Search results for: adverse drug effects

Authors: Jasna Hudek-Knezevic, Igor Kardum, Nada Krapic, Martina Jurcic

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The aim of this study was to examine the effects of self- and partner reported attachment orientations on self-reported mate retention behaviors in romantic couples using the actor-partner interdependence model. The study was carried out on 187 heterosexual couples aged from 18 to 35 years, with an average relationship length of 4.5 years. Participants were asked to complete the revised scale of adult attachment and short form of mate retention inventory. Actor and partner effects of self- and partner reported anxious and avoidant attachment orientations on mate retention categories (direct guarding, intersexual negative inducements, positive inducements, public signals of possession and intrasexual negative inducements) and domains (cost-inflicting and benefit-provisioning), as well on overall mate retention were examined. Actor effects for women estimate whether their attachment orientations predict their own mate retention behaviors, whereas men’s actor effects estimate whether their attachment orientations predict their own mate retention behaviors. Women’s partner effects estimate whether their attachment orientations predict their partner’s mate retention behaviors, whereas men’s partner effects estimate whether their attachment orientations predict their partner’s mate retention behaviors. The use of two data sources, self- and partner reports, allow the control of the effects of common method variance when exploring actor and partner effects. Positive actor and partner effects of anxious attachment, as well as negative actor and partner effects of avoidant attachment on mate retention, were expected. In other words, it was expected that more anxiously attached individuals themselves, as well as their partners, will use mate retention behaviors more frequently. On the other hand, more avoidantly attached individuals themselves, as well as their partners, will use mate retention behaviors less frequently. These hypotheses were partially confirmed. The results showed that the strongest and most consistent effects across both data sources were men’s actor effects on the cost-inflicting mate retention domain, and especially on two mate retention categories, direct guarding, and intersexual negative inducements. Additionally, a consistent positive partner effect of men’s anxious attachment orientations on direct guarding was also obtained. Avoidant attachment orientation exerted few and inconsistent actor and partner effects on mate retention domains and categories. The results are explained by theoretical propositions addressing the effects of attachment orientations on an interpersonal romantic relationship in early adulthood.

Keywords: actor and partner effects, attachment orientations, dyadic analysis, mate retention behavior

Procedia PDF Downloads 146

Authors: A. M. S. S. Amarasiri, A. P. Attanayake, K. A. P. W. Jayatilaka, L. K. B. Mudduwa

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Adriamycin (ADR) is an effective anthracyclin antitumor drug, but its clinical use is limited due to renal toxicity. The leaves of Asparagus falcatus (Family: Liliaceae) have been used in the management of renal diseases since antiquity. In the present investigation, the aqueous leaf extract of A. falcatus was evaluated for acute nephroprotective activity in ADR induced nephrotoxic rats. Nephrotoxicity was induced in healthy male Wistar rats by intraperitoneal administration of ADR 20 mg/kg. The lyophilized powder of the aqueous refluxed (4h) leaf extract of A. falcatus was administered orally at three selected doses; 200, 400 and 600 mg/kg for three consecutive days. Fosinopril sodium (0.09 mg/kg) was used as the standard drug. Administration of the plant extract and the standard drug was commenced 24 hours after the induction of nephrotoxicity to rats. The nephroprotective effect was determined by selected biochemical parameters and by the assessment of histopathology on H and E stained kidney sections. The results were compared to a group of control rats with ADR induced nephrotoxicity. A group of rats administered with the equivalent volume of normal saline served as the healthy control. Administration of ADR 20 mg/kg produced a significant increase in the concentrations of serum creatinine (61%) and urine protein (73%) followed by a significant decrease in serum total protein (21%) and albumin (44%) of the plant extract treated animals compared to the healthy control group (p < 0.05). The aqueous extract of Asparagus falcatus at the three doses; 200, 400 and 600 mg/kg and the standard drug were found to decrease the elevation of concentrations of serum creatinine (33%, 51%, 54% and 42%) and urine protein (8%, 63%, 80% and 86%) respectively. The serum concentrations of total protein (12%, 17%, 29% and 12%) and albumin (3%, 17%, 17% and 16%) were significantly increased compared to the nephrotoxic control group respectively. Assessment of histopathology on H and E stained kidney sections demonstrated that ADR induced renal injury, as evidenced by loss of brush border, cytoplasmic vacuolization, pyknosis in renal tubular epithelial cells, haemorrhages, glomerular congestion and presence of hyaline casts. Treatment with the plant extract and the standard drug resulted in attenuation of the morphological destruction in rats. The results of the present study revealed that the aqueous leaf extract of A. falcatus possesses significant nephroprotective activity against adriamycin induced acute nephrotoxicity. The improved kidney functions were supported with the results of selected biochemical parameters and histological changes observed on H and E stained sections of the kidney tissues in Wistar rats.

Keywords: adriamycin induced nephrotoxicity, asparagus falcatus, biochemical assessment, histopathological assessment, nephroprotective activity

Procedia PDF Downloads 146

Authors: Azza H. El-Medany, Hanan H. Hagar, Omnia A. Nayel, Jamila H. El-Medany

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In search for drugs that can target cancer cell micro-environment in as much as being able to halt malignant cellular transformation, the natural dietary phytochemical curcumin was currently assessed in DMH-induced colorectal cancer rat model. The study enrolled 50 animals divided into a control group (n=10) and DMH-induced colorectal cancer control group (n=20) (20mg/kg-body weight for 28 weeks) versus curcumin-treated group (n=20) (160 mg/kg suspension daily oral for further 8 weeks). Treatment by curcumin succeeded to significantly decrease the percent of ACF and tended to normalize back the histological changes retrieved in adenomatous and stromal cells induced by DMH. The drug also significantly elevated GSH and significantly reduced most of the accompanying biochemical elevations (namely MDA, TNF-α, TGF-β and COX2) observed in colonic carcinomatous tissue, induced by DMH, thus succeeding to revert that of MDA, COX2 and TGF-β back to near normal as justified by being non-significantly altered as compared to normal controls. The only exception was PAF that was insignificantly altered by the drug. When taken together, it could be concluded that curcumin possess the potentiality to halt some of the orchestrated cross-talk between cancerous transformation and its micro-environmental niche that contributes to cancer initiation, progression and metastasis in this experimental cancer colon model. Envisioning these merits to a drug with already known safety preferentiality, awaits final results of current ongoing clinical trials, before curcumin can be added to the new therapeutic armamentarium of anticancer therapy.

Keywords: curcumin, dimethyl hydralazine, aberrant crypt foci, malondialdehyde, reduced glutathione, cyclooxygenase-2, tumour necrosis factor-alpha, transforming growth factor-beta, platelet activating factor

Procedia PDF Downloads 281

Authors: Mhaned Oubounyt, Jan Baumbach

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Differences in co-expression networks between two or multiple cells (sub)types across conditions is a pressing problem in single-cell RNA sequencing (scRNA-seq). A key challenge is to define those co-variations that differ between or among cell types and/or conditions and phenotypes to examine small regulatory networks that can explain mechanistic differences. To this end, we developed SCANet, an all-in-one Python package that uses state-of-the-art algorithms to facilitate the workflow of a combined single-cell GCN (Gene Correlation Network) and GRN (Gene Regulatory Networks) pipeline, including inference of gene co-expression modules from scRNA-seq, followed by trait and cell type associations, hub gene detection, co-regulatory networks, and drug-gene interactions. In an example case, we illustrate how SCANet can be applied to identify regulatory drivers behind a cytokine storm associated with mortality in patients with acute respiratory illness. SCANet is available as a free, open-source, and user-friendly Python package that can be easily integrated into systems biology pipelines.

