Search results for: anti-tubercular therapy induced hepatotoxicity

Authors: Sharique Ahmed, Khushtar Anwar Salman

Abstract:

Alpha-1-antitrypsin (AAT) is a major plasma serine protease inhibitor (SERPIN). Hereditary AAT deficiency is one of the common diseases in some part of the world. AAT is mainly produced in the liver and functions to protect the lung against proteolytic damage (e.g., from neutrophil elastase) acting as the major inhibitor for neutrophil elastase. α (1)-Antitrypsin (AAT) deficiency is an under recognized genetic condition that affects approximately 1 in 2,000 to 1 in 5,000 individuals and predisposes to liver disease and early-onset emphysema. Not only does α-1-antitrypsin deficiency lead to disabling syndrome of pulmonary emphysema, there are other disorders too which include ANCA (antineutrophilic cytoplasmic antibody) positive Wegener's granulomatosis, diffuse bronchiectasis, necrotizing panniculitis in α-1-antitrypsin phenotype (S), idiopathic pulmonary fibrosis and steroid dependent asthma. Augmentation therapy with alpha-1 antitrypsin (AAT) from human plasma has been available for specific treatment of emphysema due to AAT deficiency. Apart from this several observations have also suggested a role for endogenous suppressors of HIV-1, alpha-1 antitrypsin (AAT) has been identified to be one of those. In view of its varied important role in humans, serum from a mammalian source was chosen for the isolation and purification. Studies were performed on the homogeneous fraction. This study suggests that the buffalo serum α-1-antritrypsin has characteristics close to ovine, dog, horse and more importantly to human α-1-antritrypsin in terms of its hydrodynamic properties such as molecular weight, carbohydrate content, etc. The similarities in the hydrodynamic properties of buffalo serum α-1-antitrypsin with other sources of mammalian α-1-antitrypsin mean that it can be further studied and be a potential source for "augmentation therapy", as well as a source of AAT replacement therapy to raise serum levels above the protective threshold. Other parameters like the amino acid sequence, the effect of denaturants, and the thermolability or thermostability of the inhibitor will be the interesting basis of future studies on buffalo serum alpha-1 antitrypsin (AAT).

Keywords: α-1-antitrypsin, augmentation therapy , hydrodynamic properties, serine protease inhibitor

Procedia PDF Downloads 489

Authors: Mansi Patel, Priti Mehta

Abstract:

Background: Ionizing radiations have detrimental effects on humans, and the growing technological encroachment has increased human exposure to it enormously. So, the safety issues have emphasized researchers to develop radioprotector from natural resources having minimal toxicity. A substance having anti-inflammatory, antioxidant, and immunomodulatory activity can be a potential candidate for radioprotection. One such plant with immense potential i.e. Bamboo was selected for the present study. Purpose: The study aims to evaluate the potential of Indian bamboo leaves for protection against the clastogenic effect of gamma radiation. Methods: The protective effect of bamboo leaf extract against gamma radiation-induced genetic damage in human peripheral blood lymphocytes (HPBLs) was evaluated in vitro using Cytokinesis blocked micronuclei assay (CBMN). The blood samples were pretreated with varying concentration of extract 30 min before the radiation exposure (4Gy & 6Gy). The reduction in the frequency of micronuclei was observed for the irradiated and control groups. The effect of various concentration of bamboo leaf extract (400,600,800 mg/kg) on the development of radiation induced sickness and altered mortality in mice exposed to 8 Gy of whole-body gamma radiation was studied. The developed symptoms were clinically scored by multiple endpoints for 30 days. Results: Treatment of HPBLs with varying concentration of extract before exposure to a different dose of γ- radiation resulted in significant (P < 0.0001) decline of radiation induced micronuclei. It showed dose dependent and concentration driven activity. The maximum protection ~ 70% was achieved at nine µg/ml concentration. Extract treated whole body irradiated mice showed 50%, 83.3% and 100% survival for 400, 600, and 800mg/kg with 1.05, 0.43 and 0 clinical score respectively when compared to Irradiated mice having 6.03 clinical score and 0% survival. Conclusion: Our findings indicate bamboo leaf extract reduced the radiation induced cytogenetic damage. It has also increased the survival ratio and reduced the radiation induced sickness and mortality when exposed to a lethal dose of gamma radiation.

Keywords: bamboo leaf extract, Cytokinesis blocked micronuclei (CBMN) assay, ionizing radiation, radio protector

Procedia PDF Downloads 145

Authors: Sadaf Ilyas

Abstract:

Recombinant cytokines have been employed successfully as potential therapeutic agent. Some cytokine therapies are already used as a part of clinical practice, ranging from early exploratory trials to well established therapies that have already received approval. Interleukin 15 is a pleiotropic cytokine having multiple roles in peripheral innate and adaptive immune cell function. It regulates the activation, proliferation and maturation of NK cells, T-cells, monocytes/macrophages and granulocytes, and the interactions between them thus acting as a bridge between innate and adaptive immune responses. Unraveling the biology of IL-15 has revealed some interesting surprises that may point toward some of the first therapeutic applications for this cytokine. In this study, the human interleukin 15 gene was isolated, amplified and ligated to a TA vector which was then transfected to a bacterial host, E. coli Top10F’. The sequence of cloned gene was confirmed and it showed 100% homology with the reported sequence. The confirmed gene was then subcloned in pET Expression system to study the IPTG induced expression of IL-15 gene. Positive expression was obtained for number of clones that showed 15 kd band of IL-15 in SDS-PAGE analysis, indicating the successful strain development that can be studied further to assess the potential therapeutic intervention of this cytokine in relevance to human diseases.

