Search results for: blood metabolites

Authors: Angkrit Phitchayangkoon, Ar-Aishah Dadeh

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Background: A key aim of triage is to identify the patients with high risk of cardiac arrest because they require intensive monitoring, resuscitation facilities, and early intervention. We aimed to identify the predicting factors such as initial vital signs, serum pH, serum lactate level, initial capillary blood glucose, and Modified Early Warning Score (MEWS) which affect the occurrence of cardiac arrest in an emergency department (ED). Methods: We conducted a retrospective data review of ED patients in an emergency department (ED) from 1 August 2014 to 31 July 2016. Significant variables in univariate analysis were used to create a multivariate analysis. Differentiation of predicting factors between cardiac arrest patient and non-cardiac arrest patients for occurrence of cardiac arrest in an emergency department (ED) was the primary outcome. Results: The data of 527 non-trauma patients with Emergency Severity Index (ESI) 1-3 were collected. The factors found to have a significant association (P < 0.05) in the non-cardiac arrest group versus the cardiac arrest group at the ED were systolic BP (mean [IQR] 135 [114,158] vs 120 [90,140] mmHg), oxygen saturation (mean [IQR] 97 [89,98] vs 82.5 [78,95]%), GCS (mean [IQR] 15 [15,15] vs 11.5 [8.815]), normal sinus rhythm (mean 59.8 vs 30%), sinus tachycardia (mean 46.7 vs 21.7%), pH (mean [IQR] 7.4 [7.3,7.4] vs 7.2 [7,7.3]), serum lactate (mean [IQR] 2 [1.1,4.2] vs 7 [5,10.8]), and MEWS score (mean [IQR] 3 [2,5] vs 5 [3,6]). A multivariate analysis was then performed. After adjusting for multiple factors, ESI level 2 patients were more likely to have cardiac arrest in the ER compared with ESI 1 (odds ratio [OR], 1.66; P < 0.001). Furthermore, ESI 2 patients were more likely than ESI 1 patients to have cardiovascular disease (OR, 1.89; P = 0.01), heart rate < 55 (OR, 6.83; P = 0.18), SBP < 90 (OR, 3.41; P = 0.006), SpO2 < 94 (OR, 4.76; P = 0.012), sinus tachycardia (OR, 4.32; P = 0.002), lactate > 4 (OR, 10.66; P = < 0.001), and MEWS > 4 (OR, 4.86; P = 0.028). These factors remained predictive of cardiac arrest at the ED. Conclusion: The factors related to cardiac arrest in the ED are ESI 1 patients, ESI 2 patients, patients diagnosed with cardiovascular disease, SpO2 < 94, lactate > 4, and a MEWS > 4. These factors can be used as markers in the event of simultaneous arrival of many patients and can help as a pre-state for patients who have a tendency to develop cardiac arrest. The hemodynamic status and vital signs of these patients should be closely monitored. Early detection of potentially critical conditions to prevent critical medical intervention is mandatory.

Keywords: cardiac arrest, predicting factor, emergency department, emergency patient

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Authors: Akhigbe Mark, Abang Roger, Mwoltu Nanaribet, Edet Blessing

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Introduction.: The introduction of pre- exposure prophylaxis (PrEP) as a biomedical prevention method for HIV/AIDS has been around for more than a decade since the first confirmed evidence of its effectiveness when used daily as an oral pill. It is now a very valuable addition for people who are at higher risk of contracting HIV. Although globalacceptanceof PrEP hasincreased, PrEP is still highly concentrated in a small number of countries and within a small sub-population, with Kenya and South Africa accounting for only 19% of people who have received PrEP in Africa region, there is still a significant regionGap in PrEP availability and use, with only 28% of the target of 3 million in low-and middle countries currently using PrEP. Description: The purpose of this study is to find out if serum creatinine could be used as an incentive to improve PrEP uptake among Key population.Numerous approaches to increasing the uptake ofPrEP as a prevention mechanism for HIV in KPs has beenemployed, and one of them is serum creatinine. This approach is a biomarker of renal function, which was used in study as an incentive to increase PrEP uptake among key population groups (female sex workers, men who have sex with men, persons who inject drugs, transgender) in 3 states from South-South Nigeria. Whole blood samples are collected from clients, analysis of the samples is done using the clinical chemistry analyzer before they are initiated onto PrEP. Lessons learned and Recommendations: Secondary data was extracted from 3 states of HALG Implementing facilities in Southern part of Nigeria, PrEP uptake before and afterthe introduction of serum creatinine between March 2020 and August 2020 among key populationsin Nigeria. A total of 5664 patients were initiated on PrEP before, and after the introduction of serum creatinine, the PrEP uptake rate before (March 2020 to May 2020) introduction of serum creatinine accounted for only 5% of the total onset, and after (June 2020 to August 2020) introduction of serum creatinine, the uptake rate accounted for 95% of the total onset. These finding shows that increased uptake of PrEP before/after serum creatineindicates that serum creatine may be an effective stimulus for promoting PrEP in key populations.

Keywords: serum creatinine, incentives, PrEP, key populations, Nigeria

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Authors: Denis V. Axenov-Gribanov, Irina V. Voytsekhovskaya, Evgenii S. Protasov, Maxim A. Timofeyev

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Isolated ecosystems existing under specific environmental conditions have been shown to be promising sources of new strains of actinobacteria. The taiga forest of Baikal Siberia has not been well studied, and its actinobacterial population remains uncharacterized. The proximity between the huge water mass of Lake Baikal and high mountain ranges influences the structure and diversity of the plant world in Siberia. Here, we report the isolation of eighteen actinobacterial strains from male cones of Pinus sylvestris trees growing on the shore of the ancient Lake Baikal in Siberia. The actinobacterial strains were isolated on solid nutrient MS media and Czapek agar supplemented with cycloheximide and phosphomycin. Identification of actinobacteria was carried out by 16S rRNA gene sequencing and further analysis of the evolutionary history. Four different liquid and solid media (NL19, DNPM, SG and ISP) were tested for metabolite production. The metabolite extracts produced by the isolated strains were tested for antibacterial and antifungal activities. Also, antiradical activity of crude extracts was carried out. Strain Streptomyces sp. IB 2014 I 74-3 that active against Gram-negative bacteria was selected for dereplication analysis with using the high-yield liquid chromatography with mass-spectrometry. Mass detection was performed in both positive and negative modes, with the detection range set to 160–2500 m/z. Data were collected and analyzed using Bruker Compass Data Analysis software, version 4.1. Dereplication was performed using the Dictionary of Natural Products (DNP) database version 6.1 with the following search parameters: accurate molecular mass, absorption spectra and source of compound isolation. Thus, in addition to more common representative strains of Streptomyces, several species belonging to the genera Rhodococcus, Amycolatopsis, and Micromonospora were isolated. Several of the selected strains were deposited in the Russian Collection of Agricultural Microorganisms (RCAM), St. Petersburg, Russia. All isolated strains exhibited antibacterial and antifungal activities. We identified several strains that inhibited the growth of the pathogen Candida albicans but did not hinder the growth of Saccharomyces cerevisiae. Several isolates were active against Gram-positive and Gram-negative bacteria. Moreover, extracts of several strains demonstrated high antioxidant activity. The high proportion of biologically active strains producing antibacterial and specific antifungal compounds may reflect their role in protecting pollen against phytopathogens. Dereplication of the secondary metabolites of the strain Streptomyces sp. IB 2014 I 74-3 was resulted in the fact that a total of 59 major compounds were detected in the culture liquid extract of strain cultivated in ISP medium. Eight compounds were preliminarily identified based on characteristics described in the Dictionary of Natural Products database, using the search parameters Streptomyces sp. IB 2014 I 74-3 was found to produce saframycin A, Y3 and S; 2-amino-3-oxo-3H-phenoxazine-1,8-dicarboxylic acid; galtamycinone; platencin A4-13R and A4-4S; ganefromycin d1; the antibiotic SS 8201B; and streptothricin D, 40-decarbamoyl, 60-carbamoyl. Moreover, forty-nine of the 59 compounds detected in the extract examined in the present study did not result in any positive hits when searching within the DNP database and could not be identified based on available mass-spec data. Thus, these compounds might represent new findings.