Keywords: single-cell, co-expression networks, drug-gene interactions, co-regulatory networks

Procedia PDF Downloads 121

Authors: Jie Gao

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The combination of chemotherapy with gene therapy is highly effective in cancer therapy. To achieve combined therapeutic effects in human gastric cancer over expressing EGFR, we developed targeted LPD (liposome-polycation-DNA complex) conjugated with anti-EGFR (epidermal growth factor receptor) Fab’ for co-delivery of doxorubicin (DOX) and ribonucleotide reductase M2 (RRM2) siRNA (DOX-RRM2-TLPD). The results showed that EGFR was over expressed in several gastric cancer cell lines and gastric cancer tissues. Gene Expression Omnibus (GEO) results showed that RRM2 expression was significantly higher in gastric cancer than in non-gastric cancer tissue, and RRM2 siRNA inhibited the proliferation of several gastric cancer cells, indicating that RRM2 is a candidate target for gastric cancer therapy. Confocal studies and flow cytometry showed that DOX-RRM2-TLPD delivered DOX and RRM2 siRNA to EGFR over expressing gastric cancer cells specifically and efficiently both in vitro and in vivo, resulting in enhanced therapeutic effects (cytotoxicity and apoptosis) compared with single-drug loaded or non-targeted controls, including DOX-NC-TLPD (targeted LPD co-delivering DOX and negative control siRNA), RRM2-TLPD (targeted LPD delivering RRM2 siRNA) and DOX-RRM2-NTLPD (non-targeted LPD co-delivering DOX and RRM2 siRNA). The in vivo antitumor assay showed that the average weight of the gastric cancer in mice treated with DOX-RRM2-TLPD was significantly lighter than that of mice treated with other controls. DOX-RRM2-TLPD represents an effective approach for combined therapy of gastric cancer over expressing EGFR.

Keywords: gene therapy, chemotherapy, immunoliposomes, gastric cancer

Procedia PDF Downloads 404

Authors: J. S. P. Barbosa, L. C. Pereira, K. R. Garcia, P. C. P. Bouchardet, S. C. T. Vieira, A. O. Gomes, S. S. Funghetto, M. G. O. Kanikowski

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For this population, height seems to be a good predictor of strength and body composition. This increase in life expectancy of the Brazilian's population is associated with sociodemographic variables, but also to more access to health services in the prevention and better living conditions. With the growth of elderly population, a problem that has been a concern to health's professionals and public health at all is the use of psychoactive substances. The purpose of this study was to identify the sociodemographic profile of the elderly people who was attended at the Center of Psychosocial Care of alcohol and other drugs in the Federal District of Brazil. 408 medical records of people aged 60 years or over were evaluated, and it is possible to know that most of them were males (85.3%), with a mean age of 64 years (DP ± 4.16), 60 and 84 years and a mean age of 64 years (DP ± 4.42); 88.2% have some family ties, are married and have children, with relatives living in masonry housing. The educational level of drug users was considered low with more emphasis on those who had elementary education being the majority retired or unemployed. Regarding the street situation, there was no significance (p = 0.084), and the women (OR = 2.98) had few chances of street situations compared to men (OR = 0.89). As for substance consumption, the highest quantity of drug consumption bids in relation to the number of illicit. It did not present significant statistical value, and there is a greater probability of consumption/abuse of legal and/or illicit drugs for both sexes (OR = 0.96) for men and (OR = 1.32) for women. In relation to the use of multiple drugs, there was no significant difference between the sexes, (OR = 1.1) male sex and (OR = 0.74) female sex. Based on the results found in the present study, it was concluded that alcohol consumption is the main agent that causes vulnerability in the elderly and predisposes the latter to the consumption of other associated drugs.

Keywords: centers of attention psychosocial alcohol and drugs, elderly, mental disorder due to drug use, street situations

Procedia PDF Downloads 193

Authors: Benguerine Zohra, Merzak Siham, Bouziane Cheimaa, Si Tayeb Fatima, Jou Siham, Belkessam

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Introduction: Antibiotics, widely produced and consumed in large quantities, have proven problematic due to various types of side effects. The development of bacterial resistance to currently available antibiotics has made the search for new antibacterial agents necessary. One alternative strategy to combat antibiotic-resistant bacteria is the use of natural antimicrobial substances such as plant extracts. The objective of this study is to provide an overview of the antibacterial effects of a plant native to the Middle East and Mediterranean regions, Salvia officinalis (sage). Materials and Methods: This review article was conducted by searching studies in the PubMed, Scopus, JSTOR, and SpringerLink databases. The search terms were "Salvia officinalis L." and "antibacterial effects." Only studies that met our inclusion criteria (in English, antibacterial effects of Salvia officinalis L., and primarily dating from 2012 to 2023) were accepted for further review. Results and Discussion: The initial search strategy identified approximately 78 references, with only 13 articles included in this review. The synthesis of the articles revealed that several data sources confirm the antimicrobial effects of S. officinalis. Its essential oil and alcoholic extract exhibit strong bactericidal and bacteriostatic effects against both Gram-positive and Gram-negative bacteria. Conclusion: The significant value of the extract, oil, and leaves of S. officinalis calls for further studies on the other useful and unknown properties of this multi-purpose plant.

Keywords: salvia officinalis, literature review, antibacterial, effects

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Authors: Amlan Kumar Das, Avinash Marwal, Vikram Pareek

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Liposome plays an important role in medical and pharmaceutical science as e.g. nano scale drug carriers. Liposomes are vesicles of varying size consisting of a spherical lipid bilayer and an aqueous inner compartment. Magnet-driven liposome used for the targeted delivery of drugs to organs and tissues1. These liposome preparations contain encapsulated drug components and finely dispersed magnetic particles. Liposomes are vesicles of varying size consisting of a spherical lipid bilayer and an aqueous inner compartment that are generated in vitro. These are useful in terms of biocompatibility, biodegradability, and low toxicity, and can control biodistribution by changing the size, lipid composition, and physical characteristics2. Furthermore, liposomes can entrap both hydrophobic and hydrophilic drugs and are able to continuously release the entrapped substrate, thus being useful drug carriers. Magnetic liposomes (MLs) are phospholipid vesicles that encapsulate magneticor paramagnetic nanoparticles. They are applied as contrast agents for magnetic resonance imaging (MRI)3. The biological synthesis of nanoparticles using plant extracts plays an important role in the field of nanotechnology4. Green-synthesized magnetite nanoparticles-protein hybrid has been produced by treating Iron (III)/Iron(II) chloride with the leaf extract of Dhatura Inoxia. The phytochemicals present in the leaf extracts act as a reducing as well stabilizing agents preventing agglomeration, which include flavonoids, phenolic compounds, cardiac glycosides, proteins and sugars. The magnetite nanoparticles-protein hybrid has been trapped inside the aqueous core of the liposome prepared by reversed phase evaporation (REV) method using oleic and linoleic acid which has been shown to be driven under magnetic field confirming the formation magnetic liposome (ML). Chemical characterization of stealth magnetic liposome has been performed by breaking the liposome and release of magnetic nanoparticles. The presence iron has been confirmed by colour complex formation with KSCN and UV-Vis study using spectrophotometer Cary 60, Agilent. This magnet driven liposome using nanoparticles-protein hybrid can be a smart vesicles for the targeted drug delivery.

