Search results for: endothelial dysfunction

Authors: A. Abdi, A. Abbasi Daloee, A. Barari

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Aim: The adaptations that occur in human body after doing exercises training are a factor to help healthy people stay away from certain diseases. One of the main adaptations is a change in blood circulation, especially in vessels. The increase of capillary density is dependent on the balance between angiogenic and angiostatic factors. Most studies show that the changes made to angiogenic developmental factors resulted from physical exercises indicate the low level of stimulators compared with inhibitors. It is believed that the plasma level of VEGF-A, the important angiogenic factor, is reduced after physical exercise. Findings indicate that the extract of crataegus plant reduces the platelet-derived growth factor receptor (PDGFR) autophosphorylation in human's fibroblast. More importantly, crataegus (1 to 100 mg in liter) clearly leads to the inhibition of PDGFR autophosphorylation in vascular smooth muscle cells (VSMCs). Angiogenesis is a process that can be classified into physiological and pathophysiological forms. collagen XVIII is a part of extracellular protein and heparan sulfate proteoglycans in vascular epithelial and endothelial basement membrane cause the release of endostatin from noncollagenous collagen XVIII. Endostatin inhibits the growth of endothelial cells, inhibits angiogenesis, weakens different types of cancer, and the growth of tumors. The purpose of the current study was to investigate the effect of intensive aerobic running with or without aqueous extraction of black Crataegus elbursensis on Collagen XVIII in male rats. Design: Thirty-two Wistar male rats (4-6 weeks old, 125-135 gr weight) were acquired from the Pasteur's Institute (Amol, Mazandaran), and randomly assigned into control (n = 16) and training (n = 16) groups. Rats were further divided into saline-control (SC) (n=8), saline-training (ST) (n=8), crataegus pentaegyna extraction -control (CPEC) (n=8), and crataegus pentaegyna extraction - training (CPET) (n=8). The control (SC and CPEC) groups remained sedentary; whereas the training groups underwent a high running exercise program. plasma were excised and immediately frozen in liquid nitrogen. Statistical analysis was performed using a one way analysis of variance and Tukey test. Significance was accepted at P = 0.05. Results: The results show that aerobic exercise group had the highest concentration collagen XVIII compared to other groups and then respectively black crataegus, training-crataegus and control groups. Conclusion: In general, researchers in this study concluded that the increase of collagen XVIII (albeit insignificant) as a result of physical activity and consumption of black crataegus extract could possibly serve as a regional inhibitor of angiogenesis and another evidence for the anti-cancer effects of physical activities. Since the research has not managed in this study to measure the amount of plasma endostatin, it is suggested that both indices are measured with important angiogenic factors so that we can have a more accurate interpretation of changes to angiogenic and angiostatic factors resulted from physical exercises.

Keywords: aerobic running, Crataegus elbursensis, Collagen XVIII

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Authors: Daniela Magalhaes, Jorge Pedro, Pedro Souteiro, Joao S. Neves, Sofia Castro-Oliveira, Vanessa Guerreiro, Rita Bettencourt- Silva, Maria M. Costa, Ana Varela, Joana Queiros, Paula Freitas, Davide Carvalho

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Introduction: Obesity is an independent risk factor for renal dysfunction. Our aims were: (1) evaluate the impact of bariatric surgery (BS) on renal function; (2) clarify the factors determining the postoperative evolution of the glomerular filtration rate (GFR); (3) access the occurrence of oxalate-mediated renal complications. Methods: We investigated a cohort of 1448 obese patients who underwent bariatric surgery. Those with basal GFR (GFR0) < 30mL/min or without information about the GFR 2-year post-surgery (GFR2) were excluded. Results: We included 725 patients, of whom 647 (89.2%) women, with 41 (IQR 34-51) years, a median weight of 112.4 (IQR 103.0-125.0) kg and a median BMI of 43.4 (IQR 40.6-46.9) kg/m2. Of these, 459 (63.3%) performed gastric bypass (RYGB), 144 (19.9%) placed an adjustable gastric band (AGB) and 122 (16.8%) underwent vertical gastrectomy (VG). At 2-year post-surgery, excess weight loss (EWL) was 60.1 (IQR 43.7-72.4) %. There was a significant improve of metabolic and inflammatory status, as well as a significant decrease in the proportion of patients with diabetes, arterial hypertension and dyslipidemia (p < 0.0001). At baseline, 38 (5.2%) of subjects had hyperfiltration with a GFR0 ≥ 125mL/min/1.73m2, 492 (67.9%) had a GFR0 90-124 mL/min/1.73m2, 178 (24.6%) had a GFR0 60-89 mL/min/1.73m2, and 17 (2.3%) had a GFR0 < 60 mL/min/1.73m2. GFR decreased in 63.2% of patients with hyperfiltration (ΔGFR=-2.5±7.6), and increased in 96.6% (ΔGFR=22.2±12.0) and 82.4% (ΔGFR=24.3±30.0) of the subjects with GFR0 60-89 and < 60 mL/min/1.73m2, respectively ( p < 0.0001). This trend was maintained when adjustment was made for the type of surgery performed. Of 321 patients, 10 (3.3%) had a urinary albumin excretion (UAE) > 300 mg/dL (A3), 44 (14.6%) had a UAE 30-300 mg/dL (A2) and 247 (82.1%) has a UAE < 30 mg/dL (A1). Albuminuria decreased after surgery and at 2-year follow-up only 1 (0.3%) patient had A3, 17 (5.6%) had A2 and 283 (94%) had A1 (p < 0,0001). In multivariate analysis, the variables independently associated with ΔGFR were BMI (positively) and fasting plasma glucose (negatively). During the 2-year follow-up, only 57 of the 725 patients had transient urinary excretion of calcium oxalate crystals. None has records of oxalate-mediated renal complications at our center. Conclusions: The evolution of GFR after BS seems to depend on the initial renal function, as it decreases in subjects with hyperfiltration, but tends to increase in those with renal dysfunction. Our results suggest that BS is associated with improvement of renal outcomes, without significant increase of renal complications. So, apart the clear benefits in metabolic and inflammatory status, maybe obese adults with nondialysis-dependent CKD should be referred for bariatric surgery evaluation.