Keywords: actinobacteria, Baikal Lake, biodiversity, male cones, Pinus sylvestris

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Authors: Fanniyah Anis, Bram Kilapong

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Myocardial reperfusion injury is defined as the cellular damage that results from a period of ischemia, followed by the reestablishment of the blood supply to the infarcted tissue. Ventricular tachycardia is one of the most commonly encountered reperfusion arrhythmia as one of the types of myocardial perfusion injury. Prompt and early treatment can reduce mortality, despite limited resources of the hospital in high risk patients with history of triple vessel disease. Case report, Male 53 years old has been diagnosed with NSTEMI with 3VD and comorbid disease of Hypertension and has undergone revascularization management with Percutaneous coronary intervention. Ventricular tachycardia leading to cardiac arrest occurred right after the stent was inserted. Resuscitation was performed for almost 2 hours until spontaneous circulation returned. Patient admitted in ICU with refractory cardiac shock despite using combination of ionotropic and vasopressor agents under standard non-invasive monitoring due to the limitation of the hospital. Angiography was performed again 5 hours later to exclude other possibilities of blockage of coronary arteries and conclude diagnosis of myocardial reperfusion injury. Patient continually managed with combination of antiplatelet agents and maintenance dose of anti-arrhythmia agents. The handling of the patient was to focus more on supportive and preventive from further deteriorating of the condition. Patient showed clinically improvement and regained consciousness within 24 hours. Patient was successfully discharged from ICU within 3 days without any neurological sequela and was discharge from hospital after 3 days observation in general ward. Limited Resource of hospital did not refrain the physician from attaining a good outcome for this myocardial reperfusion injury case and angiography alone can be used to confirm the diagnosis of myocardial reperfusion injury.

Keywords: limited resources hospital, myocardial reperfusion injury, prolonged resuscitation, refractory cardiogenic shock, reperfusion arrhythmia, revascularization, triple-vessel disease

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Authors: L. Sun, T. Hargreaves, Z. Ahmad

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Newly-qualified Foundation Year 1 doctors in the United Kingdom are frequently expected to perform practical skills involving the upper limb in clinical practice (for example, venipuncture, cannulation, and blood gas sampling). However, a move towards systems-based undergraduate medical education in the United Kingdom often precludes or limits dedicated time to anatomy teaching with cadavers or prosections, favouring only applied anatomy in the context of pathology. The authors hypothesised that detailed anatomical knowledge may consequently be adversely affected, particularly with respect to long-term retention. A simple picture quiz and accompanying questionnaire testing the identification of 7 upper limb surface landmarks was distributed to a total of 98 final year medical students from two universities - one with a systems-based curriculum, and one with a dedicated longitudinal dissection-based anatomy module in the first year of study. Students with access to dissection and prosection-based anatomy teaching performed more strongly, with a significantly higher rate of correct identification of all but one of the landmarks. Furthermore, it was notable that none of the students who had previously undertaken a systems-based course scored full marks, compared with 20% of those who had participated in the more dedicated anatomy course. This data suggests that a traditional, dissection-based approach to undergraduate anatomy teaching is superior to modern system-based curricula, in terms of aiding long-term retention of anatomical knowledge pertinent to newly-qualified doctors. The authors express concern that this deficit in proficiency could be detrimental to patient care in clinical practice, and propose that, where dissection-led anatomy teaching is not available, further anatomy revision modules are implemented throughout undergraduate education to aid knowledge retention and support clinical excellence.

Keywords: dissection, education, surface anatomy, upper limb

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Authors: Abdelkrim Khadir, Sina Kavalakatt, Preethi Cherian, Ali Tiss

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Soluble epoxide hydrolase (sEH) is an emerging therapeutic target in several chronic states that have inflammation as a common underlying cause such as immunometabolic diseases. Indeed, sEH is known to play a pro-inflammatory role by metabolizing anti-inflammatory, epoxyeicosatrienoic acids (EETs) to pro-inflammatory diols. Recently, it was shown sEH to be linked to diet and microbiota interaction in rat models of obesity. Nevertheless, the functional contribution of sEH and its anti-inflammatory substrates EETs in obesity remain poorly understood. In the current study, we compared the expression pattern of sEH between lean and obese nondiabetic human subjects using subcutaneous adipose tissue (SAT) and peripheral blood mononuclear cells (PBMCs). Using RT-PCR, western blot and immunofluorescence confocal microscopy, we show here that the level of sEH mRNA and protein to be significantly increased in obese subjects with concomitant increase in endoplasmic reticulum (ER) stress components (GRP78 and ATF6α) and inflammatory markers (TNF-α, IL-6) when compared to lean controls. The observation that sEH was overexpressed in obese subjects’ prompt us to investigate whether physical exercise could reduce its expression. In this study, we report here 3-months supervised physical exercise significantly attenuated the expression of sEH in both the SAT and PBMCs, with a parallel decrease in the expression of ER stress markers along with attenuated inflammatory response. On the other hand, homocysteine, a sulfur containing amino acid deriving from the essential amino acid methionine was shown to be directly associated with insulin resistance. When 3T3-L1 preadipocytes cells were treated with homocysteine our results show increased sEH levels along with ER stress markers. Collectively, our data suggest that sEH upregulation is strongly linked to ER stress in adiposity and that physical exercise modulates its expression. This gives further evidence that exercise might be useful as a strategy for managing obesity and preventing its associated complications.

Keywords: obesity, adipose tissue, epoxide hydrolase, ER stress

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Authors: Mustafa M. Donma, Erkut Karasu, Burcu Ozdilek, Burhan Turgut, Birol Topcu, Burcin Nalbantoglu, Orkide Donma

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The mechanisms underlying the association between obesity and asthma may be related to a decreased immunological tolerance induced by a defective function of regulatory T cells (Tregs). The aim of this study is to establish the potential link between these diseases and CD4+, CD25+ FoxP3+ Tregs as well as T helper cells (Ths) in children. This is a prospective case control study. Obese (n:40), asthmatic (n:40), asthmatic obese (n:40), and healthy children (n:40), who don't have any acute or chronic diseases, were included in this study. Obese children were evaluated according to WHO criteria. Asthmatic patients were chosen based on GINA criteria. Parents were asked to fill up the questionnaire. Informed consent forms were taken. Blood samples were marked with CD4+, CD25+ and FoxP3+ in order to determine Tregs and Ths by flow cytometric method. Statistical analyses were performed. p≤0.05 was chosen as meaningful threshold. Tregs exhibiting anti-inflammatory nature were significantly lower in obese (0,16%; p≤0,001), asthmatic (0,25%; p≤0,01) and asthmatic obese (0,29%; p≤0,05) groups than the control group (0,38%). Ths were counted higher in asthma group than the control (p≤0,01) and obese (p≤0,001)) groups. T cell immunity plays important roles in obesity and asthma pathogeneses. Decreased numbers of Tregs found in obese, asthmatic and asthmatic obese children may help to elucidate some questions in pathophysiology of these diseases. For HOMA-IR levels, any significant difference was not noted between control and obese groups, but statistically higher values were found for obese asthmatics. The values obtained in all groups were found to be below the critical cut off points. This finding has made the statistically significant difference observed between Tregs of obese, asthmatic, obese asthmatic, and control groups much more valuable. These findings will be useful in diagnosis and treatment of these disorders and future studies are needed. The production and propagation of Tregs may be promising in alternative asthma and obesity treatments.

