Search results for: tertiary treatment

Authors: P. Narrima, C. Y. Looi, M. A. Mohd, H. M. Ali

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Persea declinata (Bl.) Kosterm is a member of the Lauraceae family, widely distributed in Southeast Asia. It is from the same genus with avocado (Persea americana Mill), which is widely consumed as food and for medicinal purposes. In the present study, we examined the anticancer properties of Persea declinata (Bl.) Kosterm bark methanolic crude extract (PDM). PDM exhibited a potent antiproliferative effect in MCF-7 human breast cancer cells, with an IC50 value of 16.68 µg/mL after 48h of treatment. We observed that PDM caused cell cycle arrest and subsequent apoptosis in MCF-7 cells, as exhibited by increased population at G0/G1 phase, higher lactate dehydrogenase (LDH) release, and DNA fragmentation. Mechanistic studies showed that PDM caused significant elevation in ROS production, leading to perturbation of mitochondrial membrane potential, cell permeability, and activation of caspases-3/7. On the other hand, real-time PCR and Western blot analysis showed that PDM treatment increased the expression of the proapoptotic molecule, Bax, but decreased the expression of prosurvival proteins, Bcl-2 and Bcl-xL, in a dose-dependent manner. These findings imply that PDM could inhibit proliferation in MCF-7 cells via cell cycle arrest and apoptosis induction, indicating its potential as a therapeutic agent worthy of further development.

Keywords: antiproliferative, apoptosis, MCF-7 human breast cancer, Persea declinata

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Authors: Stephen Hamafyelto, Hussaini Garba, Mary Pindar Ndahi

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The study was carried out with the intent to mitigate the trauma experienced by victims of insurgent attacks by the so-called Boko Haram militants in Borno state of Nigeria. The area was ridden by the crisis over the past 9 years. As a result, many people were killed, maimed and raped. Some others suffered all manner of inhuman treatment at the hands of their captors. The extent to which this dehumanized treatment has gone and impacted on the people in this area has left most of them traumatised. Victims who survived the attacks have been resettled in camps provided by government where their needs have been cared for. This can never be the same with their natural habitats. Many interventions have also been done by government, non-governmental organisations and corporate and individual bodies. In this regard, social needs of the victims have been the immediate concerns of most organisations, where food, shelter, and clothing were provided. However, there is little that has been done to rehabilitate these victims psychosocially. In this regard, sports and games including the victims’ local games were used to provide psychosocial rehabilitation of victims. The intent was to bring them back to social reality, social inclusion, and stable emotions and peer integration. Descriptive statistics and Multivariate analysis were done. No statistically significant difference was found among male and female children and adults in terms of psychosocial rehabilitation using sports and games.

Keywords: social reality, social inclusion, emotional intellegence, peer model

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Authors: Jakub Młoźniak, Adam Szymański, Gabriela Stondzik, Dagny Krankowska, Tomasz Mikuła

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Nontuberculous mycobacteria (NTM) are bacterial species that cause diversely manifesting diseases mainly in immunocompromised patients. In people with HIV, NTM infection is an AIDS-defining disease and usually appears when the lymphocyte T CD4 count is below 50 cells/μl. The usage of antiretroviral therapy has decreased the prevalence of NTM among people with HIV, but the disease can still be observed especially among patients with late HIV diagnosis. Common presence in environment, human colonization, clinical similarity with tuberculosis and slow growth on culture makes NTM especially hard to diagnose. The study aimed to analyze the epidemiology and clinical course of NTM among patients with HIV. This study included patients with NTM and HIV admitted to our department between 2017 and 2023. Medical records of patients were analyzed and data on age, sex, median time from HIV diagnosis to identification of NTM infection, median CD4 count at NTM diagnosis, methods of determining NTM infection, type of species of mycobacteria identified, clinical symptoms and treatment course were gathered. Twenty-four patients (20 men, 4 women) with identified NTM were included in this study. Among them, 20 were HIV late presenters. The patients' median age was 40. The main symptoms which patients presented were fever, weight loss and cough. Pulmonary disease confirmed with positive cultures from sputum/bronchoalveolar lavage was present in 18 patients. M. avium was the most common species identified. M. marinum caused disseminated skin lesions in 1 patient. Out of all, 5 people were not treated for NTM caused by lack of symptoms and suspicion of colonization with mycobacterium. Concomitant tuberculosis was present in 6 patients. The median diagnostic time from HIV to NTM infections was 3.5 months. The median CD4 count at NTM identification was 69.5 cells/μl. Median NTM treatment time was 16 months but 7 patients haven’t finished their treatment yet. The most commonly used medications were ethambutol and clarithromycin. Among analyzed patients, 4 of them have died. NTM infections are still an important disease among patients who are HIV late presenters. This disease should be taken into consideration during the differential diagnosis of fever, weight loss and cough in people with HIV with lymphocyte T CD4 count <100 cells/μl. Presence of tuberculosis does not exclude nontuberculous mycobacterium coinfection.

Keywords: mycobacteriosis, HIV, late presenter, epidemiology

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Authors: M. S. Lu, Y. P. Tsai, H. Shu, K. F. Chen, L. L. Lai

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This study used sodium hypochlorite/sodium dodecyl sulfate method to successfully extract polyhydroxyalkanoates (PHA) from the wasted sludge of a husbandry industry wastewater treatment plant. We investigated the optimum operational conditions of three key factors with respect to effectively extract PHAs from husbandry industry wastewater sludge, including the sodium hypochlorite concentration, liquid-solid ratio, and reaction time. The experimental results showed the optimum operational conditions for polyhydroxyalkanoate recovery as follows: (1) being digested by the sodium hypochlorite/sodium dodecyl sulfate solution with 15% (v/v) of hypochlorite concentration, (2) being operated at the condition of 1.25 mLmg-1 of liquid-solid ratio, and (3) being reacted for more than 60 min. Under these conditions, the content of the recovered PHAs was about 53.2±0.66 mgPHAs/gVSS, and the purity of the recovered PHAs was about 78.5±6.91 wt%. The recovered PHAs were further used to produce biodegradable plastics for decomposition test buried in soils. The decomposition test showed 66.5% of the biodegradable plastics produced in the study remained after being buried in soils for 49 days. The cost for extracting PHAs is about 10.3 US$/kgPHAs and is lower than those produced by pure culture methods (12-15 US$/kgPHAs).

Keywords: biodegradable plastic, biopolymers, polyhydroxyalkanoates (PHAs), waste sludge

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Authors: Spira A., Marabelle A., Kientop D., Moser E., Mumm J.

