Search results for: gastric cancer surgery

Authors: Nashaat Mazrui, Oarabile Mogobe, Barbara Ngwenya, Ketlhatlogile Mosepele, Mangaliso Gondwe

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Over the last several decades, the world has seen a rapid increase in activities such as deforestation, agriculture, and energy use. Subsequently, trace elements are being deposited into our water bodies, where they can accumulate to toxic levels in aquatic organisms and can be transferred to humans through fish consumption. Thus, though fish is a good source of essential minerals and omega-3 fatty acids, it can also be a source of toxic elements. Monitoring trace elements in fish is important for the proper management of aquatic systems and the protection of human health. The aim of this study was to determine concentrations of trace elements in sediment and muscle tissues of Clarias gariepinus at Lake Ngami, in the Okavango Delta in northern Botswana, during low floods. The fish were bought from local fishermen, and samples of muscle tissue were acid-digested and analyzed for iron, zinc, copper, manganese, molybdenum, nickel, chromium, cadmium, lead, and arsenic using inductively coupled plasma optical emission spectroscopy (ICP-OES). Sediment samples were also collected and analyzed for the elements and for organic matter content. Results show that in all samples, iron was found in the greatest amount while cadmium was below the detection limit. Generally, the concentrations of elements in sediment were higher than in fish except for zinc and arsenic. While the concentration of zinc was similar in the two media, arsenic was almost 3 times higher in fish than sediment. To evaluate the risk to human health from fish consumption, the target hazard quotient (THQ) and cancer risk for an average adult in Botswana, sub-Saharan Africa, and riparian communities in the Okavango Delta was calculated for each element. All elements were found to be well below regulatory limits and do not pose a threat to human health except arsenic. The results suggest that other benthic feeding fish species could potentially have high arsenic levels too. This has serious implications for human health, especially riparian households to whom fish is a key component of food and nutrition security.

Keywords: Arsenic, African sharp tooth cat fish, Okavango delta, trace elements

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Authors: Ayda Youssef, Tarek Rafaat, Iman zaky

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

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

Procedia PDF Downloads 257

Authors: Ji Jiazheng, Wang Jingrao, Jin Xin, Zhang Hong

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Diabetes mellitus is a metabolic disease characterized by high blood sugar. A long-standing hyperglycemic state can lead to various tissue damage. Diabetic retinopathy is the most common and widely studied ocular complication and has become the leading cause of blindness in my country. At the same time, diabetes has profound clinically relevant effects on the cornea, leading to keratopathy and vision-threatening. The cornea is an avascular tissue and is sensitive to hyperglycemia, Keratopathy caused by diabetes is usually chronic, they are called diabetic keratopathy or diabetic neurotrophic keratopathy, leading to several diabetic corneal complications including delayed epithelial wound healing, recurrent erosions, neuropathy, loss of sensitivity. Corneal stem cell dysfunction in diabetic patients as an important influencing factor of diabetic keratopathy. The consequences of this condition are often underestimated. The limbus is located between the cornea and the sclera tissue. The limbal stroma consists of a series of radial elevations with fibrovascular centers known as palisades of Vogt (POV). Previous studies have shown that palisades of Vogt (POV), as the main site of limbal stem cells, plays an important role in the homeostasis of the corneal epithelium. Therefore, POV plays a vital role in the healing of corneal epithelial surgery and postoperative evaluation. IVCM can observe the condition of the corneal epithelium at the cellular level. It has profound significance and guidance for the evaluation of limbal and limbal stem cells. We have previously observed structural changes in POV in HSK and HZO patients on IVCM. At present, there have been reports involving limbal stem cell dysfunction in diabetic patients, but the specific pathogenesis is still unclear. However, there are no studies on POV morphological changes in patients with DM. Therefore, we performed statistics and compared the correlation between POV morphological changes and corneal epithelial basal cell density, corneal nerves, and length of disease in DM patients and normal humans using IVCM studies. At the same time, fundoscopy was used to observe the correlation between the thickness of RNFL and the thickness of GCC and POV in diabetic patients. And to observe the correlation between SVD, DVD and POV for research.

