Search results for: recurrent urinary tract infections
762 Oxidative Status and Some Serum Macro Minerals during Estrus, Anestrous and Repeat Breeding in Cholistani Cattle
Authors: Farah Ali, Laeeq Akbar Lodhi, Riaz Hussain, Muhammad Sufyan
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The present study was conducted to determine the macro mineral profile and biomarkers of oxidative stress in Cholistani cattle kept at a public farm and various villages in district Bahawalpur. For this purpose 90 blood samples were collected each from estrual, anestrous and repeat breeding cattle having different age and lactation number. Reproductive tract examination of all the cattle was carried out to determine the reproductive status. Blood samples without EDTA were collected for serum separation at day of estrus (normal cyclic), repeat breeder and anestrous cows. The serum calcium levels were significantly decreased (P<0.05) in anestrous (7.31±0.02 mg/dl) cattle as compared to estrus. However, these values were non-significantly different between repeat breeder and cattle having estrus phase. The concentrations of serum phosphorus were significantly higher (P<0.01) in normal estrual (4.99±0.08 mg/dl) as compared torepeat breeder (3.90±0.06 mg/dl) and anestrous (3.82±0.04 mg/dl) Cholistani cattle. Mean serum MDA (nmol/ml) levels of repeat breeder (2.68±0.18) and anestrous (2.54±0.22) were significantly(P<0.01) higher than the estrous (1.71±0.03) cattle. Moreover, the serum nitric oxide levels(µmol/L) were also increased significantly (P<0.01) in repeat breeder(58.28±4.01)and anestrous (61.40±9.40) than the normalestrous (31.67±6.71) cattle. The ratio of Ca: P in normal cyclic animals was lower (1.73:1) as compared to the anestrous animals (1.92:1). It can be concluded from the present study that the level of Ca: P should also be near to 1.5:1 for better reproductive performance.Keywords: anestrus, cholistani cattle, minerals, oxidative stress, repeat breeder
Procedia PDF Downloads 604761 Paraoxonase 1 (PON 1) Arylesterase and Lactonase Activities, Polymorphism and Conjugated Dienes in Gastroenteritis in Paediatric Population
Authors: M. R. Mogarekar, Shraddha V. More, Pankaj Kumar
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Gastroenteritis, the third leading killer of children in India today is responsible for 13% of all deaths in children <5 years of age and kills an estimated 300,000 children in India each year. We decided to investigate parameters which can help in early disease detection and prompt treatment. Serum paraoxonase is calcium dependent esterase which is widely distributed among tissues such as liver, kidney, and intestine and is located in the chromosomal region 7q21.3 22.1. Studies show the presence of excessive reactive oxygen metabolites and antioxidant imbalance in the gastrointestinal tract leading to oxidative stress in gastroenteritis. To our knowledge, this is the first ever study done. The objective of present study is to investigate the role of paraoxonase 1 (PON 1) status i.e arylesterase and lactonase activities and Q192R polymorphism and conjugated dienes, in gastroenteritis of paediatric population. The study and control group consists of 40 paediatric patients with and without gastroenteritis. Paraoxonase arylesterase and lactonase activities were assessed and phenotyping was determined. Conjugated dienes were also assessed. PON 1 arylesterase activities in cases (61.494±13.220) and controls (70.942±15.385) and lactonase activities in cases (15.702±1.036) and controls (17.434±1.176) were significantly decreased (p<0.05). There is no significant difference of phenotypic distribution in cases and controls. Conjugated dienes were found significantly increased in patients (0.086±0.024) than the control group (0.064±0.019) (p<0.05). Paraoxonase 1 activities (arylesterase and lactonase) and conjugated dienes may be useful in risk assessment and management in gastroenteritis in paediatric population.Keywords: paraoxonase 1 polymorphism, arylesterase, lactonase, conjugated dienes, p-nitrophenylacetate, DHC
Procedia PDF Downloads 306760 Response Delay Model: Bridging the Gap in Urban Fire Disaster Response System
Authors: Sulaiman Yunus
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The need for modeling response to urban fire disaster cannot be over emphasized, as recurrent fire outbreaks have gutted most cities of the world. This necessitated the need for a prompt and efficient response system in order to mitigate the impact of the disaster. Promptness, as a function of time, is seen to be the fundamental determinant for efficiency of a response system and magnitude of a fire disaster. Delay, as a result of several factors, is one of the major determinants of promptgness of a response system and also the magnitude of a fire disaster. Response Delay Model (RDM) intends to bridge the gap in urban fire disaster response system through incorporating and synchronizing the delay moments in measuring the overall efficiency of a response system and determining the magnitude of a fire disaster. The model identified two delay moments (pre-notification and Intra-reflex sequence delay) that can be elastic and collectively plays a significant role in influencing the efficiency of a response system. Due to variation in the elasticity of the delay moments, the model provides for measuring the length of delays in order to arrive at a standard average delay moment for different parts of the world, putting into consideration geographic location, level of preparedness and awareness, technological advancement, socio-economic and environmental factors. It is recommended that participatory researches should be embarked on locally and globally to determine standard average delay moments within each phase of the system so as to enable determining the efficiency of response systems and predicting fire disaster magnitudes.Keywords: delay moment, fire disaster, reflex sequence, response, response delay moment
Procedia PDF Downloads 205759 Identifying of Hybrid Lines for Lpx-B1 Gene in Durum Wheat
Authors: Özlem Ateş Sönmezoğlu, Begüm Terzi, Ahmet Yıldırım, Ramazan Özbey
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The basic criteria which determine durum wheat quality is its suitability for pasta processing that is pasta making quality. Bright yellow color is a desired property in pasta products. Durum wheat pasta making quality is affected by grain pigment content and oxidative enzymes which affect adversely bright yellow color. Of the oxidative enzymes, lipoxygenase LOX is the most effective one on oxidative bleaching of yellow pigments in durum wheat products. Thus, wheat cultivars that are high in yellow pigments but low in LOX enzyme activity should be preferred for the production of pasta with high color quality. The aim of this study was to reduce lipoxygenase activities of the backcross durum wheat lines that were previously improved for their protein quality. For this purpose, two advanced lines with different parents (TMB2 and TMB3) were used recurrent parents. Also, Gediz-75 wheat with low LOX enzyme activity was used as the gene source. In all of the generations, backcrossed plants carrying the targeted gene region (Lpx-B1.1) were selected using SSR markers by marker assisted selection method. As a result, the study will be completed in three years instead of six years required in a classical backcross breeding study, leading to the development of high-quality candidate varieties. This research has been financially supported by TÜBİTAK (Project No: 112T910).Keywords: durum wheat, lipoxygenase, LOX, Lpx-B1.1, MAS, Triticum durum
Procedia PDF Downloads 306758 The Determination of Total Microbial Count and Prevalence of Salmonella in the Shrimp Supply in Khuzestan Province