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Background: Both interleukin-2 (IL-2) and interleukin-10 (IL-10) have been extensively studied for their stimulatory function on T cells and their potential to obtain sustainable tumor control in RCC, melanoma, lung, and pancreatic cancer as monotherapy, as well as combination with PD-1 blockers, radiation, and chemotherapy. While approved, IL-2 retains significant toxicity, preventing its widespread use. The significant efforts undertaken to uncouple IL-2 toxicity from its anti-tumor function have been unsuccessful, and early phase clinical safety observed with PEGylated IL-10 was not met in a blinded Phase 3 trial. Deka Biosciences has engineered a novel molecule coupling wild-type IL-2 to a high affinity variant of Epstein Barr Viral (EBV) IL-10 via a scaffold (scFv) that binds to epidermal growth factor receptors (EGFR). This patented molecule, termed DK210 (EGFR), is retained at high levels within the tumor microenvironment for days after dosing. In addition to overlapping and non-redundant anti-tumor function, IL-10 reduces IL-2 mediated cytokine release syndrome risks and inhibits IL-2 mediated T regulatory cell proliferation. Methods: DK210 (EGFR) is being evaluated in an open-label, dose-escalation (Phase 1) study with 5 (0.025-0.3 mg/kg) monotherapy dose levels and (expansion cohorts) in combination with PD-1 blockers, or radiation or chemotherapy in patients with advanced solid tumors overexpressing EGFR. Key eligibility criteria include 1) confirmed progressive disease on at least one line of systemic treatment, 2) EGFR overexpression or amplification documented in histology reports, 3) at least a 4 week or 5 half-lives window since last treatment, and 4) excluding subjects with long QT syndrome, multiple myeloma, multiple sclerosis, myasthenia gravis or uncontrolled infectious, psychiatric, neurologic, or cancer disease. Plasma and tissue samples will be investigated for pharmacodynamic and predictive biomarkers and genetic signatures associated with IFN-gamma secretion, aiming to select subjects for treatment in Phase 2. Conclusion: Through successful coupling of wild-type IL-2 with a high affinity IL-10 and targeting directly to the tumor microenvironment, DK210 (EGFR) has the potential to harness IL-2 and IL-10’s known anti-cancer promise while reducing immunogenicity and toxicity risks enabling safe concomitant cytokine treatment with other anti-cancer modalities.

Keywords: cytokine, EGFR over expression, interleukine-2, interleukine-10, clinical trial

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Authors: Aroma Elmina Martha

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Environment affects the continuity of life and human well-being and the bodies of other living. Environmental quality is very closely related to the quality of life. Sustainability must be protected from damage due to the use of natural resources, such as tin mining in Bangka island. This research is a descriptive study, which identifies the environmental damage caused by mining land and sea in Bangka district. The approach used is juridical, social and economic. The study uses primary legal materials, secondary, and tertiary, equipped with field research. The analysis technique used is qualitative analysis. The impacts of mining on land among other physical and chemical damage, erosion and widening the depth of the river, a pool of micro-climate, the quality and feasibility, vegetation, wildlife and biodiversity, land values, social and economic. This mining causes damage to the soil structure, and puddles in the former digs which were not backfilled again. The impact of mining on the ocean such as changes in current surge, erosion and abrasion basic coastal waters, shoreline change, marine water quality changes, and changes in marine communities. The findings of the research show that tin mining in the sea also potentially have a significant impact on the life of the reef, populations of marine organisms. However, mining on land needs to consider the impact of the damage, so that the damage can be minimized. In the recovery process needs to be pursued by exploiting the rest of the pile of tin. Thus, mining activities should take into account the distance of beach sediment size, wave height, wave length, wave period, and the acceleration of gravity. The process of the tin washing should be done in a fairly safe area, thus avoiding damage to the coral reefs that will eventually reduce the population of marine life.

Keywords: abration, environmental damage, mining, shoreline

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Authors: Dheyaa Wajid Abbood, Ali Mohammed Tawfeeq Baqer, Eitizaz Awad Jasim

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The aim of this investigation is to confirm the activity of a sludge recycling process in trickling filter filled with limestone as an alternative biological process over conventional high-cost treatment process with regard to toxic matter reduction from marginal water. The combination system of stepped cascade weir with limestone trickling filter has been designed and constructed in the Environmental Hydraulic Laboratory, Al-Mustansiriya University, College of Engineering. A set of experiments has been conducted during the period from August 2013 to July 2014. Seven days of continuous operation with different continuous flow rates (0.4m3/hr, 0.5 m3/hr, 0.6 m3/hr, 0.7m3/hr,0.8 m3/hr, 0.9 m3/hr, and 1m3/hr) after ten days of acclimatization experiments were carried out. Results indicate that the concentrations of toxic matter were decreasing with increasing of operation time, sludge recirculation ratio, and flow rate. The toxic matter measured includes (Mineral oils, Petroleum products, Phenols, Biocides, Polychlorinated biphenyls (PCBs), and Surfactants) which are used in these experiments were ranged between (0.074 nm-0.156 nm). Results indicated that the overall reduction efficiency after 4, 28, 52, 76, 100, 124, and 148 hours of operation were (55%, 48%, 42%, 50%, 59%, 61%, and 64%) when the combination of stepped cascade weir with limestone trickling filter is used.

Keywords: Marginal water , Toxic matter, Stepped Cascade weir, limestone trickling filter

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Authors: Jia H. Wong, Jingli Zhang, Habsah Mohamad, Iswatun H. Abdullah Ripain, Muhammad Bilal, Amelia J. Lloyd, Abdul A. Mohamed Yusoff, Jafri M. Abdullah

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Epilepsy is one of the most common neurological diseases affecting more than 50 million of people worldwide. Epilepsy is a state of recurrent, spontaneous seizures with multiple syndromes and symptoms of different causes of brain dysfunction, prognosis, and treatments; characterized by transient, occasional and stereotyped interruptions of behavior whereby the excitatory-inhibitory activities within the central nervous system (CNS) are thrown out of balance due to various kinds of interferences. The goal of antiepileptic treatment is to enable patients to be free from seizures or to achieve control of seizures through surgical treatment and/or pharmacotherapy. Pharmacotherapy through AED plays an important role especially in countries with epilepsy treatment gap due to costs and availability of health facilities, skills and resources, yet there are about one-third of the people with epilepsy have drug-resistant seizures. Hence, this poses considerable challenges to the healthcare system and the effort in providing cost-effective treatment as well as the search for alternatives to treatment and management of epilepsy. Enhancement of γ-aminobutyric acid (GABA)-mediated inhibitory neurotransmission is one of the key mechanisms of actions of antiepileptic drugs. GABA type > a receptors (GABAAR) are ligand-gated ion channels that mediate rapid inhibitory neurotransmission upon the binding of GABA with a heteropentameric structure forming a central pore that is permeable to the influx of chloride ions in its activated state. The major isoform of GABAA receptors consists of two α1, two β2, and one γ2 subunit. It is the most abundantly expressed combinations in the brain and the most commonly researched through Xenopus laevis oocytes. With the advancing studies on ethnomedicine and traditional treatments using medicinal plants, increasing evidence reveal that spice and herb plants with medicinal properties play an important role in the treatment of ailments within communities across different cultures. Capsaicin is the primary natural capsaicinoid in hot peppers of plant genus Capsicum, consist of an aromatic ring, an amide linkage and a hydrophobic side chain. The study showed that capsaicins conferred neuroprotection in status epilepticus mouse models through anti-ictogenic, hypothermic, antioxidative, anti-inflammatory, and anti-apoptotic actions in a dose-dependent manner. In this study, five capsaicin derivatives were tested for their ability to increase the GABA-induced chloride current on α1β2γ2S of GABAAR expressed on Xenopus laevis oocytes using the method of two-microelectrode voltage clamp. Two of the capsaicin derivatives, IS5 (N-(4-hydroxy-3-methoxybenzyl)-3-methylbutyramide) and IS10 (N-(4-hydroxy-3-methoxybenzyl)-decanamide) at a concentration of 30µM were able to significantly increase the GABA-induced chloride current with p=0.002 and p=0.026 respectively. This study were able to show the enhancement effect of two capsaicin derivatives with moderate length of hydrocarbon chain on this receptor subtype, revealing the promising inhibitory activity of capsaicin derivatives through enhancement of GABA-induced chloride current and further investigations should be carried out to verify its antiepileptic effects in animal models.

