Search results for: cancer incidence

Authors: Ayda Youssef, Tarek Rafaat, Iman zaky

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Purpose: Langerhans’ cell histiocytosis (LCH) is not uncommon pathology that implies aberrant proliferation of a specific dendritic (Langerhans) cell. These atypical but mature cells of monoclonal origin can infiltrate many sites of the body and may occur as localized lesions or as widespread systemic disease. Liver is one of the uncommon sites of affection. The twofold objective of this study is to illustrate the radiological presentation of this disease, and to compare these results with previously reported series. Methods and Materials: Between 2007 and 2012, 150 patients with biopsy-proven LCH were treated in our hospital, a paediatric cancer tertiary care center. A retrospective review of radiographic images and reports was performed. There were 33 patients with liver affection are stratified. All patients underwent imaging studies, mostly US and CT. A chart review was performed to obtain demographic, clinical and radiological data. They were analyzed and compared to other published series. Results: Retrospective assessment of 150 patients with LCH was performed, among them 33 patients were identified who had liver involvement. All these patients developed multisystemic disease; They were 12 females and 21 males with (n= 32), seven of them had marked hepatomegaly. Diffuse hypodense liver parenchyma was encountered in five cases, the periportal location has a certain predilection in cases of focal affection where three cases has a hypodense periportal soft tissue sheets, one of them associated with dilated biliary radicals, only one case has multiple focal lesions unrelated to portal tracts. On follow up of the patients, two cases show abnormal morphology of liver with bossy outline. Conclusion: LCH is a not infrequent disease. A high-index suspicion should be raised in the context of diagnosis of liver affection. A biopsy is recommended in the presence of radiological suspicion. Chemotherapy is the preferred therapeutic modality. Liver histiocytosis are not disease specific features but should be interpreted in conjunction with the clinical history and the results of biopsy. Clinical Relevance/Application: Radiologist should be aware of different patterns of hepatobiliary histiocytosis, Thus early diagnosis and proper management of patient can be conducted.

Keywords: langerhans’ cell histiocytosis, liver, medical and health sciences, radiology

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Authors: Zhi Hao Chow, Cian Mulligan, Jack Walsh, Antonio Garzon Vico, Dimitar Krastev

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Drug development is resource-intensive, time-consuming, and increasingly expensive with each developmental stage. The success rates of drug development are also relatively low, and the resources committed are wasted with each failed candidate. As such, a reliable method of predicting the success of drug development is in demand. The hypothesis was that some examples of failed drug candidates are pushed through developmental pipelines based on false confidence and may possess common linguistic features identifiable through sentiment analysis. Here, the concept of using text analysis to discover such features in research publications and investor reports as predictors of success was explored. R studios were used to perform text mining and lexicon-based sentiment analysis to identify affective phrases and determine their frequency in each document, then using SPSS to determine the relationship between our defined variables and the accuracy of predicting outcomes. A total of 161 publications were collected and categorised into 4 groups: (i) Cancer treatment, (ii) Neurodegenerative disease treatment, (iii) Vaccines, and (iv) Others (containing all other drugs that do not fit into the 3 categories). Text analysis was then performed on each document using 2 separate datasets (BING and AFINN) in R within the category of drugs to determine the frequency of positive or negative phrases in each document. A relative positivity and negativity value were then calculated by dividing the frequency of phrases with the word count of each document. Regression analysis was then performed with SPSS statistical software on each dataset (values from using BING or AFINN dataset during text analysis) using a random selection of 61 documents to construct a model. The remaining documents were then used to determine the predictive power of the models. Model constructed from BING predicts the outcome of drug performance in clinical trials with an overall percentage of 65.3%. AFINN model had a lower accuracy at predicting outcomes compared to the BING model at 62.5% but was not effective at predicting the failure of drugs in clinical trials. Overall, the study did not show significant efficacy of the model at predicting outcomes of drugs in development. Many improvements may need to be made to later iterations of the model to sufficiently increase the accuracy.

Keywords: data analysis, drug development, sentiment analysis, text-mining

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Authors: Chih-Chung Huang, Po-Hsun Peng

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Ultrasound transient elastography has become a valuable tool for many clinical diagnoses, such as liver diseases and breast cancer. The pathological tissue can be distinguished by elastography due to its stiffness is different from surrounding normal tissues. An ultrafast frame rate of ultrasound imaging is needed for transient elastography modality. The elastography obtained in the ultrafast system suffers from a low quality for resolution, and affects the robustness of the transient elastography. In order to overcome these problems, a coherent plane wave compounding technique has been proposed for conventional ultrasound system which the operating frequency is around 3-15 MHz. The purpose of this study is to develop a novel beamforming technique for high frequency ultrasound coherent plane-wave compounding imaging and the simulated results will provide the standards for hardware developments. Plane-wave compounding imaging produces a series of low-resolution images, which fires whole elements of an array transducer in one shot with different inclination angles and receives the echoes by conventional beamforming, and compounds them coherently. Simulations of plane-wave compounding image and focused transmit image were performed using Field II. All images were produced by point spread functions (PSFs) and cyst phantoms with a 64-element linear array working at 35MHz center frequency, 55% bandwidth, and pitch of 0.05 mm. The F number is 1.55 in all the simulations. The simulated results of PSFs and cyst phantom which were obtained using single, 17, 43 angles plane wave transmission (angle of each plane wave is separated by 0.75 degree), and focused transmission. The resolution and contrast of image were improved with the number of angles of firing plane wave. The lateral resolutions for different methods were measured by -10 dB lateral beam width. Comparison of the plane-wave compounding image and focused transmit image, both images exhibited the same lateral resolution of 70 um as 37 angles were performed. The lateral resolution can reach 55 um as the plane-wave was compounded 47 angles. All the results show the potential of using high-frequency plane-wave compound imaging for realizing the elastic properties of the microstructure tissue, such as eye, skin and vessel walls in the future.

Keywords: plane wave imaging, high frequency ultrasound, elastography, beamforming

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Authors: Adnan A. Kadi, Nasser S. Al-Shakliah, Haitham Al-Rabiah

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Zorifertinib is a novel, potent, oral, a small molecule used to treat non-small cell lung cancer (NSCLC). zorifertinib is an Epidermal Growth Factor Receptor (EGFR) inhibitor and has good blood–brain barrier permeability for (NSCLC) patients with EGFR mutations. zorifertinibis currently at phase II/III clinical trials. The current research reports the characterization and identification of in vitro, in vivo and reactive intermediates of zorifertinib. Prediction of susceptible sites of metabolism and reactivity pathways (cyanide and GSH) of zorifertinib were performed by the Xenosite web predictor tool. In-vitro metabolites of zorifertinib were performed by incubation with rat liver microsomes (RLMs) and isolated perfused rat liver hepatocytes. Extraction of zorifertinib and it's in vitro metabolites from the incubation mixtures were done by protein precipitation. In vivo metabolism was done by giving a single oral dose of zorifertinib(10 mg/Kg) to Sprague Dawely rats in metabolic cages by using oral gavage. Urine was gathered and filtered at specific time intervals (0, 6, 12, 18, 24, 48, 72,96and 120 hr) from zorifertinib dosing. A similar volume of ACN was added to each collected urine sample. Both layers (organic and aqueous) were injected into liquid chromatography ion trap mass spectrometry(LC-IT-MS) to detect vivozorifertinib metabolites. N-methyl piperizine ring and quinazoline group of zorifertinib undergoe metabolism forming iminium and electro deficient conjugated system respectively, which are very reactive toward nucleophilic macromolecules. Incubation of zorifertinib with RLMs in the presence of 1.0 mM KCN and 1.0 Mm glutathione were made to check reactive metabolites as it is often responsible for toxicities associated with this drug. For in vitro metabolites there were nine in vitro phase I metabolites, four in vitro phase II metabolites, eleven reactive metabolites(three cyano adducts, five GSH conjugates metabolites, and three methoxy metabolites of zorifertinib were detected by LC-IT-MS. For in vivo metabolites, there were eight in vivo phase I, tenin vivo phase II metabolitesofzorifertinib were detected by LC-IT-MS. In vitro and in vivo phase I metabolic pathways wereN- demthylation, O-demethylation, hydroxylation, reduction, defluorination, and dechlorination. In vivo phase II metabolic reaction was direct conjugation of zorifertinib with glucuronic acid and sulphate.