Authors: Sana Mohammad Jafar
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Salmonella is one of the major causes of foodborne diseases throughout the world. Shrimp are an important commodity in world fishery trade. The microbiological quality of shrimp must be evaluated for assurance of shrimp. The aim of this study was to evaluate the microbiological quality and to determine the prevalence of Salmonella in shrimp sold in Khuzestan province. In this study, a total of 245 samples of shrimp sold in Khuzestan province were tested for Salmonella prevalence and total microbial population. The mean aerobic bacterial count in 50.2% of samples was 2200, in 29.8% of samples was 13,600, in 20% of samples was 36,700, and the mean aerobic bacterial count in the total samples was 20,000. (20,000 cfu/cc). Of the total samples, 33 samples were positive for Salmonella and the prevalence of Salmonella was determined 13.4%. These results indicate the possibility that shrimp contribute to foodborne infections. The improvement of shrimp quality is an important issue, and shrimp before consuming should be washed with water containing chlorine, with the aim of increasing safety. In addition, it should be avoided to eat shrimp as raw or not cooked properly.Keywords: determination, total microbial, Salmonella, shrimp
Procedia PDF Downloads 238757 Involvement of BCRP/ABCG2 in Protective Mechanisms of Resveratrol against Methotrexate-Induced Renal Damage in Rats
Authors: Mohamed A. Morsy, Azza A. El-Sheikh, Abdulla Y. Al-Taher
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Resveratrol (RES) is a well-known polyphenol antioxidant. We have previously shown that testicular protective effect of RES against the anticancer drug methotrexate (MTX)-induced toxicity involves transporter-mediated mechanisms. Here, we investigated the effect of RES on MTX-induced nephrotoxicity. Rats were administered RES (10 mg/kg/day) for 8 days, with or without a single MTX dose (20 mg/kg i.p.) at day 4 of the experiment. MTX induced nephrotoxicity evident by significantly increase in serum blood urea nitrogen and creatinine compared to control, as well as distortion of kidney microscopic structure. MTX also significantly increased renal nitric oxide level, with induction of inducible nitric oxide synthase expression. MTX also significantly up-regulated fas ligand and caspase 3. Administering RES prior to MTX significantly improved kidney function and microscopic picture, as well as significantly decreased nitrosative and apoptotic markers compared to MTX alone. RES, but not MTX, caused significant increase in expression of breast cancer resistance protein (BCRP), an apical efflux renal transporter that participates in urinary elimination of both MTX and RES. Interestingly, concomitant MTX and RES caused further up-regulation of renal Bcrp compared to RES alone. Using Human BCRP ATPase assay, both RES and MTX exhibited dose-dependent increase in ATPase activity, with Km values of 0.52 ± 0.03 and 30.9 ± 4.2 µM, respectively. Furthermore, combined RES and MTX caused ATPase activity which was significantly less than maximum ATPase activity attained by the positive control; sulfasalazine (12.5 µM). In conclusion, RES exerted nephro-protection against MTX-induced toxicity through anti-nitrosative and anti-apoptotic effects, as well as via up-regulation of renal Bcrp.Keywords: methotrexate, resveratrol, nephrotoxicity, breast cancer resistance protein
Procedia PDF Downloads 294756 Developing Effective Strategies to Reduce Hiv, Aids and Sexually Transmitted Infections, Nakuru, Kenya
Authors: Brian Bacia, Esther Githaiga, Teresia Kabucho, Paul Moses Ndegwa, Lucy Gichohi
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Purpose: The aim of the study is to ensure an appropriate mix of evidence-based prevention strategies geared towards the reduction of new HIV infections and the incidence of Sexually transmitted Illnesses Background: In Nakuru County, more than 90% of all HIV-infected patients are adults and on a single-dose medication-one pill that contains a combination of several different HIV drugs. Nakuru town has been identified as the hardest hit by HIV/Aids in the County according to the latest statistics from the County Aids and STI group, with a prevalence rate of 5.7 percent attributed to the high population and an active urban center. Method: 2 key studies were carried out to provide evidence for the effectiveness of antiretroviral therapy (ART) when used optimally on preventing sexual transmission of HIV. Discussions based on an examination, assessments of successes in planning, program implementation, and ultimate impact of prevention and treatment were undertaken involving health managers, health workers, community health workers, and people living with HIV/AIDS between February -August 2021. Questionnaires were carried out by a trained duo on ethical procedures at 15 HIV treatment clinics targeting patients on ARVs and caregivers on ARV prevention and treatment of pediatric HIV infection. Findings: Levels of AIDS awareness are extremely high. Advances in HIV treatment have led to an enhanced understanding of the virus, improved care of patients, and control of the spread of drug-resistant HIV. There has been a tremendous increase in the number of people living with HIV having access to life-long antiretroviral drugs (ARV), mostly on generic medicines. Healthcare facilities providing treatment are stressed challenging the administration of the drugs, which require a clinical setting. Women find it difficult to take a daily pill which reduces the effectiveness of the medicine. ART adherence can be strengthened largely through the use of innovative digital technology. The case management approach is useful in resource-limited settings. The county has made tremendous progress in mother-to-child transmission reduction through enhanced early antenatal care (ANC) attendance and mapping of pregnant women Recommendations: Treatment reduces the risk of transmission to the child during pregnancy, labor, and delivery. Promote research of medicines through patients and community engagement. Reduce the risk of transmission through breastfeeding. Enhance testing strategies and strengthen health systems for sustainable HIV service delivery. Need exists for improved antenatal care and delivery by skilled birth attendants. Develop a comprehensive maternal reproductive health policy covering equitability, efficient and effective delivery of services. Put in place referral systems.Keywords: evidence-based prevention strategies, service delivery, human management, integrated approach
Procedia PDF Downloads 86755 Stomach Perforation, due to Chronic External Pressure
Authors: Angelis P. Barlampas
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PURPOSE: The purpose of this paper is to demonstrate the important role of taking an appropriate and detailed history, in order to reach the best possible diagnostic conclusion. MATERIAL: A patient presented to the emergency department due to the sudden onset of continuous abdominal pain, during the last hour and with the clinical symptoms of an acute abdomen. During the clinical examination, signs of peritoneal irritation and diffuse abdominal tenderness were found. The rest of the clinical and laboratory tests did not reveal anything important. From the reported medical history, nothing of note was found, except for the report of a large liver cyst, for which he was advised not to take any further action, except from regular ultrasound examination . METHOD: A computed tomography examination was performed after per os administration of gastrografin, which revealed a hyperdense ascitic effusion, similar in density to that of gastrografin within the intestinal tract. The presence of a large cyst of the left hepatic lobe was confirmed, contacting and pushing against the stomach. In the area of the contact between the liver cyst and the pylorus, there were extraluminal air bubbles and local opacity of the peritoneal fat, with a small hyperdense effusion. Result : The above, as well as the absence of a history of stomach ulcer or recent trauma, or other pathology, argue in favor of acute pyloric perforation, due to mural necrosis, in response to chronic external pressure from the pre-existing large liver cyst.Keywords: perforation, stomach, large liver cyst, CT abdomen, acute abdominal pain, intraperitoneal leakage, constrast leakage