Keywords: confocal microscopy, fundus, limbal stem cells, diabetes

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

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

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

Procedia PDF Downloads 126

Authors: Chih-Chung Huang, Po-Hsun Peng

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

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

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

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

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

Procedia PDF Downloads 171

Authors: Iman Farasat, Howard M. Salis

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

Keywords: biophysical model, CRISPR, Cas9, genome editing

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Authors: Carl Ashworth, Matthys Campher

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Spinal anaesthesia has been identified as the “gold standard” for primary elective total hip and knee arthroplasty, which is most commonly performed using longer-acting local anaesthetics, such as hyperbaric bupivacaine, to prolong the duration of anaesthesia and analgesia suitable for these procedures. Ketamine is known to have local anaesthetic effects with potent analgesic properties and has been evaluated as a sole anaesthetic agent via intrathecal administration; however, the use of intrathecal ketamine as an adjunct to intrathecal hyperbaric bupivacaine, morphine, and fentanyl has not been extensively studied. The objective of this study was to identify the potential analgesic effects of the addition of intrathecal ketamine to spinal anaesthesia and to compare the efficacy and safety of adding intrathecal ketamine to spinal anaesthesia for hip- or knee arthroplasty with spinal anaesthesia for hip- or knee arthroplasty without intrathecal ketamine. The medical records of patients who underwent elective hip- or knee arthroplasty under spinal anaesthesia performed by an individual anaesthetist with either intrathecal hyperbaric bupivacaine, morphine and fentanyl or intrathecal hyperbaric bupivacaine, morphine, fentanyl and ketamine between June 4, 2020, and June 4, 2022, were retrospectively reviewed. These encounters were reviewed and analyzed from a perioperative pain perspective, with the primary outcome measure as the oral morphine equivalent (OME) usage in the 48 hours post-spinal anaesthesia, and secondary outcome measures including time to breakthrough analgesia, self-reported pain scores at rest and during movement at 24 and 48 hours after surgery, adverse effects of analgesia, complications, and length of stay. There were 26 patients identified who underwent TKR between June 4, 2020, and June 4, 2022, and 25 patients who underwent THR with the same conditions. It was identified that patients who underwent traditional spinal anaesthesia with the addition of ketamine for elective hip- or knee arthroplasty had a lower mean total OME in the 48 hours immediately post-spinal anaesthesia yet had a shorter time to breakthrough analgesia administration. The proposed mechanism of action for intrathecal ketamine as an additive to traditional spinal anaesthesia for elective hip- or knee arthroplasty is that it may prolong and attenuate the analgesic effect of traditional spinal anaesthesia. There were no significant differences identified in comparing the efficacy and safety of adding intrathecal ketamine to spinal anaesthesia for hip- or knee arthroplasty with spinal anaesthesia for hip- or knee arthroplasty without intrathecal ketamine.

Keywords: anaesthesia, spinal, intra-thecal, ketamine, spinal-morphine, bupivacaine

Procedia PDF Downloads 28

Authors: Bertalan Jillek, Péter Szabó, Judit Kopniczky, István Szabó, Balázs Patczai, Kinga Turzó

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Hip and knee prostheses are one of the most frequently used medical implants, that can significantly improve patients’ quality of life. Long term success and biointegration of these prostheses depend on several factors, like bulk and surface characteristics, construction and biocompatibility of the material. The applied surgical technique, the general health condition and life-quality of the patient are also determinant factors. Medical devices used in orthopedic surgeries have different surfaces depending on their function inside the human body. Surface roughness of these implants determines the interaction with the surrounding tissues. Numerous modifications have been applied in the recent decades to improve a specific property of an implant. Our goal was to compare the surface characteristics of typical implant materials used in orthopedic surgery and traumatology. Morphological and chemical structure of Vortex plate anodized titanium, cemented THR (total hip replacement) stem high nitrogen REX steel (SS), uncemented THR stem and cup titanium (Ti) alloy with titanium plasma spray coating (TPS), cemented cup and uncemented acetabular liner HXL and UHMWPE and TKR (total knee replacement) femoral component CoCrMo alloy (Sanatmetal Ltd, Hungary) discs were examined. Visualization and elemental analysis were made by scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS). Surface roughness was determined by atomic force microscopy (AFM) and profilometry. SEM and AFM revealed the morphological and roughness features of the examined materials. TPS Ti presented the highest Ra value (25 ± 2 μm, followed by CoCrMo alloy (535 ± 19 nm), Ti (227 ± 15 nm) and stainless steel (170 ± 11 nm). The roughness of the HXL and UHMWPE surfaces was in the same range, 147 ± 13 nm and 144 ± 15 nm, respectively. EDS confirmed typical elements on the investigated prosthesis materials: Vortex plate Ti (Ti, O, P); TPS Ti (Ti, O, Al); SS (Fe, Cr, Ni, C) CoCrMo (Co, Cr, Mo), HXL (C, Al, Ni) and UHMWPE (C, Al). The results indicate that the surface of prosthesis materials have significantly different features and the applied investigation methods are suitable for their characterization. Contact angle measurements and in vitro cell culture testing are further planned to test their surface energy characteristics and biocompatibility.