Keywords: in vivo metabolites, in vitro metabolites, cyano adducts, GSH conjugate

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Authors: Iman Farasat, Howard M. Salis

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The CRISPR/Cas9 system has revolutionized genome engineering by enabling site-directed and high-throughput genome editing, genome insertion, and gene knockdowns in several species, including bacteria, yeast, flies, worms, and human cell lines. This technology has the potential to enable human gene therapy to treat genetic diseases and cancer at the molecular level; however, the current CRISPR/Cas9 system suffers from seemingly sporadic off-target genome mutagenesis that prevents its use in gene therapy. A comprehensive mechanistic model that explains how the CRISPR/Cas9 functions would enable the rational design of the guide-RNAs responsible for target site selection while minimizing unexpected genome mutagenesis. Here, we present the first quantitative model of the CRISPR/Cas9 genome mutagenesis system that predicts how guide-RNA sequences (crRNAs) control target site selection and cleavage activity. We used statistical thermodynamics and law of mass action to develop a five-step biophysical model of cas9 cleavage, and examined it in vivo and in vitro. To predict a crRNA's binding specificities and cleavage rates, we then compiled a nearest neighbor (NN) energy model that accounts for all possible base pairings and mismatches between the crRNA and the possible genomic DNA sites. These calculations correctly predicted crRNA specificity across 5518 sites. Our analysis reveals that cas9 activity and specificity are anti-correlated, and, the trade-off between them is the determining factor in performing an RNA-mediated cleavage with minimal off-targets. To find an optimal solution, we first created a scheme of safe-design criteria for Cas9 target selection by systematic analysis of available high throughput measurements. We then used our biophysical model to determine the optimal Cas9 expression levels and timing that maximizes on-target cleavage and minimizes off-target activity. We successfully applied this approach in bacterial and mammalian cell lines to reduce off-target activity to near background mutagenesis level while maintaining high on-target cleavage rate.

Keywords: biophysical model, CRISPR, Cas9, genome editing

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Authors: Gabriela D. Silva, Rodrigo L. O. R. Cunha, Mauricio D. Coutinho-Neto

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In the last four decades the biological activities of selenium compounds has received great attention, particularly for hypervalent derivates from selenium (IV) used as enzyme inhibitors. The unregulated activity of cysteine proteases are related to the development of several pathologies, such as neurological disorders, cardiovascular diseases, obesity, rheumatoid arthritis, cancer and parasitic infections. These enzymes are therefore a valuable target for designing new small molecule inhibitors such as selenuranes. Even tough there has been advances in the synthesis and design of new selenuranes based inhibitors, little is known about their mechanism of action. It is a given that inhibition occurs through the reaction between the thiol group of the enzyme and the chalcogen atom. However, several open questions remain about the nature of the mechanism (associative vs. dissociative) and about the nature of the reactive species in solution under physiological conditions. In this work we performed a theoretical investigation on model systems to study the possible routes of substitution reactions. Nucleophiles may be present in biological systems, our interest is centered in the thiol groups from the cysteine proteases and the hydroxyls from the aqueous environment. We therefore expect this study to clarify the possibility of a route reaction in two stages, the first consisting of the substitution of chloro atoms by hydroxyl groups and then replacing these hydroxyl groups per thiol groups in selenuranes. The structures of selenuranes and nucleophiles were optimized using density function theory along the B3LYP functional and a 6-311+G(d) basis set. Solvent was treated using the IEFPCM method as implemented in the Gaussian 09 code. Our results indicate that hydrolysis from water react preferably with selenuranes, and then, they are replaced by the thiol group. It show the energy values of -106,0730423 kcal/mol for dople substituition by hydroxyl group and 96,63078511 kcal/mol for thiol group. The solvatation and pH reduction promotes this route, increasing the energy value for reaction with hydroxil group to -50,75637672 kcal/mol and decreasing the energy value for thiol to 7,917767189 kcal/mol. Alternative ways were analyzed for monosubstitution (considering the competition between Cl, OH and SH groups) and they suggest the same route. Similar results were obtained for aliphatic and aromatic selenuranes studied.

Keywords: chalcogenes, computational study, cysteine proteases, enzyme inhibitors

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Authors: Brian Bacia, Esther Githaiga, Teresia Kabucho, Paul Moses Ndegwa, Lucy Gichohi

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Purpose: The aim of the study is to ensure an appropriate mix of evidence-based prevention strategies geared towards the reduction of new HIV infections and the incidence of Sexually transmitted Illnesses Background: In Nakuru County, more than 90% of all HIV-infected patients are adults and on a single-dose medication-one pill that contains a combination of several different HIV drugs. Nakuru town has been identified as the hardest hit by HIV/Aids in the County according to the latest statistics from the County Aids and STI group, with a prevalence rate of 5.7 percent attributed to the high population and an active urban center. Method: 2 key studies were carried out to provide evidence for the effectiveness of antiretroviral therapy (ART) when used optimally on preventing sexual transmission of HIV. Discussions based on an examination, assessments of successes in planning, program implementation, and ultimate impact of prevention and treatment were undertaken involving health managers, health workers, community health workers, and people living with HIV/AIDS between February -August 2021. Questionnaires were carried out by a trained duo on ethical procedures at 15 HIV treatment clinics targeting patients on ARVs and caregivers on ARV prevention and treatment of pediatric HIV infection. Findings: Levels of AIDS awareness are extremely high. Advances in HIV treatment have led to an enhanced understanding of the virus, improved care of patients, and control of the spread of drug-resistant HIV. There has been a tremendous increase in the number of people living with HIV having access to life-long antiretroviral drugs (ARV), mostly on generic medicines. Healthcare facilities providing treatment are stressed challenging the administration of the drugs, which require a clinical setting. Women find it difficult to take a daily pill which reduces the effectiveness of the medicine. ART adherence can be strengthened largely through the use of innovative digital technology. The case management approach is useful in resource-limited settings. The county has made tremendous progress in mother-to-child transmission reduction through enhanced early antenatal care (ANC) attendance and mapping of pregnant women Recommendations: Treatment reduces the risk of transmission to the child during pregnancy, labor, and delivery. Promote research of medicines through patients and community engagement. Reduce the risk of transmission through breastfeeding. Enhance testing strategies and strengthen health systems for sustainable HIV service delivery. Need exists for improved antenatal care and delivery by skilled birth attendants. Develop a comprehensive maternal reproductive health policy covering equitability, efficient and effective delivery of services. Put in place referral systems.

Keywords: evidence-based prevention strategies, service delivery, human management, integrated approach

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Authors: Ludmila A. Gavriliuc, Jerry McLarty, Heather E. Kleiner, J. Michael Mathis

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Abstract -- Background: The citrus coumarine Auraptene (Aur) is an effective chemopreventive agent, as manifested in many models of diseases and cancer. Nuclear factor erythroid 2-related factor (Nrf2) is an important regulator of genes induced by oxidative stress, such as glutathione S-transferases, heme oxygenase-1, and peroxiredoxin 1, by activating the antioxidant response element (ARE). Genetic and biochemical evidence has demonstrated that glutathione (GSH) and glutathione-dependent enzymes, glutathione reductase (GR), glutathione peroxidases (GPs), glutathione S-transferases (GSTs) are responsible for the control of intracellular reduction-oxidation status and participate in cellular adaptation to oxidative stress. The effect of Aur on the activity of GR, GPs (Se-GP and Se-iGP), and content of GSH in the liver, kidney, and spleen is insufficiently explored. Aim: Our goal was the examination of the Aur influence on the redox-system of GSH in Nrf2 wild type and Nrf2 knockout mice via activation of Nrf2 and ARE. Methods: Twenty female mice, 10 Nrf2 wild-type (WT) and 10 Nrf2 (-/-) knockout (KO), were bred and genotyped for our study. The activity of GR, Se-GP, Se-iGP, GST, G6PD, CytP450 reductase, catalase (Cat), and content of GSH were analyzed in the liver, kidney, and spleen using Spectrophotometry methods. The results of the specific activity of enzymes and the amount of GSH were analyzed with ANOVA and Spearman statistical methods. Results: Aur (200 mg/kg) treatment induced hepatic GST, GR, Se-GP activity and inhibited their activity in the spleen of mice, most likely via activation of the ARE through Nrf2. Activation in kidney Se-GP and G6PD by Aur is also controlled, apparently through Nrf2. Results of the non-parametric Spearman correlation analysis indicated the strong positive correlation between GR and G6PD only in the liver in WT control mice (r=+0.972; p < 0.005) and in the kidney KO control mice (r=+0.958; p < 0.005). The observed low content of GSH in the liver of KO mice indicated an increase in its participation in the neutralization of toxic substances with the absence of induction of GSH-dependent enzymes, such as GST, GR, Se-GP, and Se-iGP. Activation of CytP450 in kidney and spleen and Cat in the liver in KO mice probably revealed another regulatory mechanism for these enzymes. Conclusion: Thereby, obtained results testify that Aur can modulate the activity of genes and antioxidant enzymatic redox-system of GSH, responsible for the control of intracellular reduction-oxidation status.

