Search results for: therapeutic efficacy

Authors: Sakshi Piplani, Ajit Kumar

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Valproic acid (VPA) is the first synthetic therapeutic agent used to treat epileptic disorders, which account for affecting nearly 1% world population. Teratogenicity caused by VPA has prompted the search for next generation drug with better efficacy and lower side effects. Recent studies have posed HDAC8 as direct target of VPA that causes the teratogenic effect in foetus. We have employed molecular dynamics (MD) and docking simulations to understand the binding mode of VPA and their analogues onto HDAC8. A total of twenty 3D-structures of human HDAC8 isoforms were selected using BLAST-P search against PDB. Multiple sequence alignment was carried out using ClustalW and PDB-3F07 having least missing and mutated regions was selected for study. The missing residues of loop region were constructed using MODELLER and energy was minimized. A set of 216 structural analogues (>90% identity) of VPA were obtained from Pubchem and ZINC database and their energy was optimized with Chemsketch software using 3-D CHARMM-type force field. Four major neurotransmitters (GABAt, SSADH, α-KGDH, GAD) involved in anticonvulsant activity were docked with VPA and its analogues. Out of 216 analogues, 75 were selected on the basis of lower binding energy and inhibition constant as compared to VPA, thus predicted to have anti-convulsant activity. Selected hHDAC8 structure was then subjected to MD Simulation using licenced version YASARA with AMBER99SB force field. The structure was solvated in rectangular box of TIP3P. The simulation was carried out with periodic boundary conditions and electrostatic interactions and treated with Particle mesh Ewald algorithm. pH of system was set to 7.4, temperature 323K and pressure 1atm respectively. Simulation snapshots were stored every 25ps. The MD simulation was carried out for 20ns and pdb file of HDAC8 structure was saved every 2ns. The structures were analysed using castP and UCSF Chimera and most stabilized structure (20ns) was used for docking study. Molecular docking of 75 selected VPA-analogues with PDB-3F07 was performed using AUTODOCK4.2.6. Lamarckian Genetic Algorithm was used to generate conformations of docked ligand and structure. The docking study revealed that VPA and its analogues have more affinity towards ‘hydrophobic active site channel’, due to its hydrophobic properties and allows VPA and their analogues to take part in van der Waal interactions with TYR24, HIS42, VAL41, TYR20, SER138, TRP137 while TRP137 and SER138 showed hydrogen bonding interaction with VPA-analogues. 14 analogues showed better binding affinity than VPA. ADMET SAR server was used to predict the ADMET properties of selected VPA analogues for predicting their druggability. On the basis of ADMET screening, 09 molecules were selected and are being used for in-vivo evaluation using Danio rerio model.

Keywords: HDAC8, docking, molecular dynamics simulation, valproic acid

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Authors: Vijaya Kumar, Vidayasagar Pagilla, Abraham Joshua, Rakshith Kedambadi, Prasanna Mithra

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Background: Post stroke rehabilitation are aimed to accelerate for optimal sensorimotor recovery, functional gain and to reduce long-term dependency. Intensive physical therapy interventions can enhance this recovery as experience-dependent neural plastic changes either directly act at cortical neural networks or at distal peripheral level (muscular components). Neuromuscular Electrical Stimulation (NMES), a traditional bottom-up approach, mirror therapy (MT), a relatively new top down approach have found to be an effective adjuvant treatment methods for lower extremity motor and functional recovery in stroke rehabilitation. However there is a scarcity of evidence to compare their therapeutic gain in stroke recovery.Aim: To compare the efficacy of neuromuscular electrical stimulation (NMES) and mirror therapy (MT) in very early phase of post stroke rehabilitation addressed to lower extremity motor recovery and balance. Design: observer blinded Randomized Clinical Trial. Setting: Neurorehabilitation Unit, Department of Physical Therapy, Tertiary Care Hospitals. Subjects: 32 acute stroke subjects with first episode of unilateral stroke with hemiparesis, referred for rehabilitation (onset < 3 weeks), Brunnstorm lower extremity recovery stages ≥3 and MMSE score more than 24 were randomized into two group [Group A-NMES and Group B-MT]. Interventions: Both the groups received eclectic approach to remediate lower extremity recovery which includes treatment components of Roods, Bobath and Motor learning approaches for 30 minutes a day for 6 days. Following which Group A (N=16) received 30 minutes of surface NMES training for six major paretic muscle groups (gluteus maximus and medius,quadriceps, hamstrings, tibialis anterior and gastrocnemius). Group B (N=16) was administered with 30 minutes of mirror therapy sessions to facilitate lower extremity motor recovery. Outcome measures: Lower extremity motor recovery, balance and activities of daily life (ADLs) were measured by Fugyl Meyer Assessment (FMA-LE), Berg Balance Scale (BBS), Barthel Index (BI) before and after intervention. Results: Pre Post analysis of either group across the time revealed statistically significant improvement (p < 0.001) for all the outcome variables for the either group. All parameters of NMES had greater change scores compared to MT group as follows: FMA-LE (25.12±3.01 vs. 23.31±2.38), BBS (35.12±4.61 vs. 34.68±5.42) and BI (40.00±10.32 vs. 37.18±7.73). Between the groups comparison of pre post values showed no significance with FMA-LE (p=0.09), BBS (p=0.80) and BI (p=0.39) respectively. Conclusion: Though either groups had significant improvement (pre to post intervention), none of them were superior to other in lower extremity motor recovery and balance among acute stroke subjects. We conclude that eclectic approach is an effective treatment irrespective of NMES or MT as an adjunct.

Keywords: balance, motor recovery, mirror therapy, neuromuscular electrical stimulation, stroke

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Authors: Kayla Murray, Andrew Green, Gopi Paliyath, Keith Warriner

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Introduction: It is now acknowledged that control of human pathogens associated with fresh produce requires an integrated approach of several interventions as opposed to relying on post-harvest washes to remove field acquired contamination. To this end, current research is directed towards identifying such interventions that can be applied at different points in leafy green processing. Purpose: In the following the efficacy of different gas phase treatments to decontaminate whole lettuce heads during pre-processing storage were evaluated. Methods: Whole Cos lettuce heads were spot inoculated with L. monocytogenes, E. coli O157:H7 or Salmonella spp. The inoculated lettuce heads were then placed in a treatment chamber and exposed to ozone, chlorine dioxide or hydroxyl radicals at different time periods under a range of relative humidity. Survivors of the treatments were enumerated along with sensory analysis performed on the treated lettuce. Results: Ozone gas reduced L. monocytogenes by 2-log10 after ten-minutes of exposure with Salmonella and E. coli O157:H7 being decreased by 0.66 and 0.56-log cfu respectively. Chlorine dioxide gas treatment reduced L. monocytogenes and Salmonella on lettuce heads by 4 log cfu but only supported a 0.8 log cfu reduction in E. coli O157:H7 numbers. In comparison, hydroxyl radicals supported a 2.9 – 4.8 log cfu reduction of model human pathogens inoculated onto lettuce heads but required extended exposure times and relative humidity < 0.8. Significance: From the gas phase sanitizers tested, chlorine dioxide and hydroxyl radicals are the most effective. The latter process holds most promise based on the ease of delivery, worker safety and preservation of lettuce sensory characteristics. Although expose times for hydroxyl radicles was relatively long (24h) this should not be considered a limitation given the intervention is applied in store rooms or in transport containers during transit.

