Search results for: chronic pulmonary disease

Authors: Mohamed Boubekri

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Daylight in general and sunlight in particular are vital to life on earth, and it is not difficult to believe that their absence fosters conditions that promote disease. Through photosynthesis and other processes, sunlight provides photochemical ingredients necessary for our lives. There are fundamental biological, hormonal, and physiological functions coordinated by cycles that are crucial to life for cells, plants, animals, and humans. Many plants and animals, including humans, develop abnormal behaviors when sunlight is absent because their diurnal cycle is disturbed. Building​ codes disregard this aspect of daylighting when promulgating windows for buildings. This paper discusses the health aspects of daylighting design.

Keywords: daylighting, health, sunlight, sleep, disorders, circadian rythm, cancer

Procedia PDF Downloads 322

Authors: Li-Ting Huang, Yu-Hsiang Shen, Cing-Ciao Ke, Sheng-Pin Tseng, Fan-Pin Tseng, Yu-Ching Ni, Chia-Yu Lin

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Chest radiography is the most common technique for the diagnosis and follow-up of pulmonary diseases. However, the lesions superimposed with normal structures are difficult to be detected in chest radiography. Chest tomosynthesis is a relatively new technique to obtain 3D section images from a set of low-dose projections acquired over a limited angular range. However, there are some limitations with chest tomosynthesis. Patients undergoing tomosynthesis have to be able to hold their breath firmly for 10 seconds. A digital tomosynthesis system with advanced reconstruction algorithm and high-stability motion mechanism was developed by our research group. The potential for the system to perform a bidirectional chest scan within 10 seconds is expected. The purpose of this study is to realize the influences of the scan speed on the image quality for our digital tomosynthesis system. The major factors that lead image blurring are the motion of the X-ray source and the patient. For the fore one, an experiment of imaging a chest phantom with three different scan speeds, which are 6 cm/s, 8 cm/s, and 15 cm/s, was proceeded to understand the scan speed influences on the image quality. For the rear factor, a normal SD (Sprague-Dawley) rat was imaged with it alive and sacrificed to assess the impact on the image quality due to breath motion. In both experiments, the profile of the ROIs (region of interest) and the CNRs (contrast-to-noise ratio) of the ROIs to the normal tissue of the reconstructed images was examined to realize the degradations of the qualities of the images. The preliminary results show that no obvious degradation of the image quality was observed with increasing scan speed, possibly due to the advanced designs for the hardware and software of the system. It implies that higher speed (15 cm/s) than that of the commercialized tomosynthesis system (12 cm/s) for the proposed system is achieved, and therefore a complete chest scan within 10 seconds is expected.

Keywords: chest radiography, digital tomosynthesis, image quality, scan speed

Procedia PDF Downloads 314

Authors: Robert E. Kenney, Efrain Antunez, Samuel Nodal, Ameer Malik, Richard B. Aguilar

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Physician burnout has gained much attention during the COVID pandemic. After-hours workload, HCC coding, HEDIS metrics, and clinical documentation negatively impact career satisfaction. These and other influences have increased the rate of physicians leaving the workforce. In addition, roughly 1% of the entire physician workforce will be retiring earlier than expected based on pre-pandemic trends. The two Medical Specialties with the highest rates of burnout are Family Medicine and Primary Care. With a predicted shortage of primary care physicians looming, the need to address physician burnout is crucial. Commonly reported issues leading to clinician burnout are clerical documentation requirements, increased time working on Electronic Health Records (EHR) after hours, and a decrease in work-life balance. Clinicians experiencing burnout with physical and emotional exhaustion are at an increased likelihood of providing lower quality and less efficient patient care. This may include a lack of suitable clinical documentation, medication reconciliation, clinical assessment, and treatment plans. While the annual baseline turnover rates of physicians hover around 6-7%, the COVID pandemic profoundly disrupted the delivery of healthcare. A report found that 43% of physicians switched jobs during the initial two years of the COVID pandemic (2020 and 2021), tripling the expected average annual rate to 21.5 %/yr. During this same time, an average of 4% and 1.5% of physicians retired or left the workforce for a non-clinical career, respectively. The report notes that 35.2% made career changes for a better work-life balance and another 35% reported the reason as being unhappy with their administration’s response to the pandemic. A physician-led primary care-focused health organization, Cano Health (CH), based out of Florida, sought to preemptively address this problem by implementing several supportive measures. Working with >120 clinics and >280 PCPs from Miami to Tampa and Orlando, managing nearly 120,000 Medicare Advantage lives, CH implemented a number of changes to assist with the clinician’s workload. Supportive services such as after hour and home visits by APRNs, in-clinic care managers, and patient educators were implemented. In 2021, assistive Artificial Intelligence Software (AIS) was integrated into the EHR platform. This AIS converts free text within PDF files into a usable (copy-paste) format facilitating documentation. The software also systematically and chronologically organizes clinical data, including labs, medical records, consultations, diagnostic images, medications, etc., into an easy-to-use organ system or chronic disease state format. This reduced the excess time and documentation burden required to meet payor and CMS guidelines. A clinician Documentation Support team was employed to improve the billing/coding performance. The effects of these newly designed workflow interventions were measured via analysis of clinician turnover from CH’s hiring and termination reporting software. CH’s annualized average clinician turnover rate in 2020 and 2021 were 17.7% and 12.6%, respectively. This represents a 30% relative reduction in turnover rate compared to the reported national average of 21.5%. Retirement rates during both years were 0.1%, demonstrating a relative reduction of >95% compared to the national average (4%). This model successfully promoted the retention of clinicians in a Value-Based Care setting.

Keywords: clinician burnout, COVID-19, value-based care, burnout, clinician retirement

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Authors: Oleg Sapelnikov, Ruslan Latypov, Darina Ardus, Samvel Aivazian, Andrey Shiryaev, Renat Akchurin

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OBJECTIVE: MAZE procedure is one of the most effective surgical methods in atrial fibrillation (AF) treatment. Nowadays we are all aware of its modifications. In our study we conducted clinical analysis of “Box lesion+” approach during MAZE procedure in two-year follow-up. METHODS: We studied the results of the open-heart on-pump procedures performed in our hospital from 2017 to 2018 years. Thirty-two (32) patients with atrial fibrillation (AF) were included in this study. Fifteen (15) patients had concomitant coronary bypass grafting and seventeen (17) patients had mitral valve repair. Mean age was 62.3±8.7 years; prevalence of men was admitted (56.1%). Mean duration of AF was 4.75±5.44 and 7.07±8.14 years. In all cases, we performed endocardial Cryo-MAZE procedure with one-time myocardium revascularization or mitral-valve surgery. All patients of this study underwent pulmonary vein (PV) isolation and ablation of mitral isthmus with additional isolation of LA posterior wall (Box-lesion+ procedure). Mean follow-up was 2 years. RESULTS: All cases were performed without any complications. Additional isolation of posterior wall did not prolong the operative time and artificial circulation significantly. Cryo-MAZE procedure directly lasted 20±2.1 min, the whole operation time was 192±24 min and artificial circulation time was 103±12 min. According to design of the study, we performed clinical investigation of the patients in 12 months and in 2 years from the initial procedure. In 12 months, the number of AF free patients 81.8% and 75.8% in two years of follow-up. CONCLUSIONS: Isolation of the left atrial posterior wall and perimitral area may considerably improve the efficacy of surgical treatment, which was demonstrated in significant decrease of AF recurrences during the whole period of follow-up.

