Search results for: bone disease

Authors: Abhaydeep Pandey, Shweta Shukla, Saptamita Goswami, Bhaswati Bandyopadhyay, Vishnampettai Ramachandran, Sudhanshu Vrati, Arup Banerjee

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Background: Long non-coding RNAs (lncRNAs) are the important regulators of gene expression and play important role in viral replication and disease progression. The role of lncRNA genes in the pathogenesis of Dengue virus-mediated pathogenesis is currently unknown. Methods: To gain additional insights, we utilized an unbiased RNA sequencing followed by in silico analysis approach to identify the differentially expressed lncRNA and genes that are associated with dengue disease progression. Further, we focused our study on lncRNAs NEAT1 (Nuclear Paraspeckle Assembly Transcript 1) as it was found to be differentially expressed in PBMC of dengue infected patients. Results: The expression of lncRNAs NEAT1, as compared to dengue infection (DI), was significantly down-regulated as the patients developed the complication. Moreover, pairwise analysis on follow up patients confirmed that suppression of NEAT1 expression was associated with rapid fall in platelet count in dengue infected patients. Severe dengue patients (DS) (n=18; platelet count < 20K) when recovered from infection showing high NEAT1 expression as it observed in healthy donors. By co-expression network analysis and subsequent validation, we revealed that coding gene; IFI27 expression was significantly up-regulated in severe dengue cases and negatively correlated with NEAT1 expression. To discriminate DI from dengue severe, receiver operating characteristic (ROC) curve was calculated. It revealed sensitivity and specificity of 100% (95%CI: 85.69 – 97.22) and area under the curve (AUC) = 0.97 for NEAT1. Conclusions: Altogether, our first observations demonstrate that monitoring NEAT1and IFI27 expression in dengue patients could be useful in understanding dengue virus-induced disease progression and may be involved in pathophysiological processes.

Keywords: dengue, lncRNA, NEAT1, transcriptome

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Authors: Kai-Yao Huang, Tzong-Yi Lee, Pin-Hao Ho, Tzu-Hao Chang, Cheng-Wei Chang

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Background: Human cytomegalovirus (HCMV) infects much people around the world, and there were many researches mention that many diseases were caused by HCMV. To understand the mechanism of HCMV lead to diseases during infection. We observe a microRNA (miRNA) – miRNA interaction between HCMV and host during infection. We found HCMV miRNA sequence component complementary with host miRNA precursors, and we also found that the host miRNA abundances were decrease in HCMV infection. Hence, we focus on the host miRNA which may target by the other HCMV miRNA to find theirs target mRNAs expression and analysis these mRNAs affect what kind of signaling pathway. Interestingly, we found the affected mRNA play an important role in some diseases related pathways, and these diseases had been annotated by HCMV infection. Results: From our analysis procedure, we found 464 human miRNAs might be targeted by 26 HCMV miRNAs and there were 291 human miRNAs shows the concordant decrease trend during HCMV infection. For case study, we found hcmv-miR-US22-5p may regulate hsa-mir-877 and we analysis the KEGG pathway which built by hsa-mir-877 validate target mRNA. Additionally, through survey KEGG Disease database found that these mRNA co-regulate some disease related pathway for instance cancer, nerve disease. However, there were studies annotated that HCMV infection casuse cancer and Alzheimer. Conclusions: This work supply a different scenario of miRNA target interactions(MTIs). In previous study assume miRNA only target to other mRNA. Here we wonder there is possibility that miRNAs might regulate non-mRNA targets, like other miRNAs. In this study, we not only consider the sequence similarity with HCMV miRNAs and human miRNA precursors but also the expression trend of these miRNAs. Then we analysis the human miRNAs validate target mRNAs and its associated KEGG pathway. Finally, we survey related works to validate our investigation.

Keywords: human cytomegalovirus, HCMV, microRNA, miRNA

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Authors: Mike Wei, Nebu Koshy, Koen van Besien, Giorgio Inghirami, Steven M. Horwitz

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T-cell prolymphocytic leukemia (T-PLL) is a rare hematologic disease characterized by a T-cell phenotype, rapid progression, and poor prognosis with median survival of less than a year. Alemtuzumab-based chemotherapy has increased the rate of complete remissions but these are often short-lived, and allogeneic transplant is considered the only curative therapy. In recent studies, JAK3 activating mutations have been identified in T-cell cancers, with T-PLL having the highest rate of JAK3 mutations (30 – 42%). As such, T-PLL is a model disease for evaluating the utility of JAK3 inhibitors. We present a case of a 64-year-old man with relapsed-refractory T-PLL. He was initially treated with alemtuzumab and obtained complete response and was consolidated with matched unrelated donor stem cell transplant. His disease stayed in remission for approximately 1.5 years before relapse, which was then treated with a clinical trial of romidepsin-lenalidomide (partial responses then progression at 6 months) and later alemtuzumab. Due to complications of myelosuppression and CMV reactivation, his treatment was interrupted leading to disease progression. The doubling time of lymphocyte count was approximately 20 days and over a span of 60 days the lymphocyte count rose from 8 x 109/L to 68 x 109/L. Exon sequencing showed a JAK3 mutation. The patient consented to and was treated with FDA-approved tofacitinib (initially 5 mg BID, increased to 10 mg BID after 15 days of treatment). An initial decrease in lymphocyte count was followed by progression. In vitro treatment of the patient’s cells showed modest effects of tofacitinib and ruxolitinib as single agents, in the range of doxorubicin, but synergy between the agents. After 40 days of treatment with tofacitinib and with a lymphocyte count of 150 x 109/L, ruxolitinib (5mg BID) was added. Over the 60 days since dual inhibition was started, the lymphocyte count has stabilized. The patient has remained completely asymptomatic during treatment with tofacitinib and ruxolitinib. Neutrophil count has remained normal. Platelet count and hemoglobin have however declined from ~50 x109/L to ~30 x109/L and from 11 g/dL to 8.1 g/dL respectively, since the introduction of ruxolitinib. The stabilization in lymphocyte count confirms the clinical activity of JAK inhibitors in T-PLL as suggested by the presence of JAK3 mutations and by in-vitro assays. It also suggests clinical synergy between ruxolitinib and tofacitinib in this setting. Prospective studies of JAK inhibitors in PLL patients with formal dose-finding studies are needed.