Keywords: morphology, PE, roughness, titanium

Procedia PDF Downloads 98

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

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

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

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Authors: Sumit Kanwar, Manisha Chand, Gregory Gilot

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Background: Septic arthritis of the shoulder has infrequently been discussed. Focus on infection of the untouched shoulder has not heretofore been described. We present four patients with glenohumeral septic arthritis. Methods: Case 1: A 59 year old male with left shoulder pain in the anterior, posterior and superior aspects. Case 2: A 60 year old male with fever, chills, and generalized muscle aches. Case 3: A 70 year old male with right shoulder pain about the anterior and posterior aspects. Case 4: A 55 year old male with global right shoulder pain, swelling, and limited ROM. Results: In case 1, the left shoulder was affected. Physical examination, swelling was notable, there was global tenderness with a painful range of motion (ROM). The lab values indicated an erythrocyte sedimentation rate (ESR) of 96, and a C-reactive protein (CRP) of 304.30. Imaging studies were performed and MRI indicated a high suspicion for an abscess with osteomyelitis of the humeral head. Our second case’s left arm was affected. He had swelling, global tenderness and painful ROM. His ESR was 38, CRP was 14.9. X-ray showed severe arthritis. Case 3 differed with the right arm being affected. Again, global tenderness and painful ROM was observed. His ESR was 94, and CRP was 10.6. X-ray displayed an eroded glenoid space. Our fourth case’s right shoulder was affected. He had global tenderness and painful, limited ROM. ESR was 108 and CRP was 2.4. X-ray was non-significant. Discussion: Monoarticular septic arthritis of the virgin glenohumeral joint is seldom diagnosed in clinical practice. Common denominators include elevated ESR, painful, limited ROM, and involvement of the dominant arm. The male population is more frequently affected with an average age of 57. Septic arthritis is managed with incision and drainage or needle aspiration of synovial fluid supplemented with 3-6 weeks of intravenous antibiotics. Due to better irrigation and joint visualization, arthroscopy is preferred. Open surgical drainage may be indicated if the above methods fail. Conclusion: If a middle-aged male presents with vague anterior or posterior shoulder pain, elevated inflammatory markers and a low grade fever, an x-ray should be performed. If this displays degenerative joint disease, the complete further workup with advanced imaging, such as an MRI, CT scan, or an ultrasound. If these imaging modalities display anterior space joint effusion with soft tissue involvement, we can suspect septic arthritis of the untouched glenohumeral joint and surgery is indicated.

Keywords: glenohumeral joint, identification, infection, septic arthritis, shoulder

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Authors: Giselle Tran, Ralitza Parina, Phuong T. Nguyen