Keywords: atrial fibrillation, cryoablation, left atrium isolation, open heart procedure

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Authors: Wilfred A. Abiaa, Chibundu N. Ezekiel, Benedikt Warth, Michael Sulyok, Paul C. Turner, Rudolf Krska, Paul F. Moundipa

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Mycotoxins are a wide range of toxic secondary metabolites of fungi that contaminate various food commodities worldwide especially in sub-Saharan Africa (SSA). Such contamination seriously compromises food safety and quality posing a serious problem for human health as well as to trade and the economy. Their concentrations depend on various factors, such as the commodity itself, climatic conditions, storage conditions, seasonal variances, and processing methods. When humans consume foods contaminated by mycotoxins, they exert toxic effects to their health through various modes of actions. Rural populations in sub-Saharan Africa, are exposed to dietary mycotoxins, but it is supposed that exposure levels and health risks associated with mycotoxins between SSA countries may vary. Dietary exposures and health risk assessment studies have been limited by lack of equipment for the proper assessment of the associated health implications on consumer populations when they eat contaminated agricultural products. As such, mycotoxin research is premature in several SSA nations with product evaluation for mycotoxin loads below/above legislative limits being inadequate. Few nations have health risk assessment reports mainly based on direct quantification of the toxins in foods ('external exposure') and linking food levels with data from food frequency questionnaires. Nonetheless, the assessment of the exposure and health risk to mycotoxins requires more than the traditional approaches. Only a fraction of the mycotoxins in contaminated foods reaches the blood stream and exert toxicity ('internal exposure'). Also, internal exposure is usually smaller than external exposure thus dependence on external exposure alone may induce confounders in risk assessment. Some studies from SSA earlier focused on biomarker analysis mainly on aflatoxins while a few recent studies have concentrated on the multi-biomarker analysis of exposures in urine providing probable associations between observed disease occurrences and dietary mycotoxins levels. As a result, new techniques that could assess the levels of exposures directly in body tissue or fluid, and possibly link them to the disease state of individuals became urgent.

Keywords: mycotoxins, biomarkers, exposure assessment, health risk assessment, sub-Saharan Africa

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Authors: Bright Chukwunwike Uzuegbunam, Wojciech Paslawski, Hans Agren, Christer Halldin, Wolfgang Weber, Markus Luster, Thomas Arzberger, Behrooz Hooshyar Yousefi

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There is a need to develop a PET tracer that will enable to diagnosis and track the progression of Alpha-synucleinopathies (Parkinson’s disease [PD], dementia with Lewy bodies [DLB], multiple system atrophy [MSA]) in living subjects over time. Alpha-synuclein aggregates (a-syn), which are present in all the stages of disease progression, for instance, in PD, are a suitable target for in vivo PET imaging. For this reason, we have developed some promising a-syn tracers based on a disarylbisthiazole (DABTA) scaffold. The precursors are synthesized via a modified Hantzsch thiazole synthesis. The precursors were then radiolabeled via one- or two-step radiofluorination methods. The ligands were initially screened using a combination of molecular dynamics and quantum/molecular mechanics approaches in order to calculate the binding affinity to a-syn (in silico binding experiments). Experimental in vitro binding assays were also performed. The ligands were further screened in other experiments such as log D, in vitro plasma protein binding & plasma stability, biodistribution & brain metabolite analyses in healthy mice. Radiochemical yields were up to 30% - 72% in some cases. Molecular docking revealed possible binding sites in a-syn and also the free energy of binding to those sites (-28.9 - -66.9 kcal/mol), which correlated to the high binding affinity of the DABTAs to a-syn (Ki as low as 0.5 nM) and selectivity (> 100-fold) over Aβ and tau, which usually co-exist with a-synin some pathologies. The log D values range from 2.88 - 2.34, which correlated with free-protein fraction of 0.28% - 0.5%. Biodistribution experiments revealed that the tracers are taken up (5.6 %ID/g - 7.3 %ID/g) in the brain at 5 min (post-injection) p.i., and cleared out (values as low as 0.39 %ID/g were obtained at 120 min p.i. Analyses of the mice brain 20 min p.i. Revealed almost no radiometabolites in the brain in most cases. It can be concluded that in silico study presents a new venue for the rational development of radioligands with suitable features. The results obtained so far are promising and encourage us to further validate the DABTAs in autoradiography, immunohistochemistry, and in vivo imaging in non-human primates and humans.

Keywords: alpha-synuclein aggregates, alpha-synucleinopathies, PET imaging, tracer development

Procedia PDF Downloads 218

Authors: Orathai Srithongtham, Ploypailin Mekathepakorn, Tossaphong Buraman, Pontida Moonpradap, Rungrueng Kitpati, Chulapon Kratet, Worayuth Nak-ai, Suwaree Charoenmukkayanan, Peeranuch Keawkanya

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The COVID-19 pandemic was effect to the health security of the Thai people. The PHEM principle was essential to the surveillance, prevention, and control of COVID-19. This study aimed to present the process of prevention and control of COVID-19 from February 29, 2021- April 30, 2022, and the factors and conditions influent the successful outcome. The study areas were three provinces. The target group was 37 people, composed of public health personnel. The data was collected in-depth, and group interviews followed the non-structure interview guide and were analyzed by content analysis. The components of COVID-19 prevention and control were found in the process of PHEM as follows; 1) Emergency Operation Center (EOC) with an incidence command system (ICS) from the district to provincial level and to propose the provincial measure, 2) Provincial Communicable Disease Committee (PCDC) to decide the provincial measure 3) The measure for surveillance, prevention, control, and treatment of COVID-19, and 4) outcomes and best practices for surveillance and control of COVID-19. The success factors of 4S and EC were as follows; Space: prepare the quarantine (HQ, LQ), Cohort Ward (CW), field hospital, and community isolation and home isolation to face with the patient and risky group, Staff network from various organization and group cover the community leader and Health Volunteer (HV), Stuff the management and sharing of the medical and non-medical equipment, System of Covid-19 respond were EOC, ICS, Joint Investigation Team (JIT) and Communicable Disease Control Unit (CDCU) for monitoring the real-time of surveillance and control of COVID-19 output, Environment management in hospital and the community with Infections Control (IC) principle, and Culture in term of social capital on “the relationship of Isan people” supported the patient provide the good care and support. The structure of PHEM, Isan’s Culture, and good preparation was a significant factor in the three provinces.

