Search results for: disease trajectory

Authors: Md. Abu Sufian, Robiqul Islam, Imam Hossain Shajid, Mahesh Hanumanthu, Jarasree Varadarajan, Md. Sipon Miah, Mingbo Niu

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Coronary Heart Disease (CHD) remains a principal cause of global morbidity and mortality, characterized by atherosclerosis—the build-up of fatty deposits inside the arteries. The study introduces an innovative methodology that leverages cloud-based platforms like AWS Live Streaming and Artificial Intelligence (AI) to early detect and prevent CHD symptoms in web applications. By employing novel simulation processes and AI algorithms, this research aims to significantly mitigate the health and societal impacts of CHD. Methodology: This study introduces a novel simulation process alongside a multi-phased model development strategy. Initially, health-related data, including heart rate variability, blood pressure, lipid profiles, and ECG readings, were collected through user interactions with web-based applications as well as API Integration. The novel simulation process involved creating synthetic datasets that mimic early-stage CHD symptoms, allowing for the refinement and training of AI algorithms under controlled conditions without compromising patient privacy. AWS Live Streaming was utilized to capture real-time health data, which was then processed and analysed using advanced AI techniques. The novel aspect of our methodology lies in the simulation of CHD symptom progression, which provides a dynamic training environment for our AI models enhancing their predictive accuracy and robustness. Model Development: it developed a machine learning model trained on both real and simulated datasets. Incorporating a variety of algorithms including neural networks and ensemble learning model to identify early signs of CHD. The model's continuous learning mechanism allows it to evolve adapting to new data inputs and improving its predictive performance over time. Results and Findings: The deployment of our model yielded promising results. In the validation phase, it achieved an accuracy of 92% in predicting early CHD symptoms surpassing existing models. The precision and recall metrics stood at 89% and 91% respectively, indicating a high level of reliability in identifying at-risk individuals. These results underscore the effectiveness of combining live data streaming with AI in the early detection of CHD. Societal Implications: The implementation of cloud-based AI for CHD symptom detection represents a significant step forward in preventive healthcare. By facilitating early intervention, this approach has the potential to reduce the incidence of CHD-related complications, decrease healthcare costs, and improve patient outcomes. Moreover, the accessibility and scalability of cloud-based solutions democratize advanced health monitoring, making it available to a broader population. This study illustrates the transformative potential of integrating technology and healthcare, setting a new standard for the early detection and management of chronic diseases.

Keywords: coronary heart disease, cloud-based ai, machine learning, novel simulation techniques, early detection, preventive healthcare

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Authors: Rijnbout-St.James Willem, Lindner Volkhard, Scholand Mary Beth, Ashton M. Tillett, Di Gennaro Michael Jude, Smith Silvia Enrica

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Introduction: Fibrosing lung diseases are characterized by changes in the lung interstitium and are classified based on etiology: 1) environmental/exposure-related, 2) autoimmune-related, 3) sarcoidosis, 4) interstitial pneumonia, and 4) idiopathic. Among interstitial lung diseases (ILD) idiopathic forms, idiopathic pulmonary fibrosis (IPF) is the most severe. Pathogenesis of IPF is characterized by an increased presence of proinflammatory mediators, resulting in alveolar injury, where injury to alveolar epithelium precipitates an increase in collagen deposition, subsequently thickening the alveolar septum and decreasing gas exchange. Identifying biomarkers implicated in the pathogenesis of lung fibrosis is key to developing new therapies and improving the efficacy of existing therapies. The transforming growth factor-beta (TGF-B1), a mediator of tissue repair associated with WNT5A signaling, is partially responsible for fibroblast proliferation in ILD and is the target of Pirfenidone, one of the antifibrotic therapies used for patients with IPF. Canonical TGF-B signaling is mediated by the proteins SMAD 2/3, which are, in turn, indirectly regulated by Collagen Triple Helix Repeat Containing 1 (CTHRC1). In this study, we tested the following hypotheses: 1) CTHRC1 is more elevated in the ILD cohort compared to unaffected controls, and 2) CTHRC1 is differently expressed among ILD types. Material and Methods: CTHRC1 levels were measured by ELISA in 171 plasma samples from the deidentified University of Utah ILD cohort. Data represent a cohort of 131 ILD-affected participants and 40 unaffected controls. CTHRC1 samples were categorized by a pulmonologist based on affectation status and disease subtypes: IPF (n = 45), sarcoidosis (4), nonspecific interstitial pneumonia (16), hypersensitivity pneumonitis (n = 7), interstitial pneumonia (n=13), autoimmune (n = 15), other ILD - a category that includes undifferentiated ILD diagnoses (n = 31), and unaffected controls (n = 40). We conducted a single-factor ANOVA of plasma CTHRC1 levels to test whether CTHRC1 variance among affected and non-affected participants is statistically significantly different. In-silico analysis was performed with Ingenuity Pathway Analysis® to characterize the role of CTHRC1 in the pathway of lung fibrosis. Results: Statistical analyses of CTHRC1 in plasma samples indicate that the average CTHRC1 level is significantly higher in ILD-affected participants than controls, with the autoimmune ILD being higher than other ILD types, thus supporting our hypotheses. In-silico analyses show that CTHRC1 indirectly activates and phosphorylates SMAD3, which in turn cross-regulates TGF-B1. CTHRC1 also may regulate the expression and transcription of TGFB-1 via WNT5A and its regulatory relationship with CTNNB1. Conclusion: In-silico pathway analyses demonstrate that CTHRC1 may be an important biomarker in ILD. Analysis of plasma samples indicates that CTHRC1 expression is positively associated with ILD affectation, with autoimmune ILD having the highest average CTHRC1 values. While characterizing CTHRC1 levels in plasma can help to differentiate among ILD types and predict response to Pirfenidone, the extent to which plasma CTHRC1 level is a function of ILD severity or chronicity is unknown.