Keywords: tofacitinib, ruxolitinib, T-cell prolymphocytic leukemia, JAK3

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Authors: Sima Parvizi Omran, Rezvan Tavakoli, Mahnaz Safari, Mohammadreza Aghasadeghi, Abolfazl Fateh, Pooneh Rahimi

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Background: SARS-CoV-2, a single-stranded RNA betacoronavirus causes the global outbreak of coronavirus disease 2019 (COVID-19). Several clinical and scientific concerns are raised by this pandemic. Genetic factors can contribute to pathogenesis and disease susceptibility. There are single nucleotide polymorphisms (SNPs) in many of the genes in the immune system that affect the expression of specific genes or functions of some proteins related to immune responses against viral infections. In this study, we analyzed the impact of polymorphism in the interferon alpha and beta receptor subunit 2 (IFNAR2) and dipeptidyl peptidase 9 (Dpp9) genes and clinical parameters on the susceptibility and resistance to Coronavirus disease (COVID-19). Methods: A total of 330- SARS-CoV-2 positive patients (188 survivors and 142 nonsurvivors) were included in this study. All single-nucleotide polymorphisms (SNPs) on IFNAR2 (rs2236757) and Dpp9 (rs2109069) were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: In survivor patients, the frequency of the favourable genotypes of IFNAR2 SNP (rs2236757 GC) was significantly higher than in nonsurvivor patients, and also Dpp9 (rs2109069 AT) genotypes were associated with the severity of COVID-19 infection. Conclusions: This study demonstrated that the severity of COVID- 19 patients was strongly associated with clinical parameters and unfavourable IFNAR2, Dpp9 SNP genotypes. In order to establish the relationship between host genetic factors and the severity of COVID-19 infection, further studies are needed in multiple parts of the world.

Keywords: SARS-CoV-2, COVID-19, interferon alpha and beta receptor subunit 2, dipeptidyl peptidase 9, single-nucleotide polymorphisms

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Authors: Fitsumbrhan Tajebe, Fadil Murad, Mitikie Tigabie, Mareye Abebaw, Tadele Alemu, Sefanit Abate, Rezika Mohammedw, Arega Yeshanew, Elias Shiferaw

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Background: Visceral leshimaniasis is a parasitic disease characterized by a systemic infection of phagocytic cells. Hematological parameters of these patients may be affected by the progress of the disease or treatment. Thus, the current study aimed to assess the hematological profiles of visceral leishmaniasis patients before and after treatment. Method: An institutional based retrospective cohort study was conducted among visceral leishmaniasis patients at University of Gondar Comprehensive Specialized Referral Hospital Leishmaniasis Research and Treatment Center from 2013 to 2018. Hematological profiles before initiation and after completion of treatment were extracted from registration book. Descriptive statics was presented using frequency and percentage. Paired t-test and Wilcoxon Signed rank test were used for comparing mean difference for normally and non- normally distributed data, respectively. Spearman and Pearson correlation analysis was used to describe the correlation of hematological parameters with different variables. P value < 0.05 was considered as statistically significant. Result: Except absolute nerutrophil count, post treatment hematological parameters show a significant increment compared to pretreatment one. The prevalence of anemia, leucopenia and thrombocytopenia was 85.5%, 83.4% and 75.8% prior to treatment and it was 58.3%, 38.2% and 19.2% after treatment, respectively. Moreover, parasite load of the disease showed statistically significant negative correlation with hematological profiles mainly with white blood cell and red blood cell. Conclusion: Majority of hematological profiles of patients with active VL have been restored after treatment, which might be associated with treatment effect on parasite proliferation and concentration of parasite in visceral organ, which directly affect hematological profiles.

Keywords: visceral leshimaniasis, hematological profile, anti-leshimanial drug, Gondar

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Authors: Sung-yong Choi, Woo-tai Jung, Young-hwan Park

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This study intends to improve the bond performance of the polypropylene fiber used as reinforcing fiber for concrete by changing its shape into double crimped type through the enhancement its fabrication process. The bond performance of such double crimped fiber is evaluated by applying the JCI SF-8 (dog-bone shape) testing method. The test results reveal that the double crimped fiber develops bond performance improved by more than 19% compared to the conventional crimped type fiber.

Keywords: Bond, Polypropylene, fiber reinforcement, macro fiber, shape change

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Authors: Getahun Lemma

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Introduction Guinea Worm Disease (GWD), also known as dracunculiasisis, is one of the oldest diseases in the history of mankind. Dracunculiasis is caused by a parasitic nematode, Dracunculus medinensis. Infection is acquired by drinking contaminated water with copepods containing infective Guinea Worm (GW) larvae). Almost one year after the infection, the worm usually emerges out through the skin on a lower, causing severe pain and disabilities. Although there is no effective drug or vaccine against the disease, the chain of transmission can be effectively prevented with simple and cost effective public health measures. Death due to dracunculiasis is very rare. However, it results in a wide range of physical, social and economic sequels. The disease is usually common in the rural, remote places of Sub-Saharan African countries among the marginalized societies. Currently, GWD is one of the neglected tropical diseases, which is on the verge of eradication. The global Guinea Worm Eradication Program (GWEP) was started in 1980. Since then, the program has achieved a tremendous success in reducing the global burden and number of GW case from 3.5 million to only 28 human cases at the end of 2018. However, it has recently been shown that not only humans can become infected, with a total of 1,105 animal infections have been reported at the end of 2018. Therefore, the objective of this study was to identify the existing challenges in the last mile of the GWEP in order To inform Policy makers and stakeholders on potential measures to finally achieve eradication. Method Systematic literature review on articles published from January 1, 2000 until May 30, 2019. Papers listed in Cochrane Library, Google Scholar, ProQuest PubMed and Web of Science databases were searched and reviewed. Results Twenty-five articles met inclusion criteria of the study and were selected for analysis. Hence, relevant data were extracted, grouped and descriptively analyzed. Results showed the main challenges complicating the last mile of global GWEP: 1. Unusual mode of transmission; 2. Rising animal Guinea Worm infection; 3. Suboptimal surveillance; 4. Insecurity; 5. Inaccessibility; 6. Inadequate safe water points; 7. Migration; 8. Poor case containment measures, 9. Ecological changes; and 10. New geographic foci of the disease. Conclusion This systematic review identified that most of the current challenges in the GWEP have been present since the start of the campaign. However, the recent change in epidemiological patterns and nature of GWD in the last remaining endemic countries illustrates a new twist in the global GWEP. Considering the complex nature of the current challenges, there seems to be a need for a more coordinated and multidisciplinary approach of GWD prevention and control measures in the last mile of the campaign. These new strategies would help to make history by eradicating dracunculiasis as the first ever parasitic disease.

Keywords: dracunculiasis, eradication program, guinea worm, last mile

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Authors: Apoorva D. R.