Keywords: α1β2γ2 GABAA receptors, α1β2γ2S, antiepileptic, capsaicin derivatives, two-microelectrode voltage clamp, Xenopus laevis oocytes

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Authors: Sheikha Turki Alketbi

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Objectives: 1. Documenting the spontaneous resolution of AML following the initiation of anti-TB therapy. 2. Presenting an uncommon type of relapse in Acute Myeloid Leukemia. 3. Highlighting the role of immune markers in the diagnosis of Leukemia cutis. 4. Exploring and highlighting the possibility of skin relapse as the exclusive manifestation, even when skin involvement is known secondary manifestation in AML. Background: Spontaneous remission of Acute Myeloid Leukemia (AML) is a rare phenomenon that has only been reported in some case reports, usually following severe infections. Some studies have described the occurrence of tuberculosis (TB) infection with AML, usually after starting chemotherapy. Spontaneous resolution of AML after starting anti TB therapy (ATT), without starting chemotherapy has never been described in the literature. Moreover, Leukemia cutis is another rare skin manifestation of Acute Myeloid Leukemia as a result of infiltration of the skin or subcutaneous tissue by leukemic cells, in which can present during, precedes, after or independently of systemic leukemia. Methods: Here, we present a case of a 13-year-old male who presented with fever, weight loss, lethargy, epistaxis, bruising and dry cough and was later diagnosed with AML. Before initiating leukemia treatment, the patient was tested for TB and was found to have active TB infection. His leukemia treatment was postponed to clear the TB infection and he was commenced on ATT. Two months later, repeat blood film and bone marrow biopsy showed resolution of his AML. The patient remained in remission for 1 month, after which he presented with symmetrical blue purple well-defined round indurated plaques on the chest and thighs. Our differentials were leukemia cutis and Kaposi sarcoma. Results: Skin Biopsy with immune markers done, showed a picture of Acute Myeloid Leukemia. Immunohistochemistry (IHC) showed neoplastic cells diffusely and strongly positive for LCA, CD2, CD31, MPO, CD117, Lysozymes and TDT, and moderately positive for CD34, CD99, CD43 and CD6 And patchy for CD68. Ki67 showed 60% proliferation index. They were negative for the remaining markers. This suggested acute myeloid leukemia (AML). Conclusion: In summary, we present a rare case of TB with AML that resolved after treatment of TB with ATT but relapsed later as leukemia cutis. While skin involvement might occur as a secondary manifestation of AML, Skin relapse could be the only one.

Keywords: Leukemia cutis, Leukemia relapse, Acute Myeloid Leukemia, spontaneous resolution of AML

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Authors: Wu Liching

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Aim This case aims to discuss the pathogenesis, clinical manifestations and medical treatment of strokes caused by mitochondrial gene mutations. Methods Diagnosis of ischemic stroke caused by mitochondrial gene defect by means of "next-generation sequencing mitochondrial DNA gene variation detection", imaging examination, neurological examination, and medical history; this study took samples from the neurology ward of a medical center in northern Taiwan cases diagnosed with acute cerebral infarction as the research objects. Result This case is a 49-year-old married woman with a rare disease, mitochondrial gene mutation inducing ischemic stroke. She has severe hearing impairment and needs to use hearing aids, and has a history of diabetes. During the patient’s hospitalization, the blood test showed that serum Lactate: 7.72 mmol/L, Lactate (CSF) 5.9 mmol/L. Through the collection of relevant medical history, neurological evaluation showed changes in consciousness and cognition, slow response in language expression, and brain magnetic resonance imaging examination showed subacute bilateral temporal lobe infarction, which was an atypical type of stroke. The lineage DNA gene has m.3243A>G known pathogenic mutation point, and its heteroplasmic level is 24.6%. This pathogenic point is located in MITOMAP and recorded as Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) , Leigh Syndrome and other disease-related pathogenic loci, this mutation is located in ClinVar and recorded as Pathogenic (dbSNP: rs199474657), so it is diagnosed as a case of stroke caused by a rare disease mitochondrial gene mutation. After medical treatment, there was no more seizure during hospitalization. After interventional rehabilitation, the patient's limb weakness, poor language function, and cognitive impairment have all improved significantly. Conclusion Mitochondrial disorders can also be associated with abnormalities in psychological, neurological, cerebral cortical function, and autonomic functions, as well as problems with internal medical diseases. Therefore, the differential diagnoses cover a wide range and are not easy to be diagnosed. After neurological evaluation, medical history collection, imaging and rare disease serological examination, atypical ischemic stroke caused by rare mitochondrial gene mutation was diagnosed. We hope that through this case, the diagnosis of rare disease mitochondrial gene variation leading to cerebral infarction will be more familiar to clinical medical staff, and this case report may help to improve the clinical diagnosis and treatment for patients with similar clinical symptoms in the future.

Keywords: acute stroke, MELAS, lactic acidosis, mitochondrial disorders

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Authors: Kruttika Bhuse

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Aim: Synergism between periodontists and orthodontists (periodontal accelerated osteogenic orthodontics- PAOO) creates crucial opportunities to enhance clinical outcomes of combined therapies regarding both disciplines and has made adult orthodontics a reality. Thus, understanding the biomechanics of bone remodelling may increase the clinical applications of corticotomy facilitated orthodontics with or without alveolar augmentation. Wilckodontics can be an attractive treatment option and be a “win-win” situation for both the dental surgeon and patient by reducing the orthodontic treatment time in adults. Materials and methods: In this review, data related to the clinical aspects, steps of procedure, biomechanics of bone, indications and contraindications and final outcome of wilckodontic shall be discussed. 50 supporting articles from various international journals and 70 clinical cases were reviewed to get a better understanding to design this wilckodontic - meta analysis. Various journals like the Journal Of Clinical And Diagnostic Research, Journal Of Indian Society Of Periodontology, Journal Of Periodontology, Pubmed, Boston Orthodontic University Journal, Good Practice Orthodontics Volume 2, have been referred to attain valuable information on wilckodontics which was then compiled in this single review study. Result: As a promising adjuvant technique based on the transient nature of demineralization-remineralisation process in healthy tissues, wilckodontics consists of regional acceleratory phenomenon by alveolar corticotomy and bone grafting of labial and palatal/lingual surfaces, followed by orthodontic force. The surgical wounding of alveolar bone potentiates tissue reorganization and healing by a way of transient burst of localized hard and soft tissue remodelling.This phenomenon causes bone healing to occur 10-50 times faster than normal bone turnover. Conclusion: This meta analysis helps understanding that the biomechanics of bone remodelling may increase the clinical applications of corticotomy facilitated orthodontics with or without alveolar augmentation. The main benefits being reduced orthodontic treatment time, increased bone volume and post-orthodontic stability.