Keywords: nanoparticles-protein hybrid, magnetic liposome, medical, pharmaceutical science

Procedia PDF Downloads 235

Authors: Josephine Muchiri, Makena Muriithi

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Adverse mental health consequences are experienced by those that have been touched by Intimate Partner Violence (IPV), whether directly or indirectly. These negative effects are felt not only in the short term but in years to come. It is important to examine the prevalence and co-occurrence of mental disorders in order to provide strategic interventions for women who have experienced IPV. The aim of this study was to examine the prevalence and comorbidity of post-traumatic stress disorder (PTSD), Depression, and Anxiety among women who had experienced intimate Partner violence in two selected informal settlements in Nairobi County, Kenya. Participants were 116 women (15-60 years) selected through purposive and snowball sampling from the low social, economic settlements (Kawangware and Kibera) in Nairobi, Kenya. A social demographic questionnaire and the Woman Abuse Screening Tool (WAST) were used to collect data on intimate partner violence experiences. The PTSD Checklist for DSM-5 (PCL-5), Beck’s Depression Inventory, and the Beck’s Anxiety Inventory assessed for post-traumatic stress disorder, depression, and anxiety, respectively. Data analysis was conducted using the Statistical Package for Social Sciences (SPSS) version 29, utilizing descriptive and correlation analyses. Findings indicated that the women had undergone various forms of abuse from their intimate partners, which were physical abuse 111(92.5%), sexual abuse 70(88.6%), and verbal abuse 92(93.9%). The prevalence of the mental disorders was PTSD 47(32.4%); M= 44.11, S.D =14.67, depression was the highest at n=131(90.3%; M=33.37±9.98) with the levels of depression having varying prevalence rates where severe depression had the highest representation [moderate: n= 35; 24.1%, severe: n=69 (47.6%) and extremely severe: n=27(18.6%)]. Anxiety had the second highest prevalence of n=99 (68.8%; M= 28.55±13.63) with differing prevalence rates in the levels of anxiety which were normal anxiety: 45(31.3%), moderate anxiety n=62(43.1%) and severe anxiety: n=37(25.7%). Regarding comorbidities, the Pearson correlation test showed that there was a significant (p=0.000) positive relationship between PTSD and depression (r=0.379; p=.000), PTSD and anxiety (r=0.624; p=.000), and depression and anxiety (r=0.386; p=.000) such that increase in one disorder concomitantly led to increase of the other two disorders; hence comorbidity of the three disorders was ascertained. Conclusion: The study asserted the adverse impacts of IPV on women’s mental well-being, where the prevalence of PTSD, depression, and anxiety was established. Almost all the women had depressive symptoms; whereas more than half had anxiety and slightly more than a third had PTSD. Regarding the severity levels of anxiety and depression, almost half of the women with depression had severe depression whereas moderate anxiety was more prevalent for those with anxiety. The three disorders were found to co-occur where comorbidities of PTSD and anxiety had the highest probability of co-occurrence. It is thus recommended that mental health interventions with a focus on the three disorders be offered for women undergoing IPV.

Keywords: anxiety, comorbidity, depression, intimate partner violence, post-traumatic stress disorder

Procedia PDF Downloads 58

Authors: Anoff Anim, Lila Mahmound, Maria Katsikogianni, Sanjit Nayak

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Sustained and controlled delivery of antimicrobial drugs have been largely studied recently using metal organic frameworks (MOFs)and different polymers. However, much attention has not been given to combining both MOFs and biodegradable polymers which would be a good strategy in providing a sustained gradual release of the drugs. Herein, we report a comparative study of the sustained and controlled release of widely used antibacterial drugs, cephalexin and metronidazole, from zinc-based MOF-5 incorporated in biodegradable polycaprolactone (PCL) and poly-lactic glycolic acid (PLGA) membranes. Cephalexin and metronidazole were separately incorporated in MOF-5 post-synthetically, followed by their integration into biodegradable PLGA and PCL membranes. The pristine MOF-5 and the loaded MOFs were thoroughly characterized by FT-IR, SEM, TGA and PXRD. Drug release studies were carried out to assess the release rate of the drugs in PBS and distilled water for up to 48 hours using UV-Vis Spectroscopy. Four bacterial strains from both the Gram-positive and Gram-negative types, Staphylococus aureus, Staphylococuss epidermidis, Escherichia coli, Acinetobacter baumanii, were tested against the pristine MOF, pure drugs, loaded MOFs and the drug-loaded MOF-polymer composites. Metronidazole-loaded MOF-5 composite of PLGA (PLGA-Met@MOF-5) was found to show highest efficiency to inhibit the growth of S. epidermidis compared to the other bacteria strains while maintaining a sustained minimum inhibitory concentration (MIC). This study demonstrates that the combination of biodegradable MOF-polymer composites can provide an efficient platform for sustained and controlled release of antimicrobial drugs, and can be a potential strategy to integrate them in biomedical devices.

Keywords: antimicrobial resistance, biodegradable polymers, cephalexin, drug release metronidazole, MOF-5, PCL, PLGA

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Authors: Emre Ünal, Hasan Başaran

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In this study, starting with a predetermined Lunar free-return trajectory, an analysis of major near-Earth perturbations is carried out. Referencing to historical Apollo-13 flight, changes in the mission’s resultant perimoon and perigee altitudes with each perturbative effect are evaluated. The perturbations that were considered are Earth oblateness effects, up to the 6^th order, atmospheric drag, third body perturbations consisting of solar and planetary effects and solar radiation pressure effects. It is found that for a Moon mission, most of the main perturbative effects spoil the trajectory significantly while some came out to be negligible. It is seen that for apparent future request of constructing low cost, reliable and safe trajectories to the Moon, most of the orbital perturbations are crucial.

