Ageing Survey” conducted in 2011 in seven states of India. Six chronic diseases used (non-communicable diseases) namely Arthritis, Hypertension, Cataract, Diabetes, Asthma and Heart diseases to understand the issues related to NCDs. Also seen the effect of NCDs on the wellbeing of the elderly, the subjective well-being consists of nine questions from which SUBI score generated for mental health status, which ranges from 9 to 27. This Index indicates that lower the score better is the mental health status. Further, this index modified and generated three categories of Better (9-15), Average (16-20) and Worse (21-27). The reliability analysis is carried out with the coefficient (Cronbach’s alpha) of the scale was 0.8884. The result shows that Orthopedic / musculoskeletal ailments involving arthritis, rheumatism and osteoarthritis are the most common type of ailment followed by hypertension. Two-thirds of the elderly reported suffering from at least one chronic ailment. Most chronic illness conditions received some form of treatment and mainly depend on public health facilities. Financial insecurity is the primary obstruction in seeking treatment for most of the chronic ailments which typically require a longer duration of medication and repeated medical consultations, both having significant economic implications. According to SUBI index, only 15 per cent of the elderly are in Better mental health status, and one-third of the elderly are with the worse score. Elderly with the ailments like Cataract, Asthma and Arthritis have worse mental health. It depicts that the burden of disease is more among the elderly and it is directly affecting the overall wellbeing of older persons.

Keywords: NCD, well-being, older person, India

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Authors: Mario Isaza-Ruget, Claudia C. Colmenares-Mejia, Nancy Yomayusa, Camilo A. González, Andres Cely, Jossie Murcia

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Quantification of risks associated with complications development from chronic kidney disease (CKD) through accurate survival models can help with patient management. A retrospective cohort that included patients diagnosed with CKD from a primary care program and followed up between 2013 and 2018 was carried out. Time-dependent and static covariates associated with demographic, clinical, and laboratory factors were included. Deep Learning (DL) survival analyzes were developed for three CKD outcomes: CKD stage progression, >25% decrease in Estimated Glomerular Filtration Rate (eGFR), and Renal Replacement Therapy (RRT). Models were evaluated and compared with Random Survival Forest (RSF) based on concordance index (C-index) metric. 2.143 patients were included. Two models were developed for each outcome, Deep Neural Network (DNN) model reported C-index=0.9867 for CKD stage progression; C-index=0.9905 for reduction in eGFR; C-index=0.9867 for RRT. Regarding the RSF model, C-index=0.6650 was reached for CKD stage progression; decreased eGFR C-index=0.6759; RRT C-index=0.8926. DNN models applied in survival analysis context with considerations of longitudinal covariates at the start of follow-up can predict renal stage progression, a significant decrease in eGFR and RRT. The success of these survival models lies in the appropriate definition of survival times and the analysis of covariates, especially those that vary over time.

Keywords: artificial intelligence, chronic kidney disease, deep neural networks, survival analysis

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Authors: Hend K. Moosa, Eman A. Rashwan, Ezzat M. Hassan, Amany A. Ghazy, Amel G. Sheredy

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The stability of microRNA (miR) in the circulation can show a great progress toward the discovery of non-invasive diagnostic and prognostic biomarkers in many diseases. In the present study, circulatory miR-122 and miR-130a were analysed in chronic hepatitis C Egyptian patients in predicting the clinical outcome of interferon treatment. In addition, their expression levels were correlated to viral RNA levels, necro-inflammatory markers (AST, ALT) and to each other. This study was conducted on 51 subjects where 36 were chronic HCV patients in which they were divided into naive and interferon treated HCV patients (responders and non-responders) and 15 matched healthy controls. Serum quantification of miR-122 and miR-130a were performed by quantitative Real-time Polymerase Chain Reaction (qRT-PCR). The results showed a significant upregulation of miR-122 in non-responder patients (P=0.049). By receiver operating characteristic analysis curve, miR-122 revealed 65% sensitivity and 92.3% specificity in predicting non-responsiveness of patients to IFN treatment, while miR-130a showed a sensitivity of 100% and specificity of 53.85%. Remarkably, there was a significant positive correlation between miR-122 and miR-130a in naive HCV patients (r=0.714, p=0.003). However, there was no significant correlation between serum miR-122, miR-130a expression levels and necro-inflammatory markers (AST, ALT). To conclude, miR-122 and miR-130a have a significant association with viral RNA levels and accordingly, they may have a synergistic power in promoting viral replication. Interestingly, miR-122 and miR-130a have a predictive power in predicting clinical outcome of IFN treatment which can be further studied in currently used drugs in order to reduce the socio-economic burden of potentially non-responders.

