Search results for: clinical/non-clinical sample

Authors: Misa Nakao, Yuta Kurashina, Chikahiro Imashiro, Kenjiro Takemura

Abstract:

The Research Goal: With the growing demand for regenerative medicine, an effective mass cell culture process is required. In a repetitive subculture process for proliferating cells, preparing single cell suspension which does not contain any cell aggregates is highly required because cell aggregates often raise various undesirable phenomena, e.g., apoptosis and decrease of cell proliferation. Since cell aggregates often occur in cell suspension during conventional subculture processes, this study proposes a single cell sorter driven by a resonance vibration of a cell culture substrate. The Method and the Result: The single cell sorter is simply composed of a cell culture substrate and a glass pipe vertically placed against the cell culture substrate with a certain gap corresponding to a cell diameter. The cell culture substrate is made of biocompatible stainless steel with a piezoelectric ceramic disk glued to the bottom side. Applying AC voltage to the piezoelectric ceramic disk, an out-of-plane resonance vibration with a single nodal circle of the cell culture substrate can be excited at 5.5 kHz. By doing so, acoustic radiation force is emitted, and then cell suspension containing only single cells is pumped into the pipe and collected. This single cell sorter is effective to collect single cells selectively in spite of its quite simple structure. We collected C2C12 myoblast cell suspension by the single cell sorter with the vibration amplitude of 12 µmp-p and evaluated the ratio of single cells in number against the entire cells in the suspension. Additionally, we cultured the collected cells for 72 hrs and measured the number of cells after the cultivation in order to evaluate their proliferation. As a control sample, we also collected cell suspension by conventional pipetting, and evaluated the ratio of single cells and the number of cells after the 72-hour cultivation. The ratio of single cells in the cell suspension collected by the single cell sorter was 98.2%. This ratio was 9.6% higher than that collected by conventional pipetting (statistically significant). Moreover, the number of cells cultured for 72 hrs after the collection by the single cell sorter yielded statistically more cells than that collected by pipetting, resulting in a 13.6% increase in proliferated cells. These results suggest that the cell suspension collected by the single cell sorter driven by the resonance vibration hardly contains cell aggregates whose diameter is larger than the gap between the cell culture substrate and the pipe. Consequently, the cell suspension collected by the single cell sorter maintains high cell proliferation. Conclusions: In this study, we developed a single cell sorter capable of sorting and pumping single cells by a resonance vibration of a cell culture substrate. The experimental results show the single cell sorter collects single cell suspension which hardly contains cell aggregates. Furthermore, the collected cells show higher proliferation than that of cells collected by conventional pipetting. This means the resonance vibration of the cell culture substrate can benefit us with the increase in efficiency of mass cell culture process for clinical applications.

Keywords: acoustic radiation force, cell proliferation, regenerative medicine, resonance vibration, single cell sorter

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Authors: Habtamu Abdisa

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Spring water is particularly valuable due to its high mineral content, which is beneficial for human health. However, anthropogenic activities usually imbalance the natural levels of its composition, which can cause adverse health effects. Regular monitoring of a naturally given environmental resource is of great concern in the world today. The spectrophotometric application is one of the best methods for qualifying and quantifying the mineral contents of environmental water samples. This research was conducted to evaluate the quality of spring water concerning its heavy metal composition. A grab sampling technique was employed to collect representative samples, including duplicates. The samples were then treated with concentrated HNO3 to a pH level below 2 and stored at 4oC. The samples were digested and analyzed for cadmium (Cd), chromium (Cr), manganese (Mn), copper (Cu), iron (Fe), and zinc (Zn) following method validation. Atomic Absorption Spectrometry (AAS) was utilized for the sample analysis. Quality control measures, including blanks, duplicates, and certified reference materials (CRMs), were implemented to ensure the accuracy and precision of the analytical results. Of the metals analyzed in the water samples, Cd and Cr were found to be below the detection limit. However, the concentrations of Mn, Cu, Fe, and Zn ranged from mean values of 0.119-0.227 mg/L, 0.142-0.166 mg/L, 0.183-0.267 mg/L, and 0.074-0.181 mg/L, respectively. Sediment analysis revealed mean concentration ranges of 348.31-429.21 mg/kg, 0.23-0.28 mg/kg, 18.73-22.84 mg/kg, 2.76-3.15 mg/kg, 941.84-1128.56 mg/kg, and 42.39-66.53 mg/kg for Mn, Cd, Cu, Cr, Fe, and Zn, respectively. The study results established that the evaluated spring water and its associated sediment met the regulatory standards and guidelines for heavy metal concentrations. Furthermore, this research can enhance the quality assurance and control processes for environmental sample analysis, ensuring the generation of reliable data.

Keywords: method validation, heavy metal, spring water, sediment, method detection limit

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Authors: Siamak Samani, Nadereh Sohrabi

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Psychological nano-therapy is a new method based on systems theory. According to the theory, systems with severe dysfunctions are resistant to changes. Psychological nano-therapy helps the therapists to break this ice. Two key concepts in psychological nano-therapy are nano-functions and nano-behaviors. The most important step in psychological nano-therapy in family therapy is selecting the most effective nano-function and nano-behavior. The aim of this study was to check the effectiveness of psychological nano-therapy for family therapy. One group pre-test-post-test design (quasi-experimental Design) was applied for research. The sample consisted of ten families with severe marital conflict. The important character of these families was resistance for participating in family therapy. In this study, sending respectful (nano-function) text massages (nano-behavior) with cell phone were applied as a treatment. Cohesion/respect sub scale from self-report family processes scale and family readiness for therapy scale were used to assess all family members in pre-test and post-test. In this study, one of family members was asked to send a respectful text massage to other family members every day for a week. The content of the text massages were selected and checked by therapist. To compare the scores of families in pre-test and post-test paired sample t-test was used. The results of the test showed significant differences in both cohesion/respect score and family readiness for therapy between per-test and post-test. The results revealed that these families have found a better atmosphere for participation in a complete family therapy program. Indeed, this study showed that psychological nano-therapy is an effective method to make family readiness for therapy.

Keywords: family therapy, family conflicts, nano-therapy, family readiness

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Authors: Shahram Naghizadeh Raeisi, Ali Alghooneh, Seyed Jalal Razavi Zahedkolaei

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Herein, a shelf stable (no refrigeration required) UHT processed, aseptically packaged whey protein drink was formulated by using a new strategy in microparticulate process. Applying thermal and two-dimensional mechanical treatments simultaneously, a modified protein (MWPC-80) was produced. Then the physical, thermal and thermodynamic properties of MWPC-80 were assessed using particle size analysis, dynamic temperature sweep (DTS), and differential scanning calorimetric (DSC) tests. Finally, using MWPC-80, a new RTD beverage was formulated, and shelf stability was assessed for three months at ambient temperature (25 °C). Non-isothermal dynamic temperature sweep was performed, and the results were analyzed by a combination of classic rate equation, Arrhenius equation, and time-temperature relationship. Generally, results showed that temperature dependency of the modified sample was significantly (Pvalue<0.05) less than the control one contained WPC-80. The changes in elastic modulus of the MWPC did not show any critical point at all the processed stages, whereas, the control sample showed two critical points during heating (82.5 °C) and cooling (71.10 °C) stages. Thermal properties of samples (WPC-80 & MWPC-80) were assessed using DSC with 4 °C /min heating speed at 20-90 °C heating range. Results did not show any thermal peak in MWPC DSC curve, which suggested high thermal resistance. On the other hands, WPC-80 sample showed a significant thermal peak with thermodynamic properties of ∆G:942.52 Kj/mol ∆H:857.04 Kj/mole and ∆S:-1.22Kj/mole°K. Dynamic light scattering was performed and results showed 0.7 µm and 15 nm average particle size for MWPC-80 and WPC-80 samples, respectively. Moreover, particle size distribution of MWPC-80 and WPC-80 were Gaussian-Lutresian and normal, respectively. After verification of microparticulation process by DTS, PSD and DSC analyses, a 10% why protein beverage (10% w/w/ MWPC-80, 0.6% w/w vanilla flavoring agent, 0.1% masking flavor, 0.05% stevia natural sweetener and 0.25% citrate buffer) was formulated and UHT treatment was performed at 137 °C and 4 s. Shelf life study did not show any jellification or precipitation of MWPC-80 contained beverage during three months storage at ambient temperature, whereas, WPC-80 contained beverage showed significant precipitation and jellification after thermal processing, even at 3% w/w concentration. Consumer knowledge on nutritional advantages of whey protein increased the request for using this protein in different food systems especially RTD beverages. These results could make a huge difference in this industry.