Keywords: interstitial lung disease, CTHRC1, idiopathic pulmonary fibrosis, pathway analyses

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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: 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: Seemab Safdar, Shazia Fatima, Ahmad Qureshy, M. Adnan Saeed, M. Faheem

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Background: Thyroid cancer has 586,000 cases per year worldwide, and this translates to 3% of all tumor diagnoses. 90% of the cases fall under differentiated thyroid carcinoma (DTC), which includes follicular thyroid cancer (FTC) and papillary thyroid cancer (PTC). During their illness, 10% of patients develop distant metastases, and two-thirds of them develop resistance to radioactive iodine (RAI) treatment. It has been shown that in some circumstances, like DTC with high TG levels and negative 131I whole-body scintigraphy (TENIS), [18F] FDG-PET-CT is an effective imaging technique. This study determines the role of [18F] FDG-PET-CT in the treatment of TENIS patients. Methods: 16 patients (n = 12 female; 4 males, age 45 ± 15 years) with histologically proven thyroid cancer (Differentiated and poorly differentiated) and high TG with negative iodine scans were included in this prospective study from January 2024 to June 2024. They underwent scanning in state-of-the-art (GE Discovery MI) [18F] FDG-PET-CT for re-staging or diagnostics of recurrent disease using a standardized protocol. All DTC subtypes and PDTC were included. The referring physicians completed standardized questionnaires both before and after PET-CT to prospectively determine the examination's effect on clinical decision-making. Patient outcomes were measured by analysis of medical records. Moreover, after PET-CT, a change in the pre-PET-CT planned therapies was documented in 32% of cases and additional invasive diagnostic procedures could be waived in 37.5 % of cases. TG levels under TSH stimulation were significantly higher in patients showing PET-CT metastases compared to patients without such findings (68.75%). Results: Without PET-CT, physicians referring to the doctors had not established a complete treatment plan for 45% of patients with thyroid carcinoma. 12/16 patients showed FDG avidity in cervical lymph nodes that were not Iodine avid previously, 2 patients had FDG avid disease in the lungs. In the process, PET-CT helped plan patient management and created a clear plan for treatment in 68.75% of patients. Conclusions: This study confirms that [18F] FDG-PET-CT used in a routine clinical setting has a very important impact on the management of patients with thyroid cancer when TG levels are persistently high in the presence of negative Iodine Scans by initiating treatments and replacing additional imaging and invasive tests.

Keywords: PET-CT, TENIS, role, FDG

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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*

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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: Majed Al Otaibi, Melissa Lessard-Beaudoin, Amel Loudghi, Raphael Chouinard-Watkins, Melanie Plourde, Frederic Calon, C. Alexandre Castellano, Stephen Cunnane, Helene Payette, Pierrette Gaudreau, Denis Gris, Rona K. Graham

