Search results for: chronic lung disease

Authors: Rezvan Hosseinian

Abstract:

Aim: Systemic sclerosis (SSc) is a chronic connective tissue disease with the clinical hallmark of skin thickening and tethering. The correlation of musculoskeletal features with other parameters should be considered in SSc patients. Methods: We reviewed the records of all patients who had more than one visit and standard anteroposterior radiography of hand. We used univariate analysis, and factors with p<0.05 were included in logistic regression to find out dependent factors. Results: Overall, 180 SSc patients were enrolled in our study, 161 (89.4%) of whom were women. The median age (IQR) was 47.0 years (16), and 52% had a diffuse subtype of the disease. In multivariate analysis, tendon friction rubs (TFRs) were associated with the presence of calcinosis, muscle tenderness, and flexion contracture (FC) on physical examination (p<0.05). Arthritis showed no differences in the two subtypes of the disease (p=0.98), and in multivariate analysis, there were no correlations between radiographic arthritis and serological and clinical features. The radiographic results indicated that disease duration correlated with joint erosion, acro-osteolysis, resorption of the distal ulna, calcinosis and radiologic FC (p< 0.05). Acro-osteolysis was more frequent in the dcSSc subtype, TFRs, and anti-TOPO I antibody. Radiologic FC showed an association with skin score, calcinosis and haematocrit <30% (p<0.05). Joint flexion on radiography was associated with disease duration, modified Rodnan skin score, calcinosis, and low hematocrit (P<0.01). Conclusion: Disease duration was a main dependent factor for developing joint erosion, acro-osteolysis, bone resorption, calcinosis, and flexion contracture on hand radiography. Acro-osteolysis presented in the severe form of the disease. Acro-osteolysis was the only dependent variable associated with bone demineralization.

Keywords: disease subsets, hand radiography, joint erosion, sclerosis

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Authors: Nasrin Azarbani

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Aim: Systemic sclerosis (SSc) is a chronic connective tissue disease with the clinical hallmark of skin thickening and tethering. Correlation of musculoskeletal features with other parameters should be considered in SSc patients. Methods: We reviewed the records of all patients who had more than one visit and standard anteroposterior radiography of hand. We used univariate analysis, and factors with p<0.05 were included in logistic regression to find out dependent factors. Results: Overall, 180 SSc patients were enrolled in our study, 161 (89.4%) of whom were women. Median age (IQR) was 47.0 years (16), and 52% had diffuse subtype of the disease. In multivariate analysis, tendon friction rubs (TFRs) was associated with the presence of calcinosis, muscle tenderness, and flexion contracture (FC) on physical examination (p<0.05). Arthritis showed no differences in the two subtypes of the disease (p=0.98), and in multivariate analysis, there were no correlations between radiographic arthritis and serological and clinical features. The radiographic results indicated that disease duration correlated with joint erosion, acro-osteolysis, resorption of distal ulna, calcinosis and radiologic FC (p< 0.05). Acro-osteolysis was more frequent in the dcSSc subtype, TFRs, and anti-TOPO I antibody. Radiologic FC showed an association with skin score, calcinosis and haematocrit <30% (p<0.05). Joint flexion on radiography was associated with disease duration, modified Rodnan skin score, calcinosis, and low haematocrit (P<0.01). Conclusion: Disease duration was a main dependent factor for developing joint erosion, acro-osteolysis, bone resorption, calcinosis, and flexion contracture on hand radiography. Acro-osteolysis presented in the severe form of the disease. Acro-osteolysis was the only dependent variable associated with bone demineralization.

Keywords: sclerosis, disease subsets, joint erosion, musculoskeletal

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Authors: Fidelis E. Uwumiro, Chimaobi O. Nwevo, Favour O. Osemwota, Victory O. Okpujie, Emeka S. Obi, Omamuyovbi F. Nwoagbe, Ejiroghene Tejere, Joycelyn Adjei-Mensah, Christopher N. Ekeh, Charles T. Ogbodo

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Several risk factors associated with cardiovascular events have been identified as specific to Chronic Kidney Disease (CKD). This study endeavors to validate these CKD-specific risk factors using up-to-date national-level data, thereby highlighting the crucial significance of confirming the validity and generalizability of findings obtained from previous studies conducted on smaller patient populations. The study utilized the nationwide inpatient sample database to identify adult hospitalizations for CKD from 2016 to 2020, employing validated ICD-10-CM/PCS codes. A comprehensive literature review was conducted to identify both traditional and CKD-specific risk factors associated with cardiovascular events. Risk factors and cardiovascular events were defined using a combination of ICD-10-CM/PCS codes and statistical commands. Only risk factors with specific ICD-10 codes and hospitalizations with complete data were included in the study. Cardiovascular events of interest included cardiac arrhythmias, sudden cardiac death, acute heart failure, and acute coronary syndromes. Univariate and multivariate regression models were employed to evaluate the association between chronic kidney disease-specific risk factors and cardiovascular events while adjusting for the impact of traditional CV risk factors such as old age, hypertension, diabetes, hypercholesterolemia, inactivity, and smoking. A total of 690,375 hospitalizations for CKD were included in the analysis. The study population was predominantly male (375,564, 54.4%) and primarily received care at urban teaching hospitals (512,258, 74.2%). The mean age of the study population was 61 years (SD 0.1), and 86.7% (598,555) had a CCI of 3 or more. At least one traditional risk factor for CV events was present in 84.1% of all hospitalizations (580,605), while 65.4% (451,505) included at least one CKD-specific risk factor for CV events. The incidence of CV events in the study was as follows: acute coronary syndromes (41,422; 6%), sudden cardiac death (13,807; 2%), heart failure (404,560; 58.6%), and cardiac arrhythmias (124,267; 18%). 91.7% (113,912) of all cardiac arrhythmias were atrial fibrillations. Significant odds of cardiovascular events on multivariate analyses included: malnutrition (aOR: 1.09; 95% CI: 1.06–1.13; p<0.001), post-dialytic hypotension (aOR: 1.34; 95% CI: 1.26–1.42; p<0.001), thrombophilia (aOR: 1.46; 95% CI: 1.29–1.65; p<0.001), sleep disorder (aOR: 1.17; 95% CI: 1.09–1.25; p<0.001), and post-renal transplant immunosuppressive therapy (aOR: 1.39; 95% CI: 1.26–1.53; p<0.001). The study validated malnutrition, post-dialytic hypotension, thrombophilia, sleep disorders, and post-renal transplant immunosuppressive therapy, highlighting their association with increased risk for cardiovascular events in CKD patients. No significant association was observed between uremic syndrome, hyperhomocysteinemia, hyperuricemia, hypertriglyceridemia, leptin levels, carnitine deficiency, anemia, and the odds of experiencing cardiovascular events.

