Search results for: deposition dose

Authors: Jasmeet Kaur, Anup Singh, Shashikant Iyengar, Arun Kumar, Ira Sahay

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Latent autoimmune diabetes in adults (LADA) is an irreversible autoimmune disease that affects insulin production. LADA is characterized by the production of Glutamic acid decarboxylase (GAD) antibodies, which is similar to type 1 diabetes. Individuals with LADA may eventually develop overt diabetes and require insulin. In this condition, the pancreas produces little or no insulin, which is a hormone used by the body to allow glucose to enter cells and produce energy. While type 1 diabetes was traditionally associated with children and teenagers, its prevalence has increased in adults as well. LADA is frequently misdiagnosed as type 2 diabetes, especially in adulthood when type 2 diabetes is more common. LADA develops in adulthood, usually after age 30. Managing LADA involves metabolic control with exogenous insulin and prolonging the life of surviving beta cells, thereby slowing the disease's progression. This case study examines the impact of approximately 3 months of low-carbohydrate dietary intervention in a 42-year-old woman with LADA who was initially misdiagnosed as having type 2 diabetes. Her c-peptide was 0.13 and her HbA1c was 9.3% when this trial began. Low-carbohydrate interventions have been shown to improve blood sugar levels, including fasting, post-meal, and random blood sugar levels, as well as haemoglobin levels, blood pressure, energy levels, sleep quality, and satiety levels. The use of low-carbohydrate dietary intervention significantly reduces both hypo- and hyperglycaemia events. During the 3 months of the study, there were 2 to 3 hyperglycaemic events owing to physical stress and a single hypoglycaemic event. Low-carbohydrate dietary therapies lessen insulin dose inaccuracy, which explains why there were fewer hyperglycaemic and hypoglycaemic events. In three months, the glycated haemoglobin (HbA1c) level was reduced from 9.3% to 6.3%. These improvements occur without the need for caloric restriction or physical activity. Stress management was crucial aspect of the treatment plan as stress-induced neuroendocrine hormones can cause immunological dysregulation. Additionally, supplements that support immune system and reduce inflammation were used as part of the treatment during the trial. Long-term studies are needed to track disease development and corroborate the claim that such dietary treatments can prolong the honeymoon phase in LADA. Various factors can contribute to additional autoimmune attacks, so measuring c-peptide is crucial on a regular basis to determine whether insulin levels need to be adjusted.

Keywords: autoimmune, diabetes, LADA, low_carb, nutrition

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Authors: Caroline Mendes, Mary McNamara, Orla Howe

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Drug delivery systems are proposed for use in cancer treatment to specifically target cancer cells and deliver a therapeutic dose without affecting normal cells. For that purpose, the use of folate receptors (FR) can be considered a key strategy, since they are commonly over-expressed in cancer cells. In this study, cyclodextrins (CD) have being used as vehicles to target FR and deliver the chemotherapeutic drug, methotrexate (MTX). CDs have the ability to form inclusion complexes, in which molecules of suitable dimensions are included within their cavities. Here, β-CD has been modified using folic acid so as to specifically target the FR. Thus, this drug delivery system consists of β-CD, folic acid and MTX (CDEnFA:MTX). Cellular uptake of folic acid is mediated with high affinity by folate receptors while the cellular uptake of antifolates, such as MTX, is mediated with high affinity by the reduced folate carriers (RFCs). This study addresses the gene (mRNA) and protein expression levels of FRs and RFCs in the cancer cell lines CaCo-2, SKOV-3, HeLa, MCF-7, A549 and the normal cell line BEAS-2B, quantified by real-time polymerase chain reaction (real-time PCR) and flow cytometry, respectively. From that, four cell lines with different levels of FRs, were chosen for cytotoxicity assays of MTX and CDEnFA:MTX using the MTT assay. Real-time PCR and flow cytometry data demonstrated that all cell lines ubiquitously express moderate levels of RFC. These experiments have also shown that levels of FR protein in CaCo-2 cells are high, while levels in SKOV-3, HeLa and MCF-7 cells are moderate. A549 and BEAS-2B cells express low levels of FR protein. FRs are highly expressed in all the cancer cell lines analysed when compared to the normal cell line BEAS-2B. The cell lines CaCo-2, MCF-7, A549 and BEAS-2B were used in the cell viability assays. 48 hours treatment with the free drug and the complex resulted in IC50 values of 93.9 µM ± 15.2 and 56.0 µM ± 4.0 for CaCo-2 for free MTX and CDEnFA:MTX respectively, 118.2 µM ± 16.8 and 97.8 µM ± 12.3 for MCF-7, 36.4 µM ± 6.9 and 75.0 µM ± 10.5 for A549 and 132.6 µM ± 16.1 and 288.1 µM ± 26.3 for BEAS-2B. These results demonstrate that free MTX is more toxic towards cell lines expressing low levels of FR, such as the BEAS-2B. More importantly, these results demonstrate that the inclusion complex CDEnFA:MTX showed greater cytotoxicity than the free drug towards the high FR expressing CaCo-2 cells, indicating that it has potential to target this receptor, enhancing the specificity and the efficiency of the drug. The use of cell imaging by confocal microscopy has allowed visualisation of FR targeting in cancer cells, as well as the identification of the interlisation pathway of the drug. Hence, the cellular uptake and internalisation process of this drug delivery system is being addressed.

Keywords: cancer treatment, cyclodextrins, drug delivery, folate receptors, reduced folate carriers

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Authors: Elaine Wong

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Introduction: The Singapore Physical Activity and Nutrition Study (SPANS) aimed to assess the effects of a community-based intervention on physical activity (PA) and nutrition behaviours as well as chronic disease risk factors for Singaporean women aged above 50 years. This article examines the participation, dose, fidelity, reach, satisfaction and reasons for completion and non-completion of the SPANS. Methods: The SPANS program integrated constructs of Social Cognitive Theory (SCT) and is composed of PA activities; nutrition workshops; dietary counselling coupled with motivational interviewing (MI) through phone calls; and text messages promoting healthy behaviours. Printed educational resources and health incentives were provided to participants. Data were collected via a mixed-method design strategy from a sample of 295 intervention participants. Quantitative data were collected using self-completed survey (n = 209); qualitative data were collected via research assistants’ notes, post feedback sessions and exit interviews with program completers (n = 13) and non-completers (n = 12). Results: Majority of participants reported high ‘satisfactory to excellent’ ratings for the program pace, suitability of interest and overall program (96.2-99.5%). Likewise, similar ratings for clarity of presentation; presentation skills, approachability, knowledge; and overall rating of trainers and program ambassadors were achieved (98.6-100%). Phone dietary counselling had the highest level of participation (72%) at less than or equal to 75% attendance rate followed by nutrition workshops (65%) and PA classes (60%). Attrition rate of the program was 19%; major reasons for withdrawal were personal commitments, relocation and health issues. All participants found the program resources to be colourful, informative and practical for their own reference. Reasons for program completion and maintenance were: desired health benefits; social bonding opportunities and to learn more about PA and nutrition. Conclusions: Process evaluation serves as an appropriate tool to identify recruitment challenges, effective intervention strategies and to ensure program fidelity. Program participants were satisfied with the educational resources, program components and delivery strategies implemented by the trainers and program ambassadors. The combination of printed materials and intervention components, when guided by the SCT and MI, were supportive in encouraging and reinforcing lifestyle behavioural changes. Mixed method evaluation approaches are integral processes to pinpoint barriers, motivators, improvements and effective program components in optimising the health status of Singaporean women.

Keywords: process evaluation, Singapore, older adults, lifestyle changes, program challenges

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Authors: María Cárdenas Gaudry, Gonzalo Ramces Fano Miranda

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Sediment removal is very important in the purification of water, not only for reasons of visual perception but also because of its association with odor and taste problems. The Cuchoquesera reservoir, which is in the Andean region of Ayacucho (Peru) at an altitude of 3,740 meters above sea level, visually presents suspended particles and organic impurities indicating that it contains water of dubious quality to deduce that it is suitable for direct consumption of human beings. In order to quantitatively know the degree of impurities, water quality monitoring was carried out from February to August 2018, in which four sampling stations were established in the reservoir. The selected measured parameters were electrical conductivity, total dissolved solids, pH, color, turbidity, and sludge volume. The indicators of the studied parameters exceed the permissible limits except for electrical conductivity (190 μS/cm) and total dissolved solids (255 mg/L). In this investigation, the best combination and the optimal doses of reagents were determined that allowed the removal of sediments from the waters of the Cuchoquesera reservoir, through the physicochemical process of coagulation-flocculation. In order to improve this process during the rainy season, six combinations of reagents were evaluated, made up of three coagulants (ferric chloride, ferrous sulfate, and aluminum sulfate) and two natural flocculants: prickly pear powder (Opuntia ficus-indica) and tara gum (Caesalpinia spinoza). For each combination of reagents, jar tests were developed following the central composite experimental design (CCED), where the design factors were the doses of coagulant and flocculant and the initial turbidity. The results of the jar tests were adjusted to mathematical models, obtaining that to treat the water from the Cuchoquesera reservoir, with a turbidity of 150 UTN and a color of 137 U Pt-Co, 27.9 mg/L of the coagulant aluminum sulfate with 3 mg/L of the natural tara gum flocculant to produce a purified water quality of 1.7 UTN of turbidity and 3.2 U Pt-Co of apparent color. The estimated cost of the dose of coagulant and flocculant found was 0.22 USD/m³. This is how “grey-green” technologies can be used as a combination in nature-based solutions in water treatment, in this case, to achieve potability, making it more sustainable, especially economically, if green technology is available at the site of application of the nature-based hybrid solution. This research is a demonstration of the compatibility of natural coagulants/flocculants with other treatment technologies in the integrated/hybrid treatment process, such as the possibility of hybridizing natural coagulants with other types of coagulants.