Keywords: asthma, flow cytometry, pediatric obesity, T cells

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Authors: Camellia Al-Ibrahim, Jenny Yiend, Sukhwinder S. Shergill

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Background: Attention bias to threat play a role in the development, maintenance, and exacerbation of delusional beliefs in schizophrenia in which patients emphasize the threatening characteristics of stimuli and prioritise them for processing. Cognitive control deficits arise when task-irrelevant emotional information elicits attentional bias and obstruct optimal performance. This study is investigating neural correlates of interference effect of linguistic threat and whether these effects are independent of delusional severity. Methods: Using an event-related functional magnetic resonance imaging (fMRI), neural correlates of interference effect of linguistic threat during the emotional Stroop task were investigated and compared patients with schizophrenia with high (N=17) and low (N=16) paranoid symptoms and healthy controls (N=20). Participants were instructed to identify the font colour of each word presented on the screen as quickly and accurately as possible. Stimuli types vary between threat-relevant, positive and neutral words. Results: Group differences in whole brain effects indicate decreased amygdala activity in patients with high paranoid symptoms compared with low paranoid patients and healthy controls. Regions of interest analysis (ROI) validated our results within the amygdala and investigated changes within the striatum showing a pattern of reduced activation within the clinical group compared to healthy controls. Delusional severity was associated with significant decreased neural activity in the striatum within the clinical group. Conclusion: Our findings suggest that the emotional interference mediated by the amygdala and striatum may reduce responsiveness to threat-related stimuli in schizophrenia and that attenuation of fMRI Blood-oxygen-level dependent (BOLD) signal within these areas might be influenced by the severity of delusional symptoms.

Keywords: attention bias, fMRI, Schizophrenia, Stroop

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Authors: Mohammad Javad Behzadnia, Amir Bahador Boroumand

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Introduction: Limited facility situations require allocating the most available resources for most casualties. Accordingly, Traumatic Brain Injury (TBI) is the one that may need to transport the patient as soon as possible. In a mass casualty event, deciding when the facilities are restricted is hard. The Extended Glasgow Outcome Score (GOSE) has been introduced to assess the global outcome after brain injuries. Therefore, we aimed to evaluate the prognostic factors associated with GOSE. Materials and Methods: In a multicenter cross-sectional study conducted on 144 patients with TBI admitted to trauma emergency centers. All the patients with isolated TBI who were mentally and physically healthy before the trauma entered the study. The patient’s information was evaluated, including demographic characteristics, duration of hospital stays, mechanical ventilation on admission laboratory measurements, and on-admission vital signs. We recorded the patients’ TBI-related symptoms and brain computed tomography (CT) scan findings. Results: GOSE assessments showed an increasing trend by the comparison of on-discharge (7.47 ± 1.30), within a month (7.51 ± 1.30), and within three months (7.58 ± 1.21) evaluations (P < 0.001). On discharge, GOSE was positively correlated with Glasgow Coma Scale (GCS) (r = 0.729, P < 0.001) and motor GCS (r = 0.812, P < 0.001), and inversely with age (r = −0.261, P = 0.002), hospitalization period (r = −0.678, P < 0.001), pulse rate (r = −0.256, P = 0.002) and white blood cell (WBC). Among imaging signs and trauma-related symptoms in univariate analysis, intracranial hemorrhage (ICH), interventricular hemorrhage (IVH) (P = 0.006), subarachnoid hemorrhage (SAH) (P = 0.06; marginally at P < 0.1), subdural hemorrhage (SDH) (P = 0.032), and epidural hemorrhage (EDH) (P = 0.037) were significantly associated with GOSE at discharge in multivariable analysis. Conclusion: Our study showed some predictive factors that could help to decide which casualty should transport earlier to a trauma center. According to the current study findings, GCS, pulse rate, WBC, and among imaging signs and trauma-related symptoms, ICH, IVH, SAH, SDH, and EDH are significant independent predictors of GOSE at discharge in TBI patients.

Keywords: field, Glasgow outcome score, prediction, traumatic brain injury.

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Authors: M. R. Vijayakumar, Sanjay Kumar Singh, Lakshmi, Hithesh Dewangan, Sanjay Singh

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Trans resveratrol (RES) is a natural molecule proved for cancer preventive and therapeutic activities devoid of any potential side effects. However, the therapeutic application of RES in disease management is limited because of its rapid elimination from blood circulation thereby low biological half life in mammals. Therefore, the main objective of this study is to enhance the circulation as well as therapeutic efficacy using PEGylated liposomes. D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) is applied as steric surface decorating agent to prepare RES liposomes by thin film hydration method. The prepared nanoparticles were evaluated by various state of the art techniques such as dynamic light scattering (DLS) technique for particle size and zeta potential, TEM for shape, differential scanning calorimetry (DSC) for interaction analysis and XRD for crystalline changes of drug. Encapsulation efficiency and invitro drug release were determined by dialysis bag method. Cancer cell viability studies were performed by MTT assay, respectively. Pharmacokinetic studies were performed in sprague dawley rats. The prepared liposomes were found to be spherical in shape. Particle size and zeta potential of prepared formulations varied from 64.5±3.16 to 262.3±7.45 nm and -2.1 to 1.76 mV, respectively. DSC study revealed absence of potential interaction. XRD study revealed presence of amorphous form in liposomes. Entrapment efficiency was found to be 87.45±2.14 % and the drug release was found to be controlled up to 24 hours. Minimized MEC in MTT assay and tremendous enhancement in circulation time of RES PEGylated liposomes than its pristine form revealed that the stearic stabilized PEGylated liposomes can be an alternative tool to commercialize this molecule for chemopreventive and therapeutic applications in cancer.

Keywords: trans resveratrol, cancer nanotechnology, long circulating liposomes, bioavailability enhancement, liposomes for cancer therapy, PEGylated liposomes

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Authors: Melba Sheila D'Souza, Anandhi Amirtharaj, Shreedevi Balachandran

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Background: Type 2 diabetes has a significant impact on individuals’ health and well-being. Glycemic control may influence self-efficacy and self-care behaviors, and reduce the risk of complications among adults with type 2 diabetes. Type 2 diabetes has substantial morbidity and mortality and 60% of adults’ poor self-care. Glycemic control is associated with reported self-efficacy and self-care behavior. Adults with type 2 diabetes with less information were less likely to take diabetes self-care. Aim: To examine the relationship between glycemic control, demographic factors, clinical factors on self-efficacy, self-care behaviors among Omani adults with type 2 diabetes. Methods: A correlational, descriptive study was used. Omani adults with type 2 diabetes (n=140) were recruited from a public hospital in Oman. The data were collected during January-March 2015. Ethical approval was given by the college research and ethics committee, College of Nursing, and the Hospital, Sultan Qaboos University Data was collected on self-efficacy, self-care behaviors and glycemic control. The study was approved by the Institution Ethics and Research Committee. Bivariate and multivariate analyses were conducted. Results: Most adults had a fasting blood glucose >7.2mmol/L (90.7%), with the majority demonstrating ‘uncontrolled or poor HbA1c of > 8%’ (65%). Variance of self-care behavior (20.6%) and 31.3% of the variance of the self-efficacy was explained by the age, duration of diabetes, medication, HbA1c and prevention of activities of living. Adults with type 2 diabetes with poor glycemic control were more likely to have poor self-efficacy and poor self-care behaviors. Conclusion: This study confirms that self-efficacy model on outcome predicts self-efficacy and self-care behavior. Higher understanding of diabetes, prevention of normal daily activities, higher ability to fit diabetes life in a positive manner and high patient-physician communication were significant with self-efficacy and self-care behaviors. Hence, glycemic control has a high effect on improving self-care behaviors like diet, exercise, medication, foot care and self-efficacy among type 2 diabetes. Implications: Using these findings to improve self-efficacy, individualized self-care management is recommended for better self-efficacy and self-care behaviors among adults with type 2 diabetes.