Keywords: auraptene, glutathione, GST, Nrf2

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Authors: Tanu Sharma, Bikramjit Singh Bajwa, Inderpreet Kaur

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Monitoring of groundwater in Tarn-Taran, Bathinda, Faridkot and Mansa districts of Punjab state, India is essential where this freshwater resource is being over-exploited causing quality deterioration, groundwater depletion and posing serious threats to residents. The present integrated study was done to appraise quality and suitability of groundwater for drinking/irrigation purposes, hydro-geochemical characteristics, source identification and associated health risks. In the present study, groundwater of various districts of Punjab state was found to be heavily contaminated with As followed by U, thus posing high cancerous risks to local residents via ingestion, along with minor contamination of Fe, Mn, Pb and F−. Most health concerns in the study region were due to the elevated concentrations of arsenic in groundwater with average values of 130 µg L-1, 176 µg L-1, 272 µg L-1 and 651 µg L-1 in Tarn-Taran, Bathinda, Faridkot and Mansa districts, respectively, which is quite high as compared to the safe limit as recommended by BIS i.e. 10 µg L-1. In Tarn-Taran, Bathinda, Faridkot and Mansa districts, average uranium contents were found to be 37 µg L-1, 88 µg L-1, 61 µg L-1 and 104 µg L-1, with 51 %, 74 %, 61 % and 71 % samples, respectively, being above the WHO limit of 30 µg L-1 in groundwater. Further, the quality indices showed that groundwater of study region is suited for irrigation but not appropriate for drinking purposes. Hydro-geochemical studies revealed that most of the collected groundwater samples belonged to Ca2+ - Mg2+ - HCO3- type showing dominance of MgCO3 type which indicates the presence of temporary hardness in groundwater. Rock-water reactions and reverse ion exchange were the predominant factors for controlling hydro-geochemistry in the study region. Dissolution of silicate minerals caused the dominance of Na+ ions in the aquifers of study region. Multivariate statistics revealed that along with geogenic sources, contribution of anthropogenic activities such as injudicious application of agrochemicals and domestic waste discharge was also very significant. The results obtained abolished the myth that uranium is only root cause for large number of cancer patients in study region as arsenic and mercury were also present in groundwater at levels that were of health concern to groundwater.

Keywords: uranium, trace elements, multivariate data analysis, risk assessment

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Authors: Heba A. Hazzah, Ragwa M. Farid, Maha M. A. Nasra, Mennatallah Zakria, Magda A. El Massik, Ossama Y. Abdallah

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Introduction: Curcumin (Cur) is a polyphenol derived from the herbal remedy and dietary spice turmeric. It possesses diverse anti-inflammatory and anti-cancer properties following oral or topical administration. The buccal delivery of curcumin can be useful for both systemic and local disease treatments such as gingivitis, periodontal diseases, oral carcinomas, and precancerous oral lesions. Despite of its high activity, it suffers a limited application due to its low oral bioavailability, poor aqueous solubility, and instability. Aim: Preparation and characterization of curcumin solid lipid nanoparticles with a high loading capacity into a mucoadhesive gel for buccal application. Methodology: Curcumin was formulated as nanoparticles using different lipids, namely Gelucire 39/01, Gelucire 50/13, Precirol, Compritol, and Polaxomer 407 as a surfactant. The SLN were dispersed in a mucoadhesive gel matrix to be applied to the buccal mucosa. All formulations were evaluated for their content, entrapment efficiency, particle size, in vitro drug dialysis, ex vivo mucoadhesion test, and ex vivo permeation study using chicken buccal mucosa. Clinical evaluation was conducted on 15 cases suffering oral erythroplakia and erosive lichen planus. Results: The results showed high entrapment efficiency reaching almost 90 % using Gelucire 50, the loaded gel with Cur-SLN showed good adhesion property and 25 minutes in vivo residence time. In addition to stability enhancement for the Cur powder. All formulae did not show any drug permeated however, a significant amount of Cur was retained within the mucosal tissue. Pain and lesion sizes were significantly reduced upon topical treatment. Complete healing was observed after 6 weeks of treatment. Conclusion: These results open a room for the pharmaceutical technology to optimize the use of this golden magical powder to get the best out of it. In addition, the lack of local anti-inflammatory compounds with reduced side effects intensifies the importance of studying natural products for this purpose.

Keywords: curcumin, erythroplakia, mucoadhesive, pain, solid lipid nanoparticles

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Authors: Miriam Borchardt, Agata M. Ritter, Macaliston G. da Silva, Mauricio N. de Carvalho, Giancarlo M. Pereira

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This paper aims to analyze the barriers faced by social enterprises and based on that to propose a social business model framework that helps them to leverage their businesses and the social value delivered. A business model for social enterprises should amplify the value perception including social value for the beneficiaries while generating enough profit to escalate the business. Most of the social value beneficiaries are people from the base of the economic pyramid (BOP) or the ones that have specific needs. Because of this, products and services should be affordable to consumers while solving social needs of the beneficiaries. Developing products and services with social value require tie relationship among the social enterprises and universities, public institutions, accelerators, and investors. Despite being focused on social value and contributing to the beneficiaries’ quality of life as well as contributing to the governments that cannot properly guarantee public services and infrastructure to the BOP, many barriers are faced by the social enterprises to escalate their businesses. This is a work in process and five micro- and small-sized social enterprises in Brazil have been studied: (i) one has developed a kit for cervical uterine cancer detection to allow the BOP women to collect their own material and deliver to a laboratory for U$1,00; (ii) other has developed special products without lactose and it is about 70% cheaper than the traditional brands in the market; (iii) the third has developed prosthesis and orthosis to surplus needs that health public system have not done efficiently; (iv) the fourth has produced and commercialized menstrual panties aiming to reduce the consumption of dischargeable ones while saving money to the consumers; (v) the fifth develops and commercializes clothes from fabric wastes in a partnership with BOP artisans. The preliminary results indicate that the main barriers are related to the public system to recognize these products as public money that could be saved if they bought products from these enterprises instead of the multinational pharmaceutical companies, to the traditional distribution system (e.g. pharmacies) that avoid these products because of the low or non-existing profit, to the difficulty buying raw material in small quantities, to leverage investment by the investors, to cultural barriers and taboos. Interesting strategies to reduce the costs have been observed: some enterprises have focused on simplifying products, others have invested in partnerships with local producers and have developed their machines focusing on process efficiency to leverage investment by the investors.

Keywords: base of the pyramid, business model, social business, social business model, social enterprises

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Authors: Ivna Mororó, Lise P. Labéjof, Stephanie Ribeiro, Kely Almeida

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Lipid droplets (LDs) are normally presented in greater or lesser number in the cytoplasm of almost all eukaryotic and some prokaryotic cells. They are independent organelles composed of a lipid ester core and a surface phospholipid monolayer. As a lipid storage form, they provide an available source of energy for the cell. Recently it was demonstrated that they play an important role in other many cellular processes. Among the many unresolved questions about them, it is not even known how LDs is formed, how lipids are recruited to LDs and how they interact with the other organelles. Excess fat in the organism is pathological and often associated with the development of some genetic, hormonal or behavioral diseases. The formation and accumulation of lipid droplets in the cytoplasm can be increased by exogenous physical or chemical agents. It is well known that ionizing radiation affects lipid metabolism resulting in increased lipogenesis in cells, but the details of this process are unknown. To better understand the mode of formation of LDs in liver cells, we investigate their ultrastructural morphology after irradiation. For that, Wistar rats were exposed to whole body gamma radiation from 60-cobalt at various single doses. Samples of the livers were processed for analysis under a conventional transmission electron microscope. We found that when compared to controls, morphological changes in liver cells were evident at the higher doses of radiation used. It was detected a great number of lipid droplets of different sizes and homogeneous content and some of them merged each other. In some cells, it was observed diffused LDs, not limited by a monolayer of phospholipids. This finding suggests that the phospholipid monolayer of the LDs was disrupted by ionizing radiation exposure that promotes lipid peroxydation of endo membranes. Thus the absence of the phospholipid monolayer may prevent the realization of some cellular activities as follow: - lipid exocytosis which requires the merging of LDs membrane with the plasma membrane; - the interaction of LDs with other membrane-bound organelles such as the endoplasmic reticulum (ER), the golgi and mitochondria and; - lipolysis of lipid esters contained in the LDs which requires the presence of enzymes located in membrane-bound organelles as ER. All these impediments can contribute to lipid accumulation in the cytoplasm and the development of diseases such as liver steatosis, cirrhosis and cancer.