Keywords: albuminuria, bariatric surgery, glomerular filtration rate, renal function

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Authors: Elidrissi Laila, El Rhaoussi Fatima-Zahra, Haddad Fouad, Tahiri Mohamed, Hliwa Wafaa, Bellabah Ahmed, Badre Wafaa

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Introduction: Metabolic Dysfunction Associated with Non-Alcoholic Fatty Liver Disease (MASLD), formerly known as Non-Alcoholic Fatty Liver Disease (NAFLD), is the leading cause of chronic liver disease. The cardiometabolic risk factors associated with MASLD represent common health issues and significant public health challenges. Medical students, being active participants in the healthcare system and a young demographic, are particularly relevant for understanding this entity to prevent its occurrence on a personal and collective level. The objective of our study is to assess the level of knowledge among medical students regarding MASLD, its risk factors, and its long-term consequences. Materials and Methods: We conducted a descriptive cross-sectional study using an anonymous questionnaire distributed through social media over a period of 2 weeks. Medical students from various faculties in Morocco answered 22 questions about MASLD, its etiological factors, diagnosis, complications, and principles of treatment. All responses were analyzed using the Jamovi software. Results: A total of 124 students voluntarily provided complete responses. 59% of our participants were in their 3rd year, with a median age of 21 years. Among the respondents, 27% were overweight, obese, or diabetic. 83% correctly answered more than half of the questions, and 77% believed they knew about MASLD. However, 84% of students were unaware that MASLD is the leading cause of chronic liver disease, and 12% even considered it a rare condition. Regarding etiological factors, overweight and obesity were mentioned in 93% of responses, and type 2 diabetes in 84%. 62% of participants believed that type 1 diabetes could not be implicated in MASLD. For 83 students, MASLD was considered a diagnosis of exclusion, while 41 students believed that a biopsy was mandatory for diagnosis. 12% believed that MASLD did not lead to long-term complications, and 44% were unaware that MASLD could progress to hepatocellular carcinoma. Regarding treatment, 85% included weight loss, and 19% did not consider diabetes management as a therapeutic approach for MASLD. At the end of the questionnaire, 89% of the students expressed a desire to learn more about MASLD and were invited to access an informative sheet through a hyperlink. Conclusion: MASLD represents a significant public health concern due to the prevalence of its risk factors, notably the obesity pandemic, which is widespread among the young population. There is a need for awareness about the seriousness of this emerging and long-underestimated condition among young future physicians.

Keywords: MASLD, medical students, obesity, diabetes

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Authors: Aastha Arora, Vikas Bhuria, Saurabh Singh, Uma Pathak, Shweta Mathur, Puja P. Hazari, Rajat Sandhir, Ravi Soni, Anant N. Bhatt, Bilikere S. Dwarakanath

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Radiotherapy is an effective curative and palliative option for patients with thoracic malignancies. However, lung injury, comprising of pneumonitis and fibrosis, remains a significant clin¬ical complication of thoracic radiation, thus making it a dose-limiting factor. Also, injury to the lung is often reported as part of multi-organ failure in victims of accidental radiation exposures. Radiation induced inflammatory response in the lung, characterized by leukocyte infiltration and vascular changes, is an important contributing factor for the injury. Therefore, countermeasure agents to attenuate radiation induced inflammatory response are considered as an important approach to prevent chronic lung damage. Although Amifostine, the widely used, FDA approved radio-protector, has been found to reduce the radiation induced pneumonitis during radiation therapy of non-small cell lung carcinoma, its application during mass and field exposure is limited due to associated toxicity and ineffectiveness with the oral administration. The amifostine analogue (DRDE-30) overcomes this limitation as it is orally effective in reducing the mortality of whole body irradiated mice. The current study was undertaken to investigate the potential of DRDE-30 to ameliorate radiation induced lung damage. DRDE-30 was administered intra-peritoneally, 30 minutes prior to 13.5 Gy thoracic (60Co-gamma) radiation in C57BL/6 mice. Broncheo- alveolar lavage fluid (BALF) and lung tissues were harvested at 12 and 24 weeks post irradiation for studying inflammatory and fibrotic markers. Lactate dehydrogenase (LDH) leakage, leukocyte count and protein content in BALF were used as parameters to evaluate lung vascular permeability. Inflammatory cell signaling (p38 phosphorylation) and anti-oxidant status (MnSOD and Catalase level) was assessed by Western blot, while X-ray CT scan, H & E staining and trichrome staining were done to study the lung architecture and collagen deposition. Irradiation of the lung increased the total protein content, LDH leakage and total leukocyte count in the BALF, reflecting endothelial barrier dysfunction. These disruptive effects were significantly abolished by DRDE-30, which appear to be linked to the DRDE-30 mediated abrogation of activation of the redox-sensitive pro- inflammatory signaling cascade, the MAPK pathway. Concurrent administration of DRDE-30 with radiation inhibited radiation-induced oxidative stress by strengthening the anti-oxidant defense system and abrogated p38 mitogen-activated protein kinase activation, which was associated with reduced vascular leak and macrophage recruitment to the lungs. Histopathological examination (by H & E staining) of the lung showed radiation-induced inflammation of the lungs, characterized by cellular infiltration, interstitial oedema, alveolar wall thickening, perivascular fibrosis and obstruction of alveolar spaces, which were all reduced by pre-administration of DRDE-30. Structural analysis with X-ray CT indicated lung architecture (linked to the degree of opacity) comparable to un-irradiated mice that correlated well with the lung morphology and reduced collagen deposition. Reduction in the radiation-induced inflammation and fibrosis brought about by DRDE-30 resulted in a profound increase in animal survival (72 % in the combination vs 24% with radiation) observed at the end of 24 weeks following irradiation. These findings establish the potential of the Amifostine analogue, DRDE-30, in reducing radiation induced pulmonary injury by attenuating the inflammatory and fibrotic responses.

Keywords: amifostine, fibrosis, inflammation, lung injury radiation

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Authors: Venoos Iman, Suzita Mohd Noor, Syam Mohan, Mohamad Ibrahim Noordin

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Girinimbine, a carbazole alkaloid was isolated from the stem bark and root of Murraya koenigii and its structure and purity was identified by HPLC and LC-MS. Here we report that Girinimbine strongly inhibit angiogenesis activity both in vitro and in vivo. MTT result showed that girinimbine inhibits cell proliferation of the HUVECS cell line in vitro. Result of endothelial cell invasion, migration, tube formation and wound healing assays also demonstrated significant time and does dependent inhibition by girinimbine. Moreover, girinibine mediates its anti-angiogenic activity through up- and down-regulation of angiogenic and anti-aniogenic proteins. Furthermore, anti-angiogenic potential of girinimbine was evidenced in vivo on zebrafish model. Girinimbine inhibited neo-vessels formation in zebrafish embryos during 24 hours exposure time. Together, these results demonstrated for the first time that girinimbine could effectively suppress angiogenesis and strongly suggest that it might be a novel angiogenesis inhibitor.

Keywords: anti-angiogenic, carbazole alkaloid, girinimbine, zebrafish

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Authors: T. N. Goh, M. Hashmi, O. Hussain