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INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a severe, potentially fatal syndrome in which there is excessive immune activation. The disease is seen in children and people of all ages, but infants from birth to 18 months are most frequently affected. HLH is a sporadic or familial condition that can be triggered by various events that disturb immunological homeostasis. In cases with a genetic predisposition and sporadic occurrences, infection is a frequent trigger. Because of the rarity of this disease, the diverse clinical presentation, and the lack of specificity in the clinical and laboratory results, prompt treatment is essential, but the biggest obstacle to a favorable outcome is frequently a delay in identification. CASE REPORT: Here we report a case of a 6-month-old male infant who presented to the dermatology outpatient with disseminated skin lesions present over the face, abdomen, scalp, and bilateral upper and lower limbs for the past month. The lesions were insidious in onset, initially started over the abdomen, and gradually progressed to involve other body parts. The patient also had a history of fever which was moderate in grade, on and off in nature for 1 month. There were no significant complaints in the past, family, or drug history. There was no history of feeding difficulties in the baby. Parents gave a history of developmental milestones appropriate for age. Examination findings include multiple well-defined monomorphic erythematous papules with a central crater present over bilateral cheeks. Few lichenoid shiny papules present over bilateral arms, legs, and abdomen. Ultrasound of the abdomen and pelvis showed mild degree hepatosplenomegaly, intraabdominal lymphadenopathy, and bilateral inguinal lymphadenopathy. Routine blood investigations showed anemia and lymphopenia. Multiple X-rays of the skull, chest, and bilateral upper and lower limbs were done and were normal. Histopathology features were suggestive of non-Langerhans cell cutaneous histiocytosis. CONCLUSION: HLH is a fatal and rare disease. A high level of suspicion and an interdisciplinary approach among experienced clinicians, pathologists, and microbiologists to define the diagnosis and causative disease are key to diagnosing this case. Early detection and treatment can reduce patient morbidity and mortality.

Keywords: histiocytosis, non langerhans cell, case report, fatal, rare

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Authors: Temitayo Tosin Alawiye

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Plant disease control is important in maintaining plant vigour, grain quantity, abundance of food, feed, and fibre produced by farmers all over the world. Farmers make use of different methods in controlling these diseases but one of the commonly used method is the use of chemicals. However, the continuous and excessive usages of these agrochemicals pose a danger to the environment, man and wildlife. The more the population growth the more the food security challenge which leads to more pressure on agronomic growth. Agricultural waste also known as green waste are the residues from the growing and processing of raw agricultural products such as fruits, vegetables, rice husk, corn cob, mushroom growth medium waste, coconut husk. They are widely used in land bioremediation, crop production and protection which include disease control. These agricultural wastes help the crop by improving the soil fertility, increase soil organic matter and reduce in many cases incidence and severity of disease. The objective was to review the agricultural waste that has worked effectively against certain soil-borne diseases such as Fusarium oxysporum, Pythiumspp, Rhizoctonia spp so as to help minimize the use of chemicals. Climate change is a major problem of agriculture and vice versa. Climate change and agriculture are interrelated. Change in climatic conditions is already affecting agriculture with effects unevenly distributed across the world. It will increase the risk of food insecurity for some vulnerable groups such as the poor in Sub Saharan Africa. The food security challenge will become more difficult as the world will need to produce more food estimated to feed billions of people in the near future with Africa likely to be the biggest hit. In order to surmount this hurdle, smallholder farmers in Africa must embrace climate-smart agricultural techniques and innovations which includes the use of green waste in agriculture, conservative agriculture, pasture and manure management, mulching, intercropping, etc. Training and retraining of smallholder farmers on the use of green energy to mitigate the effect of climate change should be encouraged. Policy makers, academia, researchers, donors, and farmers should pay more attention to the use of green energy as a way of reducing incidence and severity of soilborne plant diseases to solve looming food security challenges.

Keywords: agricultural waste, climate change, green energy, soil borne plant disease

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Authors: Christine Ysabelle G. Roman, Pauline Torres

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Background: Hypertrophic cardiomyopathy is a disease of marked heterogeneity. It is a genetically determined heart disease characterized by significant myocardium hypertrophy that results in diastolic dysfunction, left ventricular outflow tract obstruction, and an increased risk of arrhythmias. The primary treatment in patients with such conditions is negative inotropic drugs, such as beta-blockers, calcium channel antagonists, and disopyramide. However, for those who remain symptomatic and need septal reduction therapy, surgical septal myectomy or alcohol septal ablation are options. Case Summary: A 19 – year old female presented in the authors’ institution with easy fatigability. The consult was done a year prior, and 2D echocardiography was requested which showed concentric left ventricular hypertrophy, asymmetrically hypertrophied interventricular septum (IVS) with the largest diameter of 3.3cm & subaortic dynamic obstruction with a maximum gradient of 47 mmHg. A repeat echo a year later showed asymmetric septal hypertrophy (IVS measuring at 3cm) with the systolic anterior motion of anterior mitral valve leaflet and left ventricular outflow tract obstruction (peak gradient of 50mmHg). The patient then underwent alcohol septal ablation and was discharged stable after four days of admission. Conclusion: Hypertrophic obstructive cardiomyopathy, a cardiovascular genetic disease, results in various patterns of left ventricular hypertrophy and abnormality of mitral valve apparatus. The patient is managed medically initially. However, despite optimal drug therapy and significant left ventricular outflow tract obstruction, significant heart failure symptoms or syncope require invasive treatment.

Keywords: hypertrophic obstructive cardiomyopathy, left ventricular outflow tract obstruction, alcohol septal ablation, alcohol

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Authors: Sina Mahdavi, Mahdi Asghari Ozma

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Multiple sclerosis (MS) is the most common inflammatory autoimmune disease of the CNS that affects the myelination process in the central nervous system (CNS). Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially human Varicella-zoster virus (VZV) and MS is one potential cause that is not well understood. This study aims to summarize the available data on VZV retrovirus infection in MS disease progression. For this study, the keywords "Multiple sclerosis", " Human Varicella-zoster virus ", and "central nervous system" in the databases PubMed, Google Scholar, Sid, and MagIran between 2016 and 2022 were searched and 14 articles were chosen, studied, and analyzed. Analysis of the amino acid sequences of HNRNPA1 with VZV proteins has shown a 62% amino acid sequence similarity between VZV gE and the PrLD/M9 epitope region (TNPO1 binding domain) of mutant HNRNPA1. A heterogeneous nuclear ribonucleoprotein (hnRNP), which is produced by HNRNPA1, is involved in the processing and transfer of mRNA and pre-mRNA. Mutant HNRNPA1 mimics gE of VZV as an antigen that leads to autoantibody production. Mutant HnRNPA1 translocates to the cytoplasm, after aggregation is presented by MHC class I, followed by CD8 + cells. Of these, antibodies and immune cells against the gE epitopes of VZV remain due to the memory immune response, causing neurodegeneration and the development of MS in genetically predisposed individuals. VZV expression during the course of MS is present in genetically predisposed individuals with HNRNPA1 mutation, suggesting a link between VZV and MS, and that this virus may play a role in the development of MS by inducing an inflammatory state. Therefore, measures to modulate VZV expression may be effective in reducing inflammatory processes in demyelinated areas of MS patients in genetically predisposed individuals.