Keywords: Interleukin 15, pET expression system, immune therapy, protein purification

Procedia PDF Downloads 413

Authors: Akshada Amit Koparde, Candrakant S. Magdum

Abstract:

Objective: To investigate the anti-arthritic activity of chloroform extract and Isolate 1 of Eulophia ochreata Lindl and dichloromethane extract and Isolate 2 of Zingiber cassumunar Roxb in adjuvant arthritic (AA) rat model induced by Freund’s complete adjuvant (FCA). Methods: Forty two healthy albino rats were selected and randomly divided into six groups. Freund’s complete adjuvant (FCA) was used to induce arthritis and then treated with chloroform extract, isolate 1 and dichloromethane extract, isolate 2 for 28 days. The various parameters like paw volume, haematological parameters (RBC, WBC, Hb and ESR), were studied. Structural elucidation of active constituents isolate 1 and isolate 2 from Eulophia ochreata Lindl and Zingiber cassumunar Roxb will be done using GCMS and H1NMR. Results: In FCA induced arthritic rats, there was significant increase in rat paw volume whereas chloroform extract and Isolate 1 of Eulophia ochreata Lindl and dichloromethane extract and Isolate 2 of Zingiber cassumunar Roxb treated groups showed strong significant reduction in paw volume. The altered haematological parameters in the arthritic rats were significantly recovered to near normal by the treatment with extracts at the dose of 200 mg/kg. Further histopathological studies revealed the anti-arthritic activity of Eulophia ochreata Lindl and Zingiber cassumunar Roxb by preventing cartilage and bone destruction of the arthritic joints of AA rats. Conclusion: Extracts and isolates of Eulophia ochreata Lindl and Zingiber cassumunar Roxb have shown anti-arthritic activity. Decrease in paw volume and normalization of haematological abnormalities in adjuvant induced arthritic rats is significantly seen in the experiment. Further histopathological studies confirmed the anti-arthritic activity of Eulophia ochreata Lindl and Zingiber cassumunar Roxb.

Keywords: arthritis, Eulophia ochreata Lindl, Freund's complete adjuvant, paw volume, Zingiber cassumunar Roxb

Procedia PDF Downloads 176

Authors: Mohammed F. Alhaddad

Abstract:

Vortex induced Vibrations (VIV) is a phenomenon that occurs as a result of a flow passing by a bluff body. This phenomenon has been mainly studied to be suppressed to prevent fatigue and instability in offshore platforms. In 2006, some studies were conducted to maximize VIV instead of suppressing it, as these studies claimed that VIV is a potential method of generating energy. The aim of this paper is to identify factors for maximizing oscillation amplitude generated by VIV in order to enhance the energy harnessed through this method. The experimental study in this paper will examine the effect of oscillating cylinder diameter, surface roughness, the location of surface roughness with respect to the centerline of the oscillating cylinder and the velocity on the oscillation amplitude of the used module.

Keywords: energy, generation, generating, vibration, vortex.

Procedia PDF Downloads 61

Authors: Mohamed Amine Adaour, Mohamed Sadek Bachene, Mosaab Fortassi, Wafaa Siouda

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Foot infections are responsible for a significant number of hospitalizations and amputations in diabetic patients. The objective of our study is to analyze and evaluate the management of diabetic foot in a surgical setting. A retrospective study was conducted based on a selected case of suspected diabetic foot infections of osteitis treated at the Mohamed Boudiaf hospital in Medea. The case was reiterated as a therapeutic charge, consisting of treating first the infection of the soft tissues, then the osteitis: biopsy after at least 15 days of cessation of antibiotic therapy. Successful treatment of osteitis was defined at the end of a follow-up period of complete wound healing, lack of bone resection/amputation surgery at the initial bone site during follow-up , Instead, biopsies are prescribed in the treatment of soft tissue infection. The mean duration of treatment for soft tissue infection was 2-3 weeks, the duration of the antibiotic-free window of therapy prior to bone biopsy was 2-4 weeks. This patient received medical management without surgical resection. The success rate for treating osteitis at one year was 73%, and healing at one year was 88%.It is often limited to a sausage of the foot at the cost of repeated amputations. The best management remains prevention, which necessarily involves setting up a specialized and adapted centre.

Keywords: osteitis, antibiotic therapy, bone biopsy, diabetic foot

Procedia PDF Downloads 79

Authors: Alan S. Weber

Abstract:

This contribution reviews the current biomedical and qualitative arts research on arts-in-health interventions to improve both individual and population health outcomes. Arts therapies–for example, music therapy with roots in Aristoxenus’s Ἁρμονικὰ στοιχεῖα and the Pythagorean sect–have long been employed in therapeutic contexts. However, the 20th century witnessed the increasing use of the visual and plastic arts (drawing, painting, sculpting), performing arts (drama and dance), and other expressive arts modalities into occupational therapy, well-being medicine, and psychological and psychiatric counselling, diagnosis, and treatment. A significant body of peer-reviewed evidence in the medical and neurological sciences on the role of arts-in-health has developed, and specifically, research on music and art therapy has led to their inclusion within the current biomedical paradigm of evidence-based practice. The arts cannot only aid in public and population health promotion (promoting healthy behaviors and lifestyles, preventing disease onset) but also in addressing psychological issues (regulation of emotion; stress, anxiety, and depression reduction), behavioural issues (basic life skills, coping), and physiological response (immune system function, hormonal regulation, homeostatis). Working as a cross-disciplinary researcher in the arts in an American medical college, the author has developed several successful arts-in-health programs at the national and international level.

Keywords: arts-in-health, evidence based medicine, arts for health, expressive arts therapies

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Authors: Hamad Alhamad, Catriona Khamisha, Emma Green, Yvonne Robb

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Introduction: Practice education is a key component of occupational therapy education. This critical review aimed to explore students’ and clinical supervisors’ experiences of practice education, and to make recommendations for research. Method: The literature was systematically searched using five databases. Qualitative, quantitative and mixed methods studies were included. Critical Appraisal Skills Programme checklist for qualitative studies and Mixed Methods Assessment Tool for quantitative and mixed methods studies were used to assess study quality. Findings: Twenty-two studies with high quality scores were included: 16 qualitative, 3 quantitative and 3 mixed methods. Studies were conducted in Australia, Canada, USA and UK. During practice education, students learned professional skills, practical skills, clinical skills and problem-solving skills, and improved confidence and creativity. Supervisors had an opportunity to reflect on their practice and get experience of supervising students. However, clear objectives and expectations for students, and sufficient theoretical knowledge, preparation and resources for supervisors were required. Conclusion: Practice education provides different skills and experiences, necessary to become competent professionals; but some areas of practice education need to improve. Studies in non-western countries are needed to explore the perspectives of students and clinical supervisors in different cultures, to ensure the practice education models adopted are relevant.