Keywords: cardiovascular events, cardiovascular risk factors in CKD, chronic kidney disease, nationwide inpatient sample

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Authors: Parisa Mansour

Abstract:

Introduction: Early diagnosis of coronavirus disease (COVID-19) is extremely important to isolate and treat patients in time, thus preventing the spread of the disease, improving prognosis and reducing mortality. High-resolution computed tomography (HRCT) chest imaging and artificial intelligence (AI)-based analysis of HRCT chest images can play a central role in the treatment of patients with COVID-19. Objective: To investigate different chest HRCT findings in different stages of COVID-19 pneumonia and to evaluate the potential role of artificial intelligence in the quantitative assessment of lung parenchymal involvement in COVID-19 pneumonia. Materials and Methods: This retrospective observational study was conducted between May 1, 2020 and August 13, 2020. The study included 2169 patients with COVID-19 who underwent chest HRCT. HRCT images showed the presence and distribution of lesions such as: ground glass opacity (GGO), compaction, and any special patterns such as septal thickening, inverted halo, mark, etc. HRCT findings of the breast at different stages of the disease (early: andlt) 5 days, intermediate: 6-10 days and late stage: >10 days). A CT severity score (CTSS) was calculated based on the extent of lung involvement on HRCT, which was then correlated with clinical disease severity. Use of artificial intelligence; Analysis of CT pneumonia and quot; An algorithm was used to quantify the extent of pulmonary involvement by calculating the percentage of pulmonary opacity (PO) and gross opacity (PHO). Depending on the type of variables, statistically significant tests such as chi-square, analysis of variance (ANOVA) and post hoc tests were applied when appropriate. Results: Radiological findings were observed in HRCT chest in 1438 patients. A typical pattern of COVID-19 pneumonia, i.e., bilateral peripheral GGO with or without consolidation, was observed in 846 patients. About 294 asymptomatic patients were radiologically positive. Chest HRCT in the early stages of the disease mostly showed GGO. The late stage was indicated by such features as retinal enlargement, thickening and the presence of fibrous bands. Approximately 91.3% of cases with a CTSS = 7 were asymptomatic or clinically mild, while 81.2% of cases with a score = 15 were clinically severe. Mean PO and PHO (30.1 ± 28.0 and 8.4 ± 10.4, respectively) were significantly higher in the clinically severe categories. Conclusion: Because COVID-19 pneumonia progresses rapidly, radiologists and physicians should become familiar with typical TC chest findings to treat patients early, ultimately improving prognosis and reducing mortality. Artificial intelligence can be a valuable tool in treating patients with COVID-19.

Keywords: chest, HRCT, covid-19, artificial intelligence, chest HRCT

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Authors: Shu-Lien Chou, Chung-Feng Liu

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Self-health management of chronic illnesses plays an important part in chronic illness treatments. However, various kinds of health information (health education materials) which government or healthcare institutions provide for patients may not achieve the expected outcome. One of the critical reasons affecting patients’ use intention could be patients’ perceived Information overload regarding the health information. This study proposed an extended model of Theory of Planned Behavior, which integrating perceived information overload as another construct to explore patients’ use intention of the health information for self-health management. The independent variables are attitude, subject norm, perceived behavior control and perceived information overload while the dependent variable is behavior intention to use the health information. The cross-sectional study used a structured questionnaire for data collection, focusing on the chronic patients with coronary artery disease (CAD), who are the potential users of the health information, in a medical center in Taiwan. Data were analyzed using descriptive statistics of the basic information distribution of the questionnaire respondents, and the Partial Least Squares (PLS) structural equation model to study the reliability and construct validity for testing our hypotheses. A total of 110 patients were enrolled in this study and 106 valid questionnaires were collected. The PLS analysis result indicates that the patients’ perceived information overload of health information contributes the most critical factor influencing the behavioral intention. Subjective norm and perceived behavioral control of TPB constructs had significant effects on patients’ intentions to use health information also, whereas the attitude construct did not. This study demonstrated a comprehensive framework, which extending perceived information overload into TPB model to predict patients’ behavioral intention of using heath information. We expect that the results of this study will provide useful insights for studying health information from the perspectives of academia, governments, and healthcare providers.

Keywords: chronic patients, health information, information overload, theory of planned behavior

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Authors: Amy Pullen, Samantha Rodrigues, David Kieser, Brian Shaw

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The aim of the study was to determine if a projectile interacting with the lungs increases the severity of injury in comparison to a projectile interacting with the ribs or intercostal muscle. This comparative study employed a 10% gelatine based model with either porcine ribs or balloons embedded to represent a lung. Four sample groups containing five samples were evaluated; these were control (plain gel), intercostal impact, rib impact, and lung impact. Two ammunition natures were evaluated at a range of 10m; these were 5.56x45mm and 7.62x51mm. Aspects of projectile behavior were quantified including exiting projectile weight, location of yawing, projectile fragmentation and distribution, location and area of the temporary cavity, permanent cavity formation, and overall energy deposition. Major findings included the cavity showing a higher percentage of the projectile weight exit the block than the intercostal and ribs, but similar to the control for the 5.56mm ammunition. However, for the 7.62mm ammunition, the lung was shown to have a higher percentage of the projectile weight exit the block than the control, intercostal and ribs. The total weight of projectile fragments as a function of penetration depth revealed large fluctuations and significant intra-group variation for both ammunition natures. Despite the lack of a clear trend, both plots show that the lung leads to greater projectile fragments exiting the model. The lung was shown to have a later center of the temporary cavity than the control, intercostal and ribs for both ammunition types. It was also shown to have a similar temporary cavity volume to the control, intercostal and ribs for the 5.56mm ammunition and a similar temporary cavity to the intercostal for the 7.62mm ammunition The lung was shown to leave a similar projectile tract than the control, intercostal and ribs for both ammunition types. It was also shown to have larger shear planes than the control and the intercostal, but similar to the ribs for the 5.56mm ammunition, whereas it was shown to have smaller shear planes than the control but similar shear planes to the intercostal and ribs for the 7.62mm ammunition. The lung was shown to have less energy deposited than the control, intercostal and ribs for both ammunition types. This comparative study provides insights into the influence of the lungs on thoracic gunshot trauma. It indicates that the lungs limits projectile deformation and causes a later onset of yawing and subsequently limits the energy deposited along the wound tract creating a deeper and smaller cavity. This suggests that lung impact creates an altered pattern of local energy deposition within the target which will affect the severity of trauma.

