Search results for: gastric cancer surgery

Authors: William Elnemer, Nauman Hussain, Samir Al-Ali, Henry Shu, Diane Ghanem, Babar Shafiq

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Introduction: The incidence of infection in open tibial shaft injuries varies depending on the severity of the injury, with rates ranging from 1.8% for Gustilo-Anderson type I to 42.9% for type IIIB fractures. The timely administration of antibiotics upon presentation to the emergency department (ED) is an essential component of fracture management, and evidence indicates that prompt delivery of antibiotics is associated with improved outcomes. The objective of this study is to identify factors that contribute to the expedient administration of antibiotics. Methods: This is a retrospective study of open tibial shaft fractures at an academic Level I trauma center. Current Procedural Terminology (CPT) codes identified all patients treated for open tibial shaft fractures between 2015 and 2021. Open fractures were identified by reviewing ED and provider notes, and with ballistic fractures were considered open. Chart reviews were performed to extract demographics, fracture characteristics, postoperative outcomes, time to operative room, time to antibiotic order, and delivery. Univariate statistical analysis compared patients who received early antibiotics (EA), which were delivered within one hour of ED presentation, and those who received late antibiotics (LA), which were delivered outside of one hour of ED presentation. A multivariate analysis was performed to investigate patient, fracture, and transport/ED characteristics contributing to faster delivery of antibiotics. The multivariate analysis included the dependent variables: ballistic fracture, activation of Delta Trauma, Gustilo-Andersen (Type III vs. Type I and II), AO-OTA Classification (Type C vs. Type A and B), arrival between 7 am and 11 pm, and arrival via Emergency Medical Services (EMS) or walk-in. Results: Seventy ED patients with open tibial shaft fractures were identified. Of these, 39 patients (55.7%) received EA, while 31 patients (44.3%) received LA. Univariate analysis shows that the arrival via EMS as opposed to walk-in (97.4% vs. 74.2%, respectively, p = 0.01) and activation of Delta Trauma (89.7% vs. 51.6%, respectively, p < 0.001) was significantly higher in the EA group vs. the LA group. Additionally, EA cases had significantly shorter intervals between the antibiotic order and delivery when compared to LA cases (0.02 hours vs. 0.35 hours, p = 0.007). No other significant differences were found in terms of postoperative outcomes or fracture characteristics. Multivariate analysis shows that a Delta Trauma Response, arrival via EMS, and presentation between 7 am and 11 pm were independent predictors of a shorter time to antibiotic administration (Odds Ratio = 11.9, 30.7, and 5.4, p = 0.001, 0.016, and 0.013, respectively). Discussion: Earlier antibiotic delivery is associated with arrival to the ED between 7 am and 11 pm, arrival via EMS, and a coordinated Delta Trauma activation. Our findings indicate that in cases where administering antibiotics is critical to achieving positive outcomes, it is advisable to employ a coordinated Delta Trauma response. Hospital personnel should be attentive to the rapid administration of antibiotics to patients with open fractures who arrive via walk-in or during late-night hours.

Keywords: antibiotics, emergency department, fracture management, open tibial shaft fractures, orthopaedic surgery, time to or, trauma fractures

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Authors: Idowu R. Akomolafe, Naven Chetty

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Background: The widespread medical application of ionizing radiation has raised public concern about radiation exposure and, thus, associated cancer risk. The production of reactive oxygen species and free radicals as a result of radiation exposure can cause severe damage to deoxyribonucleic acid (DNA) of cells, thus leading to biological effect. Radiotherapy is an excellent modality in the treatment of cancerous cells, comes with a few challenges. A significant challenge is the exposure of healthy cells surrounding the tumour to radiation. The last few decades have witnessed lots of attention shifted to plants, herbs, and natural product as an alternative to synthetic compound for radioprotection. Thus, the study investigated the radioprotective efficacy of Costus afer against whole-body radiation-induced haematological, histopathological disorder in mice. Materials and Method: Fifty-four mice were randomly divided into nine groups. Animals were pretreated with the extract of Costus afer by oral gavage for six days before irradiation. Control: 6 mice received feed and water only; 6 mice received feed, water, and 3Gy; 6 mice received feed, water, and 6Gy; experimental: 6 mice received 250 mg/kg extract; 6 mice received 500 mg/kg extract; 6 mice received 250 mg/kg extract and 3Gy; 6 mice received 500 mg/kg extract and 3Gy; 6 mice received 250 mg/kg extract and 6Gy; 6 mice received 500 mg/kg extract and 6Gy in addition to feeding and water. The irradiation was done at the Radiotherapy and Oncology Department of Grey's Hospital using linear accelerator (LINAC). Thirty-six mice were sacrificed by cervical dislocation 48 hours after irradiation, and blood was collected for haematology tests. Also, the liver and kidney of the sacrificed mice were surgically removed for histopathology tests. The remaining eighteen (18) mice were used for mortality and survival studies. Data were analysed by one-way ANOVA, followed by Tukey's multiple comparison test. Results: Prior administration of Costus afer extract decreased the symptoms of radiation sickness and caused a significant delay in the mortality as demonstrated in the experimental mice. The first mortality was recorded on day-5 post irradiation, and this happened to the group E- that is, mice that received 6Gy but no extract. There was significant protection in the experimental mice, as demonstrated in the blood counts against hematopoietic and gastrointestinal damage when compared with the control. The protection was seen in the increase in blood counts of experimental animals and the number of survivor. The protection offered by Costus afer may be due to its ability to scavenge free radicals and restore gastrointestinal and bone marrow damage produced by radiation. Conclusions: The study has demonstrated that exposure of mice to radiation could cause modifications in the haematological and histopathological parameters of irradiated mice. However, the changes were relieved by the methanol extract of Costus afer, probably through its free radical scavenging and antioxidant properties.

Keywords: costus afer, hematological, mortality, radioprotection, radiotherapy

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Authors: Vivian Caroline Koerbel Dombrowski

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Armed conflicts have always meant the ultimate expression of power and at the same time, lack of understanding among nations. Cities were destroyed, people were killed, assets were devastated. But these are not only the loss of a war: the environmental damage comes to be considered immeasurable losses in the short, medium and long term. And this is because no nation wants to bear that cost. They invest in military equipment, training, technical equipment but the environmental account yet finds gaps in international law. Considering such a generalization in rights protection, many nations are at imminent danger in a conflict if the water will be used as a mass weapon, especially if we consider important rivers such as Jordan, Euphrates and Nile. The top three international documents were analyzed on the subject: the Stockholm Convention (1972), Additional Protocol I to the Geneva Convention (1977) and the Rome Statute (1998). Indeed, some references are researched in doctrine, especially scientific articles, to substantiate with consistent data about the extent of the damage, historical factors and decisions which have been successful. However, due to the lack of literature about this subject, the research tends to be exhaustive. From the study of the indicated material, it was noted that international law - humanitarian and environmental - calls in some of its instruments the environmental protection in war conflicts, but they are generic and vague rules that do not define exactly what is the environmental damage , nor sets standards for measure them. Taking into account the mains conflicts of the century XX: World War II, the Vietnam War and the Gulf War, one must realize that the environmental consequences were of great rides - never deactivated landmines, buried nuclear weapons, armaments and munitions destroyed in the soil, chemical weapons, not to mention the effects of some weapons when used (uranium, agent Orange, etc). Extending the search for more recent conflicts such as Afghanistan, it is proven that the effects on health of the civilian population were catastrophic: cancer, birth defects, and deformities in newborns. There are few reports of nations that, somehow, repaired the damage caused to the environment as a result of the conflict. In the pitch of contemporary conflicts, many nations fear that water resources are used as weapons of mass destruction, because once contaminated - directly or indirectly - can become a means of disguised genocide side effect of military objective. In conclusion, it appears that the main international treaties governing the subject mention the concern for environmental protection, however leave the normative specifications vacancies necessary to effectively there is a prevention of environmental damage in armed conflict and, should they occur, the repair of the same. Still, it appears that there is no protection mechanism to safeguard natural resources and avoid them to become a mass destruction weapon.

Keywords: armed conflicts, criminal liability, environmental damages, humanitarian law, mass weapon

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Authors: Nguyen J. M., Lucas G., Ruan S., Digonnet H., Antonioli D.

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Introduction: Deep Learning (DL) is a very powerful tool for analyzing image data. But for tabular data, it cannot compete with machine learning methods like XGBoost. The research question becomes: can tabular data be transformed into images that can be analyzed by simple CNNs (Convolutional Neuron Networks)? Will DL be the absolute tool for data classification? All current solutions consist in repositioning the variables in a 2x2 matrix using their correlation proximity. In doing so, it obtains an image whose pixels are the variables. We implement a technology, DeepNIC, that offers the possibility of obtaining an image for each variable, which can be analyzed by simple CNNs. Material and method: The 'ROP' (Regression OPtimized) model is a binary and atypical decision tree whose nodes are managed by a new artificial neuron, the Neurop. By positioning an artificial neuron in each node of the decision trees, it is possible to make an adjustment on a theoretically infinite number of variables at each node. From this new decision tree whose nodes are artificial neurons, we created the concept of a 'Random Forest of Perfect Trees' (RFPT), which disobeys Breiman's concepts by assembling very large numbers of small trees with no classification errors. From the results of the RFPT, we developed a family of 10 statistical information criteria, Nguyen Information Criterion (NICs), which evaluates in 3 dimensions the predictive quality of a variable: Performance, Complexity and Multiplicity of solution. A NIC is a probability that can be transformed into a grey level. The value of a NIC depends essentially on 2 super parameters used in Neurops. By varying these 2 super parameters, we obtain a 2x2 matrix of probabilities for each NIC. We can combine these 10 NICs with the functions AND, OR, and XOR. The total number of combinations is greater than 100,000. In total, we obtain for each variable an image of at least 1166x1167 pixels. The intensity of the pixels is proportional to the probability of the associated NIC. The color depends on the associated NIC. This image actually contains considerable information about the ability of the variable to make the prediction of Y, depending on the presence or absence of other variables. A basic CNNs model was trained for supervised classification. Results: The first results are impressive. Using the GSE22513 public data (Omic data set of markers of Taxane Sensitivity in Breast Cancer), DEEPNic outperformed other statistical methods, including XGBoost. We still need to generalize the comparison on several databases. Conclusion: The ability to transform any tabular variable into an image offers the possibility of merging image and tabular information in the same format. This opens up great perspectives in the analysis of metadata.