Keywords: prickly pear powder, tara gum, nature-based solutions, aluminum sulfate, jar test, turbidity, coagulation, flocculation

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Authors: Huan Peng, Chenye Zeng, Zhao Wang

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

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

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Authors: Kamolvara Sirisuksakulchai, Soamwadee Chaianansutcharit, Kazunori Sato

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Solid Oxide Fuel Cells (SOFCs) have been considered as one of the most efficient large unit power generators for household and industrial applications. The efficiency of an electronic cell depends mainly on the electrochemical reactions in the anode. The development of anode materials has been intensely studied to achieve higher kinetic rates of redox reactions and lower internal resistance. Recent studies have introduced an efficient cermet (ceramic-metallic) material for its ability in fuel oxidation and oxide conduction. This could expand the reactive site, also known as the triple-phase boundary (TPB), thus increasing the overall performance. In this study, a bimetallic catalyst Ni₀.₇₅Co₀.₂₅Oₓ was combined with Gd₀.₁Ce₀.₉O₁.₉₅ (GDC) to be used as a cermet anode (NiCo-GDC) for an anode-supported type SOFC. The synthesis of Ni₀.₇₅Co₀.₂₅Oₓ was carried out by ball milling NiO and Co3O4 powders in ethanol and calcined at 1000 °C. The Gd₀.₁Ce₀.₉O₁.₉₅ was prepared by a urea co-precipitation method. Precursors of Gd(NO₃)₃·6H₂O and Ce(NO₃)₃·6H₂O were dissolved in distilled water with the addition of urea and were heated subsequently. The heated mixture product was filtered and rinsed thoroughly, then dried and calcined at 800 °C and 1500 °C, respectively. The two powders were combined followed by pelletization and sintering at 1100 °C to form an anode support layer. The fabrications of an electrolyte layer and cathode layer were conducted. The electrochemical performance in H₂ was measured from 800 °C to 600 °C while for CH₄ was from 750 °C to 600 °C. The maximum power density at 750 °C in H₂ was 13% higher than in CH₄. The difference in performance was due to higher polarization resistances confirmed by the impedance spectra. According to the standard enthalpy, the dissociation energy of C-H bonds in CH₄ is slightly higher than the H-H bond H₂. The dissociation of CH₄ could be the cause of resistance within the anode material. The results from lower temperatures showed a descending trend of power density in relevance to the increased polarization resistance. This was due to lowering conductivity when the temperature decreases. The long-term stability was measured at 750 °C in CH₄ monitoring at 12-hour intervals. The maximum power density tends to increase gradually with time while the resistances were maintained. This suggests the enhanced stability from charge transfer activities in doped ceria due to the transition of Ce⁴⁺ ↔ Ce³⁺ at low oxygen partial pressure and high-temperature atmosphere. However, the power density started to drop after 60 h, and the cell potential also dropped from 0.3249 V to 0.2850 V. These phenomena was confirmed by a shifted impedance spectra indicating a higher ohmic resistance. The observation by FESEM and EDX-mapping suggests the degradation due to mass transport of ions in the electrolyte while the anode microstructure was still maintained. In summary, the electrochemical test and stability test for 60 h was achieved by NiCo-GDC cermet anode. Coke deposition was not detected after operation in CH₄, hence this confirms the superior properties of the bimetallic cermet anode over typical Ni-GDC.

Keywords: bimetallic catalyst, ceria-based SOFCs, methane oxidation, solid oxide fuel cell

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Authors: Rizvi Hasan

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Male factor infertility due to abnormalities in prolactin levels is encountered in a significant proportion. This was a case-control study carried out to determine the effects of prolactin abnormalities in normal males with infertility, recruiting 297 male infertile patients with informed written consent. All underwent a Basic Seminal Fluid Analysis (BSA) and endocrine profiles of FSH, LH, testosterone and prolactin (PRL) hormones using the random access chemiluminescent immunoassay method (normal range 2.5-17ng/ml). Age, weight, and height matched voluntary controls were recruited for comparison. None of the cases had anatomical, medical or surgical disorders related to infertility. Among the controls; mean age 33.2yrs ± 5.2, BMI 21.04 ± 1.39kgm-2, BSA 34×106, a number of children fathered 2±1, PRL 6.78 ± 2.92ng/ml. Of the 297 patients, 28 were hyperprolactinaemic while one was hypoprolactinaemic. All the hyperprolactinaemic patients had oligoasthenospermia, abnormal morphology and decreased viability. The serum testosterone levels were markedly lowered in 26 (92.86%) of the hyperprolactinaemic subjects. In the other 2 hyperprolactinaemic subjects and the single hypoprolactinaemic subject, the serum testosterone levels were normal. FSH and LH were normal in all patients. The 29 male patients with abnormalities in their serum PRL profiles were followed up for 12 months. The 28 patients suffering from hyperprolactinaemia were treated with oral bromocriptine in a dose of 2.5 mg twice daily. The hypoprolactinaemic patient defaulted treatment. From the follow-up, it was evident that 19 (67.86%) of the treated patients responded after 3 months of therapy while 4 (14.29%) showed improvement after approximately 6 months of bromocriptine therapy. One patient responded after 1 year of therapy while 2 patients showed improvements although not up to normal levels within the same period. Response to treatment was assessed by improvement in their BSA parameters. Prolactin abnormalities affect the male reproductive system and semen parameters necessitating further studies to ascertain the exact role of prolactin on the male reproductive tract. A parallel study was carried out incorporating 200 male white rats that were grouped and subjected to variations in their serum PRL levels. At the end of 100 days of treatment, these rats were subjected to morphological studies of their male reproductive tracts.Varying morphological changes depending on the levels of PRL changes induced were evident. Notable changes were arrest of spermatogenesis at the spermatid stage, a reduced testicular cellularity, a reduction in microvilli of the pseudostratified epithelial lining of the epididymis, while measurement of the tubular diameter showed a 30% reduction compared to normal tissue. There were no changes in the vas deferens, seminal vesicles, and the prostate. It is evident that both hyperprolactinaemia and hypoprolactinaemia have a direct effect on the morphology and function of the male reproductive tract. The morphological studies carried out on the groups of rats who were subjected to variations in their PRL levels could be the basis for infertility in male human beings.

Keywords: male factor infertility, morphological studies, prolactin, seminal fluid analysis

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Authors: Thao Nguyen, Maximiliano Hyon, Sany Rajagukguk, Anna Melkonyan

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Introduction: Type 2 Diabetes is a well-established risk factor for severe SARS-CoV-2 infection. Uncontrolled hyperglycemia in patients with established or newly diagnosed diabetes is associated with poor outcomes, including increased mortality and hospital length of stay. Objectives: Our study aims to compare three different glycemic management strategies and their association with clinical outcomes in patients hospitalized for moderate to severe SARS-CoV-2 infection. Identifying optimal glycemic management strategies will improve the quality of patient care and improve their outcomes. Method: This is a retrospective observational study on patients hospitalized at Adventist Health White Memorial with severe SARS-CoV-2 infection from 11/1/2020 to 02/28/2021. The following inclusion criteria were used: positive SARS-CoV-2 PCR test, age >18 yrs old, diabetes or random glucose >200 mg/dL on admission, oxygen requirement >4L/min, and treatment with glucocorticoids. Our exclusion criteria included: ICU admission within 24 hours, discharge within five days, death within five days, and pregnancy. The patients were divided into three glycemic management groups: Group 1, managed solely by the Primary Team, Group 2, by Pharmacy; and Group 3, by Endocrinologist. Primary outcomes were average glucose on Day 5, change in glucose between Days 3 and 5, and average insulin dose on Day 5 among groups. Secondary outcomes would be upgraded to ICU, inpatient mortality, and hospital length of stay. For statistics, we used IBM® SPSS, version 28, 2022. Results: Most studied patients were Hispanic, older than 60, and obese (BMI >30). It was the first CV-19 surge with the Delta variant in an unvaccinated population. Mortality was markedly high (> 40%) with longer LOS (> 13 days) and a high ICU transfer rate (18%). Most patients had markedly elevated inflammatory markers (CRP, Ferritin, and D-Dimer). These, in combination with glucocorticoids, resulted in severe hyperglycemia that was difficult to control. Average glucose on Day 5 was not significantly different between groups primary vs. pharmacy vs. endocrine (220.5 ± 63.4 vs. 240.9 ± 71.1 vs. 208.6 ± 61.7 ; P = 0.105). Change in glucose from days 3 to 5 was not significantly different between groups but trended towards favoring the endocrinologist group (-26.6±73.6 vs. 3.8±69.5 vs. -32.2±84.1; P= 0.052). TDD insulin was not significantly different between groups but trended towards higher TDD for the endocrinologist group (34.6 ± 26.1 vs. 35.2 ± 26.4 vs. 50.5 ± 50.9; P=0.054). The endocrinologist group used significantly more preprandial insulin compared to other groups (91.7% vs. 39.1% vs. 65.9% ; P < 0.001). The pharmacy used more basal insulin than other groups (95.1% vs. 79.5% vs. 79.2; P = 0.047). There were no differences among groups in the clinical outcomes: LOS, ICU upgrade, or mortality. Multivariate regression analysis controlled for age, sex, BMI, HbA1c level, renal function, liver function, CRP, d-dimer, and ferritin showed no difference in outcomes among groups. Conclusion: Given high-risk factors in our population, despite efforts from the glycemic management teams, it’s unsurprising no differences in clinical outcomes in mortality and length of stay.

Keywords: glycemic management, strategies, hospitalized, SARS-CoV-2, outcomes

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Authors: F. O’Dowd, G. Murphy, M. Roche, E. Shudell, F. Keane, M. O’Kane

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Intoduction: Apremilast (Otezla®) is an oral phosphodiesterase-4 (PDE4) inhibitor indicated for treatment of adult patients with moderate to severe plaque psoriasis who have contraindications to have failed or intolerant of standard systemic therapy and/or phototherapy; and adult patients with active psoriatic arthritis. Apremilast influences intracellular regulation of inflammatory mediators. Two randomized, placebo-controlled trials evaluating apremilast in 1426 patients with moderate to severe plague psoriasis (ESTEEM 1 and 2) demonstrated that the commonest adverse reactions (AE’s) leading to discontinuation were nausea (1.6%), diarrhoea (1.0%), and headaches (0.8%). The overall proportion of subjects discontinuing due to adverse reactions was 6.1%. At week 16 these trials demonstrated significant more apremilast-treated patients (33.1%) achieved the primary end point PASI-75 than placebo (5.3%). We began prescribing apremilast in July 2015. Aim: To evaluate efficacy and tolerability of apremilast in an Irish teaching hospital psoriasis population. Methods: A proforma documenting clinical evaluation parameters, prior treatment experience and AE’s; was completed prospectively on all patients commenced on apremilast since July 2015 – July 2017. Data was collected at week 0,6,12,24,36 and week 52 with 20/71 patients having passed week 52. Efficacy was assessed using Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI). AE’s documented included GI effects, infections, changes in weight and mood. Retrospective chart review and telephone review was utilised for missing data. Results: A total of 71 adult subjects (38 male, 33 female; age range 23-57), with moderate to severe psoriasis, were evaluated. Prior treatment: 37/71 (52%) were systemic/biologic/phototherapy naïve; 14/71 (20%) has prior phototherapy alone;20/71 (28%) had previous systemic/biologic exposure; 12/71 (17%) had both psoriasis and psoriatic arthritis. PASI responses: mean baseline PASI was 10.1 and DLQI was 15.Week 6: N=71, n=15 (21%) achieved PASI 75. Week 12: N= 48, n=6 (13%) achieved a PASI 100%; n=16 (34.5%) achieved a PASI 75. Week 24: N=40, n=10 (25%) achieved a PASI 100; n=15 (37.5%) achieved a PASI 75. Week 52: N= 20, n=4 (20%) achieved a PASI 100; n= 16 (80%) achieved a PASI 75. (N= number of pts having passed the time point indicated, n= number of pts (out of N) achieving PASI or DLQI responses at that time). DLQI responses: week 24: N= 40, n=30 (75%) achieved a DLQI score of 0; n=5 (12.5%) achieved a DLQI score of 1; n=1 (2.5%) achieved a DLQI score of 10 (due to lack of efficacy). Adverse Events: The proportion of patients that discontinued treatment due to AE’s was n=7 (9.8%). One patient experienced nausea alleviated by dose reduction; another developed significant dysgeusia for certain foods, both continued therapy. Two patients lost 2-3 kg. Conclusion: Initial Irish patient experience of Apremilast appears comparable to that observed in trials with good efficacy and tolerability.