Keywords: self-efficacy, self-care behaviors, self-care management, glycemic control, type 2 diabetes, nurse

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Authors: Masome Moeni, Roya Abedizadeh, Elham Aram, Hamid Sadeghi-Abandansari, Davood Sabour, Robert Menzel, Ali Hassanpour

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Mitochondria- targeting immunogenic cell death inducers (MT-ICD) have been designed to trigger intrinsic apoptosis signalling pathway in malignant cells and revive the antitumour immune system. MT-ICD inducers have considered to be non-specific, which can deteriorate the ability to initiate mitochondria-selective oxidative stress, causing high toxicity. Iron oxide nanoparticles (IONPs) can be an ideal candidate as vehicles for utilizing in immunotherapy due to their biocompatibility, modifiable surface chemistry, magnetic characteristics and multi-functional applications in single platform. These types of NPs can facilitate a real time imaging which can provide an effective strategy to analyse pharmacokinetic parameters of nano-formula, including blood circulation time, targeted and controlled release at tumour microenvironment. To our knowledge, the conjugation of IONPs with MT-ICD and oxaliplatin (a chemotherapeutic agent used for the treatment of colorectal cancer) for immunotherapy have not been investigated. Herein, IONPs were generated via co-precipitation reaction at high temperatures, followed by coating the colloidal suspension with tetraethyl orthosilicate and 3-aminopropyltriethoxysilane to optimize their bio-compatibility, preventing aggregation and maintaining stability at physiological pH, then functionalized with (3-carboxypropyl) triphenyl phosphonium bromide for mitochondrial delivery. Analytical results demonstrated the successful process of IONPs functionalization. In particular, the colloidal particles of doped IONPs exhibited an excellent stability and dispersibility. The resultant particles were also successfully loaded with the oxaliplatin for an active mitochondrial targeting in immunotherapy, resulting in well-maintained super-paramagnetic characteristics and stable structure of the functionalized IONPs with nanoscale particle sizes.

Keywords: Immunotherapy, mitochondria, cancer, iron oxide nanoparticle

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Authors: Kehinde Joseph Awosan, Balarabe Adami Isah, Edzu Usman Yunusa, Sarafadeen Adeniyi Arisegi, Izuchukwu Obasi, Oluchi Solomon-Anucha

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Background: Metabolic syndrome (MetS) is prevalent in patients with diabetes mellitus and a significant risk for major cardiovascular events. Identifying its burden and peculiarities is crucial to preventing complications among those at risk. Aim: This study was conducted to determine the prevalence and predictors of metabolic syndrome among diabetes clinic attendees in Sokoto, Nigeria. Materials and Methods: A cross-sectional study was conducted among 365 patients with type 2 diabetes attending the diabetes clinic of Specialist Hospital, Sokoto, Nigeria. A structured questionnaire was used to obtain data on the respondents’ socio-demographic variables, treatment history, and lifestyle. Blood pressure and anthropometric measurements (including weight, height, and waist circumference) were done for the patients. Likewise, biochemical assessment (including fasting plasma glucose, high-density lipoprotein cholesterol (HDL-c), and triglyceride (TG) was done. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III). Data were analyzed using the IBM Statistical Package for Social Sciences (SPSS) version 25. Results: The ages of the patients ranged from 30 to 78 (mean = 50.9 ±11.7) years. The overall prevalence of MetS was 57.3%, with a higher prevalence in females (68.1%) than males (43.0%). The most common components of MetS observed were hypertension (69.2%), and elevated fasting plasma glucose (65.7%); while the predictors of MetS were age > 50 years (OR 6.960, 95% CI: 3.836-12.628, p < 0.001), female sex (OR 2.300, 95% CI: 1.355-3.903, p = 0.002), physical activity (OR 0.214, 95% CI: 0.126-0.363, p < 0.001), and overweight/obesity (OR 3.356, 95% CI: 1.838-6.127, p < 0.001). Conclusion: Metabolic syndrome is prevalent among patients with type 2 diabetes in Sokoto, Nigeria, and the predictors were age > 50 years, female sex, physical activity, and overweight/obesity. Diabetes care providers should screen their patients for MetS to prevent adverse cardiovascular events.

Keywords: prevalence, predictors, metabolic syndrome, diabetes

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Authors: Sonal Tuljaram Kame

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Growth and development is based on proper diet. A balanced diet contains all the nutrients in required quantum. Although physical growth is completed by young adulthood, the body tissues remain in a dynamic state with catabolism slightly exceeding anabolism, resulting in a net decrease in the number of cells. After the years of adolescence which cause upheavals in the life of the person, the individual struggle to emerge as an adult who know who he is and what his goals are. During this period nutrients are needed for maintaining the health and energy is required for physical functions and physical activities. The nutritional requirement in young adulthood differs from other periods of life. Iron is needed for haemoglobin synthesis and necessitates by the considerable examination of blood volume. Young adult girls need to ensure adequate intake of iron as they loose 0.5 mg/day by way of menstruation. This is complete awareness about nutritional and health on the other side there is widespread ignorance about nutrition and health among young adult girls. The young adult girls who are aware about nutrition and health seem to be very conscious about nutritional intake and health. Figure consciousness and fear of obesity leads to self imposed intake of nutrients. It may result in various health problems. The study was planned to investigate nutrient intake, find relation between nutritional intake, clinical examination score and health status of young adult girls. The present study is based on the data collected from 120 young adult girls studying in four different competitive exams coaching academies in Akola city of Maharashtra. It was found that nutritional intake of these young adult girls was below the recommended level, nutritional knowledge level and nutritional intake are associated attributes, calories, calcium and protein intake is positively correlated with clinical examination and health status. It was concluded that well planned nutritional counseling for the young adult girls can help prevent nutritional deficiency diseases and disorders which may lead to anaemic condition in young adult girls. Girls need to be educated on intake of iron and vitamin B12.

Keywords: nutritional intake, health status, young adult girls, correlation studies

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Authors: Rasha Ahmadi

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In December 2019, a coronavirus, currently identified as SARS-CoV-2, produced a series of acute atypical respiratory illnesses in Wuhan, Hubei Province, China. The sickness induced by this virus was named COVID-19. The virus is transmittable between humans and has caused pandemics worldwide. The number of death tolls continues to climb and a huge number of countries have been obliged to perform social isolation and lockdown. Lack of focused therapy continues to be a problem. Epidemiological research showed that senior patients were more susceptible to severe diseases, whereas children tend to have milder symptoms. In this study, we focus on other possible side effects of COVID-19 and more detailed treatment strategies. Using bioinformatics analysis, we first isolated the gene expression profile of patients with severe COVID-19 from the GEO database. Patients' blood samples were used in the GSE183071 dataset. We then categorized the genes with high and low expression. In the next step, we uploaded the genes separately to the Enrichr database and evaluated our data for signs and symptoms as well as related medication regimens. The results showed that 138 genes with high expression and 108 genes with low expression were observed differentially in the severe COVID-19 VS control group. Symptoms and diseases such as embolism and thrombosis of the abdominal aorta, ankylosing spondylitis, suicidal ideation or attempt, regional enteritis were observed in genes with high expression and in genes with low expression of acute and subacute forms of ischemic heart, CNS infection and poliomyelitis, synovitis and tenosynovitis. Following the detection of diseases and possible signs and symptoms, Carmustine, Bithionol, Leflunomide were evaluated more significantly for high-expression genes and Chlorambucil, Ifosfamide, Hydroxyurea, Bisphenol for low-expression genes. In general, examining the different and invisible aspects of COVID-19 and identifying possible treatments can help us significantly in the emergency and hospitalization of patients.