Keywords: public health, emergency management, covid-19, pandemic

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Authors: Mohammed Al-Zubaidi, Katherine Ong, Pravin Viswambaram, Steve McCombie, Oliver Oey, Jeremy Ong, Richard Gauci, Ronny Low, Dickon Hayne

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Objective: Lymph node involvement along with distant metastasis in a patient with invasive bladder cancer determines the disease survival, therefeor, it is an essential determinant of the therapeutic management and outcome. This retrospective study aims to determine the accuracy of FDG PET scan in detecting lymphatic involvement and distant metastatic urothelial cancer compared to conventional CT staging. Method: A retrospective review of 76 patients with UC or BC who underwent surgery or confirmatory biopsy that was staged with both CT and 18F-FDG-PET (up to 8 weeks apart) between 2015 and 2020. Fifty-sevenpatients (75%) had formal pelvic LN dissection or biopsy of suspicious metastasis. 18F-FDG-PET reports for positive sites were qualitative depending on SUV Max. On the other hand, enlarged LN by RECIST criteria 1.1 (>10 mm) and other qualitative findings suggesting metastasis were considered positive in CT scan. Histopathological findings from surgical specimens or image-guided biopsies were considered the gold standard in comparison to imaging reports. 18F-FDG-avid or enlarged pelvic LNs with surgically proven nodal metastasis were considered true positives. Performance characteristics of 18F-FDG-PET and CT, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (PPV), were calculated. Results: Pelvic LN involvement was confirmed histologically in 10/57 (17.5%) patients. Sensitivity, specificity, PPV and NPV of CT for detecting pelvic LN metastases were 41.17% (95% CI:18-67%), 100% (95% CI:90-100%) 100% (95% CI:59-100%) and 78.26% (95% CI:64-89%) respectively. Sensitivity, specificity, PPV and NPV of 18F-FDG-PET for detecting pelvic LN metastases were 62.5% (95% CI:35-85%), 83.78% (95% CI:68-94%), 62.5% (95% CI:35-85%), and 83.78% (95% CI:68-94%) respectively. Pre-operative staging with 18F-FDG-PET identified the distant metastatic disease in 9/76 (11.8%) patients who were occult on CT. This retrospective study suggested that 18F-FDG-PET may be more sensitive than CT for detecting pelvic LN metastases. 7/76 (9.2%) patients avoided cystectomy due to 18F-FDG-PET diagnosed metastases that were not reported on CT. Conclusion: 18F-FDG-PET is more sensitive than CT for pelvic LN metastases, which can be used as the standard modality of bladder cancer staging, as it may change the treatment by detecting lymph node metastasis that was occult in CT. Further research involving randomised controlled trials comparing the diagnostic yield of 18F-FDG-PET and CT in detecting nodal and distant metastasis in UC or BC is warranted to confirm our findings.

Keywords: FDG PET, CT scan, urothelial cancer, bladder cancer

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Authors: Aarti Singh, Anees Ahmad

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Carotenoids comprise a group of isoprenoid pigments. Carotenes, xanthophylls and their derivatives have been found to play an important role in all living beings through foods, neutraceuticals and pharmaceuticals. α-carotene, β-carotene and β-cryptoxanthin play a vital role in humans to provide vitamin A source for the growth, development and proper functioning of immune system and vision. They are very crucial for plants and humans as they protect from photooxidative damage and are excellent antioxidants quenching singlet molecular oxygen and peroxyl radicals. Diet including more intake of carotenoids results in reduced threat of various chronic diseases such as cancer (lung, breast, prostate, colorectal and ovarian cancers) and coronary heart diseases. The blue light filtering efficiency of the carotenoids in liposomes have been reported to be maximum in lutein followed by zeaxanthin, β-carotene and lycopene. Lycopene play a vital role for the protection from CVD. Lycopene in serum is directly related to reduced risk of osteoporosis in postmenopausal women. Carotenoids have the major role in the treatment of skin disorders. There is a need to identify and isolate novel carotenoids from diverse natural sources for human health benefits.

Keywords: antioxidants, carotenoids, neutraceuticals, osteoporosis, pharmaceuticals

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Authors: Luciano Tarantino, Emanuele Balzano, Paolo Tarantino, Riccardo Aurelio Nasto, Aurelio Nasto

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Liver transplantation (OLT) is contraindicate in Portal Vein tumor Thrombosis (PVTT) from Hepatocellular Carcinoma at hepatic hilum(pH-HCC) Surgery,Thermal ablation and chemotherapy show poorer outcomes Electrochemotherapy (ECT) has been successfully used in patients with pH-HCC with PVTT. We report the results of ECT as downstaging aimed to definitive cure by OLT. F.P. 53 years HBV related Cirrhosis Child-Pugh B7 class; EGDS F2 aesophageal Varices. Diabetes. April 2016 : Enhanced Computed Tomography (CT) detected HCC(n.3 nodules in VII-VIII-VI;diameter range=25 cm) and PVTT of right portal vein. The patient was considered ineligible for OLT. May 2016: first ablation session with percutaneous Radiofrequency-ablation(RFA) of 3 HCC-nodules . August 2016: second ablation session with ECT of PVTT. CT october 2016: disappearance of PVTT and patent right portal vein. No intraparenchymal recurrence. CT march 2017: No recurrence in portal vein and in the left lobe. local recurrence in the VII-VIII segments. May 2017 : transarterial chemoembolization (TACE) of right lobe recurrences. CT October 2017: patent right portal vein. No recurrence. The patient was reconsidered for OLT. He underwent OLT in April 2018. At 36-months follow-up , no intrahepatic recurrence of HCC occurred. March 2021: enhanced CT and PET/CT detected a single small nodule (1.5 cm) uptaking tracer in the left upper pulmonary lobe, no hepatic recurrence . CT-guided FNB showed metastasis from HCC . June 2021: left lung upper lobectomy . At the current time the patient is alive and recurrence-free at 64 months follow-up. ECT Could be aneffective technique as pre-OLT dowstaging in HCC with PVTT.

Keywords: liver tumor ablation, interventional ultrasound, electrochemotherapy, liver transplantation

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Authors: Kimberly Winnie Achieng Otieno

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The Nairobi Hospital plays a pivotal role in healthcare provision in East and Central Africa, yet it faces challenges in providing accessible dialysis care. This paper explores strategic interventions to enhance dialysis care, improve access and streamline health information management, with an aim of fostering an integrated and patient-centered healthcare system in our region. Challenges at The Nairobi Hospital The Nairobi Hospital currently grapples with insufficient dialysis machines which results in extended turn around times. This issue stems from both staffing bottle necks and infrastructural limitations given our growing demand for renal care services. Our Paper-based record keeping system and fragmented flow of information downstream hinders the hospital’s ability to manage health data effectively. There is also a need for investment in expanding The Nairobi Hospital dialysis facilities to far reaching communities. Setting up satellite clinics that are closer to people who live in areas far from the main hospital will ensure better access to underserved areas. Community Outreach and Education Implementing education programs on kidney health within local communities is vital for early detection and prevention. Collaborating with local leaders and organizations can establish a proactive approach to renal health hence reducing the demand for acute dialysis interventions. We can amplify this effort by expanding The Nairobi Hospital’s corporate social responsibility outreach program with weekend engagement activities such as walks, awareness classes and fund drives. Enhancing Efficiency in Dialysis Care Demand for dialysis services continues to rise due to an aging Kenyan population and the increasing prevalence of chronic kidney disease (CKD). Present at this years International Nursing Conference are a diverse group of caregivers from around the world who can share with us their process optimization strategies, patient engagement techniques and resource utilization efficiencies to catapult The Nairobi Hospital to the 21st century and beyond. Plans are underway to offer ongoing education opportunities to keep staff updated on best practices and emerging technologies in addition to utilizing a patient feedback mechanisms to identify areas for improvement and enhance satisfaction. Staff empowerment and suggestion boxes address The Nairobi Hospital’s organizational challenges. Current financial constraints may limit a leapfrog in technology integration such as the acquisition of new dialysis machines and an investment in predictive analytics to forecast patient needs and optimize resource allocation. Streamlining Health Information Management Fully embracing a shift to 100% Electronic Health Records (EHRs) is a transformative step toward efficient health information management. Shared information promotes a holistic understanding of patients’ medical history, minimizing redundancies and enhancing overall care quality. To manage the transition to community-based care and EHRs effectively, a phased implementation approach is recommended. Conclusion By strategically enhancing dialysis care access and streamlining health information management, The Nairobi Hospital can strengthen its position as a leading healthcare institution in both East and Central Africa. This comprehensive approach aligns with the hospital’s commitment to providing high-quality, accessible, and patient-centered care in an evolving landscape of healthcare delivery.