Keywords: gas phase sanitizers, iceberg lettuce heads, leafy green processing

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Authors: Liya Abraham

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Eritrea is located along the Red Sea, north of the Horn of Africa, between Djibouti and Sudan and has a population of about 3.2 million as of 2010. It has six administrative regions; Anseba, Debub, Debubawi K’eyih Bahri, Gash-Barka, Ma'akel, and Semenawi K’eyih Bahri. Eritrea has got its independence in 1991 after 30 years war of liberation. The country is blessed with various medicinal flora and fauna, and marine and terrestrial biodiversity. Traditional Medicine (TM) has been an integral part of the Eritrean culture for centuries. So far, more than 19 TM modalities have been recognized, and are broadly categorized as; herbal, procedure-based and spiritual. Despite the availability of modern medicine to the majority of the population, TM is still widely practiced. The rationale behind widespread use is accessibility, affordability and cultural acceptability. Hence, TM is of great contribution to the Eritrean health care system. As a matter of fact, harnessing the potential contribution of effective and safe TM in order to attain Universal Health Coverage (UHC) has been emphasized in the WHO TM strategy 2014-2023. The Eritrean TM, however, was operating without regulation and reliable scientific justification behind its safety and efficacy. Thus, the Ministry of Health (MoH), in recognition of the role of TM in primary healthcare and safeguard public health, established a regulatory body for TM so-called as Traditional Medicine Unit (TMU) in 2012. The mission of the unit is to ensure rational TM use through an integrated health service delivery system and contribute to the country’s economic and social development. The unit has established its national TM policy in 2017. The activities of the unit are guided by the National TM Advisory Committee (TMAC), responsible for the provision of technical assistance and advisory role. Moreover, the Legal Framework and Code of Ethics and Practice which provide a legal basis for the regulation of TM have also been drafted. In recognition of the importance of TM research and development, the unit launched a nationwide TM survey in 2017 and had surveyed two zones (Gash-Barka and Debub). The findings of the survey were subjected to a research dissemination workshop and publication in international journals. Furthermore, TM-related adverse events reporting tool (Green Form) aiming to guide regulatory interventions and researches have been established by the unit, and ever since reports are flowing. The unit has also been offering training to THPs, pharmacy students and health care professionals regarding TM and its regulatory activities. In addition, as part of the establishment of the national medicinal plants' database and herbal monograph, more than 329 and 30 medicinal plants, have been compiled respectively. In conclusion, TM is still widely accepted and practiced in Eritrea. The TMU ever since its establishment is endeavoring to ensure the safety and efficacy of the TM, and its integration in the mainstream health service delivery system.

Keywords: efficacy, regulation, safety, traditional medicine, traditional medicine unit, universal health coverage

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Authors: Geoffrey A. Wright

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Over the past year we have developed and implemented a blended STEM curriculum based on ROV (Remotely Operated Vehicle) underwater technology with over 300 students in grades 2–9. This paper presents an overview of the curriculum, what we have learned from the development and implementation, with suggestions of how to build a similar statewide ROV program, and how we will continue and enhance the effort this next year with more than 300 additional students. The benefits of the program are the application and blending of STEM principles using inquiry based instruction, where students have shown to increase in STEM self-efficacy and interest.

Keywords: STEM, technology, engineering, ROV

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Authors: Eun-Seop Kim, Eun-Ha Jang, Rana R. Kim, Sae-Byul Jang

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Objective: Preterm labor is the most common antecedent of preterm birth(PTB), which is characterized by regular uterine contraction before 37 weeks of pregnancy and cervical change. In acute preterm labor, tocolytics are administered as the first-line medication to suppress uterine contractions but rarely delay pregnancy to 37 weeks of gestation. On the other hand, according to the Korean Traditional Medicine, PTB is caused by the deficiency of Qi and unnecessary energy in the body of the mother. The aim of this study was to demonstrate the benefit of Traditional Korean Medicine as an adjuvant therapy in management of early uterine contractions and the prevention of PTB. Methods: It is a case report of a 38-year-old woman (0-0-6-0) hospitalized for irregular uterine contractions and cervical change at 33+3/7 weeks of gestation. Past history includes chemical pregnancies achieved by Artificial Rroductive Technology(ART), one stillbirth (at 7 weeks) and a laparoscopic surgery for endometriosis. After seven trials of IVF and articificial insemination, she had succeeded in conception via in-vitro fertilization (IVF) with help of Traditional Korean Medicine (TKM) treatments. Due to irregular uterine contractions and cervical changes, 2 TKM were prescribed: Gami-Dangguisan, and Antae-eum, known to nourish blood and clear away heat. 120ml of Gami-Dangguisan was given twice a day monring and evening along with same amount of Antae-eum once a day from 31 August 2013 to 28 November 2013. Tocolytics (Ritodrine) was administered as a first aid for maintenance of pregnancy. Information regarding progress until the delivery was collected during the patient’s visit. Results: On admission, the cervix of 15mm in length and cervical os with 0.5cm-dilated were observed via ultrasonography. 50% cervical effacement was also detected in physical examination. Tocolysis had been temporarily maintained. As a supportive therapy, TKM herbal preparations(gami-dangguisan and Antae-eum) were concomitantly given. As of 34+2/7 weeks of gestation, however intermittent uterine contractions appeared (5-12min) on cardiotocography and vaginal bleeding was also smeared at 34+3/7 weeks. However, enhanced tocolytics and continuous administration of herbal medicine sustained the pregnancy to term. At 37+2/7 weeks, no sign of labor with restored cervical length was confirmed. The woman gave a term birth to a healthy infant via vaginal delivery at 39+3/7 gestational weeks. Conclusions: This is the first successful case report about a preter labor patient administered with conventional tocolytic agents as well as TKM herbal decoctions, delaying delivery to term. This case deserves attention considering it is rare to maintain gestation to term only with tocolytic intervention. Our report implies the potential of herbal medicine as an adjuvant therapy for preterm labor treatment. Further studies are needed to assess the safety and efficacy of TKM herbal medicine as a therapeutic alternative for curing preterm birth.

Keywords: preterm labor, traditional Korean medicine, herbal medicine, integrative treatment, complementary and alternative medicine

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Authors: I.J. Kim, B.C. Kim, J.H. Kim, C.-Y. Yi

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Heat transfer in a graphite calorimeter is analyzed by using the finite elements method. The calorimeter is modeled in 3D geometry. Quasi-adiabatic mode operation is realized in the simulation and the temperature rise by different sources of the ionizing radiation and electric heaters is compared, directly. The temperature distribution caused by the electric power was much different from that by the ionizing radiation because of its point-like localized heating. However, the temperature rise which was finally read by sensing thermistors agreed well to each other within 0.02 %.

Keywords: graphite calorimeter, finite element analysis, heat transfer, quasi-adiabatic mode

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Authors: Kumari Rekha, Mathur K Dhananjay, Maheshwari Deepanshu, Nautiyal Nidhi, Shubham Smriti, Laal Deepika, Sinha Swati, Kumar Anupam, Biswas Subhrajit, Shiv Kumar Sarin

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Background: Mesenchymal stem cells are multipotent stem cells derived from mesoderm and are used for therapeutic purposes because of their self-renewal, homing capacity, Immunomodulatory capability, low immunogenicity and mitochondrial transfer signaling. MSCs have the ability to regulate the mechanism of both innate as well as adaptive immune responses through the modulation of cellular response and the secretion of inflammatory mediators. Different sources of MSC are UC MSC, BM MSC, Dental Pulp, and Adipose MSC. The most frequent source used is umbilical cord tissue due to its being easily available and free of limitations of collection procedures from respective hospitals. The immunosuppressive role of MSCs is particularly interesting for clinical use since it confers resistance to rejection by the host immune response. Methodology: In this study, T helper cells (TH4), Cytotoxic T cells (CD-8), immunoregulatory cells (CD25 +FOXP3+) are compared from isolated MSC from three different methods, UC Dissociation Kit (Miltenyi), Explant Culture and Collagenase Type-IV. To check the immunomodulatory property, these MSCs were seeded with PBMC(Coculture) in CD3 coated 24 well plates. Cd28 antibody was added in coculture for six days. The coculture was analyzed in FACS Verse flow cytometry. Results: From flow cytometry analysis of coculture, it found that All over T helper cells (CD4+) number p<0.0264 increases in (All Enzymes) MSC rather than explant MSC(p>0.0895) as compared to Collagenase(p>0.7889) in a coculture of Activated T cell and Mesenchymal Stem Cell. Similar T reg cells (CD25+, FOXP3+) expression p<0.0234increases in All Enzymes), decreases in Explant and Collagenase. Experiments have shown that MSCs can also directly prevent the cytotoxic activity of CD8 lymphocytes mainly by blocking their proliferation rather than by inhibiting the cytotoxic effect. And promoting the t-reg cells, which helps in the mediation of immune response in various diseases. Conclusion: MSC suppress Cytotoxic CD8 T cell and Enhance immunoregulatory T reg (CD4+, CD25+, FOXP3+) Cell expression. Thus, MSC maintains a proper balance(ratio) between CD4 T cells and Cytotoxic CD8 T cells.