Keywords: tabular data, CNNs, NICs, DeepNICs, random forest of perfect trees, classification

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Authors: Angela Evans, Gabriel Gijon-Nogueron, Alfonso Martinez-Nova

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Background The health sector, whose mission is protecting health, also contributes to the climate crisis, the greatest health threat of the 21st century. The carbon footprint from healthcare exceeds 5% of emissions globally, surpassing 7% in the USA and Australia. Global recognition has led to the Paris Agreement, the United Nations Sustainable Development Goals, and the World Health Organization's Climate Change Action Plan. It is agreed that the majority of health impacts stem from energy and resource consumption, as well as the production of greenhouse gases in the environment and deforestation. Many professional medical associations and healthcare providers advocate for their members to take the lead in environmental sustainability. Objectives To avail and expand ‘Green Podiatry’ via the three pillars of: Exercise ; Evidence ; Everyday changes; to highlight the benefits of physical activity and exercise for both human health and planet health. Walking and running are beneficial for health, provide low carbon transport, and have evidence-based health benefits. Podiatrists are key healthcare professionals in the physical activity space and can influence and guide their patients to increase physical activity and avert the many non-communicable diseases that are decimating public health, eg diabetes, arthritis, depression, cancer, obesity. Methods Publications, conference presentations, and pilot projects pertinent to ‘Green Podiatry’ have been activated since 2021, and a survey of podiatrist’s knowledge and awareness has been undertaken.The survey assessed attitudes towards environmental sustainability in work environment. The questions addressed commuting habits, hours of physical exercise per week, and attitudes in the clinic, such as prescribing unnecessary treatments or emphasizing sports as primary treatment. Results Teaching and Learning modules have been developed for podiatric medicine students and graduates globally. These will be availed. A pilot foot orthoses recycling project has been undertaken and will be reported, in addition to established footwear recycling. The preliminary survey found almost 90% of respondents had no knowledge of green podiatry or footwear recycling. Only 30% prescribe sports/exercise as the primary treatment for patients, and 45% do not to prescribe unnecessary treatments. Conclusions Podiatrists are in a good position to lead in the crucial area of healthcare and climate change implications. Sufficient education of podiatrists is essential for the profession to beneficially promote health and physical activity, which is beneficial for the health of all peoples and all communities.

Keywords: climate change, gait, green, healthcare, sustainability

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Authors: Apurva Singh, S. P. Jaiswar, Apala Priyadarshini, Akancha Pandey

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Objective: The aim of this study is to find the association of PON1 gene polymorphism with pesticides In RPL subjects. Background: Recurrent pregnancy loss (RPL) is defined as three or more sequential abortions before the 20th week of gestation. Pesticides and its derivatives (organochlorine and organophosphate) are proposed to accommodate a ruler chemical for RPL in the sub-humid region of India. The paraoxonase-1 enzyme (PON1) plays an important role in the toxicity of some organophosphate pesticides, with low PON1 activity being associated with higher pesticide sensitivity Methodology: This is a case-control study done in Department of Obstetrics & Gynaecology & Department of Biochemistry, K.G.M.U, Lucknow, India. The subjects were enrolled after fulfilling the inclusion & exclusion criteria. Inclusion criteria: Cases- Subject having two or more spontaneous abortions & Control- Healthy female having one or more alive child was selected. Exclusion criteria: Cases & Control- Subject having the following disease will be excluded from the study Diabetes mellitus, Hypertension, Tuberculosis, Immunocompromised patients, any endocrine disorder and genital, colon or breast cancer any other malignancies. Blood samples were collected in EDTA tubes from cases & healthy control women & genomic DNA was extracted by phenol-chloroform method. The estimation of pesticides residue from blood was done by HPLC. Biochemical estimation was also performed. Genotyping of PON1 gene polymorphism was performed by RFLP. Statistical analysis of the data was performed using the SPSS16.3 software. Results: A sum of total 14 pesticides (12 organochlorine and 2 organophosphate) selected on the basis of their persistent nature and consumption rate. The significant level of pesticide (ppb) estimated by the Mann whiney test and it was found to be significant at higher level of β-HCH (p:0.04), γ-HCH (p:0.001), δ-HCH (p: 0.002), chloropyrifos (p:0.001), pp-DDD (p:0.001) and fenvalrate (p: 0.001) in case group compare to its control. The level of antioxidant enzymes were found to be significantly decreased among the cases. Wild homozygous TT was more frequent and prevalent among control groups. However, heterozygous group (Tt) was more in cases than control groups (CI-0.3-1.3) (p=0.06). Conclusion: Higher levels of pesticides with endocrine disrupting potential in cases indicate the possible role of these compounds as one of the causes of recurrent pregnancy loss. Possibly, increased pesticide level appears to indicate increased levels of oxidative damage that has been associated with the possible cause of Recurrent Miscarriage, it may reflect indirect evidence of toxicity rather than the direct cause. Since both factors are reported to increase risk, individuals with higher levels of these 'Toxic compounds' especially in 'high-risk genotypes' might be more susceptible to recurrent pregnancy loss.

Keywords: paraoxonase, pesticides, PON1, RPL

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Authors: Yang Yang, Luciana Magalhães Rebelo Alencar, Martha Sahylí Ortega Pijeira, Beatriz da Silva Batista, Alefe Roger Silva França, Erick Rafael Dias Rates, Ruana Cardoso Lima, Sara Gemini-Piperni, Ralph Santos-Oliveira

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Radium-²²³ dichloride ([²²³Rₐ]RₐCl₂) is an alpha particle-emitting radiopharmaceutical currently approved for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases, and no known visceral metastatic disease. [²²³Rₐ]RₐCl₂ is bone-seeking calcium mimetic that bonds into the newly formed bone stroma, especially osteoblastic or sclerotic metastases, killing the tumor cells by inducing DNA breaks in a potent and localized manner. Nonetheless, the successful therapy of osteosarcoma as primary bone tumors is still a challenge. Nanomicelles are colloidal nanosystems widely used in drug development to improve blood circulation time, bioavailability, and specificity of therapeutic agents, among other applications. In addition, the enhanced permeability and retention effect of the nanosystems, and the renal excretion of the nanomicelles reported in most cases so far, are very attractive to achieve selective and increased accumulation in tumor site as well as to increase the safety of [²²³Rₐ]RₐCl₂ in the clinical routine. In the present work, [²²³Rₐ]RₐCl₂ nanomicelles were produced, characterized, in vitro evaluated, and compared with pure [²²³Rₐ]RₐCl2 solution using SAOS2 osteosarcoma cells. The [²²³Rₐ]RₐCl₂ nanomicelles were prepared using the amphiphilic copolymer Pluronic F127. The dynamic light scattering analysis of freshly produced [²²³Rₐ]RₐCl₂ nanomicelles demonstrated a mean size of 129.4 nm with a polydispersity index (PDI) of 0.303. After one week stored in the refrigerator, the mean size of the [²²³Rₐ]RₐCl₂ nanomicelles increased to 169.4 with a PDI of 0.381. Atomic force microscopy analysis of [223Rₐ]RₐCl₂ nanomicelles exhibited spherical structures whose heights reach 1 µm, suggesting the filling of 127-Pluronic nanomicelles with [²²³Rₐ]RₐCl₂. The viability assay with [²²³Rₐ]RₐCl₂ nanomicelles displayed a dose-dependent response as it was observed using pure [²²³Rₐ]RₐCl2. However, at the same dose, [²²³Rₐ]RₐCl₂ nanomicelles were 20% higher efficient in killing SAOS2 cells when compared with pure [²²³Rₐ]RₐCl₂. These findings demonstrated the effectiveness of the nanosystem validating the application of nanotechnology in targeted alpha therapy with [²²³Ra]RₐCl₂. In addition, the [²²³Rₐ]RaCl₂nanomicelles may be decorated and incorporated with a great variety of agents and compounds (e.g., monoclonal antibodies, aptamers, peptides) to overcome the limited use of [²²³Ra]RₐCl₂.

Keywords: nanomicelles, osteosarcoma, radium dichloride, targeted alpha therapy

Procedia PDF Downloads 111

Authors: Sonia Butalia, Huong Luu, Alexis Guigue, Karen J. B. Martins, Khanh Vu, Scott W. Klarenbach