Keywords: Africa, urology, diaylsis, healthcare

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Authors: Poonam Goswami

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Background: The diagnosis of a serious illness like cancer can have an impact on a patient’s emotional well-being and may result in psychological symptoms, anxiety, depression, and loss of control. Advance care planning discussions ensure patients’ values and goals of care, including patients’ freedom to choose their place of death, are respected. Unfortunately, these discussions are often delayed and are not initiated early in patients’ cancer trajectory. As a result, patients’ wishes often remains unknown until the last phase of their life. Evidence suggests that many patients inappropriately receive aggressive treatment near the end of life, which does lead to higher resource utilization, decreased quality of life, and increased cost. Additionally, the novel coronavirus disease 2019 (COVID-19) pandemic challenged the health care systems worldwide and raised important ethical issues, especially regarding the potential need for rationing health care in the context of scarce resources and crisis capacity. The importance of goal concordant care is now even substantially important and is heightened in the context of this pandemic. Problem: Although there is growing evidence on the effects of the ACP on the completion of advanced directives, improved patient and family concordance for preferences for medical care, and receipt of care, there is still a lack of standardized ACP conversation strategies for patients with cancer. Methods: The Key concepts of ACP include (1) assessing patient and family readiness, (2) identifying a surrogate decision maker ( medical power of attorney), (3) exploring patient and family understanding of the disease and treatment options,(4) discussing the values and goals of care, and options for end-of-life care, (5) documenting patient preferences in the medical record, and (6) revisiting the discussions at every change in the treatment plan and /or change in clinical status, including at every hospitalization. Conclusion/Implication for practice: Advance Care Planning (ACP) and end-of-life (EOL) discussions are important for patients, families, and health care providers. Adopting the verbal and nonverbal communication strategies can help overcome the barriers to effective communication on these difficult discussions. ACP with goals of care discussions should not be delayed until the patient is hospitalized.

Keywords: advance care planning, end of life, cancer, global, pandemic

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Authors: Yuguang Gao, Mingtao Deng

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The integration of independently operating hospitals into a unified healthcare service system has become a strategic imperative in the pursuit of hospitals’ high-quality development. Central to the concept of group governance over such transformation, exemplified by a collaborative medical alliance, is the delineation of shared value, vision, and goals. Given the inherent disparity in capabilities among hospitals within the alliance, particularly in the treatment of different diseases characterized by Disease Related Groups (DRG) in terms of effectiveness, efficiency and resource utilization, this study aims to address the centralized decision-making of intra-hospital patient referral within the medical alliance to enhance the overall production and quality of service provided. We first introduce the notion of production utility, where a higher production utility for a hospital implies better performance in treating patients diagnosed with that specific DRG group of diseases. Then, a Discrete-Event Simulation (DES) framework is established for patient referral among hospitals, where patient flow modeling incorporates a queueing system with fixed capacities for each hospital. The simulation study begins with a two-member alliance. The pivotal strategy examined is a "whether-to-refer" decision triggered when the bed usage rate surpasses a predefined threshold for either hospital. Then, the decision encompasses referring patients to the other hospital based on DRG groups’ production utility differentials as well as bed availability. The objective is to maximize the total production utility of the alliance while minimizing patients’ average length of stay and turnover rate. Thus the parameter under scrutiny is the bed usage rate threshold, influencing the efficacy of the referral strategy. Extending the study to a three-member alliance, which could readily be generalized to multi-member alliances, we maintain the core setup while introducing an additional “which-to-refer" decision that involves referring patients with specific DRG groups to the member hospital according to their respective production utility rankings. The overarching goal remains consistent, for which the bed usage rate threshold is once again a focal point for analysis. For the two-member alliance scenario, our simulation results indicate that the optimal bed usage rate threshold hinges on the discrepancy in the number of beds between member hospitals, the distribution of DRG groups among incoming patients, and variations in production utilities across hospitals. Transitioning to the three-member alliance, we observe similar dependencies on these parameters. Additionally, it becomes evident that an imbalanced distribution of DRG diagnoses and further disparity in production utilities among member hospitals may lead to an increase in the turnover rate. In general, it was found that the intra-hospital referral mechanism enhances the overall production utility of the medical alliance compared to individual hospitals without partnership. Patients’ average length of stay is also reduced, showcasing the positive impact of the collaborative approach. However, the turnover rate exhibits variability based on parameter setups, particularly when patients are redirected within the alliance. In conclusion, the re-structuring of diagnostic disease groups within the medical alliance proves instrumental in improving overall healthcare service outcomes, providing a compelling rationale for the government's promotion of patient referrals within collaborative medical alliances.

Keywords: collaborative medical alliance, disease related group, patient referral, simulation

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Authors: Atlal El-Assaad

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Viruses change with time through mutations and result in new variants that may persist or disappear. A Mutation refers to an actual change in the virus genetic sequence, and a variant is a viral genome that may contain one or more mutations. Critical mutations may cause the virus to be more transmissible, with high disease severity, and more vulnerable to diagnostics, therapeutics, and vaccines. Thus, variants carrying such mutations may increase the risk to human health and are considered variants of concern (VOC). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) - the contagious in humans, positive-sense single-stranded RNA virus that caused coronavirus disease 2019 (COVID-19) - has been studied thoroughly, and several variants were revealed across the world with their corresponding mutations. SARS-CoV-2 has four structural proteins, known as the S (spike), E (envelope), M (membrane), and N (nucleocapsid) proteins, but prior study and vaccines development focused on genetic mutations in the S protein due to its vital role in allowing the virus to attach and fuse with the membrane of a host cell. Specifically, subunit S1 catalyzes attachment, whereas subunit S2 mediates fusion. In this perspective, we studied all charged amino acid mutations of the SARS-CoV-2 viral spike protein S1 when bound to Antibody CC12.1 in a crystal structure and assessed the effect of different mutations. We generated all missense mutants of SARS-CoV-2 protein amino acids (AAs) within the SARS-CoV-2:CC12.1 complex model. To generate the family of mutants in each complex, we mutated every charged amino acid with all other charged amino acids (Lysine (K), Arginine (R), Glutamic Acid (E), and Aspartic Acid (D)) and studied the new binding of the complex after each mutation. We applied Poisson-Boltzmann electrostatic calculations feeding into free energy calculations to determine the effect of each mutation on binding. After analyzing our data, we identified charged amino acids keys for binding. Furthermore, we validated those findings against published experimental genetic data. Our results are the first to propose in silico potential life-threatening mutations of SARS-CoV-2 beyond the present mutations found in the five common variants found worldwide.