Keywords: MSC, disease, T cell, T regulatory

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Authors: Josline Salib, Sayed El-Toumy, Abeer Salama, Enayat Omara, Emad Hassan

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Diabetic nephropathy is an important cause of morbidity and mortality and is now among the most common causes of end-stage renal failure (ESRF) in developed countries. Thus, the aim of the present study was to investigate the phenolic compounds content of Cichorium intybus aerial parts extracts as well as the therapeutic effects on diabetic nephropathy, oxidative stress, and anti-inflammatory by characterizing biochemical, histopathological changes and immunohistochemistry in an experimental diabetic rat model as compared with Amaryl. Ten known compounds of flavonoids, coumarins and phenolic acid derivatives were isolated from the C. intybus aqueous methanolic extract. Structures of the isolated compounds were established by chromatography, UV and 1D⁄2D 1H⁄ 13C spectroscopy. The aqueous methanol extract of C. intybus aerial parts was administered to Streptozotocin diabetes rats at doses (100 and 200 mg/kg) for 21 days. After treatment, blood glucose, serum insulin, urea, creatinine, and TNF-α were evaluated. Enzymatic scavengers including catalase (CAT), glutathione (GSH), malondialdehyde (MDA) and nitric oxide (NO) were determined to evaluate the oxidative status in the renal tissue. Diabetic rats treated with C. intybus extract showed a dose-dependent reduction of fasting blood glucose and kidney antioxidant status in comparison to the diabetic control group. The extract was able to enhance the antioxidant defenses of the kidney by increasing the reduced GSH and CAT content and decreasing MDA content in addition to significantly decreasing kidney nitric oxide content compared to diabetic control rats. Furthermore, the histopathological findings in C. intybus extract administered rats were observed at markedly lesser extent than the diabetic control group. Also, inducible nitric oxide synthase (iNOS) levels were decreased significantly after the administration of high-dose C. intybus extract in diabetic rats. Showing significant antihyperglycemic and antioxidant properties of C. intybus aerial parts extract, which is attributed to its polyphenolic content, may offer a potential source for the treatment of diabetes.

Keywords: antioxidant activity, anti-diabetic nephropathy, cichorium intybus aerial parts, phenolic compounds

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Authors: Keng H. Kong, Louis C. Tan, Wing L. Aw, Kay Y. Tay

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Background: Fatigue is a common problem in patients with Parkinson's disease, with reported prevalence of up to 70%. Fatigue can be disabling and has adverse effects on patients' quality of life. There is currently no satisfactory treatment of fatigue. Acupuncture is effective in the treatment of fatigue, especially that related to cancer. Its role in Parkinson's disease-related fatigue is uncertain. Aims: To evaluate the clinical efficacy of acupuncture treatment in Parkinson's disease-related fatigue. Hypothesis: We hypothesize that acupuncture is effective in alleviating Parkinson's disease-related fatigue. Design: A single center, randomized, controlled study with two parallel arms. Participants: Forty participants with idiopathic Parkinson's disease will be enrolled. Interventions: Participants will be randomized to receive verum (real) acupuncture or placebo acupuncture. The retractable non-invasive sham needle will be used in the placebo group. The intervention will be administered twice a week for five weeks. Main outcome measures: The primary outcome will be the change in general fatigue score of the multidimensional fatigue inventory at week 5. Secondary outcome measures include other subscales of the multidimensional fatigue inventory, movement disorders society-unified Parkinson's disease rating scale, Parkinson's disease questionnaire-39 and geriatric depression scale. All outcome measures will be assessed at baseline (week 0), completion of intervention (week 5) and 4 weeks after completion of intervention (week 9). Results: To date, 23 participants have been recruited and nine have completed the study. The mean age is 63.5±14.2 years, mean duration of Parkinson’s disease is 6.4±1.8 years and mean MDS-UPDRS score is 8.3±2.8. The mean general fatigue score of the multidimensional fatigue inventory is 13.5±4.6. No significant adverse event related to acupuncture is noted. Potential significance: If the results are as expected, this study will provide preliminary scientific evidence for the efficacy of acupuncture in Parkinson's Disease-related fatigue, and opens the door for a larger multicentre trial to be performed. In the longer term, it may lead to the integration of acupuncture in the care of patients with Parkinson's disease.

Keywords: acupuncture, fatigue, Parkinson's disease, trial

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Authors: Armando T. Zúñiga

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As the number of English Language Learners (ELLs) in public schools continues to grow, so does the achievement gap between ELLs and other student populations. In an effort to support classroom teachers with effective instructional strategies for this student population, many districts have created instructional coaching positions specifically to support classroom teachers of ELLs—ELL Teachers on Special Assignment (ELL TOSAs). This study employed a gap analysis framework to the ELL TOSA professional support program in one California school district to examine knowledge, motivation, and organizational influences (KMO) on the ELL TOSAs’ goal of supporting classroom teachers of ELLs. Three themes emerged as a result of data analysis. First, there was evidence to illustrate the interaction between knowledge and the organization. Data from ELL TOSAs indicated an understanding of the role that collaboration plays in coaching and how to operationalize it in their support of teachers. Further, all of the ELL TOSAs indicated they have received professional development on effective strategies for instructional coaching. Additionally, a large percentage of the ELL TOSAs indicated a knowledge of modeling as an effective coaching practice. Accordingly, all of the ELL TOSAs indicated that they had knowledge of feedback as an effective coaching strategy. However, there was not sufficient evidence to support that they learned the latter two strategies through professional development. A second theme surfaced as there was evidence to illustrate an interaction between motivation and the organization. Some ELL TOSAs indicated that their sense of self-efficacy was affected by conflicting roles and expectations for the job. Most of the ELL TOSAs indicated that their sense of self-efficacy was affected by an increased workload brought about by fiscal decision making. Finally, there was evidence illustrating the interaction between the organization and motivation. The majority of the of ELL TOSAs indicated that there is confusion about how their roles are perceived, leaving the ELL TOSAs to feel that their actions did not contribute to instructional change. In conclusion, five research-based recommendations to support ELL TOSA goal attainment and considerations for future research on instructional coaches for classroom teachers of ELLs are provided.

Keywords: English language development, English language acquisition, language and leadership, language coaching, English language learners, second language acquisition

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Authors: Taku Numao, Kazu Amimoto, Tomoko Shimada, Kyohei Ichikawa

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Background: Unilateral spatial neglect (USN) is a common syndrome following damage to one hemisphere of the brain (usually the right side), in which a patient fails to report or respond to stimulation from the contralesional side. These symptoms are not due to primary sensory or motor deficits, but instead, reflect an inability to process input from that side of their environment. Prism adaptation (PA) is a therapeutic treatment for USN, wherein a patient’s visual field is artificially shifted laterally, resulting in a sensory-motor adaptation. However, patients with USN also tend to perceive a left-leaning subjective vertical in the frontal plane. The traditional PA cannot be used to correct a tilt in the subjective vertical, because a prism can only polarize, not twist, the surroundings. However, this can be accomplished using a head mounted display (HMD) and a web-camera. Therefore, this study investigated whether an HMD system could be used to correct the spatial perception of USN patients in the frontal as well as the horizontal plane. We recruited healthy subjects in order to collect data for the refinement of USN patient therapy. Methods: Eight healthy subjects sat on a chair wearing a HMD (Oculus rift DK2), with a web-camera (Ovrvision) displaying a 10 degree leftward rotation and a 10 degree counter-clockwise rotation along the frontal plane. Subjects attempted to point a finger at one of four targets, assigned randomly, a total of 48 times. Before and after the intervention, each subject’s body-centre judgment (BCJ) was tested by asking them to point a finger at a touch panel straight in front of their xiphisternum, 10 times sight unseen. Results: Intervention caused the location pointed to during the BCJ to shift 35 ± 17 mm (Ave ± SD) leftward in the horizontal plane, and 46 ± 29 mm downward in the frontal plane. The results in both planes were significant by paired-t-test (p<.01). Conclusions: The results in the horizontal plane are consistent with those observed following PA. Furthermore, the HMD and web-camera were able to elicit 3D effects, including in both the horizontal and frontal planes. Future work will focus on applying this method to patients with and without USN, and investigating whether subject posture is also affected by the HMD system.