Keywords: phenotypes, drug regimens, gene expression profiles, bioinformatics analysis, severe COVID-19

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Authors: Geraldine Landon, Enora Clero, Jean-Rene Jourdain

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In 2005, the Institut de Radioprotection et de Sûreté Nucléaire (IRSN, France) launched a research program named EPICE (acronym for 'Evaluation of Pathologies potentially Induced by CaEsium') to collect scientific information on non-cancer effects possibly induced by chronic exposures to low doses of ionizing radiation with the view of addressing a question raised by several French NGOs related to health consequences of the Chernobyl nuclear accident in children. The implementation of the program was preceded by a pilot phase to ensure that the project would be feasible and determine the conditions for implementing an epidemiological study on a population of several thousand children. The EPICE program focused on childhood cardiac arrhythmias started in May 2009 for 4 years, in partnership with the Russian Bryansk Diagnostic Center. The purpose of this cross-sectional study was to determine the prevalence of cardiac arrhythmias in the Bryansk oblast (depending on the contamination of the territory and the caesium-137 whole-body burden) and to assess whether caesium-137 was or not a factor associated with the onset of cardiac arrhythmias. To address these questions, a study bringing together 18 152 children aged 2 to 18 years was initiated; each child received three medical examinations (ECG, echocardiography, and caesium-137 whole-body activity measurement) and some of them were given with a 24-hour Holter monitoring and blood tests. The findings of the study, currently submitted to an international journal justifying that no results can be given at this step, allow us to answer clearly to the issue of radiation-induced childhood arrhythmia, a subject that has been debated for many years. Our results will be certainly helpful for health professionals responsible for the monitoring of population exposed to the releases from the Fukushima Dai-ichi nuclear power plant and also useful for future comparative study in children exposed to ionizing radiation in other contexts, such as cancer radiation therapies.

Keywords: Caesium-137, cardiac arrhythmia, Chernobyl, children

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Authors: Fatimah A. Alhomaid

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The present study was planned to investigate the role of molecular changes and immunohistochemical in early detection of liver cancer in Saudi patients. our results were carried out on 54 patients liver cancer. We obtained our data from laboratory in King Khalid University Hospital. The specimens were taken (54) patients with liver cancer 34 male and 14 female and 2 control. The average age of varied from 37-85 years. The tumor was diagnosed as grade I in tow patients (male and female) and grade 2 in 45 patients (28 male and 17 female) while the grade 3 in 4 patients (all males). The specimens were processed for haematoxylin and eosin staining, immunohistochemical technique and flow cytometry analysis. Our study noted that most patients had adenocarcinoma which characterized by presence of signet-ring cells were very clear in advanced patients with adenocarcinoma. Our sections in adenocarcinoma in grade 2 and stage 3 had an increase in signet ring cells,an increase in the acini of glands and an increase in number of lymphocytes which spread to the muscular layer. With advancing the disease, there were haemorrhage in blood and increase in lymphocytes and increase in the number of nuclei in the tubular glands. Our study was carried on 48 patients, immunohistochemical diagnosis (CK20, PCNA, P53) and the analysis of DNA content by flow cytometry technique. Our study indicated that the presence of correlation between the immunohistochemical analysis for P53 and the grades. The reaction of P53 appeared as strong in nucleus in grades &stage 3 and appeared in other sections as dark brown pigment. Our study indicated that the absence of correlation between the immunohistochemical analysis for PCAN and the grades. In our sections there were strong reaction in the more 80% of nuclei in grade 1& stage 2. Our study indicated that the presence of correlation between the immunohistochemical analysis for CK20 and the grades. Our results indicated the presence of positive reaction in cytoplasm varied from weak to moderate in grade 3 & stage 4. Concerning the Flow cytometry technique our results indicated that the presence of correlation between the DNA and different stages of liver cancer.

Keywords: cancer, CK20, DNA, cytometry analysis, liver, immunohistochemical, molecular changes, PCNA, p53

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Authors: Sangeeta Girdhar, Amanat Grewal, Nahush Bansal

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Introduction: There is an increasing burden of hypertension in India. The morbidity and mortality arising from complications are mainly due to non-adherence to medication, unhealthy dietary habits, and lack of physical activity. Non-adherence is a well-recognised factor contributing to inadequate control of high blood pressure. Adherence to pharmacotherapy for hypertension varies from 43% to 88%. Non-adherence is influenced by various socio-demographic factors. Understanding these factors is useful in managing non-adherence. Therefore, the study was planned to determine adherence among hypertensives and factors associated with non-adherence to treatment. Methodology: A cross-sectional study was conducted at Urban Health Training Centre of Dayanand Medical College and Hospital Ludhiana. Patients attending the OPD over a period of 3 months were included in the study. Prior ethical approval was obtained, and informed consent was taken from subjects. A predesigned semi-structured questionnaire was applied, which included socio-demographic profile, treatment-seeking behaviour, adherence to the antihypertensive medication, lifestyle factors (intake of alcohol, smoking, consumption of junk food, high salt intake) contributing to the development of the disease. Reasons for non-adherence to the therapy were also explored. Data was entered into excel, and SPSS 26 version was used for analysis. Results: A total of 186 individuals were interviewed. Out of these, 113 females (60.8%) and 73 males (39.2%) participated in the study. Mean age of participants was 60.9 ± 10.7 years. Adherence to anti-hypertensive treatment was found in 68.3% of the participants. It was observed that adherence was more in literate individuals as compared to illiterate (p value- 0.78). Adherence was lower among smokers (33.3%) and alcohol consumers (53.8%) as compared to non-users (69.4% and 70.6%, respectively). The predominant reasons for skipping medications were discontinuing medication when feeling well, forgetfulness and unawareness. Conclusion: There is a need to generate awareness regarding the importance of adherence to therapy among patients. Intensive health education and counselling of the patients is the need of the hour.