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Obesity-related health conditions impose a substantial economic burden on payers due to increased healthcare use. Estimates of healthcare resource use and costs associated with obesity-related comorbidities are needed to inform policies and interventions targeting these conditions. Methods: Adults living with obesity were identified (a procedure-related body mass index code for class 2/3 obesity between 2012 and 2019 in Alberta, Canada; excluding those with bariatric surgery), and outcomes were compared over 1-year (2019/2020) between those who had and did not have specific obesity-related comorbidities. The probability of using a healthcare service (based on the odds ratio of a zero [OR-zero] cost) was compared; 95% confidence intervals (CI) were reported. Logistic regression and a generalized linear model with log link and gamma distribution were used for total healthcare cost comparisons ($CDN); cost ratios and estimated cost differences (95% CI) were reported. Potential socio-demographic and clinical confounders were adjusted for, and incremental cost differences were representative of a referent case. Results: A total of 220,190 adults living with obesity were included; 44% had hypertension, 25% had osteoarthritis, 24% had type-2 diabetes, 17% had cardiovascular disease, 12% had insulin resistance, 9% had chronic back pain, and 4% of females had polycystic ovarian syndrome (PCOS). The probability of hospitalization, ED visit, and ambulatory care was higher in those with a following obesity-related comorbidity versus those without: chronic back pain (hospitalization: 1.8-times [OR-zero: 0.57 [0.55/0.59]] / ED visit: 1.9-times [OR-zero: 0.54 [0.53/0.56]] / ambulatory care visit: 2.4-times [OR-zero: 0.41 [0.40/0.43]]), cardiovascular disease (2.7-times [OR-zero: 0.37 [0.36/0.38]] / 1.9-times [OR-zero: 0.52 [0.51/0.53]] / 2.8-times [OR-zero: 0.36 [0.35/0.36]]), osteoarthritis (2.0-times [OR-zero: 0.51 [0.50/0.53]] / 1.4-times [OR-zero: 0.74 [0.73/0.76]] / 2.5-times [OR-zero: 0.40 [0.40/0.41]]), type-2 diabetes (1.9-times [OR-zero: 0.54 [0.52/0.55]] / 1.4-times [OR-zero: 0.72 [0.70/0.73]] / 2.1-times [OR-zero: 0.47 [0.46/0.47]]), hypertension (1.8-times [OR-zero: 0.56 [0.54/0.57]] / 1.3-times [OR-zero: 0.79 [0.77/0.80]] / 2.2-times [OR-zero: 0.46 [0.45/0.47]]), PCOS (not significant / 1.2-times [OR-zero: 0.83 [0.79/0.88]] / not significant), and insulin resistance (1.1-times [OR-zero: 0.88 [0.84/0.91]] / 1.1-times [OR-zero: 0.92 [0.89/0.94]] / 1.8-times [OR-zero: 0.56 [0.54/0.57]]). After fully adjusting for potential confounders, the total healthcare cost ratio was higher in those with a following obesity-related comorbidity versus those without: chronic back pain (1.54-times [1.51/1.56]), cardiovascular disease (1.45-times [1.43/1.47]), osteoarthritis (1.36-times [1.35/1.38]), type-2 diabetes (1.30-times [1.28/1.31]), hypertension (1.27-times [1.26/1.28]), PCOS (1.08-times [1.05/1.11]), and insulin resistance (1.03-times [1.01/1.04]). Conclusions: Adults with obesity who have specific disease-related health conditions have a higher probability of healthcare use and incur greater costs than those without specific comorbidities; incremental costs are larger when other obesity-related health conditions are not adjusted for. In a specific referent case, hypertension was costliest (44% had this condition with an additional annual cost of $715 [$678/$753]). If these findings hold for the Canadian population, hypertension in persons with obesity represents an estimated additional annual healthcare cost of $2.5 billion among adults living with obesity (based on an adult obesity rate of 26%). Results of this study can inform decision making on investment in interventions that are effective in treating obesity and its complications.

Keywords: administrative data, healthcare cost, obesity-related comorbidities, real world evidence

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Authors: Nir Nissim, Erez Shalom, Tomer Lancewiki, Yuval Elovici, Yuval Shahar

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Background: A Medical Device (MD) is an instrument, machine, implant, or similar device that includes a component intended for the purpose of the diagnosis, cure, treatment, or prevention of disease in humans or animals. Medical devices play increasingly important roles in health services eco-systems, including: (1) Patient Diagnostics and Monitoring; Medical Treatment and Surgery; and Patient Life Support Devices and Stabilizers. MDs are part of the medical device eco-system and are connected to the network, sending vital information to the internal medical information systems of medical centers that manage this data. Wireless components (e.g. Wi-Fi) are often embedded within medical devices, enabling doctors and technicians to control and configure them remotely. All these functionalities, roles, and uses of MDs make them attractive targets of cyber-attacks launched for many malicious goals; this trend is likely to significantly increase over the next several years, with increased awareness regarding MD vulnerabilities, the enhancement of potential attackers’ skills, and expanded use of medical devices. Significance: We propose to develop and implement Cyber-Med, a unique collaborative project of Ben-Gurion University of the Negev and the Clalit Health Services Health Maintenance Organization. Cyber-Med focuses on the development of a comprehensive detection framework that relies on a critical attack repository that we aim to create. Cyber-Med will allow researchers and companies to better understand the vulnerabilities and attacks associated with medical devices as well as providing a comprehensive platform for developing detection solutions. Methodology: The Cyber-Med detection framework will consist of two independent, but complementary detection approaches: one for known attacks, and the other for unknown attacks. These modules incorporate novel ideas and algorithms inspired by our team's domains of expertise, including cyber security, biomedical informatics, and advanced machine learning, and temporal data mining techniques. The establishment and maintenance of Cyber-Med’s up-to-date attack repository will strengthen the capabilities of Cyber-Med’s detection framework. Major Findings: Based on our initial survey, we have already found more than 15 types of vulnerabilities and possible attacks aimed at MDs and their eco-system. Many of these attacks target individual patients who use devices such pacemakers and insulin pumps. In addition, such attacks are also aimed at MDs that are widely used by medical centers such as MRIs, CTs, and dialysis engines; the information systems that store patient information; protocols such as DICOM; standards such as HL7; and medical information systems such as PACS. However, current detection tools, techniques, and solutions generally fail to detect both the known and unknown attacks launched against MDs. Very little research has been conducted in order to protect these devices from cyber-attacks, since most of the development and engineering efforts are aimed at the devices’ core medical functionality, the contribution to patients’ healthcare, and the business aspects associated with the medical device.

Keywords: medical device, cyber security, attack, detection, machine learning

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Authors: Edite Kulmane, Mara Pilmane, Romans Lacis

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Introduction: Acquired heart diseases remain one of the leading health care problems in the world. Changes in myocardium of the diseased hearts are complex and pathogenesis is still not fully clear. The aim of this study was to identify appearance and distribution of apoptosis, homeostasis regulating factors, and innervation and ischemia markers in right atrial tissue in different acquired heart diseases. Methods: During elective open heart surgery were taken right atrial tissue fragments from 12 patients. All patients were operated because of acquired heart diseases- aortic valve stenosis (5 patients), coronary heart disease (5 patients), coronary heart disease and secondary mitral insufficiency (1 patient) and mitral disease (1 patient). The mean age was (mean±SD) 70,2±7,0 years (range 58-83 years). The tissues were stained with haematoxylin and eosin methods for routine light-microscopical examination and for immunohistochemical detection of protein gene peptide 9.5 (PGP 9.5), human atrial natriuretic peptide (hANUP), vascular endothelial growth factor (VEGF), chromogranin A and endothelin. Apoptosis was detected by TUNEL method. Results: All specimens showed degeneration of cardiomyocytes with lysis of myofibrils, diffuse vacuolization especially in perinuclear region, different size of cells and their nuclei. The severe invasion of connective tissue was observed in main part of all fragments. The apoptotic index ranged from 24 to 91%. One specimen showed region of newly performed microvessels with cube shaped endotheliocytes that were positive for PGP 9.5, endothelin, chromogranin A and VEGF. From all fragments, taken from patients with coronary heart disease, there were observed numerous PGP 9.5-containing nerve fibres, except in patient with secondary mitral insufficiency, who showed just few PGP 9.5 positive nerves. In majority of specimens there were regions observed with cube shaped mixed -VEGF immunoreactive endocardial and epicardial cells. Only VEGF positive endothelial cells were observed just in few specimens. There was no significant difference of hANUP secreting cells among all specimens. All patients operated due to the coronary heart disease moderate to numerous number of chromogranin A positive cells were seen while in patients with aortic valve stenosis tissue demonstrated just few factor positive cells. Conclusions: Complex detection of different factors may indicate selectively disordered morphopathogenetical event of heart disease: decrease of PGP 9.5 nerves suggests the decreased innervation of organ; increased apoptosis indicates the cell death without ingrowth of connective tissue; persistent presence of hANUP proves the unchanged homeostasis of cardiomyocytes probably supported by expression of chromogranins. Finally, decrease of VEGF detects the regions of affected blood vessels in heart affected by acquired heart disease.

Keywords: heart, apoptosis, protein-gene peptide 9.5, atrial natriuretic peptide, vascular endothelial growth factor, chromogranin A, endothelin

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Authors: Antonio J. Melendez-Martinez

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Beyond their role as natural colorants, some carotenoids are provitamins A and may be involved in health-promoting biological actions and contribute to reducing the risk of developing non-communicable diseases, including several types of cancer, cardiovascular disease, eye conditions, skin disorders or metabolic disorders. Given the versatility of carotenoids, the COST-funded European network to advance carotenoid research and applications in agro-food and health (EUROCAROTEN) is aimed at promoting health through the diet and increasing well-being by means. Stakeholders from 38 countries participate in this network, and one of its main objectives is to promote research on little-studied carotenoids. In this contribution, recent advances of our research group and collaborators in the study of two such understudied carotenoids, namely phytoene and phytofluene, the colorless carotenoids, are outlined. The study of these carotenoids is important as they have been largely neglected despite they are present in our diets, fluids, and tissues, and evidence is accumulating that they may be involved in health-promoting actions. More specifically, studies on their levels in diverse tomato and orange varieties were carried out as well as on their potential bioavailability from different dietary sources. Furthermore, the potential effect of these carotenoids on an animal model subjected to oxidative stress was evaluated. The tomatoes were grown in research greenhouses, and some of them were subjected to regulated deficit irrigation, a sustainable agronomic practice. The citrus samples were obtained from an experimental field. The levels of carotenoids were assessed using HPLC according to routine methodologies followed in our lab. Regarding the potential bioavailability (bioaccessibility) studies, different products containing colorless carotenoids, like fruits, juices, were subjected to simulated in vitro digestions, and their incorporation into mixed micelles was assessed. The effect of the carotenoids on oxidative stress was evaluated on the Caenorhabditis elegans model. For that purpose, the worms were subjected to oxidative stress by means of a hydrogen peroxide challenge. In relation to the presence of colorless carotenoids in tomatoes and orange varieties, it was observed that they are widespread in such products and that there are mutants with very high quantities of them, for instance, the Cara Cara or Pinalate mutant oranges. The studies on their bioaccessibility revealed that, in general, phytoene and phytofluene are more bioaccessible than other common dietary carotenoids, probably due to their distinctive chemical structure. About the in vivo antioxidant capacity of phytoene and phytofluene, it was observed that they both exerted antioxidant effects at certain doses. In conclusion, evidence on the importance of phytoene and phytofluene as dietary easily bioavailable and antioxidant carotenoids has been obtained in recent studies from our group, which can be important shortly to innovate in health-promotion through the development of functional foods and related products.