Keywords: multiple sclerosis, varicella-zoster virus, central nervous system, autoimmunity

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Authors: Ruolan Zhou

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Trisomy of human chromosome 21 is the primary cause of Down Syndrome (DS), and this genetic disease has significantly burdened families and countries, causing great controversy. To address this problem, the research takes an approach in exploring the relationship between genetic abnormality and this disease's symptoms, adopting several techniques, including data analysis and enrichment analysis. It also explores open-source websites, such as NCBI, DAVID, SOURCE, STRING, as well as UCSC, to complement its result. This research has analyzed the variety of genes on human chromosome 21 with simple coding, and by using analysis, it has specified the protein-coding genes, their function, and their location. By using enrichment analysis, this paper has found the abundance of keratin production-related coding-proteins on human chromosome 21. By adopting past researches, this research has attempted to disclose the relationship between trisomy of human chromosome 21 and keratin production abnormality, which might be the reason for common diseases in patients with Down Syndrome. At last, by addressing the advantage and insufficiency of this research, the discussion has provided specific directions for future research.

Keywords: Down Syndrome, protein production, genome, enrichment analysis

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Authors: Rutanachai Thaipratum

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At present, it is widely-known that free radicals are the causes of illness such as cancers, coronary heart disease, Alzheimer’s disease and aging. One method of protection from free radical is the consumption of antioxidant-containing foods or herbs. Several analytical methods have been used for qualitative and quantitative determination of antioxidants. This project aimed to evaluate antioxidant activity of ethanolic and aqueous extracts from cabbage (Brassicca oleracea L. var. capitata L.) measured by DPPH and hydroxyl radical scavenging method. The results show that averaged antioxidant activity measured in ethanolic extract (µmol ascorbic acid equivalent/g fresh mass) were 7.316 ± 0.715 and 4.66 ± 1.029 as determined by DPPH and hydroxyl radical scavenging activity assays, respectively. Averaged antioxidant activity measured in aqueous extract (µmol ascorbic acid equivalent/g fresh mass) were 15.141 ± 2.092 and 4.955 ± 1.975 as determined by DPPH and hydroxyl radical scavenging activity assays respectively.

Keywords: free radical, antioxidant, cabbage, Brassica oleracea L. var. capitata L.

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Authors: Siyuan Cai

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COVID-19 has triggered the planning circles to think about how to improve the city's ability to respond to public health emergencies. From the perspective of the community, this article reviews the risk cases in Wuhan Chenjiadun Community and other communities under the epidemic, and analyzes the response to public health emergencies such as infectious disease outbreaks in the excellent cases of resilient epidemic prevention communities. Then, combined with the planning of the living circle, it demonstrates the necessity of integrating the concept of resilience into the 15-minute community living circle to make up for the shortcomings of infectious disease prevention. Finally, it is proposed to strictly control the source and tail of the epidemic in the layout of the living circle, daily health and epidemic emergency should be taken into account in planning, community medical resources should be decentralized in management, and the application of smart technologies in the planning of living circle should be fully emphasized, so as to improve the community's ability to respond to public health emergencies.

Keywords: pandemic, resilient cities, resilient community, 15-minute community life circle

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Authors: Min Ju Kim, Beom Jin Park, Deuk Jae Sung, Na Yeon Han, Kichoon Sim

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Purpose: The purpose of this study is to determine the significant magnetic resonance (MR) imaging factors of lateral pelvic lymph node (LPLN) on the assessment of survival outcomes of neoadjuvant combined chemotherapy and radiation therapy (CRT) in patients with mid/low rectal cancer. Materials and Methods: The institutional review board approved this retrospective study of 63 patients with mid/low rectal cancer who underwent MR before and after CRT and patient consent was not required. Surgery performed within 4 weeks after CRT. The location of LPLNs was divided into following four groups; 1) common iliac, 2) external iliac, 3) obturator, and 4) internal iliac lymph nodes. The short and long axis diameters, numbers, shape (ovoid vs round), signal intensity (homogenous vs heterogenous), margin (smooth vs irregular), and diffusion-weighted restriction of LPLN were analyzed on pre- and post-CRT images. For treatment response using size, lymph node groups were defined as group 1) short axis diameter ≤ 5mm on both MR, group 2) > 5mm change into ≤ 5mm after CRT, and group 3) persistent size > 5mm before and after CRT. Clinical findings were also evaluated. The disease-free survival and overall survival rate were evaluated and the risk factors for survival outcomes were analyzed using cox regression analysis. Results: Patients in the group 3 (persistent size >5mm) showed significantly lower survival rates than the group 1 and 2 (Disease-free survival rates of 36.1% and 78.8, 88.8%, p < 0.001). The size response (group 1-3), multiplicity of LPLN, the level of carcinoembryonic antigen (CEA), patient’s age, T and N stage, vessel invasion, perineural invasion were significant factors affecting disease-free survival rate or overall survival rate using univariate analysis (p < 0.05). The persistent size (group 3) and multiplicity of LPLN were independent risk factors among MR imaging features influencing disease-free survival rate (HR = 10.087, p < 0.05; HR = 4.808, p < 0.05). Perineural invasion and T stage were shown as independent histologic risk factors (HR = 16.594, p < 0.05; HR = 15.891, p < 0.05). Conclusion: The persistent size greater than 5mm and multiplicity of LPLN on both pre- and post-MR after CRT were significant MR factors affecting survival outcomes in the patients with mid/low rectal cancer.

Keywords: rectal cancer, MRI, lymph node, combined chemoradiotherapy

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Authors: Wissame Gouigah, Amina Medellel, Mahmoud Trachi, Djedjiga Benamara, Salem Benamara

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The purpose of this work is to investigate, by UV/VIS spectrophotometry, the distribution of L-dopa, known as precursor of dopamine which is used in the treatment of Parkinson's disease, in broad beans (Vicia faba) (Vf) and chickpea (Cicer aritinum L.) (CA). In the case of Vf, the different organs were analyzed separately: 1) First, in the fresh state: pod (GF), cotyledons (CF), green shell (EF) and placenta (PF) which is the organ through which the seed is attached to the pod, 2) in the dry state (S): peel of the dry seed (ES) and cotyledons (CS), and 3) in the germinated state: peel (EGe), cotyledons (CGe) and germ (GeVf). Results showed that the content of L-dopa is unevenly distributed between different parts of fresh Vf. But the most important result concerns the predominance of L-dopa in placenta with an L-dopa content (~ 60 mg/g of wet weight, ww) sometimes 7-fold higher (p≤0.05) than those of other considered parts of fresh Vf. In the case of CA, the L-dopa concentration in germinated gains was higher than those found in all analyzed Vf organs, excepted PF.