Keywords: head mounted display, posture, prism adaptation, unilateral spatial neglect

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Authors: Maryam Radan, Fereshteh Nejad Dehbashi, Vahid Bayati, Mahin Dianat, Seyyed Ali Mard, Zahra Mansouri

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Pulmonary emphysema is a pathological respiratory condition identified by alveolar destruction which leads to limitation of airflow and diminished lung function. A substantial body of evidence suggests that mesenchymal stem cells (MSCs) have the ability to induce tissue repair primarily through a paracrine effect. In this study, we aimed to determine the efficacy of Intratracheal adipose-derived mesenchymal stem cells (ADSCs) therapy in comparison to this approach with that of Intravenous (Systemic) therapy. Fifty adult male Sprague–Dawley rats weighing between 180 and 200 g were used in this experiment. The animals were randomized to Control groups (Intratracheal or Intravenous vehicle), Elastase group (intratracheal administration of porcine pancreatic elastase; 25 U/kg on day 0 and day 10th), Elastase+Intratracheal ADSCs therapy (1x107 Cells, on day 28) and Elastase+Systemic ADSCs therapy (1x107 Cells, on day 28). The rats which not subjected to any treatment, considered as the control. All rats were sacrificed 3 weeks later. Morphometric findings in lung tissues (Mean linear intercept) confirmed the establishment of the emphysema model via alveolar disruption. Contrarily, ADSCs administration partially restored alveolar architecture. These results were associated with improving arterial oxygenation, reducing lung edema, and decreasing lung inflammation with higher significant effects in the Intratracheal therapy route. These results documented that the efficacy of intratracheal ADSCs was comparable with intravenous ADSCs therapy. Accordingly, the obtained data suggested that intratracheal delivery of ADSCs would enhance lung repair in pulmonary emphysema. Moreover, this method provides benefits over a systemic administration, such as the reduction of cell number and the low risk to engraft other organs.

Keywords: mesenchymal stem cell, emphysema, Intratracheal, systemic

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Authors: Sara Taghdisi, Mehrosadat Mirmohammadi, Mostafa Mokhtarian, Mohammad Hossein Pazandeh

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Leishmaniasis is one of the 10 most important diseases of the World Health Organization with health problems in more than 90 countries. Over one billion people are at risk of these diseases on almost every continent. The present human study was performed to evaluate the therapeutic effect of cotton plant on cutaneous leishmaniasis leision. firstly, the cotton seeds were cleaned and grinded to smaller particles. In the second step, the seeds were oiled by cold press method. In order to separate bioactive compound, after saponification of the oil, its gossypol was hydrolyzed and crystalized. finally, the therapeutic effect of Cottonseed Oil on cutaneous leishmaniasis was investigated. In the current project, Gossypol was extracted with a liquid-liquid extraction method in 120 minutes in the presence of Phosphoric acid from the cotton seed oil of Golestan beach varieties, then got crystallized in darkness using Acetic acid and isolated as Gossypol Acetic acid. The efficiency of the extracted crystal was obtained at 1.28±0.12. the cotton plant could be efficient in the treatment of Cutaneous leishmaniasis. This double-blind randomized controlled clinical trial was performed on 88 cases of leishmaniasis wounds. Patients were randomly divided into two groups of 44 cases. two groups received conventional treatment. In addition to the usual treatment (glucantime), the first group received cottonseed oil and the control group received placebo. The results of the present study showed that the surface of lesion before the intervention and in the first to fourth weeks after the intervention was not significantly different between the two groups (P-value> 0.05). But the surface of lesion in the Intervention group in the eighth and twelfth weeks was lower than the control group (P-value <0.05). This study showed that the improvement of leishmaniasis lesion using topical cotton plant mark in the eighth and twelfth weeks after the intervention was significantly more than the control group. Considering the most common chemical drugs for Cutaneous leishmaniasis treatment are sodium stibogluconate, and meglumine antimonate, which not only have relatively many side effects, but also some species of the Leishmania genus have become resistant to them. Therefore, a plant base bioactive compound such as cottonseed oil can be useful whit fewer side effects.

Keywords: cottonseed oil, crystallization, gossypol, leishmaniasis

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Authors: Tauseef Ahmad, Muhammad Ishaq, Mathew Eapen, Ahyoung Park, Sam Karpiniec, Vanni Caruso, Rajaraman Eri

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Fucoidans are complex, fucose-rich sulfated polymers discovered in brown seaweeds. Fucoidans are popular around the world, particularly in the nutraceutical and pharmaceutical industries, due to their promising medicinal properties. Fucoidans have been shown to have a variety of biological activities, including anti-inflammatory effects. They are known to inhibit inflammatory processes through a variety of mechanisms, including enzyme inhibition and selectin blockade. Inflammation is a part of the complicated biological response of living systems to damaging stimuli, and it plays a role in the pathogenesis of a variety of disorders, including arthritis, inflammatory bowel disease, cancer, and allergies. In the current investigation, various fucoidan extracts from Undaria pinnatifida, Fucus vesiculosus, Macrocystis pyrifera, Ascophyllum nodosum, and Laminaria japonica were assessed for inhibition of pro-inflammatory cytokine production (TNF-α, IL-1β, and IL-6) in LPS induced human macrophage cell line (THP-1) and human peripheral blood mononuclear cells (PBMCs). Furthermore, we also sought to catalogue these extracts based on their anti-inflammatory effects in the current in-vitro cell model. Materials and Methods: To assess the cytotoxicity of fucoidan extracts, MTT (3-[4,5-dimethylthiazol-2-yl]-2,5, -diphenyltetrazolium bromide) cell viability assay was performed. Furthermore, a dose-response for fucoidan extracts was performed in LPS induced THP-1 cells and PBMCs after pre-treatment for 24 hours, and levels of TNF-α, IL-1β, and IL-6 cytokines were measured using Enzyme-Linked Immunosorbent Assay (ELISA). Results: The MTT cell viability assay demonstrated that fucoidan extracts exhibited no evidence of cytotoxicity in THP-1 cells or PBMCs after 48 hours of incubation. The results of the sandwich ELISA revealed that all fucoidan extracts suppressed cytokine production in LPS-stimulated PBMCs and human THP-1 cells in a dose-dependent manner. Notably, at lower concentrations, the lower molecular fucoidan (5-30 kDa) extract from Macrocystis pyrifera was a highly efficient inhibitor of pro-inflammatory cytokines. Fucoidan extracts from all species including Undaria pinnatifida, Fucus vesiculosus, Macrocystis pyrifera, Ascophyllum nodosum, and Laminaria japonica exhibited significant anti-inflammatory effects. These findings on several fucoidan extracts provide insight into strategies for improving their efficacy against inflammation-related diseases. Conclusion: In the current research, we have successfully catalogued several fucoidan extracts based on their efficiency in LPS-induced macrophages and PBMCs in downregulating the key pro-inflammatory cytokines (TNF-, IL-1 and IL-6), which are prospective targets in human inflammatory illnesses. Further research would provide more information on the mechanism of action, allowing it to be tested for therapeutic purposes as an anti-inflammatory medication.