Keywords: hypertension, anti-hypertensive, adherence, counselling

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Authors: Hanaa M. M. El-Khayat, Hoda Abdel-Hamid, Kadria M. A. Mahmoud, Hanan S. Gaber, Hoda, M. A. Abu Taleb, Hassan E. Flefel

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Snails are considered as suitable diagnostic organisms for heavy metal–contaminated sites. Biomphalaria alexandrina snails are used in this work as pollution bioindicators after exposure to chemical mixtures consisted of heavy metals (HM); zinc (Zn), copper (Cu) and lead (Pb); and persistent organic pollutants; Decabromodiphenyl ether 98% (D) and Aroclor 1254 (A). The impacts of these tested chemicals, individual and mixtures, on liver and kidney functions, antioxidant enzymes, complete blood picture, and tissue histology were studied. Results showed that Cu was proved to be the highly toxic against snails than Zn and Pb where LC₅₀ values were 1.362, 213.198 and 277.396 ppm, respectively. Also, B. alexandrina snails exposed to the mixture of HM (¼ LC₅ Cu, Pb and Zn) showed the highest bioaccumulation of Cu and Zn in their whole tissue, the most significant increase in AST, ALT & ALP activities and the highest significant levels of total protein, albumin and globulin. Results showed significant alterations in CAT activity in snail tissue extracts while snail samples exposed to most experimental tests showed significant increase in GST activity. Snail samples that exposed to HM mixtures showed a significant decrease in total hemocytes count while snail samples that exposed to mixtures containing A & D showed a significant increase in total hemocytes and Hyalinocytes. Histopathological alterations in snail samples exposed to individual HM and their mixtures for 4 weeks showed degeneration, edema, hyper trophy and vaculation in head-foot muscle, degeneration and necrotic changes in the digestive gland and accumulation in most tested organs. Also, the hermaphrodite gland showed mature ova with irregular shape and reduction in sperm number. In conclusion, the resulted damage and alterations in B. alexandrina studied parameters can be used as bioindicators to the presence of pollutants in its habitats.

Keywords: Biomphalaria, Zn, Cu, Pb, AST, ALT, ALP, total protein albumin, globulin, CAT, histopathology

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Authors: Samar Saadeldin Abdelmotalab Omer, Ikram Mohammed Eltayeb Elsiddig, Amna Beshir Medani Ahmed, Saad Mohammed Hussein Ayoub

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Many herbal medicinal products are considered as potential hypocholesterolemic agents with encouraging safety profiles, however, only a limited amount of clinical research exists to support their efficacy. The present study was designed to compare the antihypercholesterolaemic and antioxidant activities of the crude ethanolic extracts of Citrus reticulata peel, Zingiber officinale rhizome, and Sesamum indicum seeds. Forty-five rats were used throughout the experiment, which were divided into nine groups, five rats in each as follows; normal control group (normal rats fed with standard normal diet), rats fed hypercholesterolemic diet consisting of 1% cholesterol and 10% saturated animal fat, which were further divided into eight groups; hypercholesterolemic control group (rats only fed hypercholesterolemic diet), groups 3,4,5,6,7, and 8 were given Citrus reticulata, Zingiber officinale, and Sesamum indicum ethanolic extracts at doses of (250mg/kg and 500mg/kg, respectively) orally; and group 9 rats were given atorvastatin (0.18mg/kg) orally as a reference antihypercholesterolaemic drug. Blood samples were obtained four weeks following treatment from the retro-orbital venous plexus after fasting overnight from all groups and the lipid profile (serum total cholesterol (TC), high-density-lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and triglycerides levels) was measured and the risk ratio (TC/HDL-C) was assessed. The antioxidant activity of the three plant extracts was determined using DPPH free-radical assay. Results of in vivo and in vitro antihypercholesterolaemic and antioxidant assay, respectively, revealed that the three extracts possess comparable antioxidant and anti-hypercholesterolaemic activities.

Keywords: anti hypercholesterolemic effects, antioxidant activity, HDL, LDL, TC, TGs, citrus reticulata, sesamum indicum, zingiber officinale

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Authors: Aliya Sekenova, Vyacheslav Ogay

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The derivation of human induced pluripotent stem cells (iPSCs) from somatic cells by direct reprogramming opens wide perspectives in the regenerative medicine. It means the possibility to develop the personal and, consequently, any immunologically compatible cells for applications in cell-based therapy. The purpose of our study was to develop the technology for the production of NK cells from T cell-derived induced pluripotent stem cells (TiPSCs) for subsequent application in adoptive cancer immunotherapy. Methods: In this study iPSCs were derived from peripheral blood T cells using Sendai virus vectors expressing Oct4, Sox2, Klf4 and c-Myc. Pluripotent characteristics of TiPSCs were examined and confirmed with alkaline phosphatase staining, immunocytochemistry and RT-PCR analysis. For NK cell differentiation, embryoid bodies (EB) formed from (TiPSCs) were cultured in xenogeneic serum-free medium containing human serum, IL-3, IL-7, IL-15, SCF, FLT3L without using M210-B4 and AFT-024 stromal feeder cells. After differentiation, NK cells were characterized with immunofluorescence analysis, flow cytometry and cytotoxicity assay. Results: Here, we for the first time demonstrate that TiPSCs can effectively differentiate into functionally active NK cells without M210-B4 and AFT-024 xenogeneic stroma cells. Immunofluorescence and flow cytometry analysis showed that EB-derived cells can differentiate into a homogeneous population of NK cell expressing high levels of CD56, CD45 and CD16 specific markers. Moreover, these cells significantly express killing activation receptors such as NKp44 and NKp46. In the comparative analysis, we observed that NK cells derived using feeder-free culture system have more high killing activity against K-562 tumor cells, than NK cells derived by feeder-dependent method. Thus, we think that our obtained data will be useful for the development of large-scale production of NK cells for translation into cancer immunotherapy.

Keywords: induced pluripotent stem cells, NK cells, T cells, cell diffentiation, feeder cell-free culture system

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Authors: Syed Dawood Md. Taimur, Md. Hasanur Rahman, Syeda Fahmida Afrin, Farzana Islam

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The concept of myocardial injury, although first recognized from animal studies, is now recognized as a clinical phenomenon that may result in microvascular damage, no-reflow phenomenon, myocardial stunning, myocardial hibernation and ischemic preconditioning. The final consequence of this event is left ventricular (LV) systolic dysfunction leading to increased morbidity and mortality. The typical clinical case of reperfusion injury occurs in acute myocardial infarction (MI) with ST segment elevation in which an occlusion of a major epicardial coronary artery is followed by recanalization of the artery. This may occur either spontaneously or by means of thrombolysis and/or by primary percutaneous coronary intervention (PCI) with efficient platelet inhibition by aspirin (acetylsalicylic acid), clopidogrel and glycoprotein IIb/IIIa inhibitors. In recent years, percutaneous coronary intervention (PCI) has become a well-established technique for the treatment of coronary artery disease. PCI improves symptoms in patients with coronary artery disease and it has been increasing the safety of procedures. However, peri- and post-procedural myocardial injury, including angiographical slow coronary flow, microvascular embolization, and elevated levels of cardiac enzyme, such as creatine kinase and troponin-T and -I, has also been reported even in elective cases. Furthermore, myocardial reperfusion injury at the beginning of myocardial reperfusion, which causes tissue damage and cardiac dysfunction, may occur in cases of the acute coronary syndrome. Because patients with myocardial injury is related to larger myocardial infarction and have a worse long-term prognosis than those without myocardial injury, it is important to prevent myocardial injury during and/or after PCI in patients with coronary artery disease. To date, many studies have demonstrated that adjunctive pharmacological treatment suppresses myocardial injury and increases coronary blood flow during PCI procedures. In this review, we highlight the usefulness of pharmacological treatment in combination with PCI in attenuating myocardial injury in patients with coronary artery disease.