Keywords: carotenoids, health, functional foods, nutrition, phytoene, phytofluene

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Authors: Delphine Morales, Florian Lombart, Agathe Truchot, Pauline Maire, Pascale Vigneron, Antoine Galmiche, Catherine Lok, Muriel Vayssade

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Targeted therapy molecules are used as a first-line treatment for metastatic melanoma with B-Raf mutation. Nevertheless, these molecules can cause side effects to patients and are efficient on 50 to 60 % of them. Indeed, melanoma cell sensitivity to targeted therapy molecules is dependent on tumor microenvironment (cell-cell and cell-extracellular matrix interactions). To better unravel factors modulating cell sensitivity to B-Raf inhibitor, we have developed and compared several melanoma models: from metastatic melanoma cells cultured as monolayer (2D) to a co-culture in a 3D dermal equivalent. Cell response was studied in different melanoma cell lines such as SK-MEL-28 (mutant B-Raf (V600E), sensitive to Vemurafenib), SK-MEL-3 (mutant B-Raf (V600E), resistant to Vemurafenib) and a primary culture of dermal human fibroblasts (HDFn). Assays have initially been performed in a monolayer cell culture (2D), then a second time on a 3D dermal equivalent (dermal human fibroblasts embedded in a collagen gel). All cell lines were treated with Vemurafenib (a B-Raf inhibitor) for 48 hours at various concentrations. Cell sensitivity to treatment was assessed under various aspects: Cell proliferation (cell counting, EdU incorporation, MTS assay), MAPK signaling pathway analysis (Western-Blotting), Apoptosis (TUNEL), Cytokine release (IL-6, IL-1α, HGF, TGF-β, TNF-α) upon Vemurafenib treatment (ELISA) and histology for 3D models. In 2D configuration, the inhibitory effect of Vemurafenib on cell proliferation was confirmed on SK-MEL-28 cells (IC50=0.5 µM), and not on the SK-MEL-3 cell line. No apoptotic signal was detected in SK-MEL-28-treated cells, suggesting a cytostatic effect of the Vemurafenib rather than a cytotoxic one. The inhibition of SK-MEL-28 cell proliferation upon treatment was correlated with a strong expression decrease of phosphorylated proteins involved in the MAPK pathway (ERK, MEK, and AKT/PKB). Vemurafenib (from 5 µM to 10 µM) also slowed down HDFn proliferation, whatever cell culture configuration (monolayer or 3D dermal equivalent). SK-MEL-28 cells cultured in the dermal equivalent were still sensitive to high Vemurafenib concentrations. To better characterize all cell population impacts (melanoma cells, dermal fibroblasts) on Vemurafenib efficacy, cytokine release is being studied in 2D and 3D models. We have successfully developed and validated a relevant 3D model, mimicking cutaneous metastatic melanoma and tumor microenvironment. This 3D melanoma model will become more complex by adding a third cell population, keratinocytes, allowing us to characterize the epidermis influence on the melanoma cell sensitivity to Vemurafenib. In the long run, the establishment of more relevant 3D melanoma models with patients’ cells might be useful for personalized therapy development. The authors would like to thank the Picardie region and the European Regional Development Fund (ERDF) 2014/2020 for the funding of this work and Oise committee of "La ligue contre le cancer".

Keywords: 3D human skin model, melanoma, tissue engineering, vemurafenib efficiency

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Authors: Manushi Srivastava

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Introduction: Doctor’s role, and relation with respect to patient care is at the core of medical ethics. The rapid pace of medical advances along with increasing consumer awareness about their rights and hike in cost of effective health care demand a robust, transparent and patient-friendly medical care system. However, doctors’ role performance is still in the frame of activity-passivity model of Doctor-Patient Relationship (DPR) where doctors act as parent and use to instruct their patients, without their consensus that is not going to help in the 21st century. Thus the current situation is a new challenge for traditional doctor-patient relationship after the introduction of Consumer Protection Act (CPA) in medical profession and the same is evidenced by increasing cases of medical litigation. To strengthen this system of medical services, the doctor plays a vital role, and the same should be reviewed in the present context. Objective: To understand the opinion of consultants regarding medical negligence and effect of Consumer Protection Act in terms of current practices of patient care. Method: This is a cross-sectional study in which both quantitative and qualitative methods are applied. Total 69 consultants were selected from multi-specialty hospitals of densely populated Varanasi city catering a population of about 1.8 million. Two-stage sampling was used for selection of respondents. At the first stage, selection of major wards (Medicine, Surgery, Ophthalmology, Gynaecology, Orthopaedics, and Paediatrics) was carried out, which are more susceptible to medical negligence. At the second stage, selection of consultants from the respective wards was carried out. In-depth Interviews were conducted with the help of semi-structured schedule. Two case studies of medical negligence were also carried out as part of the qualitative study. Analysis: Data were analyzed with the help of SPSS software (21.0 trial version). Semi-structured research tool was used to know consultant’s opinion about the pattern of medical negligence cases, litigations and claims made by patient community and inclusion of government medical services in CPA. Statistical analysis was done to describe data, and non-parametric test was used to observe the association between the variables. Analysis of Verbatim was used in case-study. Findings and Conclusion: Majority (92.8%) of consultants felt changes in the behaviour of community (patient) after implementation of CPA, as it had increased awareness about their rights. Less than half of the consultants opined that Medical Negligence is an Unintentional act of doctors and generally occurs due to communication gap and behavioural problem between doctor and patients. Experienced consultants ( > 10 years) pointed out that unethical practice by doctors and mal-intention of patient to harass doctors were additional reasons of Medical Negligence. In-depth interview revealed that now patients’ community expects more transparency and hence they demand cafeteria approach in diagnosis and management of cases. Thus as study results, we propose ‘Agreement Model’ of DPR to re-ensure ethical practice in medical profession.

Keywords: doctors, communication, consumer protection act (CPA), medical error

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Authors: Josef Uher, Jana Boháčová, Richard Kadeřábek

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In this paper, we present a multi-robot imaging and irradiation research platform referred to as Irradion, with full capabilities of portable arbitrary path computed tomography (CT). Irradion is an imaging and irradiation unit entirely based on robotic arms for research on cancer treatment with ion beams on small animals (mice or rats). The platform comprises two subsystems that combine several imaging modalities, such as 2D X-ray imaging, CT, and particle tracking, with precise positioning of a small animal for imaging and irradiation. Computed Tomography: The CT subsystem of the Irradion platform is equipped with two 6-joint robotic arms that position a photon counting detector and an X-ray tube independently and freely around the scanned specimen and allow image acquisition utilizing computed tomography. Irradiation measures nearly all conventional 2D and 3D trajectories of X-ray imaging with precisely calibrated and repeatable geometrical accuracy leading to a spatial resolution of up to 50 µm. In addition, the photon counting detectors allow X-ray photon energy discrimination, which can suppress scattered radiation, thus improving image contrast. It can also measure absorption spectra and recognize different materials (tissue) types. X-ray video recording and real-time imaging options can be applied for studies of dynamic processes, including in vivo specimens. Moreover, Irradion opens the door to exploring new 2D and 3D X-ray imaging approaches. We demonstrate in this publication various novel scan trajectories and their benefits. Proton Imaging and Particle Tracking: The Irradion platform allows combining several imaging modules with any required number of robots. The proton tracking module comprises another two robots, each holding particle tracking detectors with position, energy, and time-sensitive sensors Timepix3. Timepix3 detectors can track particles entering and exiting the specimen and allow accurate guiding of photon/ion beams for irradiation. In addition, quantifying the energy losses before and after the specimen brings essential information for precise irradiation planning and verification. Work on the small animal research platform Irradion involved advanced software and hardware development that will offer researchers a novel way to investigate new approaches in (i) radiotherapy, (ii) spectral CT, (iii) arbitrary path CT, (iv) particle tracking. The robotic platform for imaging and radiation research developed for the project is an entirely new product on the market. Preclinical research systems with precision robotic irradiation with photon/ion beams combined with multimodality high-resolution imaging do not exist currently. The researched technology can potentially cause a significant leap forward compared to the current, first-generation primary devices.

Keywords: arbitrary path CT, robotic CT, modular, multi-robot, small animal imaging

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Authors: Despina Giannadaki, Jos Lelieveld, Andrea Pozzer, John Evans

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Outdoor air pollution by fine particles ranks among the top ten global health risk factors that can lead to premature mortality. Epidemiological cohort studies, mainly conducted in United States and Europe, have shown that the long-term exposure to PM2.5 (particles with an aerodynamic diameter less than 2.5μm) is associated with increased mortality from cardiovascular, respiratory diseases and lung cancer. Fine particulates can cause health impacts even at very low concentrations. Previously, no concentration level has been defined below which health damage can be fully prevented. The World Health Organization ambient air quality guidelines suggest an annual mean PM2.5 concentration limit of 10μg/m3. Populations in large parts of the world, especially in East and Southeast Asia, and in the Middle East, are exposed to high levels of fine particulate pollution that by far exceeds the World Health Organization guidelines. The aim of this work is to evaluate the implementation of recent air quality standards for PM2.5 in the EU, the US and other countries worldwide and estimate what measures will be needed to substantially reduce premature mortality. We investigated premature mortality attributed to fine particulate matter (PM2.5) under adults ≥ 30yrs and children < 5yrs, applying a high-resolution global atmospheric chemistry model combined with epidemiological concentration-response functions. The latter are based on the methodology of the Global Burden of Disease for 2010, assuming a ‘safe’ annual mean PM2.5 threshold of 7.3μg/m3. We estimate the global premature mortality by PM2.5 at 3.15 million/year in 2010. China is the leading country with about 1.33 million, followed by India with 575 thousand and Pakistan with 105 thousand. For the European Union (EU) we estimate 173 thousand and the United States (US) 52 thousand in 2010. Based on sensitivity calculations we tested the gains from PM2.5 control by applying the air quality guidelines (AQG) and standards of the World Health Organization (WHO), the EU, the US and other countries. To estimate potential reductions in mortality rates we take into consideration the deaths that cannot be avoided after the implementation of PM2.5 upper limits, due to the contribution of natural sources to total PM2.5 and therefore to mortality (mainly airborne desert dust). The annual mean EU limit of 25μg/m3 would reduce global premature mortality by 18%, while within the EU the effect is negligible, indicating that the standard is largely met and that stricter limits are needed. The new US standard of 12μg/m3 would reduce premature mortality by 46% worldwide, 4% in the US and 20% in the EU. Implementing the AQG by the WHO of 10μg/m3 would reduce global premature mortality by 54%, 76% in China and 59% in India. In the EU and US, the mortality would be reduced by 36% and 14%, respectively. Hence, following the WHO guideline will prevent 1.7 million premature deaths per year. Sensitivity calculations indicate that even small changes at the lower PM2.5 standards can have major impacts on global mortality rates.