Keywords: high protein whey beverage, micropartiqulation, two-dimentional mechanical treatments, thermodynamic properties

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Authors: Alireza Monzavi Chaleshtari, Mahnaz Aliakbari Dehkordi, Afsaneh Bayat, Amin Asadi Hieh

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The purpose of this research was to investigate the pattern of structural relationships of quality of life based on anxiety and rumination with the mediation of personality types in psoriasis patients. Methods: The community of this research is made up of the members of Psoriasis Society of Iran - Sadafak. In the sample size of 2266 people, according to Morgan's table, 327 people will be considered as a statistical sample. To assess the quality of life, the 26-item questionnaire of the World Health Organization, anxiety with software SPSS and appropriate to the conditions were used to test the hypotheses, correlation matrix tests and factor analysis. Results: There is a relationship between quality of life with anxiety and rumination in psoriasis patients. The mediating role of personality types showed Psychotic annoyance has a significant relationship with anxiety (physical and emotional symptoms). Extraversion, agreeing and being conscientious play a mediating role in a significant relationship between quality of life in psoriasis patients. Also, irritability plays a mediating role in a meaningful relationship between rumination in psoriasis patients. Conclusion: According to the obtained results, it can be said that psoriasis patients with physical and emotional symptoms of anxiety and rumination have a low quality of life. Also, negative personality types (perfectionism and neuroticism) can cause or aggravate skin disorders in these patients. In other words, psychological factors are considered predisposing, accelerating and perpetuating factors in psoriasis skin disorders, so it is suggested to pay attention to these variables in the success of treating patients with psoriasis.

Keywords: quality of life, anxiety, rumination, personality types, psoriasis.

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Authors: Angela U. Makolo

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Protein-coding and Non-coding regions determine the biology of a sequenced transcriptome. Research advances have shown that Non-coding regions are important in disease progression and clinical diagnosis. Existing bioinformatics tools have been targeted towards Protein-coding regions alone. Therefore, there are challenges associated with gaining biological insights from transcriptome sequence data. These tools are also limited to computationally intensive sequence alignment, which is inadequate and less accurate to identify both Protein-coding and Non-coding regions. Alignment-free techniques can overcome the limitation of identifying both regions. Therefore, this study was designed to develop an efficient sequence alignment-free model for identifying both Protein-coding and Non-coding regions in sequenced transcriptomes. Feature grouping and randomization procedures were applied to the input transcriptomes (37,503 data points). Successive iterations were carried out to compute the gradient vector that converged the developed Protein-coding and Non-coding Region Identifier (PNRI) model to the approximate coefficient vector. The logistic regression algorithm was used with a sigmoid activation function. A parameter vector was estimated for every sample in 37,503 data points in a bid to reduce the generalization error and cost. Maximum Likelihood Estimation (MLE) was used for parameter estimation by taking the log-likelihood of six features and combining them into a summation function. Dynamic thresholding was used to classify the Protein-coding and Non-coding regions, and the Receiver Operating Characteristic (ROC) curve was determined. The generalization performance of PNRI was determined in terms of F1 score, accuracy, sensitivity, and specificity. The average generalization performance of PNRI was determined using a benchmark of multi-species organisms. The generalization error for identifying Protein-coding and Non-coding regions decreased from 0.514 to 0.508 and to 0.378, respectively, after three iterations. The cost (difference between the predicted and the actual outcome) also decreased from 1.446 to 0.842 and to 0.718, respectively, for the first, second and third iterations. The iterations terminated at the 390th epoch, having an error of 0.036 and a cost of 0.316. The computed elements of the parameter vector that maximized the objective function were 0.043, 0.519, 0.715, 0.878, 1.157, and 2.575. The PNRI gave an ROC of 0.97, indicating an improved predictive ability. The PNRI identified both Protein-coding and Non-coding regions with an F1 score of 0.970, accuracy (0.969), sensitivity (0.966), and specificity of 0.973. Using 13 non-human multi-species model organisms, the average generalization performance of the traditional method was 74.4%, while that of the developed model was 85.2%, thereby making the developed model better in the identification of Protein-coding and Non-coding regions in transcriptomes. The developed Protein-coding and Non-coding region identifier model efficiently identified the Protein-coding and Non-coding transcriptomic regions. It could be used in genome annotation and in the analysis of transcriptomes.

Keywords: sequence alignment-free model, dynamic thresholding classification, input randomization, genome annotation

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Authors: B. Wattanakul, G. Ngamwongwan, S. Ngamkham

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Exposure to different learning experiences contributes to changing in learning style. Addressing students’ learning preference could help teachers provide different learning activities that encourage the student to learn effectively. Purpose: The purpose of this descriptive study was to describe learning styles of nursing students at Boromarajonani College of Nursing Chon Buri. Sample: The purposive sample was 463 nursing students who were enrolled in a nursing program at different academic levels. The 16-item VARK questionnaire with 4 multiple choices was administered at one time data collection. Choices have consisted with modalities of Visual, Aural, Read/write, and Kinesthetic measured by VARK. Results: Majority of learning preference of students at different levels was visual and read/write learning preference. Almost 67% of students have a multimodal preference, which is visual learning preference associated with read/write or kinesthetic preference. At different academic levels, multimodalities are greater than single preference. Over 30% of students have one dominant learning preference, including visual preference, read/write preference and kinesthetic preference. Analysis of Variance (ANOVA) with Bonferroni adjustment revealed a significant difference between students based on their academic level (p < 0.001). Learning style of the first-grade nursing students differed from the second-grade nursing students (p < 0.001). While learning style of nursing students in the second-grade has significantly varied from the 1st, 3rd, and 4th grade (p < 0.001), learning preference of the 3rd grade has significantly differed from the 4th grade of nursing students (p > 0.05). Conclusions: Nursing students have varied learning styles based on their different academic levels. Learning preference is not fixed attributes. This should help nursing teachers assess the types of changes in students’ learning preferences while developing teaching plans to optimize students’ learning environment and achieve the needs of the courses and help students develop learning preference to meet the need of the course.