Keywords: Apollo-13 trajectory, atmospheric drag, lunar trajectories, oblateness effect, perturbative effects, solar radiation pressure, third body perturbations

Procedia PDF Downloads 131

Authors: Ashwini Patil

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Caudal block is one of the most commonly used regional anesthetic techniques in children. Currently, fentanyl is used as an adjuvant to bupivacaine to prolong analgesia but fentanyl is a narcotic. Dexamethasone, a glucocorticoid with strong anti-inflammatory effects provides improvement in post-operative analgesia and post-operative side effects. However, its analgesic efficacy and safety in comparison with fentanyl has not been extensively studied. So the objective of this randomized controlled study is to compare dexamethasone with fentanyl as an adjuvant to bupivacaine for caudal block in children in relation to the duration of caudal analgesia, post-operative analgesic requirement and incidence of post-operative nausea and vomiting. This study included 100 children, aged 1–6 years, undergoing lower abdominal surgeries. Patients were randomized into two groups, 50 each to receive a combination of dexamethasone 0.2 mg/kg along with 1 ml/kg bupivacaine 0.25% (group A) or combination of fentanyl (1 ug/kg) along with 1ml/kg bupivacaine 0.25% (group B). In the post-operative period, pain was assessed using a Modified Objective Pain Scale (MOPS) until 12 hr after surgery and rescue analgesia is administered when MOPS score 4 or more is recorded. Residual motor block, number of analgesic doses required within 24 hr after surgery, sedation scores, intra-operative and post-operative hemodynamic variables, post-operative nausea and vomiting (PONV), and other adverse effects were recorded. Data is analysed using unpaired t test and Significance level of P< 0.05 is considered statistically significant. Group A showed a significantly longer time to first analgesic requirement than group B (p<0.05). The number of rescue analgesic doses required in the first 24 h was significantly less in group A (p<0.05). Group A showed significantly lower MOPS scores than group B(p<0.05). Intra-operative and post-operative hemodynamic variables, Modified Bromage Scale scores, and sedation scores were comparable in both the groups. Group A showed significantly fewer incidences of PONV compared with group B(p<0.05). This study reveals that adding dexamethasone to bupivacaine prolongs the duration of postoperative analgesia and decreases the incidence of PONV as compared to combination of fentanyl to bupivacaine after a caudal block in pediatric patients.

Keywords: bupivacaine, caudal analgesia, dexamethasone, pediatric

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Authors: Phuc D. Nguyen, Kristy L. Hansen, Branko Zajamsek

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The existence of special characteristics of wind farm noise such as amplitude modulation (AM) contributes significantly to annoyance, which could ultimately result in sleep disturbance and other adverse health effects for residents living near wind farms. In order to detect and quantify this phenomenon, several methods have been developed which can be separated into three types: time-domain, frequency-domain and hybrid methods. However, due to a lack of systematic validation of these methods, it is still difficult to select the best method for identifying AM. Furthermore, previous comparisons between AM methods have been predominantly qualitative or based on synthesised signals, which are not representative of the actual noise. In this study, a comparison between methods for detecting and quantifying AM has been carried out. The results are based on analysis of real noise data which were measured at a wind farm in South Australia. In order to evaluate the performance of these methods in terms of detecting AM, an approach has been developed to select the most successful method of AM detection. This approach uses a receiver operating characteristic (ROC) curve which is based on detection of AM in audio files by experts.

Keywords: amplitude modulation, wind farm noise, ROC curve

Procedia PDF Downloads 125

Authors: Marina Passero, Tianhua Zhai, Zuyi (Jacky) Huang

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Alzheimer’s disease has become a major public health issue, as indicated by the increasing populations of Americans living with Alzheimer’s disease. After decades of extensive research in Alzheimer’s disease, only seven drugs have been approved by Food and Drug Administration (FDA) to treat Alzheimer’s disease. Five of these drugs were designed to treat the dementia symptoms, and only two drugs (i.e., Aducanumab and Lecanemab) target the progression of Alzheimer’s disease, especially the accumulation of amyloid-b plaques. However, controversial comments were raised for the accelerated approvals of either Aducanumab or Lecanemab, especially with concerns on safety and side effects of these two drugs. There is still an urgent need for further drug discovery to target the biological processes involved in the progression of Alzheimer’s disease. Excessive cholesterol has been found to accumulate in the brain of those with Alzheimer’s disease. Cholesterol can be synthesized in both the blood and the brain, but the majority of biosynthesis in the adult brain takes place in astrocytes and is then transported to the neurons via ApoE. The blood brain barrier separates cholesterol metabolism in the brain from the rest of the body. Various proteins contribute to the metabolism of cholesterol in the brain, which offer potential targets for Alzheimer’s treatment. In the astrocytes, SREBP cleavage-activating protein (SCAP) binds to Sterol Regulatory Element-binding Protein 2 (SREBP2) in order to transport the complex from the endoplasmic reticulum to the Golgi apparatus. Cholesterol is secreted out of the astrocytes by ATP-Binding Cassette A1 (ABCA1) transporter. Lipoprotein receptors such as triggering receptor expressed on myeloid cells 2 (TREM2) internalize cholesterol into the microglia, while lipoprotein receptors such as Low-density lipoprotein receptor-related protein 1 (LRP1) internalize cholesterol into the neuron. Cytochrome P450 Family 46 Subfamily A Member 1 (CYP46A1) converts excess cholesterol to 24S-hydroxycholesterol (24S-OHC). Cholesterol has been approved for its direct effect on the production of amyloid-beta and tau proteins. The addition of cholesterol to the brain promotes the activity of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), secretase, and amyloid precursor protein (APP), which all aid in amyloid-beta production. The reduction of cholesterol esters in the brain have been found to reduce phosphorylated tau levels in mice. In this work, a computational pipeline was developed to identify the protein targets involved in cholesterol regulation in brain and further to identify chemical compounds as the inhibitors of a selected protein target. Since extensive evidence shows the strong correlation between brain cholesterol regulation and Alzheimer’s disease, a detailed literature review on genes or pathways related to the brain cholesterol synthesis and regulation was first conducted in this work. An interaction network was then built for those genes so that the top gene targets were identified. The involvement of these genes in Alzheimer’s disease progression was discussed, which was followed by the investigation of existing clinical trials for those targets. A ligand-protein docking program was finally developed to screen 1.5 million chemical compounds for the selected protein target. A machine learning program was developed to evaluate and predict the binding interaction between chemical compounds and the protein target. The results from this work pave the way for further drug discovery to regulate brain cholesterol to combat Alzheimer’s disease.

Keywords: Alzheimer’s disease, drug discovery, ligand-protein docking, gene-network analysis, cholesterol regulation

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Authors: Ankur P. Sati, Manju Mohan

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The hazardous combination of smoke and pollutant gases, smog, is harmful for health. There are strong evidences that the Agricultural waste burning (AWB) in the Northern India leads to adverse air quality in Delhi and its surrounding regions. A severe smog episode was observed over Delhi, India during November 2012 which resulted in very low visibility and various respiratory problems. Very high values of pollutants (PM10 as high as 989 µg m-3, PM2.5 as high as 585 µg m-3 an NO2 as high as 540 µg m-3) were measured all over Delhi during the smog episode. Ultra Violet Aerosol Index (UVAI) from Aura satellite and Aerosol Optical Depth (AOD) are used in the present study along with the output trajectories from HYSPLIT model and the in-situ data. Satellite data also reveal that AOD, UVAI are always at its highest during the farmfires duration in Punjab region of India and the extent of these farmfires may be increasing. It is observed that during the smog episode all the AOD, UVAI, PM2.5 and PM10 values surpassed those of the Diwali period (one of the most polluted events in the city) by a considerable amount at all stations across Delhi. The parameters used from the remote sensing data and the ground based observations at various stations across Delhi are very well in agreement about the intensity of Smog episode. The analysis clearly shows that regional pollution can have greater contributions in deteriorating the air quality than the local under adverse meteorological conditions.