Keywords: air quality guidelines, outdoor air pollution, particulate matter, premature mortality

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Authors: Camille Plant, Katherine McGill, Pek Ang

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Oncology patients face a host of unique challenges, which are physical, psychological and philosophical in nature. This preliminary study aimed to explore the psychiatric morbidity of oncology patients in an outpatient setting at a major public hospital in Australia. The study found that 33 patients were referred to a Psychiatrist by a Clinical Psychologist or treating Oncologist. These patients attended an outpatient Psychiatry appointment at the Calvary Mater Hospital, Newcastle, over a 7 month period (June 2017-January 2018). Of these, 45% went on to have a follow-up appointment. The Clinical Global Impressions Scale (CGI) was used to gather symptom severity scores at baseline and at follow-up. The CGI is a clinician determined instrument that provides an assessment of global functioning. It is comprised of two companion one-item measures: the CGI-Severity (CGI-S) rates mental illness severity, and the CGI-Improvement (CGI-I) rates change in condition or improvement from initiation of treatment. Patients referred to a Psychiatrist were observed to be on average in the Markedly ill approaching Severely ill range (CGI-S average of 5.5). However, those patients who attended a follow-up appointment were on average only Moderately Ill at baseline (CGI-S average of 3.9). Despite these follow patients not being severely mentally ill initially, the contact was helpful, as their CGI-S scores improved on average to the Mildly Ill range (CGI-S average of 2.8). A Mixed ANOVA revealed that there was a significant improvement in mental illness severity post-follow-up appointment (Greenhouse-Geisser .000). There was a near even proportion of males and females attending appointments (58% female), and slightly more females attended a follow-up (60% female). Males were on average more mentally ill at baseline compared to females at baseline (male average M=3.86, female average M=3.56), and males had a greater reduction in mental illness severity on average compared to females (male average M=2.71, female average 3.00). This was approaching significance (.073) and would be important to explore with a larger sample size. Change in clinical condition for follow-up patients was also recorded. It was found that more than half of patients (53%) were observed to experience Minimal improvement in attending at least one follow-up appointment. There was no change for 27% of patients, and there were no patients who were worse at follow up. As this was a preliminary study with small sample size, future research conducted could explore whether there are any significant gender differences, such as whether males experience the significantly greater reduction in symptoms of mental illness compared to females, as well as any effects of cancer stage or type on psychiatric outcomes. Future research could also investigate outcomes for those patients who concurrently access a Clinical Psychologist alongside the Psychiatrist. A limitation of the study is that the outcome measure is a brief item rating completed by the clinician.

Keywords: clinical global impressions scale, psychiatry, morbidity, oncology, outcomes, psychiatry

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Authors: Vineet Agrawal, Deepanjali S., Medha R., Subitha L.

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Background. Hospital malnutrition is a highly prevalent issue and is known to increase the morbidity, mortality, length of hospital stay, and cost of care. In India, studies on hospital malnutrition have been restricted to ICU, post-surgical, and cancer patients. We designed this study to assess the impact of hospital malnutrition on 30-day post-discharge and in-hospital mortality in patients admitted in the general medicine department, irrespective of diagnosis. Methodology. All patients aged above 18 years admitted in the medicine wards, excluding medico-legal cases, were enrolled in the study. Nutritional assessment was done within 72 h of admission, using Subjective Global Assessment (SGA), which classifies patients into three categories: Severely malnourished, Mildly/moderately malnourished, and Normal/well-nourished. Anthropometric measurements like Body Mass Index (BMI), Triceps skin-fold thickness (TSF), and Mid-upper arm circumference (MUAC) were also performed. Patients were followed-up during hospital stay and 30 days after discharge through telephonic interview, and their final diagnosis, comorbidities, and cause of death were noted. Multivariate logistic regression and cox regression model were used to determine if the nutritional status at admission independently impacted mortality at one month. Results. The prevalence of malnourishment by SGA in our study was 67.3% among 395 hospitalized patients, of which 155 patients (39.2%) were moderately malnourished, and 111 (28.1%) were severely malnourished. Of 395 patients, 61 patients (15.4%) expired, of which 30 died in the hospital, and 31 died within 1 month of discharge from hospital. On univariate analysis, malnourished patients had significantly higher morality (24.3% in 111 Cat C patients) than well-nourished patients (10.1% in 129 Cat A patients), with OR 9.17, p-value 0.007. On multivariate logistic regression, age and higher Charlson Comorbidity Index (CCI) were independently associated with mortality. Higher CCI indicates higher burden of comorbidities on admission, and the CCI in the expired patient group (mean=4.38) was significantly higher than that of the alive cohort (mean=2.85). Though malnutrition significantly contributed to higher mortality on univariate analysis, it was not an independent predictor of outcome on multivariate logistic regression. Length of hospitalisation was also longer in the malnourished group (mean= 9.4 d) compared to the well-nourished group (mean= 8.03 d) with a trend towards significance (p=0.061). None of the anthropometric measurements like BMI, MUAC, or TSF showed any association with mortality or length of hospitalisation. Inference. The results of our study highlight the issue of hospital malnutrition in medicine wards and reiterate that malnutrition contributes significantly to patient outcomes. We found that SGA performs better than anthropometric measurements in assessing under-nutrition. We are of the opinion that the heterogeneity of the study population by diagnosis was probably the primary reason why malnutrition by SGA was not found to be an independent risk factor for mortality. Strategies to identify high-risk patients at admission and treat malnutrition in the hospital and post-discharge are needed.

Keywords: hospitalization outcome, length of hospital stay, mortality, malnutrition, subjective global assessment (SGA)

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Authors: Salman Imran, Chris Healey

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Traditionally, medical care of children in England and Wales starts from primary care with a referral to secondary care paediatricians who may not investigate further. Many primary care doctors do not undergo a paediatric rotation/exposure in training. As a result, there are many who have not acquired the necessary skills to manage children hence increasing hospital referral. With the current demand on hospitals in the National Health Service managing more problems in the community is needed. One way of handling this is to set up clinics, meetings and huddles in GP surgeries where professionals involved (general practitioner, paediatrician, health visitor, community nurse, dietician, school nurse) come together and share information which can help improve communication and care. The increased awareness and education that paediatricians can impart in this way will help boost confidence for primary care professionals to be able to be more self-sufficient. This has been tried successfully in other regions e.g., St. Mary’s Hospital in London but is crucial for a more rural setting like ours. The primary aim of this project would be to educate specifically GP’s and generally all other health professionals involved. Additional benefits would be providing care nearer home, increasing patient’s confidence in their local surgery, improving communication and reducing unnecessary patient flow to already stretched hospital resources. Methods: This was done as a plan do study act cycle (PDSA). Three clinics were delivered in different practices over six months where feedback from staff and patients was collected. Designated time for teaching/discussion was used which involved some cases from the actual clinics. Both new and follow up patients were included. Two clinics were conducted by a paediatrician and nurse whilst the 3rd involved paediatrician and local doctor. The distance from hospital to clinics varied from two miles to 22 miles approximately. All equipment used was provided by primary care. Results: A total of 30 patients were seen. All patients found the location convenient as it was nearer than the hospital. 70-90% clearly understood the reason for a change in venue. 95% agreed to the importance of their local doctor being involved in their care. 20% needed to be seen in the hospital for further investigations. Patients felt this to be a more personalised, in-depth, friendly and polite experience. Local physicians felt this to be a more relaxed, familiar and local experience for their patients and they managed to get immediate feedback regarding their own clinical management. 90% felt they gained important learning from the discussion time and the paediatrician also learned about their understanding and gaps in knowledge/focus areas. 80% felt this time was valuable for targeted learning. Equipment, information technology, and office space could be improved for the smooth running of any future clinics. Conclusion: The acute paediatric outpatient clinic can be successfully established in primary care facilities. Careful patient selection and adequate facilities are important. We have demonstrated a further step in the reduction of patient flow to hospitals and upskilling primary care health professionals. This service is expected to become more efficient with experience.