Keywords: periodontal osteogenic accelerated orthodontics, alveolar corticotomy, bone augmentation, win-win situation

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Authors: F. O’Dowd, G. Murphy, M. Roche, E. Shudell, F. Keane, M. O’Kane

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Intoduction: Apremilast (Otezla®) is an oral phosphodiesterase-4 (PDE4) inhibitor indicated for treatment of adult patients with moderate to severe plaque psoriasis who have contraindications to have failed or intolerant of standard systemic therapy and/or phototherapy; and adult patients with active psoriatic arthritis. Apremilast influences intracellular regulation of inflammatory mediators. Two randomized, placebo-controlled trials evaluating apremilast in 1426 patients with moderate to severe plague psoriasis (ESTEEM 1 and 2) demonstrated that the commonest adverse reactions (AE’s) leading to discontinuation were nausea (1.6%), diarrhoea (1.0%), and headaches (0.8%). The overall proportion of subjects discontinuing due to adverse reactions was 6.1%. At week 16 these trials demonstrated significant more apremilast-treated patients (33.1%) achieved the primary end point PASI-75 than placebo (5.3%). We began prescribing apremilast in July 2015. Aim: To evaluate efficacy and tolerability of apremilast in an Irish teaching hospital psoriasis population. Methods: A proforma documenting clinical evaluation parameters, prior treatment experience and AE’s; was completed prospectively on all patients commenced on apremilast since July 2015 – July 2017. Data was collected at week 0,6,12,24,36 and week 52 with 20/71 patients having passed week 52. Efficacy was assessed using Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI). AE’s documented included GI effects, infections, changes in weight and mood. Retrospective chart review and telephone review was utilised for missing data. Results: A total of 71 adult subjects (38 male, 33 female; age range 23-57), with moderate to severe psoriasis, were evaluated. Prior treatment: 37/71 (52%) were systemic/biologic/phototherapy naïve; 14/71 (20%) has prior phototherapy alone;20/71 (28%) had previous systemic/biologic exposure; 12/71 (17%) had both psoriasis and psoriatic arthritis. PASI responses: mean baseline PASI was 10.1 and DLQI was 15.Week 6: N=71, n=15 (21%) achieved PASI 75. Week 12: N= 48, n=6 (13%) achieved a PASI 100%; n=16 (34.5%) achieved a PASI 75. Week 24: N=40, n=10 (25%) achieved a PASI 100; n=15 (37.5%) achieved a PASI 75. Week 52: N= 20, n=4 (20%) achieved a PASI 100; n= 16 (80%) achieved a PASI 75. (N= number of pts having passed the time point indicated, n= number of pts (out of N) achieving PASI or DLQI responses at that time). DLQI responses: week 24: N= 40, n=30 (75%) achieved a DLQI score of 0; n=5 (12.5%) achieved a DLQI score of 1; n=1 (2.5%) achieved a DLQI score of 10 (due to lack of efficacy). Adverse Events: The proportion of patients that discontinued treatment due to AE’s was n=7 (9.8%). One patient experienced nausea alleviated by dose reduction; another developed significant dysgeusia for certain foods, both continued therapy. Two patients lost 2-3 kg. Conclusion: Initial Irish patient experience of Apremilast appears comparable to that observed in trials with good efficacy and tolerability.

Keywords: Apremilast, introduction, Ireland, clinical audit

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Authors: Andrew Anis Fakhrey Mosaad

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The goal of this study is to compare the efficacy of polarised light therapy with low-intensity laser therapy in treating oral mucositis brought on by chemotherapy in cancer patients. Evaluation procedures are the measurement of the WHO oral mucositis scale and the Common toxicity criteria scale. Techniques: Cancer patients (men and women) who had oral mucositis, ulceration, and discomfort and whose ages varied from 30 to 55 years were separated into two groups and received 40 chemotherapy treatments. Twenty patients in Group (A) received low-level laser therapy (LLLT) along with their regular oral mucositis medication treatment, while twenty patients in Group (B) received Bioptron light therapy (BLT) along with their regular oral mucositis medication treatment. Both treatments were applied for 10 minutes each day for 30 days. Conclusion and results: This study showed that the use of both BLT and LLLT on oral mucositis in cancer patients following chemotherapy greatly improved, as seen by the sharp falls in both the WHO oral mucositis scale (OMS) and the common toxicity criteria scale (CTCS). However, low-intensity laser therapy (LLLT) was superior to Bioptron light therapy in terms of benefits (BLT).

Keywords: Bioptron light therapy, low level laser therapy, oral mucositis, WHO oral mucositis scale, common toxicity criteria scale

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Authors: Shizra Waris, Bilal Shoaib, Munib Ahmad

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Background; The using of clinical decision support systems (CDSSs) may recover unceasing disease organization, which requires regular visits to multiple health professionals, treatment monitoring, disease control, and patient behavior modification. The objective of this survey is to determine if these CDSSs improve the processes of unceasing care including diagnosis, treatment, and monitoring of diseases. Though artificial intelligence is not a new idea it has been widely documented as a new technology in computer science. Numerous areas such as education business, medical and developed have made use of artificial intelligence Methods: The survey covers articles extracted from relevant databases. It uses search terms related to information technology and viral hepatitis which are published between 2000 and 2016. Results: Overall, 80% of studies asserted the profit provided by information technology (IT); 75% of learning asserted the benefits concerned with medical domain;25% of studies do not clearly define the added benefits due IT. The CDSS current state requires many improvements to hold up the management of liver diseases such as HCV, liver fibrosis, and cirrhosis. Conclusion: We concluded that the planned model gives earlier and more correct calculation of hepatitis B and it works as promising tool for calculating of custom hepatitis B from the clinical laboratory data.