Keywords: Apremilast, introduction, Ireland, clinical audit

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Authors: Joanna Cydejko, Paulina Mika

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Hypersensitivity reactions are side effects of medications that resemble an allergic reaction. Anaphylaxis is a generalized, severe allergic reaction of the body caused by exposure to a specific agent at a dose tolerated by a healthy body. The most common causes of anaphylaxis are food (about 70%), Hymenoptera venoms (22%), and medications (7%), despite detailed diagnostics in 1% of people, the cause of the anaphylactic reaction was not indicated. Contrast media are anaphylactic agents of unknown mechanism. Hypersensitivity reactions can occur with both immunological and non-immunological mechanisms. Symptoms of anaphylaxis occur within a few seconds to several minutes after exposure to the allergen. Contrast agents are chemical compounds that make it possible to visualize or improve the visibility of anatomical structures. In the diagnosis of computed tomography, the preparations currently used are derivatives of the triiodide benzene ring. Pharmacokinetic and pharmacodynamic properties, i.e., their osmolality, viscosity, low chemotoxicity and high hydrophilicity, have an impact on better tolerance of the substance by the patient's body. In MRI diagnostics, macrocyclic gadolinium contrast agents are administered during examinations. The aim of this study is to present the results of the number and severity of anaphylactic reactions that occurred in patients in all age groups undergoing diagnostic imaging with intravenous administration of contrast agents. In non-ionic iodine CT and in macrocyclic gadolinium MRI. A retrospective assessment of the number of adverse reactions after contrast administration was carried out on the basis of data from the Department of Radiology of the University Clinical Center in Gdańsk, and it was assessed whether their different physicochemical properties had an impact on the incidence of acute complications. Adverse reactions are divided according to the severity of the patient's condition and the diagnostic method used in a given patient. Complications following the administration of a contrast medium in the form of acute anaphylaxis accounted for less than 0.5% of all diagnostic procedures performed with the use of a contrast agent. In the analysis period from January to December 2022, 34,053 CT scans and 15,279 MRI examinations with the use of contrast medium were performed. The total number of acute complications was 21, of which 17 were complications of iodine-based contrast agents and 5 of gadolinium preparations. The introduction of state-of-the-art contrast formulations was an important step toward improving the safety and tolerability of contrast agents used in imaging. Currently, contrast agents administered to patients are considered to be one of the best-tolerated preparations used in medicine. However, like any drug, they can be responsible for the occurrence of adverse reactions resulting from their toxic effects. The increase in the number of imaging tests performed with the use of contrast agents has a direct impact on the number of adverse events associated with their administration. However, despite the low risk of anaphylaxis, this risk should not be marginalized. The growing threat associated with the mass performance of radiological procedures with the use of contrast agents forces the knowledge of the rules of conduct in the event of symptoms of hypersensitivity to these preparations.

Keywords: anaphylactic, contrast medium, diagnostic, medical imagine

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Authors: Chen Jiang, Eric Jordan, Maurice Gell, Balakrishnan Nair

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Nuclear fusion, one of the most promising options for reliably generating large amounts of carbon-free energy in the future, has seen a plethora of ground-breaking technological advances in recent years. An efficient and durable “breeding blanket”, needed to ensure a reactor’s self-sufficiency by maintaining the optimal coolant temperature as well as by minimizing radiation dosage behind the blanket, still remains a technological challenge for the various reactor designs for commercial fusion power plants. A relatively new dual-coolant lead-lithium (DCLL) breeder design has exhibited great potential for high-temperature (>700oC), high-thermal-efficiency (>40%) fusion reactor operation. However, the structural material, namely reduced activation ferritic-martensitic (RAFM) steel, is not chemically stable in contact with molten Pb-17%Li coolant. Thus, to utilize this new promising reactor design, the demand for effective corrosion-resistant coatings on RAFM steels represents a pressing need. Solution Spray Technologies LLC (SST) is developing a double-layer ceramic coating design to address the corrosion protection of RAFM steels, using a novel solution and solution/suspension plasma spray technology through a US Department of Energy-funded project. Plasma spray is a coating deposition method widely used in many energy applications. Novel derivatives of the conventional powder plasma spray process, known as the solution-precursor and solution/suspension-hybrid plasma spray process, are powerful methods to fabricate thin, dense ceramic coatings with complex compositions necessary for the corrosion protection in DCLL breeders. These processes can be used to produce ultra-fine molten splats and to allow fine adjustment of coating chemistry. Thin, dense ceramic coatings with chosen chemistry for superior chemical stability in molten Pb-Li, low activation properties, and good radiation tolerance, is ideal for corrosion-protection of RAFM steels. A key challenge is to accommodate its CTE mismatch with the RAFM substrate through the selection and incorporation of appropriate bond layers, thus allowing for enhanced coating durability and robustness. Systematic process optimization is being used to define the optimal plasma spray conditions for both the topcoat and bond-layer, and X-ray diffraction and SEM-EDS are applied to successfully validate the chemistry and phase composition of the coatings. The plasma-sprayed double-layer corrosion resistant coatings were also deposited onto simulated RAFM steel substrates, which are being tested separately under thermal cycling, high-temperature moist air oxidation as well as molten Pb-Li capsule corrosion conditions. Results from this testing on coated samples, and comparisons with bare RAFM reference samples will be presented and conclusions will be presented assessing the viability of the new ceramic coatings to be viable corrosion prevention systems for DCLL breeders in commercial nuclear fusion reactors.

Keywords: breeding blanket, corrosion protection, coating, plasma spray

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Authors: Agnieszka Antończyk, MałGorzata Ochota, Wojciech Niżański, ZdzisłAw Kiełbowicz

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The goal of the cesarean section (CS) is the delivery of healthy, vigorous pups with the provision of surgical plane anesthesia, appropriate analgesia, and rapid recovery of the dam. In human medicine, spinal or epidural anesthesia is preferred for a cesarean section as associated with a lower risk of neonatal asphyxia and the need for resuscitation. Nevertheless, the specificity of veterinary patients makes the application of regional anesthesia as a sole technique impractical, thus to obtain patient compliance the general anesthesia is required. This study aimed to compare the influence of balanced (inhalant with epidural) and inhalant anesthesia on neonatal umbilical cord blood gas (UCBG) parameters and vitality (modified Apgar scoring). The bitches (31) undergoing elective CS were enrolled in this study. All females received a single dose of 0.2 mg/kg s.c. Meloxicam. Females were randomly assigned into two groups: Gr I (Isoflurane, n=16) and Gr IE (Isoflurane plus Epidural, n=15). Anesthesia was induced with propofol at 4-6 mg/kg to effect, and maintained with isoflurane in oxygen; in IE group epidural anesthesia was also done using lidocaine (3-4 mg/kg) into the lumbosacral space. CSs were performed using a standard mid-line approach. Directly after the puppy extraction, the umbilical cord was double clamped before the placenta detachment. The vessels were gently stretched between forceps to allow blood sampling. At least 100 mcl of mixed umbilical cord blood was collected into a heparinized syringe for further analysis. The modified Apgar scoring system (AS) was used to objectively score neonatal health and vitality immediately after birth (before first aid or neonatal care was instituted), at 5 and 20 min after birth. The neonates were scored as normal (AS 7-10), weak (AS 4-6), or critical (AS 0-3). During surgery, the IE group required a lower isoflurane concentration compared to the females in group I (MAC 1.05±0.2 and 1.4±0.13, respectively, p<0.01). All investigated UCBG parameters were not statistically different between groups. All pups had mild acidosis (pH 7.21±0.08 and 7.21±0.09 in Gr I and IE, respectively) with moderately elevated pCO2 (Gr I 57.18±11.48, Gr IE 58.74±15.07), HCO3- on the lower border (Gr I 22.58±3.24, Gr IE 22.83±3.6), lowered BE (Gr I -6.1±3.57, Gr IE -5.6±4.19) and mildly elevated level of lactates (Gr I 2.58±1.48, Gr IE2.53±1.03). The glucose levels were above the reference limits in both groups of puppies (74.50±25.32 in Gr I, 79.50±29.73 in Gr IE). The initial Apgar score results were similar in I and IE groups. However, the subsequent measurements of AS revealed significant differences between both groups. Puppies from the IE group received better AS scores at 5 and 20 min compared to the I group (6.86±2.23 and 8.06±2.06 vs 5.11±2.40 and 7.83±2.05, respectively). The obtained results demonstrated that administration of epidural anesthesia reduced the requirement for isoflurane in dams undergoing cesarean section and did not affect the neonatal umbilical blood gas results. Moreover, newborns from the epidural anesthesia group were scored significantly higher in AS at 5 and 20 min, indicating their better vitality and quicker improvement post-surgery.