Keywords: occupational therapy, practice education, fieldwork, students, clinical supervisors

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Authors: Turker Yardan, Bahattin Avci, S. Sirri Bilge, Ayhan Bozkurt

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Sinapic acid (SA) is a phenylpropanoid compound with anti-inflammatory, antioxidant, and neuroprotective activities. The purpose of this study was to characterize the possible protective effect of sinapic acid on chlorpyrifos (CPF), a common organophosphorus pesticide used worldwide, induced toxicity in rats. Forty male and female rats (240-270 g) were used in this study. Each group was composed of 5 male and 5 female rats. Sinapic acid (20 mg/kg or 40 mg/kg) or vehicle (olive oil, 1 ml ⁄ rat) were given orally for 5 days. CPF (279 mg/kg) or vehicle (peanut oil, 2 ml ⁄ kg, s.c.) was administered on the sixth day, immediately after the recording of the body weight of the animals. Twenty four hours following CPF administration body weight, body temperature and locomotor activity values were recorded before decapitation of the animals. Trunk blood, brain, and liver samples were collected for biochemical examinations. Chlorpyrifos administration decreased butyrylcholinesterase activity in blood, brain, and liver, while it increased malondialdehyde (MDA) levels and advanced oxidation protein products (AOPPs) (p < 0.01 - 0.001). Additionally, CPF administration reduced the body weight, body temperature, and locomotor activity values of the animals (p < 0.01 - 0.001). All these physiological and biochemical changes induced by CPF were reduced with the 40 mg/kg dose of SA (p < 0.05 - 0.001). Our results suggest that SA administration ameliorates CPF induced toxicity in rats, possibly by supporting the antioxidant mechanism.

Keywords: antioxidant, Chlorpyrifos, poisoning, sinapic acid

Procedia PDF Downloads 178

Authors: Michela Terlizzi, Chiara Colarusso, Aldo Pinto, Rosalinda Sorrentino

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Sphingosine-1-phosphate (S1P) is a membrane-derived bioactive phospholipid exerting a multitude of effects on respiratory cell physiology and pathology through five S1P receptors (S1PR1-5). Higher levels of S1P have been registered in a broad range of respiratory diseases, including inflammatory disorders and cancer, although its exact role is still elusive. Based on our previous study in which we found that S1P/S1PR3 is involved in an inflammatory pattern via the activation of Toll-like Receptor 9 (TLR9), highly expressed on lung cancer cells, the main goal of the current study was to better understand the involvement of S1P/S1PR3 pathway/signaling during lung carcinogenesis, taking advantage of a mouse model of first-hand smoke exposure and of carcinogen-induced lung cancer. We used human samples of Non-Small Cell Lung Cancer (NSCLC), a mouse model of first-hand smoking, and of Benzo(a)pyrene (BaP)-induced tumor-bearing mice and A549 lung adenocarcinoma cells. We found that the intranuclear, but not the membrane, localization of S1PR3 was associated to the proliferation of lung adenocarcinoma cells, the mechanism that was correlated to human and mouse samples of smoke-exposure and carcinogen-induced lung cancer, which were characterized by higher utilization of S1P. Indeed, the inhibition of the membrane S1PR3 did not alter tumor cell proliferation after TLR9 activation. Instead, according to the nuclear localization of sphingosine kinase (SPHK) II, the enzyme responsible for the catalysis of the S1P last step synthesis, the inhibition of the kinase completely blocked the endogenous S1P-induced tumor cell proliferation. These results prove that the endogenous TLR9-induced S1P can on one side favor pro-inflammatory mechanisms in the tumor microenvironment via the activation of cell surface receptors, but on the other tumor progression via the nuclear S1PR3/SPHK II axis, highlighting a novel molecular mechanism that identifies S1P as one of the crucial mediators for lung carcinogenesis-associated inflammatory processes and that could provide differential therapeutic approaches especially in non-responsive lung cancer patients.

Keywords: sphingosine-1-phosphate (S1P), S1P Receptor 3 (S1PR3), smoking-mice, lung inflammation, lung cancer

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Authors: Sultana Razia

Abstract:

The number of children whose social, communication and behavior pattern is affected due to mental and developmental conditions is on the rise. Most of these conditions develop to uncontrollable levels because of ignorance and unaware about their child’s condition. The many myths surrounding mental or developmental conditions are a major cause of families of affected children to develop bitterness and to shy off from seeking appropriate help in time. Several early intervention programs have been put in place, and the number of beneficiaries of these programs is increasing by the day. This research seeks to look into early intervention programs and their effectiveness. The purpose of this study was to investigate the effect of early therapeutic intervention for the children with autism spectrum disorder. Participants were 140 children with autism spectrum disorder from Autism Corner in a selected rehabilitation center of Bangladesh. This study included children who are at age of 18-month to 36-month and who were taking occupational therapy and speech and language therapy from the autism center. They were primarily screened using M-CHAT; however, children with other physical disability or medical conditions excluded. 3-months interventions of 6 sessions per week are a minimum of 45-minutes long per session, one to one interaction followed by parent-led structured home-based therapy were provided. The results indicated that early intensive therapeutic intervention improve understanding, social skills and sensory skills. It can be concluded that therapeutic early intervention a positive effect on diminishing symptoms of Autism Spectrum Disorder.