Keywords: ballistics, lung, trauma, wounding

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Authors: Mona Hamdy, Iman Shaheen, Hadeel Seif Eldin, Basma Ali, Omnia Abdeldayem

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Summary: Bone involvement of sickle cell disease (SCD) patients varies from acute clinical manifestations of painful vaso-occlusive crises or osteomyelitis to more chronic affection of bone mineral density (BMD) and debilitating osteonecrosis and osteoporosis. Secreted klotho protein is involved in calcium (Ca) reabsorption in the kidney. This study aimed to measure serum klotho levels in children with SCD to determine the possibility of using it as a marker of low BMD in children with SCD in correlation with a dual-energy radiograph absorptiometry scan. This study included 60 sickle disease patients and 30 age-matched and sex-matched control participants without SCD. A highly statistically significant difference was found between patients with normal BMD and those with low BMD, with serum Ca and klotho levels being lower in the latter group. Klotho serum level correlated positively with both serum Ca and BMD. Serum klotho level showed 94.9% sensitivity and 95.2% specificity in the detection of low BMD. Both serum Ca and klotho serum levels may be useful markers for detection of low BMD related to SCD with high sensitivity and specificity; however, klotho may be a better indicator as it is less affected by the nutritional and endocrinal status of patients or by intake of Ca supplements.

Keywords: sickle cell disease, BMD, osteoporosis, DEXA, klotho

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Authors: Jun Yang, Ching-Liang Hsieh, Yi-Wen Lin

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Chronic inflammatory pain results from peripheral tissue injury or local inflammation to increase the release of protons, histamines, adenosine triphosphate, and several proinflammatory cytokines. Transient receptor potential vanilloid 1 (TRPV1) is involved in fibromyalgia, neuropathic, and inflammatory pain; however, its exact mechanisms in chronic inflammatory pain are still unclear. We investigate the analgesic effect of EA by injecting complete Freund’s adjuvant (CFA) in the hind paw of mice to induce chronic inflammatory pain ( > 14 d). Our results showed that EA significantly reduced chronic mechanical and thermal hyperalgesia in the chronic inflammatory pain model. Chronic mechanical and thermal hyperalgesia was also abolished in TRPV1−/− mice. TRPV1 increased in the dorsal root ganglion (DRG) and spinal cord (SC) at 2 weeks after CFA injection. The expression levels of downstream molecules such as pPKA, pPI3K, and pPKC increased, as did those of pERK, pp38, and pJNK. Transcription factors (pCREB and pNFκB) and nociceptive ion channels (Nav1.7 and Nav1.8) were involved in this process. Inflammatory mediators such as GFAP (Glial fibrillary acidic protein), S100B, and RAGE (Receptor for advanced glycation endproducts) were also involved. The expression levels of these molecules were reduced in EA (electroacupuncture) and TRPV1−/−mice but not in the sham EA group. The present study demonstrated that EA or TRPV1 gene deletion reduced chronic inflammatory pain through TRPV1 and related molecules. In addition, our data provided evidence to support the clinical use of EA for treating chronic inflammatory pain.

Keywords: auricular electric-stimulation, epileptic seizures, anti-inflammation, electroacupuncture

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Authors: Azar Sharafianpor, Hossein Rassi, Fahimeh Nemati Mansur

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Cardiovascular diseases (CVD) are the most important cause of death in industrialized and developing countries such as Iran. The most important risk factors for the CVD, genetic factors and chronic infectious agents, such as Helicobacter pylori, can be mentioned. The TNFα gene is one of the most important anti-inflammatory cytokines that can affect the sensitivity, efficacy, and ability of the immune response to chronic infections. Some TNF-α gene polymorphisms, including the replacement of the G nucleotide G with A at position 308 in the promoter region of TNF-α, increase the transcription of cytokines in the target cells and thus predispose a person to chronic infections. This study examines the TNF-α 308 polymorphism and its association with Helicobacter pylori infection in this disease. This study was a case-control study in which 154 patients were examined as cases or patients with symptoms of myocardial infarction or angina and 160 as controls or healthy subjects. All of the subjects at different ages were given venous blood and age, BMI, cholesterol, LDL, and HDL were determined. DNA was extracted from the specimens, and the cagA gene from H. pylori and the TNF-α-308 polymorphism were determined by PCR in patients and healthy subjects. Statistical analysis was performed with Epi Info software. The results showed that the frequency of H. pylori infection in the patients and healthy group were 53.23% (82 out of 154) and 47.5% (76 out of 160). There was no significant difference in H. pylori outbreak between the two groups. The frequencies of TNF-α-308 genotype for GG, GA, and AA in patients were 0.17, 0.49, and 0.34, respectively, whereas for controls 0.47, 0.35, and 0.18 for GG, GA, and AA, respectively. The frequency of genotype analysis of TNF-α-308 polymorphisms in both patients and healthy groups showed that there was a significant difference in the frequency of genotypes and the AA genotype was higher in the affected individuals. Also, there was a significant relationship between the genotype and the contamination with H. pylori and changes in cholesterol, LDL, and HDL levels were observed. The results of the study indicate that H. pylori detection in individuals with AA genotype in people under 50 years of age can play an important role in early diagnosis and treatment of cardiovascular disease.

Keywords: Helicobacter pylori, TNFα gene, cardiovascular diseases, TNFα-308 polymorphism

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Authors: Grygorii Kostromin, Vladyslav Povoroznyuk

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Chronic venous diseases (CVD) are one of the common, though controversial problems in medicine. It is generally accepted that this pathology predominantly occurs in women. The issue of excessive weight as a risk factor for CVD is still considered debatable. To the author's best knowledge, today in Ukraine, there are barely any studies that describe the relationship between CVD and obesity. Our study aims to determine the association between age, body composition, obesity and CVD in postmenopausal women. The study was conducted in D. F. Chebotarev Institute of Gerontology, National Academy of Medical Sciences of Ukraine. We have examined 96 postmenopausal women aged 46-85 years (mean age – 66.19 ± 0.96 years), who were divided into two groups depending on the presence of CVD. The women were examined by vascular surgeons. For the diagnosis of CVD, we used clinical, anatomic and pathophysiologic classifications. We also performed clinical, ultrasound and densitometry examinations. We found that the CVD frequency in postmenopausal women increased with age (from 72% in those aged 45-59 years to 84% in those aged 75-89 years). A significant correlation between the total fat mass and age was determined in postmenopausal women with CVD. We also observed a significant correlation between the lower extremities’ fat mass and age in both examined groups. A significant correlation between body mass index and age was determined only in postmenopausal women without CVD.