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Background/Aims: Pancreatic cysts (PC) have recently become an increasingly common entity, often diagnosed as incidental findings on cross-sectional imaging. Clinically, management of the lesions is difficult because of uncertainties in their potential for malignant degeneration. Prior series have reported that carcinoembryonic antigen (CEA), a biomarker collected from cyst fluid aspiration, has a high diagnostic accuracy for discriminating between mucinous and non-mucinous lesions, at the patient’s initial presentation. To the author’s best knowledge, no prior studies have reported PC CEA levels obtained from endoscopic ultrasound fine-needle aspiration (EUS-FNA) over years of serial EUS surveillance imaging. Methods: We report a consecutive retrospective series of 624 patients who underwent EUS evaluation for a PC between 11/20/2009 and 11/13/2018. Of these patients, 401 patients had CEA values obtained at the point of entry. Of these, 157 patients had two or more CEA values obtained over the course of their EUS surveillance. Of the 157 patients (96 F, 61 M; mean age 68 [range, 62-76]), the mean interval of EUS follow-up was 29.7 months [3.5-128]. The mean number of EUS procedures was 3 [2-7]. To assess CEA value fluctuations, we defined an appreciable increase in CEA as "spikes" – two-times increase in CEA on a subsequent EUS-FNA of the same cyst, with the second CEA value being greater than 1000 ng/mL. Using this definition, cysts with a spike in CEA were compared to those without a spike in a bivariate analysis to determine if a CEA spike is associated with poorer outcomes and the presence of high-risk features. Results: Of the 157 patients analyzed, 29 had a spike in CEA. Of these 29 patients, 5 had a cyst with size increase >0.5cm (p=0.93); 2 had a large cyst, >3cm (p=0.77); 1 had a cyst that developed a new solid component (p=0.03); 7 had a cyst with a solid component at any time during surveillance (p=0.08); 21 had a complex cyst (p=0.34); 4 had a cyst categorized as "Statistically Higher Risk" based on molecular analysis (p=0.11); and 0 underwent surgical resection (p=0.28). Conclusion: With serial EUS imaging in the surveillance of PC, an increase in CEA level defined as a spike did not predict poorer outcomes. Most notably, a spike in CEA did not correlate with the number of patients sent to surgery or patients with an appreciable increase in cyst size. A spike in CEA did not correlate with the development of a solid nodule within the PC nor progression on molecular analysis. Future studies should focus on the selected use of CEA analysis when patients undergo EUS surveillance evaluation for PCs.

Keywords: carcinoembryonic antigen (CEA), endoscopic ultrasound (EUS), fine-needle aspiration (FNA), pancreatic cyst, spike

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

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

Keywords: auraptene, glutathione, GST, Nrf2

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Authors: Ane Escobar, Paula Angelomé, Mihaela Delcea, Marek Grzelczak, Sergio Enrique Moya

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The antibacterial capacity of bone-anchoring implants can be improved by the use of antibiotics that can be delivered to the media after the surgery. Mesoporous films have shown great potential in drug delivery for orthopedic applications, since pore size and thickness can be tuned to produce different surface area and free volume inside the material. This work shows the synthesis of mesoporous titania films (MTF) by sol-gel chemistry and evaporation-induced self-assembly (EISA) on top of glass substrates. Pores with a diameter of 12nm were observed by Transmission Electron Microscopy (TEM). A film thickness of 100 nm was measured by Scanning Electron Microscopy (SEM). Gentamicin was used to study the antibiotic delivery from the film by means of High-performance liquid chromatography (HPLC). The Staphilococcus aureus strand was used to evaluate the effectiveness of the penicillin loaded films toward inhibiting bacterial colonization. MC3T3-E1 pre-osteoblast cell proliferation experiments proved that MTFs have a good biocompatibility and are a suitable surface for MC3T3-E1 cell proliferation. Moreover, images taken by Confocal Fluorescence Microscopy using labeled vinculin, showed good adhesion of the MC3T3-E1 cells to the MTFs, as well as complex actin filaments arrangement. In order to improve cell proliferation Bone Morphogenetic Protein-2 (BMP-2) was adsorbed on top of the mesoporous film. The deposition of the protein was proved by measurements in the contact angle, showing an increment in the hydrophobicity while the protein concentration is higher. By measuring the dehydrogenase activity in MC3T3-E1 cells cultured in dually functionalized mesoporous titatina films with gentamicin and BMP-2 is possible to find an improvement in cell proliferation. For this purpose, the absorption of a yellow-color formazan dye, product of a water-soluble salt (WST-8) reduction by the dehydrogenases, is measured. In summary, this study proves that by means of the surface modification of MTFs with proteins and loading of gentamicin is possible to achieve an antibacterial effect and a cell growth improvement.