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Introduction: Alzheimer disease (AD) is a chronic disorder that affects millions of individuals worldwide. Symptoms include memory dysfunction, and also alterations in attention, planning, language and overall cognitive function. Olfactory dysfunction is a common symptom of several neurological disorders including AD. Studying the mechanisms underlying the olfactory dysfunction may therefore lead to the discovery of potential biomarkers and/or treatments for neurodegenerative diseases. Objectives: To determine if olfactory dysfunction predicts future cognitive impairment in the aging population and to characterize the olfactory system in a murine model expressing a genetic factor of AD. Method: For the human study, quantitative olfactory tests (UPSIT and OMT) have been done on 93 subjects (aged 80 to 94 years) from the Quebec Longitudinal Study on Nutrition and Successful Aging (NuAge) cohort accepting to participate in the ORCA secondary study. The telephone Modified Mini Mental State examination (t-MMSE) was used to assess cognition levels, and an olfactory self-report was also collected. In a separate cohort, olfactory cortical volume was calculated using MRI results from healthy old adults (n=25) and patients with AD (n=18) using the AAL single-subject atlas and performed with the PNEURO tool (PMOD 3.7). For the murine study, we are using Western blotting, RT-PCR and immunohistochemistry. Result: Human Study: Based on the self-report, 81% of the participants claimed to not suffer from any problem with olfaction. However, based on the UPSIT, 94% of those subjects showed a poor olfactory performance and different forms of microsmia. Moreover, the results confirm that olfactory function declines with age. We also detected a significant decrease in olfactory cortical volume in AD individuals compared to controls. Murine study: Preliminary data demonstrate there is a significant decrease in expression levels of the proform of caspase-3 and the caspase substrate STK3, in the olfactory bulb of mice expressing human APOE4 compared with controls. In addition, there is a significant decrease in the expression level of the caspase-9 proform and caspase-8 active fragment. Analysis of the mature neuron marker, NeuN, shows decreased expression levels of both isoforms. The data also suggest that Iba-1 immunostaining is increased in the olfactory bulb of APOE4 mice compared to wild type mice. Conclusions: The activation of caspase-3 may be the cause of the decreased levels of STK3 through caspase cleavage and may play role in the inflammation observed. In the clinical study, our results suggest that seniors are unaware of their olfactory function status and therefore it is not sufficient to measure olfaction using the self-report in the elderly. Studying olfactory function and cognitive performance in the aging population will help to discover biomarkers in the early stage of the AD.

Keywords: Alzheimer's disease, APOE4, cognition, caspase, brain atrophy, neurodegenerative, olfactory dysfunction

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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

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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: Sidra Shaw, Sarenna Shaw, Chae Joon Lee, Irimpan Mathews, Eric Koehn

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One of the biggest public health concerns of our time is increasing antimicrobial resistance. As of 2019, the CDC has documented more than 2.8 million serious antibiotic resistant infections in the United States. Currently, antibiotic resistant infections are directly implicated in over 750,000 deaths per year globally. On our current trajectory, British economist Jim O’Neill predicts that by 2050, an additional 10 million people (about half the population of New York) will die annually due to drug resistant infections. As a result, new biochemical pathways must be targeted to generate next generation antibiotic drugs that will be effective against drug resistant bacteria. One enticing target is the biosynthesis of DNA within bacteria, as few drugs interrupt this essential life process. Thymidylate synthase enzymes are essential for life as they catalyze the synthesis of a DNA building block, 2′-deoxythymidine-5′-monophosphate (dTMP). In humans, the thymidylate synthase enzyme (TSase) has been shown to be distinct from the flavin-dependent thymidylate synthase (FDTS) produced by many pathogenic bacteria. TSase and FDTS have distinct structures and mechanisms of catalysis, which should allow selective inhibition of FDTS over human TSase. Currently, C. diff is one of the most antibiotic resistant bacteria, and no drugs that target thymine biosynthesis exist for C. diff. Here we present the initial biochemical characterization of FDTS from C. diff. Specifically, we examine enzyme kinetics and binding features of this enzyme to determine the nature of interaction with ligands/inhibitors and understand the molecular mechanism of catalysis. This research will provide more insight into the targetability of the C. diff FDTS enzyme for novel antibiotic drugs.

Keywords: flavin-dependent thymidylate synthase, FDTS, clostridioides difficile, C. diff, antibiotic resistance, DNA synthesis, enzyme kinetics, binding features

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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: Chinyere Ori Elom, Ikechukwu Ogeze Ukeje, Chukwudum Collins Umoke

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This paper aims to stimulate scholarly interest in AI, ICT and the existing (complex) systems trajectory- theory, practice, and aspirations within the African continent and to shed fresh light on the shortcomings of the higher education sector (HEs) through the prism of AI-driven Solutions for enhancing Guidance and Counseling and sound governance framework (SGF) in higher education modeling. It further seeks to investigate existing prospects yet to be realized in Nigerian universities by probing innovation neglect in the localities, exploring practices in the global ICT spaces neglected by Nigeria universities’ governance regimes (UGRs), and suggesting area applicability, sustainability and solution modeling in response to peculiar ‘wicked ICT-driven problems’ and or issues facing the continent as well as other universities in emerging societies. This study will adopt a mixed-method approach to collect both qualitative and quantitative data. This paper argues that it will command great relevance in the local and global university system by developing ICT relevance sustainability policy initiatives (SPIs) powered by a multi-stakeholder engagement governance model (MSEGm) that is sufficiently dynamic, eclectic and innovative to surmount complex and constantly rising challenges of the modern-developing world. Hence, it will consider diverse actors both as producers and users alike as victims and beneficiaries of common concerns in the ICT world; thereby providing pathways on how AI’s integration into education governance can significantly reduce counseling gaps, ensuring more students are attended to especially when human counselors are unavailable.