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Temporomandibular joint (TMJ) dysfunction (TMD) is a condition that may affect patients via restricted mouth opening, significant pain during normal functioning, and/or reproducible joint noise. TMD includes myofascial pain, TMJ functional derangements (internal derangement, dislocation), and TMJ degenerative/inflammatory joint disease. Internal derangement (ID) is the most common cause of TMD-related clicking and locking. These patients are managed in a stepwise approach, from patient education (homecare advice and analgesia), splint therapy, physiotherapy, botulinum toxin treatment, to arthrocentesis. Arthrotomy is offered when the aforementioned treatment options fail to alleviate symptoms and improve quality of life. The aim of this prospective study was to review the outcomes of jaw joint open surgery in TMD patients. Patients who presented from 2015-2022 at the Oral and Maxillofacial Surgery Department in the Doncaster NHS Foundation Trust, UK, with a Wilkes classification of III -V were included. These patients underwent either i) discopexy with bone-anchoring suture (9); ii) intrapositional temporalis flap (ITF) with bone-anchoring suture (3); iii) eminoplasty and discopexy with suturing to the capsule (3); iii) discectomy + ITF with bone-anchoring suture (1); iv) discoplasty + bone-anchoring suture (1); v) ITF (1). Maximum incisal opening (MIO) was assessed pre-operatively and at each follow-up. Pain score, determined via the visual analogue scale (VAS, with 0 being no pain and 10 being the worst pain), was also recorded. A total of 18 eligible patients were identified with a mean age of 45 (range 22 - 79), of which 16 were female. The patients were scored by Wilkes Classification as III (14), IV (1), or V (4). Twelve patients had anterior disc displacement without reduction (66%) and six had degenerative/arthritic changes (33%) to the TMJ. The open joint procedure resulted in an increase in MIO and reduction in pain VAS and for the majority of patients, across all Wilkes Classifications. Pre-procedural MIO was 22.9 ± 7.4 mm and VAS was 7.8 ± 1.5. At three months post-procedure there was an increase in MIO to 34.4 ± 10.4 mm (p < 0.01) and a decrease in the VAS to 1.5 ± 2.9 (p < 0.01). Three patients were lost to follow-up prior to six months. Six were discharged at six month review and five patients were discharged at 12 months review as they were asymptomatic with good mouth opening. Four patients are still attending for annual botulinum toxin treatment. Two patients (Wilkes III and V) subsequently underwent TMJ replacement (11%). One of these patients (Wilkes III) had improvement initially to MIO of 40 mm, but subsequently relapsed to less than 20 mm due to lack of compliance with jaw rehabilitation device post-operatively. Clinical improvements in 89% of patients within the study group were found, with a return to near normal MIO range and reduced pain score. Intraoperatively, the operator found bone-anchoring suture used for discopexy/discoplasty more secure than the soft tissue anchoring suturing technique.

Keywords: bone anchoring suture, open temporomandibular joint surgery, temporomandibular joint, temporomandibular joint dysfunction

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Authors: M. Hakami, A. Jammaly, I. Attafi, M. Oraiby, M. Jeraiby

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We reviewed an unusual case of a 65-year-old male taking an herbal mixture containing compounds with anticholinesterase activity for a long period of time, presented with acute my myocardial infarction and multiple organ dysfunction syndrome followed by death. Clinically, there are findings correlated with anticholinesterase activity, such as bilateral miosis, diaphoresis, vomiting and fasciculation without a history of any toxic ingestion or exposure. Gas chromatography–mass spectrometry screening studies identified the presence of thymol, anethole in the herbal extract and butylated hydroxytoluene in the blood sample. Hence, with this case report, we intend to highlight the necessity of evaluating the long-term use of the herbal mixture.

Keywords: cholinesterase inhibitors, thymole, anethole, butylatedhydroxytoluene, cardiac toxicity, myocardial infarction

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Authors: Revathi S. Rajan, Pratibha Malik, Nupur Garg, Smitha Avula, Kamini A. Rao

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This study aimed to analyse the pregnancy outcomes in patients with TPO positivity after appropriate L-Thyroxin supplementation with close surveillance. All pregnant women attending the antenatal clinic at Milann-The Fertility Center, Bangalore, India- from Aug 2013 to Oct 2014 whose booking TSH was more than 2.5 mIU/L were included along with those pregnant women with prior hypothyroidism who were TPO positive. Those with TPO positive status were vigorously managed with appropriate thyroxin supplementation and the doses were readjusted every 3 to 4 weeks until delivery. Women with recurrent pregnancy loss were also tested for TPO positivity and if tested positive, were monitored serially with TSH and fT4 levels every 3 to 4 weeks and appropriately supplemented with thyroxin when the levels fluctuated. The testing was done after an informed consent in all these women. The statistical software namely SAS 9.2, SPSS 15.0, Stata 10.1, MedCalc 9.0.1, Systat 12.0 and R environment ver.2.11.1 were used for the analysis of the data. 460 pregnant women were screened for thyroid dysfunction at booking of which 52% were hypothyroid. Majority of them (31.08%) were subclinically hypothyroid and the remaining were overt. 25% of the total no. of patients screened were TPO positive. The various pregnancy complications that were observed in the TPO positive women were gestational glucose intolerance [60%], threatened abortion [21%], midtrimester abortion [4.3%], premature rupture of membranes [4.3%], cervical funneling [4.3%] and fetal growth restriction [3.5%]. 95.6% of the patients who followed up till the end delivered beyond 30 weeks. 42.6% of these patients had previous history of recurrent abortions or adverse obstetric outcome and 21.7% of the delivered babies required NICU admission. Obstetric outcomes in our study in terms of midtrimester abortions, placental abruption, and preterm delivery improved for the better after close monitoring of the thyroid hormone [TSH and fT4] levels every 3 to 4 weeks with appropriate dose adjustment throughout pregnancy. Euthyroid women with TPO positive status enrolled in the study incidentally were those with recurrent abortions/infertility and required thyroxin supplements due to elevated Thyroid hormone (TSH, fT4) levels during the course of their pregnancy. Significant associations were found with age>30 years and Hyperhomocysteinemia [p=0.017], recurrent pregnancy loss or previous adverse obstetric outcomes [p=0.067] and APLA [p=0.029]. TPO antibody levels >600 I U/ml were significantly associated with development of gestational hypertension [p=0.041] and fetal growth restriction [p=0.082]. Euthyroid women with TPO positivity were also screened periodically to counter fluctuations of the thyroid hormone levels with appropriate thyroxin supplementation. Thus, early identification along with aggressive management of thyroid dysfunction and stratification of these patients based on their TPO status with appropriate thyroxin supplementation beginning in the first trimester will aid risk modulation and also help avert complications.

Keywords: TPO antibody, subclinical hypothyroidism, anti nuclear antibody, thyroxin

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Authors: Roman Major, Klaudia Trembecka- Wojciga, Juergen Markus Lackner, Boguslaw Major

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The future and the development of science is therefore seen in interdisciplinary areas such as bio medical engineering. Self-assembled structures, similar to stem cell niches would inhibit fast division process and subsequently capture the stem cells from the blood flow. By means of surface topography and the stiffness as well as micro structure progenitor cells should be differentiated towards the formation of endothelial cells monolayer which effectively will inhibit activation of the coagulation cascade. The idea of the material surface development met the interest of the clinical institutions, which support the development of science in this area and are waiting for scientific solutions that could contribute to the development of heart assist systems. This would improve the efficiency of the treatment of patients with myocardial failure, supported with artificial heart assist systems. Innovative materials would enable the redesign, in the post project activity, construction of ventricular heart assist.