Keywords: detection, hapataties, observation, disesese

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Authors: Joao Paulo De Oliveira Paschoal, Andre Victor Rodrigues Dantas, Fernando Almeida Da Silva Fernandes, Eugenio Jose Zoqui

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With the adoption of High Pressure Die Casting technologies for the production of automotive bodies by the famous Giga Castings, the technology of processing metal alloys in the semi-solid state (SSM) becomes interesting because it allows for higher product quality, such as lower porosity and shrinkage voids. However, the alloys currently processed are derived from the foundry industry and are based on the Al-Si-(Cu-Mg) system. High-strength alloys, such as those of the Al-Zn-Mg-Cu system, are not usually processed, but the benefits of using this system, which is susceptible to heat treatments, can be associated with the advantages obtained by processing in the semi-solid state, promoting new possibilities for production routes and improving product performance. The current work proposes a new range of alloys to be processed in the semi-solid state through the modification of aluminum alloys of the Al-Zn-Mg-Cu system by the in-situ formation of Al3Ti intermetallic. Such alloys presented the thermodynamic stability required for semi-solid processing, with a sensitivity below 0.03(Celsius degrees * -1), in a wide temperature range. Furthermore, these alloys presented high hardness after aging heat treatment, reaching 190HV. Therefore, they are excellent candidates for the manufacture of parts that require low levels of defects and high mechanical strength.

Keywords: aluminum alloys, semisolid metals processing, intermetallics, heat treatment, titanium aluminide

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Authors: S. I. Nwadioha, M. S. Odimayo, G. T. A. Jombo, E. O. P. Nwokedi

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Aims and Objectives: To determine the baseline CD4 positive T lymphocytes count of HIV/AIDS treatment naïve adults clients presenting for the first time treatment in Benue State University Teaching Hospital. Subjects and Methods: A total of 700 subjects age between 18 years to 70 years, were recruited for the study, comprising 600 HIV sero-positive patients and 100 healthy controls in Benue State University Teaching Hospital, Makurdi from 2013 to 2014. The CD4 counts of the subjects were evaluated using a Partec flow cytometer. Results: CD4 count of 200-299 cells/μl peaked with 25% (n=150/600)[control; 0%( n= 0/100)]. The study also showed that 44% (266/600) of HIV subjects had acquired immunodeficiency syndrome as defined by low CD4 counts below 200 cells/μl. Seventy-five per cent (n=451/600)of our patients would require to be placed on antiretroviral therapy with CD4 count of less than 350 cells/μl. At CD4 350 baseline criterion, age group 20-29 years had the highest demand 35%(160/451) for ARV followed by age groups 30-39 and 40-49 years with 28%(128/451) and 22%(98/451) respectively. Conclusion: There is a high prevalence of acquired immunodeficiency syndrome as defined by CD4 counts below 200 cells/μl, among the young active productive age group. The strict adopting of the ART WHO 2010 scale- up criteria doubles the number of the HIV clients that would qualify for ART with its attendant health benefits on the long run.

Keywords: CD4 counts, HIV patients, young age group, Nigeria

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Authors: Ahmed A. Abd El Rahim, Andrew Anis Fakhrey Mosaad

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Background: An important psychological issue that has an impact on both mental and physical function is anxiety disorders. The general consensus is that aerobic exercise and physical activity are good for lowering anxiety and mood. Purpose: This study's goal was to look into how patients with anxiety disorders responded to aerobic exercise. Subjects: Anxiety disorders were identified in 30 individuals from the psychiatric hospital at Sohag University who were chosen based on inclusive criteria and had ages ranging from 25 to 45. Methods: Patients were split into two equal groups at random: For four weeks, three sessions per week, fifteen patients in group A (the study group), seven men and eight women, underwent medication therapy and aerobic exercise. Age (28.4 ± 2.11 years), weight (72.5 ± 10.06 kg), height (164.8 ± 9.64 cm), and BMI (26.65 ± 2.68 kg/m2) were all mean SD values. And in Group B (Control Group), only medication therapy was administered to 15 patients (9 males and 6 females). Age (29.6 ± 3.68), weight (75 ± 7.07 kg), height (166.9 ± 6.75) cm, and BMI (26.87 ± 1.11) kg/m2 were the mean SD values. Before and after the treatment, the Hamilton Anxiety Scale was used to gauge the patient's degree of anxiety. Results: Within the two groups, there were significant differences both before and after the treatment. Following therapy, there was a significant difference between the two groups; the study group displayed better improvement on the Hamilton Anxiety Scale. Conclusion: Patients with anxiety problems can benefit from aerobic activities and antianxiety drugs as effective treatments for lowering anxiety levels.

Keywords: aerobic exercises, anxiety disorders, antianxiety medications, Hamilton anxiety scale

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Authors: Vibha Kriti

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Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder generally found in reproductive women. It is associated with significant reproductive, metabolic, cosmetic, and psychological consequences. Objective: There is a high prevalence of PCOS found among reproductive-age women, therefore, the major objective of the present study is to identify the illness perception of PCOS women and to explore the relationship between illness perception and health-related quality of life (HRQoL). Material and Method: A cross-sectional study was conducted in a university tertiary-care center, Sir Sunder Lal Hospital, Banaras Hindu University (B.H.U). Tools used for data collection were self-structured, which included socio-demographic status, illness perception questionnaire (revised version), and short-form 36 for assessing illness perception and health-related quality of life, respectively. Statistical analysis was done by SPSS version ‘24’. Results: The results of correlation analyses indicated that there is a strong relationship between strong illness perception and HRQoL. Stepwise regression indicated that illness identity, long illness duration, and severe consequences were associated with the worse outcome on emotional functioning and on social functioning. A high score on the controllability of the disease and seeking social support was significantly related to better functioning. Conclusion: Illness perception is an important factor in self-care behaviors in PCOS females and has a strong association with health-related quality of life and has a profound effect on it.

Keywords: polycystic ovary syndrome, illness perception, quality of life, young females, mental health

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Authors: A. A. M. Azoddein, R. M. Yunus, N. M. Sulaiman, A. B. Bustary, K. Sabar

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Microbes have been used to solve environmental problems for many years. The use microorganism to sequester, precipitate or alter the oxidation state of various heavy metals has been extensively studied. Processes by which microorganism interacts with toxic metal are very diverse. The purpose of this research is to remove the mercury using Pseudomonas putida, pure culture ATTC 49128 at optimum growth parameters such as techniques of culture, acclimatization time and speed of incubator shaker. Thus, in this study, the optimum growth parameters of P.putida were obtained to achieve the maximum of mercury removal. Based on the optimum parameters of Pseudomonas putida for specific growth rate, the removal of two different mercury concentration, 1 ppm and 4 ppm were studied. A mercury-resistant bacterial strain which is able to reduce ionic mercury to metallic mercury was used to reduce ionic mercury from mercury nitrate solution. The overall levels of mercury removal in this study were between 80% and 90%. The information obtained in this study is of fundamental for understanding of the survival of P.putida ATTC 49128 in mercury solution. Thus, microbial mercury environmental pollutants removal is a potential biological treatment for waste water treatment especially in petrochemical industries in Malaysia.