Keywords: radiobiology, hepatocytes, lipid metabolism, transmission electron microscopy

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Authors: Ifeoma Anozie, Teka Apalata, Dominic Abaver

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Introduction: Despite use of Anti-retroviral therapy to reduce the incidence of opportunistic infections among HIV/AIDS patients, rapid episodes of re-infection after deworming are still common occurrences because pharmaceutical intervention alone does not prevent reinfection. Unsafe water and inadequate personal hygiene and parasitic infections are widely expected to accelerate the progression of HIV infection. This is because the chronic immunosuppression of HIV infection encourages susceptibility to opportunistic (including parasitic) infections which is linked to CD4+ cell count of <200 cells/μl. Intestinal parasites such as G. intestinalis and Entamoeba spp are ubiquitous protozoa that remain infectious over a long time in an environment and show resistance to standard disinfection. To control re-infection, the social factors that underpin the prevention need to be controlled. This study aims at prevention of intestinal parasites in people living with HIV/AIDS by using a treatment, hygiene education and sanitation (THEdS) bundle approach. Methods: This study was conducted in four clinics (Ngangelizwe health centre, Tsolo gateway clinic, Idutywa health centre and Nqamakwe health centre) across the seven districts in Eastern cape, South Africa. The four clinics were divided in two: experimental and control, for the purpose of intervention. Data was collected from March 2019 to February 2020. Six hundred participants were screened for intestinal parasitic infections. Stool samples were collected and analysed twice: before (Pre-test infection screening) and after (Post-test re-infection) THEdS bundle intervention. The experimental clinics received full intervention package, which include therapeutic treatment, health education on personal hygiene and sanitation training, while the control clinics received only therapeutic treatment for those found with intestinal parasitic infections. Results: Baseline prevalence of Intestinal Parasites isolated shows 12 intestinal parasites with overall frequency of 65, with Ascaris lumbricoides having most frequency (44.6%). The intervention had a cure rate of 60%, with odd ratio of 1.42, which indicates that the intervention group is 1.42 times more likely of parasite clearing as compared to the control group. The relative risk ratio of 1.17 signifies that there is 1.17 times more likelihood to clear intestinal parasite if there no intervention. Discussion and conclusion: Infection with multiple parasites can cause health defects, especially among HIV/AIDS patients. Efficiency of some HIV vaccines in HIV/AIDS patients is affected because treatment of re-infection amplifies drug resistance, affects the efficacy of the front-line drugs, and still permits transmission. In South Africa, treatment of intestinal parasites is usually offered to clinic attending HIV/AIDS patients upon suspicion but not as a mandate for patients being initiated into Antiretroviral (ART) program. The effectiveness of THEdS bundle advocates for inclusiveness of mandatory screening for intestinal parasitic infections among attendees of HIV/Aids clinics on regular basis.

Keywords: cure rate, , HIV/AIDS patients, intestinal parasites, intervention studies, reinfection rate

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Authors: Devyani Shete, Sudeep Rai

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Background: The COVID-19 pandemic has caused one of the highest disruptions to the NHS (National Health Service), especially to the fundamental cervical cancer screening service. To prioritize screening response effectively, it is vital to understand the underlying disease risks amongst groups of women who are less likely to resume their screening/follow up at General Practices. The current government target is to have>=80% of women have an adequate test within the previous 3.5 years (ages 25-49) or 5.5 years (ages 50-64). Aims/Objectives: To increase the number of eligible people aged 25-49 attending cervical screening by 5% at Lakeside Healthcare (a General Practice in Corby). Methods: An online survey was posted on the Lakeside Healthcare website to find out what the barriers towards cervical screening were. It was apparent that patients needed more information catered to their responses. 6 informational videos and a “Cervical Screening Guide” were created for Lakeside patients about cervical screening, which were posted on the Healthcare website. Lakeside also started sending reminder texts to those eligible, with a link to a booking form. Results: On 18th January 2022, 69.7% of patients aged 25-49 years (7207) had an adequate cervical screening test in the last 3.5 years. There were 80 total responders to the online survey. In response to “which of the following are reasons why you have not attended screening”, 30% ticked “I kept putting it off/did not get around to it,” and 13% ticked “I was worried it would be painful or daunting.” In response to “which of the following would make you more likely to book an appointment”, 23% ticked “More detailed explanations of what the risks are if I don’t have screening,” and 20% ticked “I would like more information about the test and what the smear entails.” 10% of responders had previous trauma, whilst 28% of responders said the pandemic had impacted them getting a smear. Survey results were used to carry out interventions to increase smear uptake. On 23rdMarch 2022 (after a 2-month period), 75%of patients aged 25-49 (7119) attended the screening, which was a 5.3% increase from January. Discussion/Conclusion: The survey was vital in carrying out the exact interventions that were required for patients to increase screening uptake, as it is important to know what the populations’ needs are in order to create personalized invitations. This helps to optimise response during a pandemic. A HPV self-sample kit at home could be a popular method of dealing with further outbreaks.

Keywords: gynaecology, cervical screening, public health, COVID-19

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Authors: Anupama Singh, Papia Raj

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Though Municipal Solid Waste (MSW) is a worldwide problem, yet its implications are enormous in developing countries, as they are unable to provide proper Municipal Solid Waste Management (MSWM) for the large volume of MSW. As a result, the collected wastes are dumped in open dumping at landfilling sites while the uncollected wastes remain strewn on the roadside, many-a-time clogging drainage. Such unsafe and inadequate management of MSW causes various public health hazards. For example, MSW directly on contact or by leachate contaminate the soil, surface water, and ground water; open burning causes air pollution; anaerobic digestion between the piles of MSW enhance the greenhouse gases i.e., carbon dioxide and methane (CO2 and CH4) into the atmosphere. Moreover, open dumping can cause spread of vector borne disease like cholera, typhoid, dysentery, and so on. Patna, the capital city of Bihar, one of the most underdeveloped provinces in India, is a unique representation of this situation. Patna has been identified as the ‘garbage city’. Over the last decade there has been an exponential increase in the quantity of MSW generation in Patna. Though a large proportion of such MSW is recyclable in nature, only a negligible portion is recycled. Plastic constitutes the major chunk of the recyclable waste. The chemical composition of plastic is versatile consisting of toxic compounds, such as, plasticizers, like adipates and phthalates. Pigmented plastic is highly toxic and it contains harmful metals such as copper, lead, chromium, cobalt, selenium, and cadmium. Human population becomes vulnerable to an array of health problems as they are exposed to these toxic chemicals multiple times a day through air, water, dust, and food. Based on analysis of health data it can be emphasized that in Patna there has been an increase in the incidence of specific diseases, such as, diarrhoea, dysentry, acute respiratory infection (ARI), asthma, and other chronic respiratory diseases (CRD). This trend can be attributed to improper MSWM. The results were reiterated through a survey (N=127) conducted during 2014-15 in selected areas of Patna. Random sampling method of data collection was used to better understand the relationship between different variables affecting public health due to exposure to MSW and lack of MSWM. The results derived through bivariate and logistic regression analysis of the survey data indicate that segregation of wastes at source, segregation behavior, collection bins in the area, distance of collection bins from residential area, and transportation of MSW are the major determinants of public health issues. Sustainable recycling is a robust method for MSWM with its pioneer concerns being environment, society, and economy. It thus ensures minimal threat to environment and ecology consequently improving public health conditions. Hence, this paper concludes that sustainable recycling would be the most viable approach to manage MSW in Patna and would eventually reduce public health hazards.