Keywords: M-CHAT, ASD, sensory cheeklist, OT

Procedia PDF Downloads 74

Authors: Charles Shang, Salina Ramirez, Stephen Shang, Maria Estrada, Timothy R. Williams

Abstract:

Purpose: Over the past decade, proton therapy utilizing pencil beam scanning has emerged as a preferred treatment modality in radiation oncology, particularly for prostate cancer. This retrospective study aims to assess the clinical and radiobiological efficacy of proton scanning beam therapy in the treatment of localized salvage prostate cancer, following initial radiation therapy with a different modality. Despite the previously delivered high radiation doses, this investigation explores the potential of proton reirradiation in controlling recurrent prostate cancer and detrimental quality of life side effects. Methods and Materials: A retrospective analysis was conducted on 45 cases of locally recurrent prostate cancer that underwent salvage proton reirradiation. Patients were followed for 24.6 ± 13.1 months post-treatment. These patients had experienced an average remission of 8.5 ± 7.9 years after definitive radiotherapy for localized prostate cancer (n=41) or post-prostatectomy (n=4), followed by rising PSA levels. Recurrent disease was confirmed by FDG-PET (n=31), PSMA-PET (n=10), or positive local biopsy (n=4). Gross tumor volume (GTV) was delineated based on PET and MR imaging, with the planning target volume (PTV) expanding to an average of 10.9 cm³. Patients received proton reirradiation using two oblique coplanar beams, delivering total doses ranging from 30.06 to 60.00 GyE in 17–30 fractions. All treatments were administered using the ProBeam Compact system with CT image guidance. The International Prostate Symptom Scores (IPSS) and prostate-specific antigen (PSA) levels were evaluated to assess treatment-related toxicity and tumor control. Results and Discussions: In this cohort (mean age: 76.7 ± 7.3 years), 60% (27/45) of patients showed sustained reductions in PSA levels post-treatment, while 36% (16/45) experienced a PSA decline of more than 0.8 ng/mL. Additionally, 73% (33/45) of patients exhibited an initial PSA reduction, though some showed later PSA increases, indicating the potential presence of undetected metastatic lesions. The median post-retreatment IPSS score was 4, significantly lower than scores reported in other treatment studies. Overall, 69% of patients reported mild urinary symptoms, with 96% (43/45) experiencing mild to moderate symptoms. Three patients experienced grade I or II proctitis, while one patient reported grade III proctitis. These findings suggest that regional organs, including the urethra, bladder, and rectum, demonstrate significant radiobiological recovery from prior radiation exposure, enabling tolerance to additional proton scanning beam therapy. Conclusions: This retrospective analysis of 45 patients with recurrent localized prostate cancer treated with salvage proton reirradiation demonstrates favorable outcomes, with a median follow-up of two years. The post-retreatment IPSS scores were comparable to those reported in follow-up studies of initial radiation therapy treatments, indicating stable or improved urinary symptoms compared to the end of initial treatment. These results highlight the efficacy of proton scanning beam therapy in providing effective salvage treatment while minimizing adverse effects on critical organs. The findings also enhance the understanding of radiobiological responses to reirradiation and support proton therapy as a viable option for patients with recurrent localized prostate cancer following previous definitive radiation therapy.

Keywords: prostate salvage radiotherapy, proton therapy, biological radiation tolerance, radiobiology of organs

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Authors: Seyhan Sahan-Firat, Meryem Temiz-Resitoglu, Demet Sinem Guden, Sefika Pinar Kucukkavruk, Bahar Tunctan, Ayse Nihal Sari, Zumrut Kocak

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We hypothesized that mTOR inhibition may prevent the multiple organ failures following severe multiple tissue injury associated with increased NADPH oxidase system activity occur in zymosan-induced systemic inflammation. Therefore, we investigated the role of mTOR in oxidative/nitrosative stress associated with increase in NADPH oxidase activity in zymosan-induced systemic inflammation model in rats. Male Wistar rats received saline (4 ml/kg, i.p.) and zymosan (500 mg/kg, i.p.) at time 0. Saline, or zymosan-treated rats were given rapamycin (1 mg/kg, i.p.) 1 h after saline or zymosan injections. Rats were sacrified 4 h after zymosan challenge and kidney, heart, thoracic aorta, and superior mesenteric artery were collected. NADPH oxidase activity, p22phox, gp91phox, and p47phox protein expression and nitrotyrosine levels were measured in tissue samples. Zymosan administration caused an increase in NADPH oxidase activity, p22phox, gp91phox, and p47phox protein expression and nitrotyrosine levels in kidney, heart, thoracic aorta, and superior mesenteric artery. These changes caused by zymosan reversed by rapamycin, a selective mTOR inhibitor. Rapamycin alone had no effect on the parameters measured. Our results demonstrated that zymosan-induced oxidative/nitrosative stress presumably due to enhanced activity of NADPH oxidase, expression of p22phox, gp91phox, and p47phox and production of peroxynitrite were mediated by mTOR. [This work was financially supported by Research Foundation of Mersin University (2016-2-AP3-1900)].

Keywords: oxidative stress, mTOR, nitrosative stress, zymosan

Procedia PDF Downloads 314

Authors: Mohammad Aziz Shah Mohamed Arip, Aslina Ahmad, Fauziah Mohd Sa'ad, Samsiah Mohd Jais, Syed Sofian Syed Salim

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This experimental study evaluates the effect of using Cognitive-Behavioral Therapy (CBT) and Multidimensional Self-Concept Model (MSCM) in a drug prevention programme to increase resiliency and reduce aggression among at-risk youth in Malaysia. A number of 60 (N=60) university students who were at-risk of taking drugs were involved in this study. Participants were identified with self-rating scales, Adolescent Resilience Attitude Scale (ARAS) and Aggression Questionnaire. Based on the mean score of these instruments, the participants were divided into the treatment group, and the control group. Data were analyzed using t-test. The finding showed that the mean score of resiliency was increased in the treatment group compared to the control group. It also shows that the mean score of aggression was reduced in the treatment group compared to the control group. Drug Prevention Programme was found to help in enhancing resiliency and reducing aggression among participants in the treatment group compared to the controlled group. Implications were given regarding the preventive actions on drug abuse among youth in Malaysia.