Procedia PDF Downloads 94754 Outcomes of Live Renal Donors with a History of Nephrolithiasis
Authors: Bin Mohamed Ebrahim, Aminesh Singla, Henry Pleass
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Aim: There is an ongoing gap in renal transplantation between organs available for donation and recipients on the waiting list. Live donors with pre-existing or a history of renal calculi were thought to be a relative contraindication due to safety concerns for donors. We aim to review current literature assessing outcomes of donors who were found to have a history of renal calculi. Methods: Ovid and Embase were searched between 1960 to 2021 using key terms and Medical Subject Headings (MeSH) – nephrolithiasis, renal stones, renal transplantation and renal graft. Articles included conference proceedings and journal articles and were not excluded based on patient numbers. Studies were excluded if the specific organ was not identified, duplicated reports found or if post-transplant outcomes were not recorded. Outcomes were donor’s renal function or renal calculi recurrence postoperatively. Results: Upon reviewing 344 articles, 14 manuscripts met inclusion criteria. A total of 152 live donors were identified as having pre-existing or with a history of renal calculi at pre-operative workup. The mean stone size was 2.6 4mm (1 – 16) with a mean follow-up duration of 31.8 months (1 – 96). Seven studies had both outcomes. None showed renal complications or stone recurrence. The remaining studies contained 2 out of 84 patients having recurrent nephrolithiasis. Conclusion: Data suggests minimal morbidity involved for live renal donors with a history of nephrolithiasis. This should encourage surgeons to continue recruiting such donors for kidney transplantation.Keywords: renal transplantation, renal graft, nephrolithiasis, renal calculi, live donor
Procedia PDF Downloads 179753 The Effect of Particulate Matter on Cardiomyocyte Apoptosis Through Mitochondrial Fission
Authors: Tsai-chun Lai, Szu-ju Fu, Tzu-lin Lee, Yuh-Lien Chen
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There is much evidence that exposure to fine particulate matter (PM) from air pollution increases the risk of cardiovascular morbidity and mortality. According to previous reports, PM in the air enters the respiratory tract, contacts the alveoli, and enters the blood circulation, leading to the progression of cardiovascular disease. PM pollution may also lead to cardiometabolic disturbances, increasing the risk of cardiovascular disease. The effects of PM on cardiac function and mitochondrial damage are currently unknown. We used mice and rat cardiomyocytes (H9c2) as animal and in vitro cell models, respectively, to simulate an air pollution environment using PM. These results indicate that the apoptosis-related factor PUMA, a regulator of apoptosis upregulated by p53, is increased in mice treated with PM. Apoptosis was aggravated in cardiomyocytes treated with PM, as measured by TUNEL assay and Annexin V/PI. Western blot results showed that CASPASE3 was significantly increased and BCL2 (B-cell lymphoid 2) was significantly decreased under PM treatment. Concurrent exposure to PM increases mitochondrial reactive oxygen species (ROS) production by MitoSOX Red staining. Furthermore, using Mitotracker staining, PM treatment significantly shortened mitochondrial length, indicating mitochondrial fission. The expression of mitochondrial fission-related proteins p-DRP1 (phosphodynamics-related protein 1) and FIS1 (mitochondrial fission 1 protein) was significantly increased. Based on these results, the exposure to PM worsens mitochondrial function and leads to cardiomyocyte apoptosis.Keywords: particulate matter, cardiomyocyte, apoptosis, mitochondria
Procedia PDF Downloads 100752 Study of the Antimicrobial Activity of Aminoreductone against Pathogenic Bacteria in Comparison with Other Antibiotics
Authors: Vu Thu Trang, Lam Xuan Thanh, Samira Sarter, Tomoko Shimamura, Hiroaki Takeuchi
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Antimicrobial activities of aminoreductone (AR), a product formed in the initial stage of Maillard reaction, were screened against pathogenic bacteria. A significant growth inhibition of AR against all 7 isolates (Staphylococcus aureus ATCC® 25923™, Salmonella Typhimurium ATCC® 14028™, Bacillus cereus ATCC® 13061™, Bacillus subtilis ATCC® 11774™, Escherichia coli ATCC® 25922™, Enterococcus faecalis ATCC® 29212™, Listeria innocua ATCC® 33090™) were observed by the standard disc diffusion methods. The inhibition zone for each isolate by AR (2.5 mg) ranged from 15±0 mm to 28.3±0.4 mm in diameter. The minimum inhibitory concentration (MIC) of AR ranging from 20 mM to 26 mM was proven in the seven isolates tested. AR also showed the similar effect of growth inhibition in comparison with antibiotics frequently used for the treatment of infections bacteria, such as amikacin, ciprofloxacin, meropennem, and levofloxacin. The results indicated that foods containing AR are valuable sources of bioactive compounds towards pathogenic bacteria.Keywords: pathogenic bacteria, aminoreductone, Maillard reaction, antimicrobial activity
Procedia PDF Downloads 380751 Efficacy of Carvacrol as an Antimicrobial Wash Treatment for Reducing Both Campylobacter jejuni and Aerobic Bacterial Counts on Chicken Skin
Authors: Sandip Shrestha, Ann M. Donoghue, Komala Arsi, Basanta R. Wagle, Abhinav Upadhyay, Dan J. Donoghue
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Campylobacter, one of the major cause of foodborne illness worldwide, is commonly present in the intestinal tract of poultry. Many strategies are currently being investigated to reduce Campylobacter counts on commercial poultry during processing with limited success. This study investigated the efficacy of the generally recognized as safe compound, carvacrol (CR), a component of wild oregano oil as a wash treatment for reducing C. jejuni and aerobic bacteria on chicken skin. A total of two trials were conducted, and in each trial, a total of 75 skin samples (4cm × 4cm each) were randomly allocated into 5 treatment groups (0%, 0.25%, 0.5%, 1% and 2% CR). Skin samples were inoculated with a cocktail of four wild strains of C. jejuni (~ 8 log10 CFU/skin). After 30 min of attachment, inoculated skin samples were dipped in the respective treatment solution for 1 min, allowed to drip dry for 2 min and processed at 0, 8, 24 h post treatment for enumeration of C. jejuni and aerobic bacterial counts (n=5/treatment/time point). The data were analyzed by ANOVA using PROC GLM procedure of SAS 9.3. All the tested doses of CR suspension consistently reduced C. jejuni counts across all time points. The 2% CR wash was the most effective treatment and reduced C. jejuni counts by ~4 log₁₀ CFU/sample (P < 0.05). Aerobic counts were reduced for the 0.5% CR dose at 0 and 24h in Trial 1 and at 0, 8 and 24h in Trial 2. The 1 and 2% CR doses consistently reduced aerobic counts in both trials up to 2 log₁₀ CFU/skin.Keywords: Campylobacter jejuni, carvcrol, chicken skin, postharvest
Procedia PDF Downloads 179750 Routine pus Swabs for Uncomplicated Abscesses – Do They Alter Our Management Plan?