Keywords: learning preference, VARK, learning style, nursing

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Authors: Fares Mahdi

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Background: Infection control is an important concern for all health care professionals, especially nurses. Nurses have a higher risk for both self-acquiring and transmitting infections to other patients. Aim of this study: to assess nurses' knowledge regarding infection control for wound care. Methodology: a descriptive research design was used in the study. The total number studied sample was 200 nurses, were conducting in Amran Public Hospitals in Amran City- Yemen. The study covered sample nurses in the hospital according to the study population; a standard closed-ended questionnaire was used to collect the data. Results: The results showed less than half (37.5 %) of nurses were from 22 May Hospital, also followed by (62.5%) of them were from Maternal and Child Hospital. Also according to the department name. Most (22.5%) of nurses worked in an intensive care unit, followed by (20%) of them were working in the pediatric world, also about (19%) of them were working in the surgical department. While in finally, only about (8.5%) of them worked from another department. According to course training, The results showed about (21%) of nurses had course training in wound care management. At the same time, others (79%) of them have not had course training in wound care management. According to the total nurse's knowledge of infection control for wound care, that find more than two-thirds (68%) of nurses had fair knowledge according to total all of nurse's knowledge of infection control wound care. Conclusion:The results showed that more than two-thirds (68%) of nurses had fair knowledge according to total all of the nurse's knowledge of infection control for wound care. Recommendations: There should be providing training program about infection control masseurs and it's important for new employees of nurses. Providing continuing refreshment training courses about infection control programs and about evidence-based practice in infection control for all health care teams.

Keywords: assessment, knowledge, infection control, wound care, nurses, amran hospitals

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Authors: Jing Chen, Jun-E Liu, Peng Yue

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Objective: The objective of this study was to develop a psychological adjustment and adaptation status scale for breast cancer survivors, and to examine the reliability and validity of the scale. Method: 37 breast cancer survivors were recruited in qualitative research; a five-subject theoretical framework and an item pool of 150 items of the scale were derived from the interview data. In order to evaluate and select items and reach a preliminary validity and reliability for the original scale, the suggestions of study group members, experts and breast cancer survivors were taken, and statistical methods were used step by step in a sample of 457 breast cancer survivors. Results: An original 24-item scale was developed. The five dimensions “domestic affections”, “interpersonal relationship”, “attitude of life”, “health awareness”, “self-control/self-efficacy” explained 58.053% of the total variance. The content validity was assessed by experts, the CVI was 0.92. The construct validity was examined in a sample of 264 breast cancer survivors. The fitting indexes of confirmatory factor analysis (CFA) showed good fitting of the five dimensions model. The criterion-related validity of the total scale with PTGI was satisfactory (r=0.564, p<0.001). The internal consistency reliability and test-retest reliability were tested. Cronbach’s alpha value (0.911) showed a good internal consistency reliability, and the intraclass correlation coefficient (ICC=0.925, p<0.001) showed a satisfactory test-retest reliability. Conclusions: The scale was brief and easy to understand, was suitable for breast cancer patients whose physical strength and energy were limited.

Keywords: breast cancer survivors, rehabilitation, psychological adaption and adjustment, development of scale

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Authors: Abdulbaset Mazarzaei

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Natural killer (NK) cells are innate immune effectors that play a pivotal role in combating tumors and infected cells. In recent years, the therapeutic potential of NK cells has gained significant attention due to their remarkable cytotoxic ability. This study focuses on investigating the cytotoxic effect of expanded NK cells enriched with interleukin 12 (IL12) and interleukin 15 (IL15), derived from the leukoreduction filter, on the K562 cell line. Firstly, NK cells were isolated from whole blood samples obtained from healthy volunteers. These cells were subsequently expanded ex vivo using a combination of feeder cells, IL12, and IL15. The expanded NK cells were then harvested and assessed for their cytotoxicity against K562, a well-established human chronic myelogenous leukemia cell line. The cytotoxicity was evaluated using flow cytometry assay. Results demonstrate that the expanded NK cells significantly exhibited enhanced cytotoxicity against K562 cells compared to non-expanded NK cells. Interestingly, the expanded NK cells derived specifically from IL12 and IL15-enriched leukoreduction filters showed a robust cytotoxic effect similar to the whole blood-derived NK cells. These findings suggest that IL12 and IL15 in the leukoreduction filter are crucial in promoting NK cell cytotoxicity. Furthermore, the expanded NK cells displayed relatively similar cytotoxicity profiles to whole blood-derived NK cells, indicating their comparable capability in targeting and eliminating tumor cells. This observation is of significant relevance as expanded NK cells from the leukoreduction filter could potentially serve as a readily accessible and efficient source for adoptive immunotherapy. In conclusion, this study highlights the significant cytotoxic effect of expanded NK cells enriched with IL12 and IL15 obtained from the leukoreduction filter on the K562 cell line. Moreover, it emphasizes that these expanded NK cells exhibit comparable cytotoxicity to whole blood-derived NK cells. These findings reinforce the potential clinical utility of using expanded NK cells from the leukoreduction filter as an effective strategy in adoptive immunotherapy for the treatment of cancer. Further studies are warranted to explore the broader implications of this approach in clinical settings.

Keywords: natural killer (NK) cells, Cytotoxicity, Leukoreduction filter, IL-12 and IL-15 Cytokines

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Authors: Kwadwo Yeboah

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Background and Aims: The adoption of International Accounting Standards (IAS) is considered to be one of the most significant developments in the accounting profession. The adoption of IAS aims to improve financial reporting quality by ensuring that financial information is transparent and comparable across borders. However, there is a lack of research on the impact of IAS on financial reporting quality in emerging economies. This study aims to fill this gap by evaluating the impact of IAS on financial reporting quality in emerging economies. Methods: This study uses a sample of firms from emerging economies that have adopted IAS. The sample includes firms from different sectors and industries. The financial reporting quality of these firms is measured using financial ratios, such as earnings quality, financial leverage, and liquidity. The data is analyzed using a regression model that controls for firm-specific factors, such as size and profitability. Results: The results show that the adoption of IAS has a positive impact on financial reporting quality in emerging economies. Specifically, firms that adopt IAS exhibit higher earnings quality and lower financial leverage compared to firms that do not adopt IAS. Additionally, the adoption of IAS has a positive impact on liquidity, suggesting that firms that adopt IAS have better access to financing. Conclusions: The findings of this study suggest that the adoption of IAS has a positive impact on financial reporting quality in emerging economies. The results indicate that IAS adoption can improve transparency and comparability of financial information, which can enhance the ability of investors to make informed investment decisions. The study contributes to the literature by providing evidence of the impact of IAS adoption in emerging economies. The findings of this study have implications for policymakers and regulators in emerging economies, as they can use this evidence to support the adoption of IAS and improve financial reporting quality in their respective countries.

Keywords: accounting, international, standards, finance

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Authors: Cristina Damian, Eduard Malcek, Ana Leahu, Sorina Ropciuc, Andrei Lobiuc

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Given the high rivalry nowadays, the food sector must offer the markets an attractive product, which at the same time has good quality and is safe from health aspects for the consumers. Known for their high content of antioxidant compounds, especially anthocyanins, which proven human health benefits, berries from the Rosaceae family plants have a significantly high level of phytochemicals: phenolic flavonoids, such as anthocyanins, ellagic acid (tannin), quercetin, gallic acid, cyanidin, pelargonidine, catechins, kaempferol and salicylic acid. Colour and bioactive compounds, such as vitamin C and anthocyanins, are important for the attractiveness of berries and their preserved products. The levels of bioactive compounds and sensory properties of the product as it reaches the consumer are dependent on raw material, i.e., berries used, processing, and storage conditions. In this study, four varieties of raspberry jam were analyzed, 3 of them purchased commercially; they were purchased at reasonable prices, precisely to include as large a sample of the consumer population as possible. The fourth assortment was made at home according to the traditional recipe without the addition of sweeteners or preservatives. As for the homemade red raspberry jam, it had a sugar concentration of 64.9%, being the most appreciated of all assortments. The homemade raspberry jam was most appreciated due to the taste and aroma of the product. The SCHWARTAU assortment was chosen in second place by the participants in the study (sensory analysis). The quality/price ratio is also valid this time, finding that a high-quality product will have a higher purchase price. Thus, the study had the role of presenting the preferences of the sample participating in the study by age categories.