Keywords: fucoidan, PBMCs, THP-1, TNF-α, IL-1β, IL-6, inflammation

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Authors: Imalka Wasana Rathnayaka, Rasheda Khanam, Mohammad Mafizur Rahman

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TheCOVID-19 pandemic has created unprecedented challenges to both the health and economic states in countries around the world. This study aims to evaluate the effectiveness of governments' decisions to mitigate the risks of COVID-19 through proposing policy directions to reduce its magnitude. The study is motivated by the ongoing coronavirus outbreaks and comprehensive policy responses taken by countries to mitigate the spread of COVID-19 and reduce death rates. This study contributes to filling the knowledge by exploiting the long-term efficacy of extensive plans of governments. This study employs a Panel autoregressive distributed lag (ARDL) framework. The panels incorporate both a significant number of variables and fortnightly observations from22 countries. The dependent variables adopted in this study are the fortnightly death rates and the rates of the spread of COVID-19. Mortality rate and the rate of infection data were computed based on the number of deaths and the number of new cases per 10000 people.The explanatory variables are fortnightly values of indexes taken to investigate the efficacy of government interventions to control COVID-19. Overall government response index, Stringency index, Containment and health index, and Economic support index were selected as explanatory variables. The study relies on the Oxford COVID-19 Government Measure Tracker (OxCGRT). According to the procedures of ARDL, the study employs (i) the unit root test to check stationarity, (ii) panel cointegration, and (iii) PMG and ARDL estimation techniques. The study shows that the COVID-19 pandemic forced immediate responses from policymakers across the world to mitigate the risks of COVID-19. Of the four types of government policy interventions: (i) Stringency and (ii) Economic Support have been most effective and reveal that facilitating Stringency and financial measures has resulted in a reduction in infection and fatality rates, while (iii) Government responses are positively associated with deaths but negatively with infected cases. Even though this positive relationship is unexpected to some extent in the long run, social distancing norms of the governments have been broken by the public in some countries, and population age demographics would be a possible reason for that result. (iv) Containment and healthcare improvements reduce death rates but increase the infection rates, although the effect has been lower (in absolute value). The model implies that implementation of containment health practices without association with tracing and individual-level quarantine does not work well. The policy implication based on containment health measures must be applied together with targeted, aggressive, and rapid containment to extensively reduce the number of people infected with COVID 19. Furthermore, the results demonstrate that economic support for income and debt relief has been the key to suppressing the rate of COVID-19 infections and fatality rates.

Keywords: COVID-19, infection rate, deaths rate, government response, panel data

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Authors: Hafiza Javaria Ashraf, Asim Abbasi, Muhammad Hussnain Babar, Muhammad Sufyan

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Brevicoryne brassicae (Aphid) is not only the major biotic constraint of rapeseed crop but also transmits 20 different viral pathogens that cause diseases in crucifers. Aphids cause major losses to rapeseed by stunting growth and yield, with real damage being contamination of harvested heads. The misuse of pesticides has led to tremendous economic losses and hazards to human health and environmental pollution. Thus, newer approaches for pest control are continuously being sought. The naturally occurring, biologically active plant-based products seem to have a prominent role in the development of future commercial pesticides not only for increased productivity but their eco-friendly nature. The present experiment was carried out in Research Area of Ayub Agriculture Research Institute, Faisalabad to check the efficacy of different botanicals against rapeseed aphid. The tested botanicals were, neem seed extract, neem leaf extract, dathora seed extract, kaner leaf extract and aak leaf extract. Insecticide, advantage 20 EC served as the positive control in the experiment. Data was recorded before and after 1, 3 and 7 days of treatment application. The results of the experiment revealed that neem seed extract exhibited maximum mortality (48.42%) followed by dathora (45.54%) and kaner leaf extract (40.29%) after 7 days of treatment application. However minimum mortality i.e. 26.64% was observed in case of aak leaf extract. Advantage encountered maximum mortality i.e. 86.14%. All treatments caused maximum mortality after 7 days of treatment application. In case of pollinators maximum population reduction was observed in case of insecticide (74.29%) while minimum reduction was observed in neem leaf extract (11.57%). Hence it was concluded that unlike insecticides, plant based products can be a better option for regulating pests and conserving beneficial insect fauna.

Keywords: Aphid, mortality, plant based, pollinators

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Authors: Suman Chaudhary, Rupinder K. Kanwar, Jagat R. Kanwar

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Azadirachta indica, also known as Neem belonging to the mahogany family is actively gaining interest in the era of modern day medicine due to its extensive applications in homeopathic medicine such as Ayurveda and Unani. More than 140 phytochemicals have been extracted from neem leaves, seed, bark and flowers for agro-medicinal applications. Among the various components, neem leaf protein (NLP) is currently the most investigated active ingredient, due to its immunomodulatory activities against tumor growth. However, these therapeutic ingredients of neem are susceptible to degradation and cannot withstand the drastic pH changes under physiological environment, and therefore, there is an urgent need of an alternative strategy such as a nano-delivery system to exploit its medicinal benefits. This study hypothesizes that guar gum (GG) derived biodegradable nano-carrier based encapsulation of NLP will improve its stability, specificity and sensitivity, thus facilitating targeted anti-cancer therapeutics. GG is a galactomannan derived from the endosperm of the guar beans seeds. Synthesis of guar nanocapsules (NCs) was performed using nanoprecipitation technique where the GG was encapsulated with NLP. Preliminary experiments conducted to characterize the NCs confirmed spherical morphology with a narrow size distribution of 30-40 nm. Differential scanning colorimetric analysis (DSC) validated the stability of these NCs even at a temperature range of 50-60°C which was well within the physiological and storage conditions. Thermogravimetric (TGA) analysis indicated high decomposition temperature of these NCs ranging upto 350°C. Additionally, Fourier Transform Infrared spectroscopy (FTIR) and the SDS-PAGE data acquired confirmed the successful encapsulation of NLP in the NCs. The anti-cancerous therapeutic property of this NC was tested on colon cancer cells (caco-2) as they are one of the most prevalent form of cancer. These NCs (both NLP loaded and void) were also tested on human intestinal epithelial cells (FHs 74) cells to evaluate their effect on normal cells. Cytotoxicity evaluation of the NCs in the cell lines confirmed that the IC50 for NLP in FHs 74 cells was ~2 fold higher than in caco-2 cells, indicating that this nanoformulation system possessed biocompatible anti-cancerous properties Immunoconfocal microscopy analysis confirmed the time dependent internalization of the NCs within 6h. Recent findings performed using Annexin V and PI staining indicated a significant increase (p ≤ 0.001) in the early and late apoptotic cell population when treated with the NCs signifying the role of NLP in inducing apoptosis in caco-2 cells. This was further validated using Western blot, Polymerase chain reaction (PCR) and Fluorescence activated cell sorter (FACS) aided protein expressional analysis which presented a downregulation of survivin, an anti-apoptotic cell marker and upregulation of Bax/Bcl-2 ratio (pro-apoptotic indicator). Further, both the NLP NC and unencapsulated NLP treatment destabilized the mitochondrial membrane potential subsequently facilitating the release of the pro-apoptotic caspase cascade initiator, cytochrome-c. Future studies will be focused towards granting specificity to these NCs towards cancer cells, along with a comprehensive analysis of the anti-cancer potential of this naturally occurring compound in different cancer and in vivo animal models, will validate the clinical application of this unprecedented protein therapeutic.