Keywords: SARS-CoV-2, variant, ionic amino acid, protein-protein interactions, missense mutation, AESOP

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Authors: A. Hoppe, T. Kagele, B. Hall, A. Nichols, B. Messner

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The Spokane Street Medicine (SSM) Program aims to deliver medical care to members of Spokane, Washington, experiencing homelessness. Street medicine is designed to function in a non-traditional setting to help deliver healthcare to the underserved homeless population. In this analysis, clinical charts from street and shelter encounters made by the Spokane Street Medicine Program in early 2021 were reviewed in order to better understand the healthcare inequities prevalent among people experiencing homelessness in Spokane, WA. Pain, wound-care, and follow-up efforts were predominant concerns among the homeless population. More than half of the conditions addressed were acute, and almost a quarter of all chief complaints involved chronic unmanaged conditions. This analysis gives reason for the priorities of the SSM Program to be focused on pain, wound-care, and follow-up efforts. Understanding the specific medical needs of this population will allow for better resource allocation and improved health outcomes among people experiencing homelessness.

Keywords: equity issues in public health, health disparities, health services accessibility, medical public health, street medicine

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Authors: Joanna Marie A. Paulino-Morente, Vaneza Valentina L. Penolio, Grace Sabado

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Ovarian cancer is extremely hard to diagnose in its early stages, and those afflicted at the time of diagnosis are typically asymptomatic and in the late stages of the disease, with metastasis to other organs. Ovarian cancers often occur sporadically, with only 5% associated with hereditary mutations. Mutations in the BRCA1 and BRCA2 tumor suppressor genes have been found to be responsible for the majority of hereditary ovarian cancers. One type of ovarian tumor is Malignant Mixed Mullerian Tumor (MMMT), which is a very rare and aggressive type, accounting for only 1% of all ovarian cancers. Reported is a case of a 43-year-old G3P3 (3003), who came into our institution due to a 2-month history of difficulty of breathing. Family history reveals that her eldest and younger sisters both died of ovarian malignancy, with her younger sister having a histopathology report of endometrioid ovarian carcinoma, left ovary stage IIIb. She still has 2 asymptomatic sisters. Physical examination pointed to pleural effusion of right lung, and presence of bilateral ovarian new growth, which had a Sassone score of 13. Admitting Diagnosis was G3P3 (3003), Ovarian New Growth, bilateral, Malignant; Pleural effusion secondary to malignancy. BRCA was requested to establish a hereditary mutation; however, the patient had no funds. Once the patient was stabilized, TAHBSO with surgical staging was performed. Intraoperatively, the pelvic cavity was occupied by firm, irregularly shaped ovaries, with a colorectal metastasis. Microscopic sections from both ovaries and the colorectal metastasis had pleomorphic tumor cells lined by cuboidal to columnar epithelium exhibiting glandular complexity, displaying nuclear atypia and increased nuclear-cytoplasmic ratio, which are infiltrating the stroma, consistent with the features of Malignant Mixed Mullerian Tumor, since MMMT is composed histologically of malignant epithelial and sarcomatous elements. In conclusion, discussed is the clinic-pathological feature of a patient with primary ovarian Malignant Mixed Mullerian Tumor, a rare malignancy comprising only 1% of all ovarian neoplasms. Also, by understanding the hereditary ovarian cancer syndromes and its relation to this patient, it cannot be overemphasized that a comprehensive family history is really fundamental for early diagnosis. The familial association of the disease, given that the patient has two sisters who were diagnosed with an advanced stage of ovarian cancer and succumbed to the disease at a much earlier age than what is reported in the general population, points to a possible hereditary syndrome which occurs in only 5% of ovarian neoplasms. In a low-resource setting, being in a third world country, the following will be recommended for monitoring and/or screening women who are at high risk for developing ovarian cancer, such as the remaining sisters of the patient: 1) Physical examination focusing on the breast, abdomen, and rectal area every 6 months. 2) Transvaginal sonography every 6 months. 3) Mammography annually. 4) CA125 for postmenopausal women. 5) Genetic testing for BRCA1 and BRCA2 will be reserved for those who are financially capable.

Keywords: BRCA, hereditary breast-ovarian cancer syndrome, malignant mixed mullerian tumor, ovarian cancer

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Authors: Zoltan Horvath, Dora Nagy

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In this research, it was examined whether individual COVID variants cause differences in the lactate curve of cyclists. After all, the virus variants attacked different organs in our body during the infections. During our tests, we used a traditional lactate step test, the results of which were compared with the values before the infection. In the tests, it has been proven that different virus variants show unique lactate curves. In this way, based on the lactate curve, it is possible to identify which variant caused the disease. Thanks to this, it has been shorten the return time, because we can apply the best return protocol after infection to the competitors.

Keywords: COVID-Sars19, lactate, virus mutation, lactate profile

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Authors: Maria Lopez-Ibarra, Ana Velazquez-Wong, Lucelli Yañez-Gutierrez, Maria Araujo-Solis, Fabio Salamanca-Gomez, Alfonso Mendez-Tenorio, Haydeé Rosas-Vargas

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Congenital heart diseases (CHD) are the most common congenital abnormalities. These conditions can occur as both an element of distinct chromosomal malformation syndromes or as non-syndromic forms. Their etiology is not fully understood. Genetic variants such copy number variants have been associated with CHD. The aim of our study was to analyze these genomic variants in peripheral blood from Mexican children diagnosed with non-syndromic CHD. We included 16 children with atrial and ventricular septal defects and 5 healthy subjects without heart malformations as controls. To exclude the most common heart disease-associated syndrome alteration, we performed a fluorescence in situ hybridization test to identify the 22q11.2, responsible for congenital heart abnormalities associated with Di-George Syndrome. Then, a microarray based comparative genomic hybridization was used to identify global copy number variants. The identification of copy number variants resulted from the comparison and analysis between our results and data from main genetic variation databases. We identified copy number variants gain in three chromosomes regions from pediatric patients, 4q13.2 (31.25%), 9q34.3 (25%) and 20q13.33 (50%), where several genes associated with cellular, biosynthetic, and metabolic processes are located, UGT2B15, UGT2B17, SNAPC4, SDCCAG3, PMPCA, INPP6E, C9orf163, NOTCH1, C20orf166, and SLCO4A1. In addition, after a hierarchical cluster analysis based on the fluorescence intensity ratios from the comparative genomic hybridization, two congenital heart disease groups were generated corresponding to children with atrial or ventricular septal defects. Further analysis with a larger sample size is needed to corroborate these copy number variants as possible biomarkers to differentiate between heart abnormalities. Interestingly, the 20q13.33 gain was present in 50% of children with these CHD which could suggest that alterations in both coding and non-coding elements within this chromosomal region may play an important role in distinct heart conditions.