Keywords: apgar scoring, balanced anesthesia, cesarean section, umbilical blood gas

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Authors: N. Renuka, R. Ramesh Babu, N. Vijayan

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Ion beams play a significant role in the process of tuning the properties of materials. Based on the radiation behavior, the engineering materials are categorized into two different types. The first one comprises organic solids which are sensitive to the energy deposited in their electronic system and the second one comprises metals which are insensitive to the energy deposited in their electronic system. However, exposure to swift heavy ions alters this general behavior. Depending on the mass, kinetic energy and nuclear charge, an ion can produce modifications within a thin surface layer or it can penetrate deeply to produce long and narrow distorted area along its path. When a high energetic ion beam impinges on a material, it causes two different types of changes in the material due to the columbic interaction between the target atom and the energetic ion beam: (i) inelastic collisions of the energetic ion with the atomic electrons of the material; and (ii) elastic scattering from the nuclei of the atoms of the material, which is extremely responsible for relocating the atoms of matter from their lattice position. The exposure of the heavy ions renders the material return to equilibrium state during which the material undergoes surface and bulk modifications which depends on the mass of the projectile ion, physical properties of the target material, its energy, and beam dimension. It is well established that electronic stopping power plays a major role in the defect creation mechanism provided it exceeds a threshold which strongly depends on the nature of the target material. There are reports available on heavy ion irradiation especially on crystalline materials to tune their physical and chemical properties. L-Arginine Acetate [LAA] is a potential semi-organic nonlinear optical crystal and its optical, mechanical and thermal properties have already been reported The main objective of the present work is to enhance or tune the structural and optical properties of LAA single crystals by heavy ion irradiation. In the present study, a potential nonlinear optical single crystal, L-arginine acetate (LAA) was grown by slow evaporation solution growth technique. The grown LAA single crystal was irradiated with oxygen ions at the dose rate of 600 krad and 1M rad in order to tune the structural and optical properties. The structural properties of pristine and oxygen ions irradiated LAA single crystals were studied using Powder X- ray diffraction and Fourier Transform Infrared spectral studies which reveal the structural changes that are generated due to irradiation. Optical behavior of pristine and oxygen ions irradiated crystals is studied by UV-Vis-NIR and photoluminescence analyses. From this investigation we can concluded that oxygen ions irradiation modifies the structural and optical properties of LAA single crystals.

Keywords: heavy ion irradiation, NLO single crystal, photoluminescence, X-ray diffractometer

Procedia PDF Downloads 230

Authors: Aboli Gore, Aritra Das, Sunil Sonthalia, Tanmay Mahapatra, Sridhar Srikantiah, Hemant Shah

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AMANAT is an initiative, taken in collaboration with the Government of Bihar, aimed at improving the Quality of Maternal and Neonatal care services at Bihar’s public health facilities – those offering either the Basic Emergency Obstetric and Neonatal care (BEmONC) or Comprehensive Emergency Obstetric and Neonatal care (CEmONC) services. The effectiveness of this program is evaluated by conducting cross-sectional assessments at the concerned facilities prior to (baseline) and following completion (endline) of intervention. Direct Observation of Delivery (DOD) methodology is employed for carrying out the baseline and endline assessments – through which key obstetric and neonatal care practices among the Health Care Providers (especially the nurses) are assessed quantitatively by specially trained nursing professionals. Assessment of vitals prior to delivery improved during all three phases of BEmONC and all four phases of CEmONC training with statistically significant improvement noted in: i) pulse measurement in BEmONC phase 2 (9% to 68%), 3 (4% to 57%) & 4 (14% to 59%) and CEmONC phase 2 (7% to 72%) and 3 (0% to 64%); ii) blood pressure measurement in BEmONC phase 2 (27% to 84%), 3 (21% to 76%) & 4 (36% to 71%) and CEmONC phase 2 (23% to 76%) and 3 (2% to 70%); iii) fetal heart rate measurement in BEmONC phase 2 (10% to 72%), 3 (11% to 77%) & 4 (13% to 64%) and CEmONC phase 1 (24% to 38%), 2 (14% to 82%) and 3 (1% to 73%); and iv) abdominal examination in BEmONC phase 2 (14% to 59%), 3 (3% to 59%) & 4 (6% to 56%) and CEmONC phase 1 (0% to 24%), 2 (7% to 62%) & 3 (0% to 62%). Regarding infection control, wearing of apron, mask and cap by the delivery conductors improved significantly in all BEmONC phases. Similarly, the practice of handwashing improved in all BEmONC and CEmONC phases. Even on disaggregation, the handwashing showed significant improvement in all phases but CEmONC phase-4. Not only the positive practices related to handwashing improved but also negative practices such as turning off the tap with bare hands declined significantly in the aforementioned phases. Significant decline was also noted in negative maternal care practices such as application of fundal pressure for hastening the delivery process and administration of oxytocin prior to delivery. One of the notable achievement of AMANAT is an improvement in active management of the third stage of labor (AMTSL). The overall AMTSL (including administration of oxytocin or other uterotonics uterotonic in proper dose, route and time along with controlled cord traction and uterine massage) improved in all phases of BEmONC and CEmONC mentoring. Another key area of improvement, across phases, was in proper cutting/clamping of the umbilical cord. AMANAT mentoring also led to improvement in important immediate newborn care practices such as initiation of skin-to-skin care and timely initiation of breastfeeding. The next phase of the mentoring program seeks to institutionalize mentoring across the state that could potentially perpetuate improvement with minimal external intervention.

Keywords: capacity building, nurse-mentoring, quality of care, pregnancy, newborn care

Procedia PDF Downloads 134

Authors: M. Naveed Yasin, Robert Brooke, Andrew Chan, Geoffrey I. N. Waterhouse, Drew Evans, Darren Svirskis, Ilva D. Rupenthal

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Poly(3,4-ethylenedioxythiophene) (PEDOT) is a robust conducting polymer (CP) exhibiting high conductivity and environmental stability. It can be synthesized by either chemical, electrochemical or vapour phase polymerization (VPP). Dexamethasone sodium phosphate (dexP) is an anionic drug molecule which has previously been loaded onto PEDOT as a dopant via electrochemical polymerisation; however this technique requires conductive surfaces from which polymerization is initiated. On the other hand, VPP produces highly organized biocompatible CP structures while polymerization can be achieved onto a range of surfaces with a relatively straight forward scale-up process. Following VPP of PEDOT, dexP can be loaded and subsequently released via ion-exchange. This study aimed at preparing and characterising both non-porous and porous VPP PEDOT structures including examining drug loading and release via ion-exchange. Porous PEDOT structures were prepared by first depositing a sacrificial polystyrene (PS) colloidal template on a substrate, heat curing this deposition and then spin coating it with the oxidant solution (iron tosylate) at 1500 rpm for 20 sec. VPP of both porous and non-porous PEDOT was achieved by exposing to monomer vapours in a vacuum oven at 40 mbar and 40 °C for 3 hrs. Non-porous structures were prepared similarly on the same substrate but without any sacrificial template. Surface morphology, compositions and behaviour were then characterized by atomic force microscopy (AFM), scanning electron microscopy (SEM), x-ray photoelectron spectroscopy (XPS) and cyclic voltammetry (CV) respectively. Drug loading was achieved by 50 CV cycles in a 0.1 M dexP aqueous solution. For drug release, each sample was exposed to 20 mL of phosphate buffer saline (PBS) placed in a water bath operating at 37 °C and 100 rpm. Film was stimulated (continuous pulse of ± 1 V at 0.5 Hz for 17 mins) while immersed into PBS. Samples were collected at 1, 2, 6, 23, 24, 26 and 27 hrs and were analysed for dexP by high performance liquid chromatography (HPLC Agilent 1200 series). AFM and SEM revealed the honey comb nature of prepared porous structures. XPS data showed the elemental composition of the dexP loaded film surface, which related well with that of PEDOT and also showed that one dexP molecule was present per almost three EDOT monomer units. The reproducible electroactive nature was shown by several cycles of reduction and oxidation via CV. Drug release revealed success in drug loading via ion-exchange, with stimulated porous and non-porous structures exhibiting a proof of concept burst release upon application of an electrical stimulus. A similar drug release pattern was observed for porous and non-porous structures without any significant statistical difference, possibly due to the thin nature of these structures. To our knowledge, this is the first report to explore the potential of VPP prepared PEDOT for stimuli-responsive drug delivery via ion-exchange. The produced porous structures were ordered and highly porous as indicated by AFM and SEM. These porous structures exhibited good electroactivity as shown by CV. Future work will investigate porous structures as nano-reservoirs to increase drug loading while sealing these structures to minimize spontaneous drug leakage.

Keywords: PEDOT for ion-exchange drug delivery, stimuli-responsive drug delivery, template based porous PEDOT structures, vapour phase polymerization of PEDOT

Procedia PDF Downloads 213

Authors: Rijnbout-St.James Willem, Lindner Volkhard, Scholand Mary Beth, Ashton M. Tillett, Di Gennaro Michael Jude, Smith Silvia Enrica

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Introduction: Fibrosing lung diseases are characterized by changes in the lung interstitium and are classified based on etiology: 1) environmental/exposure-related, 2) autoimmune-related, 3) sarcoidosis, 4) interstitial pneumonia, and 4) idiopathic. Among interstitial lung diseases (ILD) idiopathic forms, idiopathic pulmonary fibrosis (IPF) is the most severe. Pathogenesis of IPF is characterized by an increased presence of proinflammatory mediators, resulting in alveolar injury, where injury to alveolar epithelium precipitates an increase in collagen deposition, subsequently thickening the alveolar septum and decreasing gas exchange. Identifying biomarkers implicated in the pathogenesis of lung fibrosis is key to developing new therapies and improving the efficacy of existing therapies. The transforming growth factor-beta (TGF-B1), a mediator of tissue repair associated with WNT5A signaling, is partially responsible for fibroblast proliferation in ILD and is the target of Pirfenidone, one of the antifibrotic therapies used for patients with IPF. Canonical TGF-B signaling is mediated by the proteins SMAD 2/3, which are, in turn, indirectly regulated by Collagen Triple Helix Repeat Containing 1 (CTHRC1). In this study, we tested the following hypotheses: 1) CTHRC1 is more elevated in the ILD cohort compared to unaffected controls, and 2) CTHRC1 is differently expressed among ILD types. Material and Methods: CTHRC1 levels were measured by ELISA in 171 plasma samples from the deidentified University of Utah ILD cohort. Data represent a cohort of 131 ILD-affected participants and 40 unaffected controls. CTHRC1 samples were categorized by a pulmonologist based on affectation status and disease subtypes: IPF (n = 45), sarcoidosis (4), nonspecific interstitial pneumonia (16), hypersensitivity pneumonitis (n = 7), interstitial pneumonia (n=13), autoimmune (n = 15), other ILD - a category that includes undifferentiated ILD diagnoses (n = 31), and unaffected controls (n = 40). We conducted a single-factor ANOVA of plasma CTHRC1 levels to test whether CTHRC1 variance among affected and non-affected participants is statistically significantly different. In-silico analysis was performed with Ingenuity Pathway Analysis® to characterize the role of CTHRC1 in the pathway of lung fibrosis. Results: Statistical analyses of CTHRC1 in plasma samples indicate that the average CTHRC1 level is significantly higher in ILD-affected participants than controls, with the autoimmune ILD being higher than other ILD types, thus supporting our hypotheses. In-silico analyses show that CTHRC1 indirectly activates and phosphorylates SMAD3, which in turn cross-regulates TGF-B1. CTHRC1 also may regulate the expression and transcription of TGFB-1 via WNT5A and its regulatory relationship with CTNNB1. Conclusion: In-silico pathway analyses demonstrate that CTHRC1 may be an important biomarker in ILD. Analysis of plasma samples indicates that CTHRC1 expression is positively associated with ILD affectation, with autoimmune ILD having the highest average CTHRC1 values. While characterizing CTHRC1 levels in plasma can help to differentiate among ILD types and predict response to Pirfenidone, the extent to which plasma CTHRC1 level is a function of ILD severity or chronicity is unknown.