Keywords: bio-inspired materials, electron microscopy, haemocompatibility, niche-like structures, thin coatings

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Authors: Yung-Chih Kuo, I-Hsuan Lee

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Solid lipid nanoparticles (SLNs) conjugated with aprotinin (Apr) and melanotransferrin antibody (Anti-MTf) were used to carry doxorubicin (Dox) across the blood–brain barrier (BBB) for glioblastoma multiforme (GBM) chemotherapy. Dox-entrapped SLNs with grafted Apr and Anti-MTf (Apr-Anti-MTf-Dox-SLNs) were applied to a cultured monolayer comprising human brain-microvascular endothelial cells (HBMECs) with regulation of human astrocyte (HAs) and to a proliferated colony of U87MG cells. Based on the average particle diameter, zeta potential, entrapping efficiency of Dox, and grafting efficiency of Apr and Anti-MTf, we found that 40% (w/w) 1,2-dipalmitoyl-sn-glycero-3-phosphocholine in lipids were appropriate for fabricating Apr-Anti-MTf-Dox-SLNs. In addition, Apr-Anti-MTf-Dox-SLNs could prevent Dox from fast dissolution and did not induce a serious cytotoxicity to HBMECs and HAs when compared with free Dox. Moreover, the treatments with Apr-Anti-MTf-Dox-SLNs enhanced the ability of Dox to infuse the BBB and to inhibit the growth of GBM. The current Apr-Anti-MTf-Dox-SLNs can be a promising pharmacotherapeutic preparation to penetrate the BBB for malignant brain tumor treatment.

Keywords: solid lipid nanoparticle, glioblastoma multiforme, blood–brain barrier, doxorubicin

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Authors: Kim Kennedy, Daren Gibson, Stephanie Flukes, Chandra Diwakarla, Lisa Spalding, Leanne Pilkington, Andrew Redfern

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Introduction: Head and neck cancer and treatments are known for their profound effect on nutrition and tube feeding is a common requirement to maintain nutrition. Aim: We aimed to evaluate the frequency of tube feeding in Aboriginal and non-Aboriginal patients, and to examine the relapse and survival outcomes in patients who require enteral tube feeding. Methods: We performed a retrospective cohort analysis of 320 head and neck cancer patients from a single centre in Western Australia, identifying 80 Aboriginal patients and 240 non-Aboriginal patients matched on a 1:3 ratio by site, histology, rurality, and age. Data collected included patient demographics, tumour features, treatment details, and cancer and survival outcomes. Results: Aboriginal and non-Aboriginal patients required feeding tubes at similar rates (42.5% vs 46.2% respectively), however Aboriginal patients were far more likely to fail to return to oral nutrition, with 26.3% requiring long-term tube feeding versus only 15% of non-Aboriginal patients. In the overall study population, 27.5% required short-term tube feeding, 17.8% required long-term enteral tube nutrition, and 45.3% of patients did not have a feeding tube at any point. Relapse was more common in patients who required tube feeding, with relapses in 42.1% of the patients requiring long-term tube feeding, 31.8% in those requiring a short-term tube, versus 18.9% in the ‘no tube’ group. Survival outcomes for patients who required a long-term tube were also significantly poorer when compared to patients who only required a short-term tube, or not at all. Long-term tube-requiring patients were half as likely to survive (29.8%) compared to patients requiring a short-term tube (62.5%) or no tube at all (63.5%). Patients requiring a long-term tube were twice as likely to die with active disease (59.6%) as patients with no tube (28%), or a short term tube (33%). This may suggest an increased relapse risk in patients who require long-term feeding, due to consequences of malnutrition on cancer and treatment outcomes, although may simply reflect that patients with recurrent disease were more likely to have longer-term swallowing dysfunction due to recurrent disease and salvage treatments. Interestingly long-term tube patients were also more likely to die with no active disease (10.5%) (compared with short-term tube requiring patients (4.6%), or patients with no tube (8%)), which is likely reflective of the increased mortality associated with long-term aspiration and malnutrition issues. Conclusions: Requirement for tube feeding was associated with a higher rate of cancer relapse, and in particular, long-term tube feeding was associated with a higher likelihood of dying from head and neck cancer, but also a higher risk of dying from other causes without cancer relapse. This data reflects the complex effect of head and neck cancer and its treatments on swallowing and nutrition, and ultimately, the effects of malnutrition, swallowing dysfunction, and aspiration on overall cancer and survival outcomes. Tube feeding was seen at similar rates in Aboriginal and non-Aboriginal patient, however failure to return to oral intake with a requirement for a long-term feeding tube was seen far more commonly in the Aboriginal population.

Keywords: head and neck cancer, enteral tube feeding, malnutrition, survival, relapse, aboriginal patients

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Authors: Dost Muhammad Halepoto, Laila AL-Ayadhi

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Neurodevelopmental disorders such as autism can cause lifelong disability. Genetic and environmental factors are believed to contribute to the development of autism spectrum disorder (ASD), but relatively few studies have considered potential environmental risks. Several industrial chemicals and other environmental exposures are recognized causes of neurodevelopmental disorders and subclinical brain dysfunction. The toxic effects of such chemicals in the developing human brain are not known. This review highlights the role of environmental risk factors including drugs, toxic chemicals, heavy metals, pesticides, vaccines, and other suspected neurotoxicants including persistent organic pollutants for ASD. It also provides information about the environmental toxins to yield new insights into factors that affect autism risk as well as an opportunity to investigate the relation between autism and environmental exposure.

Keywords: Autism Spectrum Disorder, ASD, environmental factors, neurodevelopmental disorder

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Authors: Nasiruddin Khan

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The action of (-)-epicatechin, a cocoa (Theobroma cacao) flavanol that modulates redox/oxidative stress are contributed mainly to their antioxidant properties. The present study investigates the concentration and time dependent effect of (-)-epicatechin metabolites 3MeEc, 4MeEc, and 4SulEc on the production of ROS on BAEC using L-012, Lucigenin as chemiluminescence dye and XO/HX system. Our result demonstrates that 3MeEc shows significant (P <0.05) lowering effect of ROS production in BAEC with increasing concentration of metabolite while L-012 was used as chemiluminescence dye but not in the case of Lucigenin. In XO/HX system, using L-012 as chemiluminescence dye, 3MeEc and 4MeEc showed significant lowering effect on ROS production with increasing concentration from 100-500nM as compared to the positive control (SOD). When Lucigenin was used as chemiluminescence dye, 3MeEc exerted significant lowering effect with increasing concentration when compared to the positive control (SOD) whereas 4MeEc showed significant lowering effect in ROS production from 250 nM on as compared to positive control. For 4SulEc, a significant lowering effect of ROS production was only observed at 100 and 250 nM. Overall, although each metabolite shows considerable effect, 3MeEc exhibited more pronounced effect on decreasing the production of ROS as compared to other two metabolites.

Keywords: epicatechin metabolites, HO-1, Nrf2, ROS

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Authors: Fakhrosadat Sajjadian, Ramin Ghasemi Shayan

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The tumor microenvironment plays an fundamental part in tumor start, movement, metastasis, and treatment resistance. It varies from ordinary tissue in terms of its extracellular network, vascular and lymphatic arrange, as well as physiological conditions. The clinical application of atomic cancer imaging is regularly prevented by the tall commercialization costs of focused on imaging operators as well as the constrained clinical applications and little showcase measure of a few operators. . Since numerous cancer types share comparable characteristics of the tumor microenvironment, the capacity to target these biomarkers has the potential to supply clinically translatable atomic imaging advances for numerous types encompassing cancer and broad clinical applications. Noteworthy advance has been made in focusing on the tumor microenvironment for atomic cancer imaging. In this survey, we summarize the standards and methodologies of later progresses in atomic imaging of the tumor microenvironment, utilizing distinctive imaging modalities for early discovery and conclusion of cancer. To conclude, The tumor microenvironment (TME) encompassing tumor cells could be a profoundly energetic and heterogeneous composition of safe cells, fibroblasts, forerunner cells, endothelial cells, flagging atoms and extracellular network (ECM) components.