Keywords: aCGH, bioinformatics, congenital heart diseases, copy number variants, fluorescence in situ hybridization

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Authors: Ghebremedhin Tsegay, Weldu Tesfagaber, Yuanmao Zhu, Xijun He, Wan Wang, Zhenjiang Zhang, Encheng Sun, Jinya Zhang, Yuntao Guan, Fang Li, Renqiang Liu, Zhigao Bu, Dongming Zhao*

Abstract:

African swine fever (ASF) is a highly infectious viral disease of pigs, resulting in significant economic loss worldwide. As there is no approved vaccines and treatments, the control of ASF entirely depends on early diagnosis and culling of infected pigs. Thus, highly specific and sensitive diagnostic assays are required for accurate and early diagnosis of ASF virus (ASFV). Currently, only a few recombinant proteins have been tested and validated for use as reagents in ASF diagnostic assays. The most promising ones for ASFV antibody detection were p72, p30, p54, and pp62. So far, three ELISA kits based on these recombinant proteins have been commercialized. Due to the complex nature of the virus and variety forms of the disease, robust serodiagnostic assays are still required. ASFV p22 protein, encoded by KP177R gene, is located in the inner membrane of viral particle and appeared transiently in the plasma membrane early after virus infection. The p22 protein interacts with numerous cellular proteins, involved in processes of phagocytosis and endocytosis through different cellular pathways. However, p22 does not seem to be involved in virus replication or swine pathogenicity. In this study, E.coli expressed recombinant p22 protein was used to generate a monoclonal antibody (mAb), and its potential use for the development of blocking ELISA (bELISA) was evaluated. A total of 806 pig serum samples were tested to evaluate the bELISA. Acording the ROC (Reciever operating chracteristic) analysis, 100% sensitivity and 98.10% of specificity was recorded when the PI cut-off value was set at 47%. The novel assay was able to detect the antibodies as early as 9 days post infection. Finaly, a highly sensitive, specific and rapid novel p22-mAb based bELISA assay was developed, and optimized for detection of antibodies against genotype I and II ASFVs. It is a promising candidate for an early and acurate detection of the antibodies and is highly expected to have a valuable role in the containment and prevention of ASF.

Keywords: ASFV, blocking ELISA, diagnosis, monoclonal antibodies, sensitivity, specificity

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Authors: Elmeliani M’Hammed

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The work is carried out for the synthesis of antifungal effective against the fungus Fusarium oxysporum, Albedinis (Foa), the causative agent of bayoud, dates palm disease, through the use of raw clay as a green catalyst. The Aza-Michael reaction of amine addition to α, β-unsaturated alkene was carried out using the crude clay as a green catalyst to synthesize the antifungal agent bayoud. The reaction was carried out under favorable conditions, ambient temperature, without solvent, and a green catalyst "loves the environment" that the product that was synthesized gave us a high yield and excellent chemo selectivity.

Keywords: raw clay, amines, alkenes, environment, antifungal, bayoud, date palms

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Authors: Anna Cameron, Chunxia Zhao, Haofei Wang, Yun Liu, Guang Ze Yang

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Since the first publication in 1775, cancer research has built a comprehensive understanding of how cellular components of the tumor niche promote disease development. However, only within the last decade has research begun to establish the impact of non-cellular components of the niche, particularly the extracellular matrix (ECM). The ECM, a three-dimensional scaffold that sustains the tumor microenvironment, plays a crucial role in disease progression. Cancer cells actively deregulate and remodel the ECM to establish a tumor-promoting environment. Recent work has highlighted the need to further our understanding of the complexity of this cancer-ECM relationship. In vitro models use hydrogels to mimic the ECM, as hydrogel matrices offer biological compatibility and stability needed for long term cell culture. However, natural hydrogels are being used in these models verbatim, without tuning their biophysical characteristics to achieve pathophysiological relevance, thus limiting their broad use within cancer research. The biophysical attributes of these gels dictate cancer cell proliferation, invasion, metastasis, and therapeutic response. Evaluating the three most widely used natural hydrogels, Matrigel, collagen, and agarose gel, the permeability, stiffness, and pore-size of each gel were measured and compared to the in vivo environment. The pore size of all three gels fell between 0.5-6 µm, which coincides with the 0.1-5 µm in vivo pore size found in the literature. However, the stiffness for hydrogels able to support cell culture ranged between 0.05 and 0.3 kPa, which falls outside the range of 0.3-20,000 kPa reported in the literature for an in vivo ECM. Permeability was ~100x greater than in vivo measurements, due in large part to the lack of cellular components which impede permeation. Though, these measurements prove important when assessing therapeutic particle delivery, as the ECM permeability decreased with increasing particle size, with 100 nm particles exhibiting a fifth of the permeability of 10 nm particles. This work explores ways of adjusting the biophysical characteristics of hydrogels by changing protein concentration and the trade-off, which occurs due to the interdependence of these factors. The global aim of this work is to produce a more pathophysiologically relevant model for each tumor type.

Keywords: cancer, extracellular matrix, hydrogel, microfluidic

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Authors: Jonnalagadda Naveen, M. P. S. Tomar, Putluru Satish, Palanisamy Dharani

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Present investigation was carried out on a single specimen of the heart of yellow-bellied sea snake, which accidentally came to the seashore with the fisherman’s net. After the death, these specimens was preserved in 10% neutral buffered formalin and observe for its morphology. The literature cited revealed that meager information was available on the anatomy of the heart of this species of snake thus present study was planned on the gross anatomy of the heart of yellow-bellied sea snake. The heart of yellow-bellied sea snake was located between 28-35th rib in an oblique direction in the pericardial sac. It was three chambered with the complete division of atria but the ventricular cavity was incompletely divided. The apex did not show any gubernaculum cordis. The sinus venosus was the common cavity for confluence of anterior and posterior vana cava and the jugular vein was opened with anterior vena cava. The opening of posterior vena cava was slit-like and it was guarded by membranous valves whereas no valve could be observed at the opening of anterior vana cava and the jugular vein. Both the caval veins ran along the right border of the heart. Pulmonary vein was single which later divided into two branches. The length-width index for the atria was 1.33 whereas it was 1.67 for the ventricle. The atrioventricular canal was situated slightly towards the left of the midline of the heart and was divided into a right cavum pulmonale and left cavum arteriosum of which the right one was slightly larger and longer than the left. The cavum venosum was present in between the cavum pulmonale and the cavum arteriosum. The Ventricle was elongated triangle muscular compartment with ventrally located apex. Internally the cavity of ventricle was divided into two partial chambers dorsally by a muscular ridge and ventrally by an incomplete inter ventricular septum.

Keywords: aorta, atrium, heart, sea snake, sinus venosus, ventricle

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Authors: Jin-Ming Wu, Te-Wei Ho, Yu-Wen Tien

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Background: The aim of this population-based study was to determine the occurrence of diabetes and exocrine pancreatic insufficiencies (EPI) on non-diabetes subjects receiving distal pancreatectomy (DP). Method: A nationwide cohort study between 2000 and 2010 was collected from the Taiwan National Health Insurance Research Database. Among 3264 DP patients, we identified 1410 non-diabetes and 966 non-diabetes non-EPI. Results. Of 1410 non-diabetes DP subjects, 312 patients (22.1%) developed newly-diagnosed diabetes after PD. On a multiple logistic regression model, co-morbid hyperlipidemia (odds ratio, 1.640; 95% CI, 1.362–2.763; P < 0.001) and pancreatitis (odds ratio, 2.428; 95% CI, 1.889–3.121; P < 0.001) significantly contributed to higher incidences of diabetes after DP. Moreover, 380 subjects (39.3%) developed EPI, and pancreatic cancer is the statistically significant risk factor (odds ratio, 4.663; 95% CI, 2.108–6.085; P < 0.001). Conclusion: The patients with co-morbid hyperlipidemia and chronic pancreatitis had higher rates of newly-diagnosed diabetes after DP, moreover, pancreatic cancer subjects had higher rates of pancreatic exocrine insufficiency after DP. The clinicians should be alert to follow up glucose metabolism and clinical symptoms of fat intolerance for DP patients.