Keywords: broad bean (Vicia faba L.), chickpea (Cicer aritinum L.), L-dopa, Parkinson disease, placenta

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Authors: Y. Kunitani, Y. Nakashima, S. Yamauchi, Y. Ishigami, K. Naito, K. Numata, M. Mizobe, Y. Homma, J. Takahashi, T. Inoue, T. Shiga, H. Funakoshi

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Background: Japanese Spotted Fever (JSF) is one of the Rickettsial infections, caused by Rickettsia japonica, which is transmitted by ticks. JSF is seen in limited area, such as Japan and South Korea. Its clinical triad is rash, eschar and fever. It often shows leukocytopenia, thrombopenia, elevated transaminase and high C-reactive protein (CRP). Sometimes it can be life-threatening due to disseminated intravascular coagulation or multiple organ failure. Study Aim: The aim of this study is to describe the features of JSF, as this unique infection is rapidly growing in Japan. Methods: This is a case series of JSF from 2009 to 2016, in Mie Prefectural Hospital in Japan. We collected JSF cases, which were diagnosed by polymerase chain reaction (PCR) of the skin or blood serum, or the elevation of the antibody titer of paired blood samples. Results: There were 43 JSF patients (19 male, 24 female) with a median age of 71 years [IQR:65-80]. The median body temperature was 38.1°C[IQR: 37.5-39.0]. 95% had a rash, 67% had eschar and 50% had fever. The median WBC count was 6,700 [IQR: 5,750-8,200] and leukocytopenia was observed in only 7%. The median platelet count was 14x104 [IQR10x104-17x104], thrombopenia was observed in 65%. The median aspartate transaminase (AST) was 53 IU/L [IQR: 41-93]; the median alanine aminotransferase (ALT) was 34 IU/L [IQR: 24-54]; the median CRP was 10.4 mg/dL [IQR:7.2-13.9]; the median lactate dehydrogenase (LDH) was 352IU/L [IQR:282-451]. CRP and LDH were elevated in almost all of the patients. Median length of stay in hospital was 8 days [IQR: 6-11]. All patients were treated with tetracycline and quinolone on the day of the presentation. There was no fatality from JSF. Conclusion: The patients with JSF classically presents with eschar, rash and fever. However, in this study, the half of the patients were afebrile. Although JSF is not a common infectious disease worldwide, if the patient had previously visited Japan or South Korea and presented with rash and eschar with or without fever, we should consider JSF as a potential diagnosis.

Keywords: infectious disease, Japanese spotted fever, Rickettsial disease, Rickettsia japonica

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Authors: Mahsa Hadipour Jahromy, Sara Rezaii

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Parkinson’s disease (PD) results primarily from the death of dopaminergic neurons in the substantia nigra. Soon after the discovery of levodopa and its beneficial effects in chronic administration, debilitating involuntary movements observed, termed levodopa-induced dyskinesia (LID) with poorly understood pathogenesis. Polyphenol-rich compounds, like pomegranate, provided neuroprotection in several animal models of brain diseases. In the present work, we investigated whether pomegranate has preventive effects following 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic degenerations and the potential to diminish LID in mice. Mice model of PD was induced by MPTP (30 mg/kg daily for five consecutive days). To induce a mice model of LID, valid PD mice were treated with levodopa (50 mg/kg, i.p) for 15 days. Then the effects of chronic co-administration of pomegranate juice (20 ml/kg) with levodopa and continuing for 10 days, evaluated. Behavioural tests were performed in all groups, every other day including: Abnormal involuntary movements (AIMS), forelimb adjusting steps, cylinder, and catatonia tests. Finally, brain tissue sections were prepared to study substantia nigra changes and dopamine neuron density after treatments. With this MPTP regimen, significant movement disorders revealed in AIMS tests and there was a reduction in dopamine striatal density. Levodopa attenuates their loss caused by MPTP, however, in chronic administration, dyskinesia observed in forelimb adjusting step and cylinder tests. Besides, catatonia observed in some cases. Chronic pomegranate co-administration significantly improved LID in both tests and reduced dopaminergic loss in substantia nigra. These data indicate that pomegranate might be a good adjunct for preserving dopaminergic neurons in the substantia nigra and reducing LID in mice.

Keywords: levodopa-induced dyskinesia, MPTP, Parkinson’s disease, pomegranate

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Authors: Josine Beek, S. Agten, R. Del Pozo, B. Balis

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The objective of the present study was to compare the safety of intramuscular administration of Zuprevo® (tildipirosin, 40 mg/mL) with Draxxin® (tulathromycin, 100 mg/mL) in the treatment of swine respiratory disease at weaning age. The trial was carried out in two farrow-to-finish farms with 300 sows (farm A) and 500 sows (farm B) in a batch-production system. Farm A had no history of respiratory problems, whereas farm B had a history of respiratory outbreaks with increased mortality ( > 2%) in the nursery. Both farms were positive to Pasteurella multocida, Bordetella bronchiseptica, Actinobacillus pleuropneumoniae and Haemophilus parasuis. From each farm, one batch of piglets was included (farm A: 644 piglets; farm B: 963 piglets). One day before weaning (day 0; 18-21 days of age), piglets were identified by an individual ear tag and randomly assigned to a treatment group. At day 0, Group 1 was treated with a single intramuscular injection with Zuprevo® (tildipirosin, 40 mg/mL; 1 mL/10 kg) and group 2 with Draxxin® (tulathromycin, 100 mg/mL; 1 mL/40 kg). For practical reasons, dosage of the product was adjusted according to three weight categories: < 4 kg, 4-6 kg and > 6 kg. Within each farm, piglets of both groups were comingled at weaning and subsequently managed and located in the same facilities and with identical environmental conditions. Our study involved the period from day 0 until 10 weeks of age. Safety of treatment was evaluated by 1) visual examination for signs of discomfort directly after treatment and after 15 min, 1 h and 24 h and 2) mortality rate within 24 h after treatment. Efficacy of treatment was evaluated based on mortality rate from day 0 until 10 weeks of age. Each piglet that died during the study period was necropsied by the herd veterinarian to determine the probable cause of death. Data were analyzed using binary logistic regression and differences were considered significant if p < 0.05. The pig was the experimental unit. In total, 848 piglets were treated with tildipirosin and 759 piglets with tulathromycin. In farm A, one piglet with retarded growth ( < 1 kg at 18 days of age) showed an adverse reaction after injection of tildipirosin: lateral recumbence and dullness for ± 30 sec. The piglet recovered after 1-2 min. This adverse reaction was probably due to overdosing (12 mg/kg). No adverse effect of treatment was observed in any other piglet. There was no mortality within 24 h after treatment. No significant difference was found in mortality rate between both groups from day 0 until 10 weeks of age. In farm A, overall mortality rate was 0.3% (2/644). In farm B, mortality rate was 0.2% (1/502) in group 1 (tildipirosin) and 0.9% (4/461) in group 2 (tulathromycin)(p=0.60). The necropsy of piglets that died during the study period revealed no macroscopic lesions of the respiratory tract. In conclusion, Zuprevo® (tildipirosin, 40 mg/mL) was shown to be a safe and efficacious alternative to Draxxin® (tulathromycin, 100 mg/mL) for the early treatment of swine respiratory disease at weaning age.