Keywords: interstitial lung disease, CTHRC1, idiopathic pulmonary fibrosis, pathway analyses

Procedia PDF Downloads 170

Authors: Amine Alaoui Sanae, Tagjdid Reda, Loutfi Chafiqa, Melloul Merouane, Laloui Aziz, Touil Nadia, El Fahim, E. Mostafa

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Background: Rotavirus group A (RVA) strains with G8P[14] specificities are usually detected in calves and goats. However, these strains have been reported globally in humans and have often been characterized as originating from zoonotic transmissions, particularly in area where ruminants and humans live side-by-side. Whether human P[14] genotypes are two-way and can be transmitted to animal species remains to be established. Here we describe VP4 deduced amino-acid relationships of three Moroccan P[14] genotypes originating from different species and the receptiveness of an alpine goat to a human G8P[14] through an experimental infection. Material/methods: the human MA31 RVA strain was originally identified in a four years old girl presenting an acute gastroenteritis hospitalized at the pediatric care unit in Rabat Hospital in 2011. The virus was isolated and propagated in MA104 cells in the presence of trypsin. Ch_10S and 8045_S animal RVA strains were identified in fecal samples of a 2-week-old native goat and 3-week-old calf with diarrhea in 2011 in Bouaarfa and My Bousselham respectively. Genomic RNAs of all strains were subjected to a two-step RT-PCR and sequenced using the consensus primers VP4. The phylogenetic tree for MA31, Ch_10S and 8045_S VP4 and a set of published P[14] genotypes was constructed using MEGA6 software. The receptivity of MA31 strain by an eight month-old alpine goat was assayed. The animal was orally and intraperitonally inoculated with a dose of 8.5 TCID50 of virus stock at passage level 3. The shedding of the virus was tested by a real time RT-PCR assay. Results: The phylogenetic tree showed that the three Moroccan strains MA31, Ch_10S and 8045_S VP4 were highly related to each other (100% similar at the nucleotide level). They were clustered together with the B10925, Sp813, PA77 and P169 strains isolated in Belgium, Spain and Italy respectively. The Belgian strain B10925 was the most closely related to the Moroccan strains. In contrast, the 8045_S and Ch_10S strains were clustered distantly from the Tunisian calf strain B137 and the goat strain cap455 isolated in South Africa respectively. The human MA31 RVA strain was able to induce bloody diarrhea at 2 days post infection (dpi) in the alpine goat kid. RVA virus shedding started by 2 dpi (Ct value of 28) and continued until 5 dpi (Ct value of 25) with a concomitant elevation in the body temperature. Conclusions: Our study while limited to one animal, is the first study proving experimentally that a human P[14] genotype causes diarrhea and virus shedding in the goat. This result reinforce the potential role of inter- species transmission in generating novel and rare rotavirus strains such G8P[14] which infect humans.

Keywords: interspecies transmission, rotavirus, goat, human

Procedia PDF Downloads 261

Authors: Caroline Lavratti, Pedro Dal Lago, Gustavo Reinaldo, Gilson Dorneles, Andreia Bard, Laira Fuhr, Daniela Pochmann, Alessandra Peres, Luciane Wagner, Viviane Elsner

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Approximately 1% of the world's population is affected by schizophrenia (SZ), a chronic and debilitating neurodevelopmental disorder. Among possible factors, reduced levels of Brain-derived neurotrophic factor (BDNF) has been recognized in physiopathogenesis and course of SZ. In this context, peripheral BDNF levels have been used as a biomarker in several clinical studies, since this neurotrophin is able to cross the blood-brain barrier in a bi-directional manner and seems to present a strong correlation with the central nervous system fluid levels. The patients with SZ usually adopts a sedentary lifestyle, which has been partly associated with the increase in obesity incidence rates, metabolic syndrome, type 2 diabetes and coronary heart disease. On the other hand, exercise, a non-invasive and low cost intervention, has been considered an important additional therapeutic option for this population, promoting benefits to physical and mental health. To our knowledge, few studies have been pointed out that the positive effects of exercise in SZ patients are mediated, at least in part, to enhanced levels of BDNF after training. However, these studies are focused on evaluating the effect of single bouts of exercise of chronic interventions, data concerning the short- and long-term exercise outcomes on BDNF are scarce. Therefore, this study aimed to evaluate the effect of a concurrent exercise protocol (CEP) on plasma BDNF levels of SZ patients in different time-points. Material and Methods: This study was approved by the Research Ethics Committee of the Centro Universitário Metodista do IPA (no 1.243.680/2015). The participants (n=15) were subbmited to the CEP during 90 days, 3 times a week for 60 minutes each session. In order to evaluate the short and long-term effects of exercise, blood samples were collected pre, 30, 60 and 90 days after the intervention began. Plasma BDNF levels were determined with the ELISA method, from Sigma-Aldrich commercial kit (catalog number RAB0026) according to manufacturer's instructions. Results: A remarkable increase on plasma BDNF levels at 90 days after training compared to baseline (p=0.006) and 30 days (p=0.007) values were observed. Conclusion: Our data are in agreement with several studies that show significant enhancement on BDNF levels in response to different exercise protocols in SZ individuals. We might suggest that BDNF upregulation after training in SZ patients acts in a dose-dependent manner, being more pronounced in response to chronic exposure. Acknowledgments: This work was supported by Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS)/Brazil.

Keywords: exercise, BDNF, schizophrenia, time-points

Procedia PDF Downloads 232

Authors: Diego Giuseppe Romano, Gianvito Apuleo, Jiri Duda

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Mobility is one of the most important societal needs for amusement, business activities and health. Thus, transport needs are continuously increasing, with the consequent traffic congestion and pollution increase. Aeronautic effort aims at smarter infrastructures use and in introducing greener concepts. A possible solution to address the abovementioned topics is the development of Small Air Transport (SAT) system, able to guarantee operability from today underused airfields in an affordable and green way, helping meanwhile travel time reduction, too. In the framework of Horizon2020, EU (European Union) has funded the Clean Sky 2 SAT TA (Transverse Activity) initiative to address market innovations able to reduce SAT operational cost and environmental impact, ensuring good levels of operational safety. Nowadays, most of the key technologies to improve passenger comfort and to reduce community noise, DOC (Direct Operating Costs) and pilot workload for SAT have reached an intermediate level of maturity TRL (Technology Readiness Level) 3/4. Thus, the key technologies must be developed, validated and integrated on dedicated ground and flying aircraft demonstrators to reach higher TRL levels (5/6). Particularly, SAT TA focuses on the integration at aircraft level of the following technologies [1]: 1)    Low-cost composite wing box and engine nacelle using OoA (Out of Autoclave) technology, LRI (Liquid Resin Infusion) and advance automation process. 2) Innovative high lift devices, allowing aircraft operations from short airfields (< 800 m). 3) Affordable small aircraft manufacturing of metallic fuselage using FSW (Friction Stir Welding) and LMD (Laser Metal Deposition). 4)       Affordable fly-by-wire architecture for small aircraft (CS23 certification rules). 5) More electric systems replacing pneumatic and hydraulic systems (high voltage EPGDS -Electrical Power Generation and Distribution System-, hybrid de-ice system, landing gear and brakes). 6) Advanced avionics for small aircraft, reducing pilot workload. 7) Advanced cabin comfort with new interiors materials and more comfortable seats. 8) New generation of turboprop engine with reduced fuel consumption, emissions, noise and maintenance costs for 19 seats aircraft. (9) Alternative diesel engine for 9 seats commuter aircraft. To address abovementioned market innovations, two different platforms have been designed: Reference and Green aircraft. Reference aircraft is a virtual aircraft designed considering 2014 technologies with an existing engine assuring requested take-off power; Green aircraft is designed integrating the technologies addressed in Clean Sky 2. Preliminary integration of the proposed technologies shows an encouraging reduction of emissions and operational costs of small: about 20% CO₂ reduction, about 24% NO_x reduction, about 10 db (A) noise reduction at measurement point and about 25% DOC reduction. Detailed description of the performed studies, analyses and validations for each technology as well as the expected benefit at aircraft level are reported in the present paper.

Keywords: affordable, European, green, mobility, technologies development, travel time reduction

Procedia PDF Downloads 79

Authors: Ruslin, R. E. Kartasasmita, M. S. Wibowo, S. Ibrahim

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An aphrodisiac is a substance contained in food or drug that can arouse sexual instinct and increase pleasure while working, these substances derived from plants, animals, and minerals. When consuming substances that have aphrodisiac activity and duration can improve the sexual instinct. The natural aphrodisiac effect can be obtained through plants, animals, and minerals. Leonurine compound has aphrodisiac activity, these compounds can be isolated from plants of Leonurus Sp, Sundanese people is known as deundereman, this plant is empirical has aphrodisiac activity and based on the isolation of active compounds from plants known to contain compounds leonurine, so that the compound is expected to have activity aphrodisiac. Leonurine compound can be isolated from plants or synthesized chemically with material dasa siringat acid. Leonurine compound can be obtained commercial and derivatives of these compounds can be synthesized in an effort to increase its activity. This study aims to obtain derivatives leonurine better aphrodisiac activity compared with the parent compound, modified the structure of the compounds in the form leonurin guanidino butyl ester group with butyl amin and bromoetanol. ArgusLab program version 4.0.1 is used to determine the binding energy, hydrogen bonds and amino acids involved in the interaction of the compound PDE5 receptor. The in vivo test leonurine compounds and derivatives as an aphrodisiac ingredients and hormone testosterone levels using 27 male rats Wistar strain and 9 female mice of the same species, ages ranged from 12 weeks rats weighing + 200 g / tail. The test animal is divided into 9 groups according to the type of compounds and the dose given. Each treatment group was orally administered 2 ml per day for 5 days. On the sixth day was observed male rat sexual behavior and taking blood from the heart to measure testosterone levels using ELISA technique. Statistical analysis was performed in this study is the ANOVA test Least Square Differences (LSD) using the program Statistical Product and Service Solutions (SPSS). Aphrodisiac efficacy of the leonurine compound and its derivatives have proven in silico and in vivo test, the in silico testing leonurine derivatives have smaller binding energy derivatives leonurine so that activity better than leonurine compounds. Testing in vivo using rats of wistar strain that better leonurine derivative of this compound shows leonurine that in silico studies in parallel with in vivo tests. Modification of the structure in the form of guanidine butyl ester group with butyl amin and bromoethanol increase compared leonurine compound for aphrodisiac activity, testosterone derivatives of compounds leonurine experienced a significant improvement especial is 1RD compounds especially at doses of 100 and 150 mg/bb. The results showed that the compound leonurine and its compounds contain aphrodisiac activity and increase the amount of testosterone in the blood. The compound test used in this study acts as a steroid precursor resulting in increased testosterone.