Keywords: red raspberry, jam, antioxidant, colour, sensory analysis

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Authors: Seyedeh Mehri Hamidi, Nasrin Asgari, Foozieh Sohrabi, Mohammad Ali Ansari

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New neuro plasmonic sensor based on one dimensional plasmonic nano-grating has been prepared. To record neural activity, the sample has been exposed under different infrared laser and then has been calculated by ellipsometry parameters. Our results show that we have efficient sensitivity to different laser excitation.

Keywords: neural activity, Plasmonic sensor, Nanograting, Gold thin film

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Authors: Amina Farooq, Nauman Zafar Butt

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This paper is about methods and tools for counting particles of interest, such as cells. A microfluidic system with interconnected electronics on a flexible substrate, inlet-outlet ports and interface schemes, sensitive and selective detection of cells specificity, and processing of cell counting at polymer interfaces in a microscale biosensor for use in the detection of target biological and non-biological cells. The development of fluidic channels, planar fluidic contact ports, integrated metal electrodes on a flexible substrate for impedance measurements, and a surface modification plasma treatment as an intermediate bonding layer are all part of the fabrication process. Magnetron DC sputtering is used to deposit a double metal layer (Ti/Pt) over the polypropylene film. Using a photoresist layer, specified and etched zones are established. Small fluid volumes, a reduced detection region, and electrical impedance measurements over a range of frequencies for cell counts improve detection sensitivity and specificity. The procedure involves continuous flow of fluid samples that contain particles of interest through the microfluidic channels, counting all types of particles in a portion of the sample using the electrical differential counter to generate a bipolar pulse for each passing cell—calculating the total number of particles of interest originally in the fluid sample by using MATLAB program and signal processing. It's indeed potential to develop a robust and economical kit for cell counting in whole-blood samples using these methods and similar devices.

Keywords: impedance, biochip, cell counting, microfluidics

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Authors: Iliana Georganta, Clare Deehan, Marysia Thomson, Miriam McDonald, Kerrie McNulty, Anna Strachan, Elizabeth Anderson, Alyaa Mostafa

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Context: A meta-analysis of randomized controlled trials (RCTs) comparing hysterectomy versus endometrial ablation and resection in the management of heavy menstrual bleeding. Objective: To evaluate the clinical efficacy, satisfaction rates and adverse events of hysterectomy compared to more minimally invasive techniques in the treatment of HMB. Evidence Acquisition: A literature search was performed for all RCTs and quasi-RCTs comparing hysterectomy with either endometrial ablation endometrial resection of both. The search had no language restrictions and was last updated in June 2020 using MEDLINE, EMBASE, Cochrane Central Register of Clinical Trials, PubMed, Google Scholar, PsycINFO, Clinicaltrials.gov and Clinical trials. EU. In addition, a manual search of the abstract databases of the European Haemophilia Conference on women's health was performed and further studies were identified from references of acquired papers. The primary outcomes were patient-reported and objective reduction in heavy menstrual bleeding up to 2 years and after 2 years. Secondary outcomes included satisfaction rates, pain, adverse events short and long term, quality of life and sexual function, further surgery, duration of surgery and hospital stay and time to return to work and normal activities. Data were analysed using RevMan software. Evidence synthesis: 12 studies and a total of 2028 women were included (hysterectomy: n = 977 women vs endometrial ablation or resection: n = 1051 women). Hysterectomy was compared with endometrial ablation only in five studies (Lin, Dickersin, Sesti, Jain, Cooper) and endometrial resection only in five studies (Gannon, Schulpher, O’Connor, Crosignani, Zupi) and a mixture of the Ablation and Resection in two studies (Elmantwe, Pinion). Of the 1² studies, 10 reported women’s perception of bleeding symptoms as improved. Meta-analysis showed that women in the hysterectomy group were more likely to show improvement in bleeding symptoms when compared with endometrial ablation or resection up to 2-year follow-up (RR 0.75, 95% CI 0.71 to 0.79, I² = 95%). Objective outcomes of improvement in bleeding also favored hysterectomy. Patient satisfaction was higher after hysterectomy within the 2 years follow-up (RR: 0.90, 95%CI: 0.86 to 0.94, I²:58%), however, there was no significant difference between the two groups at more than 2 years follow up. Sepsis (RR: 0.03, 95% CI 0.002 to 0.56; 1 study), wound infection (RR: 0.05, 95% CI: 0.01 to 0.28, I²: 0%, 3 studies) and Urinary tract infection (UTI) (RR: 0.20, 95% CI: 0.10 to 0.42, I²: 0%, 4 studies) all favoured hysteroscopic techniques. Fluid overload (RR: 7.80, 95% CI: 2.16 to 28.16, I² :0%, 4 studies) and perforation (RR: 5.42, 95% CI: 1.25 to 23.45, I²: 0%, 4 studies) however favoured hysterectomy in the short term. Conclusions: This meta-analysis has demonstrated that endometrial ablation and endometrial resection are both viable options when compared with hysterectomy for the treatment of heavy menstrual bleeding. Hysteroscopic procedures had better outcomes in the short term with fewer adverse events including wound infection, UTI and sepsis. The hysterectomy performed better when measuring more long-term impacts such as recurrence of symptoms, overall satisfaction at two years and the need for further treatment or surgery.

Keywords: menorrhagia, hysterectomy, ablation, resection

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Authors: Jonathan Soliman, Thomas Cavasino, Virginie Pommelet, Lahouari Amor, Pierre Mornand, Simon Escoda, Nina Droz, Soraya Matczak, Julie Toubiana, François Angoulvant, Etienne Carbonnelle, Albert Faye, Loic de Pontual, Luu-Ly Pham

Abstract:

Background: Typhoid and paratyphoid fever are systemic infections caused by Salmonella enterica serovar Typhi or paratyphi (A, B, C). Children traveling to tropical areas are at risk to contract these diseases which can be complicated. Methods: Clinical, biological and bacteriological data were collected from 78 pediatric cases reported between 2000 and 2017 in six Parisian hospitals. Children aged 0 to 18 years old, with a diagnosis of typhoid or paratyphoid fever confirmed by bacteriological exams, were included. Epidemiologic, clinical, biological features and presence of multidrug-resistant (MDR) bacteria or intermediate susceptibility to ciprofloxacin (nalidixic acid resistant) were examined by univariate analysis and by logistic regression analysis to identify risk factors of severe typhoid in children. Results: 84,6% of the children were imported cases of typhoid fever (n=66/78) and 15,4% were autochthonous cases (n=12/78). 89,7% were caused by S.typhi (n=70/78) and 12,8% by S.paratyphi (n=10/78) including 2 co-infections. 19,2% were intrafamilial cases (n=15/78). Median age at diagnosis was 6,4 years-old [6 months-17,9 years]. 28,2% of the cases were complicated forms (n=22/78): digestive (n=8; 10,3%), neurological (n=7; 9%), pulmonary complications (n=4; 5,1%) and hemophagocytic syndrome (n=4; 5,1%). Only 5% of the children had prior immunization with typhoid non-conjugated vaccine (n=4/78). 28% of the cases (n=22/78) were caused by resistant bacteria. Thrombocytopenia and diagnosis delay was significantly associated with severe infection (p= 0.029 and p=0,01). Complicated forms were more common with MDR (p=0,1) and not statistically associated with a young age or sex in this study. Conclusions: Typhoid and paratyphoid fever are not rare in children back from tropical areas. This multicentric pediatric study seems to show that thrombocytopenia, diagnosis delay, and multidrug resistant bacteria are associated with severe typhoid fever and complicated forms in children.