Keywords: anti-tumor, guar gum, nanocapsules, neem leaf protein

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Authors: Muhammad Naveed Ali, Hamad Bin Rashid, Muhammad Arif Khan, Abdul Basit, Hafiz Muhammad Arshad

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Abdominal defects are very common in pigeons. A new technique is known as intraabdominal mesh transplant that give better protection for herniorrhaphy. The aim of this study was to determine the performance of hernia mesh. In this study, an efficacy of two synthetic hernia mesh implants viz. conventional Prolene and a lightweight mesh monofilament polyester were assessed for the abdominal wall repair in pigeons. Twenty four healthy pigeons were selected and randomly distributed into three groups, A, B and C (n=8). In all groups, experimental laparotomy was performed; thereafter, abdominal muscles and peritoneum were sutured together, while, a 2 x 2 cm defect was created in the abdominal muscles. For onlay hernioplasty, the hernia mesh (Prolene mesh: group A; Polyester mesh: group B) was implanted over the external oblique muscles of the abdomen. In group C (control), the mesh was not implanted; instead, the laparotomy incision was closed after a herniorrhaphy. Post-operative pain wound healing, adhesion formation, histopathological findings and formation of hematoma, abscess and seroma were assessed as short-term complications. Post-operatively, pain at surgical site was significantly less (P < 0.001) in group B (Polyester mesh); wound healing was also significantly better and rapid in group B (P < 0.05) than in group A (Prolene mesh). Group B (Polyester mesh) also depicted less than 25% adhesions when assessed on the basis of a Quantitative Modified Diamond scale; a Qualitative Adhesion Tenacity scale also depicted either no adhesions or flimsy adhesions (n=2) in group B (Polyester mesh), in contrast to group A (Prolene), which manifested greater adhesion formation and presence of dense adhesions requiring blunt dissection. There were observed hematoma, seroma and abscess formations in birds treated by Prolene mesh only. Conclusively, the polyester mesh proved superior to the Prolene mesh regarding lesser adhesion, better in wound healing, and no short-term follow-up complications.

Keywords: adhesion, mesh, polyester, prolene

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Authors: Ila Gupta

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The government hospitals in India by and large lack the necessary aesthetic therapeutic components, both in their interior and exterior space designs. These components especially in terms of color application are important to the emotional as well as physical well being of the patients and other participants of the space. The preliminary survey of few government hospitals in Uttarakhand, India, reveals that the government health care industry provides a wide scope for intervention. All most all of the spaces do not adhere to a proper therapeutic color scheme which directly helps the well-being of their patients and workers. The paper aims to conduct a survey and come up with recommendations in this regard. The government hospitals also lack a proper signage system which allows the space to be more user-friendly. The hospital spaces in totality also have scope for improvement in terms of space/landscape design which enhances the work environment in an efficient and positive way. This study will thus enable to come up with feasible recommendations for healthcare and built environment as well as retrofitting the existing spaces. The objective of the paper is mainly on few case studies. The present ambience in many government hospitals generally lacks a welcoming ambience. It is proposed to select one or two government hospitals and demonstrate application of appropriate and self-sustainable color schemes, placement of artifacts, changes in outdoor and indoor space design to bring about a change that is conducive for cognitive healing. Exterior changes to existing and old hospital buildings in depressed historic areas signify financial investment and change, and have the potential to play a significant role in both urban preservation and revitalization. Changes to exterior architectural colors are perhaps the most visible signifier of such revitalization, as the use of color changes as a tool in façade and interior improvement programs. The present project will provide its recommendations on the basis of case studies done in the Indian Public Health Care system. Furthermore, the recommendations will be in accordance with the extended study conducted in Indian Ayurvedic, Yogic texts as well as Vastu texts, which provides knowledge about built environments and healing properties of color.

Keywords: color, environment, facade, architectural color history, interior improvement programs, community development, district/government hospitals

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Authors: George Madalin Danila, Mihaiella Cretu, Cristian Puscasu

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The recycling of used antifreeze/coolant is a widely discussed and intricate issue. Complying with government regulations for the proper disposal of hazardous waste poses a significant challenge for today's automotive and industrial industries. In recent years, global focus has shifted toward Earth's fragile ecology, emphasizing the need to restore and preserve the natural environment. The business and industrial sectors have undergone substantial changes to adapt and offer products tailored to these evolving markets. The global antifreeze market size was evaluated at US 5.4 billion in 2020 to reach USD 5,9 billion by 2025 due to the increased number of vehicles worldwide, but also to the growth of HVAC systems. This study presents the evaluation of an ion exchange resin-based installation designed for the recycling of engine coolants, specifically ethylene glycol (EG) and propylene glycol (PG). The recycling process aims to restore the coolant to meet the stringent ASTM standards for both new and recycled coolants. A combination of physical-chemical methods, gas chromatography-mass spectrometry (GC-MS), and inductively coupled plasma mass spectrometry (ICP-MS) was employed to analyze and validate the purity and performance of the recycled product. The experimental setup included performance tests, namely corrosion to glassware and the tendency to foaming of coolant, to assess the efficacy of the recycled coolants in comparison to new coolant standards. The results demonstrate that the recycled EG coolants exhibit comparable quality to new coolants, with all critical parameters falling within the acceptable ASTM limits. This indicates that the ion exchange resin method is a viable and efficient solution for the recycling of engine coolants, offering an environmentally friendly alternative to the disposal of used coolants while ensuring compliance with industry standards.

Keywords: engine coolant, glycols, recycling, ion exchange resin, circular economy

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Authors: Abdus-Samiᶜi Imam Arikewuyo

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Islam enjoins the spirit of cooperation among fellow mankind. This is particularly entrenched in the brotherhood phenomenon advocated by Islam. With cooperation, a group of people with diverse qualities and opportunities can facilitate a breakthrough in what is seemingly difficult, if not impossible. This understanding underscores the initiative of establishing multi-purpose cooperative societies for thrifts and savings among bonafide members, especially in developing nations. The spirit and objectives of the Multi-Purpose Cooperatives Societies gave birth to the founding of several of these organizations as a plausible economic outfit in Nigeria to provide succor to the socio-economic predicaments of members. Pertinently, many Islamic cooperative societies sprang up, carving a niche for themselves as Shariᶜah-based economic outfits to accommodate the yearnings of the Muslim populace. KWASU Al-Halal Cooperative Society, Malete, Nigeria, is one such organization that is not only Shariᶜah inclined but also institutional-based. This paper, therefore, aims to examine the operations and activities of this society with a view to determining its strength as a Shariᶜah-based economic outfit for the survival of its clients in a competitive multi-religious atmosphere. The study is both historical and descriptive; thus, it employed interview, observation, focus group discussion and hermeneutical methods as pertinent research tools. The research findings indicated that adopting the Shariᶜah prescriptions, KWASU Al-Halal Cooperative Society, as a representation of the Islamic cooperatives society, fulfilled the essence and goal of its establishment, serving as an outlet for meeting the socio-economic demands of its members regardless of religious inclinations. The paper recommended that stronger efforts should be made on proper record keeping, the conscientiousness of beneficiaries on loan refunds or payments on purchases and education of the loanees and guarantors.