Keywords: Pseudomonas putida, growth kinetic, biosorption, mercury, petrochemical waste water

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Authors: Khushboo Bhavsar, Nisha K. Shah, Neha Parekh

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The status of wastewater treatment needs a novel and quick method for treating the wastewater containing ammoniacal nitrogen. Adsorption behavior of ammoniacal nitrogen from wastewater using the nanoparticles loaded coconut coir was investigated in the present work. Manganese Oxide (MnO2) and Zinc Oxide (ZnO) nanoparticles were prepared and used for the further adsorption study. Manganese nanoparticles loaded coconut coir (MNLCC) and Zinc nanoparticles loaded coconut coir (ZNLCC) were prepared via a simple method and was fully characterized. The properties of both MNLCC and ZNLCC were characterized by Scanning electron microscopy, Fourier Transform Infrared Spectroscopy and X-ray diffraction. Adsorption characteristics were studied using batch technique considering various parameters like pH, adsorbent dosage, time, temperature and agitation time. The NH3-N adsorption process for MNLCC and ZNLCC was thoroughly studied from both kinetic and equilibrium isotherm view-points. The results indicated that the adsorption efficiency of ZNLCC was better when compared to MNLCC. The adsorption kinetics at different experimental conditions showed that second order kinetic model best fits ensuring the monovalent binding sites existing in the present experimental system. The outcome of the entire study suggests that the ZNLCC can be a smart option for the treatment of the ammoniacal nitrogen containing wastewater.

Keywords: ammoniacal nitrogen, MnO2, Nanoparticles, ZnO

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Authors: Ikram Elsiddig, Yacouba Djamila, Amna Hamad

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Abstract—The worldwide increasing of using herbs in form of medicine with or without prescription medications potentiates the interactions between herbal products and conventional medicines; due to more research for herb-drug interactions are needed. for a long time hyperglycemia had been treated with several medicinal plants. A. sativum, belonging to the Liliaceae family is well known for its medicinal uses in African traditional medicine, it used for treating of many human diseases mainly diabetes, high cholesterol and high blood pressure. The purpose of this study is to determine the interaction effect between A. sativum bulb extracts and metformin drug used in diabetes treatment. The in vitro and in vivo evaluation were conducted by glucose reuptake using isolated rats hemidiaphgrams tissue and by estimate glucose tolerance in glucose-loaded wistar albino rats. The results showed that, petroleum ether, chloroform and ethyl acetate extracts were found to have activity of glucose uptake in isolated rats hemidiaphgrams of 24.11 mg/g, 19.07 mg/g and 15.66 mg/g compared to metformin drug of 17 mg/g. These activity were reducded to 17.8 mg/g, 13.59 mg/g and 14.46 mg/g after combination with metformin, metformin itself reduced to 13.59 mg/g, 14.46 mg/g and 12.71 mg/g in comination with chloroform and ethyl acetate. These decrease in activity could be due to herbal–drug interaction between the extracts of A. sativum bulb and metformin drug. The interaction between A. sativum extract and metformin was also shown by in vivo study on the induced hyperglycemic rats. The glucose level after administered of 200 mg/kg was found to be increase with 47.2 % and 17.7% at first and second hour compared to the increase of blood glucose in the control group of 82.6% and76.7%.. At fourth hour the glucose level was became less than normal with 3.4% compared to control which continue to increase with 68.2%. Dose of 400 mg/kg at first hour showed increase in blood glucose of 31.5 %, at second and fourth hours the glucose level was became less than normal with decrease of 3.2 % and 30.4%. After combination the activity was found to be less than that of extract at both high and low dose, whereas, at first and second hour, the glucose level was found to be increase with 50.4% and 21.2%, at fourth hour the glucose level was became less than normal with 14%. Therefore A. sativum could be a potential source for anti-diabetic when it used alone, and it is significant important to use the garlic extract alone instead of combined with Metformin drug in diabetes- treatment.

Keywords: Antagonistic, Garlic, Metformin, Synergistic

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Authors: Sumeeta Khurana, Kirti Megha, Amit Gupta, Rakesh Sehgal

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Background: Amoebic keratitis is a painful vision threatening infection caused by a free living pathogenic amoeba Acanthamoeba. It can be misdiagnosed and very difficult to treat if not suspected early. The epidemiology of Acanthamoeba genotypes causing infection in our geographical area is not yet known to the best of our knowledge. Objective: To characterize Acanthamoeba isolates from amoebic keratitis patients. Methods: A total of 19 isolates obtained from patients with amoebic keratitis presenting to the Advanced Eye Centre at Postgraduate Institute of Medical Education and Research, a tertiary care centre of North India over a period of last 10 years were included. Their corneal scrapings, lens solution and lens case (in case of lens wearer) were collected for microscopic examination, culture and molecular diagnosis. All the isolates were maintained in the Non Nutrient agar culture medium overlaid with E.coli and 13 strains were axenised and maintained in modified Peptone Yeast Dextrose Agar. Identification of Acanthamoeba genotypes was based on amplification of diagnostic fragment 3 (DF3) region of the 18srRNA gene followed by sequencing. Nucleotide similarity search was performed by BLAST search of sequenced amplicons in GenBank database (http//www.ncbi.nlm.nih.gov/blast). Multiple Sequence alignments were determined by using CLUSTAL X. Results: Nine out of 19 Acanthamoeba isolates were found to belong to Genotype T4 followed by 6 isolates of genotype T11, 3 T5 and 1 T3 genotype. Conclusion: T4 is the predominant Acanthamoeba genotype in our geographical area. Further studies should focus on differences in pathogenicity of these genotypes and their clinical significance.

Keywords: Acanthamoeba, free living amoeba, keratitis, genotype, ocular

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Authors: Tewelde Gebreslassie Gebreanenia, Frie Ayalew Yimam, Seada Hussen Adem

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Patient safety and quality of care are essential goals of health care delivery, but they are often compromised by human errors, system failures, or resource constraints. In a variety of healthcare contexts, artificial intelligence (AI), a quickly developing field, can provide fresh approaches to enhancing patient safety and treatment quality. Artificial Intelligence (AI) has the potential to decrease errors and enhance patient outcomes by carrying out tasks that would typically require human intelligence. These tasks include the detection and prevention of adverse events, monitoring and warning patients and clinicians about changes in vital signs, symptoms, or risks, offering individualized and evidence-based recommendations for diagnosis, treatment, or prevention, and assessing and enhancing the effectiveness of health care systems and services. This study examines the state-of-the-art and potential future applications of AI-based technologies for enhancing patient safety and care quality, as well as the opportunities and problems they present for patients, policymakers, researchers, and healthcare providers. In order to ensure the safe, efficient, and responsible application of AI in healthcare, the paper also addresses the ethical, legal, social, and technical challenges that must be addressed and regulated.