Keywords: antibacterial, biocompatibility, bone morphogenetic protein-2, cell proliferation, gentamicin, implants, mesoporous titania films, osteoblasts

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Authors: Joshua Russell, Omar Zubair, Reuben Ndegwa

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Introduction: Mesenteric ischemia is an uncommon condition that can be challenging to diagnose in the acute setting, with the potential for significant morbidity and mortality. Very rarely has acute acalculous cholecystitis been described in the setting of mesenteric ischemia. Case: This was the case in a 78-year-old male, who initially presented with clinical and radiological evidence of small bowel obstruction, thought likely secondary to malignancy. The patient had a 6-week history of anorexia, worsening lower abdominal pain, and ~30kg of unintentional weight loss over a 12-month period and a CT- scan demonstrated a transition point in the distal ileum. The patient became increasingly hemodynamically unstable and peritonitic, and an emergency laparotomy was performed. Intra-operatively, however, no obvious transition point was identified, and instead, the gallbladder was markedly gangrenous and oedematous, consistent with acalculous cholecystitis. An open total cholecystectomy was subsequently performed. The patient was admitted to the Intensive Care Unit post-operatively and continued to deteriorate over the proceeding 48 hours, with two re-look laparotomies demonstrating progressively worsening bowel ischemia, initially in the distribution of the superior mesenteric artery and then the coeliac trunk. On review, the patient was found to have an aberrant right hepatic artery arising from the superior mesenteric artery. The extent of ischemia was considered non-survivable, and the patient was palliated. Discussion: Multiple theories currently exist for the underlying pathophysiology of acalculous cholecystitis, including biliary stasis, sepsis, and ischemia. This case lends further support to ischemia as the underlying etiology of acalculous cholecystitis. This is particularly the case when considered in the context of the patient’s aberrant right hepatic artery arising from the superior mesenteric artery, which occurs in 11-14% of patients. Conclusion: This case report adds further insight to the debate surrounding the pathophysiology of acalculous cholecystitis. It also presents acalculous cholecystitis as a complication of mesenteric ischemia that should always be considered, especially in the elderly patient and in the context of relatively common anatomical variations. Furthermore, the case brings to attention the importance of maintaining dynamic working diagnoses in the setting of evolving pathophysiology and clinical presentations.

Keywords: acalculous cholecystitis, anatomical variation, general surgery, mesenteric ischemia

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Authors: Ana Beltran Sanahuja, A. Valdés García, Saray Lopez De Pablo Gallego, Maria Soledad Prats Moya

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Tomato consumption has greatly increased worldwide in the last few years, mostly due to a growing demand for products like sofrito. In this sense, regular consumption of tomato-based products has been consistently associated with a reduction in the incidence of chronic degenerative diseases. The sofrito is a homemade tomato sauce typical of the Mediterranean area, which contains as main ingredients: tomato, onion, garlic and olive oil. There are also sofrito’s variations by adding other spices which bring at the same time not only color, flavor, smell and or aroma; they also provide medicinal properties, due to their antioxidant power. This protective effect has mainly been attributed to the predominant bioactive compounds present in sofrito, such as lycopene and other carotenoids as well as more than 40 different polyphenols. Regarding the cooking process, it is known that it can modify the properties and the availability of nutrients in sofrito; however, there is not enough information regarding this issue. For this reason, the aim of the present work is to evaluate the cooking effect on the antioxidant capacity of different variants of tomato-based sofrito combined with other spices, through the analysis of total phenols content (TPC) and to evaluate the antioxidant capacity by using the method of free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH). Based on the results obtained, it can be confirmed that the basic sofrito composed of tomato, onion, garlic and olive oil and the sofrito with 1 g of rosemary added, are the ones with the highest content of phenols presenting greater antioxidant power than other industrial sofrito, and that of other variables of sofrito with added thyme or higher amounts of garlic. Moreover, it has been observed that in the elaboration of the tomato-based sofrito, it is possible to cook until 60 minutes, since the cooking process increases the bioavailability of the carotenoids when breaking the cell walls, which weakens the binding forces between the carotenoids and increases the levels of antioxidants present, confirmed both with the TPC and DPPH methods. It can be concluded that the cooking process of different variants of tomato-based sofrito, including spices, can improve the antioxidant capacity. The synergistic effects of different antioxidants may have a greater protective effect; increasing, also, the digestibility of proteins. In addition, the antioxidants help to deactivate the free radicals of diseases such as atherosclerosis, aging, immune suppression, cancer, and diabetes.