Authors: Abdelrahman Abdelrahman, Lawrence Nip, Seun Ikotun, Iman Satar, Anur Miah
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Introduction: Incision and drainage of an abscess is a common procedure performed by the general surgeon. Pus swabs are often obtained routinely for MC&S.Our study aimed to investigate whether swabs taken at our local institution had any impact on the overall management plan for uncomplicated abscesses. Methods: We retrospectively assessed all patients presenting to University Hospital Lewisham with an abscess between October 2020 – April 2021. Exclusion criteria were recurrent abscesses, patients admitted with sepsis, known inflammatory bowel disease, immunocompromised, and those managed non-operatively. Results: We identified 131 patients who met the inclusion criteria. Two thirds were performed in theatre under general anaesthetic and the other one third under local. 63% of patients had a pus swab collected. Of these, 96% were not followed up by the requesting doctor, and there was no further patient contact. In the other 4%, the organisms cultured were flagged as atypical such as MRSA. In these cases, microbiology advice was that if the patient was clinically well and adequate drainage was achieved, then no furtherantibiotics were required. All patients were discharged before any microbiology results had come back with no subsequent change in the management plan. Average cost of pus swab = £10.10 – potentially cost saving of £1656.4 annually. Conclusion: Our study reveals that the majority of pus swabs taken from uncomplicated abscessesare not followed up by requesting doctor with no impact on the overall management plan. We, therefore, do not recommend the routine use of pus swabs for uncomplicated abscesses.Keywords: pus swabs, uncomplated abscess, Pus MCS, follow up of uncomplicated abscess
Procedia PDF Downloads 175749 Technology Transfer and FDI: Some Lessons for Tunisia
Authors: Assaad Ghazouani, Hedia Teraoui
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The purpose of this article is to try to see if the FDI actually contributes to technology transfer in Tunisia or are there other sources that can guarantee this transfer? The answer to this problem was gradual as we followed an approach using economic theory, the reality of Tunisia and econometric and statistical tools. We examined the relationship between technology transfer and FDI in Tunisia over a period of 40 years from 1970 to 2010. We estimated in two stages: first, a growth equation, then we have learned from this regression residue (proxy technology), secondly, we regressed on European FDI, exports of manufactures, imports of goods from the European Union in addition to other variables to test the robustness of the results and describing the level of infrastructure in the country. It follows from our study that technology transfer does not originate primarily and exclusively in the FDI and the latter is econometrically weakly with technology transfer and spill over effect of FDI does not seem to occur according to our results. However, the relationship between technology transfer and imports is negative and significant. Although this result is cons-intuitive, is recurrent in the literature of panel data. It has also given rise to intense debate on the microeconomic modelling as well as on the empirical applications. Technology transfer through trade or foreign investment has become a catalyst for growth recognized by numerous empirical studies in particular. However, the relationship technology transfer FDI is more complex than it appears. This complexity is due, primarily, but not exclusively to the close link between FDI and the characteristics of the host country. This is essentially the host's responsibility to establish general conditions, transparent and conducive to investment, and to strengthen human and institutional capacity necessary for foreign capital flows that can have real effects on growth.Keywords: technology transfer, foreign direct investment, economics, finance
Procedia PDF Downloads 320748 Performance Assessment of Ventilation Systems for Operating Theatres
Authors: Clemens Bulitta, Sasan Sadrizadeh, Sebastian Buhl
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Introduction: Ventilation technology in operating theatres (OT)is internationally regulated by dif-ferent standards, which define basic specifications for technical equipment and many times also the necessary operating and performance parameters. This confronts the operators of healthcare facilities with the question of finding the best ventilation and air conditioning system for the OT in order to achieve the goal of a large and robust surgicalworkzone with appropriate air quality and climate for patient safety and occupational health. Additionally, energy consumption and the potential need for clothing that limits transmission of bacteria must be considered as well as the total life cycle cost. However, the evaluation methodology of ventilation systems regarding these matters are still a topic of discussion. To date, there are neither any uniform standardized specifications nor any common validation criteria established. Thus, this study aimed to review data in the literature and add ourown research results to compare and assess the performance of different ventilations systems regarding infection preventive effects, energy efficiency, and staff comfort. Methods: We have conducted a comprehensive literature review on OT ventilation-related topics to understand the strengths and limitations of different ventilation systems. Furthermore, data from experimental assessments on OT ventilation systems at the University of Amberg-Weidenin Germany were in-cluded to comparatively assess the performance of Laminar Airflow (LAF), Turbulent Mixing Air-flow(TMA), and Temperature-controlled Airflow (TcAF) with regards to patient and occupational safety as well as staff comfort including indoor climate.CFD simulations from the Royal Institute of Technology in Sweden (KTH) were also studied to visualize the differences between these three kinds of ventilation systems in terms of the size of the surgical workzone, resilience to obstacles in the airflow, and energy use. Results: A variety of ventilation concepts are in use in the OT today. Each has its advantages and disadvantages, and thus one may be better suited than another depend-ing on the built environment and clinical workflow. Moreover, the proper functioning of OT venti-lation is also affected by multiple external and internal interfering factors. Based on the available data TcAF and LAF seem to provide the greatest effects regarding infection control and minimizing airborne risks for surgical site infections without the need for very tight surgical clothing systems. Resilience to obstacles, staff comfort, and energy efficiency seem to be favourable with TcAF. Conclusion: Based on literature data in current publications and our studies at the Technical Uni-versity of Applied Sciences Amberg-Weidenand the Royal Institute of Technoclogy, LAF and TcAF are more suitable for minimizing the risk for surgical site infections leading to improved clin-ical outcomes. Nevertheless, regarding the best management of thermal loads, atmosphere, energy efficiency, and occupational safety, overall results and data suggest that TcAF systems could pro-vide the economically most efficient and clinically most effective solution under routine clinical conditions.Keywords: ventilation systems, infection control, energy efficiency, operating theatre, airborne infection risks