Keywords: artificial intelligence, health care, human intelligence, patient safty, quality of care

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Authors: Andrea Ghermandi

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Constructed wetlands have long been recognized as sources of ancillary benefits such as support for recreational activities. To date, there is a lack of quantitative understanding of the extent and welfare impact of such benefits. Here, it is shown how geotagged, passively crowdsourced data from online social networks (e.g., Flickr and Panoramio) and Geographic Information Systems (GIS) techniques can: (1) be used to infer annual recreational visits to 273 engineered wetlands worldwide; and (2) be integrated with non-market economic valuation techniques (e.g., travel cost method) to infer the monetary value of recreation in these systems. Counts of social media photo-user-days are highly correlated with the number of observed visits in 62 engineered wetlands worldwide (Pearson’s r = 0.811; p-value < 0.001). The estimated, mean willingness to pay for access to 115 wetlands ranges between $5.3 and $374. In 50% of the investigated wetlands providing polishing treatment to advanced municipal wastewater, the present value of such benefits exceeds that of the capital, operation and maintenance costs (lifetime = 45 years; discount rate = 6%), indicating that such systems are sources of net societal benefits even before factoring in benefits derived from water quality improvement and storage. Based on the above results, it is argued that recreational benefits should be taken into account in the design and management of constructed wetlands, as well as when such green infrastructure systems are compared with conventional wastewater treatment solutions.

Keywords: constructed wetlands, cultural ecosystem services, ecological engineering, social media

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Authors: Khairy M. A. Zoheir, Nehma A. Ali, Ahmed M. Darwish, Mohamed S. Kishta, Ahmed A. Abd-Rabou, Mohamed A. Abdelhafez, Karima F. Mahrous

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The study comprehensively investigated the multifaceted therapeutic properties of the IQGAP1shRNA plasmid, encompassing its hepatoprotective, immunomodulatory, and anticancer activities. The study employed a Prednisolone-induced immunosuppressed rat model to assess the hepatoprotective and immunomodulatory effects of IQGAP1shRNA plasmid. Using this model, IQGAP1shRNA plasmid was found to modulate haematopoiesis, improving RBC, platelet, and WBC counts, underscoring its potential in hematopoietic homeostasis. Organ atrophy, a hallmark of immunosuppression in spleen, heart, liver, ovaries, and kidneys, was reversed with IQGAP1shRNA plasmid treatment, reinforcing its hepatotrophic and organotropic capabilities. Elevated hepatic biomarkers (ALT, AST, ALP, LPO) indicative of hepatocellular injury and oxidative stress were reduced with GST, highlighting its hepatoprotective and antioxidative effects. IQGAP1shRNA plasmid also restored depleted antioxidants (GSH and SOD), emphasizing its potent antioxidative and free radical scavenging capabilities. Molecular insights into immune dysregulation revealed downregulation of IQGAP1, IQGAP3 interleukin-2 (IL-2), and interleukin-4 (IL-4) mRNA expression in the liver of immunosuppressed rats. IL-2 and IL-4 play pivotal roles in immune regulation, T-cell activation, and B-cell differentiation. Notably, treatment with IQGAP1shRNA plasmid exhibited a significant upregulation of IL-2 and IL-4 mRNA expression, thereby accentuating its immunomodulatory potential in orchestrating immune homeostasis. Additionally, immune dysregulation was associated with increased levels of TNF-α. However, treatment with IQGAP1shRNA plasmid effectively decreased the levels of TNF-α, further underscoring its role in modulating inflammatory responses and restoring immune balance in immunosuppressed rats. Additionally, pharmacokinetics, bioavailability, drug-likeness, and toxicity risk assessment prediction suggest its potential as a pharmacologically favourable agent with no serious adverse effects. In conclusion, this study confirms the therapeutic potential of the IQGAP1shRNA plasmid, showcasing its effectiveness against hepatotoxicity, oxidative stress, immunosuppression, and its notable anticancer activity.

Keywords: IQGAP1, shRNA, cancer, liver, rat

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Authors: Sarayu Vanga, Jorge Galeano-Cabral, Kaya Wei

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Cerebral hypoxia refers to a condition in which there is a decrease in oxygen supply to the brain. Patients suffering from this condition experience a decrease in their body temperature. While there isn't any cure to treat cerebral hypoxia as of date, certain procedures are utilized to help aid in the treatment of the condition. Regulating the body temperature is an example of one of those procedures. Hypoxia is well known to reduce the body temperature of mammals, although the neural origins of this response remain uncertain. In order to speed recovery from this condition, it is necessary to maintain a stable body temperature. In this study, we present an approach to regulating body temperature for patients who suffer from cerebral hypoxia or other similar conditions. After a thorough literature study, we propose the use of thermoelectric blankets, which are temperature-controlled thermal blankets based on thermoelectric devices. These blankets are capable of heating up and cooling down the patient to stabilize body temperature. This feature is possible through the reversible effect that thermoelectric devices offer while behaving as a thermal sensor, and it is an effective way to stabilize temperature. Thermoelectricity is the direct conversion of thermal to electrical energy and vice versa. This effect is now known as the Seebeck effect, and it is characterized by the Seebeck coefficient. In such a configuration, the device has cooling and heating sides with temperatures that can be interchanged by simply switching the direction of the current input in the system. This design integrates various aspects, including a humidifier, ventilation machine, IV-administered medication, air conditioning, circulation device, and a body temperature regulation system. The proposed design includes thermocouples that will trigger the blanket to increase or decrease a set temperature through a medical temperature sensor. Additionally, the proposed design allows an efficient way to control fluctuations in body temperature while being cost-friendly, with an expected cost of 150 dollars. We are currently working on developing a prototype of the design to collect thermal and electrical data under different conditions and also intend to perform an optimization analysis to improve the design even further. While this proposal was developed for treating cerebral hypoxia, it can also aid in the treatment of other related conditions, as fluctuations in body temperature appear to be a common symptom that patients have for many illnesses.

Keywords: body temperature regulation, cerebral hypoxia, thermoelectric, blanket design

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Authors: R. G. Shemi, M. A. Abo Horish, Kh. M. A. Mekled

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The utilization of silicon (Si) sources is a crucial agricultural tool that requires optimization to promote sustainable practices. The application of Si provides the implementation of biological mechanisms of plant nutrition, growth promotion, and protection. The aims of this experiment were to investigate the relative efficacy of Si sources and levels on the growth, yield, and mineral content of wheat. The study examined the effects of silicon sulphate and silicic acid levels on growth, spike characteristics, yield parameters, and macro- and micronutrient concentrations of wheat during the 2-season. The entire above-indicated parameters were significantly (p < 0.05) increased with increasing levels of silicon sulphate and silicic acid compared to the control. Foliar application of silicon sulphate 150 ppm and silicic acid 60 ppm statistically (p < 0.05) enhanced grain N concentration and the grain yield by 136.14 and 77.85%, 43.49 and 34.52% in the 1st season, and by 78.62 and 54.40%, 43.53 and 33.18% in the 2nd season, respectively, as compared with control. Overall, foliar applications of silicon sulphate at 150 ppm and silicic acid at 60 ppm were greatly efficient amongst all Si levels and sources in improving growth and spike characters, increasing yield parameters, and elevating grain nutrients. Finally, the treatment of silicon sulfate at 150 ppm was more effective than the treatment of silicic acid at 60 ppm in increasing growth, grain nutrients, and productivity of wheat and attaining agricultural sustainability under experiment conditions.