Keywords: hepatitis C, microRNA, miR-122, miR-130a

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Authors: Adam Bownik, Małgorzata Adamczuk, Barbara Pawlik-Skowrońska

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Certain strains of cyanobacteria, microorganisms forming water blooms, produce toxic secondary metabolites. Although various effects of cyanotoxins in aquatic animals are known, little data can be found on the influence of some cyanobacterial oligopeptides beyond microcystins. The aim of the present study was to determine the toxicity of novel pure cyanobacterial oligopeptides: microginin FR-1 (MGFR1) and anabaenopeptin-A (ANA-A) on a transparent model rotifer Brachionus calyciflorus with the use of fluorescent double staining with Hoechst 34580 and propidium iodide. The obtained results showed that both studied oligopeptides decreased the fluorescence intensity of animals stained with Hoechst 34580 in a concentration-dependent manner. On the other hand, a concentration-dependent increase of propidium iodide fluorescence was noted in the exposed rotifers. The results suggest that MGFR-1 and ANA-A should be considered as a potent toxic agent to freshwater rotifers, and fluorescent staining with Hoechst and propidium iodide may be a valuable tool for determination of toxicity of cyanobacterial oligopeptides in rotifers.

Keywords: cyanobacteria, brachionus, oligopeptides, fluorescent staining, hoechst, propidium iodide

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Authors: Ghulam Hasan Abbasi, Moazzam Jamil, M. Anwar-Ul-Haq

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Heavy metals are significant pollutants in environment and their toxicity is a problem for survival of living things while Silicon (Si) is one of the most ubiquitous macroelements, performing an essential function in healing plants in response to environmental stresses. A hydroponic experiment was conducted to investigate the role of exogenous application of silicon under cadmium stress in six different maize hybrids with five treatments comprising of control, 7.5 µM Cd + 5 mM Si, 7.5 µM Cd + 10 mM Si, 15 µM Cd + 5 mM Si and 15 µM Cd + 10 mM Si. Results revealed that treatments of plants with 10mM Si application under both 7.5µM Cd and 15 µM Cd stress resulted in maximum improvement in plant morphological attributes (root and shoot length, root and shoot fresh and dry weight, leaf area and relative water contents) and antioxidant enzymes (POD and CAT) relative to 5 mM Si application in all maize hybrids. Results regarding Cd concentrations showed that Cd was more retained in roots followed by shoots and then leaves and maximum reduction in Cd uptake was observed at 10mM Si application. Maize hybrid 6525 showed maximum growth and least concentration of Cd whereas maize hybrid 1543 showed the minimum growth and maximum Cd concentration among all maize hybrids.

Keywords: antioxidant, cadmium, maize, silicon

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Authors: Narin Ozturk, Xiao-Mei Li, Sylvie Giachetti, Francis Levi, Alper Okyar