Keywords: molecular, imaging, TME, medicine

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Authors: Anna Mirczak

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Introduction: In connection with the aging of the population and the increase in the number of people with chronic illnesses, the priority objective for public health has become not only lengthening life, but also improving quality of life in older persons, as well as maintenance of their relative independence and active participation in social life. The most important determinant of a person’s quality of life is health. According to the literature, older people with chronic illness who live in rural settings are at greater risk for poor outcomes than their urban counterparts. Furthermore research characterizes the rural elderly as having a higher incidence of sickness, dysfunction, disability, restricted mobility, and acute and chronic conditions than their urban citizens. It is dictated by the overlapping certain specific socio-economic factors typical for rural areas which include: social and geography exclusion, limited access to health care centers, and low socioeconomic status. Aim of the study: The objective of this study was to recognize health status and needs of older people living in selected rural areas in Poland and evaluate the impacts of working in the farm on their health status. Material and methods: The study was performed personally, using interviews based on the structural questionnaires, during the period from March 2011 to October 2012. The group of respondents consisted 203 people aged 65 years and over living in selected rural areas in Poland. The analysis of collected research material was performed using the statistical package SPSS 19 for Windows. The level of significance for the tested the hypotheses assumed value of 0.05. Results: The mean age of participants was 75,5 years (SD=5,7) range from 65 to 94 years. Most of the interviewees had children (89.2%) and grandchildren (83.7) and lived mainly with family members (75.9%) mostly in double (46.8%) and triple (20.8%) household. The majority of respondents (71,9%) were physical working on the farm. At the time of interview, each of the respondents reported that they had been diagnosed with at least one chronic diseases by their GP. The most common were: hypertension (67,5%), osteoarthritis (44,8%), atherosclerosis (43,3%), cataract (40,4%), arrhythmia (28,6%), diabetes mellitus (19,7%) and stomach or duodenum ulcer diseases (17,2%).The number of diseases occurring of the sample was dependent on gender and age. Significant associations were observed between working on the farm and frequency of occurrence cardiovascular diseases, the gastrointestinal tract dysfunction and sensory disorders. Conclusions: The most common causes of disability among older citizens were: chronic diseases, malnutrition and complaints about access to health services (especially to cardiologist and an ophthalmologist). Health care access and health status are a particular concern in rural areas where the population is older, has lower education and income levels, and is more likely to be living in medically underserved areas than is the case in urban areas.

Keywords: ageing, health status, older people, rural

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Authors: Giovana Vesentini, Fernanda Piculo, Gabriela Marini, Debora Damasceno, Angelica Barbosa, Selma Martheus, Marilza Rudge

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Problem statement: Skeletal muscle is highly adaptable, muscle fiber composition and size can respond to a variety of stimuli, such physiologic, as pregnancy, and metabolic abnormalities, as Diabetes mellitus. This study aimed to analyze the effects of pregnancy-associated diabetes on the rectus abdominis muscle (RA), and to compare this changes in rats and women. Methods: Female Wistar rats were maintained under controlled conditions and distributed in Pregnant (P) and Long-term mild pregnant diabetic (LTMd) (n=3 r/group). Diabetes in rats was induced by streptozotocin (100mg/Kg, sc) on the first day of life, for a hyperglycemic state between 120-300 mg/dL in adult life. Female rats were mated overnight, at day 21 of pregnancy were anesthetized, and killed for the harvesting of maternal RA. Pregnant women who attended the Diabetes Prenatal Care Clinic of Botucatu Medical School were distributed in Pregnant non-diabetic (Pnd) and Gestational Diabetic (GDM) (n=3 w/group). The diagnosis of GDM was established according to ADA’s criteria (2016). The harvesting of RA was during the cesarean section. Transversal cross-sections of the RA of both women and rats were analyzed by transmission electron microscopy. All procedures were approved by the Ethics Committee on Animal Experiments of the Botucatu Medical School (Protocol Number 1003/2013) and by the Botucatu Medical School Ethical Committee for Human Research in Medical Sciences (CAAE: 41570815.0.0000.5411). Results: The photomicrographs of the RA of rats revealed disorganized Z lines, thinning sarcomeres, and a usual quantity of intermyofibrillar mitochondria in the P group. The LTMd group showed swollen sarcoplasmic reticulum, dilated T tubes and areas with sarcomere disruption. The ultrastructural analysis of Pnd non-diabetic women in the RA showed well-organized myofibrils forming intact sarcomeres, organized Z lines and a normal distribution of intermyofibrillar mitochondria. The GDM group revealed increase in intermyofibrillar mitochondria, areas with sarcomere disruption and increased lipid droplets. Conclusion: Pregnancy and diabetes induce adaptations in the ultrastructure of the rectus abdominis muscle for both women and rats, changing the architectural design of these tissues. However, in rats these changes are more severe maybe because, besides the high blood glucose levels, the quadrupedal animal may suffer an excessive mechanical tension during pregnancy by gravity. Probably, these findings may suggest that these alterations are a risk factor that contributes to the development of muscle dysfunction in women with GDM and may motivate treatment strategies in these patients.

Keywords: gestational diabetes, muscle dysfunction, pregnancy, rectus abdominis

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Authors: Rajeswari Raguraman, Sowmya Parameswaran, Krishnakumar Subramanian, Jagat Kanwar, Rupinder Kanwar