Keywords: chronic venous disease, risk factors, age, obesity, postmenopausal women

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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: Chang Liu, Hanwen Zhang, Vikash Sharma, Don Eliseo Lucerno-Prisno III, Emmanuel Yujuico, Maulik Chokshi, Prashanthi Krishnakumar, Bach Xuan Tran, Giang Thu Vu, Kamilla Anna Pinter, Shenglan Tang

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Background and Aims: Globally, many health systems focus on hospital-based healthcare models targeting acute care and disease treatment, which are not effective in addressing the challenges of ageing populations, chronic conditions, multi-morbidities, and increasingly unhealthy lifestyles. Recently, integrated care programs on chronic diseases have been developed, piloted, and implemented to meet such challenges. However, integrated care programs in the Asia-Pacific region vary in the levels of integration from linkage to coordination to full integration. This study aims to identify and analyze existing cases of integrated care in the Asia-Pacific region and identify the facilitators and barriers in order to improve existing cases and inform future cases. Methods: The study is a comparative study, with a combination approach of desk-based research and key informant interviews. The selected countries included in this study represent a good mix of lower-middle income countries (the Philippines, India, Vietnam, and Fiji), upper-middle income country (China), and high-income country (Singapore) in the Asia-Pacific region. Existing integrated care programs were identified through the scoping review approach. Trigger, history, general design, beneficiaries, and objectors were summarized with barriers and facilitators of integrated care based on key informant interviews. Representative case(s) in each country were selected and comprehensively analyzed through deep-dive case studies. Results: A total of 87 existing integrated care programs on chronic diseases were found in all countries, with 44 in China, 21 in Singapore, 12 in India, 5 in Vietnam, 4 in the Philippines, and 1 in Fiji. 9 representative cases of integrated care were selected for in-depth description and analysis, with 2 in China, the Philippines, and Vietnam, and 1 in Singapore, India, and Fiji. Population aging and the rising chronic disease burden have been identified as key drivers for almost all the six countries. Among the six countries, Singapore has the longest history of integrated care, followed by Fiji, the Philippines, and China, while India and Vietnam have a shorter history of integrated care. Incentives, technologies, education, and performance evaluation would be crucial for developing strategies for implementing future programs and improve already existing programs. Conclusion: Integrated care is important for addressing challenges surrounding the delivery of long-term care. To date, there is an increasing trend of integrated care programs on chronic diseases in the Asia-Pacific region, and all six countries in our study set integrated care as a direction for their health systems transformation.

Keywords: integrated healthcare, integrated care delivery, chronic diseases, Asia-Pacific region

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Authors: Farideh Halakou, Emel Sen, Attila Gursoy, Ozlem Keskin

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Protein–Protein Interactions (PPIs) mediate major biological processes in living cells. The study of PPIs as networks and analyze the network properties contribute to the identification of genes and proteins associated with diseases. In this study, we have created the sub-networks of brain and lung metastasis from primary tumor in breast cancer. To do so, we used seed genes known to cause metastasis, and produced their interactions through a network-topology based prioritization method named GUILDify. In order to have the experimental support for the sub-networks, we further curated them using STRING database. We proceeded by modeling structures for the interactions lacking complex forms in Protein Data Bank (PDB). The functional enrichment analysis shows that KEGG pathways associated with the immune system and infectious diseases, particularly the chemokine signaling pathway, are important for lung metastasis. On the other hand, pathways related to genetic information processing are more involved in brain metastasis. The structural analyses of the sub-networks vividly demonstrated their difference in terms of using specific interfaces in lung and brain metastasis. Furthermore, the topological analysis identified genes such as RPL5, MMP2, CCR5 and DPP4, which are already known to be associated with lung or brain metastasis. Additionally, we found 6 and 9 putative genes that are specific for lung and brain metastasis, respectively. Our analysis suggests that variations in genes and pathways contributing to these different breast metastasis types may arise due to change in tissue microenvironment. To show the benefits of using structural PPI networks instead of traditional node and edge presentation, we inspect two case studies showing the mutual exclusiveness of interactions and effects of mutations on protein conformation which lead to different signaling.

Keywords: breast cancer, metastasis, PPI networks, protein conformational changes

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Authors: J. B. Clapp, S. Croarkin, C. Dolphin, S. K. Lyons

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Chronic pain or stress in farm animals impacts both on their welfare and productivity. Measuring chronic pain or stress can be problematic using hormonal or behavioural changes because hormones are modulated by homeostatic mechanisms and observed behaviour can be highly subjective. We propose that heart rate variability (HRV) can quantify chronic pain or stress in farmed animal and represents a more robust and objective measure of their welfare.

Keywords: dairy calf, welfare, heart rate variability, non-invasive, biomonitor

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Authors: Getachew Adugna

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Background: Chronic energy malnutrition and human immune deficiency virus among pregnant women are highly prevalent in Sub-Saharan Africa, and they are interrelated in a vicious cycle. However, the prevalence of chronic energy malnutrition and its determinant factors among human immune deficiency virus-positive pregnant women is not well studied in Ethiopia and Addis Ababa in particular. Objective: To determine the prevalence & associated factors of chronic energy malnutrition among human immune deficiency virus-positive pregnant women in health centres of Addis Ababa Ethiopia. Methods: An institution-based cross-sectional study was conducted and a systematic random sampling technique was used to select study subjects. A total of 253 study subjects were enrolled in the study—a structured and pre-tested questionnaire collected sociodemographic, maternal health-related, and nutritional-related variables. MUAC measurements were taken and medical charts were reviewed. Bi-variable and multi-variable logistic regression analyses were used to assess the effect of different factors on chronic energy malnutrition. Result: The overall prevalence of chronic energy malnutrition was 32.0%. It was significantly associated with dietary counselling (AOR: 0.062; 95%CI: 0.007, 0.549), CD4 level (AOR: 0.219; 95%CI: 0.025, 1.908), and clinical stage (AOR: 0.127; 95%CI: 0.053, 0.305). Conclusions: The prevalence of chronic energy malnutrition among Human Immune deficiency virus-infected pregnant women in Addis Ababa was high and Nutritional Intervention should be an integral part of the HIV care program.