Keywords: AI-counseling solution, stakeholder engagement, university governance, higher education

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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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Authors: Abu S. Mustafa, Mohammad W. Khan, Faraz Shaheed Khan, Nazima Habibi

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Brucellosis is a zoonotic disease of worldwide prevalence. There are at least four species and several strains of Brucella that cause human disease. Brucella genomes have very limited variation across strains, which hinder strain identification using classical molecular techniques, including PCR and 16 S rDNA sequencing. The aim of this study was to perform whole genome sequencing of clinical isolates of Brucella and perform bioinformatics and comparative genomics analyses to determine the existence of genetic differences across the isolates of a single Brucella species and strain. The draft sequence data were generated from 15 clinical isolates of Brucella melitensis (biovar 2 strain 63/9) using MiSeq next generation sequencing platform. The generated reads were used for further assembly and analysis. All the analysis was performed using Bioinformatics work station (8 core i7 processor, 8GB RAM with Bio-Linux operating system). FastQC was used to determine the quality of reads and low quality reads were trimmed or eliminated using Fastx_trimmer. Assembly was done by using Velvet and ABySS softwares. The ordering of assembled contigs was performed by Mauve. An online server RAST was employed to annotate the contigs assembly. Annotated genomes were compared using Mauve and ACT tools. The QC score for DNA sequence data, generated by MiSeq, was higher than 30 for 80% of reads with more than 100x coverage, which suggested that data could be utilized for further analysis. However when analyzed by FastQC, quality of four reads was not good enough for creating a complete genome draft so remaining 11 samples were used for further analysis. The comparative genome analyses showed that despite sharing same gene sets, single nucleotide polymorphisms and insertions/deletions existed across different genomes, which provided a variable extent of diversity to these bacteria. In conclusion, the next generation sequencing, bioinformatics, and comparative genome analysis can be utilized to find variations (point mutations, insertions and deletions) across different genomes of Brucella within a single strain. This information could be useful in surveillance and epidemiological studies supported by Kuwait University Research Sector grants MI04/15 and SRUL02/13.

Keywords: brucella, bioinformatics, comparative genomics, whole genome sequencing

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Authors: Farideh Doostan, Sahar Mohseni Taklloo, Mohammad Nosrati

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Chronic diseases are non-communicable and largely preventable by lifestyle changes including healthy diet consumption. They are the most common cause of death in the world and projected to increase by 15% globally between 2010 and 2020.The hazardous effects of behavioral and dietary risk factors on chronic disease have been established in prospective cohort studies and randomized trials. Because of some changes occur in college students’ lifestyle, assessment of dietary risk factors is important in these populations. Objective: This research was the first study that conducted to evaluate dietary intakes of Kermanian college students with WHO/FAO nutritional objectives. Material and Methods: In this descriptive cross-sectional study, 229 healthy college students of health faculty in Kerman University of Medical Sciences that do not intake any medical drugs were recruited using multistage sampling in 2013.Usual dietary intake was collected using a valid Food Frequency Questionnaire (FFQ) and diet quality was calculated based on WHO nutrient goals. To analysis of data between two groups, independent sample t. test and man whitney were applied. Results: Two hundred and twenty-nine college students; 151 females (65.9%) and 78 males (34.1%), the mean age of 21.9 years were studied. The mean of the Body Mass Index (Kg/m2) and Waist Circumference (cm) in males were 22.34 ±3.52 and 80.76±11.16 and in females were 21.19±2.62 and 73.67±7.65 respectively. Mean of daily cholesterol intake in males was significantly more than females (305±101 VS 268±98; P=0.008) and more than WHO/FAO recommendation (less than 300 mg/day). The mean of daily sodium intake in men and women were 10.4±1 and 10.9±5.3 respectively. These amounts were more than WHO/FAO recommendation (less than 2g/day). In addition, women were consumed fruit and vegetables more than men (839±336 VS 638±281; p ‹ 0.001) and these amounts were more than WHO/FAO recommendation (more than 400g/day) in both groups. Other intake indices were in the range of WHO/FAO recommendations, So that Percent of calories intake from total fat, saturated fatty acids, polyunsaturated fatty acids and added sugar were in compliance with WHO/FAO recommendations. Conclusion: Cholesterol intake in men and sodium intake in all participants were more than WHO/FAO recommendation. These dietary components are the most important causes of cardiovascular disease (one of the main causes of death in our population). These results indicated that proper nutritional education and interventions are needed in this population.