Keywords: aphrodisiac dysfunction erectile leonurine 1-RD 2-RD, dysfunction, erectile leonurine, 1-RD 2-RD

Procedia PDF Downloads 255

Authors: Shahid Noor, Kazim Najjad, Muhammad Nasir, Irshad Bhutto, Abdul Samad Memon, Khurram Anwar, Tehseen Riaz, Mian Muhammad Hanif, Nauman A. Mallik, Saeed Ahmed, Israr Ahmed, Ali Yasir

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Background: Musculoskeletal pain is the most common complaint presented to the health practitioner. It is well known that untreated or under-treated pain can have a significant negative impact on an individual’s quality of life (QoL). Objectives: This study was conducted across 10 sites in six (6) major cities of Pakistan to evaluate the tolerability, safety, and the clinical response of Nuberol Forte® (Paracetamol 650 mg + Orphenadrine 50 mg) to musculoskeletal pain in routine Pakistani practice and its impact on improving the patient’s QoL. Design & Methods: This NFORT-EFFECT observational, prospective multicenter study was conducted in compliance with Good Clinical Practice guidelines and local regulatory requirements. The study sponsor was "The Searle Company Limited, Pakistan. To maintain the GCP compliances, the sponsor assigned the CRO for the site and data management. Ethical approval was obtained from an independent ethics committee. The IEC reviewed the progress of the study. Written informed consent was obtained from the study participants, and their confidentiality was maintained throughout the study. A total of 399 patients with known prescreened musculoskeletal conditions and pain who attended the study sites were recruited, as per the inclusion/exclusion criteria (clinicaltrials.gov ID# NCT04765787). The recruited patients were then prescribed Paracetamol (650 mg) and Orphenadrine (50 mg) combination (Nuberol Forte®) for 7 to 14 days as per the investigator's discretion based on the pain intensity. After the initial screening (visit 1), a follow-up visit was conducted after 1-2 weeks of the treatment (visit 2). Study Endpoints: The primary objective was to assess the pain management response of Nuberol Forte treatment and the overall safety of the drug. The Visual Analogue Scale (VAS) scale was used to measure pain severity. Secondary to pain, the patients' health-related quality of life (HRQoL) was also assessed using the Muscle, Joint Measure (MJM) scale. The safety was monitored on the first dose by the patients. These assessments were done on each study visit. Results: Out of 399 enrolled patients, 49.4% were males, and 50.6% were females with a mean age of 47.24 ± 14.20 years. Most patients were presented with Knee Osteoarthritis (OA), i.e., 148(38%), followed by backache 70(18.2%). A significant reduction in the mean pain score was observed after the treatment with the combination of Paracetamol and Orphenadrine (p<0.05). Furthermore, an overall improvement in the patient’s QoL was also observed. During the study, only ten patients reported mild adverse events (AEs). Conclusion: The combination of Paracetamol and Orphenadrine (Nuberol Forte®) exhibited effective pain management among patients with musculoskeletal conditions and also improved their QoL.

Keywords: musculoskeletal pain, orphenadrine/paracetamol combination, pain management, quality of life, Pakistani population

Procedia PDF Downloads 141

Authors: Nyathi Mpumelelo; Moeng Thabiso Maria

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BACKGROUND AND OBJECTIVES: Radiopharmaceuticals are used for diagnosis, treatment, staging and follow up of various diseases. However, there is concern that the ionizing radiation (gamma rays, α and ß particles) emitted by radiopharmaceuticals may result in exposure of radiographers and nurses with limited knowledge of the principles of radiation protection and safety, raising the risk of cancer induction. This study aimed at investigation radiation safety awareness levels among radiographers and nurses at a small tertiary hospital in South Africa. METHODS: An analytical cross-sectional study. A validated two-part questionnaire was implemented to consenting radiographers and nurses working in a Nuclear Medicine Department. Part 1 gathered demographic information (age, gender, work experience, attendance to/or passing ionizing radiation protection courses). Part 2 covered questions related to knowledge and awareness of radiation protection principles. RESULTS: Six radiographers and five nurses participated (27% males and 73% females). The mean age was 45 years (age range 20-60 years). The study revealed that neither professional development courses nor radiation protection courses are offered at the Nuclear Medicine Department understudy. However, 6/6 (100%) radiographers exhibited a high level of awareness of radiation safety principles on handling and working with radiopharmaceuticals which correlated to their years of experience. As for nurses, 4/5 (80%) showed limited knowledge and awareness of radiation protection principles irrespective of the number of years in the profession. CONCLUSION: Despite their major role of caring for patients undergoing diagnostic and therapeutic treatments, the nurses showed limited knowledge of ionizing radiation and associated side effects. This was not surprising since they never received any formal basic radiation safety course. These findings were not unique to this Centre. A study conducted in a Kuwaiti Radiology Department also established that the vast majority of nurses did not understand the risks of working with ionizing radiation. Similarly, nurses in an Australian hospital exhibited knowledge limitations. However, nursing managers did provide the necessary radiation safety training when requested. In Guatemala and Saudi Arabia, where there was shortage of professional radiographers, nurses underwent radiography training, a course that equipped them with basic radiation safety principles. The radiographers in the Centre understudy unlike others in various parts of the world demonstrated substantial knowledge and awareness on radiation protection. Radiations safety courses attended when an opportunity arose played a critical role in their awareness. The knowledge and awareness levels of these radiographers were comparable to their counterparts in Sudan. However, it was much more above that of their counterparts in Jordan, Nigeria, Nepal and Iran who were found to have limited awareness and inadequate knowledge on radiation dose. Formal radiation safety and awareness courses and workshops can play a crucial role in raising the awareness of nurses and radiographers on radiation safety for their personal benefit and that of their patients.

Keywords: radiation safety, radiation awareness, training, nuclear medicine

Procedia PDF Downloads 47

Authors: Katarína Koňariková, Georgios A. Perdikaris, Lucia Andrezálová, Zdeňka Ďuračková, Lucia Laubertová, Helena Gbelcová, Ingrid Žitňanová

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Introduction: The continuous demand for new anti-cancer drugs has stimulated chemotherapeutic research based on the use of essential metalloelements with the aim to develop potential drugs with lower toxicity and higher antiproliferative activity against tumors. Copper(II) and its complexes play an important role as suitable species for antiproliferative tests. Objectives: The central objective of the current study was to investigate the potential in vitro anti-proliferative effects of N-salicylidene-L-glutamato copper (II) complexes and molecular mechanism of apoptosis induced by tested complexes. In our project we tested N-salicylidene-L-glutamato copper (II) complexes ZK1 - [Cu(N-salicylidene-L-glutamato)(H2O)2].H2O; MK0 - ([Cu2(N-sal-D,L-glu)2(isoquinoline)2].2H2O); MK1 - [Cu(N-salicylidene-5-methyl-L-glutamato)(H2O)].H2O; MK3 - transbis(ethanol)tetrakis(imidazol)Cu(II)(2+)bis(N-salicylidene-D,L-glutamato-N,O)-KO:KO´-(imidazol); MK5 - [Cu(N-salicylidene-D,L- glutamato)(2-methylimidazol] at concentration range 0.001-100 µmol/L against human colon carcinoma cell line HT-29 and human breast carcinoma cell line MCF-7. Methods: Viability was assessed by direct counting of 0.4% trypan blue dye-excluding cells after 24, 48 and 72 hour cultivations with or without copper complex and by MTT assay. To analyze the type of cell death and its mechanism induced by our copper complex we used different methods. To distinguish apoptosis from necrosis we used electrophoretic analysis, to study the activity of caspases 8 and 9 – luminometric analysis and caspase activity 3 colorimetric assay. Results: The observed anti-proliferative effect of the copper complexes appeared to be dose-, time- and cell line- dependent. Human colon carcinoma cells HT-29 appeared to be more sensitive to the complex MK0 ([Cu2(N-sal-D,L-glu)2(isoquinoline)2].2H2O) than to ZK1 ([Cu(N-salicylidene-L-glutamato)(H2O)2].H2O) and MK1 ([Cu(N-salicylidene-5-methyl-L-glutamato)(H2O)].H2O)). Human colon carcinoma cells HT-29 appeared to be more sensitive to the complex than human breast carcinoma cells MCF-7. IC50 decreased with time of incubation (24, 48 and 72h) for HT-29, but increased for MCF-7. By electrophoresis we found apoptotic cell death induced by our copper complexes in HT-29 at concentrations 1, 10, 50 and 100 µmol/L after 48h (ZK1) and 72h (MK0, MK1) and in MCF-7 we did not find apoptosis. We also studied molecular mechanism of apoptosis in HT-29 induced by copper complexes. We found active caspase 9 in HT-29 after ZK1 ([Cu(N-salicylidene-L-glutamato)(H2O)2].H2O) and MK1 ([Cu(N-salicylidene-5-methyl-L-glutamato)(H2O)].H2O)) influence and active caspase 8 after MK0 ([Cu2(N-sal-D,L-glu)2(isoquinoline)2].2H2O) influence. Conclusion: Our copper complexes showed cytotoxic activities against human colon carcinoma cells HT-29 and breast cancer cell line MCF-7 in vitro. Apoptosis was activated by mitochondrial pathway (intrinsic pathway) in case of ZK1 [Cu(N-salicylidene-L-glutamato)(H2O)2].H2O; MK1 [Cu(N-salicylidene-5-methyl-L-glutamato)(H2O)].H2O; MK3 - transbis(ethanol)tetrakis(imidazol)Cu(II)(2+)bis(N-salicylidene-D,L-glutamato-N,O)-KO:KO´-(imidazol) and MK5 - [Cu(N-salicylidene-D,L- glutamato)(2-methylimidazol] copper complexes and by death receptors (extrinsic pathway) in case of MK0 [Cu2(N-sal-D,L-glu)2(isoquinoline)2].2H2O copper complex in HT-29.