Keywords: chronic energy malnutrition, HIV, MUAC, Addis Ababa

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Authors: Janani Selvaraj, M. Prashanthi Devi, P. B. Harathi

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Epidemiologic studies conducted over several decades have provided evidence to suggest that long-term exposure to elevated ambient levels of particulate air pollution is associated with increased mortality. Air quality risk management is significant in developing countries and it highlights the need to understand the role of ecologic covariates in the association between air pollution and mortality. Several new methods show promise in exploring the geographical distribution of disease and the identification of high risk areas using epidemiological maps. However, the addition of the temporal attribute would further give us an in depth idea of the disease burden with respect to forecasting measures. In recent years, new methods developed in the reanalysis were useful for exploring the spatial structure of the data and the impact of spatial autocorrelation on estimates of risk associated with exposure to air pollution. Based on this, our present study aims to explore the spatial and temporal distribution of the lung cancer cases in the Coimbatore district of Tamil Nadu in relation to air pollution risk areas. A spatio temporal moving average method was computed using the CrimeStat software and visualized in ArcGIS 10.1 to document the spatio temporal movement of the disease in the study region. The random walk analysis performed showed the progress of the peak cancer incidences in the intersection regions of the Coimbatore North and South taluks that include major commercial and residential regions like Gandhipuram, Peelamedu, Ganapathy, etc. Our study shows evidence that daily exposure to high air pollutant concentration zones may lead to the risk of lung cancer. The observations from the present study will be useful in delineating high risk zones of environmental exposure that contribute to the increase of cancer among daily commuters. Through our study we suggest that spatially resolved exposure models in relevant time frames will produce higher risks zones rather than solely on statistical theory about the impact of measurement error and the empirical findings.

Keywords: air pollution, cancer, spatio-temporal analysis, India

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Authors: Vassilena Dakova, Mariana Panayotova-Pencheva

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The present work focused on the study of pulmonary helminth-fauna of the stone marten in Bulgaria in terms of which the data are little. For the purpose, four stone martens were helminthologically necropsied according to the common technique. In addition, some of the injured lung parts were investigated after their boiling in lactic acid and subsequent compression. Four nematode species from different families of order Strongylida and Trichocephalida were found in the lungs. These were Crenosoma petrowi Morosov, 1939; Eucoleus aerophilus Creplin, 1839; Filaroides martis Werner, 1782 and Sobolevingylus petrowi Romanov, 1952. Some of the parasite structures with taxonomic importance were measured and described. According to our best knowledge, the species F. martis and S. petrowi are recorded for the first time as a part of the helminth-fauna of Southeast Europe and Bulgaria in particular.

Keywords: Bulgaria, Crenosoma petrowi, Eucoleus aerophilus, Filaroides martis, lung parasites, Sobolevingylus petrowi, stone martens

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Authors: Liudmila Garzanova, Lidia Ananyeva, Olga Koneva, Olga Ovsyannikova, Oxana Desinova, Mayya Starovoytova, Rushana Shayahmetova

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Objectives. Gastrointestinal involvement is one of the most common manifestations of systemic sclerosis (SSc). The aim of our study was to assess the frequency of gastrointestinal manifestations in SSc patients (pts) with interstitial lung disease (ILD) and their changes to rituximab (RTX) therapy. Methods. There were 103 pts with SSc in this study. The mean follow-up period was 12.6±10.7 months. The mean age was 47±12.9 years, females - 87 pts (84%), and the diffuse cutaneous subset of the disease 55 pts (53%). The mean disease duration was 6.2±5.5 years. All pts had ILD and were positive for ANA. 67% of them were positive for anti-topoisomerase-1. All patients received prednisolone at a dose of 11.3±4.5 mg/day, and immunosuppressants at inclusion received 47% of them. Pts received RTX due to the ineffectiveness of previous therapy for ILD. The cumulative mean dose of RTX was 1.7±0.6 grams. 90% of pts received omeprazole at a dose of 20-40 mg/day. Results. At inclusion, dysphagia was observed in 76 pts (74%), early satiety or vomiting in 32 pts (31%), and diarrhea in 20 pts (19%). We didn't observe any changes in gastrointestinal manifestation during RTX therapy. There was a decrease in the number of pts with dysphagia from 76 (74%) to 66 (64%), but it was insignificant. The number of pts with early satiety or vomiting and diarrhea didn't change. Conclusion. In our study, gastrointestinal involvement was observed in most of the pts with SSc-ILD. We didn't find any significant changes in gastrointestinal manifestations during RTX therapy. RXT does not worsen gastrointestinal manifestations in SSc-ILD.

Keywords: systemic sclerosis, dysphagia, rituximab, gastrointestinal manifestations

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Authors: Eunhwa Jun

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This case report describes the misdiagnosis of a patient who presented with right arm pain as cervical disc herniation. The patient had several underlying conditions, including hypertension, diabetes mellitus, liver cirrhosis, a history of lung cancer with left lower lobe lobectomy, and adjuvant chemoradiotherapy. An external cervical spine MRI revealed central protruding discs at the C4-5-6-7 levels. Despite treatment with medication and epidural blocks, the patient's pain persisted. A C-RACZ procedure was planned, but the patient's pain had worsened before admission. Using ultrasound, a brachial plexus block was attempted, but the brachial plexus eluded clear visualization, hinting at underlying neurological complexities. Chest CT revealed a new, large soft tissue mass in the right supraclavicular region with adjacent right axillary lymphadenopathy, leading to the diagnosis of metastatic squamous cell carcinoma. Palliative radiation therapy and chemotherapy were initiated as part of the treatment plan, and the patient's pain score decreased to 3 out of 10 on the Numeric Rating Scale (NRS), revealing the pain was due to metastatic lung cancer.