Keywords: smog, farmfires, AOD, remote sensing

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Authors: Natsuda Rattamanee

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Like other countries, Thailand continually experiences strong protests against dam and reservoir proposals, especially large-scale projects. The protestors are constantly worried about the potential significant adverse impacts of the projects on the environment and society. Although project proponents are required by laws to assess the environmental and social impacts of the dam proposals by making environmental impact assessment (EIA) reports and finding mitigation measures before implementing the plans, the outcomes of the assessments often do not lessen the affected people and public’s concerns about the potential negative effects of the projects. One of the main reasons is that Thailand does not have a proper and efficient law to regulate project proponents when determining the scope of environmental impact assessments. Scoping is the crucial second stage of the preparation of an EIA report. The appropriate scope of assessments will allow EIA studies to focus only on the significant effects of the proposed project on particular resources, areas, and communities. It will offer crucial and sufficient information to the decision-makers and the public. The decision to implement the dam and reservoir projects considered based on the assessments with a proper scoping will eventually be more widely accepted by the public and reduce community opposition. The research work seeks to identify flaws in the current requirements of scoping steps under Thai laws and regulations and proposes recommendations to improve the legal scheme. The paper explores the well-established United States laws and relevant rules regulating how lead agencies determine the scope of their environmental impact assessments and some guidelines concerning scoping published by dominant institutions. Policymakers and legislature will find the results of studies helpful in improving the scoping-step requirements of EIA for dam and reservoir projects and reducing the level of anti-dam protests in Thailand.

Keywords: dam and reservoir, EIA, environmental impact assessment, law, scoping, Thailand

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Authors: Zhongyang Sun, Shu Zhang

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In osteoblasts, L-type voltage sensitive calcium channels (LTCCs), especially the Cav1.2 LTCCs, play fundamental roles in cellular responses to external stimuli including both mechanical forces and hormonal signals. Several lines of evidence have revealed that the density of bone is increased and the resorption of bone is decreased when these calcium channels in osteoblasts are activated. And numerous studies have shown that mechanical loading promotes bone formation in the modeling skeleton, whereas removal of this stimulus in microgravity results in a reduction in bone mass. However, the effect of microgravity on LTCCs in osteoblasts is still unknown. The aim of this study was to determine whether microgravity exerts influence on LTCCs in osteoblasts and the possible mechanisms underlying. In this study, we demonstrate that simulated microgravity substantially inhibits LTCCs in osteoblast by suppressing the expression of Cav1.2. Then we show that the up-regulation of miR-103 is involved in the down-regulation of Cav1.2 expression and inhibition of LTCCs by simulated microgravity in osteoblasts. Our study provides a novel mechanism of simulated microgravity-induced adverse effects on osteoblasts, offering a new avenue to further investigate the bone loss caused by microgravity.

Keywords: L-type voltage sensitive calcium channels, Cav1.2, osteoblasts, microgravity

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Authors: Akbar Esmaeili, Fateme Dadashi

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Bismuth can increase radiation and reduce the dose of radiotherapy. On the other hand, hyaluronic acid plays a role in healing damaged cells, and melittin has been used to destroy cancer cells. This research aims to destroy eye cancer cells and accelerate the recovery of damaged healthy cells during treatment. In this research, we used this nanoparticle, the sol-gel method. According to the optimization process that was carried out, we obtained the optimal value of the desired variables for the manufacture of nanoparticles. The advantage of doing this is reducing the amount of medicine used, as a result of reducing the number of side effects during the treatment and using melittin as an anti-eye cancer drug and the presence of hyaluronic acid to accelerate the recovery of cells, as well as coating the bismuth nanoparticle with chitosan to increase the half-life of the nanoparticle and prevent its adhesion.

Keywords: synthesis, nanoparticles, coated, cancer

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Authors: Tamrat Girma Biru

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Multidrug-resistant tuberculosis (MDR-TB) is defined as resistant to at least Refampicin and Isoniazed: the most two power full TB drugs. It is a leading cause of high rates of morbidity and mortality, and increasing psychosocial challenges to patients, especially when co-infected with Human Immunodeficiency Virus (HIV). Ethiopia faces the highest rates of MDR-TB infection in the world. Objectives: The main objective of this study was to identify the psychosocial challenges of MDR-TB patients, to investigate the extent of the psychosocial challenges on (self-esteem, depression, and stigma) that MDR-TB patients encounter, to examine whether there is a sex difference in experiencing psychosocial challenges and assess the counseling needs of MDR-TB patients. Methodology: A cross-sectional study was conducted at St. Peter TB Specialized Hospital, Addis Ababa on 40 patients (25 males and 15 females) who are hospitalized for treatment. The patients were identified by using purposive sampling and made fill a questionnaire measuring their level of self-esteem, depression and stigma. Besides, data were collected from 16 participants, 28 care providers and 8 guardians, using semi-structured interview. The obtained data were analyzed using SPSS statistical program, descriptive statistics, independent t-test, and qualitative description. Results and Discussion: The results of the study showed that the majority (80%) of the respondents had suffered psychological challenges and social discriminations. Thus, the significance of MDR-TB and its association with HIV/AIDS problems is considered. Besides the psychosocial challenges, various aggravating factors such as length of treatment, drug burden and insecurity in economy together highly challenges the life of patients. In addition, 60% of participants showed low level of self-esteem. The patients also reported that they experienced high self-stigma and stigma by other members of the society. The majority of the participants (75%) showed moderate and severe level of depression. In terms of sex there is no difference between the mean scores of males and females in the level of depression and stigmatization by others and by themselves. But females showed lower level of self-esteem than males. The analysis of the t-test also shows that there were no statistically significant sex difference on the level of depression and stigma. Based on the qualitative data MDR-TB patients face various challenges in their life sphere such as: Psychological (depression, low self value, lowliness, anxiety), social (stigma, isolation from social relations, self-stigmatization,) and medical (drug side effect, drug toxicity, drug burden, treatment length, hospital stays). Recommendations: Based on the findings of this study possible recommendations were forwarded: develop and extend MDR-TB disease awareness creation through by media (printing and electronic), school net TB clubs, and door to door community education. Strengthen psychological wellbeing and social relationship of MDR-TB patients using proper and consistent psychosocial support and counseling. Responsible bodies like Ministry of Health (MOH) and its stakeholders and Non Governmental Organizations (NGOs) need to assess the challenges of patients and take measures on this pressing issue.