Procedia PDF Downloads 96747 Investigating the Association between Escherichia Coli Infection and Breast Cancer Incidence: A Retrospective Analysis and Literature Review
Authors: Nadia Obaed, Lexi Frankel, Amalia Ardeljan, Denis Nigel, Anniki Witter, Omar Rashid
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Breast cancer is the most common cancer among women, with a lifetime risk of one in eight of all women in the United States. Although breast cancer is prevalent throughout the world, the uneven distribution in incidence and mortality rates is shaped by the variation in population structure, environment, genetics and known lifestyle risk factors. Furthermore, the bacterial profile in healthy and cancerous breast tissue differs with a higher relative abundance of bacteria capable of causing DNA damage in breast cancer patients. Previous bacterial infections may change the composition of the microbiome and partially account for the environmental factors promoting breast cancer. One study found that higher amounts of Staphylococcus, Bacillus, and Enterobacteriaceae, of which Escherichia coli (E. coli) is a part, were present in breast tumor tissue. Based on E. coli’s ability to damage DNA, it is hypothesized that there is an increased risk of breast cancer associated with previous E. coli infection. Therefore, the purpose of this study was to evaluate the correlation between E. coli infection and the incidence of breast cancer. Holy Cross Health, Fort Lauderdale, provided access to the Health Insurance Portability and Accountability (HIPAA) compliant national database for the purpose of academic research. International Classification of Disease 9th and 10th Codes (ICD-9, ICD-10) was then used to conduct a retrospective analysis using data from January 2010 to December 2019. All breast cancer diagnoses and all patients infected versus not infected with E. coli that underwent typical E. coli treatment were investigated. The obtained data were matched for age, Charlson Comorbidity Score (CCI score), and antibiotic treatment. Standard statistical methods were applied to determine statistical significance and an odds ratio was used to estimate the relative risk. A total of 81286 patients were identified and analyzed from the initial query and then reduced to 31894 antibiotic-specific treated patients in both the infected and control group, respectively. The incidence of breast cancer was 2.51% and present in 2043 patients in the E. coli group compared to 5.996% and present in 4874 patients in the control group. The incidence of breast cancer was 3.84% and present in 1223 patients in the treated E. coli group compared to 6.38% and present in 2034 patients in the treated control group. The decreased incidence of breast cancer in the E. coli and treated E. coli groups was statistically significant with a p-value of 2.2x10-16 and 2.264x10-16, respectively. The odds ratio in the E. coli and treated E. coli groups was 0.784 and 0.787 with a 95% confidence interval, respectively (0.756-0.813; 0.743-0.833). The current study shows a statistically significant decrease in breast cancer incidence in association with previous Escherichia coli infection. Researching the relationship between single bacterial species is important as only up to 10% of breast cancer risk is attributable to genetics, while the contribution of environmental factors including previous infections potentially accounts for a majority of the preventable risk. Further evaluation is recommended to assess the potential and mechanism of E. coli in decreasing the risk of breast cancer.Keywords: breast cancer, escherichia coli, incidence, infection, microbiome, risk
Procedia PDF Downloads 252746 Novel Ultrasensitive Point of Care Device for Diagnosis of Human Schistosomiasis Mansoni
Authors: Ibrahim Aly, Waleed Elawamy, Hanan Taher, Amira Matar
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Schistosomiasis is infection with blood flukes of the genus Schistosoma, which are acquired trans-cutaneously by swimming or wading in contaminated freshwater. The present study was proposed to produce ultra-sensitive, field-friendly high-throughput rapid immunochromatography diagnostic device for accurate detection of asymptomatic parasite carriers in schistosomiasis pre-elimination settings.For assessing diagnostic potential of rapid device, 50 blood samples from patients with schistosomiasis mansoni, 29 other proven parasitic diseases and 25 blood samples as negative control were from healthy individuals were used. The sensitivity of Quantitative antigen-capture nano-ELISAwas 82 %, and specificity was 87.1 %, where the sensitivity of Nano Dot- ELISA was 86 % and specificity was 90.7 %. The sensitivity of diagnostic device was 78 % and specificity was 85.2 %, with PPV and NPV of 86.2 % and 83.1 %, respectively.The Point of care device resulted in a good performance for the diagnosis of low-intensity infections, it was able to identify 19 out of 25 (76 %) individuals with ⩽7 eggs, 10 out of 14 individuals (71.4 %) with 11–99 eggs and 100 % of individuals with 100–399 eggs.Keywords: schistosomiasis, immunochromatography, naon-dot-ELISa, diagnostis device
Procedia PDF Downloads 74745 Inhibitory Mechanism of Ag and Fe Colloidal Nanoparticles on P. aeruginosa and E.coli Growth
Authors: Fatemeh Moradian, Razieh Ghorbani, Poria Biparva
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Growing resistance of microorganisms to potent antibiotics has renewed a great interest towards investigating bactericidal properties of nanoparticles and their Nano composites as an alternative. The use of metal nanoparticles to combat bacterial infections is one of the most wide spread applications of nanotechnology in the field of antibacterial. Nanomaterials have unique properties compared to their bulk counterparts. In this report, we demonstrate the antimicrobial activity of zerovalent Iron(ZVI) and Ag(silver) nanoparticles against Gram-negative bacteria E.coli(DH5α) and Pseudomonas aeruginosa. At first ZVI and Ag nanoparticles were synthesized by chemical reduction method and using scanning electron microscopy (SEM) the nanoparticle size determined. Different concentrations of Ag and ZVI nanoparticles were added to bacteria on nutrient agar medium. Minimum inhibitory concentration (MIC) of Ag and Fe nanoparticles for P. aeruginosa were 5µM and 1µg as well as for E.coli were 6µM. and 10 µg, respectively. Among the two nanoparticles, ZVI showed that the greatest antimicrobial activity against E.coli and Ag nanoparticle on P.aeruginosa. Results suggested that the bactericidal effect of metal nanoparticles has been attributed to their small size as well as high surface to volume ratio and NPs could be used as an effective antibacterial material.Keywords: bactericidal properties, MIC, nanoparticle, SEM
Procedia PDF Downloads 598744 Screening for Women with Chorioamnionitis: An Integrative Literature Review
Authors: Allison Herlene Du Plessis, Dalena (R.M.) Van Rooyen, Wilma Ten Ham-Baloyi, Sihaam Jardien-Baboo