Keywords: college students, food intake, WHO /FAO nutrient intake goals, Kerman

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Authors: A. Mirzaei, S. Zolghadri, M. Athari-Allaf, H. Yousefnia, A. R. Jalilian

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Rheumatoid arthritis is the most common autoimmune disease, leading to the destruction of the joints. The aim of this study was the preparation of 90Y-chitosan complex as a novel agent for radiosynovectomy. The complex was prepared in the diluted acetic acid solution. At the optimized condition, the radiochemical purity of higher than 99% was obtained by ITLC method on Whatman No. 1 and by using a mixture of methanol/water/acetic acid (4:4:2) as the mobile phase. The complex was stable in acidic media (pH=3) and its radiochemical purity was above 98% even after 48 hours. The biodistribution data in rats showed that there was no significant leakage of the injected activity even after 48 h. Considering all of the excellent features of the complex, 90Y-chitosan can be used to manipulate synovial inflammation effectively.

Keywords: chitosan, Y-90, radiosynovectomy, biodistribution

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Authors: Sara Zelman, Courtney Meyer, Hiren Patel, Lisa Philpotts, Sue Lahey, Thomas Burke

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Background: As the global burden of disease shifts from infectious diseases to noncommunicable diseases, there is growing urgency to provide treatment for time-sensitive illnesses, such as ST-Elevation Myocardial Infarctions (STEMIs). The standard of care for STEMIs in developed countries is Percutaneous Coronary Intervention (PCI). However, this is inaccessible in resource-limited settings. Before the discovery of PCI, Streptokinase (STK) and other thrombolytic drugs were first-line treatments for STEMIs. STK has been recognized as a cost-effective and safe treatment for STEMIs; however, in settings which lack access to PCI, it has not become the established second-line therapy. A systematic literature review was conducted to geographically map the use of STK for STEMIs in resource-limited settings. Methods: Our literature review group searched the databases Cinhal, Embase, Ovid, Pubmed, Web of Science, and WHO’s Index Medicus. The search terms included ‘thrombolytics’ AND ‘myocardial infarction’ AND ‘resource-limited’ and were restricted to human studies and papers written in English. A considerable number of studies came from Latin America; however, these studies were not written in English and were excluded. The initial search yielded 3,487 articles, which was reduced to 3,196 papers after titles were screened. Three medical professionals then screened abstracts, from which 291 articles were selected for full-text review and 94 papers were chosen for final inclusion. These articles were then analyzed and mapped geographically. Results: This systematic literature review revealed that STK has been used for the treatment of STEMIs in 33 resource-limited countries, with 18 of 94 studies taking place in India. Furthermore, 13 studies occurred in Pakistan, followed by Iran (6), Sri Lanka (5), Brazil (4), China (4), and South Africa (4). Conclusion: Our systematic review revealed that STK has been used for the treatment of STEMIs in 33 resource-limited countries, with the highest utilization occurring in India. This demonstrates that even though STK has high utility for STEMI treatment in resource-limited settings, it still has not become the standard of care. Future research should investigate the barriers preventing the establishment of STK use as second-line treatment after PCI.

Keywords: cardiovascular disease, global health, resource-limited setting, ST-Elevation Myocardial Infarction, Streptokinase

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Authors: Marko Jankovic, Aleksandra Knezevic, Maja Cupic, Dragana Vujic, Zeljko Zecevic, Borko Gobeljic, Marija Simic, Tanja Jovanovic

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The human cytomegalovirus (CMV) is a notorious pathogen in the pediatric transplant setting. Although studies on factors in complicity with CMV infection abound, the role of age, gender, allogeneic hematopoietic stem cell transplantation (alloHSCT) modality, and underlying disease as regards CMV infection and viral load in children are poorly explored. We examined the significance of various factors related to the risk of CMV infection and viral load in Serbian children and adolescents undergoing alloHSCT. This was a prospective single centre study of thirty two pediatric patients in receipt of alloHSCT for various malignant and non-malignant disorders. Screening for active viral infection was performed by regular weekly monitoring. The Real-Time PCR method was used for CMV DNA detection and quantitation. Statistical analysis was performed using the IBM SPSS Statistics v20 software. Chi-square test was used to evaluate categorical variables. Comparison between scalar and nominal data was done by Wilcoxon-Mann-Whitney test. Pearson correlation was applied for studying the association between patient age and viral load. CMV was detected in 23 (71.9%) patients. Infection occurred significantly more often (p=0.015) in patients with haploidentical donors. The opposite was noted for matched sibling grafts (p=0.006). The viral load was higher in females (p=0.041) and children in the aftermath of alloHSCT with malignant diseases (p=0.019). There was no significant relationship between the viral infection dynamics and overt medical consequences. This is the first study of risk factors for CMV infection in Serbian pediatric alloHSCT patients. Transplanted patients presented with a high incidence of CMV viremia. The HLA compatibility of donated graft is associated with the frequency of CMV positive events. Age, gender, underlying disease, and medically relevant events were not conducive to occurrences of viremia. Notably, substantial viral burdens were evidenced in females and patients with neoplastic diseases. Studies comprising larger populations are clearly needed to scrutinize current results.