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P-glycoprotein (P-gp, MDR1, ABCB1) is a transmembrane protein acting as an ATP-dependent efflux pump and functions as a biological barrier by extruding drugs and xenobiotics out of cells in healthy tissues especially in intestines, liver and brain as well as in tumor cells. The circadian timing system controls a variety of biological functions in mammals including xenobiotic metabolism and detoxification, proliferation and cell cycle events, and may affect pharmacokinetics, toxicity and efficacy of drugs. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer drug that is active against many cancers, and its pharmacokinetics depend on P-gp. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus with respect to the intestinal P-gp expression rhythms in mdr1a::Luc mice using Real Time-Biolumicorder (RT-BIO) System. Mdr1a::Luc male mice were synchronized with 12 h of Light and 12 h of Dark (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding Light onset). After 1-week baseline recordings, everolimus (5 mg/kg/day x 14 days) was administered orally at ZT1-resting period- and ZT13-activity period- to mdr1a::Luc mice singly housed in an innovative monitoring device, Real Time-Biolumicorder units which let us monitor real-time and long-term gene expression in freely moving mice. D-luciferin (1.5 mg/mL) was dissolved in drinking water. Mouse intestinal mdr1a::Luc oscillation profile reflecting P-gp gene expression and locomotor activity pattern were recorded every minute with the photomultiplier tube and infrared sensor respectively. General behavior and clinical signs were monitored, and body weight was measured every day as an index of toxicity. Drug-induced body weight change was expressed relative to body weight on the initial treatment day. Statistical significance of differences between groups was validated with ANOVA. Circadian rhythms were validated with Cosinor Analysis. Everolimus toxicity changed as a function of drug timing, which was least following dosing at ZT13, near the onset of the activity span in male mice. Mean body weight loss was nearly twice as large in mice treated with 5 mg/kg everolimus at ZT1 as compared to ZT13 (8.9% vs. 5.4%; ANOVA, p < 0.001). Based on the body weight loss and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13. Both rest-activity and mdr1a::Luc expression displayed stable 24-h periodic rhythms before everolimus and in both vehicle-treated controls. Real-time bioluminescence pattern of mdr1a revealed a circadian rhythm with a 24-h period with an acrophase at ZT16 (Cosinor, p < 0.001). Mdr1a expression remained rhythmic in everolimus-treated mice, whereas down-regulation was observed in P-gp expression in 2 of 4 mice. The study identified the circadian pattern of intestinal P-gp expression with an unprecedented precision. The circadian timing depending on the P-gp expression rhythms may play a crucial role in the tolerability/toxicity of everolimus. The circadian changes in mdr1a genes deserve further studies regarding their relevance for in vitro and in vivo chronotolerance of mdr1a-transported anticancer drugs. Chronotherapy with P-gp-effluxed anticancer drugs could then be applied according to their rhythmic patterns in host and tumor to jointly maximize treatment efficacy and minimize toxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, mdr1a::Luc mice, p-glycoprotein

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Authors: Gayathri Vijayakumar, Preethi Baskaran

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The effluents that are let down by the industries mix with the water bodies and drastically affect the aquatic life, which leads to pollution and bio magnifications. Effluents mostly contain chemicals, heavy metals etc., and cause toxicity to the environment. The pharmaceutical industries too contribute. The by-products and other unwanted waste are discharged without any treatment; these causes DNA damage and affect behavior of aquatic life. The study was conducted on koi carp (Cyprinus carpio) the ornamental variety of common carp. A two week long study was conducted on them using common anti-depressant drug (Diazepam) in various concentrations. These drugs are known to cause behavioral damage and organ malfunctions (muscle twitch). The histopathological study conducted showed permanent muscle twitching and lesions in the fish samples studied. The sociability was also affected in the span of 14 days. Higher concentrations of this drug showed severe damage in the muscle structures. Thus, this drug can cause adverse effects on marine ecosystem and eventually cause bio magnification of drug by running through the food chain.

Keywords: pollution, toxicity, bio-magnifications, koi carp, muscle twitch, diazepam, histopathology

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Authors: Zubana Afzal, Afsheen Massod

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This quantitative study was carried out in order to explore the role of coping strategies as an explanatory mechanism in the relationship between self-determination needs and quality of life. A cross-sectional survey research design was conducted using scales such as the Basic Psychological Needs Scale (Deci&Ryan, 2000) to measure self-determination-based needs, Pain Coping Strategies Questionnaire (Harland &Georgieff, 2003), and Quality of Life Brief (The WHOQOL Group, 1998), in translated form in addition to a demographic information sheet. The sample comprised 120 (Women=63, Men=57), taken from different hospitals in Lahore, Multan, and Gojra. Descriptive and Inferential analyses were executed through SPSS version 23.00. All self-determination needs were found in result to be significantly and positively correlated with diversion and cognitive pain coping strategies, physical, psychological, social, and environmental quality of life, and significantly negatively correlated with catastrophizing and reinterpreting pain coping strategies. Cognitive and diversion pain coping strategies were found to be significantly and positively associated with all physical, psychological, social, and environmental quality of life. The regression analyses revealed that the strongest predictors were autonomy, cognitive and diversion pain coping strategies in predicting quality of life. All coping strategies except reinterpreting played a mediating role between self-determination needs and quality of life. The findings can lead to a better understanding of the role of self-determination needs and pain coping strategies in determining the quality of life among chronic non-specific lower back pain patients.