Keywords: psychosocial challenges, counseling, multi-drug resistant tuberculosis (MDR-TB), tuberculosis therapy

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Authors: Xiaofei Li, Zhiwei Zhong, Deli Wang

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Large herbivores affect plant growth not only through their direct, consumptive effects, but also through indirect effects that alter species interactions. Indirect effects can be either positive or negative, therefore having the potential to mitigate or enhance the direct impacts of herbivores. However, until recently, we know considerably less about the indirect effects than the direct effects of large herbivores on plants, and few studies have explored multiple indirect pathways simultaneously. Here, we investigated how large domestic herbivores, cattle (Bos taurus), can shape population growth of an intermediately preferred forb species, Artemsisa scoparia, through diverse pathways in a temperate grassland of northeast China. We found that, although exposure to direct consumption of cattle, A. scoparia growth was not inhibited, but rather showed a significant increase in the grazed than ungrazed areas. This unexpected result was due to grazing-induced multiple indirect, positive effects overwhelmed the direct, negative consumption effects of cattle on plant growth. The much more intensive consumption on the dominant Leymus chinensis grass, ground litter removal, and increases in ant nest abundance induced by cattle, exerted significant indirect, positive effects on A. scoparia growth. These pathways benefited A.scoparia growth by lessening interspecific competition, mitigating negative effects of litter accumulation, and increasing soil nutrient availability, respectively. Our results highlight the need to integrate indirect effects into the traditional food web theory, which is based primary on direct, trophic linkages, to fully understand community organization and dynamics. Large herbivores are important conservation and management targets, our results suggest that these mammals should be managed with the understanding that they can affect primary producers through diverse paths.

Keywords: grasslands, large herbivores, plant growth, indirect effects

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Authors: Soroosh Torabi, Brad Berron, Ren Xu, Christine Trinkle

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Microfluidics integrated with 3D cell culture is a powerful technology to mimic cellular environment, and can be used to study cell activities such as proliferation, migration and response to drugs. This technology has gained more attention in cancer studies over the past years, and many organ-on-a-chip systems have been developed to study cancer cell behaviors in an ex-vivo tumor microenvironment. However, there are still some barriers to adoption which include low throughput, complexity in 3D cell culture integration and limitations on non-optical analysis of cells. In this study, a user-friendly microfluidic multi-well plate was developed to mimic the in vivo tumor microenvironment. The microfluidic platform feeds multiple 3D cell culture sites at the same time which enhances the throughput of the system. The platform uses hydrophobic Cassie-Baxter surfaces created by microchannels to enable convenient loading of hydrogel/cell suspensions into the device, while providing barrier free placement of the hydrogel and cells adjacent to the fluidic path. The microchannels support convective flow and diffusion of nutrients to the cells and a removable lid is used to enable further chemical and physiological analysis on the cells. Different breast cancer cell lines were cultured in the device and then monitored to characterize nutrient delivery to the cells as well as cell invasion and proliferation. In addition, the drug response of breast cancer cell lines cultured in the device was compared to the response in xenograft models to the same drugs to analyze relevance of this platform for use in future drug-response studies.

Keywords: microfluidics, multi-well 3d cell culture, tumor microenvironment, tumor-on-a-chip

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Authors: Tadele Araya, Tsehaye Asmelash, Girmatsion Fiseha

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Background: Hepatitis B virus (HBV), Hepatitis C virus (HCV) and Human Immunodeficiency Virus (HIV) constitute serious healthcare problems worldwide. Blood-borne pathogens HBV, HCV and HIV are commonly associated with infections among substance or Injection Drug Users (IDUs). The objective of this study was to determine the prevalence of HBV, HCV, and HIV infections among substance users in Mekelle Substance users Treatment and Rehabilitation Centers. Methods: A cross-sectional study design was used from Dec 2020 to Sep / 2021 to conduct the study. A total of 600 substance users were included. Data regarding the socio-demographic, clinical and sexual behaviors of the substance users were collected using a structured questionnaire. For laboratory analysis, 5-10 ml of venous blood was taken from the substance users. The laboratory analysis was performed by Enzyme-Linked Immunosorbent Assay (ELISA) at Mekelle University, Department of Medical Microbiology and Immunology Research Laboratory. The Data was analyzed using SPSS and Epi-data. The association of variables with HBV, HCV and HIV infections was determined using multivariate analysis and a P value < 0.05 was considered statistically significant. Result: The overall prevalence rate of HBV, HCV and HIV infections were 10%, 6.6%, and 7.5%, respectively. The mean age of the study participants was 28.12 ± 6.9. A higher prevalence of HBV infection was seen in participants who were users of drug injections and in those who were infected with HIV. HCV was comparatively higher in those who had a previous history of unsafe surgical procedures than their counterparts. Homeless participants were highly exposed to HCV and HIV infections than their counterparts. The HBV/HIV Co-infection prevalence was 3.5%. Those doing unprotected sexual practices [P= 0.03], Injection Drug users [P= 0.03], those who had an HBV-infected person in their family [P=0.02], infected with HIV [P= 0.025] were statistically associated with HBV infection. HCV was significantly associated with Substance users and previous history of unsafe surgical procedures [p=0.03, p=0.04), respectively. HIV was significantly associated with unprotected sexual practices and being homeless [p=0.045, p=0.05) respectively. Conclusion-The highly prevalent viral infection was HBV compared to others. There was a High prevalence of HBV/HIV co-infection. The presence of HBV-infected persons in a family, unprotected sexual practices and sharing of needles for drug injection were the risk factors associated with HBV, HIV, and HCV. Continuous health education and screening of the viral infection coupled with medical and psychological treatment is mandatory for the prevention and control of the infections.

Keywords: hepatitis b virus, hepatitis c virus, HIV, substance users

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Authors: Ali Ghorbanipour

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The aim of this study is to investigate the drug resistance pattern and the value of the MIC (minimum inhibitory concentration)method to reduce the impact of infectious diseases and the slow development of resistance. Method: The study was conducted on clinical specimens collected between 2018 to 2021. identification of isolates and antibiotic susceptibility testing were performed using conventional biochemical tests. Antibiotic resistance was determined using kibry-Bauer disk diffusion and MIC by E-test methods comparative with microdilution plate elisa method. Results were interpreted according to CLSI. Results: Out of 249600 different clinical specimens, 18720 different pathogenic bacteria by overall detection ratio 7.7% were detected. Among pathogen bacterial were Gram negative bacteria (70%,n=13000) and Gram positive bacteria(30%,n=5720).Medically relevant gram-negative bacteria include a multitude of species such as E.coli , Klebsiella .spp , Pseudomonas .aeroginosa , Acinetobacter .spp , Enterobacterspp ,and gram positive bacteria Staphylococcus.spp , Enterococcus .spp , Streptococcus .spp was isolated . Conclusion: Our results highlighted that the resistance ratio among Gram Negative bacteria and Gram positive bacteria with different infection is high it suggest constant screening and follow-up programs for the detection of antibiotic resistance and the value of MIC drug susceptibility reporting that provide a new way to the usage of resistant antibiotic in combination with other antibiotics or accurate weight of antibiotics that inhibit or kill bacteria. Evaluation of wrong medication in the expansion of resistance and side effects of over usage antibiotics are goals. Ali ghorbanipour presently working as a supervision at the microbiology department of Massoud medical laboratory. Iran. Earlier, he worked as head department of pulmonary infection in firoozgarhospital, Iran. He received master degree in 2012 from Fergusson College. His research prime objective is a biologic wound dressing .to his credit, he has Published10 articles in various international congresses by presenting posters.