Keywords: allogeneic hematopoietic stem cell transplantation, children, cytomegalovirus, risk factors, viral load

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Authors: Michael Naderhirn, Marco Pavone

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Problem statement, motivation, and aim of work: So far, the development of control algorithms was done by control engineers in a way that the controller would fit a specification by testing. When it comes to the certification of an autonomous car in highly complex scenarios, the challenge is much higher since such a controller must mathematically guarantee to implement the rules of the road while on the other side guarantee aspects like safety and real time executability. What if it becomes reality to solve this demanding problem by combining Formal Verification and System Theory? The aim of this work is to present a workflow to solve the above mentioned problem. Summary of the presented results / main outcomes: We show the usage of an English like language to transform the rules of the road into system specification for an autonomous car. The language based specifications are used to define system functions and interfaces. Based on that a formal model is developed which formally correctly models the specifications. On the other side, a mathematical model describing the systems dynamics is used to calculate the systems reachability set which is further used to determine the system input boundaries. Then a motion planning algorithm is applied inside the system boundaries to find an optimized trajectory in combination with the formal specification model while satisfying the specifications. The result is a control strategy which can be applied in real time independent of the scenario with a mathematical guarantee to satisfy a predefined specification. We demonstrate the applicability of the method in simulation driving scenarios and a potential certification. Originality, significance, and benefit: To the authors’ best knowledge, it is the first time that it is possible to show an automated workflow which combines a specification in an English like language and a mathematical model in a mathematical formal verified way to synthesizes a controller for potential real time applications like autonomous driving.

Keywords: formal system verification, reachability, real time controller, hybrid system

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Authors: Gabriella Jorge, Carlos A. Pérez, Hanna Friberg, Sara Söderlund, Jan Lagerlöf

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Fusarium Head Blight (FHB) is one of the most important Fusarium-caused diseases, which affects cereals with serious detrimental effects on yield and grain quality worldwide. Earthworms have been suggested as an alternative to control this disease, which requires a combination of preventive methods to reduce level of damage, although it has been proven that their effect is species dependent. Our objective was to evaluate the effect of the earthworms Aporrectodea longa and Lumbricus rubellus, on the inoculum of Fusarium graminearum on wheat straw. To test this we kept earthworms in vessels with soil, and F. graminearum-inoculated straw covering the surface, under controlled conditions for 6 weeks. Two factors were evaluated with a complete factorial design: earthworms (three levels: without earthworms, A. longa, and L. rubellus), and straw (two levels: inoculated with the pathogen, and sterile). The presence of L. rubellus significantly (P<0.05) reduced the amount of inoculated straw at the soil surface 31% after 6 weeks, while the presence of A. longa, most found in quiescence, did not have any significant effect on the amount of straw when compared to the control. After incubation, F. graminearum was detected by qPCR, only in the surface straw in those treatments inoculated with the pathogen but without earthworms. None of the treatments showed presence of Fusarium in the buried straw, soil or earthworm casts. Both earthworm species decreased in body weight during incubation, most likely due to the decrease in soil water content during the experiment, from 25% to 20%, and/or inadequate food supply, since no other source of food was added. However, this reduction in weight occurred indistinctly of the presence or not of Fusarium (P<0.05). This indicates that both species, of different ecological groups, anecic and epigeic, can reduce F. graminearum inoculum present in wheat straw, while their growth is not negatively affected by this pathogen. These promising results place A. longa, and L. rubellus as potential biocontrol agents of this fungal plant pathogen responsible for Fusarium Head Blight disease in wheat, although further ongoing experiments are needed to confirm the repeatability of these results.

Keywords: Aporrectodea longa, biological control, fungal plant pathogen, Lumbricus rubellus, qPCR, wheat straw

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Authors: Maha M. Eissa, Safia M. Ali, Sonia R. Allam, Ezzat A. Badawy, Nahed M. Baddour

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The obligate follicle mite Demodex folliculorum (Df) has been demonstrated in increased numbers in patients with rosacea. The significance of this finding is still not completely understood because many people free of skin disease may also have mites. So, the aim of this work was to study the possible role of Df in patients with rosacea. Facial punch biopsy specimens were taken from patients with rosacea (either telangiectatic, papulopustular, squamous, granulomatous form or with rhinophyma) and age and sex-matched healthy subjects. Results of this study showed that 63.3% of the rosacea patients were harbouring the mite, with a higher incidence in patients with papulopustular form.