Keywords: clinics, education, paediatricians, primary care

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Authors: U. E. Mochalova, A. V. Demeneva, Shilkin A. G., J. Yu. Artiushina

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Objective. In medical ophthalmology OCT has been actively used in the last decade. It is a modern non-invasive method of high-precision hardware examination, which gives a detailed cross-sectional image of eye tissues structure with a high level of resolution, which provides in vivo morphological information at the microscopic level about corneal tissue, structures of the anterior segment, retina and optic nerve. The purpose of this study was to explore the possibility of using the OCT technology in complex ophthalmological examination in dogs and cats, to characterize the revealed pathological structural changes in corneal tissue in cats and dogs with some of the most common corneal diseases. Procedures. Optical coherence tomography of the cornea was performed in 112 animals: 68 dogs and 44 cats. In total, 224 eyes were examined. Pathologies of the organ of vision included: dystrophy and degeneration of the cornea, endothelial corneal dystrophy, dry eye syndrome, chronic superficial vascular keratitis, pigmented keratitis, corneal erosion, ulcerative stromal keratitis, corneal sequestration, chronic glaucoma and also postoperative period after performed keratoplasty. When performing OCT, we used certified medical devices: "Huvitz HOCT-1/1F», «Optovue iVue 80» and "SOCT Copernicus Revo (60)". Results. The results of a clinical study on the use of optical coherence tomography (OCT)of the cornea in cats and dogs, performed by the authors of the article in the complex diagnosis of keratopathies of variousorigins: endothelial corneal dystrophy, pigmented keratitis, chronic keratoconjunctivitis, chronic herpetic keratitis, ulcerative keratitis, traumatic corneal damage, sequestration of the cornea of cats, chronic keratitis, complicating the course of glaucoma. The characteristics of the OCT scans are givencorneas of cats and dogs that do not have corneal pathologies. OCT scans of various corneal pathologies in dogs and cats with a description of the revealed pathological changes are presented. Of great clinical interest are the data obtained during OCT of the cornea of animals undergoing keratoplasty operations using various forms of grafts. Conclusions. OCT makes it possible to assess the thickness and pathological structural changes of the corneal surface epithelium, corneal stroma and descemet membrane. We can measure them, determine the exact localization, and record pathological changes. Clinical observation of the dynamics of the pathological process in the cornea using OCT makes it possible to evaluate the effectiveness of drug treatment. In case of negative dynamics of corneal disease, it is necessary to determine the indications for surgical treatment (to assess the thickness of the cornea, the localization of its thinning zones, to characterize the depth and area of pathological changes). According to the OCT of the cornea, it is possible to choose the optimal surgical treatment for the patient, the technique and depth of optically constructive surgery (penetrating or anterior lamellar keratoplasty).; determine the depth and diameter of the planned microsurgical trepanation of corneal tissue, which will ensure good adaptation of the edges of the donor material.

Keywords: optical coherence tomography, corneal sequestration, optical coherence tomography of the cornea, corneal transplantation, cat, dog

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Authors: Matthew Edmunds, Andrew Hunter, Clare Littlewood, Wisha Gul, Gabriel Heppenstall-Harris, Thomas Humphries

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Background: Revision courses for medical students undertaking their final examinations are commonplace throughout the UK. Traditionally these take the form of a series of lectures over multiple weeks or a single day of intensive lectures. The COVID-19 pandemic, however, has required medical educators to create new teaching formats to ensure they adhere to social distancing requirements. It has provided an unexpected opportunity to accelerate the development of students proficiency in the use of ‘technology-enabled communication platforms’, as mandated in the 2018 GMC Outcomes of Graduates. Recent advances in technology have made distance learning possible, whilst also providing novel and more engaging learning opportunities for students. Foundation Year 2 doctors at Aintree University Hospital developed an online series of videos to help prepare medical students in the North West and byond for their final medical school examinations. Method: Eight hour-long videos covering the key topics in medicine and surgery were posted on the Peer Learning Liverpool Youtube channel. These videos were created using new technology such as the screen and audio recording platform, Loom. Each video compromised at least 20 single best answer (SBA) questions, in keeping with the format in most medical school finals. Explanations of the answers were provided, and additional important material was covered. Students were able to ask questions by commenting on the videos, with the authors replying as soon as possible. Feedback was collated using an online Google form. Results: An average of 327 people viewed each video, with 113 students filling in the feedback form. 65.5% of respondents were within one month of their final medical school examinations. The average rating for how well prepared the students felt for their finals was 6.21/10 prior to the course and 8.01/10 after the course. A paired t-test demonstrated a mean increase of 1.80 (95% CI 1.66-1.93). Overall, 98.2% said the online format worked well or very well, and 99.1% would recommend the course to a peer. Conclusions: Based on the feedback received, the online revision course was successful both in terms of preparing students for their final examinations, and with regards to how well the online format worked. Free-text qualitative feedback highlighted advantages such as; students could learn at their own pace, revisit key concepts important to them, and practice exam style questions via the case-based format. Limitations identified included inconsistent audiovisual quality, and requests for a live online Q&A session following the conclusion of the course. This course will be relaunched later in the year with increased opportunities for students to access live feedback. The success of this online course has shown the roll that technology can play in medical education. As well as providing novel teaching modes, online learning allows students to access resources that otherwise would not be available locally, and ensure that they do not miss out on teaching that was previously provided face to face, in the current climate of social distancing.

Keywords: COVID-19 pandemic, Medical School, Online learning, Revision course

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Authors: Agnieszka Markowska-Radomska, Ewa Dluska

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Maintaining a bioactive substances dense diet is important for the elderly, especially to prevent diseases and to support healthy ageing. Adequate bioactive substances intake can reduce the risk of developing chronic diseases (e.g. cardiovascular, osteoporosis, neurodegenerative syndromes, diseases of the oral cavity, gastrointestinal (GI) disorders, diabetes, and cancer). This can be achieved by introducing a comprehensive supplementation of components necessary for the proper functioning of the ageing body. The paper proposes the multiple emulsions of the W1/O/W2 (water-in-oil-in-water) type as carriers for effective co-encapsulation and co-delivery of bioactive substances in supplementation of the elderly. Multiple emulsions are complex structured systems ("drops in drops"). The functional structure of the W1/O/W2 emulsion enables (i) incorporation of one or more bioactive components (lipophilic and hydrophilic); (ii) enhancement of stability and bioavailability of encapsulated substances; (iii) prevention of interactions between substances, as well as with the external environment, delivery to a specific location; and (iv) release in a controlled manner. The multiple emulsions were prepared by a one-step method in the Couette-Taylor flow (CTF) contactor in a continuous manner. In general, a two-step emulsification process is used to obtain multiple emulsions. The paper contains a proposal of emulsion functionalization by introducing pH-responsive biopolymer—carboxymethylcellulose sodium salt (CMC-Na) to the external phase, which made it possible to achieve a release of components controlled by the pH of the gastrointestinal environment. The membrane phase of emulsions was soybean oil. The W1/O/W2 emulsions were evaluated for their characteristics (drops size/drop size distribution, volume packing fraction), encapsulation efficiency and stability during storage (to 30 days) at 4ºC and 25ºC. Also, the in vitro multi-substance co-release process were investigated in a simulated gastrointestinal environment (different pH and composition of release medium). Three groups of stable multiple emulsions were obtained: emulsions I with co-encapsulated vitamins B12, B6 and resveratrol; emulsions II with vitamin A and β-carotene; and emulsions III with vitamins C, E and D3. The substances were encapsulated in the appropriate emulsion phases depending on the solubility. For all emulsions, high encapsulation efficience (over 95%) and high volume packing fraction of internal droplets (0.54-0.76) were reached. In addition, due to the presence of a polymer (CMC-Na) with adhesive properties, high encapsulation stability during emulsions storage were achieved. The co-release study of encapsulated bioactive substances confirmed the possibility to modify the release profiles. It was found that the releasing process can be controlled through the composition, structure, physicochemical parameters of emulsions and pH of the release medium. The results showed that the obtained multiple emulsions might be used as potential liquid complex carriers for controlled/modified/site-specific co-delivery of bioactive substances in dietary supplementation in the elderly.

Keywords: bioactive substance co-release, co-encapsulation, elderly supplementation, multiple emulsion

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Authors: Kamal Tolani, Sandeep Kumar, Rohit Luthra, Ankit Dadhania, Krishnaprasad K., Ram Gupta, Deepa Joshi

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Background: Post-operative analgesia remains a clinical challenge, with central and peripheral sensitization playing a pivotal role in treatment-related complications and impaired quality of life. Centrally acting opioids offer poor risk benefit profile with increased intensity of gastrointestinal or central side effects and slow onset of clinical analgesia. The objective of this study was to assess the clinical feasibility of induction and maintenance therapy with Tapentadol Nasal Spray (NS) in moderate to severe acute post-operative pain. Methods: Phase III, randomized, active-controlled, non-inferiority clinical trial involving 294 cases who had undergone surgical procedures under general anesthesia or regional anesthesia. Post-surgery patients were randomized to receive either Tapentadol NS 45 mg or Tramadol 100mg IV as a bolus and subsequent 50 mg or 100 mg dose over 2-3 minutes. The frequency of administration of NS was at every 4-6 hours. At the end of 24 hrs, patients in the tramadol group who had a pain intensity score of ≥4 were switched to oral tramadol immediate release 100mg capsule until the pain intensity score reduced to <4. All patients who had achieved pain intensity ≤ 4 were shifted to a lower dose of either Tapentadol NS 22.5 mg or oral Tramadol immediate release 50mg capsule. The statistical analysis plan was envisaged as a non-inferiority trial involving comparison with Tramadol for Pain intensity difference at 60 minutes (PID60min), Sum of Pain intensity difference at 60 minutes (SPID60min), and Physician Global Assessment at 24 hrs (PGA24 hrs). Results: The per-protocol analyses involved 255 hospitalized cases undergoing surgical procedures. The median age of patients was 38.0 years. For the primary efficacy variables, Tapentadol NS was non-inferior to Inj/Oral Tramadol in relief of moderate to severe post-operative pain. On the basis of SPID60min, no clinically significant difference was observed between Tapentadol NS and Tramadol IV (1.73±2.24 vs. 1.64± 1.92, -0.09 [95% CI, -0.43, 0.60]). In the co-primary endpoint PGA24hrs, Tapentadol NS was non–inferior to Tramadol IV (2.12 ± 0.707 vs. 2.02 ±0.704, - 0.11[95% CI, -0.07, 0.28). However, on further assessment at 48hr, 72 hrs, and 120hrs, clinically superior pain relief was observed with the Tapentadol NS formulation that was statistically significant (p <0.05) at each of the time intervals. Secondary efficacy measures, including the onset of clinical analgesia and TOTPAR, showed non-inferiority to Tramadol. The safety profile and need for rescue medication were also similar in both the groups during the treatment period. The most common concomitant medications were anti-bacterial (98.3%). Conclusion: Tapentadol NS is a clinically feasible option for improved compliance as induction and maintenance therapy while offering a sustained and persistent patient response that is clinically meaningful in post-surgical settings.