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Background: Tumor microenvironment has been implicated in several cancers to regulate cell growth, invasion and metastasis culminating in outcome of therapy. Tumor stroma consists of multiple cell types that are in constant cross-talk with the tumor cells to favour a pro-tumorigenic environment. Not much is known about the existence of tumor microenvironment in the pediatric intraocular malignancy, Retinoblastoma (RB). In the present study, we aim to understand the multiple stromal cellular subtypes and tumor stromal interactions expressed in RB tumors. Materials and Methods: Immunohistochemistry for stromal cell markers CD31, CD68, alpha-smooth muscle (α-SMA), vimentin and glial fibrillary acidic protein (GFAP) was performed on formalin fixed paraffin embedded tissues sections of RB (n=12). The differential expression of stromal target molecules; fibroblast activation protein (FAP), tenascin-C (TNC), osteopontin (SPP1), bone marrow stromal antigen 2 (BST2), stromal derived factor 2 and 4 (SDF2 and SDF4) in primary RB tumors (n=20) and normal retina (n=5) was studied by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blotting. The differential expression was correlated with the histopathological features of RB. The interaction between RB cell lines (Weri-Rb-1, NCC-RbC-51) and Bone marrow stromal cells (BMSC) was also studied using direct co-culture and indirect co-culture methods. The functional effect of the co-culture methods on the RB cells was evaluated by invasion and proliferation assays. Global gene expression was studied by using Affymetrix 3’ IVT microarray. Pathway prediction was performed using KEGG and the key molecules were validated using qRT-PCR. Results: The immunohistochemistry revealed the presence of several stromal cell types such as endothelial cells (CD31+;Vim+/-); macrophages (CD68+;Vim+/-); Fibroblasts (Vim+; CD31-;CD68- );myofibroblasts (α-SMA+/ Vim+) and invading retinal astrocytes/ differentiated retinal glia (GFAP+; Vim+). A characteristic distribution of these stromal cell types was observed in the tumor microenvironment, with endothelial cells predominantly seen in blood vessels and macrophages near actively proliferating tumor or necrotic areas. Retinal astrocytes and glia were predominant near the optic nerve regions in invasive tumors with sparse distribution in tumor foci. Fibroblasts were widely distributed with rare evidence of myofibroblasts in the tumor. Both gene and protein expression revealed statistically significant (P<0.05) up-regulation of FAP, TNC and BST2 in primary RB tumors compared to the normal retina. Co-culture of BMSC with RB cells promoted invasion and proliferation of RB cells in direct and indirect contact methods respectively. Direct co-culture of RB cell lines with BMSC resulted in gene expression changes in ECM-receptor interaction, focal adhesion, IL-8 and TGF-β signaling pathways associated with cancer. In contrast, various metabolic pathways such a glucose, fructose and amino acid metabolism were significantly altered under the indirect co-culture condition. Conclusion: The study suggests that the close interaction between RB cells and the stroma might be involved in RB tumor invasion and progression which is likely to be mediated by ECM-receptor interactions and secretory factors. Targeting the tumor stroma would be an attractive option for redesigning treatment strategies for RB.

Keywords: gene expression profiles, retinoblastoma, stromal cells, tumor microenvironment

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Authors: Ruslin, R. E. Kartasasmita, M. S. Wibowo, S. Ibrahim

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An aphrodisiac is a substance contained in food or drug that can arouse sexual instinct and increase pleasure while working, these substances derived from plants, animals, and minerals. When consuming substances that have aphrodisiac activity and duration can improve the sexual instinct. The natural aphrodisiac effect can be obtained through plants, animals, and minerals. Leonurine compound has aphrodisiac activity, these compounds can be isolated from plants of Leonurus Sp, Sundanese people is known as deundereman, this plant is empirical has aphrodisiac activity and based on the isolation of active compounds from plants known to contain compounds leonurine, so that the compound is expected to have activity aphrodisiac. Leonurine compound can be isolated from plants or synthesized chemically with material dasa siringat acid. Leonurine compound can be obtained commercial and derivatives of these compounds can be synthesized in an effort to increase its activity. This study aims to obtain derivatives leonurine better aphrodisiac activity compared with the parent compound, modified the structure of the compounds in the form leonurin guanidino butyl ester group with butyl amin and bromoetanol. ArgusLab program version 4.0.1 is used to determine the binding energy, hydrogen bonds and amino acids involved in the interaction of the compound PDE5 receptor. The in vivo test leonurine compounds and derivatives as an aphrodisiac ingredients and hormone testosterone levels using 27 male rats Wistar strain and 9 female mice of the same species, ages ranged from 12 weeks rats weighing + 200 g / tail. The test animal is divided into 9 groups according to the type of compounds and the dose given. Each treatment group was orally administered 2 ml per day for 5 days. On the sixth day was observed male rat sexual behavior and taking blood from the heart to measure testosterone levels using ELISA technique. Statistical analysis was performed in this study is the ANOVA test Least Square Differences (LSD) using the program Statistical Product and Service Solutions (SPSS). Aphrodisiac efficacy of the leonurine compound and its derivatives have proven in silico and in vivo test, the in silico testing leonurine derivatives have smaller binding energy derivatives leonurine so that activity better than leonurine compounds. Testing in vivo using rats of wistar strain that better leonurine derivative of this compound shows leonurine that in silico studies in parallel with in vivo tests. Modification of the structure in the form of guanidine butyl ester group with butyl amin and bromoethanol increase compared leonurine compound for aphrodisiac activity, testosterone derivatives of compounds leonurine experienced a significant improvement especial is 1RD compounds especially at doses of 100 and 150 mg/bb. The results showed that the compound leonurine and its compounds contain aphrodisiac activity and increase the amount of testosterone in the blood. The compound test used in this study acts as a steroid precursor resulting in increased testosterone.

Keywords: aphrodisiac dysfunction erectile leonurine 1-RD 2-RD, dysfunction, erectile leonurine, 1-RD 2-RD

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Authors: Feng Zhang, Li Chen, Desong Kong, Xiaoping Zhang, Xiaojing Zhu, Yin Lu, Shizhong Zheng

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Sinusoidal pathological angiogenesis is a novel therapeutic target for liver fibrosis. We demonstrated that curcumin ameliorated fibrotic injury and sinusoidal angiogenesis in rat liver with fibrosis caused by carbon tetrachloride. Curcumin reduced the expression of angiogenic markers in fibrotic liver. Experiments in vitro showed that the viability and vascularization of rat liver sinusoidal endothelial cells (LSECs) were not impaired by curcumin. Further investigations showed that curcumin inhibited VEGF expression in hepatic stellate cells (HSCs) by disrupting PDGF-βR/ERK and mTOR pathways. HSC motility and vascularization were also suppressed by curcumin via blocking PDGF-βR/FAK/RhoA cascade. Gain- or loss-of-function analyses revealed that activation of PPARγ was required for curcumin to inhibit angiogenic properties of HSCs. We concluded that curcumin attenuated sinusoidal angiogenesis in liver fibrosis possibly by targeting HSCs via a PPARγ activation-dependent mechanism. PPARγ could be a target molecule for reducing pathological angiogenesis during liver fibrosis.

Keywords: angiogenesis, hepatic stellate cell, curcumin, peroxisome proliferator-activated receptor-γ

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Authors: Shao-Ju Chien, Yi-Chien Wu, Ting-Ying Huang, Li-Tsen Li, You-Jin Chen, Cheng-Nan Chen

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Homocysteine and pro-inflammatory mediators such as cyclooxygenase-2 (COX-2) have been linked to vascular dysfunction and risks of cardiovascular diseases. Fulvic acid (FA) is class of compounds of humic substances and possesses various pharmacological properties. However, the effect of FA on inflammatory responses of the monocytes remains unclear. We investigated the regulatory effect of FA on homocysteine-induced COX-2 expression in human monocytes. Peripheral blood monocytes and U937 cells were kept as controls or pre-treated with FA, and then stimulated with homocysteine. The results show that pretreating monocytes with FA inhibited the homocysteine-induced COX-2 expression in a dose-dependent manner. The inhibitor for nuclear factor-kB (NF-kB) attenuated homocysteine-induced COX-2 expression. Our findings provide a molecular mechanism by which FA inhibit homocysteine-induced COX-2 expression in monocytes, and a basis for using FA in pharmaceutical therapy against inflammation.