Keywords: Demodex folliculorum, histopathology, punch biopsy, rosacea

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Authors: Kumari Rekha, Mathur K Dhananjay, Maheshwari Deepanshu, Nautiyal Nidhi, Shubham Smriti, Laal Deepika, Sinha Swati, Kumar Anupam, Biswas Subhrajit, Shiv Kumar Sarin

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Background: Mesenchymal stem cells are multipotent stem cells derived from mesoderm and are used for therapeutic purposes because of their self-renewal, homing capacity, Immunomodulatory capability, low immunogenicity and mitochondrial transfer signaling. MSCs have the ability to regulate the mechanism of both innate as well as adaptive immune responses through the modulation of cellular response and the secretion of inflammatory mediators. Different sources of MSC are UC MSC, BM MSC, Dental Pulp, and Adipose MSC. The most frequent source used is umbilical cord tissue due to its being easily available and free of limitations of collection procedures from respective hospitals. The immunosuppressive role of MSCs is particularly interesting for clinical use since it confers resistance to rejection by the host immune response. Methodology: In this study, T helper cells (TH4), Cytotoxic T cells (CD-8), immunoregulatory cells (CD25 +FOXP3+) are compared from isolated MSC from three different methods, UC Dissociation Kit (Miltenyi), Explant Culture and Collagenase Type-IV. To check the immunomodulatory property, these MSCs were seeded with PBMC(Coculture) in CD3 coated 24 well plates. Cd28 antibody was added in coculture for six days. The coculture was analyzed in FACS Verse flow cytometry. Results: From flow cytometry analysis of coculture, it found that All over T helper cells (CD4+) number p<0.0264 increases in (All Enzymes) MSC rather than explant MSC(p>0.0895) as compared to Collagenase(p>0.7889) in a coculture of Activated T cell and Mesenchymal Stem Cell. Similar T reg cells (CD25+, FOXP3+) expression p<0.0234increases in All Enzymes), decreases in Explant and Collagenase. Experiments have shown that MSCs can also directly prevent the cytotoxic activity of CD8 lymphocytes mainly by blocking their proliferation rather than by inhibiting the cytotoxic effect. And promoting the t-reg cells, which helps in the mediation of immune response in various diseases. Conclusion: MSC suppress Cytotoxic CD8 T cell and Enhance immunoregulatory T reg (CD4+, CD25+, FOXP3+) Cell expression. Thus, MSC maintains a proper balance(ratio) between CD4 T cells and Cytotoxic CD8 T cells.

Keywords: MSC, disease, T cell, T regulatory

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Authors: Ledi Neçaj

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Introduction: Cardio-respiratory rehabilitation is the set of coordinated interventions needed to provide the best physical, psychological, and social conditions so that patients with chronic or post-acute cardiopulmonary disease, with their efforts, maintain or resume optimal functioning in society through improved health behaviors. Purpose: To study the effectiveness of the application of Cardio-Respiratory Rehabilitation in the typology of patients with chronic or post-acute cardiomyopathy and chronic respiratory diseases in order to facilitate their therapeutic use and to improve the overall quality of life. Material and Method: This is a prospective study including patients with COPD and cardiac disease who were included in the rehabilitation program during the period January 2019 - November 2021. The study was conducted at the University Hospital Center "Mother Teresa" in Tirana, University Hospital "SHEFQET NDROQI", AMERICAN Hospital, HYGEA Hospital, and "Our Lady of Good Counsel, Tirana". An individual chart was used to collect sociodemographic, physical, clinical, and functional examinations for each patient. Results: The study included 253 patients, with a mean age of 62.1 (± 7.9) years, ranging from 48 to 82 years. (67.6%) of the patients were males, and (32.4%) female. Male patients predominated in all age groups, with a statistically significant difference with females (p<0.01). The most common cardiac pathologies are coronary artery bypass (24%), cerebral stroke (9%), myocardial infarction (17%), Stent placement (8%) (p<0.01). Correlation matrix of risk factors found a significant correlation of alcohol consumption with diabetes, smoking, dyslipidemia, sedentary life, obesity, AVC, and hypertension. Functional capacity estimated by change in metabolic equivalents (MET) improved by 46% from 4. ±2.2 to 7.2± .8 METs (p<0.01). Duration of exercise after rehabilitation was increased by 21% compared to baseline (p<0.01). The mean score of all three subscales of the questionnaire: symptoms (p=0.03), activity (p<0.01), and impact (p<0.01) after rehabilitation, was lower compared to pre-rehabilitation. Conclusions: The rehabilitation program has impacted on improving the quality of life, reducing symptoms, reducing the impact of negative factors on daily life, and reducing dyspnea during daily activities.