Keywords: antioxidants, cooking process, phenols sofrito

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Authors: Tanu Sharma, Bikramjit Singh Bajwa, Inderpreet Kaur

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

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

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Authors: Amirreza Razzaghipour Sorkhab

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One of the most common disorders among humans is hearing impairment. This paper provides an evidence base that recovers understanding of Meniere’s disease and highlights the physical and mental health correlates of the disorder. Meniere's disease is more common in the elderly. The term idiopathic endolymphatic hydrops has been attributed to this disease by some in the previous. Meniere’s disease demonstrations a genetic tendency, and a family history is found in 10% of cases, with an autosomal dominant inheritance pattern. The COCH gene may be one of the hereditary factors contributing to Meniere’s disease, and the possibility of a COCH mutation should be considered in patients with Meniere’s disease symptoms. Should be considered Missense mutations in the COCH gene cause the autosomal dominant sensorineural hearing loss and vestibular disorder. Meniere’s disease is a complex, heterogeneous disorder of the inner ear and that is characterized by episodes of vertigo lasting from minutes to hours, fluctuating sensorineural hearing loss, tinnitus, and aural fullness. The existing evidence supports the suggestion that age and sleep disorder are risk factors for Meniere's disease. Many factors have been reported to precipitate the progress of Menier, including endolymphatic hydrops, immunology, viral infection, inheritance, vestibular migraine, and altered intra-labyrinthine fluid dynamics. Although there is currently no treatment that has a proven helpful effect on hearing levels or on the long-term evolution of the disease, however, in the primary stages, the hearing may improve among attacks, but a permanent hearing loss occurs in the majority of cases. Current publications have proposed a role for the intratympanic use of medicine, mostly aminoglycosides, for the control of vertigo. more than 85% of patients with Meniere's disease are helped by either changes in lifestyle and medical treatment or minimally aggressive surgical procedures such as intratympanic steroid therapy, intratympanic gentamicin therapy, and endolymphatic sac surgery. However, unilateral vestibular extirpation methods (intratympanic gentamicin, vestibular nerve section, or labyrinthectomy) are more predictable but invasive approaches to control the vertigo attacks. Medical therapy aimed at reducing endolymph volume, such as low-sodium diet, diuretic use, is the typical initial treatment.

Keywords: meniere's disease, endolymphatic hydrops, hearing loss, vertigo, tinnitus, COCH gene

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Authors: Muhandiram Rallage Ruvini Nisansala Yatigammana, Anuruddhika Kumudu Kumari Rajakaruna Jayathilaka

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Sports injuries are common among teenagers and children engaged in organized sports. While most sports injuries are typical, some rare occurrences involve conditions such as eye, dental, cervical, and rare internal organ injuries, such as pancreatic injuries. These injuries, especially traumatic pancreatitis, require prompt attention due to their potential for severe and sometimes fatal complications. This case revolves around a real accident involving a 12-year-old girl, Piyumi, who suffered a face-to-face collision during netball practice, resulting in severe abdominal pain. After a medical examination, she was diagnosed with a rare pancreatic injury, uncommon in children compared to adults. In Piyumi’s case, she had a grade 3 pancreatic injury and underwent non-surgical management, successfully healing her wound without surgery. The study attempts to fill empirical and population gaps, addressing a rarely discussed injury experienced by a 12-year-old female netball player. The paper will also provide an in-depth understanding of pancreatic injury, which is a rare sports injury. The study’s main objective was to investigate the incidence and characteristics of pancreatic injury, particularly focusing on pancreatic trauma, among children and adolescents engaged in high-impact sports, such as netball. This research adopted a case study strategy, employing interviews as the primary data collection method. Interviews were conducted with Piyumi, her parents, and the two specialist doctors directly involved in her treatment, providing firsthand accounts and insights. By examining the case, the paper arrives at three main conclusions. Firstly, pancreatic damage is uncommon, especially in the sports world, and proper diagnosis is essential to avoiding health concerns, particularly for minors. Secondly, CT (Computed Tomography) was useful in locating the injury, as injuries can be diagnosed very well with Computed Tomography (CT) images. Finally, and most importantly, pancreatic injuries are infrequent, but trauma can still occur, particularly in high-impact sports or accidents involving extreme force or falls. These injuries should be accurately diagnosed and treated promptly.