Keywords: antimicrobial resistance, children, Salmonella enterica typhi and paratyphi, severe typhoid

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Authors: Liliana Zura-Brravo, Antonio Vega-Galvez, Roberto Lemus-Mondaca, Jessica Lopez

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Murta (Ugni molinae T.) is an endemic fruit of Southern Chile, possesses qualities exceptional as its high antioxidants content, that make it increasingly more appreciated for marketing. Dehydration has the potential providing safe food products through the decreased activity water while maintaining their functional properties. The objective of this study was to evaluate the effect of different drying methods on the antioxidant capacity (AC), total flavonoid content (TFC), rehydration indexes and texture the dried murta berry. Five drying technologies were used: convective drying, vacuum drying, sun-air drying, infrared drying and freezing-drying. The antioxidant capacity was measured by the ORAC method, CFT was determined by spectrophotometry, rehydration capacity (CR) and water retention (WHC) by gravimetry, texture profile (TPA) by a texture analyzer TA-XT2 and microstructure by SEM. The results showed that the lyophilized murta had smaller losses AC and TFC with values of 2886.27 routine mg rutin/ 100 g dm and 23359.99 μmol ET/100 g dm, respectively. According to the rehydration indexes, these were affected by the drying methods, where the maximum value of WHC was 92.60 g retained water/100 g sample for the vacuum drying, and the lowest value of CR was 1.43 g water absorbed/g dm for the sun-air drying. Furthermore, the microstructure and TPA showed that lyophilized samples had characteristics similar to the fresh sample. Therefore, it is possible to mention that lyophilization achieved greater extent preserving the characteristics of the murta samples, showing that this method can be used in the food industry and encourage the consumption of dried fruit and thus give it greater added value.

Keywords: antioxidant, drying method, flavonoid, murta berry, texture

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Authors: Rohit Kumar Shrivastava, Amalia Thomas, Nathalie Vriend, Stefan Luding

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A mechanical wave or vibration propagating through granular media exhibits a specific signature in time. A coherent pulse or wavefront arrives first with multiply scattered waves (coda) arriving later. The coherent pulse is micro-structure independent i.e. it depends only on the bulk properties of the disordered granular sample, the sound wave velocity of the granular sample and hence bulk and shear moduli. The coherent wavefront attenuates (decreases in amplitude) and broadens with distance from its source. The pulse attenuation and broadening effects are affected by disorder (polydispersity; contrast in size of the granules) and have often been attributed to dispersion and scattering. To study the effect of disorder and initial amplitude (non-linearity) of the pulse imparted to the system on the coherent wavefront, numerical simulations have been carried out on one-dimensional sets of particles (granular chains). The interaction force between the particles is given by a Hertzian contact model. The sizes of particles have been selected randomly from a Gaussian distribution, where the standard deviation of this distribution is the relevant parameter that quantifies the effect of disorder on the coherent wavefront. Since, the coherent wavefront is system configuration independent, ensemble averaging has been used for improving the signal quality of the coherent pulse and removing the multiply scattered waves. The results concerning the width of the coherent wavefront have been formulated in terms of scaling laws. An experimental set-up of photoelastic particles constituting a granular chain is proposed to validate the numerical results.

Keywords: discrete elements, Hertzian contact, polydispersity, weakly nonlinear, wave propagation

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Authors: Najlae Bendou, Jean-Jacques Lilti, Khalid Elbadraoui

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In this paper, we examine stock market integration of emerging markets around the global financial turmoil of 2007-2008. Following Pukthuanthong and Roll (2009), we measure the integration of 46 emerging countries using the adjusted R-square from the regression of each country's daily index returns on global factors extracted from the covariance matrix computed using dollar-denominated daily index returns of 17 developed countries. Our sample surrounds the global financial crisis and ranges between 2000 and 2018. We analyze results using four cohorts of emerging countries: East Asia & Pacific and South Asia, Europe & Central Asia, Latin America & Caribbean, Middle East & Africa. We find that the level of integration of emerging countries increases at the commencement of the crisis and during the booming phase of the business cycles. It reaches a maximum point in the middle of the crisis and then tends to revert to its pre-crisis level. This pattern tends to be common among the four geographic zones investigated in this study. Finally, we investigate the determinants of stock market integration of emerging countries in our sample using panel regressions. Our results suggest that the degree of stock market integration of these countries should be put into perspective by some macro-economic factors, such as the size of the equity market, school enrollment rate, international liquidity level, stocks traded volume, tax revenue level, imports and exports volumes.

Keywords: correlations, determinants of integration, diversification, emerging markets, financial crisis, integration, markets co-movement, panel regressions, r-square, stock markets

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Authors: Suwarno, D. Jongudomkarn

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Family Health Assessment (FHA) is a key process to identify the family health needs, family health problems, and family health history. Assessing the family health is not only from the assessment tool but also from health care provider especially Nurse. Nurses’ have duties to assess the family as holistic view and they have to increase their capacities (knowledge, skills and experiences) in FHA. Thus, the continuing nursing education-training program on using the KKU FHA Tool was aimed to enhance the participant nurses’ capacities in (FHA) based on such tool. The aim of this study was to evaluate the KKU FHA Tool training program on PCU nurses’ capacity before and after training program in Primary Care Unit Bantul, Yogyakarta. The Quasi-Experiment with one group pre-, post-test design as a research design with convenient sampling technique and one group pre- post test formula for Nurses who work in Six PCU Bantul, Yogyakarta as much as fourteen respondents. The research processes were used training program with module, video and handbook KKU FHA Tool, KKU FHA tool form and capacities questionnaires. It was analyzed by descriptive data, Kolmogorov-Smirnov and Paired Sample t-test. The overall comparing analysis of paired sample t-test revealed that the mean values of pre-test were 3.35 with SD 0.417, post-test was 3.86 with SD 0.154 and post-test in later two weeks was 4.00 with SD 0.243. It was found that the p value of among the pre-test, the intermediate post-test and the post–test in later two weeks were 0.000. The p value of the intermediate post-test and post-test in later two weeks was 0.053. KKU FHA Tool training program in PCU Bantul Yogyakarta was enhanced the participant nurses’ capacities significantly. In conclusion, we are recommending KKU FHA Tool forms have to develop and implement with qualitative research as complementary data in PCU Bantul Yogyakarta by Focus Group Discussion.

Keywords: family health assessment, KKU FHA tool, training program, nurses capacities

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Authors: Islam Nowisser, Noha Farag, Mohamed El Azizi

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Helicobacter pylori is a highly important human pathogen which inhabits about 50% of the population worldwide. Infection with this bacteria is very hard to treat, with high probability of recurrence. H. pylori causes severe gastric diseases, including peptic ulcer, gastritis, and gastric cancer, which has been linked to chronic inflammation. The infection has been reported to be associated with high levels of pro-inflammatory cytokines, especially IL-1β and TNF-α. The aim of the current study is to investigate the molecular mechanisms by which H. pylori activates NLRP3 inflammasome and its contribution to Il-1 β production in an innate cellular model. H. pylori PMSS1 and G27 standard strains, as well as the PMSS1 isogenic mutant strain PMSS1ΔVacA and G27ΔVacA, G27ΔCagA in addition to clinical isolates obtained from biopsy samples from the antrum and corpus mucosa of chronic gastritis patients, were used to establish infection in RAW-264.7 macrophages. The production levels of TNF-α and IL-1β was assessed using ELISA. Since expression of these cytokines is often regulated by the transcription factor complex, nuclear factor-kB (NF-kB), the activation of NF-κB in H. pylori infected cells was also evaluated by luciferase assay. Genomic DNA was extracted from bacterial cultures of H. pylori clinical isolates as well as the standard strains and their corresponding mutants, where they were evaluated for the cagA pathogenicity island and vacA expression. The correlation between these findings and expression of the cagA Pathogenicity Island and vacA in the bacteria was also investigated. The results showed IL-1β, and TNF-α production significantly increased in raw macrophages following H. pylori infection. The cagA+ and vacA+ H. pylori strains induced significant production of IL-1β compared to cagA- and vacA- strains. The activation pattern of NF-κB was correlated in the isolates to their cagA and vacA expression profiles. A similar finding could not be confirmed for TNF-α production. Our study shows the ability of H. pylori to activate NF-kB and induce significant IL-1β production as a possible mechanism for the augmented inflammatory response seen in subjects infected with cagA+ and vacA+ H. pylori strains that would lead to the progression to more severe form of the disease.