Keywords: distal pancreatectomy, National database, diabetes, exocrine insufficiency

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Authors: Marcin Jakiel, Maria Kurek, Karolina Gutkowska, Sylwia Sanakiewicz, Dominika Stolarczyk, Jakub Batko, Rafał Jakiel, Mateusz K. Hołda

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The geometry of RVOT is extremely complicated. It is an irregular block with an ellipsoidal cross-section, whose dimensions decrease toward the pulmonary valve and measure 33.82 (IQR 30,51-39,36), 28.82 (IQR 26,11-32,22), 27.95 ± 4,11 for width [mm] and 33.41 ± 6,14, 26.99 ± 4,41, 26.91 ± 4,00 [mm] for depth, in the basal, middle and subpulmonary parts, respectively. In a sagittal section view, the RVOT heads upward and slightly backward. Its anterior perimeter has an average length of 41.96 mm and inclines to the transverse plane at an angle of 50.77° (IQR 46,53°-58,70°). In the posterior region, the RVOT is shorter (18.17mm) and flexes anteriorly. Therefore, the slope of the upper part of the rear wall to the transverse plane is an acute angle (open toward the rear) of 44,58° (IQR 37,30°-51,25°), while in the lower part it is an angle close to a right angle of 94,30°±15,44°. In addition, the thickness of the RVOT wall in the diastolic phase, at the posterior perimeter at the base, in the middle of the length and subpulmonary measure 3,80 mm ± 0,88 mm, 3,56 mm ± 0,73 mm, 3,56 mm ± 0,65 mm, respectively. In frontal cross-section, the RVOT rises on the interventricular septum, which makes it possible to distinguish the septal and supraseptal parts on its left periphery. The angles (facing the vertices to the right) of the inclination of these parts to the transverse plane are 75.5° (IQR 66,44°-81,11°) and 107.01° (IQR 99,09 – 115,23°), respectively, which allows us to conclude that the direction of the RVOT long axis changes from left to right. The above analysis shows that there is no single RVOT axis. Two axes can be distinguished, the one for the upper RVOT being more backward and leftward. The aforementioned forward deflection of the posterior wall and the RVOT's elevation over the interventricular septum, suggest that access to the subpulmonary region may be difficult. It should be emphasized that this area is often the target for ablation of ventricular arrhythmias. The small thickness of the RVOT posterior wall, with its difficult geometry, may favor its perforation into the pericardium or ascending aorta.

Keywords: angle, geometry, operation access, position, RVOT, shape

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Authors: Vahid Nademi

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In response to widely used wearable medical devices equipped with a continuous glucose monitor (CGM) and insulin pump, the advanced control methods are still demanding to get the full benefit of these devices. Unlike costly clinical trials, implementing effective insulin-glucose control strategies can provide significant contributions to the patients suffering from chronic diseases such as diabetes. This study deals with a key role of two-layer insulin-glucose regulator based on model-predictive-control (MPC) scheme so that the patient’s predicted glucose profile is in compliance with the insulin level injected through insulin pump automatically. It is achieved by iterative optimization algorithm which is called an integrated perturbation analysis and sequential quadratic programming (IPA-SQP) solver for handling uncertainties due to unexpected variations in glucose-insulin values and body’s characteristics. The feasibility evaluation of the discussed control approach is also studied by means of numerical simulations of two case scenarios via measured data. The obtained results are presented to verify the superior and reliable performance of the proposed control scheme with no negative impact on patient safety.

Keywords: blood glucose monitoring, insulin pump, predictive control, optimization

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Authors: R. Pardo, P. Menendez, MA Gil-Olarte, S. Sanchez, E. García, R. Quintana, J. Martín

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Introduction : Within oncoplastic breast techniques there is increased interest in immediate partial breast reconstruction. The volume resected is greater than that of conventional conservative techniques. Central tumours of the breast have classically been treated with a mastectomy with regard to oncological safety and cosmetic secondary effects after wide central resection of the nipple and breast tissue beneath. Oncological results for central quadrantectomy have a recurrence level, disease- free period and survival identical to mastectomy. Grissoti flap is an oncoplastic surgical technique that allows the surgeon to perform a safe central quadrantectomy with excellent cosmetic results. Material and methods: The Grissoti flap is a glandular cutaneous advancement rotation flap that can fill the defect in the central portion of the excised breast. If the inferior border is affected by tumour and further surgery is decided upon at the Multidisciplinary Team Meeting, it will be necessary to perform a mastectomy. All patients with a Grisotti flap undergoing surgery since 2009 were reviewed obtaining the following data: age, hystopathological diagnosis, size, operating time, volume of tissue resected, postoperative admission time, re-excisions due to positive margins affected by tumour, wound dehiscence, complications and recurrence. Analysis and results of sentinel node biopsy were also obtained. Results: 12 patients underwent surgery between 2009-2015. The mean age was 54 years (34-67) . All had a preoperative diagnosis of ductal infiltrative carcinoma of less than 2 cm,. Diagnosis was made with Ultrasound, Mamography or both . Magnetic resonance was used in 5 cases. No patients had preoperative positive axilla after ultrasound exploration. Mean operating time was 104 minutes (84-130). Postoperative stay was 24 hours. Mean volume resected was 159 cc (70-286). In one patient the surgical border was affected by tumour and a further procedure with resection of the affected border was performed as ambulatory surgery. The sentinel node biopsy was positive for micrometastasis in only two cases. In one case lymphadenectomy was performed in 2009. In the other, treated in 2015, no lymphadenectomy was performed as the patient had a favourable histopathological prognosis and the multidisciplinary team meeting agreed that lymphadenectomy was not required. No recurrence has been diagnosed in any of the patients who underwent surgery and they are all disease free at present. Conclusions: Conservative surgery for retroareolar central tumours of the breast results in good local control of the disease with free surgical borders, including resection of the nipple areola complex and pectoral major muscle fascia. Reconstructive surgery with the inferior Grissoti flap adequately fills the defect after central quadrantectomy with creation of a new cutaneous disc where a new nipple areola complex is reconstructed with a local flap or micropigmentation. This avoids the need for contralateral symmetrization. Sentinel Node biopsy can be performed without added morbidity. When feasible, the Grissoti flap will avoid skin-sparing mastectomy for central breast tumours that will require the use of an expander, prosthesis or myocutaneous flap, with all the complications of a more complex operation.