Keywords: efficacy, Islamic cooperatives society, Kwasu al-halal cooperative society, shariᶜah

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Authors: Shohreh Ghasemi

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Introduction: Managing oral and maxillofacial trauma is a multifaceted challenge, as it can have life-threatening consequences and significant functional and aesthetic impact. Navigation techniques have been introduced to improve surgical precision to meet this challenge. A machine learning algorithm was also developed to support clinical decision-making regarding treating oral and maxillofacial trauma. Given these advances, this systematic meta-analysis aims to assess the efficacy of navigational techniques in treating oral and maxillofacial trauma and explore the impact of machine learning on their management. Methods: A detailed and comprehensive analysis of studies published between January 2010 and September 2021 was conducted through a systematic meta-analysis. This included performing a thorough search of Web of Science, Embase, and PubMed databases to identify studies evaluating the efficacy of navigational techniques and the impact of machine learning in managing oral and maxillofacial trauma. Studies that did not meet established entry criteria were excluded. In addition, the overall quality of studies included was evaluated using Cochrane risk of bias tool and the Newcastle-Ottawa scale. Results: Total of 12 studies, including 869 patients with oral and maxillofacial trauma, met the inclusion criteria. An analysis of studies revealed that navigation techniques effectively improve surgical accuracy and minimize the risk of complications. Additionally, machine learning algorithms have proven effective in predicting treatment outcomes and identifying patients at high risk for complications. Conclusion: The introduction of navigational technology has great potential to improve surgical precision in oral and maxillofacial trauma treatment. Furthermore, developing machine learning algorithms offers opportunities to improve clinical decision-making and patient outcomes. Still, further studies are necessary to corroborate these results and establish the optimal use of these technologies in managing oral and maxillofacial trauma

Keywords: trauma, machine learning, navigation, maxillofacial, management

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Authors: Yogesh Rai, Saurabh Singh, Sanjay Pandey, Dhananjay K. Sah, B. G. Roy, B. S. Dwarakanath, Anant N. Bhatt

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One of the most common signatures of highly malignant gliomas is their capacity to metabolize more glucose to lactic acid than normal brain tissues, even under normoxic conditions (Warburg effect), indicating that aerobic glycolysis is constitutively upregulated through stable genetic or epigenetic changes. However, oxidative phosphorylation (OxPhos) is also required to maintain the mitochondrial membrane potential for tumor cell survival. In the process of tumorigenesis, tumor cells during fastest growth rate exhibit both high glycolytic and high OxPhos. Therefore, metabolically reprogrammed cancer cells with combination of both aerobic glycolysis and altered OxPhos develop a robust metabolic phenotype, which confers a selective growth advantage. In our study, we grew the high glycolytic BMG-1 (glioma) cells with continuous exposure of mitochondrial uncoupler 2, 4, dinitro phenol (DNP) for 10 passages to obtain a phenotype of high glycolysis with enhanced altered OxPhos. We found that OxPhos modified BMG (OPMBMG) cells has similar growth rate and cell cycle distribution but high mitochondrial mass and functional enzymatic activity than parental cells. In in-vitro studies, OPMBMG cells showed enhanced invasion, proliferation and migration properties. Moreover, it also showed enhanced angiogenesis in matrigel plug assay. Xenografted tumors from OPMBMG cells showed reduced latent period, faster growth rate and nearly five folds reduction in the tumor take in nude mice compared to BMG-1 cells, suggesting that robust metabolic phenotype facilitates tumor formation and growth. OPMBMG cells which were found radio-resistant, showed enhanced radio-sensitization by 2-DG as compared to the parental BMG-1 cells. This study suggests that metabolic reprogramming in cancer cells enhances the potential of migration, invasion and proliferation. It also strengthens the cancer cells to escape the death processes, conferring resistance to therapeutic modalities. Our data also suggest that combining metabolic inhibitors like 2-DG with conventional therapeutic modalities can sensitize such metabolically aggressive cancer cells more than the therapies alone.

Keywords: 2-DG, BMG, DNP, OPM-BMG

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Authors: Kohkan Shamsi

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Background: MRI and PET are now extensively utilized in Alzheimer's disease (AD) trials for patient eligibility, efficacy assessment, and safety evaluations but including imaging in AD trials impacts site selection process, patient recruitment, and patient retention. Methods: PET/MRI are performed at baseline and at multiple follow-up timepoints. This requires prospective site imaging qualification, evaluation of phantom data, training and continuous monitoring of machines for acquisition of standardized and consistent data. This also requires prospective patient/caregiver training as patients must go to multiple facilities for imaging examinations. We will share our experience form one of the largest AD programs. Lesson learned: Many neurological diseases have a similar presentation as AD or could confound the assessment of drug therapy. The inclusion of wrong patients has ethical and legal issues, and data could be excluded from the analysis. Centralized eligibility evaluation read process will be discussed. Amyloid related imaging abnormalities (ARIA) were observed in amyloid-β trials. FDA recommended regular monitoring of ARIA. Our experience in ARIA evaluations in large phase III study at > 350 sites will be presented. Efficacy evaluation: MRI is utilized to evaluate various volumes of the brain. FDG PET or amyloid PET agents has been used in AD trials. We will share our experience about site and central independent reads. Imaging logistic issues that need to be handled in the planning phase will also be discussed as it can impact patient compliance thereby increasing missing data and affecting study results. Conclusion: imaging must be prospectively planned to include standardizing imaging methodologies, site selection process and selecting assessment criteria. Training should be transparently conducted and documented. Prospective patient/caregiver awareness of imaging requirement is essential for patient compliance and reduction in missing imaging data.

Keywords: Alzheimer's disease, ARIA, MRI, PET, patient recruitment, retention

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Authors: Mehrosadat Mirmohammadi, Sara Taghdisi, Ali Padash, Mohammad Hossein Pazandeh

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Gossypol, a yellowish anti-nutritional compound found in cotton plants, exists in various plant parts, including seeds, husks, leaves, and stems. Chemically, gossypol is a potent polyphenolic aldehyde with antioxidant and therapeutic properties. However, its free form can be toxic, posing risks to both humans and animals. Initially, we extracted gossypol from cotton seeds using n-hexane as a solvent (yield: 84.0 ± 4.0%). We also obtained cotton seed and cotton boll extracts via Soxhlet extraction (25:75 hydroalcoholic ratio). These extracts, combined with cornstarch, formed four herbal medicinal formulations. Ethical approval allowed us to investigate their effects on Leishmania-caused skin wounds, comparing them to glucantime (local ampoule). Herbal formulas outperformed the control group (ethanol only) in wound treatment (p-value 0.05). The average wound diameter after two months did not significantly differ between plant extract ointments and topical glucantime. Notably, cotton boll extract with 1% extra gossypol crystal showed the best therapeutic effect. We extracted gossypol from cotton seeds using n-hexane via Soxhlet extraction. Saponification, acidification, and recrystallization steps followed. FTIR, UV-Vis, and HPLC analyses confirmed the product’s identity. Herbal medicines from cotton seeds effectively treated chronic wounds compared to the ethanol-only control group. Wound diameter differed significantly between extract ointments and glucantime injections. It seems that due to the presence of large amounts of fat in the oil, the extraction of gossypol from it faces many obstacles. The extraction of this compound with our technique showed that extraction from oil has a higher efficiency, perhaps because of the preparation of oil by cold pressing method, the possibility of losing this compound is much less than when extraction is done with Soxhlet. On the other hand, the gossypol in the oil is mostly bound to the protein, which somehow protects the gossypol until the last stage of the extraction process. Since this compound is very sensitive to light and heat, it was extracted as a derivative with acetic acid. Also, in the treatment section, it was found that the ointment prepared with the extract is more effective and Gossypol is one of the effective ingredients in the treatment. Therefore, gossypol can be extracted from the oil and added to the extract from which gossypol has been extracted to make an effective medicine with a certain dose.