Keywords: homocysteine, monocytes, cyclooxygenase-2, fulvic acid, anti-inflammation

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Authors: Mohammed A. Alfayyadh, Halla A. AlAbdulhadi, Mahdi H. Almubarak

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Purpose: Eales’ disease is an idiopathic vasculitis that affects the peripheral retina. It is characterized by recurrent vitreous hemorrhage as a complication of retinal neovascularization. It is more prevalent in India and affects young males. Here we present a patient with neovascular glaucoma as a rare first presentation of Eales’ disease. Observations: This is a 24-year-old Indian gentleman, who complained of a sudden decrease in vision in the left eye over less than 24 hours, along with frontal headache and eye pain for the last three weeks. Ocular examination revealed peripheral retinal ischemia in the right eye, very high intraocular pressure, rubeosis iridis, vitreous hemorrhage and extensive retinal ischemia in the left eye, vascular sheathing and neovascularization in both eyes. Purified protein derivative skin test was positive. The patient was managed with anti-glaucoma, intravitreal anti-vascular endothelial growth factor and laser photocoagulation. Systemic steroids and anti-tuberculous therapy were also initiated. Conclusions: Neovascular glaucoma is an infrequent complication of Eales’ disease. However, the lack of early detection of the disease in the early stages might lead to such serious complication.

Keywords: case report, Eales’ disease, mycobacterium tuberculosis, neovascular glaucoma

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Authors: Fardis Teifoori, Mehdi Dehghani, Idoia Postigo, Jorge Martinez

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Introduction: Many skin disorders, such as atopic dermatitis (AD), is characterized by inflammation, infection, and hyperplasia. In this work, keratinocytes from AD patients are used to study the pomegranate seed oil properties for skin care. Material and methods: Isolated keratinocytes from patients with AD were cultured and stimulated by IL-9 (20 ng/ml) and TNF-α (50ng/ml) for 48h to induce vascular endothelial growth factor (VEGF) and Regulated upon activation, normal T cell expressed and secreted (RANTES) production, respectively, in the presence of different concentrations of pomegranate seed oil (20, 50, 100, and 200 µM). Finally, the concentrations of RANTES and VEGF in the cell culture supernatant were quantified according to the standard protocol of commercial ELISA kits. Results: The results indicated that pomegranate seed oil concentrations of 50, 100, and 200 µM could significantly inhibit the production of VEGF and RANTES by stimulating keratinocytes with IL-9 (20 ng/ml) and TNF-α (50ng/ml), respectively. The decrease in VEGF and RANTES concentration in the presence of the pomegranate seed oil concentrations of 20 and 50 uM was not significant. Conclusion: It was concluded that pomegranate seed oil (PSO) counteracts atopic dermatitis conditions dose-dependently: with the highest effect at the concentration of 200 µM. We suggest that the inexpensive and easily available pomegranate seed oil is a good candidate for cosmetics and clinical utilization for skin care.

Keywords: atopic dermatitis, pomegranate, Punica granatum, RANTES, VEGF

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Authors: Abdallah Mohamed Kamel Mohamed Ali, Samah Saad Zahran, Mohamed Hamed Rashad

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Background: Flexible flatfoot (FFF) has been considered as a risk factor for several lower limb injuries and mechanical low back pain. This was attributed to the dysfunction of the lumbopelvic-hip complex musculature. Objective: To investigate the influence of FFF on electromyographic activities of erector spinae and multifidus. Methods: A cross-section study was held between an FFF group (20 subjects) and a normal foot group (20 subjects). A surface electromyography was used to assess the electromyographic activity of erector spinae and multifidus. Group differences were assessed by the T-test. Results: There was a significant increase in EMG activities of erector spinae and multifidus in the FFF group compared with the normal group. Conclusion: There is an increase in EMG activities in erector spinae and multifidus in FFF subjects compared with normal subjects.

Keywords: electromyography, flatfoot, low back pain, paraspinal muscles

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Authors: Moumita Chanda, Md. Fazlul Karim Patwary

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Smoking is one of the most popular recreational drug use behaviors, and it contributes to birth defects, COPD, heart attacks, and erectile dysfunction. To completely eradicate this disease, it is imperative that it be identified and treated. Numerous smoking cessation programs have been created, and they demonstrate how beneficial it may be to help someone stop smoking at the ideal time. A tomography meter is an effective smoking detector. Other wearables, such as RF-based proximity sensors worn on the collar and wrist to detect when the hand is close to the mouth, have been proposed in the past, but they are not impervious to deceptive variables. In this study, we create a machine that can discriminate between smokers and non-smokers in real-time with high sensitivity and specificity by watching and collecting the human lung and analyzing the X-ray data using machine learning. If it has the highest accuracy, this machine could be utilized in a hospital, in the selection of candidates for the army or police, or in university entrance.

Keywords: CNN, smoker detection, non-smoker detection, OpenCV, artificial Intelligence, X-ray Image detection

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Authors: Omonov Jahongir Mahmatkulovic

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Purpose: To study the significance of D-dimer (DD), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen coagulation parameters (Fg) in predicting the course, severity and prognosis of COVID-19. Source and method of research: From September 15, 2021, to November 5, 2021, 93 patients aged 25 to 60 with suspected COVID-19, who are under inpatient treatment at the multidisciplinary clinic of the Tashkent Medical Academy, were retrospectively examined. DD, PT, APTT, and Fg were studied in dynamics and studied changes. Results: Coagulation disorders occurred in the early stages of COVID-19 infection with an increase in DD in 54 (58%) patients and an increase in Fg in 93 (100%) patients. DD and Fg levels are associated with the clinical classification. Of the 33 patients who died, 21 had an increase in DD in the first laboratory study, 27 had an increase in DD in the second and third laboratory studies, and 15 had an increase in PT in the third test. The results of the ROC analysis of mortality showed that the AUC DD was three times 0.721, 0.801, and 0.844, respectively; PT was 0.703, 0.845, and 0.972. (P<0:01). Conclusion”: Coagulation dysfunction is more common in patients with severe and critical conditions. DD and PT can be used as important predictors of mortality from COVID-19.

Keywords: Covid19, DD, PT, Coagulogram analysis, APTT

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Authors: Masaki Yamaguchi, Daimei Sasayama, Shinsuke Washizuka

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The goal of this study was to examine the possibility of salivary cytokines for the screening of attention deficit hyperactivity disorder (ADHD) in children. We carried out a case-control study, including 19 children with ADHD and 17 healthy children (controls). A multiplex bead array immunoassay was used to conduct a multi-analysis of 27 different salivary cytokines. Six salivary cytokines (interleukin (IL)-1β, IL-8, IL12p70, granulocyte colony-stimulating factor (G-CSF), interferon gamma (IFN-γ), and vascular endothelial growth factor (VEGF)) were significantly associated with the presence of ADHD (p < 0.05). An informative salivary cytokine panel was developed using VEGF by logistic regression analysis (odds ratio: 0.251). Receiver operating characteristic analysis revealed that assessment of a panel using VEGF showed “good” capability for discriminating between ADHD patients and controls (area under the curve: 0.778). ADHD has been hypothesized to be associated with reduced cerebral blood flow in the frontal cortex, due to reduced VEGF levels. Our study highlights the possibility of utilizing differential salivary cytokine levels for point-of-care testing (POCT) of biomarkers in children with ADHD.