Keywords: quality of life, chronic lower back pain, coping strategies, self determination needs

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Authors: A. Ojha, Y. K. Gupta

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Organophosphate (OP) pesticides are among the most widely used synthetic chemicals for controlling a wide variety of pests throughout the world. Chlorpyrifos (CPF), methyl parathion (MPT), and malathion (MLT) are among the most extensively used OP pesticides in India. DNA strand breaks and DNA-protein crosslinks (DPC) are toxic lesions associated with the mechanisms of toxicity of genotoxic compounds. In the present study, we have examined the potential of CPF, MPT, and MLT individually and in combination, to cause DNA strand breakage and DPC formation. Peripheral blood lymphocytes of rat were exposed to 1/4 and 1/10 LC50 dose of CPF, MPT, and MLT for 2, 4, 8, and 12h. The DNA strand break was measured by the comet assay and expressed as DNA damage index while DPC estimation was done by fluorescence emission. There was significantly marked increase in DNA damage and DNA-protein crosslink formation in time and dose dependent manner. It was also observed that MPT caused the highest level of DNA damage as compared to other studied OP compounds. Thus, from present study, we can conclude that studied pesticides have genotoxic potential. The pesticides mixture does not potentiate the toxicity of each other. Nonetheless, additional in vivo data are required before a definitive conclusion can be drawn regarding hazard prediction to humans.

Keywords: organophosphate, pesticides, DNA damage, DNA protein crosslink, genotoxic

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Authors: Hee-Young Song

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Background and objectives: In 2011, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations proposed a multidimensional assessment of patients’ conditions that included both functional parameters and patient-reported outcomes, with the aim to provide a comprehensive assessment of the disease, thus meeting both the needs of the patient and the role of the physician. However, few studies have evaluated patient-reported outcomes as well as objective functional assessments among individuals with chronic obstructive pulmonary disease (COPD) in clinical practice in Korea. This study was undertaken to explore the relationship between functional status assessed by the 6-minute walking distance (MWD) test and subjective health status reported by stable patients with COPD residing in community. Methods: A cross-sectional descriptive study was conducted with 118 stable COPD patients aged 69.4 years old and selected by a convenient sampling from an outpatient department of pulmonology in a tertiaryhospitals. The 6-MWD test was conducted according to standardized instructions. Participants also completed a constructed questionnaire including general characteristics, smoking history, dyspnea by modified medical research council (mMRC) scale, and health status by COPD assessment test (CAT). Anthropometric measurements were performed for body mass index (BMI). Medical records were reviewed to obtain disease-related characteristics including duration of the disease and forced expiratory volume in 1 second (FEV1). Data were analyzed using PASW statistics 20.0. Results: Mean FEV1% of participants was 63.51% and mean 6-MWD and CAT scores were 297.54m and 17.7, respectively. The 6-MWD and CAT showed significant negative correlations (r= -.280, p=.002); FEV1 and CAT did as well correlations (r= -.347, p < .001). Conclusions: Findings suggest that the better functional status an individual with COPD has, the better subjective health status is, and provide the support for using patient-reported outcomes along with functional parameters to facilitate comprehensive assessment of COPD patients in real clinical practices.

Keywords: chronic obstructive pulmonary disease, COPD assessment test, functional status, patient-reported outcomes

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Authors: Babu Shersad, Partha Banerjee