Keywords: coronary artery disease, percutaneous coronary intervention, myocardial injury, pharmacology

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Authors: Gusa Hall, Barrie Keeler, Achal Khanna

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Introduction: NICE guidelines have highlighted the consequences of IV fluid mismanagement. The main aim of this study was to audit fluid prescribing post laparotomies to identify if fluids were prescribed in accordance to NICE guidelines. Methodology: Retrospective database search of eight specific laparotomy procedures (colectomy right and left, Hartmann’s procedure, small bowel resection, perforated ulcer, abdominal perineal resection, anterior resection, pan proctocolectomy, subtotal colectomy) highlighted 29 laparotomies between April 2019 and May 2019. Two of 29 patients had secondary procedures during the same admission, n=27 (patients). Database case notes were reviewed for date of procedure, length of admission, fluid prescribed and amount, nasal gastric tube output, daily bloods results for electrolytes sodium and potassium and operational losses. Results: n=27 based on 27 identified patients between April 2019 – May 2019, 93% (25/27) received IV fluids, only 19% (5/27) received the correct IV fluids in accordance to NICE guidelines, 93% (25/27) who received IV fluids had the correct electrolytes levels (sodium & potassium), 100% (27/27) patients received blood tests (U&E’s) for correct electrolytes levels. 0% (0/27) no documentation on operational losses. IV fluids matched nasogastric tube output in 100% (3/3) of the number of patients that had a nasogastric tube in situ. Conclusion: A PubMed database literature review on barriers to safer IV prescribing highlighted educational interventions focused on prescriber knowledge rather than how to execute the prescribing task. This audit suggests IV fluids post laparotomies are not being prescribed consistently in accordance to NICE guidelines. Surgical management plans should be clearer on IV fluids and electrolytes requirements for the following 24 hours after the plan has been initiated. In addition, further teaching and training around IV prescribing is needed together with frequent surgical audits on IV fluid prescribing post-surgery to evaluate improvements.

Keywords: audit, IV Fluid prescribing, laparotomy, NICE guidelines

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Authors: Nicholas Bayfield, Liam Bibo, Charley Budgeon, Robert Larbalestier, Tom Briffa

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Introduction: Stress hyperglycaemia is common following cardiac surgery. Its optimal management is uncertain and may differ by diabetic status. This study assesses the in-hospital glycaemic management of cardiac surgery patients and associated postoperative outcomes. Methods: A retrospective cohort analysis of all patients undergoing cardiac surgery at Fiona Stanley Hospital from February 2015 to May 2019 was undertaken. Management and outcomes of hyperglycaemia following cardiac surgery were assessed. Follow-up was assessed to 1 year postoperatively. Multivariate regression modelling was utilised. Results: 1050 non-diabetic patients and 689 diabetic patients were included. In the non-diabetic cohort, patients with mild (peak blood sugar level [BSL] < 14.3), transient stress hyperglycaemia managed without insulin were not at an increased risk of wound-related morbidity (P=0.899) or mortality at 1 year (P=0.483). Insulin management was associated with wound-related readmission to hospital (P=0.004) and superficial sternal wound infection (P=0.047). Prolonged or severe stress hyperglycaemia was predictive of hospital re-admission (P=0.050) but not morbidity or mortality (P=0.546). Diabetes mellitus was an independent risk factor 1-year mortality (OR; 1.972 [1.041–3.736], P=0.037), graft harvest site wound infection (OR; 1.810 [1.134–2.889], P=0.013) and wound-related readmission (OR; 1.866 [1.076–3.236], P=0.026). In diabetics, postoperative peak BSL > 13.9mmol/L was predictive of graft harvest site infections (OR; 3.528 [1.724-7.217], P=0.001) and wound-related readmission OR; 3.462 [1.540-7.783], P=0.003) regardless of modality of management. A peak BSL of 10.0-13.9 did not increase the risk of morbidity/mortality compared to a peak BSL of < 10.0 (P=0.557). Diabetics with a peak BSL of 13.9 or less did not have significantly increased morbidity/mortality outcomes compared to non-diabetics (P=0.418). Conclusion: In non-diabetic patients, transient mild stress hyperglycaemia following cardiac surgery does not uniformly require treatment. In diabetic patients, postoperative hyperglycaemia with peak BSL exceeding 13.9mmol/L was associated with wound-related morbidity and hospital readmission following cardiac surgery.

Keywords: cardiac surgery, pulmonary embolism, pulmonary embolectomy, cardiopulmonary bypass

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Authors: Reza Safdari, Goli Arji, Robab Abdolkhani Maryam zahmatkeshan

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Background and purpose: Cardiovascular diseases are among the most common diseases in all societies. The most important step in minimizing myocardial infarction and its complications is to minimize its risk factors. The amount of medical data is increasingly growing. Medical data mining has a great potential for transforming these data into information. Using data mining techniques to generate predictive models for identifying those at risk for reducing the effects of the disease is very helpful. The present study aimed to collect data related to risk factors of heart infarction from patients’ medical record and developed predicting models using data mining algorithm. Methods: The present work was an analytical study conducted on a database containing 350 records. Data were related to patients admitted to Shahid Rajaei specialized cardiovascular hospital, Iran, in 2011. Data were collected using a four-sectioned data collection form. Data analysis was performed using SPSS and Clementine version 12. Seven predictive algorithms and one algorithm-based model for predicting association rules were applied to the data. Accuracy, precision, sensitivity, specificity, as well as positive and negative predictive values were determined and the final model was obtained. Results: five parameters, including hypertension, DLP, tobacco smoking, diabetes, and A+ blood group, were the most critical risk factors of myocardial infarction. Among the models, the neural network model was found to have the highest sensitivity, indicating its ability to successfully diagnose the disease. Conclusion: Risk prediction models have great potentials in facilitating the management of a patient with a specific disease. Therefore, health interventions or change in their life style can be conducted based on these models for improving the health conditions of the individuals at risk.

Keywords: decision trees, neural network, myocardial infarction, Data Mining

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Authors: Mohd Asharf Ganie, Aafia Rashid, Mohd Afzal Zargar, Showkat Ali Zargar, Syed Mudasar, Tabasum Parvaiz, Zafar Amin Shah

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Accumulating evidence suggests that Vitamin D deficiency (VDD) might at least contribute to the metabolic co-morbidities in PCOS. Hence, we aimed to study the effect of vitamin D supplementation in co-prescription with insulin sensitizers like metformin and pioglitazone on clinical, hormonal and metabolic parameters in women with PCOS. In this open label randomized, controlled trial a total of 120 women with PCOS diagnosis (AE-PCOS 2009 Criteria) were assigned to four treatment groups (n= 30 in each): group I (metformin 1 gm/day in combination with cholecalciferol 4000 IU/day), group II (pioglitazone 30 mg/day in combination with cholecalciferol 4000 IU/day), group III (metformin 1 gm /day) and group IV (pioglitazone 30 mg/day). Vitamin D supplementation was given as 60,000 units every two weeks for 24 weeks. All the subjects were routinely evaluated for clinical, biochemical, hormonal and insulin sensitivity parameters in addition to various safety parameters especially serum calcium levels at baseline and after 24 weeks of the treatment. Our results indicate that 95.5% of PCOS women were vitamin D deficient at baseline. Serum 25 (OH) D levels increased significantly (p < 0.001) in groups I and II without any adverse effects after 24 weeks of oral administration of 4000 IU cholecalciferol daily. However, serum 25 (OH) D levels remained unchanged in group III and IV. By six months, number of menstrual cycles per year increased whereas Ferriman-Gallwey score, serum total testosterone and HOMA-IR decreased significantly (P < 0.001) in the treatment groups supplemented with cholecalciferol as compared to those treated either drug alone. No significant beneficial changes were observed on weight, BMI, blood pressure, glucose tolerance and serum lipids in any of the groups supplemented with cholecalciferol. We conclude that daily dose of 4000 IU cholecalciferol might be a useful adjunct in complex treatment of PCOS with fewer adverse events. Furthermore, pioglitazone and cholecalciferol combination seems to be marginally better although there was no statistical significance.