Keywords: drug prevention programme, cognitive-behavioral therapy (CBT), multidimensional self concept model (MSCM), resiliency, aggression, at-risk youth

Procedia PDF Downloads 726

Authors: Adaour Mohamed Amine, Bachene Mohamed Sadek, Fortassi Mosaab, Siouda Wafaa

Abstract:

Foot infections are responsible for a significant number of hospitalizations and amputations in diabetic patients. The objective of our study is to analyze and evaluate the management of diabetic foot in a surgical setting. A retrospective study was conducted based on a selected case of suspected diabetic foot infections of osteitis treated at the Mohamed Boudiaf hospital in Medea. The case was reiterated as a therapeutic charge, consisting of treating first the infection of the soft tissues, then the osteitis: biopsy after at least 15 days of cessation of antibiotic therapy. Successful treatment of osteitis was defined at the end of a follow-up period of complete wound healing, lack of bone resection/amputation surgery at the initial bone site during follow-up , Instead, biopsies are prescribed in the treatment of soft tissue infection. The mean duration of treatment for soft tissue infection was 2-3 weeks, the duration of the antibiotic-free window of therapy prior to bone biopsy was 2-4 weeks. This patient received medical management without surgical resection. The success rate for treating osteitis at one year was 73% and healing at one year was 88%.It is often limited to a sausage of the foot at the cost of repeated amputations. The best management remains prevention, which necessarily involves setting up a specialized and adapted centre.

Keywords: osteitis, antibiotic therapy, bone biopsy, diabetic foot

Procedia PDF Downloads 103

Authors: Gerard Bray, Arya Bahadori, Sachinka Ranasinghe

Abstract:

Renal cell carcinoma (RCC) is among the top 10 most common cancers worldwide, where metastatic disease carries a poor prognosis. Herein, we present a 74-year-old male presenting with asymptomatic solitary metachronous metastasis to the gall bladder 4 years following nephrectomy for clear cell RCC. Solitary RCC metastasis to the gall bladder following nephrectomy is rarely reported in the literature and brings with it a clinical conundrum of whether surgical resection or systemic therapy should be utilized. In this case, surgical excision with cholecystectomy was employed without systemic therapy. We, therefore, contribute a rare and interesting case that highlights that metastasectomy of a solitary metastasis can improve survival according to current literature.

Keywords: renal cell carcinoma, gall bladder metastasis, solitary metastasectomy, metachronous

Procedia PDF Downloads 172

Authors: Rina Lee, Chung-Hun Oh, Eunjin Lee, Jeongyun Kim

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The Photodynamic therapy (PDT) is a treatment that uses a photosensitizer as a drug to damage and kill cancer cells. After injecting the photosensitizer into the bloodstream, the drug is absorbed by cancer cells selectively. Then the area to be treated is exposed to specific wavelengths of light and the photosensitizer produces a form of oxygen that kills nearby cancer cells. PDT is has an advantage to destroy the tumor with minimized side-effects on normal cells. But, PDT is not a completed method for cancer therapy. Because the mechanism of PDT is quite clear yet and the parameters such as intensity of light and dose of photosensitizer are not optimized for different types of cancers. To optimize these parameters, we suggest a novel microfluidic system to automatically control intensity of light exposure with a personal computer (PC). A polydimethylsiloxane (PDMS) microfluidic chip is composed with (1) a cell culture channels layer where cancer cells were trapped to be tested with various dosed photofrin (1μg/ml used for the test) as the photosensitizer and (2) a color dye layer as a neutral density (ND) filter to reduce intensity of light which exposes the cell culture channels filled with cancer cells. Eight different intensity of light (10%, 20%, …, 100%) are generated through various concentrations of blue dye filling the ND filter. As a light source, a light emitting diode (LED) with 635nm wavelength was placed above the developed PDMS microfluidic chip. The total time for light exposure was 30 minutes and HeLa and PC3 cell lines of cancer cells were tested. The cell viability of cells was evaluated with a Live/Dead assay kit (L-3224, Invitrogen, USA). The stronger intensity of light exposed, the lower viability of the cell was observed, and vice versa. Therefore, this system was demonstrated through investigating the PDT against cancer cell to optimize the parameters as critical light intensity and dose of photosensitizer. Our results suggest that the system can be used for optimizing the combinational parameters of light intensity and photosensitizer dose against diverse cancer cell types.

Keywords: photodynamic therapy, photofrin, high throughput screening, hela

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Authors: Zhang Zhenzhen

Abstract:

Valproate (VPA) is commonly used in the treatment of bipolar disorder and epilepsy. The mechanism is complicated, including its ability to inhibit histone deacetylases (HDACs). Here, we show that VPA attenuated VEGF gene expression and the morphological changes in choroidal neovascularization (CNV) induced by photocoagulation in retina. C57BL/6 mice were injected subcutaneously at 300mg/kg twice daily with VPA before insult. Vascular endothelial growth factor (VEGF)-A and VEGF-B were examined in the eyes of VPA-treated mice and in human retinal pigment epithelial cell lines (ARPE-19) exposed to VPA. In addition, CNV was induced by photocoagulation in mice injected with VPA, and the volume of CNV was compared by fluorescence-labeled choroidal flat mount. Morphological changes were analyzed on stained histological sections. Western blot analysis was used to determine protein levels of VEGF-A and VEGF-B, and acetylation of histone H3 in each group. VPA injected intraperitoneally attenuated the VEGF-A and VEGF-B expression in the retina, accompanied by the hyperacetylation of retina tissue, indicating that VPA acts directly on retina tissues through acetylation to reduce the expression of VEGF. VPA also attenuated the VEGF-A mRNA expression in the retinal pigment epithelium showed by immunohistochemistry. Moreover, the administration of VPA significantly attenuated photocoagulation-induced CNV in mice. These results demonstrate that VPA attenuated VEGF production in retina associated with choroidal neovascularization possibly via the HDAC inhibition.

Keywords: retina, acetylation, chorodial neovascularization, vascular endothelial growth factor

Procedia PDF Downloads 204

Authors: Eman Alhajjar, Albatool Jamjoom, Fatmah Bugshan

Abstract:

This research aims to investigate the artificial intelligence (AI) application Jung GPT and how helpful it is, as a therapy AI, to users. Jung GPT has the potential to make mental health care more accessible and cheaper while also providing tailored support and advice. However, it is not intended to be a substitute for human therapists. Jung GPT is instructed to understand a wide range of concepts, including emojis, sensitive subjects, and various languages. Furthermore, participants were asked to fill out a survey based on their experience with Jung GPT. Additionally, analysis of the responses indicated that Jung GPT was helpful in identifying and exploring challenges, and the use of Jung GPT by participants in the future is highly possible. The results demonstrate that Jung GPT does help in recognizing challenges or problems within the users. On this basis, it is recommended that individuals use Jung GPT to explore their thoughts, feelings, and challenges. Moreover, further research is needed to better evaluate the effectiveness of Jung GPT.