Keywords: cytokine, saliva, attention deficit hyperactivity disorder, child

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Authors: Maria Luisa Barcena De Arellano, Sofya Pozdniakova, Pavelas Karkacas, Anja Kuhl, Istvan Baczko, Yury Ladilov, Vera Regitz-Zagrosek

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Introduction: Aging is associated with deterioration of the physiological function, leading to systemic inflammation and mitochondrial dysfunction that promote the development of cardiovascular diseases. Sex differences in aging-related cardiovascular diseases have been postulated. However, their precise mechanisms remain unclear. In the current study, we aimed to investigate the sex difference in the age-related alteration in Sirt1-AMPK signaling and its relation to the mitochondrial biogenesis and inflammation. Methods: Male and female human non-disease lateral left ventricular wall tissue (young (17–40 years; n= 7 male and 7 female) and old (50–68 years; n= 9 male and 8 female)) were used. qRT-PCR, western blot and immunohistochemistry assays were performed for expression analyses of Sirt1, AMPK, pAMPK, ac-Ku70, TFAM, PGC-1α, Sirt3, SOD2 and catalase. CD68 was used as a marker for macrophages and the ratio of IL-12:IL10 (pro-inflammatory phenotype (high IL-12/low IL-10) and anti-inflammatory phenotype (low IL-12/high IL-10) was used to examine the inflammatory stage in the heart. Results: Sirt1 expression was significantly higher in young females compared to young males, whereas in aged hearts Sirt1 expression was significantly downregulated in females, but not in males. In line with the Sirt1 downregulation in aged females, acetylation of nuclear Ku70, a direct target of Sirt1, in aged female hearts was significantly elevated. The activity of AMPK was significantly decreased in aged individuals, however no sex differences in the AMPK expression or activity were found in young or old individuals. The expression of mitochondrial proteins TOM40, SOD2 and Sirt3 was significantly higher in young females compared to young males, while in aged female hearts SOD2 and TOM40 were downregulated. In addition, the expression of catalase, a key cytosolic and mitochondrial anti-oxidative enzyme was significantly higher in young females and this female sex benefit was lost in aged hearts. In addition, the number of cardiac macrophages was significantly increased in old female, but not in male hearts. Consistently, the pro-inflammatory shift in old females was further confirmed by differences in the IL12/IL10 ratio in young female cardiac tissue in a favour of the anti-inflammatory mediator IL-10 (ratio 1:4) compared to young males (ratio 1:1). The anti-inflammatory environment in the heart was lost in aged females (ratio 1:1). Conclusion: Aging leads to the significant downregulation of Sirt1 expression and elevated acetylation of Ku70 in female, but not in male hearts. Furthermore, a beneficial upregulation of mitochondrial and anti-oxidative proteins in young females is lost with aging. Moreover, the malfunctions in the expression of Sirt1 and mitochondrial proteins in aged female hearts is accompanied by a significant pro-inflammatory shift. The study provides a molecular basis for the increased incidence of cardiovascular diseases in old women.

Keywords: inflammation, mitochondrial dysfunction, aging, Sirt1-AMPK axis

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Authors: Aml M. El-Sharkawy, Hossam M. Darwesh

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Abstract— Background/Aim: Hepatocellular carcinoma (HCC) is often diagnosed at advanced stage where effective therapies are lacking. Identification of new scoring system is needed to discriminate HCC patients from those with chronic liver disease. Based on the link between tumor associated trypsin inhibitor (TATI) and HCC progression, we aimed to develop a novel score based on combination of TATI and routine laboratory tests for early prediction of HCC. Methods: TATI was assayed for HCC group (123), liver cirrhosis group (210) and control group (50) by Enzyme Linked Immunosorbent Assay (ELISA). Data from all groups were retrospectively analyzed including α feto protein (AFP), international normalized ratio (INR), albumin and platelet count, transaminases, and age. Areas under ROC curve were used to develop the score. Results: A novel index named hepatocellular carcinoma-vascular endothelial growth factor score (HCC-TATI score) = 3.1 (numerical constant) + 0.09 ×AFP (U L-1) + 0.067 × TATI (ng ml-1) + 0.16 × INR – 1.17 × Albumin (g l-1) – 0.032 × Platelet count × 109 l-1 was developed. HCC-TATI score produce area under ROC curve of 0.98 for discriminating HCC patients from liver cirrhosis with sensitivity of 91% and specificity of 82% at cut-off 6.5 (ie less than 6.5 considered cirrhosis and greater than 4.4 considered HCC). Conclusion: Hepatocellular carcinoma-TATI score could replace AFP in HCC screening and follow up of cirrhotic patients.

Keywords: Hepatocellular carcinoma, cirrhosis, HCV, diagnosis, TATI

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Authors: Hye Jin Kim, Hwa Sung Shin

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Ischemic stroke means the caused brain damage due to neurological defects, occurring occlusion of cerebral vascular resulting in thrombus or embolism. t-PA (tissue Plasminogen Activator) is the only thrombolytic agent passed the FDA (Food and Drug Administration). However, t-PA directly dissolves the thrombus (direct activity) through fibrinolysis, showing side effects such as re-occlusion. In this study, we evaluated the thrombolytic activities of the serine protease extracted from lugworms inhabiting tidal flats. The new serine protease identified as 38 kDa by SDS-PAGE was not toxic to brain endothelial cells line (hCMEC/D3). Also, the plasmin synthesis inhibition activity (indirect activity) of the new serine protease was confirmed through fibrin zymography assay and fibrin plate assay. It was higher than direct activity as compared to u-PA (urokinase Plasminogen Activator). The activities were found to be maintained at a wide range of temperature (4-70 ℃) and pH 7-10 compared to previous thrombolytic agents from the azocasein assay. In addition, the new serine protease has shown anticoagulant activity from fibrinogenolytic activity assay. In conclusion, the serine protease in lug worms inhabiting the tidal flats could be considered a promising thrombolytic candidate for the treatment of ischemic stroke.

Keywords: alkaline serine protease, bifunctional thrombolytic activity, fibrinolytic activity, ischemic stroke, lug worms

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Authors: Jisun Jun, Eun Ko, Sooim Shin, Kitae Kim, Moonsung Choi

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Diabetes is a metabolic disease characterized by hyperglycemia, insulin resistant, mitochondrial dysfunction. Diabetes is associated with the development of diabetic retinopathy resulting in worsening vision and eventual blindness. In this study, eyes were enucleated from glucose-immersed zebrafish which is a good animal model to generate diabetes, and then mitochondria were isolated to evaluate activities of mitochondrial electron transfer complexes. Surprisingly, the amount of isolated mitochondria was increased in eyes from glucose-immersed zebrafish compared to those from non-glucose-immerged zebrafish. Spectrophotometric analysis for measuring activities of mitochondrial complex I, II, III, and IV revealed that mitochondria functions was even enhanced in eyes from glucose-immersed zebrafish. These results indicated that 3 days or 7 days glucose-immersion on zebrafish to induce diabetes might contribute metabolic compensatory mechanism to restore their mitochondrial homeostasis on the early stage of diabetes in eyes.

Keywords: diabetes, glucose immersion, mitochondrial complexes, zebrafish

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