Keywords: PCOS, vitamin D supplementation, insulin resistance, spironolactone, metformin, pioglitazone

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Authors: Nicole Ramlachan, Samuel Mark West

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Lung cancer is the leading cause of cancer-associated deaths in North America, with the vast majority being non-small cell lung cancer (NSCLC), with a five-year survival rate of only 24%. Non-invasive discovery of biomarkers associated with early-diagnosis of NSCLC can enable precision oncology efforts using liquid biopsy-based multiomics profiling of plasma. Although tissue biopsies are currently the gold standard for tumor profiling, this method presents many limitations since these are invasive, risky, and sometimes hard to obtain as well as only giving a limited tumor profile. Blood-based tests provides a less-invasive, more robust approach to interrogate both tumor- and non-tumor-derived signals. We intend to examine 30 stage III-IV NSCLC patients pre-surgery and collect plasma samples.Cell-free DNA (cfDNA) will be extracted from plasma, and next-generation sequencing (NGS) performed. Through the analysis of tumor-specific alterations, including single nucleotide variants (SNVs), insertions, deletions, copy number variations (CNVs), and methylation alterations, we intend to identify tumor-derived DNA—ctDNA among the total pool of cfDNA. This would generate data to be used as an accurate form of cancer genotyping for diagnostic purposes. Using liquid biopsies offer opportunities to improve the surveillance of cancer patients during treatment and would supplement current diagnosis and tumor profiling strategies previously not readily available in Trinidad and Tobago. It would be useful and advantageous to use this in diagnosis and tumour profiling as well as to monitor cancer patients, providing early information regarding disease evolution and treatment efficacy, and reorient treatment strategies in, timethereby improving clinical oncology outcomes.

Keywords: genomics, multiomics, clinical genetics, genotyping, oncology, diagnostics

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Authors: Annika Stechemesser, Rachel Pounds, Emma Lucas, Chris Dawson, Julia Lipecki, Pavle Vrljicak, Jan Brosens, Sean Kehoe, Jason Yap, Lawrence Young, Sascha Ott

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Advances in technology make it now possible to retrieve the genetic information of thousands of single cancerous cells. One of the key challenges in single cell analysis of cancerous tissue is to determine the number of different cell types and their characteristic genes within the sample to better understand the tumors and their reaction to different treatments. For this analysis to be possible, it is crucial to filter out background noise as it can severely blur the downstream analysis and give misleading results. In-depth analysis of the state-of-the-art filtering methods for single cell data showed that they do, in some cases, not separate noisy and normal cells sufficiently. We introduced an algorithm that filters and clusters single cell data simultaneously without relying on certain genes or thresholds chosen by eye. It detects communities in a Shared Nearest Neighbor similarity network, which captures the similarities and dissimilarities of the cells by optimizing the modularity and then identifies and removes vertices with a weak clustering belonging. This strategy is based on the fact that noisy data instances are very likely to be similar to true cell types but do not match any of these wells. Once the clustering is complete, we apply a set of evaluation metrics on the cluster level and accept or reject clusters based on the outcome. The performance of our algorithm was tested on three datasets and led to convincing results. We were able to replicate the results on a Peripheral Blood Mononuclear Cells dataset. Furthermore, we applied the algorithm to two samples of ovarian cancer from the same patient before and after chemotherapy. Comparing the standard approach to our algorithm, we found a hidden cell type in the ovarian postchemotherapy data with interesting marker genes that are potentially relevant for medical research.

Keywords: cancer research, graph theory, machine learning, single cell analysis

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Authors: F. Saleh, F. Lyall, A. Abdulsid, L. Marks

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Background: Labour in human is a complex biological process that involves interactions of neurological, hormonal and inflammatory pathways, with the placenta being a key regulator of these pathways. It is known that uterine contractions and labour pain cause physiological changes in gene expression in maternal and fetal blood, and in placenta during labour. Oxidative and inflammatory stress pathways are implicated in labour and they may cause alteration of placental gene expression. Additionally, in placental tissues, labour increases the expression of genes involved in placental oxidative stress, inflammatory cytokines, angiogenic regulators and apoptosis. Recently, Hydrogen Sulphide (H2S) has been considered as an endogenous gaseous mediator which promotes vasodilation and exhibits cytoprotective anti-inflammatory properties. The endogenous H2S is synthesised predominantly by two enzymes: cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE). As the H2S pathway has anti-oxidative and anti-inflammatory characteristics thus, we hypothesised that the expression of CBS and CSE in placental tissues would alter during labour. Methods: CBS and CSE expressions were examined in placentas using western blotting and RT-PCR in inner, middle and outer placental zones in placentas obtained from healthy non labouring women who delivered by caesarian section. These were compared with the equivalent zone of placentas obtained from women who had uncomplicated labour and delivered vaginally. Results: No differences in CBS and CSE mRNA or protein levels were found between the different sites within placentas in either the labour or non-labour group. There were no significant differences in either CBS or CSE expression between the two groups at the inner site and middle site. However, at the outer site there was a highly significant decrease in CBS protein expression in the labour group when compared to the non-labour group (p = 0.002). Conclusion: To the best of author’s knowledge, this is the first report to suggest that, CBS is expressed in a spatial manner within the human placenta. Further work is needed to clarify the precise function and mechanism of this spatial regulation although it is likely that inflammatory pathways regulation is a complex process in which this plays a role.

Keywords: anti-inflammatory, hydrogen sulphide, labour, oxidative stress

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Authors: Kirsten Wilson, Patrick M. Brauer, Sandra Babic, Diana Golubeva, Jessica Van Eyk, Tinya Wang, Avanti Karkhanis, Tim A. Le Fevre, Andy I. Kokaji, Allen C. Eaves, Sharon A. Louis, , Nooshin Tabatabaei-Zavareh

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Long-lived plasma cells are rare, non-proliferative B cells generated from antibody-secreting cells (ASCs) following an immune response to protect the host against pathogen re-exposure. Despite their therapeutic potential, the lack of in vitro protocols in the field makes it challenging to use B cells as a cellular therapeutic tool. As a result, there is a need to establish robust and reproducible methods for the generation of B cells. To address this, we have developed a culture system for generating B cells from hematopoietic stem and/or progenitor cells (HSPCs) derived from human umbilical cord blood (CB) or pluripotent stem cells (PSCs). HSPCs isolated from CB were cultured using the StemSpan™ B Cell Generation Kit and produced CD19+ B cells at a frequency of 23.2 ± 1.5% and 59.6 ± 2.3%, with a yield of 91 ± 11 and 196 ± 37 CD19+ cells per input CD34+ cell on culture days 28 and 35, respectively (n = 50 - 59). CD19+IgM+ cells were detected at a frequency of 31.2 ± 2.6% and were produced at a yield of 113 ± 26 cells per input CD34+ cell on culture day 35 (n = 50 - 59). The B cell receptor loci of CB-derived B cells were sequenced to confirm V(D)J gene rearrangement. ELISpot analysis revealed that ASCs were generated at a frequency of 570 ± 57 per 10,000 day 35 cells, with an average IgM+ ASC yield of 16 ± 2 cells per input CD34+ cell (n = 33 - 42). PSC-derived HSPCs were generated using the STEMdiff™ Hematopoietic - EB reagents and differentiated to CD10+CD19+ B cells with a frequency of 4 ± 0.8% after 28 days of culture (n = 37, 1 embryonic and 3 induced pluripotent stem cell lines tested). Subsequent culture of PSC-derived HSPCs increased CD19+ frequency and generated ASCs from 1 - 2 iPSC lines. This method is the first report of a serum- and feeder-free system for the generation of B cells from CB and PSCs, enabling further B lineage-specific research for potential future clinical applications.

Keywords: stem cells, B cells, immunology, hematopoiesis, PSC, differentiation

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