Keywords: Jung GPT, artificial intelligence, therapy, mental health, AI application

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Authors: Adrian Craig, Jonathan Easaw, Rose Jordan, Ben Hall

Abstract:

The prescription of intravenous fluids is a fundamental component of inpatient management, but it is one which usually lacks thought. Fluids are a drug, which like any other can cause harm when prescribed inappropriately or wrongly. However, it is well recognised that it is poorly done, especially in the acute portals. The National Institute for Health and Care Excellence (NICE) recommends 1mmol/kg of potassium, sodium, and chloride per day. With various options of fluids, clinicians tend to face difficulty in choosing the most appropriate maintenance fluid, and there is a reluctance to prescribe potassium as part of an intravenous maintenance fluid regime. The aim was to prospectively audit the prescription of the first bag of intravenous maintenance fluids, the use of urea and electrolytes results to guide the choice of fluid and the use of fluid prescription charts, in a busy emergency department of a major trauma centre in Stoke-on-Trent, United Kingdom. This was undertaken over a week in early November 2016. Of those prescribed maintenance fluid only 8.9% were prescribed a fluid which was most appropriate for their daily electrolyte requirements. This audit has helped to highlight further the issues that are faced in busy Emergency Departments within hospitals that are stretched and lack capacity for prompt transfer to a ward. It has supported the findings of NICE, that emergency admission portals such as Emergency Departments poorly prescribed intravenous fluid therapy. The findings have enabled simple steps to be taken to educate clinicians about their fluid of choice. This has included: posters to remind clinicians to consider the urea and electrolyte values before prescription, suggesting the inclusion of a suggested intravenous fluid of choice in the prescription chart of the trust and the inclusion of a session within the introduction programme revising intravenous fluid therapy and daily electrolyte requirements. Moving forward, once the interventions have been implemented then, the data will be reaudited in six months to note any improvement in maintenance fluid choice. Alongside this, an audit of the rate of intravenous maintenance fluid therapy would be proposed to further increase patient safety by avoiding unintentional fluid overload which may cause unnecessary harm to patients within the hospital. In conclusion, prescription of maintenance fluid therapy was poor within the Emergency Department, and there is a great deal of opportunity for improvement. Therefore, the measures listed above will be implemented and the data reaudited.

Keywords: chloride, electrolyte, emergency department, emergency medicine, fluid, fluid therapy, intravenous, maintenance, major trauma, potassium, sodium, trauma

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Authors: Azeez Yusuf, Alan Casey

Abstract:

Silver nanoparticles (AgNP) are one of the most widely investigated metallic nanoparticles due to their promising antibacterial activities. In recent years, AgNP research has shifted beyond antimicrobial use to potential applications in the medical arena. This shift coupled with the extensive commercial applications of AgNP will further increase human exposure, and the subsequent risk of adverse effects that may result from repeated exposures and inefficient delivery meaning research into improved AgNP delivery is of paramount importance. In this study, AgNP were encapsulated in a natural bio-surfactant, dipalmitoylphosphatyidyl choline (DPPC), in an attempt to enhance the intracellular delivery and simultaneously mediate the associated cytotoxicity of the AgNP. It was noted that as a result of the encapsulation, liposomal-AgNP (Lipo-AgNP) at 0.625 μg/ml induced significant cell death in THP1 cell lines a notably lower dose than that of the uncoated AgNP induced cytotoxicity. The induced cytotoxicity was shown to result in an increased level of DNA fragmentation resulting in a cell cycle interruption at the S phase of the cell cycle. It was shown that the predominate form of cell death upon exposure to both uncoated and Lipo-AgNP was apoptosis, however, a ROS-independent activation of the executioner caspases 3/7 occurred when exposed to the Lipo-AgNP. These findings showed that encapsulation of AgNP enhances AgNP cytotoxicity and mediates an ROS-independent induction of apoptosis.

Keywords: silver nanoparticles, AgNP, cytotoxicity, encapsulation, liposome

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Authors: Eva Tolmeijer, Emmanuelle Peters, Veena Kumari, Liam Mason

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Cognitive behavioral therapy for psychosis (CBTp) is effective in many but not all patients, making it important to better understand the factors that determine treatment outcomes. To date, no studies have examined whether neuroimaging can make clinically useful predictions about who will respond to CBTp. To this end, we used machine learning methods that make predictions about symptom improvement at the individual patient level. Prior to receiving CBTp, 22 patients with a diagnosis of schizophrenia completed a social-affective processing task during functional MRI. Multivariate pattern analysis assessed whether treatment response could be predicted by brain activation responses to facial affect that was either socially threatening or prosocial. The resulting models did significantly predict symptom improvement, with distinct multivariate signatures predicting psychotic (r=0.54, p=0.01) and affective (r=0.32, p=0.05) symptoms. Psychotic symptom improvement was accurately predicted from relatively focal threat-related activation across hippocampal, occipital, and temporal regions; affective symptom improvement was predicted by a more dispersed profile of responses to prosocial affect. These findings enrich our understanding of the neurobiological underpinning of treatment response. This study provides a foundation that will hopefully lead to greater precision and tailoring of the interventions offered to patients.