Keywords: cardio-respiratory rehabilitation, physical exercise, quality of life, diseases

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Authors: Mohamed Ahmed Tony, Mohamed Hamoud

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The present study was conducted to determine the effect of commercially coated slow-release sodium butyrate (CM3000®) as a feed additive on zootechnical performance, immune status and Clostridium perfringens severity after experimental infection. Three hundred 1-d-old broiler chicks (Cobb 500) were randomly distributed into 3 treatment groups (4 replicates each) using 25 chicks per replicate on floor pens. Control (C) birds were offered non-supplemented basal diets. Treatments 1 and 2 (T1 and T2) were fed diets containing CM3000® at 300 and 500 g/ton feed, respectively, during the entire experimental period (35 days). Feed and water were offered ad-libitum. Feed consumption and body weight were recorded weekly to calculate body weight gain and feed conversion. Blood samples were collected to evaluate the immune status of the birds against Newcastle disease vaccines using HI test. At the end of the experimental period, 20 birds were chosen randomly from each group (5 birds from each pen) to compare carcass yield. At day 16 of age 20 birds from each group (5 birds/replicate) were bacteriologically examined and proved to be free from Clostridium perfringens. The isolated birds were challenged orally with 1 ml buffer containing 106 CFU/ml Clostridium perfringens local isolate and prepared from necrotic enteritis (NE) diseased farms. Birds were observed on a regular basis daily for any signs of NE. Birds that died in the challenged group were necropsied to determine the cause of death. On day 28 of age, the surviving chickens were killed by cervical dislocation and necropsied immediately. Intestinal tracts were removed and intestinal lesions were scored. Tissue samples of the duodenum, jejunum, ileum and cecum for histopathological examination were collected. All collected data were statistically analyzed using IBM SPSS® version 19 software for personal computers. Means were compared by one-way ANOVA (P<0.05) followed by the Duncan Post Hoc test. The results revealed that body weight gain was significantly (P<0.05) improved in chicks fed on both doses of CM3000® compared to the control one. Final body weight gain in T1 and T2 were 2064.94 and 2141.37 g/bird, respectively, while in the control group, the weight gain showed 1952.78 g/bird. In addition, supplementation of diets with CM3000® increased significantly feed intake (P<0.05). Total feed intake in T1 and T2 were 3186.32 and 3273.29 g/bird, respectively; however, feed intake in the control group recorded 3081.95 g/bird. The best feed conversion was recorded in T2 group (1.53). Feed conversion in the control and T1 groups were 1.58 and 1.54, respectively. Dressing percentage, liver weights and the other carcasses yields were not different between treatments. The butyrate significantly enhanced immune responses measured against Newcastle disease vaccines. Sodium butyrate significantly reduced NE lesions and healthy improved the intestinal tissues in the samples collected from T1 and T2-challenged chickens versus those collected from the control group. In conclusion, exogenous administration of slow-release butyrate (CM3000®) is capable of improving performance, enhancing immunity and NE disease resistance in broiler chickens.

Keywords: sodium butyrate, broiler chicken, zootechnical performance, immunity, necrotic enteritis

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Authors: Edilei Reis, Jose Carlos Felix

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This paper explores Waldir Dupont’s translations of William Faulkner’s novels to Brazilian Portuguese language in order to comprehend how his translation project regarding Faulkner’s works has addressed modernist traits of the novelist fiction, particularly the ambivalence of language, multiple and fragmented points of view and syntax. Wladir Dupont (1939-2014) was a prolific Brazilian journalist who benefitted from his experiences as an international correspondent living abroad (EUA and Mexico) to become an acclaimed translator later in life. He received a Jabuiti Award (Brazilian most prestigious literary award) for his translation of ‘La Otra Voz’ (1994), by Mexican poet, critic and translator Octavio Paz, a writer to whom he devoted the first years of his carrier as a translator. As Dupont pointed out in some interviews, the struggles in finding a way out to overcome linguistic and cultural obstacles in the process of translating texts from Spanish to Portuguese was paramount for ascertaining his engagement in the long-term project of translating to Brazilian Portuguese the fiction of William Faulkner. His first enterprise was the translation of Faulkner’s trilogy Snopes: The Hamlet (1940) and The Town (1957), the first two novels, were published in 1997 as O povoado and A cidade; in 1999 the last novel, The mansion (1959), was published as A mansão. In 2001, Dupont tackled what is considered one of the most challenging novels by the author due to his use of multiple points of view, As I lay dying (1930). In 2003, The Reivers (1962) was published under the title Os invictos. His enterprise finishes in 2012 with the publication of an anthology of Faulkner’s thriller short-stories Knight’s Gambit (1932) as Lance mortal. Hence, in this paper we will consider the Dupont’s trajectory as a translator, paying special attention to the way in which his identity as such is constituted through the process of translating Faulkner’s works.

Keywords: literary translation, translator’s identity, William Faulkner, Wladir DuPont

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