Keywords: child athlete, pancreatic injury, rare sports injuries, sportswoman

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

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

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

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

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

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

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

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

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

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Authors: Humaira M. Khan, Kanwal Asif

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Ischemic stroke is a neurological disorder with a complex pathophysiology associated with motor, sensory and cognitive deficits. Major approaches developed to treat acute ischemic stroke fall into two categories, thrombolysis and neuroprotection. The objectives of this study were to evaluate the neuroprotective and anti-thrombolytic effects of Olea europaea (olive oil) and Malus domestica (apple cider vinegar) and their combination in rat stroke model. Furthermore, histopathological analysis was also performed to assess the severity of ischemia among treated and reference groups. Male albino rats (12 months age) weighing 300- 350gm were acclimatized and subjected to middle cerebral artery occlusion method for stroke induction. Olea europaea and Malus domestica was administered orally in dose of 0.75ml/kg and 3ml/kg and combination was administered at dose of 0.375ml/kg and 1.5ml/kg prophylactically for consecutive 21 days. Negative control group was dosed with normal saline whereas piracetam (250mg/kg) was administered as reference. Neuroprotective activity of standard piracetam, Olea europaea, Malus domestica and their combination was evaluated by performing functional outcome tests i.e. Cylinder, pasta, ladder run, pole and water maize tests. Rats were subjected to surgery after 21 days of treatment for analysis from stroke recovery. Olea europaea and Malus domestica in individual doses of 0.75ml/kg and 3ml/kg respectively showed neuroprotection by significant improvement in ladder run test (121.6± 0.92;128.2 ± 0.73) as compare to reference (125.4 ± 0.74). Both test doses showed significant neuroprotection as compare to reference (9.60 ± 0.50) in pasta test (8.40 ± 0.24;9.80 ± 0.37) whereas with cylinder test, experimental groups showed significant increase in movements (6.60 ± 0.24; 8.40 ± 0.24) in contrast to reference (7.80 ± 0.37).There was a decrease in percentage time taken f to reach the hidden maize in water maize test (56.80 ± 0.58;61.80 ± 0.66) at doses 0.75ml/kg and 3ml/kg respectively as compare to piracetam (59.40 ± 1.07). Olea europaea and Malus domestica individually showed significant reduction in duration of mobility (127.0 ± 0.44; 123.0 ± 0.44) in pole test as compare to piracetam (124.0 ± 0.70). Histopathological analysis revealed the significant extent of protection from ischemia after prophylactic treatments. Hence it is concluded that Olea europaea and Malus domestica are effective neuroprotective agents alone as compare to their combination.

Keywords: ischemia, Malus domestica, neuroprotection, Olea europaea

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Authors: Devyani Shete, Sudeep Rai

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

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

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Authors: Alina Beraudi, Simona Catalani, Dalila De Pasquale, Eva Bianconi, Umberto Santoro, Susanna Stea, Pietro Apostoli

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Recently the European Community, in line with the international scientific community such as with the Consensus Statement, has determined to stop the use of metal-on-metal big head stemmed hip prosthesis. Among the factors accounted as responsible for the high failure rates of these hip implants are the release and accumulation of metal ions. Many studies have correlated the presence of these ions, besides other factors, with the induction of oxidative stress response. In our study on 12 subjects, we observed the patient specific capability to eliminate metal ions after revision surgery. While for cobalt all the patients were able to completely excrete cobalt ions within 5-7 months after metal-on-metal bearing removal, for chromium ions it didn’t happen. If on the one hand the toxicokinetic differences between the two types of ions are confirmed by toxicological and occupational studies, on the other hand, this peculiar way of exposition represents a novel and important point of view. Thus, two different approaches were performed to better understand the subject specific capability to transport metal ions (albumin study) and to manage the response to them (heme-oxygenase-1 study): - a mutational screening of ALBUMIN gene was conducted in 30 MoM prosthetic patients resulting in the absence of nucleotidic changes compared with the ALB reference sequence. To this study was also added the analysis of expression of modified albumin protein; - a gene and protein expression study on 44 patients of heme-oxygenase-1, that is one of the most important antioxidant enzyme induced by metallic ions, was performed. This study resulted in no statistically significant differences in the expression of the gene and protein heme-oxygenase-1 between prosthetic and non-prosthetic patients, as well as between patients with high and low ions levels. Our results show that the protein studied (albumin and heme-oxygenase-1) seem to be not involved in determining chromium and cobalt ions level. On the other hand, achromium and cobalt elimination rates are different, but similar in all patients analyzed, suggesting that this process could be not patient-related. We support the importance of researching more about ions transport within the organism once released by hip prosthesis, about the chemical species involved, the districts where they are contained and the mechanisms of elimination, not excluding the existence of a subjective susceptibility to these metals ions.