Keywords: cognitive behavioral therapy, machine learning, psychosis, schizophrenia

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Authors: Rabson Banda

Abstract:

This abstract delves into the transformative journey of Rabson Banda, a visionary leader in Zambia who has harnessed the power of photovoice, mental fitness, and entrepreneurship to combat substance use disorders in the face of limited job opportunities in Africa. Rabson's personal battle with alcohol-induced disorder serves as the foundation for his pioneering work in establishing Elevated Initiatives, a grassroots organization dedicated to empowering individuals struggling with addiction through innovative approaches. Through the lens of photovoice, Rabson Banda amplifies the voices of those affected by substance abuse, providing a platform for self-expression and healing. By intertwining mental fitness techniques and entrepreneurial skills, he equips individuals with the tools needed to break free from the cycle of addiction and chart a new path toward holistic wellness and economic independence. Rabson Banda's story embodies resilience, hope, and the unwavering belief in the transformative power of community-driven initiatives. His work not only addresses the immediate challenges of substance use disorders but also addresses the root causes of addiction by advocating for increased job opportunities and economic empowerment in Zambia and across Africa for decent job creation and Entrepreneurship: A Lived Experience of Alcohol-Induced Disorder and Recovery in Zambia.

Keywords: mental fitness, entrepreneurship, photovoice, descent jobs

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Authors: Kittitara Chunlakittiphan, Patompong Satapornpong

Abstract:

Introduction: The variation of genetics affects how our body responds to pharmaceuticals elucidates the correlation between long-term use of medical cannabis and adverse drug reactions (ADRs). Medical cannabis is regarded as the treatment for chronic pain, cancer pain, acute pain, psychological disorders, multiple sclerosis and migraine management. However, previous studies have shown that delta-9-Tetrahydrocannabinol (THC), an ingredient found in cannabis, was the cause of ADRs in CB1 receptors found in humans. Previous research suggests that distributions of the cannabinoid type 1 (CB1) receptor gene and pharmacogenetic markers, which vary amongst different populations, might affect incidences of ADRs. Although there is an evident need to investigate the level of the CB1 receptor gene (rs806365), studies on the distribution of CB1-pharmacogenetics markers in Thai patients are limited. Objective: Therefore, the aim of this study is to investigate the distribution of the rs806365 polymorphism in Thai patients who have been treated with medical cannabis. Materials and Methods: We enrolled 31 Thai patients with THC-induced ADRs and 34 THC-tolerant controls to take part in this study. All patients with THC-induced ADRs were accessed through a review of medical records by physicians. EDTA blood of 3ml was collected to obtain the CNR1 gene (rs806365) and genotyping of this gene was conducted using the real-time PCR ViiA7 (ABI, Foster City, CA, USA) following the manufacturer’s instruction. Results: The sample consisted of 65 patients (40/61.54%) were females and (25/38.46%) were males, with an age range of 19-87 years, who have been treated with medical cannabis. In this study, the most common THC-induced ADRs were dry mouth and/or dry throat, tachycardia, nausea, and arrhythmia. Across the whole sample, we found that 52.31% of Thai patients carried a heterozygous variant (rs806365, CT allele). Moreover, the number of rs806365 (CC, homozygous variant) carriers totaled seventeen people (26.15%) amongst the subjects of Thai patients treated with medical cannabis. Furthermore, 17 out of 22 patients (77.27%) who experienced severe ADRs: Tachycardia and/or arrhythmia, carried an abnormal rs806365 gene (CT and CC alleles). Conclusions: The results propose that the rs806365 gene is widely distributed amongst the Thai population and there is a link between this gene and vulnerability to developing THC-induced ADRs after being treated with medical cannabis. Therefore, it is necessary to screen for the rs806365 gene before using medical cannabis to treat a patient.

Keywords: rs806365, THC-induced adverse drug reactions, CB1 receptor, Thai population

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Authors: Tan Hui Ying Renee, Stella Rizalina Sasha, Farah Safdar Husain

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Introduction: Menopause Hormone Therapy (MHT) is an effective drug indicated for the treatment of menopausal symptoms and as replacement therapy in women who undergo premature menopause. In 2020, less than 8.8% of perimenopausal Singaporean women are on hormonal therapy, as compared to the Western population, where up to 50% may be on MHT. Factors associated with MHT utilization have been studied from patient characteristics, but the impact of locally prescribing physicians resulting in low MHT utilization has yet to be evaluated. The aim of the study is to determine the level of knowledge physicians in the Obstetrics and Gynaecology specialty have and their attitudes toward MHT. We believe that knowledge of MHT is lacking and that negative attitudes towards MHT may influence its use and undermine the benefits MHT may have for women. This paper is a part of a larger study on Singaporean physicians’ knowledge and attitudes towards MHT. Methods: This is a cross-sectional study intended to assess the knowledge and attitudes of physicians toward Menopausal Hormone Therapy. An anonymous questionnaire was disseminated via institutional internal circulations to optimize reach to physicians who may prescribe MHT, particularly in the fields of Gynaecology, Family Medicine and Endocrinology. Responses were completed voluntarily. Physicians had the option for each question to declare that they were ‘unsure’ or that the question was ‘beyond their expertise’. 21 knowledge questions tested factual recall on indications, contraindications, and risks of MHT. The remaining 6 questions were clinical scenarios crafted with the intention of testing specific principles related to the use of MHT. These questions received face validation from experts in the field. 198 responses were collected, 79 of which were from physicians in the Obstetrics and Gynaecology specialty. The data will be statistically analyzed to investigate areas that can be improved to increase the overall benefits of MHT for the Singaporean population. Results: Preliminary results show that the prevailing factors that limit Singaporean gynecologists and obstetricians from prescribing MHT are a lack of knowledge of MHT and a lack of confidence in prescribing MHT. Risks and indications of MHT were not well known by many physicians, with the majority of the questions having more than 25% incorrect and ‘unsure’ as their reply. The clinical scenario questions revealed significant shortcomings in knowledge on how to navigate real-life challenges in MHT use, with 2 of 6 questions with more than 50% incorrect or ‘beyond their expertise’ as their reply. The portion of the questionnaire that investigated the attitudes of physicians showed that though a large majority believed MHT to be an effective drug, only 40.5% were confident in prescribing it. Conclusion: Physicians in the Obstetrics and Gynaecology specialty lack knowledge and confidence in MHT. Therefore, it is imperative to formulate solutions on both the individual and institutional levels to fill these gaps and ensure that MHT is used appropriately and prescribed to the patients who need it.