Keywords: tapentadol nasal spray, acute pain, tramadol, post-operative pain

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Authors: Nyathi Mpumelelo; Moeng Thabiso Maria

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

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

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Authors: Cibele F. Oliveira, Debora P. Jaeschke, Rodrigo R. Laurino, Amanda R. Andrade, Ligia D. F. Marczak

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Raspberry is well-known as a good source of phenolic compounds, mainly anthocyanin. Some studies pointed out the importance of these bioactive compounds consumption, which is related to the decrease of the risk of cancer and cardiovascular diseases. The most consumed raspberry products are juices, yogurts, ice creams and jellies and, to ensure the safety of these products, raspberry is commonly pasteurized, for enzyme and microorganisms inactivation. Despite being efficient, the pasteurization process can lead to degradation reactions of the bioactive compounds, decreasing the products healthy benefits. Therefore, the aim of the present work was to evaluate moderate electric field (MEF) and ultrasound (US) technologies application on the pasteurization process of raspberry juice and compare the results with conventional pasteurization process. For this, phenolic compounds, anthocyanin content and physical-chemical parameters (pH, color changes, titratable acidity) of the juice were evaluated before and after the treatments. Moreover, microbiological analyses of aerobic mesophiles microorganisms, molds and yeast were performed in the samples before and after the treatments, to verify the potential of these technologies to inactivate microorganisms. All the pasteurization processes were performed in triplicate for 10 min, using a cylindrical Pyrex® vessel with a water jacket. The conventional pasteurization was performed at 90 °C using a hot water bath connected to the extraction cell. The US assisted pasteurization was performed using 423 and 508 W cm-2 (75 and 90 % of ultrasound intensity). It is important to mention that during US application the temperature was kept below 35 °C; for this, the water jacket of the extraction cell was connected to a water bath with cold water. MEF assisted pasteurization experiments were performed similarly to US experiments, using 25 and 50 V. Control experiments were performed at the maximum temperature of US and MEF experiments (35 °C) to evaluate only the effect of the aforementioned technologies on the pasteurization. The results showed that phenolic compounds concentration in the juice was not affected by US and MEF application. However, it was observed that the US assisted pasteurization, performed at the highest intensity, decreased anthocyanin content in 33 % (compared to in natura juice). This result was possibly due to the cavitation phenomena, which can lead to free radicals formation and accumulation on the medium; these radicals can react with anthocyanin decreasing the content of these antioxidant compounds in the juice. Physical-chemical parameters did not present statistical differences for samples before and after the treatments. Microbiological analyses results showed that all the pasteurization treatments decreased the microorganism content in two logarithmic cycles. However, as values were lower than 1000 CFU mL-1 it was not possible to verify the efficacy of each treatment. Thus, MEF and US were considered as potential alternative technologies for pasteurization process, once in the right conditions the application of the technologies decreased microorganism content in the juice and did not affected phenolic and anthocyanin content, as well as physical-chemical parameters. However, more studies are needed regarding the influence of MEF and US processes on microorganisms’ inactivation.

Keywords: MEF, microorganism inactivation, anthocyanin, phenolic compounds

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Authors: Elizabeth Adebomi Akinlotan, Olukemi Odukoya

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INTRODUCTION: Physical Activity is defined as activity that involves bodily movement which is done as a part of daily activity in the form of working, playing, active transportation such as walking and also as a form of recreational activity. Physical inactivity has been identified as the fourth leading risk factor for global mortality and morbidity causing an estimated 3.2 million deaths globally and 5.5% of total deaths and it remains a pressing public health issue. There is a shift in the major causes of death from communicable to non-communicable diseases in many developed countries and this is fast becoming the case in developing countries. Physical activity is an important determinant of health and has been associated with lower mortality rates as it reduces the risk of developing chronic diseases such as diabetes mellitus, hypertension, stroke, cancer and osteoporosis. It improves musculoskeletal health, controls weight and reduces symptoms of depression. AIM: The aim is to study the knowledge, attitude and practices of physical activity among adults in Alimosho local government area. METHODOLOGY: This was a descriptive cross sectional survey designed to study the knowledge, attitude and practice of physical activity among adults in Alimosho Local Government Area. The study population were 250 adults aged 18-65 who were residents of the area of more than 6 months duration and had no chronic disease condition or physical disability. A multistage sampling method was used to select the respondents and data was collected using interviewer administered questionnaires. The data was analyzed with the use of EPI-info 2007 statistical software. Chi Square was thereafter used to test the association between selected variables. The level of statistical significance was set at 5% (p<0.05). RESULTS: In general, majority (61.6%) of the respondents had a good knowledge of what physical activity entails, 34.0% had fair knowledge and 4.4% had poor knowledge. There was a favorable attitude towards physical activity among the respondents with 82.4% having an overall positive attitude. Below a third of the respondents (26.4%) reported having a high physical activity (METS > 3001) while 40.0% had moderate (601-3000 METS) levels of activity and 33.6% were inactive (<600METS). There is statistical significance between the gender of the respondent and the levels of physical activity (p=0.0007); 75.2% males reached the minimum recommendations while 24.8% were inactive and 55.0% females reached the minimum recommendations while 45.0% were inactive. Results also showed that of 95 respondents who were satisfied with their levels of physical activity, 33.7% were insufficiently active while 66.3% were either minimally active or highly active and of 110 who were unsatisfied with their levels of physical activity, 72.0% were above the minimum recommendations while 38.0% were insufficiently active. CONCLUSION: In contrast to the high level of knowledge and favorable attitude towards physical activity, there was a lower level of practice of high or moderate physical activities. It is recommended that more awareness should be created on the recommended levels of physical activity especially for the vigorous intensity and moderate intensity physical activity.

Keywords: METS, physical activity, physical inactivity, public health

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Authors: Milu T. Cherian, Sergio C. Chai, Morgan A. Casal, Taosheng Chen

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This study aims to use CINPA1, a recently discovered small-molecule inhibitor of the xenobiotic receptor CAR (constitutive androstane receptor) for understanding the binding modes of CAR and to guide CAR-mediated gene expression profiling studies in human primary hepatocytes. CAR and PXR are xenobiotic sensors that respond to drugs and endobiotics by modulating the expression of metabolic genes that enhance detoxification and elimination. Elevated levels of drug metabolizing enzymes and efflux transporters resulting from CAR activation promote the elimination of chemotherapeutic agents leading to reduced therapeutic effectiveness. Multidrug resistance in tumors after chemotherapy could be associated with errant CAR activity, as shown in the case of neuroblastoma. CAR inhibitors used in combination with existing chemotherapeutics could be utilized to attenuate multidrug resistance and resensitize chemo-resistant cancer cells. CAR and PXR have many overlapping modulating ligands as well as many overlapping target genes which confounded attempts to understand and regulate receptor-specific activity. Through a directed screening approach we previously identified a new CAR inhibitor, CINPA1, which is novel in its ability to inhibit CAR function without activating PXR. The cellular mechanisms by which CINPA1 inhibits CAR function were also extensively examined along with its pharmacokinetic properties. CINPA1 binding was shown to change CAR-coregulator interactions as well as modify CAR recruitment at DNA response elements of regulated genes. CINPA1 was shown to be broken down in the liver to form two, mostly inactive, metabolites. The structure-activity differences of CINPA1 and its metabolites were used to guide computational modeling using the CAR-LBD structure. To rationalize how ligand binding may lead to different CAR pharmacology, an analysis of the docked poses of human CAR bound to CITCO (a CAR activator) vs. CINPA1 or the metabolites was conducted. From our modeling, strong hydrogen bonding of CINPA1 with N165 and H203 in the CAR-LBD was predicted. These residues were validated to be important for CINPA1 binding using single amino-acid CAR mutants in a CAR-mediated functional reporter assay. Also predicted were residues making key hydrophobic interactions with CINPA1 but not the inactive metabolites. Some of these hydrophobic amino acids were also identified and additionally, the differential coregulator interactions of these mutants were determined in mammalian two-hybrid systems. CINPA1 represents an excellent starting point for future optimization into highly relevant probe molecules to study the function of the CAR receptor in normal- and pathophysiology, and possible development of therapeutics (for e.g. use for resensitizing chemoresistant neuroblastoma cells).

Keywords: antagonist, chemoresistance, constitutive androstane receptor (CAR), multi-drug resistance, structure activity relationship (SAR), xenobiotic resistance

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Authors: Simona Dostalova, Pavel Kopel, Marketa Vaculovicova, Vojtech Adam, Rene Kizek

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Protein apoferritin seems to be a very promising structure for use as a nanocarrier. It is prepared from intracellular ferritin protein naturally found in most organisms. The role of ferritin proteins is to store and transport ferrous ions. Apoferritin is a hollow protein cage without ferrous ions that can be prepared from ferritin by reduction with thioglycolic acid or dithionite. The structure of apoferritin is composed of 24 protein subunits, creating a sphere with 12 nm in diameter. The inner cavity has a diameter of 8 nm. The drug encapsulation process is based on the response of apoferritin structure to the pH changes of surrounding solution. In low pH, apoferritin is disassembled into individual subunits and its structure is “opened”. It can then be mixed with any desired cytotoxic drug and after adjustment of pH back to neutral the subunits are reconnected again and the drug is encapsulated within the apoferritin particles. Excess drug molecules can be removed by dialysis. The receptors for apoferritin, SCARA5 and TfR1 can be found in the membrane of both healthy and cancer cells. To enhance the specific targeting of apoferritin nanocarrier, it is possible to modify its surface with targeting moieties, such as antibodies. To ensure sterically correct complex, we used a a peptide linker based on a protein G with N-terminus affinity towards Fc region of antibodies. To connect the peptide to the surface of apoferritin, the C-terminus of peptide was made of cysteine with affinity to gold. The surface of apoferritin with encapsulated doxorubicin (ApoDox) was coated either with gold nanoparticles (ApoDox-Nano) or gold (III) chloride hydrate reduced with sodium borohydride (ApoDox-HAu). The applied amount of gold in form of gold (III) chloride hydrate was 10 times higher than in the case of gold nanoparticles. However, after removal of the excess unbound ions by electrophoretic separation, the concentration of gold on the surface of apoferritin was only 6 times higher for ApoDox-HAu in comparison with ApoDox-Nano. Moreover, the reduction with sodium borohydride caused a loss of doxorubicin fluorescent properties (excitation maximum at 480 nm with emission maximum at 600 nm) and thus its biological activity. Fluorescent properties of ApoDox-Nano were similar to the unmodified ApoDox, therefore it was more suited for the intended use. To evaluate the specificity of apoferritin modified with antibodies, we used ELISA-like method with the surface of microtitration plate wells coated by the antigen (goat anti-human IgG antibodies). To these wells, we applied ApoDox without targeting antibodies and ApoDox-Nano modified with targeting antibodies (human IgG antibodies). The amount of unmodified ApoDox on antigen after incubation and subsequent rinsing with water was 5 times lower than in the case of ApoDox-Nano modified with targeting antibodies. The modification of non-gold ApoDox with antibodies caused no change in its targeting properties. It can therefore be concluded that the demonstrated procedure allows us to create nanocarrier with enhanced targeting properties, suitable for nanomedicine.