Keywords: apoptosis, copper complex, cancer, carcinoma cell line

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Authors: Andrea L. Arnett, Ann T. Packard, Yolanda I. Garces, Kenneth W. Merrell

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Objective: Pathologic response following neoadjuvant chemoradiation (CRT) has been associated with improved overall survival (OS). Conflicting results have been reported regarding the pathologic predictive value of positron emission tomography (PET) response in patients with stage III lung cancer. The aim of this study was to evaluate the correlation between post-treatment PET response and pathologic response utilizing novel FDG-PET parameters. Methods: This retrospective study included patients with non-metastatic, stage IIIA (N2) NSCLC cancer treated with CRT followed by resection. All patients underwent PET prior to and after neoadjuvant CRT. Univariate analysis was utilized to assess correlations between PET response, nodal clearance, pCR, and near-complete pathologic response (defined as the microscopic residual disease or less). Maximal standard uptake value (SUV), standard uptake ratio (SUR) [normalized independently to the liver (SUR-L) and blood pool (SUR-BP)], metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured pre- and post-chemoradiation. Results: A total of 44 patients were included for review. Median age was 61.9 years, and median follow-up was 2.6 years. Histologic subtypes included adenocarcinoma (72.2%) and squamous cell carcinoma (22.7%), and the majority of patients had the T2 disease (59.1%). The rate of pCR and near-complete pathologic response within the primary lesion was 28.9% and 44.4%, respectively. The average reduction in SUVmₐₓ was 9.2 units (range -1.9-32.8), and the majority of patients demonstrated some degree of favorable treatment response. SUR-BP and SUR-L showed a mean reduction of 4.7 units (range -0.1-17.3) and 3.5 units (range –1.7-12.6), respectively. Variation in PET response was not significantly associated with histologic subtype, concurrent chemotherapy type, stage, or radiation dose. No significant correlation was found between pathologic response and absolute change in MTV or TLG. Reduction in SUVmₐₓ and SUR were associated with increased rate of pathologic response (p ≤ 0.02). This correlation was not impacted by normalization of SUR to liver versus mediastinal blood pool. A threshold of > 75% decrease in SUR-L correlated with near-complete response, with a sensitivity of 57.9% and specificity of 85.7%, as well as positive and negative predictive values of 78.6% and 69.2%, respectively (diagnostic odds ratio [DOR]: 5.6, p=0.02). A threshold of >50% decrease in SUR was also significantly associated pathologic response (DOR 12.9, p=0.2), but specificity was substantially lower when utilizing this threshold value. No significant association was found between nodal PET parameters and pathologic nodal clearance. Conclusions: Our results suggest that treatment response to neoadjuvant therapy as assessed on PET imaging can be a predictor of pathologic response when evaluated via SUV and SUR. SUR parameters were associated with higher diagnostic odds ratios, suggesting improved predictive utility compared to SUVmₐₓ. MTV and TLG did not prove to be significant predictors of pathologic response but may warrant further investigation in a larger cohort of patients.

Keywords: lung cancer, positron emission tomography (PET), standard uptake ratio (SUR), standard uptake value (SUV)

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Authors: Safa Ladhari, Alireza Saidi, Phuong Nguyen-Tri

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During health crises, such as COVID-19, using disposable protective equipment (PEs) (masks, gowns, etc.) causes long-term problems, increasing the volume of hazardous waste that must be handled safely and expensively. Therefore, producing textiles for antimicrobial and reusable materials is highly desirable to decrease the use of disposable PEs that should be treated as hazardous waste. In addition, if these items are used regularly in the workplace or for daily activities by the public, they will most likely end up in household waste. Furthermore, they may pose a high risk of contagion to waste collection workers if contaminated. Therefore, to protect the whole population in times of sanitary crisis, it is necessary to equip these materials with tools that make them resilient to the challenges of carrying out daily activities without compromising public health and the environment and without depending on them external technologies and producers. In addition, the materials frequently used for EPs are plastics of petrochemical origin. The subject of the present work is replacing petroplastics with bioplastic since it offers better biodegradability. The chosen polymer is polyhydroxybutyrate (PHB), a family of polyhydroxyalkanoates synthesized by different bacteria. It has similar properties to conventional plastics. However, it is renewable, biocompatible, and has attractive barrier properties compared to other polyesters. These characteristics make it ideal for EP protection applications. The current research topic focuses on the preparation and rapid evaluation of the biological activity of nanotechnology-based antimicrobial agents to treat textile surfaces used for PE. This work will be carried out to provide antibacterial solutions that can be transferred to a workplace application in the fight against short-term biological risks. Three main objectives are proposed during this research topic: 1) the development of suitable methods for the deposition of antibacterial agents on the surface of textiles; 2) the development of a method for measuring the antibacterial activity of the prepared textiles and 3) the study of the biodegradability of the prepared textiles. The studied textile is a non-woven fabric based on a biodegradable polymer manufactured by the electrospinning method. Indeed, nanofibers are increasingly studied due to their unique characteristics, such as high surface-to-volume ratio, improved thermal, mechanical, and electrical properties, and confinement effects. The electrospun film will be surface modified by plasma treatment and then loaded with hybrid antibacterial silver and titanium dioxide nanoparticles by the dip-coating method. This work uses simple methods with emerging technologies to fabricate nanofibers with suitable size and morphology to be used as components for protective equipment. The antibacterial agents generally used are based on silver, zinc, copper, etc. However, to our knowledge, few researchers have used hybrid nanoparticles to ensure antibacterial activity with biodegradable polymers. Also, we will exploit visible light to improve the antibacterial effectiveness of the fabric, which differs from the traditional contact mode of killing bacteria and presents an innovation of active protective equipment. Finally, this work will allow for the innovation of new antibacterial textile materials through a simple and ecological method.

Keywords: protective equipment, antibacterial textile materials, biodegradable polymer, electrospinning, hybrid antibacterial nanoparticles

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Authors: Benedict Ofori, Kwabena Sarpong, Stephen Antwi

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Background: Medicinal plants are utilized all around the world and are becoming increasingly important economically. The WHO notes that ‘inappropriate use of traditional medicines or practices can have negative or dangerous effects and that future research is needed to ascertain the efficacy and safety of such practices and medicinal plants used by traditional medicine systems. The poor around the world have limited access to palliative care or pain relief. Pharmacologists have been focused on developing safe and effective anti-inflammatory drugs. Most of the issues related to their use have been linked to the fact that numerous traditional and herbal treatments are classified in different nations as meals or dietary supplements. As a result, there is no need for evidence of the quality, efficacy, or safety of these herbal formulations before they are marketed. The fact that access to drugs meant for pain relief is limited in low-income countries means advanced studies should be done on home drugs meant for inflammation to close the gap. Methods: The ethanolic extracts of the plant were screened for the presence of 10 phytochemicals. The Pierce BCA Protein Assay Kit was used for the determination of the protein concentration of the egg white. The rats were randomly selected and put in 6 groups. The egg white was sub-plantar injected into the right-hand paws of the rats to induce inflammation. The animals were treated with the three plant extracts obtained from the root bark, stem, and leaves of the plant. The control groups were treated with normal saline, while the standard groups were treated with standard drugs indomethacin and celecoxib. Plethysmometer was used to measure the change in paw volume of the animals over the course of the experiment. Results: The results of the phytochemical screening revealed the presence of reducing sugars and saponins. Alkaloids were present in only R.L.S (1:1:1), and phytosterols were found in R.L(1:1) and R.L.S (1:1:1). The estimated protein concentration was found to be 103.75 mg/ml. The control group had an observable increase in paw volume, which indicated that inflammation was induced during the 5 hours. The increase in paw volume for the control group peaked at the 1st hour and decreased gradually throughout the experiment, with minimal changes in the paw volumes. The 2nd and 3rd groups were treated with 20 mg/kg of indomethacin and celecoxib. The anti-inflammatory activities of indomethacin and celecoxib were calculated to be 21.4% and 4.28%, respectively. The remaining 3 groups were treated with 2 dose levels of 200mg/kg plant extracts. R.L.S, R.L, and S.R.L had anti-inflammatory activities of 22.3%, 8.2%, and 12.07%, respectively. Conclusions: Egg albumin-induced paw model in rats can be used to evaluate the anti-inflammatory activity of herbs that might have potential anti-inflammatory activity. Herbal medications have potential anti-inflammatory activities and can be used to manage various inflammatory conditions if their efficacy and side effects are well studied. The three extracts all possessed anti-inflammatory activity, with R.L.S having the highest anti-inflammatory activity.