Keywords: municipal solid waste, Patna, public health, sustainable recycling

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Authors: Golson Mohamed, Yasmine Gamasy, Khaled EL-Khatib, Anas Al-Natour, Shady Fadel, Haytham Rashwan, Haytham Badawy, Nadia Farghaly

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Introduction: Wilm's tumor is the most common malignant renal tumor in children. Much progress has been made in the management of patients with this malignancy over the last 3 decades. Today treatments are based on several trials and studies conducted by the International Society of Pediatric Oncology (SIOP) in Europe and National Wilm's Tumor Study Group (NWTS) in the USA. It is necessary for us to understand why do we follow either of the protocols, NWTS which follows the upfront surgery principle or the SIOP which follows the upfront chemotherapy principle in all stages of the disease. Objective: The aim of is to assess outcome in patients treated with preoperative chemotherapy and patients treated with upfront surgery to compare their effect on overall survival. Study design: to decide which protocol to follow, study was carried out on records for patients aged 1 day to 18 years old suffering from Wilm's tumor who were admitted to Alexandria University Hospital, pediatric oncology, pediatric urology and pediatric surgery departments, with a retrospective survey records from 2010 to 2015, Design and editing of the transfer sheet with a (PRISMA flow study) Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Data were fed to the computer and analyzed using IBM SPSS software package version 20.0. (11) Qualitative data were described using number and percent. Quantitative data were described using Range (minimum and maximum), mean, standard deviation and median. Comparison between different groups regarding categorical variables was tested using Chi-square test. When more than 20% of the cells have expected count less than 5, correction for chi-square was conducted using Fisher’s Exact test or Monte Carlo correction. The distributions of quantitative variables were tested for normality using Kolmogorov-Smirnov test, Shapiro-Wilk test, and D'Agstino test, if it reveals normal data distribution, parametric tests were applied. If the data were abnormally distributed, non-parametric tests were used. For normally distributed data, a comparison between two independent populations was done using independent t-test. For abnormally distributed data, comparison between two independent populations was done using Mann-Whitney test. Significance of the obtained results was judged at the 5% level. Results: A significantly statistical difference was observed for survival between the two studied groups favoring the upfront chemotherapy(86.4%)as compared to the upfront surgery group (59.3%) where P=0.009. As regard complication, 20 cases (74.1%) out of 27 were complicated in the group of patients treated with upfront surgery. Meanwhile, 30 cases (68.2%) out of 44 had complications in patients treated with upfront chemotherapy. Also, the incidence of intraoperative complication (rupture) was less in upfront chemotherapy group as compared to upfront surgery group. Conclusion: Upfront chemotherapy has superiority over upfront surgery.As the patient who started with upfront chemotherapy shown, higher survival rate, less percent in complication, less percent needed for radiotherapy, and less rate in recurrence.

Keywords: Wilm's tumor, renal tumor, chemotherapy, surgery

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Authors: Arunas Burinskas, Aurelija Burinskiene

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On average, ten percent of drugs - commercial products are not available in pharmacies due to shortage. The shortage event disbalance sales and requires a recovery period, which is too long. Therefore, one of the critical issues that pharmacies do not record potential sales transactions during shortage and recovery periods. The authors suggest estimating outliers during shortage and recovery periods. To shorten the recovery period, the authors suggest using average sales per sales day prediction, which helps to protect the data from being downwards or upwards. Authors use the outlier’s visualization method across different drugs and apply the Grubbs test for significance evaluation. The researched sample is 100 drugs in a one-month time frame. The authors detected that high demand variability products had outliers. Among analyzed drugs, which are commercial products i) High demand variability drugs have a one-week shortage period, and the probability of facing a shortage is equal to 69.23%. ii) Mid demand variability drugs have three days shortage period, and the likelihood to fall into deficit is equal to 34.62%. To avoid shortage events and minimize the recovery period, real data must be set up. Even though there are some outlier detection methods for drug data cleaning, they have not been used for the minimization of recovery period once a shortage has occurred. The authors use Grubbs’ test real-life data cleaning method for outliers’ adjustment. In the paper, the outliers’ adjustment method is applied with a confidence level of 99%. In practice, the Grubbs’ test was used to detect outliers for cancer drugs and reported positive results. The application of the Grubbs’ test is used to detect outliers which exceed boundaries of normal distribution. The result is a probability that indicates the core data of actual sales. The application of the outliers’ test method helps to represent the difference of the mean of the sample and the most extreme data considering the standard deviation. The test detects one outlier at a time with different probabilities from a data set with an assumed normal distribution. Based on approximation data, the authors constructed a framework for scaling potential sales and estimating outliers with Grubbs’ test method. The suggested framework is applicable during the shortage event and recovery periods. The proposed framework has practical value and could be used for the minimization of the recovery period required after the shortage of event occurrence.

Keywords: drugs, Grubbs' test, outlier, shortage event

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Authors: Christina Largent, Tazley Hobbs

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Objective: A literature review was performed to examine the existing research on COVID-19 lockdown as it relates to ADHD child/adolescent individuals, media use, and impact on educational performance/learning. It was surmised that with the COVID-19 shut-down and transition to remote learning, a less structured learning environment, increased screen time, in addition to potential difficulty accessing school resources would impair ADHD individuals’ performance and learning. A resulting increase in the number of youths diagnosed and treated for ADHD would be expected. As of yet, there has been little to no published data on the incidence of ADHD as it relates to COVID-19 outside of reports from several nonprofit agencies such as CHADD (Children and Adults with Attention-Deficit/Hyperactivity Disorder ), who reported an increased number of calls to their helpline, The New York based Child Mind Institute, who reported an increased number of appointments to discuss medications, and research released from Athenahealth showing an increase in the number of patients receiving new diagnosis of ADHD and new prescriptions for ADHD medications. Methods: A literature search for articles published between 2020 and 2021 from Pubmed, Google Scholar, PsychInfo, was performed. Search phrases and keywords included “covid, adhd, child, impact, remote learning, media, screen”. Results: Studies primarily utilized parental reports, with very few from the perspective of the ADHD individuals themselves. Most findings thus far show that with the COVID-19 quarantine and transition to online learning, ADHD individuals’ experienced decreased ability to keep focused or adhere to the daily routine, as well as increased inattention-related problems, such as careless mistakes or lack of completion in homework, which in turn translated into overall more difficulty with remote learning. To add further injury, one study showed (just on evaluation of two different sites within the US) that school based services for these individuals decreased with the shift to online-learning. Increased screen time, television, social media, and gaming were noted amongst ADHD individuals. One study further differentiated the degree of digital media, identifying individuals with “problematic “ or “non-problematic” use. ADHD children with problematic digital media use suffered from more severe core symptoms of ADHD, negative emotions, executive function deficits, damage to family environment, pressure from life events, and a lower motivation to learn. Conclusions and Future Considerations: Studies found not only was online learning difficult for ADHD individuals but it, in addition to greater use of digital media, was associated with worsening ADHD symptoms impairing schoolwork, in addition to secondary findings of worsening mood and behavior. Currently, data on the number of new ADHD cases, in addition to data on the prescription and usage of stimulants during COVID-19, has not been well documented or studied; this would be well-warranted out of concern for over diagnosing or over-prescribing our youth. It would also be well-worth studying how reversible or long-lasting these negative impacts may be.

Keywords: COVID-19, remote learning, media use, ADHD, child, adolescent

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Authors: Kittitara Chunlakittiphan, Patompong Satapornpong

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Introduction: The variation of genetics affects how our body responds to pharmaceuticals elucidates the correlation between long-term use of medical cannabis and adverse drug reactions (ADRs). Medical cannabis is regarded as the treatment for chronic pain, cancer pain, acute pain, psychological disorders, multiple sclerosis and migraine management. However, previous studies have shown that delta-9-Tetrahydrocannabinol (THC), an ingredient found in cannabis, was the cause of ADRs in CB1 receptors found in humans. Previous research suggests that distributions of the cannabinoid type 1 (CB1) receptor gene and pharmacogenetic markers, which vary amongst different populations, might affect incidences of ADRs. Although there is an evident need to investigate the level of the CB1 receptor gene (rs806365), studies on the distribution of CB1-pharmacogenetics markers in Thai patients are limited. Objective: Therefore, the aim of this study is to investigate the distribution of the rs806365 polymorphism in Thai patients who have been treated with medical cannabis. Materials and Methods: We enrolled 31 Thai patients with THC-induced ADRs and 34 THC-tolerant controls to take part in this study. All patients with THC-induced ADRs were accessed through a review of medical records by physicians. EDTA blood of 3ml was collected to obtain the CNR1 gene (rs806365) and genotyping of this gene was conducted using the real-time PCR ViiA7 (ABI, Foster City, CA, USA) following the manufacturer’s instruction. Results: The sample consisted of 65 patients (40/61.54%) were females and (25/38.46%) were males, with an age range of 19-87 years, who have been treated with medical cannabis. In this study, the most common THC-induced ADRs were dry mouth and/or dry throat, tachycardia, nausea, and arrhythmia. Across the whole sample, we found that 52.31% of Thai patients carried a heterozygous variant (rs806365, CT allele). Moreover, the number of rs806365 (CC, homozygous variant) carriers totaled seventeen people (26.15%) amongst the subjects of Thai patients treated with medical cannabis. Furthermore, 17 out of 22 patients (77.27%) who experienced severe ADRs: Tachycardia and/or arrhythmia, carried an abnormal rs806365 gene (CT and CC alleles). Conclusions: The results propose that the rs806365 gene is widely distributed amongst the Thai population and there is a link between this gene and vulnerability to developing THC-induced ADRs after being treated with medical cannabis. Therefore, it is necessary to screen for the rs806365 gene before using medical cannabis to treat a patient.