Keywords: cottonseed, glucantime, gossypol, leishmaniasis

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Authors: Temesgen Sidamo, Prakruti S. Rao, Eleni Akllilu, Workineh Shibeshi, Yumi Park, Yong-Soon Cho, Jae-Gook Shin, Scott K. Heysell, Stellah G. Mpagama, Ephrem Engidawork

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The fluoroquinolones (FQs) are used off-label for the treatment of multidrug-resistant tuberculosis (MDR-TB), and for evaluation in shortening the duration of drug-susceptible TB in recently prioritized regimens. Within the class, levofloxacin (LFX) and moxifloxacin (MXF) play a substantial role in ensuring success in treatment outcomes. However, sub-therapeutic plasma concentrations of either LFX or MXF may drive unfavorable treatment outcomes. To the best of our knowledge, the pharmacokinetics of LFX and MXF in Ethiopian patients with MDR-TB have not yet been investigated. Therefore, the aim of this study was to develop a population pharmacokinetic (PopPK) model of levofloxacin (LFX) and moxifloxacin (MXF) and assess the percent probability of target attainment (PTA) as defined by the ratio of the area under the plasma concentration-time curve over 24-h (AUC0-24) and the in vitro minimum inhibitory concentration (MIC) (AUC0-24/MIC) in Ethiopian MDR-TB patients. Steady-state plasma was collected from 39 MDR-TB patients enrolled in the programmatic treatment course and the drug concentrations were determined using optimized liquid chromatography-tandem mass spectrometry. In addition, the in vitro MIC of the patients' pretreatment clinical isolates was determined. PopPK and simulations were run at various doses, and PK parameters were estimated. The effect of covariates on the PK parameters and the PTA for maximum mycobacterial kill and resistance prevention was also investigated. LFX and MXF both fit in a one-compartment model with adjustments. The apparent volume of distribution (V) and clearance (CL) of LFX were influenced by serum creatinine (Scr), whereas the absorption constant (Ka) and V of MXF were influenced by Scr and BMI, respectively. The PTA for LFX maximal mycobacterial kill at the critical MIC of 0.5 mg/L was 29%, 62%, and 95% with the simulated 750 mg, 1000 mg, and 1500 mg doses, respectively, whereas the PTA for resistance prevention at 1500 mg was only 4.8%, with none of the lower doses achieving this target. At the critical MIC of 0.25 mg/L, there was no difference in the PTA (94.4%) for maximum bacterial kill among the simulated doses of MXF (600 mg, 800 mg, and 1000 mg), but the PTA for resistance prevention improved proportionately with dose. Standard LFX and MXF doses may not provide adequate drug exposure. LFX PopPK is more predictable for maximum mycobacterial kill, whereas MXF's resistance prevention target increases with dose. Scr and BMI are likely to be important covariates in dose optimization or therapeutic drug monitoring (TDM) studies in Ethiopian patients.

Keywords: population PK, PTA, moxifloxacin, levofloxacin, MDR-TB patients, ethiopia

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Authors: Isalira Peroba Ramos, Cherley Borba Vieira de Andrade, Grazielle Suhett, Camila Salata, Paulo Cesar Canary, Guilherme Visconde Brasil, Antonio Carlos Campos de Carvalho, Regina Coeli dos Santos Goldenberg

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Background: The therapeutic options for patients with cancer now include increasingly complex combinations of medications, radiation therapy (RT), and surgical intervention. Many of these treatments have important potential adverse cardiac effects and are likely to have significant effects on patient outcomes. Cell therapy appears to be promising for the treatment of chronic and degenerative diseases, including cardiomyopathy induced by RT, as the current therapeutic options are insufficient. Aims: To evaluate the potential of bone marrow mesenchymal cells (BMMCs) in radioinduced cardiac damage Methods: Female Wistar rats, 3 months old (Ethics Committee 054/14), were divided into 2 groups, non-treated irradiated group (IR n=15) and irradiated and BMMC treated (IRT n=10). Echocardiography was performed to evaluate heart function. After euthanasia, 3 months post treatment; the left ventricle was removed and prepared for RT-qPCR (VEGF and Pro Collagen I) and histological (picrosirius) analysis. Results: In both groups, 45 days after irradiation, ejection fraction (EF) was in the normal range for these animals (> 70%). However, the BMMC treated group had EF (83.1%±2.6) while the non-treated IR group showed a significant reduction (76.1%±2.6) in relation to the treated group. In addition, we observed an increase in VEGF gene expression and a decrease in Pro Collagen I in IRT when compared to IR group. We also observed by histology that the collagen deposition was reduced in IRT (10.26%±0.83) when compared to IR group (25.29%±0.96). Conclusions: Treatment with BMMCs was able to prevent ejection fraction reduction and collagen deposition in irradiated animals. The increase of VEGF and the decrease of pro collagen I gene expression might explain, at least in part, the cell therapy benefits. All authors disclose no financial or personal relationships with individuals or organizations that could be perceived to bias their work. Sources of funding: FAPERJ, CAPES, CNPq, MCT.

Keywords: mesenchymal cells, radioation, cardiotoxicity, bone marrow

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Authors: P. P. L. Kwan, D. K. S. Chan

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Organizations are constantly changing in today’s business environment. Research findings have revealed that overcoming resistance and getting employees ready for change is a crucial driver for organizational change success. Thus, change adaptability has become a more prominent selection criterion used in many organizations. Although change readiness could be situation-specific, employees’ personality, emotion, and cognition should also be crucial factors in shaping their readiness. However, relatively little research has focused on the roles of individual characteristics in organizational changes. The present study examines the relations between individual characteristics and change readiness with the aim to validate a model, which proposes three types of individual attributes as antecedents to change readiness. The three attributes considered are trait cynicism, positive affectivity, and personal valence covering personality, emotional, and cognitive aspects respectively. The model also hypothesizes that relations between the three antecedents and change readiness will be moderated by a positive mental resource known as psychological capital (PsyCap), which consists of hope, optimism, efficacy and resilience; and a learning culture within the organization. We are currently collecting data from a targeted sample size of 300 Hong Kong employees. Specifically, participants complete a questionnaire which was designed to measure their perceived change efficacy in response to three scenarios commonly happened in the workplace (i.e., business acquisition, team restructuring, and information system change) as a measure of change readiness, as well as the aforementioned individual characteristics. Preliminary analysis provides some support to the hypotheses. That is, employees who are less cynical in personality and more positive in their cognition and affectivity particularly welcome the potential changes in their organizations. Further data collection and analyses are continuously carried out for a more definitive conclusion. Our findings will shed light on employee selection; and on how strengthening positive psychological resources and promoting the culture of learning organization among employees may enhance the chance to succeed for organizations undergoing change.

Keywords: learning organization, psychological capital, readiness for change, employee selection

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Authors: Silvia Ximena Barrios, Diego Armando Villamizar Mantilla, Raquel Elvira Ocazionez, , Elena E. Stashenko, María Pilar Vinardell, Jorge Luis Fuentes

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Introduction: Skin overexposure to solar radiation has been a serious public health concern, because of its potential carcinogenicity. Therefore, preventive protection strategies using photoprotective agents are critical to counteract the harmful effect of solar radiation. Plants may be a source of photoprotective compounds that inhibit cellular mutations involved in skin cancer initiation. This work evaluated the photoprotective and antigenotoxic effects against ultraviolet B (UVB) radiation of a mixture of Posoqueria latifolia flower extract and Kaempferol (MixPoKa). Methods: The photoprotective efficacy of MixPoka (Posoqueria latifolia flower extract 250 μg/ml and Kaempferol 349.5 μM) was evaluated using in vitro indices such as sun protection factor SPFᵢₙ ᵥᵢₜᵣₒ and critical wavelength (λc). The MixPoKa photostability (Eff) at human minimal erythema doses (MED), according to the Fitzpatrick skin scale, was also estimated. Cytotoxicity and genotoxicity/antigenotoxicity were studied in MRC5 human fibroblasts using the trypan blue exclusion and Comet assays, respectively. Kinetics of the genetic damage repair post irradiation in the presence and absence of the MixPoka, was also evaluated. Results: The MixPoka -UV absorbance spectrum was high across the spectral bands between 200 and 400 nm. The UVB photoprotection efficacy of MixPoka was high (SPFᵢₙ ᵥᵢₜᵣₒ = 25.70 ± 0.06), showed wide photoprotection spectrum (λc = 380 ± 0), and resulted photostable (Eff = 92.3–100.0%). The MixPoka was neither cytotoxic nor genotoxic in MRC5 human fibroblasts; but presented significant antigenotoxic effect against UVB radiation. Additionally, MixPoka stimulate DNA repair post-irradiation. The potential of this phytochemical mixture as sunscreen ingredients was discussed. Conclusion: MixPoka showed a significant antigenotoxic effect against UVB radiation and stimulated DNA repair after irradiation. MixPoka could be used as an ingredient in a sunscreen cream.

Keywords: flower extract, photoprotection, antigenotoxicity, cytotoxicity, genotoxicit

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