Keywords: chromium, cobalt, hip prosthesis, individual susceptibility

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Authors: Tan Xin Zhong Timothy, Chang Chen Jie Victor, Yew Kwan Tong, Lim Geok Peng Sandy

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Background: Leaders in crisis response teams such as Trauma Teams in hospitals are essential to the effective coordination and direction of the team. The response to emergency trauma situations must be accurate, rapid, and well executed. To this end, the team leader’s social, technical and leadership skills are essential factors that implicate the success of an emergency trauma intervention. While each emergency trauma case varies in severity and complexity, and the experience and expertise of team leaders may vary, it would be productive to identify certain coordinative and directive functions that improve the capacity for leading a team. Methods: This qualitative study of Trauma Team physicians in Singapore General Hospital (SGH) involved 50 in-depth interviews with doctors and nurses involved in Trauma Team activations, observations of Trauma Teams managing emergency patients, and reviews of audio/video recordings of 65 trauma activations. The interviews were conducted with doctors of various ranks across the relevant departments, 12 from the Emergency Department (ED), 11 from General Surgery (GS) and 8 from Orthopaedics, while the 6 nurses were from ED. In accordance with the grounded theory approach, the content of the interviews was coded and analysed in order to derive broad leadership themes that corresponded with certain behavioural traits exhibited by trauma team leaders, supplemented with the observational and audio/video data. Results: The leadership behaviours of the team leaders could be typified into three broad categories: team orientation, engagement and activeness. Team orientation corresponds with the source and form of cognitive responsibility, decision-making and informational contributions, divisible into individualistic and consultative sub-categories. Engagement refers to the type of activity that leaders prefer to engage in, and which implicates their attentional focus, divisible into participatory and supervisory sub-categories. Activeness is a function of the leader’s attitudes towards the behavioural regulation of the team, which manifests in inactivity or activity to augment or merely align with protocol. These factors are not exhaustive and are contextually sensitive, but collectively implicate a significant portion of the leadership activity observed in trauma teams.

Keywords: trauma team activations, critical event management, leadership, teamwork

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Authors: Maria Stepankova, Lucie Vistejnova, Pavel Klein, Tereza Blassova, Marketa Slajerova, Radek Sedlacek, Martin Bartos, Jaroslav Chlupac

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Background: Clinical outcome benefits of the segment rib fracture surgical therapy are well known and follow from better stabilization of the chest wall. Despite this, some authors still incline to conservative therapy and point out to possible rib fracture healing failure in connection with the bone vascular supply disturbance caused by metal plate implantation. This suggestion met neither experimental nor clinical verification and remains the object of discussion. In our pilot study we investigated the titanium plate fixation effect on the rib fracture healing in porcine model and its histological, biomechanical and radiological aspects. Materials and Method: Two porcine models (experimental group) underwent the operative chest wall stabilization with a titanium plate implantation after osteotomy. Two other porcine models (control group) were treated conservatively after osteotomy. Three weeks after surgery, all animals were sacrificed, treated ribs were explanted and the histological analysis, µCT imaging and biomechanical testing of the calluses tissue were performed. Results: In µCT imaging, experimental group showed a higher cortical bone volume compared to the control group. Histological analysis using the non-decalcified bone tissue blocks demonstrated more maturated callus with higher newly-formed osseous tissue ratio in experimental group in comparison to controls. In contrast, no significant differences in bone blood vessels supply in both groups were observed. This finding suggests that the bone blood supply in experimental group was not impaired. Biomechanical analysis using 3-point bending test demonstrated significantly higher bending stiffness and the maximum force in experimental group. Conclusion: Based on our observation, it could be concluded, that the titanium plate fixation of the rib fractures leads to faster bone callus maturation whereas does not cause the vascular supply impairment after 3 weeks and thus has a beneficial effect on the rib fracture healing.

Keywords: bone vascular supply, chest wall stabilization, fracture healing, histological analysis, titanium plate implantation

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Authors: Arunas Burinskas, Aurelija Burinskiene

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

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

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Authors: Kittitara Chunlakittiphan, Patompong Satapornpong

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

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

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

Abstract:

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

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

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