Keywords: Grisotti flap, oncoplastic surgery, central tumours, breast

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Authors: Ji-Chan Jang

Abstract:

Tuberculosis is still major health problem because there is an increase of multidrug-resistant and extensively drug-resistant forms of the disease. Therefore, the most urgent clinical need is to discover potent agents and develop novel drug combination capable of reducing the duration of MDR and XDR tuberculosis therapy. Three reference strains H37Rv, CDC1551, W-Beijing GC1237 and six clinical isolates of MDRTB were tested to daptomycin in the range of 0.013 to 256 mg/L. Daptomycin is resistant to all tested M. tuberculosis strains not only laboratory strains but also clinical MDR strains that were isolated at different source. Daptomycin will not be an antibiotic of choice for treating infection of Gram positive atypical slowly growing M. tuberculosis.

Keywords: tuberculosis, daptomycin, resistance, Mycobacterium tuberculosis

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Authors: Shlomit Paz, Meir Broza

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Cholera is an acute intestinal infection caused by ingestion of food or water contaminated with the bacterium Vibrio cholerae. It has a short incubation period and produces an enterotoxin that causes copious, painless, watery diarrhoea that can quickly lead to severe dehydration and death if treatment is not promptly given. In an epidemic, the source of the contamination is usually the feces of an infected person. The disease can spread rapidly in areas with poor treatment of sewage and drinking water. Cholera remains a global threat and is one of the key indicators of social development. An estimated 3-5 million cases and over 100,000 deaths occur each year around the world. The relevance of climatic events as causative factors for cholera epidemics is well known. However, the examination of the involvement of winds in intra-continental disease distribution is new. The study explore the hypothesis that the spreading of cholera epidemics may be related to the dominant wind direction over land by presenting the influence of the wind direction on windborn dissemination by flying insects, which may serve as vectors. Chironomids ("non-biting midges“) exist in the majority of freshwater aquatic habitats, especially in estuarine and organic-rich water bodies typical to Vibrio cholerae. Chironomid adults emerge into the air for mating and dispersion. They are highly mobile, huge in number and found frequently in the air at various elevations. The huge number of chironomid egg masses attached to hard substrate on the water surface, serve as a reservoir for the free-living Vibrio bacteria. Both male and female, while emerging from the water, may carry the cholera bacteria. In experimental simulation, it was demonstrated that the cholera-bearing adult midges are carried by the wind, and transmit the bacteria from one body of water to another. In our previous study, the geographic diffusions of three cholera outbreaks were examined through their linkage with the wind direction: a) the progress of Vibrio cholerae O1 biotype El Tor in Africa during 1970–1971 and b) again in 2005–2006; and c) the rapid spread of Vibrio cholerae O139 over India during 1992–1993. Using data and map of cholera dissemination (WHO database) and mean monthly SLP and geopotential data (NOAA NCEP-NCAR database), analysis of air pressure data at sea level and at several altitudes over Africa, India and Bangladesh show a correspondence between the dominant wind direction and the intra-continental spread of cholera. The results support the hypothesis that aeroplankton (the tiny life forms that float in the air and that may be caught and carried upward by the wind, landing far from their origin) carry the cholera bacteria from one body of water to an adjacent one. In addition to these findings, the current follow-up study will present new results regarding the possible involvement of winds in the spreading of cholera in recent outbreaks (2010-2013). The findings may improve the understanding of how climatic factors are involved in the rapid distribution of new strains throughout a vast continental area. Awareness of the aerial transfer of Vibrio cholerae may assist health authorities by improving the prediction of the disease’s geographic dissemination.

Keywords: cholera, Vibrio cholerae, wind direction, Vibrio cholerae dissemination

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Authors: Eti Dwi Wiraningsih, Folashade Agusto, Lina Aryati, Syamsuddin Toaha, Suzanne Lenhart, Widodo, Willy Govaerts

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This paper considers a deterministic model for the transmission dynamics of rabies virus in the wild dogs-domestic dogs-human zoonotic cycle. The effect of vaccination and culling in dogs is considered on the model, then the stability was analysed to get basic reproduction number. We use the next generation matrix method and Routh-Hurwitz test to analyze the stability of the Disease-Free Equilibrium and Endemic Equilibrium of this model.

Keywords: stability analysis, rabies model, vaccination effect, culling in dogs

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Authors: Tatiana Butkova, Nikolai Kibrik, Kristina Malsagova, Alexander Izotov, Alexander Stepanov, Anna Kaysheva

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Relevance. The genetic risk of developing schizophrenia is determined by two factors: single nucleotide polymorphisms and gene copy number variations. The search for serological markers for early diagnosis of schizophrenia is driven by the fact that the first five years of the disease are accompanied by significant biological, psychological, and social changes. It is during this period that pathological processes are most amenable to correction. The aim of this study was to analyze single nucleotide polymorphisms (SNPs) that are hypothesized to potentially influence the onset and development of the endogenous process. Materials and Methods It was analyzed 73 single nucleotide polymorphism variants. The study included 48 patients undergoing inpatient treatment at "Psychiatric Clinical Hospital No. 1" in Moscow, comprising 23 females and 25 males. Inclusion criteria: - Patients aged 18 and above. - Diagnosis according to ICD-10: F20.0, F20.2, F20.8, F21.8, F25.1, F25.2. - Voluntary informed consent from patients. Exclusion criteria included: - The presence of concurrent somatic or neurological pathology, neuroinfections, epilepsy, organic central nervous system damage of any etiology, and regular use of medication. - Substance abuse and alcohol dependence. - Women who were pregnant or breastfeeding. Clinical and psychopathological assessment was complemented by psychometric evaluation using the PANSS scale at the beginning and end of treatment. The duration of observation during therapy was 4-6 weeks. Total DNA extraction was performed using QIAamp DNA. Blood samples were processed on Illumina HiScan and genotyped for 652,297 markers on the Infinium Global Chips Screening Array-24v2.0 using the IMPUTE2 program with parameters Ne=20,000 and k=90. Additional filtration was performed based on INFO>0.5 and genotype probability>0.5. Quality control of the obtained DNA was conducted using agarose gel electrophoresis, with each tested sample having a volume of 100 µL. Results. It was observed that several SNPs exhibited gender dependence. We identified groups of single nucleotide polymorphisms with a membership of 80% or more in either the female or male gender. These SNPs included rs2661319, rs2842030, rs4606, rs11868035, rs518147, rs5993883, and rs6269.Another noteworthy finding was the limited combination of SNPs sufficient to manifest clinical symptoms leading to hospitalization. Among all 48 patients, each of whom was analyzed for deviations in 73 SNPs, it was discovered that the combination of involved SNPs in the manifestation of pronounced clinical symptoms of schizophrenia was 19±3 out of 73 possible. In study, the frequency of occurrence of single nucleotide polymorphisms also varied. The most frequently observed SNPs were rs4849127 (in 90% of cases), rs1150226 (86%), rs1414334 (75%), rs10170310 (73%), rs2857657, and rs4436578 (71%). Conclusion. Thus, the results of this study provide additional evidence that these genes may be associated with the development of schizophrenia spectrum disorders. However, it's impossible cannot rule out the hypothesis that these polymorphisms may be in linkage disequilibrium with other functionally significant polymorphisms that may actually be involved in schizophrenia spectrum disorders. It has been shown that missense SNPs by themselves are likely not causative of the disease but are in strong linkage disequilibrium with non-functional SNPs that may indeed contribute to disease predisposition.

Keywords: gene polymorphisms, genotyping, single nucleotide polymorphisms, schizophrenia.

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