Keywords: Helicobacter pylori, IL-1β, inflammatory cytokines, nuclear factor KB, TNF-α

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Authors: Antonio Lopez-Villegas, Rafael Bautista-Mesa, Emilio Robles-Musso, Daniel Catalan-Matamoros, Cesar Leal-Costa

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Objectives: The purpose of this trial was to evaluate the burden borne by and the costs to informal caregivers of users with telemonitoring of pacemakers. Methods: This is a controlled, non-randomised clinical trial, with data collected from informal caregivers, five years after implantation of pacemakers. The Spanish version of the Survey on Disabilities, Personal Autonomy, and Dependency Situations was used to get information on clinical and social characteristics, levels of professionalism, duration and types of care, difficulties in providing care, health status, economic and job aspects, impact on the family or leisure due to informal caregiving for patients with pacemakers. Results: After five years of follow-up, 55 users with pacemakers finished the study. Of which, 50 were helped by a caregiver, 18 were included in the telemonitoring group (TM) and 32 in the conventional follow-up group (HM). Overall, females represented 96.0% of the informal caregivers (88.89% in TM and 100.0% in HM group). The mean ages were 63.17 ± 15.92 and 63.13 ± 14.56 years, respectively (p = 0.83) in the groups. The majority (88.0%) of the caregivers declared that they had to provide their services between 6 and 7 days per week (83.33% in TM group versus 90.63% in HM group), without significant differences between both groups. The costs related to care provided by the informal caregivers were 47.04% higher in the conventional follow-up group than in the TM group. Conclusions: The results of this trial confirm that there were no significant differences between the informal caregivers regarding to baseline characteristics, workload and time worked in both groups of follow-up. The costs incurred by the informal caregivers providing care for users with pacemakers included in telemonitoring group are significantly lower than those in the conventional follow-up group. Trial registration: ClinicalTrials.gov NCT02234245. Funding: The PONIENTE study, has been funded by the General Secretariat for Research, Development and Innovation, Regional Government of Andalusia (Spain), project reference number PI/0256/2017, under the research call 'Development and Innovation Projects in the Field of Biomedicine and Health Sciences', 2017.

Keywords: costs, disease burden, informal caregiving, pacemaker follow-up, remote monitoring, telemedicine

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Authors: Fouad Chebib, Marie Hogan, Ziad El-Zoghby, Maria Irazabal, Sarah Senum, Christina Heyer, Charles Madsen, Emilie Cornec-Le Gall, Atta Behfar, Barbara Ehrlich, Peter Harris, Vicente Torres

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Background: Mutations in PKD1 and PKD2, the genes encoding the proteins polycystin-1 (PC1) and polycystin-2 (PC2) cause autosomal dominant polycystic kidney disease (ADPKD). ADPKD is a systemic disease associated with several extrarenal manifestations. Animal models have suggested an important role for the polycystins in cardiovascular function. The aim of the current study is to evaluate the association of various cardiomyopathies in a large cohort of patients with ADPKD. Methods: Clinical data was retrieved from medical records for all patients with ADPKD and cardiomyopathies (n=159). Genetic analysis was performed on available DNA by direct sequencing. Results: Among the 58 patients included in this case series, 39 patients had idiopathic dilated cardiomyopathy (IDCM), 17 had hypertrophic obstructive cardiomyopathy (HOCM), and 2 had left ventricular noncompaction (LVNC). The mean age at cardiomyopathy diagnosis was 53.3, 59.9 and 53.5 years in IDCM, HOCM and LVNC patients respectively. The median left ventricular ejection fraction at initial diagnosis of IDCM was 25%. Average basal septal thickness was 19.9 mm in patients with HOCM. Genetic data was available in 19, 8 and 2 cases of IDCM, HOCM, and LVNC respectively. PKD1 mutations were detected in 47.4%, 62.5% and 100% of IDCM, HOCM and LVNC cases. PKD2 mutations were detected only in IDCM cases and were overrepresented (36.8%) relative to the expected frequency in ADPKD (~15%). The prevalence of IDCM, HOCM, and LVNC in our ADPKD clinical cohort was 1:17, 1:39 and 1:333 respectively. When compared to the general population, IDCM and HOCM was approximately 10-fold more prevalent in patients with ADPKD. Conclusions: In summary, we suggest that PKD1 or PKD2 mutations may predispose to idiopathic dilated or hypertrophic cardiomyopathy. There is a trend for patients with PKD2 mutations to develop the former and for patients with PKD1 mutations to develop the latter. Predisposition to various cardiomyopathies may be another extrarenal manifestation of ADPKD.

Keywords: autosomal dominant polycystic kidney (ADPKD), polycystic kidney disease, cardiovascular, cardiomyopathy, idiopathic dilated cardiomyopathy, hypertrophic cardiomyopathy, left ventricular noncompaction

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Authors: Razan Salem

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Gender plays a vital role in the stock markets because men and women differ in their behavior when investing in stocks. Accordingly, the role of gender differences in investment behavior is an increasingly important strand in the field of behavioral finance research. The investment behaviors of women relative to men have been examined in the behavioral finance literature, mainly for comparison purposes. Women's roles in the stock market have not been examined in the behavioral finance literature, however, particularly with respect to the Arab region. This study aims to contribute towards a better understanding of the investment behavior of Arab women (in regards to their risk tolerance, investment confidence, and investment literacy levels) relative to Arab men; using a sample from Arab women and men investors living in Saudi Arabia and Jordan. In order to achieve the study's main aim, the researcher used non-parametric tests, as Mann-Whitney U test, along with frequency distribution analysis to analyze the study’s primary data. The researcher distributed close-ended online questionnaires to a sample of 550 Arab male and female individuals investing in stocks in both Saudi Arabia and Jordan. The results confirm that the sample Arab women invest less in stocks compared to Arab men due to their risk-averse behaviors and limited confidence levels. The results also reveal that due to Arab women’s very low investment literacy levels, they fear from taking the risk and invest often in stocks relative to Arab men. Overall, the study’s main variables (risk tolerance, investment confidence, and investment literacy levels) have a combined effect on the investment behavior of Arab women and their limited participation in the stock market. Hence, this study is one of the very first studies that indicate the combined effect of the three main variables (which are usually studied separately in the existing literature) on the investment behavior of women, particularly Arab women. This study makes three important contributions to the growing literature on gender differences in investment behavior. First, while the behavioral finance literature documents evidence on gender differences in investment behaviors in many developed countries, there are very limited studies that investigate such differences in Arab countries. Arab women investors, generally, are ignored from the behavioral finance literature due probably to cultural barriers and data collection difficulties. Thus, this study extends the literature to include Arab women and their investment behaviors when trading stock relative to Arab men. Moreover, the study associates women investment literacy and confidence levels with their financial risk behaviors and participation in the stock market. This study provides direct evidence on Arab women's investment behaviors when trading stocks. Overall, studying Arab women investors is important to investigate whether the investment behavior identified for Western women investors are also found in Arab women investors.