Keywords: supraclavicula brachial plexus metastasis, cervical disc herniation, brachial plexus block, metastatic lung cancer

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Authors: Milad Gholizadeh

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Asthma and chronic obstructive pulmonary disease (COPD) are very shared inflammatory diseases of the airlines. They togethercause airway tapering and are cumulative in occurrence throughout the world, imposing huge burdens on health care. It is currently recognized that some asthmatic inflammation is neutrophilic, controlled by the TH17 subset of helper T cells, and that some eosinophilic inflammation is controlled by type 2 innate lymphoid cells (ILC2 cells) temporary together with basophils. Patients who have plain asthma or are asthmatic patients who smoke with topographies of COPD-induced inflammation and might advantage from treatments targeting neutrophils, countingmacrolides, CXCR2 antagonists, phosphodiesterase 4 inhibitors, p38 mitogen-activating protein kinase inhibitors, and antibodies in contradiction of IL-1 and IL-17.Viral and bacterial infections, not only reason acute exacerbations of COPD, but also intensify and continue chronic inflammation in steady COPD through pathogen-associated molecular patterns. Present treatment plans are absorbed on titration of inhaled therapies such as long-acting bronchodilators, with cumulative interest in the usage of beleaguered biologic therapies meant at the underlying inflammatory devices. Educationssuggest that the mucosal IgA reply is abridged in COPD, and a lacking conveyance of IgA across the bronchial epithelium in COPD has been recognized, perhaps involving neutrophil proteinases, which may damage the Ig receptor mediating this transepithelialdirection-finding. Future instructions for investigation will emphasis elucidating the diverse inflammatory signatures foremost to asthma and chronic obstrucive, the development of reliable analytic standards and biomarkers of illness, and refining the clinical organization with an eye toward targeted therapies.

Keywords: imminology, asthma, COPD, CXCR2 antagonists

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Authors: Sahana Selladurai, Christine DeWolf

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Lung surfactant comprises a lipid-protein film that coats the alveolar surface and serves to prevent alveolar collapse upon repeated breathing cycles. Exposure of lung surfactant to high concentrations of airborne pollutants, for example tropospheric ozone in smog, can chemically modify the lipid and protein components. These chemical changes can impact the film functionality by decreasing the film’s collapse pressure (minimum surface tension attainable), altering it is mechanical and flow properties and modifying lipid reservoir formation essential for re-spreading of the film during the inhalation process. In this study, we use Langmuir monolayers spread at the air-water interface as model membranes where the compression and expansion of the film mimics the breathing cycle. The impact of ozone exposure on model lung surfactant films is measured using a Langmuir film balance, Brewster angle microscopy and a pendant drop tensiometer as a function of film and sub-phase composition. The oxidized films are analyzed using mass spectrometry where lipid and protein oxidation products are observed. Oxidation is shown to reduce surface activity, alter line tension (and film morphology) and in some cases visibly reduce the viscoelastic properties of the film when compared to controls. These reductions in functionality of the films are highly dependent on film and sub-phase composition, where for example, the effect of oxidation is more pronounced when using a physiologically relevant buffer as opposed to water as the sub-phase. These findings can lead to a better understanding on the impact of continuous exposure to high levels of ozone on the mechanical process of breathing, as well as understanding the roles of certain lung surfactant components in this process.

Keywords: lung surfactant, oxidation, ozone, viscoelasticity

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Authors: Elaine Wong

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This research protocol aims to explore and justify the need for nutrition and physical activity intervention to improve health outcomes among SME (Small Medium Enterprise) employees. It was found that the worksite is an ideal and convenient setting for employees to take charge of their health thru active participation in health programmes since they spent a great deal of time at their workplace. This study will examine the impact of both general or/and targeted health interventions in both SME and non-SME companies utilizing the Workplace Health Promotion (WHP) grant over a 12 months period and assessed the improvement in chronic health disease outcomes in Singapore. Random sampling of both non-SME and SME companies will be conducted to undergo health intervention and statistical packages such as Statistical Package for Social Science (SPSS) 25 will be used to examine the impact of both general and targeted interventions on employees who participate and those who do not participate in the intervention and their effects on blood glucose (BG), blood lipid, blood pressure (BP), body mass index (BMI), and body fat percentage. Using focus groups and interviews, the data results will be transcribed to investigate enablers and barriers to workplace health intervention revealed by employees and WHP coordinators that could explain the variation in the health screening results across the organisations. Dietary habits and physical activity levels of the employees participating and not participating in the intervention will be collected before and after intervention to assess any changes in their lifestyle practices. It makes economic sense to study the impact of these interventions on health screening outcomes across various organizations that are existing grant recipients to justify the sustainability of these programmes by the local government. Healthcare policy makers and employers can then tailor appropriate and relevant programmes to manage these escalating chronic health disease conditions which is integral to the competitiveness and productivity of the nation’s workforce.

Keywords: chronic diseases, health screening, nutrition and fitness intervention , workplace health

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Authors: Ecem Deniz Kırkpantur, Ozge Ecmel Onur, Tuba Cimilli Ozturk, Ebru Unal Akoglu

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Moyamoya disease is a unique chronic progressive cerebrovascular disease characterized by bilateral stenosis or occlusion of the arteries around the circle of Willis with prominent arterial collateral circulation. The occurrence of Moyamoya disease is related to immune, genetic and other factors. There is no curative treatment for Moyamoya disease. Secondary prevention for patients with symptomatic Moyamoya disease is largely centered on surgical revascularization techniques. We present here a 62-year old male presented with headache and vision loss for 2 days. He was previously diagnosed with hypertension and glaucoma. On physical examination, left eye movements were restricted medially, both eyes were hyperemic and their movements were painful. Other neurological and physical examination were normal. His vital signs and laboratory results were within normal limits. Computed tomography (CT) showed dilated vascular structures around both lateral ventricles and atherosclerotic changes inside the walls of internal carotid artery (ICA). Magnetic resonance imaging (MRI) and angiography (MRA) revealed dilated venous vascular structures around lateral ventricles and hyper-intense gliosis in periventricular white matter. Ischemic gliosis around the lateral ventricles were present in the Digital Subtracted Angiography (DSA). After the neurology, ophthalmology and neurosurgery consultation, the patient was diagnosed with Moyamoya disease, pulse steroid therapy was started for vision loss, and super-selective DSA was planned for further investigation. Moyamoya disease is a rare condition, but it can be an important cause of stroke in both children and adults. It generally affects anterior circulation, but posterior cerebral circulation may also be affected, as well. In the differential diagnosis of acute vision loss, occipital stroke related to Moyamoya disease should be considered. Direct and indirect surgical revascularization surgeries may be used to effectively revascularize affected brain areas, and have been shown to reduce risk of stroke.