Keywords: rs806365, THC-induced adverse drug reactions, CB1 receptor, Thai population

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Authors: Raphael Udeh, Luis García De Guadiana Romualdo, Xenia Dolje-Gore

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Background: Quite disturbing is the huge public health impact of COVID-19: As at today [25th March 2021, the COVID-19 global burden shows over 123 million cases and over 2.7 million deaths worldwide. Rationale: Recent evidence shows calprotectin’s potential as a therapeutic target, stating that tasquinimod, from the Quinoline-3-Carboxamide family is capable of blocking the interaction between calprotectin and TLR4. Hence preventing the cytokine release syndrome, that heralds the functional exhaustion in COVID-19. Early preclinical studies showed that tasquinimod inhibit tumor growth and prevent angiogenesis/cytokine storm. Phase I – III clinical studies in prostate cancer showed it has a good safety profile with good radiologic progression free survival but no effect on overall survival. Rationale/hypothesis: Strategic endeavors have been amplified globally to assess new therapeutic interventions for COVID-19 management – thus the clinical and antiviral efficacy of tasquinimod in COVID-19 remains to be explored. Hence the primary objective of this trial will be to evaluate the efficacy of tasquinimod in the treatment of adult patients with severe COVID-19 infections. Therefore, I hypothesise that among adults with COVID19 infection, tasquinimod will reduce the severe respiratory distress associated with COVID-19 compared to placebo, over a 28-day study period. Method: The setting is in Europe. Design – a randomized, placebo-controlled, phase II double-blinded trial. Trial lasts for 28 days from randomization, Tasquinimod capsule given as 0.5mg daily 1st fortnight, then 1mg daily 2nd fortnight. I0 outcome - assessed using six-point ordinal scale alongside eight 20 outcomes. 125 participants to be enrolled, data collection at baseline and subsequent data points, and safety reporting monitored via serological profile. Significance: This work could potentially establish tasquinimod as an effective and safe therapeutic agent for COVID-19 by reducing the severe respiratory distress, related time to recovery, time on oxygen/admission. It will also drive future research – as in larger multi-centre RCT.

Keywords: Calprotectin, COVID-19, Phase II Trial, Tasquinimod

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Authors: Kseniia Zviagintseva, Brett Buttliere

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Science is fundamentally a problem-solving enterprise, and scientists pay more attention to the negative things, that cause them dissonance and negative affective state of uncertainty or contradiction. While this is agreed upon by philosophers of science, there are few empirical demonstrations. Here we examine the keywords from those papers published by PLoS in 2014 and show with several sentiment analyzers that negative keywords are studied more than positive keywords. Our dataset is the 927,406 keywords of 32,870 scientific articles in all fields published in 2014 by the journal PLOS ONE (collected from Altmetric.com). Counting how often the 47,415 unique keywords are used, we can examine whether those negative topics are studied more than positive. In order to find the sentiment of the keywords, we utilized two sentiment analysis tools, Hu and Liu (2004) and SentiStrength (2014). The results below are for Hu and Liu as these are the less convincing results. The average keyword was utilized 19.56 times, with half of the keywords being utilized only 1 time and the maximum number of uses being 18,589 times. The keywords identified as negative were utilized 37.39 times, on average, with the positive keywords being utilized 14.72 times and the neutral keywords - 19.29, on average. This difference is only marginally significant, with an F value of 2.82, with a p of .05, but one must keep in mind that more than half of the keywords are utilized only 1 time, artificially increasing the variance and driving the effect size down. To examine more closely, we looked at those top 25 most utilized keywords that have a sentiment. Among the top 25, there are only two positive words, ‘care’ and ‘dynamics’, in position numbers 5 and 13 respectively, with all the rest being identified as negative. ‘Diseases’ is the most studied keyword with 8,790 uses, with ‘cancer’ and ‘infectious’ being the second and fourth most utilized sentiment-laden keywords. The sentiment analysis is not perfect though, as the words ‘diseases’ and ‘disease’ are split by taking 1st and 3rd positions. Combining them, they remain as the most common sentiment-laden keyword, being utilized 13,236 times. More than just splitting the words, the sentiment analyzer logs ‘regression’ and ‘rat’ as negative, and these should probably be considered false positives. Despite these potential problems, the effect is apparent, as even the positive keywords like ‘care’ could or should be considered negative, since this word is most commonly utilized as a part of ‘health care’, ‘critical care’ or ‘quality of care’ and generally associated with how to improve it. All in all, the results suggest that negative concepts are studied more, also providing support for the notion that science is most generally a problem-solving enterprise. The results also provide evidence that negativity and contradiction are related to greater productivity and positive outcomes.

Keywords: bibliometrics, keywords analysis, negativity bias, positive and negative words, scientific papers, scientometrics

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Authors: Siti Aisya Gany, Swee Ching Tan, Sook Yee Gan

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Diminished antioxidant defense or increased production of reactive oxygen species in the biological system can result in oxidative stress which may lead to various neurodegenerative diseases including Alzheimer’s disease (AD). Microglial activation also contributes to the progression of AD by producing several pro-inflammatory cytokines, nitric oxide (NO), and prostaglandin E2 (PGE2). Oxidative stress and inflammation have been reported to be possible pathophysiological mechanisms underlying AD. In addition, the cholinergic hypothesis postulates that memory impairment in patient with AD is also associated with the deficit of cholinergic function in the brain. Although a number of drugs have been approved for the treatment of AD, most of these synthetic drugs have diverse side effects and yield relatively modest benefits. Marine algae have great potential in pharmaceutical and biomedical applications as they are valuable sources of bioactive properties such as anti-coagulation, anti-microbial, anti-oxidative, anti-cancer and anti-inflammatory. Hence, this study aimed to provide an overview of the properties of Malaysian seaweeds (Padina australis, Sargassum polycystum and Caulerpa racemosa) in inhibiting oxidative stress, neuroinflammation and cholinesterase enzymes. All tested samples significantly exhibit potent DPPH and moderate Superoxide anion radical scavenging ability (P<0.05). Hexane and methanol extracts of S. polycystum exhibited the most potent radical scavenging ability with IC50 values of 0.1572 ± 0.004 mg/ml and 0.8493 ± 0.02 for DPPH and ABTS assays, respectively. Hexane extract of C. racemosa gave the strongest superoxide radical inhibitory effect (IC50 of 0.3862± 0.01 mg/ml). Most seaweed extracts significantly inhibited the production of cytokine (IL-6, IL-1 β, TNFα) and NO in a concentration-dependent manner without causing significant cytotoxicity to the lipopolysaccharide (LPS)-stimulated microglia cells (P<0.05). All extracts suppressed cytokine and NO level by more than 80% at the concentration of 0.4mg/ml. In addition, C. racemosa and S. polycystum also showed anti-acetylcholinesterase activities with the IC50 values ranging from 0.086-0.115 mg/ml. Moreover, C. racemosa and P. australis were also found to be active against butyrylcholinesterase with IC50 values ranging from 0.118-0.287 mg/ml.