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Reduction in haemoglobin levels has been implicated to be a cause for reduced exercise tolerance and cardiovascular complications of chronic renal diseases. Trends of hemoglobin levels in patients on haemodialysis could be an indicator of efficacy of hemodialysis and an indicator of quality of life in haemodialysis patients. In the UAE, the rate of growth (of patients on dialysis) is 10 to 15 per cent per year. The primary mode of haemodialysis in the region is based on in-patient hospital-based hemodialysis units. The increase in risk of cardiovascular and cerebrovascular morbidity as well as mortality in pre-dialysis Chronic Renal Disease has been reported. However, data on the health burden on haemodialysis in standalone dialysis facilities is very scarce. This is mainly due to the paucity of ambulatory centres for haemodialysis in the region. AMSA is the first center to offer standalone dialysis in the UAE and a study over a one year period was performed. Patient data was analyzed using a questionnaire for 45 patients with an average of 2.5 dialysis sessions per week. All patients were on chronic haemodialysis as outpatients. The trends of haemoglobin levels as an independent variable were evaluated. These trends were interpreted in comparison with other parameters of renal function (creatinine, uric acid, blood pressure and ferritin). Trends indicate an increase in hemoglobin levels with increased supplementation of iron and erythropoietin over time. The adequacy of hemodialysis shows improvement concomitantly. This, in turn, correlates with better patient outcomes and has a direct impact on morbidity and mortality. This study is a pilot study and further studies are indicated so that objective parameters can be studied and validated for hemodialysis in the region.

Keywords: haemodialysis, haemoglobin in haemodialysis, haemodialysis parameters, erythropoietic agents in haemodialysis

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Authors: Pulari C. Milu Maria Anto

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Background: Cognitive Rehabilitation/Retraining has been variously used in the research literature to represent non-pharmacological interventions that target the cognitive impairments with the goal of ameliorating cognitive function and functional behaviors to optimize the quality of life. Along with adult’s cognitive impairments, the need to address acquired cognitive impairments (due to any chronic illnesses like CHD - congenital heart diseases or ALL - Acute Lymphoblastic Leukemia) among child populations is inevitable. Also, it has to be emphasized as same we consider the cognitive impairments seen in the children having neurodevelopmental disorders. Methods: All published brain image studies (Hermann, B. et al,2002, Khalil, A. et al., 2004, Follin, C. et al, 2016, etc.) and studies emphasizing cognitive impairments in attention, memory, and/or executive function and behavioral aspects (Henkin, Y. et al,2007, Bellinger, D. C., & Newburger, J. W. (2010), Cheung, Y. T., et al,2016, that could be identified were reviewed. Based on a systematic review of the literature from (2000 -2021) different brain imaging studies, increased risk of neuropsychological and psychosocial impairments are briefly described. Clinical and research gap in the area is discussed. Results:30 papers, both Indian studies and foreign publications (Sage journals, Delhi psychiatry journal, Wiley Online Library, APA PsyNet, Springer, Elsevier, Developmental medicine, and child neurology), were identified. Conclusions: In India, a very limited number of brain imaging studies and neuropsychological studies have done by indicating the cognitive deficits of a child having or undergone chronic illness. None of the studies have emphasized the relevance nor the need of implementingCR among such children, even though its high time to address but still not established yet. The review of the current evidence is to bring out an insight among rehabilitation professionals in establishing a child specific CR and to publish new findings regarding the implementation of CR among such children. Also, this study will be an awareness on considering cognitive aspects of a child having acquired cognitive deficit (due to chronic illness), especially during their critical developmental period.

Keywords: cognitive rehabilitation, neuropsychological impairments, congenital heart diseases, acute lymphoblastic leukemia, epilepsy, and neuroplasticity

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Authors: Abdel Hadi N. Ebraheim, Eman Azomi, Nefisa A. Fahmy

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This paper designs and implements a computer-aided system (CAS) to help detect and diagnose liver cirrhosis in patients with Chronic Hepatitis C. Our system reduces the required features (tests) the patient is asked to do to tests to their minimal best most informative subset of tests, with a diagnostic accuracy above 99%, and hence saving both time and costs. We use the Support Vector Machine (SVM) with cross-validation, a Multilayer Perceptron Neural Network (MLP), and a Generalized Regression Neural Network (GRNN) that employs a base of radial functions for functional approximation, as classifiers. Our system is tested on 199 subjects, of them 99 Chronic Hepatitis C.The subjects were selected from among the outpatient clinic in National Herpetology and Tropical Medicine Research Institute (NHTMRI).

Keywords: liver cirrhosis, artificial neural network, support vector machine, multi-layer perceptron, classification, accuracy

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