Keywords: headache, Moyamoya disease, stroke, visual loss

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Authors: Emad A. Shalaby

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Cancer is a disease that causes abnormal cell proliferation and invades nearby tissues. Lung cancer is the second most frequent cancer worldwide. Natural anti-cancer drugs have been developed with low side effects and toxicity. Citrus peels and extracts have been demonstrated to have significant pharmacological and physiological effects as a result of the high concentration of phenolic compounds found in citrus fruits, particularly peels. Tangerine peels can serve as an effective source of bioactive substances such as phenolics, flavonoids, and catechins, which have antioxidant, antibacterial, anticancer, and anti-inflammatory properties. Consequently, this work aims to determine the anticancer activity of ethanol extract of Tangerine peels against the A549 cell line and identify the phenolic compound profile (19 compounds) by using HPLC. Anticancer and antioxidant potentials of the extract were evaluated by MTT assay and TLC- TLC-bioautography sprayed with DPPH reagent, respectively. The obtained results revealed that tangerine peel extract showed significant activity against the A549 cell line with IC50 of 97.66 μg/mL. HPLC analysis proved that the highest concentration is naringenin 464.05 mg/g. More studies indicate that naringenin has significant anticancer potential on A549 cancer cells. The results showed that naringenin binds t0 EGFR protein in A549 with high binding affinity and thus may reduce lung cancer cell migration and enhance the apoptosis of cancer cells. From the obtained results it could be concluded that tangerine peel extract is an effective anti-cancer agent that may potentially serve as a natural therapeutic option for lung cancer treatment.

Keywords: tangerine peel, A549 cell line, anticancer, naringenin, HPLC analysis, naringenin, TLC bioautography

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Authors: Rakan Hassan M. Alzahrani, Ziyad Alzahrani, Bader Bashrahil, Abdulrahman Elyasi, Abdullah a Ghaddaf, Rayan Alzahrani, Mohammed Alkathlan, Nawaf Alghamdi, Dakheelallah Almutairi

Abstract:

Background: Corticosteroid irrigations, which regularly involve the off-label use of budesonide mixed with normal saline in high volume Sino-nasal irrigations, have been more commonly used in the management of post-operative chronic rhinosinusitis (CRS). Objective: This article attempted to measure the efficacy of post-operative budesonide nasal irrigation compared to normal saline-alone nasal irrigation in the management of chronic rhinosinusitis (CRS) through a systematic review and meta-analysis of randomized controlled trials (RCTs). Methods: The databases PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched by two independent authors. Only RCTs comparing budesonide irrigation to normal saline alone irrigation for CRS with or without polyposis after functional endoscopic sinus surgery (FESS) were eligible. A random effect analysis model of the reported CRS-related quality of life (QOL) measures and the objective endoscopic assessment scales of the disease was done. Results: Only 6 RCTs met the eligibility criteria, with a total number of participants of 356. Compared to normal saline irrigation, budesonide nasal irrigation showed statically significant improvements in both the CRS-related quality of life (QOL) and the endoscopic findings (MD= -4.22 confidence interval [CI]: -5.63, -2.82 [P < 0.00001]), (SMD= -0.50 confidence interval [CI]: -0.93, -0.06 [P < 0.03]) respectively. Conclusion: Both intervention arms showed improvements in CRS-related QOL and endoscopic findings in post-FESS chronic rhinosinusitis with or without polyposis. However, budesonide irrigation seems to have a slight edge over conventional normal saline irrigation with no reported serious side effects, including hypothalamic-pituitary-adrenal (HPA) axis suppression.

Keywords: Budesonide, chronic rhinosinusitis, corticosteroids, nasal irrigation, normal saline

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Authors: Jamila Fakchich, Mostafa Jamila Lazaar Elachouri, Lakhder Fakchich, Fatna Ouali, Abd Errazzak Belkacem

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Diabetes is a chronic metabolic disease that has a significant impact on the health, quality of life, and life expectancy of patients as well as the health care system. By its nature diabetes, is a multisystem disease with wide-ranging complication that span nearly all region of the body. This epidemic problem, however, is not unique to the industrialized society, but has also hardly struck the developing countries. In Morocco, as developing country, there is an epidemic rise in diabetes, with ensuing concern about the management and control of this disease; it began a chronic burdensome disease of largely middle-aged and elderly people, with a long course and serious complications often resulting in high death-rate, the treatment of diabetes spent vast amount of resources including medicines, diets, physical training. Treatment of this disease is considered problematic due to the lack of effective and safe drugs capable of inducing sustained clinical, biochemical, and histological cure. In Moroccan society, the phytoremedies are some times the only affordable sources of healthcare, particularly for the people in remote areas. In this paper, we present a synthesis work obtained from the ethnobotanical data reported in different specialized journals. A Synthesis of four published ethnobotanical studies that have been carried out in different region of Morocco by different team seekers during the period from 1997 to 2015. Medicinal plants inventoried by different seekers in four Moroccan’s areas have been regrouped and codified, then, Factorial Analysis (FA) and Principal Components Analysis (PCA) are used to analyse the aggregated data from the four studies and plants are classified according to their frequency of use by population. Our work deals with an attempt to gather information on some traditional uses of medicinal plants from different regions of Morocco, also, it was designed to give a set of medicinal plants commonly used by Moroccan people in the treatment of diabetes; In this paper, we intended to provide a basic knowledge about plant species used by Moroccan society for treatment of diabetes. One of the most interesting aspects of this type of works is to assess the relative cultural importance of medicinal plants for specific illnesses and exploring its usefulness in the context of diabetes.

Keywords: Morocco, medicinal plants, ethnobotanical, diabetes, phytoremedies

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Authors: Kim Rod

Abstract:

People whose chronic pain limits their independence are especially likely to become anxious and depressed. Mindfulness training has shown promise for stress-related disorders. Methods: Chronic pain patients who complained of anxiety and depression and who scored higher than moderate in Hamilton Depression Rating Scale (HDRS) and Hospital Anxiety and Depression Scale (HADS) as well as moderate in Quality of Life Scale (QOLS) were observed for eight weeks, three days a week for an hour of Mindfulness Meditation training with an hour daily home Mindfulness Meditation practice. Pain was evaluated on study entry and completion, and patients were given the Patients’ Global Impression of Change (PGIC) to score at the end of the training program. Results: Forty-seven patients (47) completed the Mindfulness Meditation Training program. Over the year-long observation, patients demonstrated noticeable improvement in depression, anxiety, pain, and global impression of change. Conclusion: Chronic pain patients who suffer with anxiety and depression may benefit from incorporating Mindfulness Meditation into their treatment plans.