Keywords: Arab women, gender differences, investment behavior, stock markets

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Authors: Nautiyal Ruchira, Nautiyal Hemant, Chaudhury Devnanda, Bhargava Surbhi, Chauhan Nidhi

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Introduction: South East Asian region contributes 2.5 million cases of malaria each year to the global burden of 300 to 500 million of which 76% is reported from India. Government of India launched a national program almost half a century ago, still malaria remains a major public health challenge. Pregnant women are more susceptible to severe malaria and its fetomaternal complications. Inadequate surveillance and under-reporting underestimates the problem. Aim: Present study aimed to analyze the clinical course and pattern of malaria during pregnancy and to study the feto-maternal outcome. Methodology: This is a prospective observational study carried out at Himalayan Institute of Medical Sciences – a tertiary care center in the sub-Himalayan state of Uttarakhand, Northern India. All the pregnant women with malaria and its complications were recruited in the study during 2009 to 2014 which included referred cases from the state of western Uttar Pradesh. A thorough history and clinical examination were carried out to assess maternal and fetal condition. Relevant investigations including haemogram, platelet count, LFT, RFT, and USG was done. Blood slides and rapid diagnostic tests were done to diagnose the type of malaria.The primary outcomes measured were the type of malaria infection, maternal complications associated with malaria, outcome of pregnancy and effect on the fetus. Results: 67 antenatal cases with malaria infection were studied. 71% patients were diagnosed with plasmodium vivax infection, 25% cases were plasmodium falciparum positive and in 3% cases mixed infection was found. 38(56%) patients were primigravida and 29(43%) were multiparous. Most of the patients had already received some treatment from their local doctors and presented with severe malaria with the complications. Thrombocytopenia was the commonest manifestation seen in 35(52%) patients, jaundice in 28%, severe anemia in 18%, and severe oligohydramnios in 10% and renal failure in 6% cases. Regarding pregnancy outcome there were 44 % preterm deliveries, 22% had IUFD and abortions in 6% cases.20% of newborn were low birth weight and 6% were IUGR. There was only one maternal death which occurred due to ARDS in falciparum malaria. Although Plasmodium vivax was the main parasite considering the severity of clinical presentation, all the patients received intensive care. As most of the patients had received chloroquine therapy hence they were treated with IV artesunate followed by oral artemesinin combination therapy. Other therapies in the form of packed RBC’s and platelet transfusions, dialysis and ventilator support were provided when required. Conclusion: Even in areas with annual parasite index (API) less than 2 like ours, malaria in pregnancy could be an alarming problem. Vivax malaria cannot be considered benign in pregnancy because of high incidence of morbidity. Prompt diagnosis and aggressive treatment can reduce morbidity and mortality significantly. Increased community level research, integrating ANC checkups with the distribution of insecticide-treated nets in areas of high endemicity, imparting education and awareness will strengthen the existing control strategies.

Keywords: severe malaria, pregnancy, plasmodium vivax, plasmodium falciparum

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Authors: Fereydoon Bondarian, Samira Shaygan

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Today, many nutritionists recommend the consumption of plants, fruits, and vegetables to provide the antioxidants needed by the body because the use of plant antioxidants usually causes fewer side effects and better treatment. Natural antioxidants increase the power of plasma antioxidants and reduce the incidence of some diseases, such as cancer. Bad lifestyles and environmental factors play an important role in increasing the incidence of cancer. In this study, different extracts of white teas taken from two types of tea available in Iran (clone 100 and Chinese hybrid) due to the presence of a hydroxyl functional group in their structure to inhibit free radicals and anticancer properties, using 3 aqueous, methanolic and aqueous-methanolic methods were used. The total polyphenolic content was calculated using the Folin-Ciocalcu method, and the percentage of inhibition and trapping of free radicals in each of the extracts was calculated using the DPPH method. With the help of high-performance liquid chromatography, a small amount of each catechin in the tea samples was obtained. Clone 100 white tea was found to be the best sample of tea in terms of all the examined attributes (total polyphenol content, antioxidant properties, and individual amount of each catechin). The results showed that aqueous and aqueous-methanolic extracts of Clone 100 white tea have the highest total polyphenol content with 27.59±0.08 and 36.67±0.54 (equivalent gallic acid per gram dry weight of leaves), respectively. Due to having the highest level of different groups of catechin compounds, these extracts have the highest property of inhibiting and trapping free radicals with 66.61±0.27 and 71.74±0.27% (mg/l) of the extracted sample against ascorbic acid). Using the MTT test, the inhibitory effect of clone 100 white tea extract in inhibiting the growth of HCT-116 colon cancer cells was investigated and the best time and concentration treatments were 500, 150 and 1000 micrograms in 8, 16 and 24 hours, respectively. To investigate gene expression changes, selected genes, including tumorigenic genes, proto-oncogenes, tumor suppressors, and genes involved in apoptosis, were selected and analyzed using the real-time PCR method and in the presence of concentrations obtained for white tea. White tea extract at a concentration of 1000 μg/ml 3 times 16, 8, and 24 hours showed the highest growth inhibition in cancer cells with 53.27, 55.8, and 86.06%. The concentration of 1000 μg/ml aqueous extract of white tea under 24-hour treatment increased the expression of tumor suppressor genes compared to the normal sample.

Keywords: catechin, gene expression, suppressor genes, colon cell line

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Authors: Natalia C. E. S. Nascimento, Mercia L. Oliveira, Fernando R. A. Lima, Leonardo T. C. do Nascimento, Marina B. Silveira, Brigida G. A. Schirmer, Andrea V. Ferreira, Carlos Malamut, Juliana B. da Silva

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Tissue hypoxia is a common characteristic of solid tumors leading to decreased sensitivity to radiotherapy and chemotherapy. In the clinical context, tumor hypoxia assessment employing the positron emission tomography (PET) tracer ¹⁸F-fluoromisonidazole ([¹⁸F]FMISO) is helpful for physicians for planning and therapy adjusting. The aim of this work was to implement the synthesis of 18F-FMISO in a TRACERlab® MXFDG module and also to establish the quality control procedure. [¹⁸F]FMISO was synthesized at Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN/Brazil) using an automated synthesizer (TRACERlab® MXFDG, GE) adapted for the production of [¹⁸F]FMISO. The FMISO chemical standard was purchased from ABX. 18O- enriched water was acquired from Center of Molecular Research. Reagent kits containing eluent solution, acetonitrile, ethanol, 2.0 M HCl solution, buffer solution, water for injections and [¹⁸F]FMISO precursor (dissolved in 2 ml acetonitrile) were purchased from ABX. The [¹⁸F]FMISO samples were purified by Solid Phase Extraction method. The quality requirements of [¹⁸F]FMISO are established in the European Pharmacopeia. According to that reference, quality control of [¹⁸F]FMISO should include appearance, pH, radionuclidic identity and purity, radiochemical identity and purity, chemical purity, residual solvents, bacterial endotoxins, and sterility. The duration of the synthesis process was 53 min, with radiochemical yield of (37.00 ± 0.01) % and the specific activity was more than 70 GBq/µmol. The syntheses were reproducible and showed satisfactory results. In relation to the quality control analysis, the samples were clear and colorless at pH 6.0. The spectrum emission, measured by using a High-Purity Germanium Detector (HPGe), presented a single peak at 511 keV and the half-life, determined by the decay method in an activimeter, was (111.0 ± 0.5) min, indicating no presence of radioactive contaminants, besides the desirable radionuclide (¹⁸F). The samples showed concentration of tetrabutylammonium (TBA) < 50μg/mL, assessed by visual comparison to TBA standard applied in the same thin layer chromatographic plate. Radiochemical purity was determined by high performance liquid chromatography (HPLC) and the results were 100%. Regarding the residual solvents tested, ethanol and acetonitrile presented concentration lower than 10% and 0.04%, respectively. Healthy female mice were injected via lateral tail vein with [¹⁸F]FMISO, microPET imaging studies (15 min) were performed after 2 h post injection (p.i), and the biodistribution was analyzed in five-time points (30, 60, 90, 120 and 180 min) after injection. Subsequently, organs/tissues were assayed for radioactivity with a gamma counter. All parameters of quality control test were in agreement to quality criteria confirming that [¹⁸F]FMISO was suitable for use in non-clinical and clinical trials, following the legal requirements for the production of new radiopharmaceuticals in Brazil.