Keywords: anti-cholinesterase, anti-oxidative, neuroinflammation, seaweeds

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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: Allison Herlene Du Plessis, Dalena (R.M.) Van Rooyen, Wilma Ten Ham-Baloyi, Sihaam Jardien-Baboo

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Introduction: Women die in pregnancy and childbirth for five main reasons—severe bleeding, infections, unsafe abortions, hypertensive disorders (pre-eclampsia and eclampsia), and medical complications including cardiac disease, diabetes, or HIV/AIDS complicated by pregnancy. In 2015, WHO classified sepsis as the third highest cause for maternal mortalities in the world. Chorioamnionitis is a clinical syndrome of intrauterine infection during any stage of the pregnancy and it refers to ascending bacteria from the vaginal canal up into the uterus, causing infection. While the incidence rates for chorioamnionitis are not well documented, complications related to chorioamnionitis are well documented and midwives still struggle to identify this condition in time due to its complex nature. Few diagnostic methods are available in public health services, due to escalated laboratory costs. Often the affordable biomarkers, such as C-reactive protein CRP, full blood count (FBC) and WBC, have low significance in diagnosing chorioamnionitis. A lack of screening impacts on effective and timeous management of chorioamnionitis, and early identification and management of risks could help to prevent neonatal complications and reduce the subsequent series of morbidities and healthcare costs of infants who are health foci of perinatal infections. Objective: This integrative literature review provides an overview of current best research evidence on the screening of women at risk for chorioamnionitis. Design: An integrative literature review was conducted using a systematic electronic literature search through EBSCOhost, Cochrane Online, Wiley Online, PubMed, Scopus and Google. Guidelines, research studies, and reports in English related to chorioamnionitis from 2008 up until 2020 were included in the study. Findings: After critical appraisal, 31 articles were included. More than one third (67%) of the literature included ranked on the three highest levels of evidence (Level I, II and III). Data extracted regarding screening for chorioamnionitis was synthesized into four themes, namely: screening by clinical signs and symptoms, screening by causative factors of chorioamnionitis, screening of obstetric history, and essential biomarkers to diagnose chorioamnionitis. Key conclusions: There are factors that can be used by midwives to identify women at risk for chorioamnionitis. However, there are a paucity of established sociological, epidemiological and behavioral factors to screen this population. Several biomarkers are available to diagnose chorioamnionitis. Increased Interleukin-6 in amniotic fluid is the better indicator and strongest predictor of histological chorioamnionitis, whereas the available rapid matrix-metalloproteinase-8 test requires further testing. Maternal white blood cells count (WBC) has shown poor selectivity and sensitivity, and C-reactive protein (CRP) thresholds varied among studies and are not ideal for conclusive diagnosis of subclinical chorioamnionitis. Implications for practice: Screening of women at risk for chorioamnionitis by health care providers providing care for pregnant women, including midwives, is important for diagnosis and management before complications arise, particularly in resource-constraint settings.

Keywords: chorioamnionitis, guidelines, best evidence, screening, diagnosis, pregnant women

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Authors: Sarai Guerrero, Lijia Liu

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Zinc gallogermanate (ZGGO) is a persistent phosphor that can emit in the near infrared (NIR) range once dopped with Cr³⁺ enabling its use for in-vivo deep-tissue bio-imaging. Such a property also allows for its application in cancer diagnosis and therapy. Given this, work into developing a synthetic procedure that can be done using common laboratory instruments and equipment as well as understanding ZGGO overall, is in demand. However, the ZGGO nanoparticles must have a size compatible for cell intake to occur while still maintaining sufficient photoluminescence. The nanoparticle must also be made biocompatible by functionalizing the surface for hydrophilic solubility and for high particle uniformity in the final product. Additionally, most research is completed on doped ZGGO, leaving a gap in understanding the base form of ZGGO. It also leaves a gap in understanding how doping affects the synthesis of ZGGO. In this work, the first step of optimizing the particle size via the crystalline size of ZGGO was done with undoped ZGGO using the organic acid, oleic acid (OA) for organic ligand-assisted biphasic hydrothermal synthesis. The effects of this synthesis procedure on ZGGO’s crystallinity were evaluated using Powder X-Ray Diffraction (PXRD). OA was selected as the capping ligand as experiments have shown it beneficial in synthesizing sub-10 nm zinc gallate (ZGO) nanoparticles as well as palladium nanocrystals and magnetite (Fe₃O₄) nanoparticles. Later it is possible to substitute OA with a different ligand allowing for hydrophilic solubility. Attenuated Total Reflection Fourier-Transform Infrared (ATR-FTIR) was used to investigate the surface of the nanoparticle to investigate and verify that OA had capped the nanoparticle. PXRD results showed that using this procedure led to improved crystallinity, comparable to the high-purity reagents used on the ZGGO nanoparticles. There was also a change in the crystalline size of the ZGGO nanoparticles. ATR-FTIR showed that once capped ZGGO cannot be annealed as doing so will affect the OA. These results point to this new procedure positively affecting the crystallinity of ZGGO nanoparticles. There are also repeatable implying the procedure is a reliable source of highly crystalline ZGGO nanoparticles. With this completed, the next step will be working on substituting the OA with a hydrophilic ligand. As these ligands effect the solubility of the nanoparticle as well as the pH that the nanoparticles can dissolve in, further research is needed to verify which ligand is best suited for preparing ZGGO for bio-imaging.

Keywords: biphasic hydrothermal synthesis, crystallinity, oleic acid, zinc gallogermanate

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Authors: V. Rekha, Rama Pal

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The study examines the degree and magnitude of wealth-based inequalities in child health and its determinants in India. Despite making strides in economic growth, India has failed to secure a better nutritional status for all the children. The country currently faces the double burden of malnutrition as well as the problems of overweight and obesity. Child malnutrition, obesity, unsafe water, sanitation among others are identified as the risk factors for Non-Communicable Diseases (NCDs). Eliminating malnutrition in all its forms will catalyse improved health and economic outcomes. The assessment of the distributive dimension of child health across various segments of the population is essential for effective policy intervention. The study utilises the fourth round of District Level Health Survey for 2012-13 to analyse the inequalities among children in the age group 0-14 years in Maharashtra, a state in the western region of India with a population of 11.24 crores which constitutes 9.3 percent of the total population of India. The study considers the extent of health inequality by state, districts, sector, age-groups, and gender. The z-scores of four child health outcome variables are computed to assess the nutritional status of pre-school and school children using WHO reference. The descriptive statistics, concentration curves, concentration indices, correlation matrix, logistic regression have been used to analyse the data. The results indicate that magnitude of inequality is higher in Maharashtra and child health inequalities manifest primarily among the weaker sections of society. The concentration curves show that there exists a pro-poor inequality in child malnutrition measured by stunting, wasting, underweight, anaemia and a pro-rich overweight inequality. The inequalities in anaemia are observably lower due to the widespread prevalence. Rural areas exhibit a higher incidence of malnutrition, but greater inequality is observed in the urban areas. Overall, the wealth-based inequalities do not vary significantly between age groups. It appears that there is no gender discrimination at the state level. Further, rural-urban differentials in gender show that boys from the rural area and girls living in the urban region experience higher disparities in health. The relative distribution of undernutrition across districts in Maharashtra reveals that malnutrition is rampant and considerable heterogeneity also exists. A negative correlation is established between malnutrition prevalence and human development indicators. The findings of logistic regression analysis reveal that lower economic status of the household is associated with a higher probability of being malnourished. The study recognises household wealth, education of the parent, child gender, and household size as factors significantly related to malnutrition. The results suggest that among the supply-side variables, child-oriented government programmes might be beneficial in tackling nutrition deficit. In order to bridge the health inequality gap, the government needs to target the schemes better and should expand the coverage of services.

Keywords: child health, inequality, malnutrition, obesity

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Authors: L. Kashyap, S. Jha, D. Shende, V. K. Mohan, P. Khanna, A. Aravindan, S. Kashyap, L. Singh, S. Aggarwal

Abstract:

Obesity is associated with a chronic inflammatory state. During surgery, there is an interplay between anaesthetic and surgical stress vis-a-vis the already present complex immune state. Moreover, the postoperative period is dictated by inflammation, which is crucial for wound healing and regeneration. An excess of inflammatory response might hamper recovery besides increasing the risk for infection and complications. There is definite evidence of the immunosuppressive role of inhaled anaesthetic agents. This immune modulation may be brought into effect directly by influencing the innate and adaptive immunity cells. The effects of propofol on immune mechanisms in has been widely elucidated because of its popularity. It reduces superoxide generation, elastase release, and chemotaxis. However, there is no unequivocal proof of one’s superiority over the other. Hence, an anaesthetic regimen with lesser inflammatory potential and specific to the obese patient is needed. OBESITA trial protocol (2019) by Sousa and co-workers in progress aims to test the hypothesis that anaesthesia with sevoflurane results in a weaker proinflammatory response compared to propofol, as evidenced by lower IL-6 and other biomarkers and an increased macrophage differentiation into M2 phenotype in adipose tissue. IL-6 was used as the objective parameter to evaluate inflammation as it is regulated by both surgery and anesthesia. It is the most sensitive marker of the inflammatory response to tissue damage since it is released within minutes by blood leukocytes. We hypothesized that maintenance of anaesthesia with propofol would lead to less inflammation than that with desflurane. Aims: The effect of two anaesthetic techniques, total intravenous anaesthesia (TIVA) with propofol and desflurane, on surgical stress response was evaluated. The primary objective was to compare serum interleukin-6 (IL-6) levels before and after surgery. Methods: In this prospective single-blinded randomized controlled trial undertaken, 30 obese patients (BMI>30 kg/m2) undergoing laparoscopic bariatric surgery under general anaesthesia were recruited. Patients were randomized to receive desflurane or TIVA using a target-controlled infusion for maintenance of anaesthesia. As a marker of inflammation, pre-and post-surgery IL-6 levels were compared. Results: After surgery, IL-6 levels increased significantly in both groups. The rise in IL-6 was less with TIVA than with desflurane; however, it did not reach significance. IL-6 rise post-surgery correlated positively with the complexity of procedure and duration of surgery and anaesthesia, rather than anaesthetic technique. Both groups did not differ in terms of intra-operative hemodynamic and respiratory variables, time to awakening, postoperative pulmonary complications, and duration of hospital stay. The incidence of nausea was significantly higher with desflurane than with TIVA. Conclusion: Inflammatory response did not differ as a function of anaesthetic technique when propofol and desflurane were compared. Also, patient and surgical variables dictated post-operative inflammation more than the anaesthetic factors. Further, larger sample size is needed to confirm or refute these findings.