Keywords: antimicrobial profile, MIC & MBC Method, microplate antimicrobial assay, E-test

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Authors: Athicha Cherdpunt, Patompong Satapornpong

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The medical cannabis is made up of components also known as cannabinoids, which consists of two ingredients which are Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Interestingly, the Cannabinoid can be used for many treatments such as chemotherapy, including nausea and vomiting, cachexia, anorexia nervosa, spinal cord injury and disease, epilepsy, pain, and many others. However, the adverse drug reactions (ADRs) of THC can cause sedation, anxiety, dizziness, appetite stimulation and impairments in driving and cognitive function. Furthermore, genetic polymorphisms of CYP2C9, CYP2C19 and CYP3A4 influenced the THC metabolism and might be a cause of ADRs. Particularly, CYP2C19*17 allele increases gene transcription and therefore results in ultra-rapid metabolizer phenotype (UM). The aim of this study, is to investigate the frequency of CYP2C19*17 alleles in Thai patients who have been treated with medical cannabis. We prospectively enrolled 60 Thai patients who were treated with medical cannabis and clinical data from College of Pharmacy, Rangsit University. DNA of each patient was isolated from EDTA blood, using the Genomic DNA Mini Kit. CYP2C19*17 genotyping was conducted using the real time-PCR ViiA7 (ABI, Foster City, CA, USA). 30 patients with medical cannabis-induced ADRs group, 20 (67%) were female, and 10 (33%) were male, with an age range of 30-69 years. On the other hand, 30 patients without medical cannabis-induced ADRs (control group) consist of 17 (57%) female and 13 (43%) male. The most ADRs for medical cannabis treatment in the case group were dry mouth and dry throat (77%), tachycardia (70%), nausea (30%) and arrhythmia(10%). Accordingly, the case group carried CYP2C19*1/*1 (normal metabolizer) approximately 93%, while 7% patients carrying CYP2C19*1/*17 (ultra rapid metabolizers) exhibited in this group. Meanwhile, we found 90% of CYP2C19*1/*1 and 10% of CYP2C19*1/*17 in control group. In this study, we identified the frequency of CYP2C19*17 allele in Thai population which will support the pharmacogenetics biomarkers for screening and avoid ADRs of medical cannabis treatment.

Keywords: CYP2C19, allele frequency, ultra rapid metabolizer, medical cannabis

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Authors: Ieva Bruzauskaite, Jovile Raudoniute, Karina Poliakovaite, Danguole Zabulyte, Daiva Bironaite, Ruta Aldonyte

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Introduction: Air pollution is a growing global problem which has been shown to be responsible for various adverse health outcomes. Immunotoxicity, such as dysregulated inflammation, has been proposed as one of the main mechanisms in air pollution-associated diseases. Chronic obstructive pulmonary disease (COPD) is among major morbidity and mortality causes worldwide and is characterized by persistent airflow limitation caused by the small airways disease (obstructive bronchiolitis) and irreversible parenchymal destruction (emphysema). Exact pathways explaining the air pollution induced and mediated disease states are still not clear. However, modern societies understand dangers of polluted air, seek to mitigate such effects and are in need for reliable biomarkers of air pollution. We hypothesise that post-translational modifications of structural proteins, e.g. citrullination, might be a good candidate biomarker. Thus, we have designed this study, where mice were exposed to diesel exhaust and the ongoing protein modifications and inflammation in lungs and other tissues were assessed. Materials And Methods: To assess the effects of diesel exhaust a in vivo study was designed. Mice (n=10) were subjected to everyday 2-hour exposure to diesel exhaust for 14 days. Control mice were treated the same way without diesel exhaust. The effects within lung and other tissues were assessed by immunohistochemistry of formalin-fixed and paraffin-embedded tissues. Levels of inflammation and citrullination related markers were investigated. Levels of parenchymal damage were also measured. Results: In vivo study corroborates our own data from in vitro and reveals diesel exhaust initiated inflammatory shift and modulation of lung peptidyl arginine deiminase 4 (PAD4), citrullination associated enzyme, levels. In addition, high levels of citrulline were observed in exposed lung tissue sections co-localising with increased parenchymal destruction. Conclusions: Subacute exposure to diesel exhaust renders mice lungs inflammatory and modifies certain structural proteins. Such structural changes of proteins may pave a pathways to lost/gain function of affected molecules and also propagate autoimmune processes within the lung and systemically.

Keywords: air pollution, citrullination, in vivo, lungs

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Authors: Emmanuel Yussuf, John Muthama, John Ng'ang'A

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There has been increasing noise levels all over the world in the last decade. Many factors contribute to this increase, which is causing health related effects to humans. Developing countries are not left out of the whole picture as they are still growing and advancing their development. Motor vehicles are increasing on urban roads; there is an increase in infrastructure due to the rising population, increasing number of industries to provide goods and so many other activities. All this activities lead to the high noise levels in cities. This study was conducted in Nairobi’s Central Business District (CBD) with the main objective of simulating noise levels in order to understand the noise exposed to the people within the urban area, in relation to weather parameters namely temperature, rainfall and wind field. The study was achieved using the Neighbourhood Proximity Model and Time Series Analysis, with data obtained from proxies/remotely-sensed from satellites, in order to establish the levels of noise exposed to which people of Nairobi CBD are exposed to. The findings showed that there is an increase in temperature (0.1°C per year) and a decrease in precipitation (40 mm per year), which in comparison to the noise levels in the area, are increasing. The study also found out that noise levels exposed to people in Nairobi CBD were roughly between 61 and 63 decibels and has been increasing, a level which is high and likely to cause adverse physical and psychological effects on the human body in which air temperature, precipitation and wind contribute so much in the spread of noise. As a noise reduction measure, the use of sound proof materials in buildings close to busy roads, implementation of strict laws to most emitting sources as well as further research on the study was recommended. The data used for this study ranged from the year 2000 to 2015, rainfall being in millimeters (mm), temperature in degrees Celsius (°C) and the urban form characteristics being in meters (m).

Keywords: simulation, noise exposure, weather, proxy

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Authors: Jong Yeop Kim, Sung Young Park, Dae Hee Kim, Han Bum Joe, Ji Young Yoo, Jong Bum Choi, Sook Young Lee

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Emergence agitation (EA) is commonly reported adverse events after sevoflurane anesthesia in pediatric patients. The efficacy of prophylactic remifentanil, one of mu opioid agonist, in preventing EA is controversial. This meta-analysis assessed the effectiveness of remifentanil to decrease the incidence of EA from sevoflurane anesthesia in children. We searched for randomized controlled trials comparing sevoflurane alone anesthesia with sevoflurane and remifentanil anesthesia to prevent EA in the Cochrane Library, Embase, Pubmed, and KoreaMed, and included 6 studies with 361 patients. The number of patients of reporting EA was summarized using risk ratio (RR) with 95% confidence interval (CI), with point estimates and 95CIs derived from a random effects Mantel-Haenszel method. Overall incidence of EA was about 41%. Compared with sevoflurane alone anesthesia, intravenous infusion of remifentanil with sevoflurane significantly reduced the incidence of EA (RR 0.53, 95% CI 0.39-0.73, P < 0.0001), (heterogeneity, I2 = 0, P = 0.42). This meta-analysis suggested that continuous infusion of remifentanil could be effective in decreasing the EA of about 47% after sevoflurane anesthesia. However, considering limitations of the included studies, more randomized controlled studies are required to verify our results.