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Introduction: Women die in pregnancy and childbirth for five main reasons—severe bleeding, infections, unsafe abortions, hypertensive disorders (pre-eclampsia and eclampsia), and medical complications including cardiac disease, diabetes, or HIV/AIDS complicated by pregnancy. In 2015, WHO classified sepsis as the third highest cause for maternal mortalities in the world. Chorioamnionitis is a clinical syndrome of intrauterine infection during any stage of the pregnancy and it refers to ascending bacteria from the vaginal canal up into the uterus, causing infection. While the incidence rates for chorioamnionitis are not well documented, complications related to chorioamnionitis are well documented and midwives still struggle to identify this condition in time due to its complex nature. Few diagnostic methods are available in public health services, due to escalated laboratory costs. Often the affordable biomarkers, such as C-reactive protein CRP, full blood count (FBC) and WBC, have low significance in diagnosing chorioamnionitis. A lack of screening impacts on effective and timeous management of chorioamnionitis, and early identification and management of risks could help to prevent neonatal complications and reduce the subsequent series of morbidities and healthcare costs of infants who are health foci of perinatal infections. Objective: This integrative literature review provides an overview of current best research evidence on the screening of women at risk for chorioamnionitis. Design: An integrative literature review was conducted using a systematic electronic literature search through EBSCOhost, Cochrane Online, Wiley Online, PubMed, Scopus and Google. Guidelines, research studies, and reports in English related to chorioamnionitis from 2008 up until 2020 were included in the study. Findings: After critical appraisal, 31 articles were included. More than one third (67%) of the literature included ranked on the three highest levels of evidence (Level I, II and III). Data extracted regarding screening for chorioamnionitis was synthesized into four themes, namely: screening by clinical signs and symptoms, screening by causative factors of chorioamnionitis, screening of obstetric history, and essential biomarkers to diagnose chorioamnionitis. Key conclusions: There are factors that can be used by midwives to identify women at risk for chorioamnionitis. However, there are a paucity of established sociological, epidemiological and behavioral factors to screen this population. Several biomarkers are available to diagnose chorioamnionitis. Increased Interleukin-6 in amniotic fluid is the better indicator and strongest predictor of histological chorioamnionitis, whereas the available rapid matrix-metalloproteinase-8 test requires further testing. Maternal white blood cells count (WBC) has shown poor selectivity and sensitivity, and C-reactive protein (CRP) thresholds varied among studies and are not ideal for conclusive diagnosis of subclinical chorioamnionitis. Implications for practice: Screening of women at risk for chorioamnionitis by health care providers providing care for pregnant women, including midwives, is important for diagnosis and management before complications arise, particularly in resource-constraint settings.Keywords: chorioamnionitis, guidelines, best evidence, screening, diagnosis, pregnant women
Procedia PDF Downloads 122743 Caring for a Spinal Cord Injury Patient with Diabetic Nephropathy Receiving Hospice Palliative Care
Authors: Li-Ting Kung, Hui-Zhu Chen, Hsin-Tzu Lee, Wan-Yin Hsu
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Patients with spinal cord injury combined with diabetic nephropathy may under a lot of painful conditions due to complications related to the illness itself or treatments, such as recurrent pressure ulcers, autonomic and peripheral neuropathy, as well as dialysis, for long term. This case report illustrated the nursing experience of transferring a spine cord injure patient who received hemodialysis due to adverse lifestyle-induced diabetic nephropathy to the hospice ward. Nursing care was provided in this patient from July 25th to August 30th, 2015. The tool of 'Gordon’s 11-item functional health assessment' and clinical observation, interviews as well as physical examination were used as data collections. Based on results of health assessment as above, the patient’s health problems were identified as the following: impaired skin integrity, chronic pain, and hopeless. Besides to relieve the symptom of pain due to disease or the treatment of hemodialysis and provide wound care, the first author also played a role to assist the patient to achieve his goal of receiving the hospice palliative care. Finally, with much effort of nurses to communicate with medical teams between the surgical and hospice wards, the patient was transferred to the hospice ward to have fulfilled his last wish of having a good death. We hope this nursing experience can be applied to other similar cases in the future.Keywords: diabetic nephropathy, hospice care, palliative care, spinal cord injury
Procedia PDF Downloads 151742 Glutharaldyde Free Processing of Patch for Cardiovascular Repair Is Associated with Improved Outcomes on Rvot Repair, Rat Model
Authors: Parnaz Boodagh, Danila Vella, Antonio Damore, Laura Modica De Mohac, Sang-Ho Ye, Garret Coyan, Gaetano Burriesci, William Wagner, Federica Cosentino
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The use of cardiac patches is among the main therapeutic solution for cardiovascular diseases, a leading mortality cause in the world with an increasing trend, responsible of 19 millions deaths in 2020. Several classes of biomaterials serve that purpose, both of synthetic origin and biological derivation, and many bioengineered treatment alternatives were proposed to satisfy two main requirements, providing structural support and promoting tissue remodeling. The objective of this paper is to compare the mechanical properties and the characterization of four cardiac patches: the Adeka, PhotoFix, CorPatch, and CardioCel patches. In vitro and in vivo tests included: biaxial, uniaxial, ball burst, suture retention for mechanical characterization; 2D surface topography, 3D volume and microstructure, and histology assessments for structure characterization; in vitro test to evaluate platelet deposition, calcium deposition, and macrophage polarization; rat right ventricular outflow tract (RVOT) models at 8- and 16-week time points to characterize the patch-host interaction. Lastly, the four patches were used to produce four stented aortic valve prosthesis, subjected to hydrodynamic assessment as well as durability testing to verify compliance with the standard ISO.Keywords: cardiac patch, cardiovascular disease, cardiac repair, blood contact biomaterial
Procedia PDF Downloads 150741 Revealing Potential Drug Targets against Proto-Oncogene Wnt10B by Comparative Molecular Docking
Authors: Shazia Mannan, Zunera Khalid, Hammad-Ul-Mubeen