Keywords: inflammation, capparis erythrocarpos, anti-inflammatory activity, herbal medicine, paw volume, egg albumin

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Authors: Thauane Silva, Gabrielle do Vale, Andre Ferreira, Marilda Siqueira, Thiago Moreno L. Souza, Milene D. Miranda

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The exposure of A(H1N1)pdm09-infected epithelial cells (HeLa) to HIV-1 viral particles, or its gp120, enhanced interferon-induced transmembrane protein (IFITM3) content, a viral restriction factor (RF), resulting in a decrease in influenza replication. The gp120 binds to CCR5 (R5) or CXCR4 (X4) cell receptors during HIV-1 infection. Then, it is possible that the endogenous ligands of these receptors also modulate the expression of IFITM3 and other cellular factors that restrict influenza virus replication. Thus, the aim of this study is to analyze the role of cellular receptors R5 and X4 in modulating RFs in order to inhibit the replication of the influenza virus. A549 cells were treated with 2x effective dose (ED50) of endogenous R5 or X4 receptor agonists, CCL3 (20 ng/ml), CCL4 (10 ng/ml), CCL5 (10 ng/ml) and CXCL12 (100 ng/mL) or exogenous agonists, gp120 Bal-R5, gp120 IIIB-X4 and its mutants (5 µg/mL). The interferon α (10 ng/mL) and oseltamivir (60 nM) were used as a control. After 24 h post agonists exposure, the cells were infected with virus influenza A(H3N2) at 2 MOI (multiplicity of infection) for 1 h. Then, 24 h post infection, the supernatant was harvested and, the viral titre was evaluated by qRT-PCR. To evaluate IFITM3 and SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1 (SAMHD1) protein levels, A549 were exposed to agonists for 24 h, and the monolayer was lysed with Laemmli buffer for western blot (WB) assay or fixed for indirect immunofluorescence (IFI) assay. In addition to this, we analyzed other RFs modulation in A549, after 24 h post agonists exposure by customized RT² Profiler Polymerase Chain Reaction Array. We also performed a functional assay in which SAMHD1-knocked-down, by single-stranded RNA (siRNA), A549 cells were infected with A(H3N2). In addition, the cells were treated with guanosine to assess the regulatory role of dNTPs by SAMHD1. We found that R5 and X4 agonists inhibited influenza replication in 54 ± 9%. We observed a four-fold increase in SAMHD1 transcripts by RFs mRNA quantification panel. After 24 h post agonists exposure, we did not observe an increase in IFITM3 protein levels through WB or IFI assays, but we observed an upregulation up to three-fold in the protein content of SAMHD1, in A549 exposed to agonists. Besides this, influenza replication enhanced in 20% in cell cultures that SAMDH1 was knockdown. Guanosine treatment in cells exposed to R5 ligands further inhibited influenza virus replication, suggesting that the inhibitory mechanism may involve the activation of the SAMHD1 deoxynucleotide triphosphohydrolase activity. Thus, our data show for the first time a direct relationship of SAMHD1 and inhibition of influenza replication, and provides perspectives for new studies on the signaling modulation, through cellular receptors, to induce proteins of great importance in the control of relevant infections for public health.

Keywords: chemokine receptors, gp120, influenza, virus restriction factors

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Authors: Mohammad Shajid Rahman, Tarik Kaya, Edgar Matida

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Electronic cigarettes, also known as e-cigarettes, may have become a tool to improve smoking cessation due to their ability to provide nicotine at a selected rate. Unlike traditional cigarettes, which produce toxic elements from tobacco combustion, e-cigarettes generate aerosols by heating a liquid solution (commonly a mixture of propylene glycol, vegetable glycerin, nicotine and some flavoring agents). However, caution still needs to be taken when using e-cigarettes due to the presence of addictive nicotine and some harmful substances produced from the heating process. Particle size distribution (PSD) and associated velocities generated by e-cigarettes have significant influence on aerosol deposition in different regions of human respiratory tracts. On another note, low actuation power is beneficial in aerosol generating devices since it exhibits a reduced emission of toxic chemicals. In case of e-cigarettes, lower heating powers can be considered as powers lower than 10 W compared to a wide range of powers (0.6 to 70.0 W) studied in literature. Due to the importance regarding inhalation risk reduction, deeper understanding of particle size characteristics of e-cigarettes demands thorough investigation. However, comprehensive study on PSD and velocities of e-cigarettes with a standard testing condition at relatively low heating powers is still lacking. The present study aims to measure particle number count and size distribution of undiluted aerosols of a latest fourth-generation e-cigarette at low powers, within 6.5 W using real-time particle counter (time-of-flight method). Also, temporal and spatial evolution of particle size and velocity distribution of aerosol jets are examined using phase Doppler anemometry (PDA) technique. To the authors’ best knowledge, application of PDA in e-cigarette aerosol measurement is rarely reported. In the present study, preliminary results about particle number count of undiluted aerosols measured by time-of-flight method depicted that an increase of heating power from 3.5 W to 6.5 W resulted in an enhanced asymmetricity in PSD, deviating from log-normal distribution. This can be considered as an artifact of rapid vaporization, condensation and coagulation processes on aerosols caused by higher heating power. A novel mathematical expression, combining exponential, Gaussian and polynomial (EGP) distributions, was proposed to describe asymmetric PSD successfully. The value of count median aerodynamic diameter and geometric standard deviation laid within a range of about 0.67 μm to 0.73 μm, and 1.32 to 1.43, respectively while the power varied from 3.5 W to 6.5 W. Laser Doppler velocimetry (LDV) and PDA measurement suggested a typical centerline streamwise mean velocity decay of aerosol jet along with a reduction of particle sizes. In the final submission, a thorough literature review, detailed description of experimental procedure and discussion of the results will be provided. Particle size and turbulent characteristics of aerosol jets will be further examined, analyzing arithmetic mean diameter, volumetric mean diameter, volume-based mean diameter, streamwise mean velocity and turbulence intensity. The present study has potential implications in PSD simulation and validation of aerosol dosimetry model, leading to improving related aerosol generating devices.

Keywords: E-cigarette aerosol, laser doppler velocimetry, particle size distribution, particle velocity, phase Doppler anemometry

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Authors: Diego F. Carrillo-González, Milena Osorio, Natalia M. Cerro, Yasser Y. Lenis

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Introduction: mortality during the implantation and early embryonic development periods reach around 30% in different mammalian species. It has been described that progesterone (P4) and Arginine (Arg) play a beneficial role in establishing and maintaining early pregnancy in mammals. The combined effect between Arg and P4 on reproductive parameters in the rabbit species is not yet elucidated, to our best knowledge. Objective: to assess the effect of L-arginine and progesterone during the post-breeding period in female rabbits on the composition of the amniotic fluid, the placental structure, and the bone growth in their fetuses. Methods: crossbred female rabbits (n=16) were randomly distributed into four experimental groups (Ctrl, Arg, P4, and Arg+P4). In the control group, 0.9% saline solution was administered as a placebo, the Arg group was administered arginine (50 mg/kg BW) from day 4.5 to day 19 post-breeding, the P4 group was administered progesterone (Gestavec®, 1.5 mg/kg BW) from 24 hours to day 4 post-breeding and for the Arg+P4 group, an administration was performed under the same time and dose guidelines as the Arg and P4 treatments. Four females were sacrificed, and the amniotic fluid was collected and analyzed with rapid urine test strips, while the placenta and fetuses were processed in the laboratory to obtain histological plates. The percentage of deciduous, labyrinthine, and junctional zones was determined, and the length of the femur for each fetus was measured as an indicator of growth. Descriptive statistics were applied to identify the success rates for each of the tests. Afterwards, A one-way analysis of variance (ANOVA) was performed, and a comparison of means was conducted by Tukey's test. Results: a higher density (p<0.05) was observed in the amniotic fluid for fetuses in the control group (1022±2.5g/mL) compared to the P4 (1015±5.3g/mL) and Arg+P4 (1016±4,9g/mL) groups. Additionally, the density of amniotic fluid in the Arg group (1021±2.5g/mL) was higher (p<0.05) than in the P4 group. The concentration of protein, glucose, and ascorbic acid had no statistical difference between treatments (p>0.05). The histological analysis of the uteroplacental regions, a statistical difference (p<0,05) in the proportion of deciduous zone was found between the P4 group (9.6±2.6%) when compared with the Ctrl (28.15±12.3%), and Arg+P4 (26.3±4.9) groups. In the analysis of the fetuses, the weight was higher for the Arg group (2.69±0.18), compared to the other groups (p<0.05), while a shorter length was observed (p<0.05) in the fetuses for the Arg+P4 group (25.97±1.17). However, no difference (p>0.05) was found when comparing the length of the developing femurs between the experimental groups. Conclusion: the combination of L-arginine and progesterone allows a reduction in the density of amniotic fluid, without affecting the protein, energy, and antioxidant components. However, the use of L-arginine stimulates weight gain in fetuses, without affecting size, which could be used to improve production parameters in rabbit production systems. In addition, the modification in the deciduous zone could show a placental adaptation based on the fetal growth process, however more specific studies on the placentation process are required.

Keywords: arginine, progesterone, rabbits, reproduction

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Authors: Dipendra Kumar Yadav, Nabaraj Paudel, Anjana Yadav

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Background: Low Birth weight (LBW) is defined as the weight at birth less than 2500 grams, irrespective of the period of their gestation. LBW is an important indicator of general health status of population and is considered as the single most important predictors of infant mortality especially of deaths within the first month of life that is birth weight determines the chances of newborn survival. Objective of this study was to identify the maternal risk factors associated with low birth weight neonates. Materials and Methods: A hospital based case-control study was conducted in maternity ward of Manipal Teaching Hospital, Pokhara, Nepal from 23 September 2014 to 12 November 2014. During study period 59 cases were obtained and twice number of control group were selected with frequency matching of the mother`s age with ± 3 years and total controls were 118. Interview schedule was used for data collection along with record review. Data were entered in Epi-data program and analysis was done with help of SPSS software program. Results: From bivariate logistic regression analysis, eighteen variables were found significantly associated with LBW and these were place of residence, family monthly income, education, previous still birth, previous LBW, history of STD, history of vaginal bleeding, anemia, ANC visits, less than four ANC visits, de-worming status, counseling during pregnancy, CVD, physical workload, stress, extra meal during pregnancy, smoking and alcohol consumption status. However after adjusting confounding variables, only six variables were found significantly associated with LBW. Mothers who had family monthly income up to ten thousand rupees were 4.83 times more likely to deliver LBW with CI (1.5-40.645) and p value 0.014 compared to mothers whose family income NRs.20,001-60,000. Mothers who had previous still birth were 2.01 times more likely to deliver LBW with CI (0.69-5.87) and p value 0.02 compared to mothers who did not has previous still birth. Mothers who had previous LBW were 5.472 times more likely to deliver LBW with CI (1.2-24.93) and p value 0.028 compared to mothers who did not has previous LBW. Mothers who had anemia during pregnancy were 3.36 times more likely to deliver LBW with CI (0.77-14.57) and p value 0.014 compared to mothers who did not has anemia. Mothers who delivered female newborn were 2.96 times more likely to have LBW with 95% CI (1.27-7.28) and p value 0.01 compared to mothers who deliver male newborn. Mothers who did not get extra meal during pregnancy were 6.04 times more likely to deliver LBW with CI (1.11-32.7) and p value 0.037 compared to mothers who getting the extra meal during pregnancy. Mothers who consumed alcohol during pregnancy were 4.83 times more likely to deliver LBW with CI (1.57-14.83) and p value 0.006 compared to mothers who did not consumed alcohol during pregnancy. Conclusions: To reduce low birth weight baby through economic empowerment of family and individual women. Prevention and control of anemia during pregnancy is one of the another strategy to control the LBW baby and mothers should take full dose of iron supplements with screening of haemoglobin level. Extra nutritional food should be provided to women during pregnancy. Health promotion program will be focused on avoidance of alcohol and strengthen of health services that leads increasing use of maternity services.

Keywords: low birth weight, case-control, risk factors, hospital based study

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