Keywords: bariatric, biomarkers, inflammation, laparoscopy

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Authors: Diea Gamal Abo El-Hassan, Salwa Ahmed Aly, Abdelrahman Mahmoud Abdelgwad

Abstract:

The major conjugated linoleic acid (CLA) isomers have anticancer effect, especially breast cancer cells, inhibits cell growth and induces cell death. Also, CLA has several health benefits in vivo, including antiatherogenesis, antiobesity, and modulation of immune function. The present study aimed to assess the safety and anticancer effects of milk fat CLA against in vivo Ehrlich ascites carcinoma (EAC) in female Swiss albino mice. This was based on acute toxicity study, detection of the tumor growth, life span of EAC bearing hosts, and simultaneous alterations in the hematological, biochemical, and histopathological profiles. Materials and Methods: One hundred and fifty adult female mice were equally divided into five groups. Groups (1-2) were normal controls, and Groups (3-5) were tumor transplanted mice (TTM) inoculated intraperitoneally with EAC cells (2×106 /0.2 mL). Group (3) was (TTM positive control). Group (4) TTM fed orally on balanced diet supplemented with milk fat CLA (40 mg CLA/kg body weight). Group (5) TTM fed orally on balanced diet supplemented with the same level of CLA 28 days before tumor cells inoculation. Blood samples and specimens from liver and kidney were collected from each group. The effect of milk fat CLA on the growth of tumor, life span of TTM, and simultaneous alterations in the hematological, biochemical, and histopathological profiles were examined. Results: For CLA treated TTM, significant decrease in tumor weight, ascetic volume, viable Ehrlich cells accompanied with increase in life span were observed. Hematological and biochemical profiles reverted to more or less normal levels and histopathology showed minimal effects. Conclusion: The present study proved the safety and anticancer efficiency of milk fat CLA and provides a scientific basis for its medicinal use as anticancer attributable to the additive or synergistic effects of its isomers.

Keywords: anticancer activity, conjugated linoleic acid, Ehrlich ascites carcinoma, % increase in life span, mean survival time, tumor transplanted mice.

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Authors: Marina Gold, Yves Jackson, David Parrat

Abstract:

The high predominance of Latin American migrants in Geneva from countries where Chagas disease is endemic (Bolivia, Brazil, Argentina, Colombia) is increasing the incidence of chronic Chagas-related problems, especially cardiovascular complications. The precarious migratory status of what are mostly undocumented migrants complicates access to health and affects patients’ and doctors’ health perceptions regarding screening, treatment and monitoring of Chagas-related health concerns. This project results from a 3 year collaboration between the Geneva University Hospital and the NGO Mundo Sano to understand the following questions: 1) how do Latin American migrants perceive their health? 2) What do they understand from Chagas disease? 3) Are patients’ and doctors’ health perceptions similar or do they have competing agendas? This paper aims to present the results of a long-term study that interrogates health perceptions among Latin American migrants in Geneva. The first phase consisted in completing surveys at three community screening events (2016, 2017. 2018), and the results of these surveys reveal the subordination of the importance of health to that of having met economic family obligation. That is, health is important only when it becomes an impediment to economic gain. The contradictory result emerged that people are aware of the importance of health prevention in order to ensure long-term health, but they do not always have agency over their life-style habits (healthy food, regular exercise, emotional stability). The second phase of the research collected open-ended interviews with selected participants, in order to explore in more detail how Latin American migrants deal with Chagas in a different socio-political and economic context to that of endemic countries. These interviews (5 in total) reveal mixed methods of managing health: social networks, access to health care transnationally (in Geneva, Spain and back in their home country), and different valuations of health problems in each situation. The third phase consisted in observations of doctor-patient consultations and further extended interviews with patients to determine doctor/patient health perceptions around Chagas disease. This phase is ongoing, but it has yielded preliminarily observations regarding the expectations that patients’ have of doctors, and the understanding of doctors’ to patients’ complex situations. Positive and complementary health perceptions include patients’ feeling that doctors in Geneva are more understanding, more knowledgeable and less racist than those in their home country, who do not provide detailed information about Chagas or its treatment and discriminate against them for being indigenous or from poor rural areas, enabling a better communication between doctors and patients. Possible conflicting health perceptions include patients addressing their health concerns more holistically and encountering the specialist’s limitations to only treating one health concern, given time limitations and lack of competition with their colleagues (the general practitioner that referred the patient, for example). The implications of this study extend the case of Chagas disease in Geneva and is relevant for all chronic concerns and migratory contexts of precarity.

Keywords: chagas disease, health perceptions, Latin American Migrants, non-endemic countries

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Authors: Vasundhara Arora, Anupam Jhobta, Suresh Thakur, Sanjiv Sharma

Abstract:

Aims and Objectives: Intracranial tuberculosis (TB) is one of the most devastating manifestations of TB and a challenging public health issue of considerable importance and magnitude world over. This study elaborates on the imaging spectrum of neurotuberculosis on magnetic resonance imaging (MRI) in 29 clinically suspected cases from a tertiary care hospital. Materials and Methods: The prospective hospital based evaluation of MR imaging features of neuro-tuberculosis in 29 clinically suspected cases was carried out in Department of Radio-diagnosis, Indira Gandhi Medical Hospital from July 2017 to August 2018. MR Images were obtained on a 1.5 T Magnetom Avanto machine and were analyzed to identify any abnormal meningeal enhancement or parenchymal lesions. Microbiological and Biochemical CSF analysis was performed in radio-logically suspected cases and the results were compared with the imaging data. Clinical follow up of the patients started on anti-tuberculous treatment was done to evaluate the response to treatment and clinical outcome. Results: Age range of patients in the study was between 1 year to 73 years. The mean age of presentation was 11.5 years. No significant difference in the distribution of cerebral tuberculosis was noted among the two genders. Imaging findings of neuro-tuberculosis obtained were varied and non specific ranging from lepto-meningeal enhancement, cerebritis to space occupying lesions such as tuberculomas and tubercular abscesses. Complications presenting as hydrocephalus (n= 7) and infarcts (n=9) was noted in few of these patients. 29 patients showed radiological suspicion of CNS tuberculosis with meningitis alone observed in 11 cases, tuberculomas alone were observed in 4 cases, meningitis with parenchymal tuberculomas in 11 cases. Tubercular abscess and cerebritis were observed in one case each. Tuberculous arachnoiditis was noted in one patient. Gene expert positivity was obtained in 11 out of 29 radiologically suspected patients; none of the patients showed culture positivity. Meningeal form of the disease alone showed higher positivity rate of gene Xpert (n=5) followed by combination of meningeal and parenchymal forms of disease (n=4). The parenchymal manifestation of disease alone showed least positivity rates (n= 3) with gene xpert testing. All 29 patients were started on anti tubercular treatment based on radiological suspicion of the disease with clinical improvement observed in 27 treated patients. Conclusions: In our study, higher incidence of neuro- tuberculosis was noted in paediatric population with predominance of the meningeal form of the disease. Gene Xpert positivity obtained was low due to paucibacillary nature of cerebrospinal fluid (CSF) with even lower positivity of CSF samples in parenchymal form of the manifestation. MRI showed high accuracy in detecting CNS lesions in neuro-tuberculosis. Hence, it can be concluded that MRI plays a crucial role in the diagnosis because of its inherent sensitivity and specificity and is an indispensible imaging modality. It caters to the need of early diagnosis owing to poor sensitivity of microbiological tests more so in the parenchymal manifestation of the disease.

Keywords: neurotuberculosis, tubercular abscess, tuberculoma, tuberculous meningitis

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