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Wingless type Mouse mammary tumor virus (MMTV) Integration site-10B (Wnt10B) is an important member of the Wnt protein family that functions as cellular messenger in paracrine manner. Aberrant Wnt10B activity is the cause of several abnormalities including cancers of breast, cervix, liver, gastric tract, esophagus, pancreas as well as physiological problems like obesity, and osteoporosis. The objective of this study was to determine the possible inhibitors against aberrant expression of Wnt10B in order to prevent and treat the physiological disorders associated with it. Wnt10B3D structure was predicted by using comparative modeling and then analyzed by PROCHECK, Verify3D, and Errat. The model having 84.54% quality value was selected and acylated to satisfy the hydrophobic nature of Wnt10B. For search of inhibitors, virtual screening was performed on Natural Products (NP) database. The compounds were filtered and ligand-based screening was performed using the antagonist for mouse Wnt-3A. This resulted in a library of 272 unique compounds having most potent drug like activities for Wnt-4. Out of the 271 molecules analyzed three small molecules ZINC35442871, ZINC85876388, and ZINC00754234 having activity against Wnt4 abbarent expression were found common through docking experiment of Wnt10B. It is concluded that the three molecules ZINC35442871, ZINC85876388, and ZINC00754234 can be considered as lead compounds for performing further drug designing experiments against aberrant Wnt expressions.Keywords: Wnt10B inhibitors, comparative computational studies, proto-oncogene, molecular docking
Procedia PDF Downloads 156740 An Investigation of E. coli Contamination in Fars Province, Iran and Methods of Reducing the Contamination
Authors: Ali Mohagheghzadeh, Samad Vaez Badiegard, Bita Shomali
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Nowadays, with the increase in population, the need for protein sources is increasing. Different bacteria can cause food poisoning while most of the symptoms of food poisoning are similar to those of gastrointestinal infections. As a result, the diagnosis of bacteria and viruses causing food poisoning would not be possible without a stool culture. Cases of food poisoning are often accompanied by gastrointestinal disorders such as diarrhea, vomit, and gastrointestinal stomach cramps. Thus, providing enough food, taking into account health issues has always been a concern of authorities. Since E. coli bacterium is one of the important indicators of food hygiene and quality, producing food without being contaminated by this bacterium is desired in the food industry. This study aimed at assessing the E. coli contamination of poultry meat produced in slaughterhouses. Samples were taken from critical areas of slaughterhouses, namely the feather picking area, viscera and carcass evacuation area the area after cooling chillers. The results showed that 60% of contamination occurs in feather picking area. Among antiseptic and detergent materials, the highest reduction belongs to Epimax.Keywords: slaughterhouse, E. coli, Epimax, contamination
Procedia PDF Downloads 703739 Cloning and Analysis of Nile Tilapia Toll-like receptors Type-3 mRNA
Authors: Abdelazeem Algammal, Reham Abouelmaatti, Xiaokun Li, Jisheng Ma, Eman Abdelnaby, Wael Elfeil
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Toll-like receptors (TLRs) are the best understood of the innate immune receptors that detect infections in vertebrates. However, the fish TLRs also exhibit very distinct features and a large diversity, which is likely derived from their diverse evolutionary history and the distinct environments that they occupy. Little is known about the fish immune system structure. Our work was aimed to identify and clone the Nile tilapiaTLR-3 as a model of freshwater fish species; we cloned the full-length cDNA sequence of Nile tilapia (Oreochromis niloticus) TLR-3 and according to our knowledge, it is the first report illustrating tilapia TLR-3. The complete cDNA sequence of Nile tilapia TLR-3 was 2736 pair base and it encodes a polypeptide of 912 amino acids. Analysis of the deduced amino acid sequence indicated that Nile tilapia TLR-3 has typical structural features and main components of proteins belonging to the TLR family. Our results illustrate a complete and functional Nile tilapia TLR-3 and it is considered an ortholog of the other vertebrate’s receptor.Keywords: Nile tilapia, TLR-3, cloning, gene expression
Procedia PDF Downloads 148738 Cadaveric Assessment of Kidney Dimensions Among Nigerians - A Preliminary Report
Authors: Rotimi Sunday Ajani, Omowumi Femi-Akinlosotu
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Background: The usually paired human kidneys are retroperitoneal urinary organs with some endocrine functions. Standard text books of anatomy ascribe single value to each of the dimension of length, width and thickness. Research questions: These values do not give consideration to racial and genetic variability in human morphology. They may thus be erroneous to students and clinicians working on Nigerians. Objectives: The study aimed at establishing reference values of the kidney length, width and thickness for Nigerians using the cadaveric model. Methodology: The length, width, thickness and weight of sixty kidneys harvested from cadavers of thirty adult Nigerians (Male: Female; 27: 3) were measured. Respective volume was calculated using the ellipsoid formula. Results: The mean length of the kidney was 9.84±0.89 cm (9.63±0.88 {right}; 10.06±0.86 {left}), width- 5.18±0.70 cm (5.21±0.72 {right}; 5.14±0.70 {left}), thickness-3.45±0.56 cm (3.36±0.58 {right}, 3.53±0.55 {left}), weight-125.06±22.34 g (122.36±21.70 {right}; 127.76 ±24.02 {left}) and volume of 95.45± 24.40 cm3 (91.73± 26.84 {right}; 99.17± 25.75 {left}). Discussion: Though the values of the parameters measured were higher for the left kidney (except for the width), they were not statistically significant. The various parameters obtained by this study differ from those of similar studies from other continents. Conclusion: Stating single value for each of the parameter of length, width and thickness of the kidney as currently obtained in textbooks of anatomy may be incomplete information and hence misleading. Thus, there is the need to emphasize racial differences when stating the normal values of kidney dimensions in textbooks of anatomy. Implication for Research and Innovation: The results of the study showed the dimensions of the kidney (length, width and thickness) have interracial vagaries as they were different from those of similar studies and values stated in standard textbooks of human anatomy. Future direction: This is a preliminary report and the study will continue so that more data will be obtained.Keywords: kidney dimensions, cadaveric estimation, adult nigerians, racial differences
Procedia PDF Downloads 97737 Exploring Causes of Homelessness and Shelter Entry: A Case Study Analysis of Shelter Data in New York
Authors: Lindsay Fink, Sarha Smith-Moyo, Leanne W. Charlesworth