Keywords: wheat, silicon sulphate, silicic acid, grain nutrients

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Authors: Emad Heydarnia, Aref Sepasi, Nika Asefi, Sara Khakshournia, Javad Mohammadnejad

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Background: Despite breakthrough therapeutics in breast cancer, it is one of the main causes of mortality among women worldwide. Thus, drug therapies for treating breast cancer have recently been developed by scientists. Metformin and Sorafenib are well-known therapeutic in breast cancer. In the present study, we combined Sorafenib and PCL-sorafenib with metformin to improve drug absorption and promote therapeutic efficiency. Methods: The MCF-7 cells were treated with Metformin, Sorafenib, or PCL-sorafenib. The growth inhibitory effect of these drugs and cell viability were assessed using MTT and flow cytometry assays, respectively. The expression of targeted genes involved in cell proliferation, signaling, and the cell cycle was measured by Real-time PCR. Results: The results showed that MCF-7 cells treated with Metformin/Sorafenib and PCL-sorafenib/Metformin co-treatment contributed to 50% viability compared to untreated group. Moreover, PI and Annexin V staining tests showed that the cells viability for Metformin/Sorafenib and PCL-sorafenib/Metformin was 38% and 17%, respectively. Furthermore, Sorafenib/Metformin and PCL-sorafenib/Metformin leads to p53 gene expression increase by which they can increase ROS, thereby decreasing GPX4 gene expression. In addition, they affected the expression of BCL2, and BAX genes and altered the cell cycle. Conclusion: Together, the combination of PCL-sorafenib/Metformin and Sorafenib/Metformin increased Sorafenib absorption at lower doses and also leads to apoptosis and oxidative stress increases in MCF-7 cells.

Keywords: breast cancer, metformin, nanotechnology, sorafenib

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Authors: Delphine Morales, Florian Lombart, Agathe Truchot, Pauline Maire, Pascale Vigneron, Antoine Galmiche, Catherine Lok, Muriel Vayssade

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Targeted therapy molecules are used as a first-line treatment for metastatic melanoma with B-Raf mutation. Nevertheless, these molecules can cause side effects to patients and are efficient on 50 to 60 % of them. Indeed, melanoma cell sensitivity to targeted therapy molecules is dependent on tumor microenvironment (cell-cell and cell-extracellular matrix interactions). To better unravel factors modulating cell sensitivity to B-Raf inhibitor, we have developed and compared several melanoma models: from metastatic melanoma cells cultured as monolayer (2D) to a co-culture in a 3D dermal equivalent. Cell response was studied in different melanoma cell lines such as SK-MEL-28 (mutant B-Raf (V600E), sensitive to Vemurafenib), SK-MEL-3 (mutant B-Raf (V600E), resistant to Vemurafenib) and a primary culture of dermal human fibroblasts (HDFn). Assays have initially been performed in a monolayer cell culture (2D), then a second time on a 3D dermal equivalent (dermal human fibroblasts embedded in a collagen gel). All cell lines were treated with Vemurafenib (a B-Raf inhibitor) for 48 hours at various concentrations. Cell sensitivity to treatment was assessed under various aspects: Cell proliferation (cell counting, EdU incorporation, MTS assay), MAPK signaling pathway analysis (Western-Blotting), Apoptosis (TUNEL), Cytokine release (IL-6, IL-1α, HGF, TGF-β, TNF-α) upon Vemurafenib treatment (ELISA) and histology for 3D models. In 2D configuration, the inhibitory effect of Vemurafenib on cell proliferation was confirmed on SK-MEL-28 cells (IC50=0.5 µM), and not on the SK-MEL-3 cell line. No apoptotic signal was detected in SK-MEL-28-treated cells, suggesting a cytostatic effect of the Vemurafenib rather than a cytotoxic one. The inhibition of SK-MEL-28 cell proliferation upon treatment was correlated with a strong expression decrease of phosphorylated proteins involved in the MAPK pathway (ERK, MEK, and AKT/PKB). Vemurafenib (from 5 µM to 10 µM) also slowed down HDFn proliferation, whatever cell culture configuration (monolayer or 3D dermal equivalent). SK-MEL-28 cells cultured in the dermal equivalent were still sensitive to high Vemurafenib concentrations. To better characterize all cell population impacts (melanoma cells, dermal fibroblasts) on Vemurafenib efficacy, cytokine release is being studied in 2D and 3D models. We have successfully developed and validated a relevant 3D model, mimicking cutaneous metastatic melanoma and tumor microenvironment. This 3D melanoma model will become more complex by adding a third cell population, keratinocytes, allowing us to characterize the epidermis influence on the melanoma cell sensitivity to Vemurafenib. In the long run, the establishment of more relevant 3D melanoma models with patients’ cells might be useful for personalized therapy development. The authors would like to thank the Picardie region and the European Regional Development Fund (ERDF) 2014/2020 for the funding of this work and Oise committee of "La ligue contre le cancer".

Keywords: 3D human skin model, melanoma, tissue engineering, vemurafenib efficiency

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Authors: Kai-Cheng Hsu, Tzu-Ying Sung, Jinn-Moon Yang

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Colorectal cancer (CRC) is one of the main causes of cancer death in the world. Although several drugs have been developed to treat colorectal cancer, such as Regorafenib and 5-FU, their efficacy is often limited by the development of drug resistance. Therefore, development of new drugs with new scaffolds is necessary to treat CRC. Here, we used site-moiety maps to identify inhibitors against PIM1, LIMK1, SRC, and mTOR, which are often overexpressed in CRC. A site-moiety map represents physicochemical properties and moiety preferences of a binding site through anchors. An anchor contains three elements: (1) conserved interacting residues of a binding pocket; (2) moiety preference of the binding pocket; and (3) the type (e.g., hydrogen-bonding or van der Waals interactions) of interaction between the moieties and the binding pocket. Then, we performed a structure-based virtual screening of ~260,000 compounds and selected compound candidates with high site-moiety map scores for bioassays. Among these candidates, compound 1 and compound 2 inhibited the growth of CRC cells with IC50 values of <10 μM. The experimental result of enzyme-based assays indicated that compound 1 is a dual inhibitor against PIM1 (IC50 6 μM) and LIMK1(IC50 11 μM). Compound 2 was predicted as a SRC inhibitor and will be further validated. The compounds inhibited different protein targets compared to the current drugs. We believe that the compounds provide a starting point to design new drugs for CRC treatment.

Keywords: colorectal cancer, drug discovery, site-moiety map, virtual screening, PIM1, LIMK1

Procedia PDF Downloads 246