Keywords: mindfulness, meditation, depression, anxiety, chronic pain

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Authors: Angelis P. Barlampas

Abstract:

Target: The (SARS-CoV-2) is still a threat. AI software could be useful, categorizing the disease into different severities and indicate the extent of the lesions. Materials and methods: AI is a new revolutionary technique, which uses powered computerized systems, to do what a human being does more rapidly, more easily, as accurate and diagnostically safe as the original medical report and, in certain circumstances, even better, saving time and helping the health system to overcome problems, such as work overload and human fatigue. Results: It will be given an effort to describe to the inexperienced reader (see figures), as simple as possible, how an artificial intelligence system diagnoses computed tomography pictures. First, the computerized machine learns the physiologic motives of lung parenchyma by being feeded with normal structured images of the lung tissue. Having being used to recognizing normal structures, it can then easily indentify the pathologic ones, as their images do not fit to known normal picture motives. It is the same way as when someone spends his free time in reading magazines with quizzes, such as <> and <>. General conclusion: The AI mimics the physiological processes of the human mind, but it does that more efficiently and rapidly and provides results in a few seconds, whereas an experienced radiologist needs many days to do that, or even worse, he is unable to accomplish such a huge task.

Keywords: covid-19, artificial intelligence, automated imaging, CT, chest imaging

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Authors: Medet K. Khamitov, Marat M. Ospanov, Vasiliy M. Lozovoy, Zhenis N. Sakuov, Dastan Z. Rustemov

Abstract:

With a high rectosigmoid transitional zone in children with Hirschsprung’s disease, the upper rectal, sigmoid, left colon arteries are ligated during the pull-through of the descending part of the colon. As a result, the inferior mesenteric artery ceases to participate in the blood supply to the descending part of the colon. As a result, the reduced colon is supplied with blood only by the middle colon artery, which originates from the superior mesenteric artery. Insufficiency of blood supply to the reduced colon is the cause of the development of chronic hypoxia of the intestinal wall or necrosis of the reduced descending colon. Some surgeons prefer to preserve the left colon artery. However, it is possible to stretch the mesentery, which can lead to bowel retraction to anastomotic leaks and stenosis. Chronic hypoxia of the reduced colon, in turn, is the cause of acquired (secondary) aganglionosis. The highest frequency of anastomotic leaks is observed in children older than five years. The purpose is to reduce the risk of complications in the pull-through procedure of the descending part of the colon in patients with Hirschsprung’s disease by ensuring its sufficient mobility and maintaining blood supply to the lower mesenteric artery. Methodology and events. Two children aged 5 and 7 years with Hirschsprung’s disease were operated under the conditions of the hospital in Nur-Sultan. The diagnosis was made using x-ray contrast enema and histological examination. Operational technique. After revision of the left part of the colon and assessment of the architectonics of its blood vessels, parietal mobilization of the affected sigmoid and rectum was performed on laparotomy access, while maintaining the arterial and venous terminal arcades of the sigmoid vessels. Then, the descending branch of the left colon artery was crossed (if there is an insufficient length of the reduced intestine, the left colonic artery itself may also be crossed). This manipulation provides additional mobility of the pull-through descending part of the colon. The resulting "windows" in the mesentery of the reduced intestine were sutured to prevent the development of an internal hernia. Formed a full-blooded, sufficiently long transplant from the transverse loops of the splenic angle and the descending parts of the colon with blood supply from the upper and lower mesenteric artery, freely, without tension, is reduced to the rectal zone with the coloanal anastomosis 1.5 cm above the dentate line. Results. The postoperative period was uneventful. Patients were discharged on the 7th day. The observation was carried out for six months. In no case, there was a bowel retraction, anastomotic leak, anastomotic stenosis, or other complications. Conclusion. The presented technique of mobilization of the colon for the pull-through procedure in a high transitional rectosigmoid zone of Hirschsprung’s disease allows to maintain normal blood supply to the distal part of the colon and to avoid the tension of the colon. The technique allows reducing the risk of anastomotic leak, bowel necrosis, chronic ischemia, to exclude colon retraction and anastomotic stenosis.

Keywords: blood supply, children, colon mobilization, Hirschsprung's disease, pull-through

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Authors: Omar Youssef, Aija Knuuttila, Paivi Piirilä, Virinder Sarhadi, Sakari Knuutila

Abstract:

Exhaled breath condensate (EBC) is a unique sample that allows studying different genetic changes in lung carcinoma through a non-invasive way. With the aid of next generation sequencing (NGS) technology, analysis of genetic mutations has been more efficient with increased sensitivity for detection of genetic variants. In order to investigate the possibility of applying this method for cancer diagnostics, mutations in EBC DNA from lung cancer patients and healthy individuals were studied by using NGS. The key aim is to assess the feasibility of using this approach to detect clinically important mutations in EBC. EBC was collected from 20 healthy individuals and 9 lung cancer patients (four lung adenocarcinomas, four 8 squamous cell carcinoma, and one case of mesothelioma). Mutations in hotpot regions of 22 genes were studied by using Ampliseq Colon and Lung cancer panel and sequenced on Ion PGM. Results demonstrated that all nine patients showed a total of 19 cosmic mutations in APC, BRAF, EGFR, ERBB4, FBXW7, FGFR1, KRAS, MAP2K1, NRAS, PIK3CA, PTEN, RET, SMAD4, and TP53. In controls, 15 individuals showed 35 cosmic mutations in BRAF, CTNNB1, DDR2, EGFR, ERBB2, FBXW7, FGFR3, KRAS, MET, NOTCH1, NRAS, PIK3CA, PTEN, SMAD4, and TP53. Additionally, 45 novel mutations not reported previously were also seen in patients’ samples, and 106 novel mutations were seen in controls’ specimens. KRAS exon 2 mutations G12D was identified in one control specimen with mutant allele fraction of 6.8%, while KRAS G13D mutation seen in one patient sample showed mutant allele fraction of 17%. These findings illustrate that hotspot mutations are present in DNA from EBC of both cancer patients and healthy controls. As some of the cosmic mutations were seen in controls too, no firm conclusion can be drawn on the clinical importance of cosmic mutations in patients. Mutations reported in controls could represent early neoplastic changes or normal homeostatic process of apoptosis occurring in lung tissue to get rid of mutant cells. At the same time, mutations detected in patients might represent a non-invasive easily accessible way for early cancer detection. Follow up of individuals with important cancer mutations is necessary to clarify the significance of these mutations in both healthy individuals and cancer patients.

Keywords: exhaled breath condensate, lung cancer, mutations, next generation sequencing

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