Keywords: automatic radiosynthesis, hypoxic tumors, pharmacopeia, positron emitters, quality requirements

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Authors: Mark P. Mayala, Henry Mayala, Khuzeima Khanbhai

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Background: Heart failure has been a rising concern in Tanzania. New drugs have been introduced, including the group of drugs called Angiotensin receptor Neprilysin Inhibitor (ARNI), but due to their high cost, angiotensin-converting enzymes inhibitors (ACEIs) and Angiotensin receptor blockers (ARBs) have been mostly used in Tanzania. However, according to our knowledge, the efficacy comparison of the two groups is yet to be studied in Tanzania. The aim of this study was to compare the efficacy of ACEIs and ARBs among patients with heart failure. Methodology: This was a hospital-based prospective cohort study done at Jakaya Kikwete Cardiac Institution (JKCI), Tanzania, from June to December 2020. Consecutive enrollment was done until fulfilling the inclusion criteria. Clinical details were measured at baseline. We assessed the relationship between ARBs and ACEIs users with N-terminal pro-brain natriuretic peptide (NT pro-BNP) levels at admission and at 1-month follow-up using a chi-square test. A Kaplan-Meier curve was used to estimate the survival time of the two groups. Results: 155 HF patients were enrolled, with a mean age of 48 years, whereby 52.3% were male, and their mean left ventricular ejection fraction (LVEF) was 37.3%. 52 (33.5%) heart failure patients were on ACEIs, 57 (36.8%) on ARBs, and 46 (29.7%) were neither using ACEIs nor ARBs. At least half of the patients did not receive a guideline-directed medical therapy (GDMT), with only 82 (52.9%) receiving a GDMT. A drop in NT pro-BNP levels was observed during admission and at 1-month follow-up on both groups, from 6389.2 pg/ml to 4000.1 pg/ml for ARB users and 5877.7 pg/ml to 1328.2 pg/ml for the ACEIs users. There was no statistical difference between the two groups when estimated by the Kaplan-Meier curve, though more deaths were observed in those who were neither on ACEIs nor ARBs, with a calculated P value of 0.01. Conclusion: This study demonstrates that ACEIs have more efficacy and overall better clinical outcome than ARBs, but this should be taken under the patient-based case, considering the side effects of ACEIs and patients’ adherence.

Keywords: angiotensin converting enzymes inhibitors, angiotensin receptor blockers, guideline direct medical therapy, N-terminal pro-brain natriuretic peptide

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Authors: Maria Giovanna Lupo, Marina Camera, Marcello Rattazzi, Nicola Ferri

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A complex interplay among chronic kidney disease, lipid metabolism and aortic calcification has been recognized starting from results of many clinical and experimental studies. Here we investigated the influence of kidney function on PCSK9 levels, both in uremic rats and in clinical observation study, and its potential direct action on cultured smooth muscle cells (SMCs) calcification. In a cohort of 594 subjects enrolled in a single centre, observational, cross-sectional and longitudinal study, a negative association between GFR and plasma PCSK9 was found. Atherosclerotic cardiovascular disease (ASCVD), as co-morbidity, further increased PCSK9 plasma levels. Diet-induced uremic condition in rats, induced aortic calcification and increased total cholesterol and PCSK9 levels in plasma, livers and kidneys. Immunohistochemical analysis confirmed PCSK9 expression in aortic SMCs. SMCs overexpressing PCSK9 (SMCsPCSK9), cultured for 7-days in a pro-calcification environment (2.0mM or 2.4mM inorganic phosphate, Pi) showed a significantly higher extracellular calcium (Ca2+) deposition compared to mocked SMCs. Under the same experimental conditions, the addition of exogenous recombinant PCSK9 did not increase the extracellular calcification of SMCs. By flow cytometry analysis we showed that SMCsPCSK9, in response to 2.4mM Pi, released higher number of extracellular vesicles (EVs) positive for three tetraspanin molecules, such as CD63, CD9, and CD81. EVs derived from SMCsPCSK9 tended to be more enriched in calcium and alkaline phosphatase (ALPL), compared to EVs from mocks SMCs. In conclusion, our study reveals a direct role of PCSK9 on vascular calcification induced by higher inorganic phosphate levels associated to CKD condition. This effect appears to be mediated by a positive effect of endogenous PCSK9 on the release of EVs containing Ca2+ and ALP, which facilitate the deposition inorganic calcium phosphate crystals.

Keywords: PCSK9, calcification, extracellular vesicles, chronic kidney disease

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Authors: Leslie M. Gutman

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Conduct problems (CP) represent a major dilemma, with wide-ranging and long-lasting individual and societal impacts. Children experience heterogeneous patterns of conduct problems; based on the age of onset, developmental course and related risk factors from around age 3. Early childhood represents a potential window for intervention efforts aimed at changing the trajectory of early starting conduct problems. Using the UK Millennium Cohort Study (n = 17,206 children), this study (a) identifies trajectories of conduct problems from ages 3 to 14 years and (b) assesses the cumulative and interactive effects of individual, family and socioeconomic risk factors from ages 9 months to 14 years. The same factors according to three domains were assessed, including child (i.e., low verbal ability, hyperactivity/inattention, peer problems, emotional problems), family (i.e., single families, parental poor physical and mental health, large family size) and socioeconomic (i.e., low family income, low parental education, unemployment, social housing). A cumulative risk score for the child, family, and socioeconomic domains at each age was calculated. It was then examined how the cumulative risk scores explain variation in the trajectories of conduct problems. Lastly, interactive effects among the different domains of cumulative risk were tested. Using group-based trajectory modeling, four distinct trajectories were found including a ‘low’ problem group and three groups showing childhood-onset conduct problems: ‘school-age onset’; ‘early-onset, desisting’; and ‘early-onset, persisting’. The ‘low’ group (57% of the sample) showed a low probability of conducts problems, close to zero, from 3 to 14 years. The ‘early-onset, desisting’ group (23% of the sample) demonstrated a moderate probability of CP in early childhood, with a decline from 3 to 5 years and a low probability thereafter. The ‘early-onset, persistent’ group (8%) followed a high probability of conduct problems, which declined from 11 years but was close to 70% at 14 years. In the ‘school-age onset’ group, 12% of the sample showed a moderate probability of conduct problems from 3 and 5 years, with a sharp increase by 7 years, increasing to 50% at 14 years. In terms of individual risk, all factors increased the likelihood of being in the childhood-onset groups compared to the ‘low’ group. For cumulative risk, the socioeconomic domain at 9 months and 3 years, the family domain at all ages except 14 years and child domain at all ages were found to differentiate childhood-onset groups from the ‘low’ group. Cumulative risk at 9 months and 3 years did not differentiate between the ‘school-onset’ group and ‘low’ group. Significant interactions were found between the domains for the ‘early-onset, desisting group’ suggesting that low levels of risk in one domain may buffer the effects of high risk in another domain. The implications of these findings for preventive interventions will be highlighted.

Keywords: conduct problems, cumulative risk, developmental trajectories, early childhood, adolescence

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