Keywords: apoferritin, doxorubicin, nanocarrier, targeting antibodies

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Authors: Harriet Bothwell, Lowri Evans, Kevin Jones

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Background: The University of Bristol provides all medical students the opportunity to undertake student selected components (SSCs) at multiple stages of the undergraduate programme. SSCs enable students to explore areas of interest that are not necessarily covered by the curriculum. Students are required to produce a written report and most use SSCs as an opportunity to undertake an audit or small research project. In 2013 Swindon Academy, based at the Great Western Hospital, offered eight students the opportunity of a global health SSC which included a two week trip to rural hospital in Uganda. This SSC has since expanded and in 2017 a total of 20 students had the opportunity to undertake small research projects at two hospitals in rural Uganda. 'Tomorrows Doctors' highlights the importance of understanding healthcare from a 'global perspective' and student feedback from previous SSCs suggests that self-assessed knowledge of global health increases as a result of this SSC. Through the most recent version of this SSC students had the opportunity to undertake projects in a wide range of specialties including paediatrics, palliative care, surgery and medical education. Methods: An anonymous online questionnaire was made available to students following the SSC. There was a response rate of 80% representing 16 out of the 20 students. This questionnaire surveyed students’ satisfaction and experience of the SSC including the level of academic, project and spiritual support provided as well as perceived challenges in completing the project and barriers to healthcare delivery in the low resource setting. This survey had multiple open questions allowing the collection of qualitative data. Further qualitative data was collected from the students’ project report. The suggested format included a reflection and all students completed these. All qualitative data underwent thematic analysis. Results: All respondents rated the overall experience of the SSC as 'good' or 'excellent'. Preliminary data suggest that students’ confidence in their knowledge of global health, diagnosis of tropical diseases and management of tropical diseases improved after completing this SSC. Thematic analysis of students' reflection is ongoing but suggests that students gain far more than improved knowledge of tropical diseases. Students reflect positively on having the opportunity to research in a low resource setting and feel that by completing these projects they will be 'useful' to the hospital. Several students reflect the stark contrast to healthcare delivery in the UK and recognise the 'privilege' of having a healthcare system that is free at the point of access. Some students noted the different approaches that clinicians in Uganda had to train in 'taking ownership' of their own learning. Conclusions: Students completing this SSC report increased knowledge of global health and tropical medicine. However, their reflections reveal much broader learning outcomes and demonstrate considerable insight in multiple topics including conducting research in the low resource setting, training and healthcare inequality.

Keywords: global health, medical education, student feedback, undergraduate

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Authors: Ren-Jy Ben, Jo-Chi Jao, Chiu-Ya Liao, Ya-Ru Tsai, Lain-Chyr Hwang, Po-Chou Chen

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Cancer is still one of the serious diseases threatening the lives of human beings. How to have an early diagnosis and effective treatment for tumors is a very important issue. The animal carcinoma model can provide a simulation tool for the study of pathogenesis, biological characteristics and therapeutic effects. Recently, drug delivery systems have been rapidly developed to effectively improve the therapeutic effects. Liposome plays an increasingly important role in clinical diagnosis and therapy for delivering a pharmaceutic or contrast agent to the targeted sites. Liposome can be absorbed and excreted by the human body, and is well known that no harm to the human body. This study aimed to compare the therapeutic effects between encapsulated (doxorubicin liposomal, LipoDox) and un-encapsulated (doxorubicin, Dox) anti-tumor drugs using Magnetic Resonance Imaging (MRI). Twenty-four New Zealand rabbits implanted with VX2 carcinoma at left thigh were classified into three groups: control group (untreated), Dox-treated group and LipoDox-treated group, 8 rabbits for each group. MRI scans were performed three days after tumor implantation. A 1.5T GE Signa HDxt whole body MRI scanner with a high resolution knee coil was used in this study. After a 3-plane localizer scan was performed, Three-Dimensional (3D) Fast Spin Echo (FSE) T2-Weighted Images (T2WI) was used for tumor volumetric quantification. And Two-Dimensional (2D) spoiled gradient recalled echo (SPGR) dynamic Contrast-enhanced (DCE) MRI was used for tumor perfusion evaluation. DCE-MRI was designed to acquire four baseline images, followed by contrast agent Gd-DOTA injection through the ear vein of rabbits. Afterwards, a series of 32 images were acquired to observe the signals change over time in the tumor and muscle. The MRI scanning was scheduled on a weekly basis for a period of four weeks to observe the tumor progression longitudinally. The Dox and LipoDox treatments were prescribed 3 times in the first week immediately after VX2 tumor implantation. ImageJ was used to quantitate tumor volume and time course signal enhancement on DCE images. The changes of tumor size showed that the growth of VX2 tumors was effectively inhibited for both LipoDox-treated and Dox-treated groups. Furthermore, the tumor volume of LipoDox-treated group was significantly lower than that of Dox-treated group, which implies that LipoDox has better therapeutic effect than Dox. The signal intensity of LipoDox-treated group is significantly lower than that of the other two groups, which implies that targeted therapeutic drug remained in the tumor tissue. This study provides a radiation-free and non-invasive MRI method for therapeutic monitoring of targeted liposome on an animal tumor model.

Keywords: doxorubicin, dynamic contrast-enhanced MRI, lipodox, magnetic resonance imaging, VX2 tumor model

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Authors: Uraporn Vongvatcharanon, Kochakorn Sukjan, Wandee Udomuksorn, Ekkasit Kumarnsit, Surapong Vongvatcharanon

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Sarcopenia is a loss of muscle mass, and strength frequently found in menopause. Estrogen replacement has been shown to improve such a loss of muscle functions. However, there is an increased risk of cancer that has to be considered because of the estrogen replacement therapy. Thus, phytoestrogen supplementation has been suggested as an alternative therapy. Pueraria mirifica (PM) is a plant in the family Leguminosae, that is known to be phytoestrogen-rich and has been traditionally used for the treatment of menopausal symptoms. It contains isoflavones and other compounds such as miroestrol and its derivatives. Parvalbumin (PV) is a calcium binding protein and functions as a relaxing factor in fast twitch muscle fibers. A decrease of the PV level results in a reduction of the speed of the twitch relaxation. Therefore, this study aimed to investigate the effect of an ethanolic extract from Pueraria mirifica on the estrogen levels, skeletal muscle functions and PV levels in the extensor digitorum longus (EDL) and gastrocnemius of ovariectomized rats. Twelve-week old female Wistar rats (200-250 g) were divided into 6 groups: SHAM (un-ovariectomized rats, that received double distilled water), PM-0 (ovariectomized rats, OVX, receiving double distilled water), E (OVX, receiving an estradiol benzoate dose of 0.04 mg/kg), PM-50 (OVX receiving PM 50 mg/kg), PM-500 (OVX receiving PM 500 mg/kg), PM-1000 (OVX receiving PM 1000 mg/kg) all for 90 days. The PM-0 group had estrogen levels, uterus weights, muscle mass, myofiber cross-section areas, peak tension, fatigue resistance, speed of relaxation and parvalbumin levels of both EDL and gastrocnemius that were significantly reduced compared to those of the SHAM group (p<0.05). Also the α and β estrogen receptor immunoreactivities and the parvalbumin immunoreactivities of both EDL and gastrocnemius were decreased in the PM-0 group. In contrast the E, PM-50, PM-500 and PM-1000 group had estrogen levels, uterus weights, muscle mass, myofiber cross-section areas, peak tension, fatigue resistance, speed of relaxation of both EDL and gastrocnemius that were significantly increased compared with PM-0 group (p<0.05). In addition, the α and β estrogen receptor immunoreactivities and parvalbumin immunoreactivity of both the EDL and gastrocnemius were increased in the E, PM-50, PM-500 and PM-1000 group. In addition the extract of Pueraria mirifica replacement group at 50 and 500 mg/kg had significantly increased parvalbumin levels in the EDL muscle but in the gastrocnemius, only the dose of 500 mg/kg increased the parvalbumin levels (p<0.05). These results have demonstrated that the use of the Pueraria mirifica extract as a replacement therapy for estrogen produced estrogenic activity that was similar to that produced by the estradiol benzoate replacement. It seems that the phytoestrogens could bind with the estrogen receptors and stimulate the transcriptional activity to synthesise muscle protein that caused an increase in muscle mass and parvalbumin levels. Thus, muscle synthesis may restore parvalbumin levels resulting in an enhanced relaxation efficiency that would lead to a shortened latent period before the next contraction.

Keywords: Puereria mirifica, Parvalbumin, estrogen, ovariectomized rats

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