Keywords: antibiotic treatment, safety, swine respiratory disease, tildipirosin

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Authors: Bindu I. Somarajan, Viney Gupta, Gagandeep Kaur Walia, Jasbir Kaur, Sunil Kumar, Shikha Gupta, Abadh K. Chaurasia, Dinesh Gupa, Abhinav Kaushik, Aditi Mehta, Vipin Gupta, Arundhati Sharma

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Background: Juvenile onset primary open angle glaucoma (JOAG), affects individuals under the age of 40 years. Studies on a few families of JOAG, that led to the discovery of the Myocilin gene, reported the disease to have an autosomal dominant pattern of inheritance. However, sporadic forms of JOAG been seen to be more common in some populations. Most pathological homozygous mutations in the CYP1B1 gene associated with JOAG have been seen among sporadic cases. Given the higher prevalence of sporadic JOAG cases in our population, we aimed to look for common mutations E229K and R368H, the two most common variants in the CYP1B1 gene associated with glaucoma. Objective: To determine the frequency and evaluate genotype phenotype correlation of CYP1B1 E229K and R368H mutations in a cohort of 120 sporadic Juvenile open angle glaucoma patients.Methods: Unrelated JOAG patients whose first degree relatives had been examined and found to be unaffected were included in the study. The patients and their parents were screened for E229K and R368H mutations. The phenotypic characteristics were compared between probands with and with out these mutations by SPSS v16. Results: Out of 120 JOAG patients included in the study, the E229K mutation was seen in 9 probands (7.5%) and R368H in 7 (5.8%). The average age of onset of the disease (p=0.3) and the highest untreated IOP (p=0.4) among those carrying mutations was not significantly different from those who did not have these mutations. The proportion of probands with angle dysgenesis among those with E229K and R368H mutations was 70% (11 out of 16) in comparison to 65% (67 out of 104) of those who did not harbour these mutations (p=0.56). Similarly the probands with moderate to high myopia among those with E229K and R368H mutations was 20% (3 out of 16) in comparison to 18% (18 out of 104) of those who did not harbour these mutations(p=0.59). Conclusion: The frequency of E229K and R368H mutations of the CYP1B1 gene is low even among sporadic JOAG patients. Moreover there is no clinical correlation between the presence of these mutations and disease severity

Keywords: CYP1B1, gene, IOP, JOAG, mutation

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Authors: Darnetty Baharuddin Salleh

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Fusarium ear rot disease is one of the most important diseases of maize and not only causes significant losses but also produced harmful mycotoxins to animals and humans. A total of 141 strains of Fusarium species were isolated from maize plants showing typical ear rot symptoms in Indonesia, and Malaysia by using the semi-selective medium (peptone pentachloronitrobenzene agar, PPA). These strains were identified morphologically. For strains in Gibberella fujikuroi species complex (Gfsc), the identification was continued by using biological identification. Three species of Fusarium were morphologically identified as Fusarium in Gibberella species complex (105 strains, 74.5%), F. verticillioides (78 strains), F. proliferatum (24 strains) and F. subglutinans (3 strains) and five species from other section (36 strains, 25.5%), F. graminearum (14 strains), F. oxysporum (8 strains), F. solani ( 1 strain), and F. semitectum (13 strains). Out of 105 Fusarium species in Gfsc, 63 strains were identified as MAT-1, 25 strains as MAT-2 and 17 strains could not be identified and in crosses with nine standard testers, three mating populations of Fusarium were identified as MP-A, G. moniliformis (68 strains, 64.76%), MP-D, G. intermedia (21 strains, 20%) and MP-E, G. subglutinans (3 strains, 2.9%), and 13 strains (12.38%) could not be identified. All trains biologically identified as MP-A, MP-D, and MP-E, were identified morphologically as F. verticillioides, F. proliferatum, and F. subglutinans, respectively. Thus, the results of this study indicated that identification based on biological identification were consistent with those of morphological identification. This is the first report on the presence of MP-A, MP-D, and MP-E on ear rot-infected maize in Indonesia; MP-A and MP-E in Malaysia.

Keywords: Fusarium, MAT-1, MAT-2, MP-A, MP-D, MP-E

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Authors: Stefano A. Denes, Riccardo Tieghi, Giovanni Elia

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The buccal fat pad is a well-established tool in oral and maxillofacial surgery and its use has proved of value for the closure of oroantral communications. Oroantral communication may be a common complication after sequestrectomy in "Bisphosphonate-related osteonecrosis of the jaws". We report a clinical case of a 70-year-old female patient in bisphosphonate therapy presented with right maxillary sinusitis and oroantral communication after implants insertion. The buccal fat pad was used to close the defect. The case had an uneventful postoperative healing without dehiscence, infection and necrosis. We postulate that the primary closure of the site with buccal fat pad may ensure a sufficient blood supply and adequate protection for an effective bone-healing response to occur.

Keywords: buccal fat pad, oroantral communication, oral surgery, dehiscence

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Authors: Mabruka S. Elashheb, Adullah Ali Bakush

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Schizophrenia is referred to as a disorder, not a disease, because there has not been any clear, reliable, and specific etiological factor. Even if schizophrenia is not a very frequent disease, it is among the most burdensome and costly illnesses worldwide. Prevention of relapse is a major goal of maintenance treatment in patients with psychotic disorders. We performed a comparison of a newer, atypical antipsychotic drug, Risperidone, and an older, conventional neuroleptic drug, Haloperidol, in terms of the effect on the usual kidney and liver functions and negative and positive symptoms in patients with schizophrenia and schizoaffective disorder after three and five weeks of their treatments. It is apparent from the comparative data of Haloperidol and Risperidone treatments in schizophrenic patients that Resperidone had superior improvement of negative and positive symptoms of patients, no harmful effect on liver and kidney functions and greater efficacy and faster recovery from schizophrenic symptoms in patients. On the basis of our findings of the present study, we concluded that treatment with Risperidone is superior to Haloperidol in reducing the risk of relapse among outpatients with schizophrenic disorders.