Keywords: emergence agitation, meta-analysis, remifentanil, pediatrics

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Authors: Suliman Al-Fayoumi, Sherri Amberg, Huafeng Zhou, Jack W. Singer, James P. Dean

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Pacritinib is an oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1, and CSF1R. In clinical studies, pacritinib was well tolerated with clinical activity in patients with myelofibrosis. The most frequent adverse events (AEs) observed with pacritinib are gastrointestinal (diarrhea, nausea, and vomiting; mostly grade 1-2 in severity) and typically resolve within 2 weeks. A human ADME mass balance study demonstrated that pacritinib is predominantly cleared via hepatic metabolism and biliary excretion (>85% of administered dose). The major hepatic metabolite identified, M1, is not thought to materially contribute to the pharmacological activity of pacritinib. Hepatic diseases are known to impair hepatic blood flow, drug-metabolizing enzymes, and biliary transport systems and may affect drug absorption, disposition, efficacy, and toxicity. This phase 1 study evaluated the pharmacokinetics (PK) and safety of pacritinib and the M1 metabolite in study subjects with mild, moderate, or severe hepatic impairment (HI) and matched healthy subjects with normal liver function to determine if pacritinib dosage adjustments are necessary for patients with varying degrees of hepatic insufficiency. Study participants (aged 18-85 y) were enrolled into 4 groups based on their degree of HI as defined by Child-Pugh Clinical Assessment Score: mild (n=8), moderate (n=8), severe (n=4), and healthy volunteers (n=8) matched for age, BMI, and sex. Individuals with concomitant renal dysfunction or progressive liver disease were excluded. A single 400 mg dose of pacritinib was administered to all participants. Blood samples were obtained for PK evaluation predose and at multiple time points postdose through 168 h. Key PK parameters evaluated included maximum plasma concentration (Cmax), time to Cmax (Tmax), area under the plasma concentration time curve (AUC) from hour zero to last measurable concentration (AUC0-t), AUC extrapolated to infinity (AUC0-∞), and apparent terminal elimination half-life (t1/2). Following treatment, pacritinib was quantifiable for all study participants at 1 h through 168 h postdose. Systemic pacritinib exposure was similar between healthy volunteers and individuals with mild HI. However, there was a significant difference between those with moderate and severe HI and healthy volunteers with respect to peak concentration (Cmax) and plasma exposure (AUC0-t, AUC0-∞). Mean Cmax decreased by 47% and 57% respectively in participants with moderate and severe HI vs matched healthy volunteers. Similarly, mean AUC0-t decreased by 36% and 45% and mean AUC0-∞ decreased by 46% and 48%, respectively in individuals with moderate and severe HI vs healthy volunteers. Mean t1/2 ranged from 51.5 to 74.9 h across all groups. The variability on exposure ranged from 17.8% to 51.8% across all groups. Systemic exposure of M1 was also significantly decreased in study participants with moderate or severe HI vs. healthy participants and individuals with mild HI. These changes were not significantly dissimilar from the inter-patient variability in these parameters observed in healthy volunteers. All AEs were grade 1-2 in severity. Diarrhea and headache were the only AEs reported in >1 participant (n=4 each). Based on these observations, it is unlikely that dosage adjustments would be warranted in patients with mild, moderate, or severe HI treated with pacritinib.

Keywords: pacritinib, myelofibrosis, hepatic impairment, pharmacokinetics

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Authors: Syamimi Shamsuddin, Hanafiah Yussof, Fazah Akhtar Hanapiah, Salina Mohamed, Nur Farah Farhan Jamil, Farhana Wan Yunus

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Robot-based intervention for children with autism is an evolving research niche in human-robot interaction (HRI). Recent studies in this area mostly covered the role of robots in the clinical and experimental setting. Our previous work had shown that interaction with a robot pose no adverse effects on the children. Also, the presence of the robot, together with specific modules of interaction was associated with less autistic behavior. Extending this impact on school-going children, interactions that are in-tune with special education lessons are needed. This methodological paper focuses on how a robot can be incorporated in a current learning environment for autistic children. Six interaction scenarios had been designed based on the existing syllabus to teach communication skills, using the Applied Behavior Analysis (ABA) technique as the framework. Development of the robotic experience in class also covers the required set-up involving participation from teachers. The actual research conduct involving autistic children, teachers and robot shall take place in the next phase.

Keywords: autism spectrum disorder, ASD, humanoid robot, communication skills, robot-assisted learning

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Authors: Xiao Wang, Qinge Zhang

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Background: This randomized, open-label study examined the therapeutic effects of computerized cognitive training (CCT) combined with selective serotonin reuptake inhibitors (SSRIs) on cognitive impairment among patients with late-life depression (LLD). Method: Study data were collected from May 5, 2021, to April 21, 2023. Outpatients who met diagnostic criteria for major depressive disorder according to the fifth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria (i.e., a total score on the 17-item Hamilton Depression Rating Scale (HAMD-17) ≥ 18 and a total score on the Montreal Cognitive Assessment scale (MOCA) <26) were randomly assigned to receive up to 12 weeks of CCT and SSRIs treatment (n=57) or SSRIs and Control treatment (n=61). The primary outcome was the change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores from baseline to week 12 between the two groups. The secondary outcomes included changes in the HAMD-17 score, Hamilton Anxiety Scale (HAMA) score and Neuropsychiatric Inventory (NPI) score. Mixed model repeated measures (MMRM) analysis was performed on modified intention-to-treat (mITT) and completer populations. Results: The full analysis set (FAS) included 118 patients (CCT and SSRIs group, n=57; SSRIs and Control group, n =61). Over the 12-week study period, the reduction in the ADAS-cog total score was significant (P < 0.001) in both groups, while MMRM analysis revealed a significantly greater reduction in cognitive function (ADAS-cog total scores) from baseline to posttreatment in the CCT and SSRIs group than in the SSRI and Control group [(F (1,115) =13.65, least-squares mean difference [95% CI]: −2.77 [−3.73, −1.81], p<0.001)]. There were significantly greater improvements in depression symptoms (measured by the HAMD-17) in the CCT and SSRIs group than in the control group [MMRM, estimated mean difference (SE) between groups −3.59 [−5.02, −2.15], p < 0.001]. The least-squares mean changes in the HAMA scores and NPI scores between baseline and week 8 were greater in the CCT and SSRIs group than in the control group (all P < 0.05). There was no significant difference between groups on response rates and remission rates by using the last-observation-carried-forward (LOCF) method (all P > 0.05). The most frequent adverse events (AEs) in both groups were dry mouth, somnolence, and constipation. There was no significant difference in the incidence of adverse events between the two groups. Conclusions: CCT combined with SSRIs was efficacious and well tolerated in LLD patients with cognitive impairment.

Keywords: late-life depression, cognitive function, computerized cognitive training, SSRIs

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