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In recent years, the number of individuals experiencing homelessness has increased in the United States. This paper analyzes 2019 data from 16 different emergency shelters in Monroe County, located in Upstate New York. The data were collected through the County’s Homeless Management Information System (HMIS), and individuals were de-identified and de-duplicated for analysis. The purpose of this study is to explore the basic characteristics of the homeless population in Monroe County, and the dynamics of shelter use. The results of this study showed gender as a significant factor when analyzing the relationship between demographic variables and recorded reasons for shelter entry. Results also indicated that age and ethnicity did not significantly influence odds of re-entering a shelter, but did significantly influence reasons for shelter entry. Overall, the most common recorded cause of shelter entry in 2019 in the examined county was eviction by primary tenant. Recommendations to better address recurrent shelter entry and potential chronic homelessness include more consideration for the diversity existing within the homeless population, and the dynamics leading to shelter stays, including enhanced funding and training for shelter staff, as well as expanded access to permanent supportive housing programs.Keywords: chronic homelessness, homeless shelter stays, permanent supportive housing, shelter population dynamics
Procedia PDF Downloads 154736 Surgical Outcome of Heavy Silicone Oil in Rhegmatogenous Retinal Detachment
Authors: Pheeraphat Ussadamongkol, Suthasinee Sinawat
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Objective: The purpose of this study is to evaluate the anatomical and visual outcomes associated with the use of heavy silicone oil (HSO) during pars plana vitrectomy (PPV) in patients with rhegmatogenous retinal detachment (RRD). Materials and methods: A Total of 66 eyes of 66 patients with RRD patients who underwent PPV with HSO from 2018-2023 were included in this retrospective study. Risk factors of surgical outcomes were also investigated. Results: The mean age of the recruited patients was 55.26 ± 13.05 years. The most common diagnosis was recurrent RRD, with 43 patients (65.15%), and the majority of these patients (81.39%) had a history of multiple vitreoretinal surgeries. Inferior breaks and PVR grade ≧ C were present in 65.15% and 42.42% of cases, respectively. The mean duration of HSO tamponade was 7.77+5.19 months. The retinal attachment rate after surgery was 71.21%, with a final attachment rate of 87.88%. The mean final VA was 1.62 ± 1.11 logMAR. 54.54% of patients could achieve a final visual acuity (VA) 6/60. Multivariate analysis revealed that proliferative vitreoretinopathy (PVR) and multiple breaks were significantly associated with retinal redetachment, while initial good VA ( 6/60) was associated with good visual outcome ( 6/60). The most common complications were glaucoma (30.3%) and epimacular membrane (7.58%). Conclusion: The use of heavy silicone oil in pars plana vitrectomy for rhegmatogenous retinal detachment yields favorable anatomical and visual outcomes. Factors associated with retinal redetachment are proliferative vitreoretinopathy and multiple breaks. Good initial VA can predict good visual outcomes.Keywords: rhegmatogenous retinal detachment, heavy silicone oil, surgical outcome, visual outcome, risk factors
Procedia PDF Downloads 2735 Clostridium Glycolicum Abdominal Infection in a Patient with Small Bowel Obstruction
Authors: Benedikt Munzar, Jagraj Singh, Alice Mei, David Musheyev, Sandeep Gandhi
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Clostridium is a gram-positive, anaerobic, spore-forming rod that is not commonly identified as a primary human pathogen. Here is presented a case of a 60-year-old patient with a history of opioid use disorder who underwent a number of abdominal surgeries for small bowel obstruction. His hospital course was complicated by Clostridium glycolicum infection, resulting in an acute abdomen. The patient clinically improved with antibiotic therapy. A thorough review of the National Institute of Health database revealed that only a small number of cases have been reported since 2007, with the last postsurgical cases documented in 2009 and the last clinical case documented in 2012. Clostridium glycolicum infections have been noted in patients with immunosuppressive conditions or those undergoing medical treatments that compromise immune function. This case was unusual due to the patient being immunocompetent. We suggest that a case of an acute abdomen should consider this organism as an etiological agent.Keywords: acute abdomen, bacterial infection, clostridium glycolicum, Meckel’s diverticulum, pneumoperitoneum, small bowel obstruction
Procedia PDF Downloads 25734 Impact of Integrated Signals for Doing Human Activity Recognition Using Deep Learning Models
Authors: Milagros Jaén-Vargas, Javier García Martínez, Karla Miriam Reyes Leiva, María Fernanda Trujillo-Guerrero, Francisco Fernandes, Sérgio Barroso Gonçalves, Miguel Tavares Silva, Daniel Simões Lopes, José Javier Serrano Olmedo
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Human Activity Recognition (HAR) is having a growing impact in creating new applications and is responsible for emerging new technologies. Also, the use of wearable sensors is an important key to exploring the human body's behavior when performing activities. Hence, the use of these dispositive is less invasive and the person is more comfortable. In this study, a database that includes three activities is used. The activities were acquired from inertial measurement unit sensors (IMU) and motion capture systems (MOCAP). The main objective is differentiating the performance from four Deep Learning (DL) models: Deep Neural Network (DNN), Convolutional Neural Network (CNN), Recurrent Neural Network (RNN) and hybrid model Convolutional Neural Network-Long Short-Term Memory (CNN-LSTM), when considering acceleration, velocity and position and evaluate if integrating the IMU acceleration to obtain velocity and position represent an increment in performance when it works as input to the DL models. Moreover, compared with the same type of data provided by the MOCAP system. Despite the acceleration data is cleaned when integrating, results show a minimal increase in accuracy for the integrated signals.Keywords: HAR, IMU, MOCAP, acceleration, velocity, position, feature maps
Procedia PDF Downloads 96733 Tenofovir-Amino Acid Conjugates Act as Polymerase Substrates: Implications for Avoiding Cellular Phosphorylation in the Discovery of Nucleotide Analogs
Authors: Weijie Gu, Sergio Martinez, Hoai Nguyen, Hongtao Xu, Piet Herdewijn, Steven De Jonghe, Kalyan Das
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Nucleotide analogs are used for treating viral infections such as HIV, hepatitis B, hepatitis C, influenza, and SARS-CoV-2. To become polymerase substrates, a nucleotide analog must be phosphorylated by cellular kinases, which are rate-limiting. The goal of this study is to develop dNTP/NTP analogs directly from nucleotides. Tenofovir (TFV) analogs were synthesized by conjugating with natural or unnatural amino acids. It demonstrates that some conjugates act as dNTP analogs, and HIV-1 reverse transcriptase (RT) catalytically incorporates the TFV part as the chain terminator. X-ray structures in complex with HIV-1 RT/dsDNA showed binding of the conjugates at the polymerase active site, however, in different modes in the presence of Mg²⁺ vs. Mn²⁺ ions. The adaptability of the compounds is seemingly essential for catalytic incorporation of TFV by RT. 4d with a carboxyl sidechain demonstrated the highest incorporation. 4e showed weak incorporation and rather behaved as a dNTP-competitive inhibitor. This result advocates the feasibility of designing NTP/dNTP analogs by chemical substitutions to nucleotide analogs.Keywords: dNTP analogs, nucleotide analogs, polymerase, tenofovir, X-ray structure
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