Keywords: schizophrenia, Haloperidol, Risperidone, positive and negative symptom

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Authors: Mohammadjavad Mehrabanpour, Maryam Ranjbar Bushehri, Dorsa Mehrabanpour

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Respiratory diseases are the most important problems in the country’s poultry industry, particularly when it comes to broiler flocks. Ornithobacterium rhinotracheale (ORT) is a species that causes poor performance in growth rate, egg production, and mortality. This pathogen causes a respiratory infection including pulmonary alveolar inflammation, and pneumonia of birds throughout the world. Newcastle disease (ND) is a highly contagious disease in poultry, and also, it causes considerable losses to the poultry industry. The aim of this study was to evaluate the simultaneous occurrence of ORT and ND and NDV isolation by inoculation in embryonated eggs and confirmed by RT-PCR in broiler chicken flocks in Fars province. In this study, 318 blood and 85 tissue samples (brain, trachea, liver, and cecal tonsils) were collected from 15 broiler chicken farms. Survey serum antibody titers against ORT by using a commercial enzyme-linked immunosorbent assay (ELISA) kit performed. Evaluation of antibody titer against ND virus is performed by hemagglutination inhibition test. Virus isolation with chick embryo eggs 9-11 and RT-PCR method were carried out. A total of 318 serum samples, 135 samples (42.5%) were positive for antibodies to ORT and titer of HI antibodies against NDV in 122 serum samples (38/4%) were 7-10 (log2) and 61 serum samples (19/2%) had occurrence antibody titer against Newcastle virus and ORT. Results of the present study indicated that 20 tissue samples were positive in embryonated egg and in rapid hemagglutination (HA) test. HI test with specific ND positive serum confirmed that 6 of 20 samples. PCR confirmed that all six samples were positive and PCR products of samples indicated 535-base pair fragments in electrophrosis. Due to the great economic importance of these two diseases in the poultry industry, it is necessary to design and implement a comprehensive plan for prevention and control of these diseases.

Keywords: ELISA, Ornithobacterium rhinotracheale, newcastle disease, seroprevalence

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Authors: Sandeep Goyal, Sandeep Saluja

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Natural antioxidants have major role in maintenance of health. Green tea extract principally contains epigallocatechin-3-gallate (EGCG), as its abundant antioxidant constituent. Green tea is consumed daily worldwide as antioxidant to combat CNS diseases and has traditional importance also. EGCG has neuroprotective potential in various animal models of Parkinson disease, Alzheimer’s disease etc. but its exact mechanism has not been ruled out. The present study has been designed to investigate the anti-inflammatory, antioxidant and mitochondrial modulating mechanism of neuroprotective effect of epigallocatechin-3-gallate against rodent model of rotenone induced Parkinson’s disease (PD). The behavioural alterations were assessed by using open field test apparatus, Chatilon’s grip strength test apparatus and elevated plus maze for determining the locomotor activity, grip strength and cognition respectively. Biochemically, various parameters to assess oxidative stress, neuroinflammation and neurochemical estimations were performed on rat brain homogenates. A histological examination of rat brain striatum was done to check the neurodegeneration. Epigallocatechin-3-gallate (EGCG) at 10 & 20 mg/kg, were investigated for their neuroprotective potential along with levodopa as a standard agent. Minocycline, a microglial activation inhibitor, was administered alone and in combination with EGCG. EGCG and minocycline produced ameliorative effect against rotenone induced PD like symptoms by significantly reduced behavioral, biochemical and histological alterations. Results of our study reveal the neuroprotective effect of EGCG and minocycline against rotenone induced PD. Results of our study indicate that EGCG exerted neuroprotective effect against rotenone induced PD via its antioxidant, anti-inflammatory and mitochondrial modulating mechanisms and substantiate its previously reported and traditional claims for its use in CNS diseases.

Keywords: antioxidants, neurotoxicity, rotenone, EGCG

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Authors: M. A. Munteanu, A. M. Lungu, A. I. Chivescu, V. Teodorescu, E. Tufanoiu, C. Nicolae, T. I. Nanea

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Introduction: Sodium-glucose co-transporter 2 inhibitors (SGLT2i), which were first developed as antidiabetic medications, have demonstrated numerous positive benefits on the cardiovascular system, especially in the prevention of heart failure (HF). HF is a challenging, multifaceted disease that needs all-encompassing therapy. It should not be viewed as a limited form of heart illness but rather as a systemic disease that leads to multiple organ failure and death. SGLT2i is an extremely effective tool for treating HF by using its pleiotropic effects. In addition to its use in patients with diabetes mellitus who are at high cardiovascular risk or who have already experienced a cardiovascular event, SGLT2i administration has been shown to have positive effects on a variety of HF manifestations and stages, regardless of the patient's presence of diabetes mellitus. Material and Methods: According to the guide, 110 patients (83 males and 27 females) with heart failure with mildly reduced ejection fraction (HFmrEF), with T2D and neoplasia, were enrolled in the prospective study. The structural and functional state of the left ventricle myocardium and ejection fraction was assessed through echocardiography. Patients were randomized to receive once-daily dapagliflozin 10 mg. Results: Patients with HFmrEF were divided into 3 subgroups according to age. 7% (8) patients aged < 45 years, 35% (28) patients aged between 46-59 years, and 58% (74) patients aged> 60 years. The most prevalent comorbidities were hypertension (43.1%), coronary heart disease (40%), and obesity (33.2%). Study drug discontinuation and serious adverse events were not frequent in the subgroups, in either men or women, until now. Conclusions: SGLT-2 inhibitors are a novel class of antidiabetic agents that have demonstrated positive efficacy and safety outcomes in the setting of HFmrEF. Until now, in our study, dapagliflozin was safe and well-tolerated irrespective of sex.

Keywords: diabetes mellitus type 2, Sodium-glucose co-transporters-2 inhibitors, heart failure, neoplasia

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Authors: Kobus-Cisowska Joanna, Flaczyk Ewa, Gramza-Michalowska Anna, Kmiecik Dominik, Przeor Monika, Marcinkowska Agata, Korczak Józef

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Cereal products, including mainly bread is a staple food known from the beginning of history throughout the world. It is now believed that there is no replacement of the basic food. Bread, due to the high content of starch is the energy source for the proper functioning of our body. It also contains proteins, fats, vitamins, especially of the B group and vitamin E, a number of minerals, and fiber. The aim of the study was to evaluate the antioxidant activity of new developed bread premixes with mulberry fruits for people with anemia, diabetes, obesity and cardiovascular disease. From the finished product-bread, aqueous and methanol extracts was prepared, which in next step were analyzed to assess the activity of the radical DPPH test, ABTS, chelating activity, the ability to reduce metals. Extracts were prepared from bread were acquired with premixes directly after production and stored for three months. The resulting trial breads effect by different mechanisms of antioxidant. They showed the ability to scavenge radicals ABTS and DPPH and chelating activity. Methanol extracts showed significantly greater antioxidant activity in comparison with aqueous extracts, and the largest effect was estimated for sample of bread for anemia, diabetes and cardiovascular disease. The greatest ability to scavenging ABTS radicals showed breads for anemia, diabetes and cardiovascular disease, while smaller for anemia and control sample. It was shown that the methanol extracts of the breads samples showed no ability to chelate iron (II). These properties are observed only in the aqueous extracts. The greatest ability attempt had anemia while the lowest control sample. Financial supported by the UE Project no POIG 01.01.02-00-061/09.

Keywords: morus alba, antioxidant activity, free radicals, polyphenols

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Authors: Gamith Mendis

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Even though the doctors are knowledgeable, there's a gap between knowing and being ethical. This is a barrier to establish an ethical doctor-patient relationship. Current health system has oriented in a way that gives a meaning to both the doctor and the patient through intermediate entities. For the doctor, the meaning of the doctor-patient relationship is given through the financial benefits, promotions, and social status. For the patient, the meaning is given through curing of the disease. It is obvious that both are independent entities between the doctor and the patient. As the philosophers like Husserl and Heidegger have pointed out, our subjective world will give the immediate meaningfulness to us. We should seek this immediate meaningfulness of the doctor-patient relationship. The present research has used the existential methodology as guided self-reflections on the lived experiences of a doctor and his students. In this approach, two important aspects have been understood. The first is, establishing the fact that being ethical is itself giving meaningfulness to the doctor’s being without any mediate entities. Simply, it is enjoying being an honest being. The second is by being-with-the-patient while treating the disease; both the doctor and the patient can enjoy the meaningfulness of their human relationship. The medical students and the doctors should focus on this meaningfulness. For that, this discussion should be actively incorporated into the medical curriculum with programs of practical guidance to medical students and should be discussed in patient-care reviews in the health setting within a satisfactory framework.

Keywords: doctor-patient relationship, medical education, medical ethics, medical humanities, qualitative health research

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Authors: Lubomir Vecera, Tomas Gabrhelik, Benjamin Tolmaci, Josef Srovnal, Emil Berta, Petr Prasil, Petr Stourac

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Cancer is the second leading cause of death worldwide and colon cancer is the second most common type of cancer. Currently, there are only a few studies evaluating the effect of postoperative analgesia on the prognosis of patients undergoing radical colon cancer surgery. Postoperative analgesia in patients undergoing colon cancer surgery is usually managed in two ways, either with strong opioids (morphine, piritramide) or epidural analgesia. In our prospective study, we evaluated the effect of postoperative analgesia on the presence of circulating tumor cells or minimal residual disease after colon cancer surgery. A total of 60 patients who underwent radical colon cancer surgery were enrolled in this prospective, randomized, two-center study. Patients were randomized into three groups, namely piritramide, morphine and postoperative epidural analgesia. We evaluated the presence of carcinoembryonic antigen (CEA) and cytokeratin 20 (CK-20) mRNA positive circulating tumor cells in peripheral blood before surgery, immediately after surgery, on postoperative day two and one month after surgery. The presence of circulating tumor cells was assessed by quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR). In the priritramide postoperative analgesia group, the presence of CEA mRNA positive cells was significantly lower on a postoperative day two compared to the other groups (p=0.04). The value of CK-20 mRNA positive cells was the same in all groups on all days. In all groups, both types of circulating tumor cells returned to normal levels one month after surgery. Demographic and baseline clinical characteristics were similar in all groups. Compared with morphine and epidural analgesia, piritramide significantly reduces the amount of CEA mRNA positive circulating tumor cells after radical colon cancer surgery.

Keywords: cancer progression, colon cancer, minimal residual disease, perioperative analgesia.

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Authors: Ravinder Kaur

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Introduction Global cerebrovascular reactivity (CVR) mapping is a promising clinical assessment for stress-testing the brain using physiological challenges, such as CO₂, to elicit changes in perfusion. It enables real-time assessment of cerebrovascular integrity and health. Conventional imaging approaches solely use steady-state parameters, like cerebral blood flow (CBF), to evaluate the integrity of the resting parenchyma and can erroneously show a healthy brain at rest, despite the underlying pathogenesis in the presence of cerebrovascular disease. Conversely, coupling CO₂ inhalation with phase-contrast MRI neuroimaging interrogates the capacity of the vasculature to respond to changes under stress. It shows promise in providing prognostic value as a novel health marker to measure neurovascular function in disease and to detect early brain vasculature dysfunction. Objective This exploratory study was established to:(a) quantify the CBF response to CO₂ in hypocapnia and hypercapnia,(b) evaluate disparities in CVR between internal carotid (ICA) and vertebral artery (VA), and (c) assess sex-specific variation in CVR. Methodology Phase-contrast MRI was employed to measure the cerebrovascular reactivity to CO₂ (±10 mmHg). The respiratory interventions were presented using the prospectively end-tidal targeting RespirActTM Gen3 system. Post-processing and statistical analysis were conducted. Results In 9 young, healthy subjects, the CBF increased from hypocapnia to hypercapnia in all vessels (4.21±0.76 to 7.20±1.83 mL/sec in ICA, 1.36±0.55 to 2.33±1.31 mL/sec in VA, p < 0.05). The CVR was quantitatively higher in ICA than VA (slope of linear regression: 0.23 vs. 0.07 mL/sec/mmHg, p < 0.05). No statistically significant effect was observed in CVR between male and female (0.25 vs 0.20 mL/sec/mmHg in ICA, 0.09 vs 0.11 mL/sec/mmHg in VA, p > 0.05). Conclusions The principal finding in this investigation validated the modulation of CBF by CO₂. Moreover, it has indicated that regional heterogeneity in hemodynamic response exists in the brain. This study provides scope to standardize the quantification of CVR prior to its clinical translation.

Keywords: cerebrovascular disease, neuroimaging, phase contrast MRI, cerebrovascular reactivity, carbon dioxide

Procedia PDF Downloads 148