Keywords: menopause, menopause hormone therapy, physician factors, obstetrics and gynecology, menopausal symptoms, Singapore

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Authors: A. N. Moulai Khatir

Abstract:

SOI-Multifin-FETs are placed to be the workhorse of the industry for the coming few generations, and thus, in a few years because their excellent transistor characteristics, ideal sub-threshold swing, low drain induced barrier lowering (DIBL) without pocket implantation, and negligible body bias dependency. The corner effect may also exist in the two lower corners; this effect is called the BOX effect, which can also occur in the direction X-Z. The electric field lines from the source and drain cross the bottom oxide and arrive in the silicon. This effect is also called DIVSB (Drain Induced Virtual Substrate Basing). The potential in the silicon film in particular near the drain is increased by the drain bias. It is similar to DIBL and result in a decrease of the threshold voltage. This work provides an understanding of the limitation of this effect by reducing the fin width for components with increased fin number.

Keywords: SOI, finFET, corner effect, dual-gate, tri-gate, BOX, multi-finFET

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Authors: Rabah Iratni, Husain El Hasasna, Khawlah Athamneh, Halima Al Sameri, Nehla Benhalilou, Asma Al Rashedi

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Background: Cancer therapies have witnessed great advances in the recent past, however, cancer continues to be a leading cause of death, with colorectal cancer being the fourth cause of cancer-related deaths. Colorectal cancer affects both sexes equally with poor survival rate once it metastasizes. Phytochemicals, which are plant derived compounds, have been on a steady rise as anti-cancer drugs due to the accumulation of evidences that support their potential. Here, we investigated the anticancer effect of Rhus coriaria on colon cancer cells. Material and Method: Human colon cancer HT-29 cell line was used. Protein expression and protein phosphorylation were examined using Western blotting. Transcription activity was measure using Quantitative RT-PCR. Human tumoral clonogenic assay was used to assess cell survival. Senescence was assessed by the senescence-associated beta-galactosidase assay. Results: Rhus coriaria extract (RCE) was found to significantly inhibit the viability and colony growth of human HT-29 colon cancer cells. RCE induced senescence and cell cycle arrest at G1 phase. These changes were concomitant with upregulation of p21, p16, downregulation of cyclin D1, p27, c-myc and expression of Senescence-associated-β-Galactosidase activity. Moreover, RCE induced non-canonical beclin-1independent autophagy and subsequent apoptotic cell death through activation of activation caspase 8 and caspase 7. The blocking of autophagy by 3-methyladenine (3-MA) or chloroquine (CQ) reduced RCE-induced cell death. Further, RCE induced DNA damage, reduced mutant p53 protein level and downregulated phospho-AKT and phospho-mTOR, events that preceded autophagy. Mechanistically, we found that RCE inhibited the AKT and mTOR pathway, a regulator of autophagy, by promoting the proteasome-dependent degradation of both AKT and mTOR proteins. Conclusion: Our findings provide strong evidence that Rhus coriaria possesses strong anti-colon cancer activity through induction of senescence and autophagic cell death, making it a promising alternative or adjunct therapeutic candidate against colon cancer.

Keywords: autophagy, proteasome degradation, senescence, mTOR, apoptosis, Beclin-1

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Authors: Hsin-Lien Lin, Ju-Hui Fu

Abstract:

Dendritic cells (DCs) are the major professional antigen-presenting cells for the development of optimal T-cell immunity. DCs can be used as pharmacological targets to screen novel biological modifiers for the treatment of harmful immune responses, such as transplantation rejection. Dryopteris crassirhizoma Nakai (Aspiadaceae) is used for traditional herbal medicine in the region of East Asia. The root of this fern plant has been listed for treating inflammatory diseases. Dryocrassin is the tetrameric phlorophenone component derived from Dryopteris. Here, we tested the immunomodulatory potential of dryocrassin on lipopolysaccharide (LPS)-stimulated activation of mouse bone marrow-derived DCs in vitro and in skin allograft transplantation in vivo. Results demonstrated that dryocrassin reduced the secretion of tumor necrosis factor-α, interleukin-6, and interleukin-12p70 by LPS-stimulated DCs. The expression of LPS-induced major histocompatibility complex class II, CD40, and CD86 on DCs was also blocked by dryocrassin. Moreover, LPS-stimulated DC-elicited allogeneic T-cell proliferation was lessened by dryocrassin. In addition, dryocrassin inhibited LPS-induced activation of IϰB kinase, JNK/p38 mitogen-activated protein kinase, as well as the translocation of NF-ϰB. Treatment with dryocrassin obviously diminished 2,4-dinitro-1-fluorobenzene- induced delayed-type hypersensitivity and prolonged skin allograft survival. Dryocrassin may be one of the potent immunosuppressive agents for transplant rejection through the destruction of DC maturation and function.

Keywords: dryocrassin, dendritic cells, immunosuppression, skin allograft

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Authors: Natalia A. Salazar, Erika K. Méndez, Catalina Álvarez, Carlos E. Orrego

Abstract:

Lyophilization, also called freeze-drying, is an important dehydration technique mainly used for pharmaceuticals. Food industry also uses lyophilization when it is important to retain most of the nutritional quality, taste, shape and size of dried products and to extend their shelf life. Vacuum-Induced during freezing cycle (VI) has been used in order to control ice nucleation and, consequently, to reduce the time of primary drying cycle of pharmaceuticals preserving quality properties of the final product. This procedure has not been applied in freeze drying of foods. The present work aims to investigate the effect of VI on the lyophilization drying time, final moisture content, density and reconstitutional properties of mango (Mangifera indica L.) slices (MS) and mango pulp-maltodextrin dispersions (MPM) (30% concentration of total solids). Control samples were run at each freezing rate without using induced vacuum. The lyophilization endpoint was the same for all treatments (constant difference between capacitance and Pirani vacuum gauges). From the experimental results it can be concluded that at the high freezing rate (0.4°C/min) reduced the overall process time up to 30% comparing process time required for the control and VI of the lower freeze rate (0.1°C/min) without affecting the quality characteristics of the dried product, which yields a reduction in costs and energy consumption for MS and MPM freeze drying. Controls and samples treated with VI at freezing rate of 0.4°C/min in MS showed similar results in moisture and density parameters. Furthermore, results from MPM dispersion showed favorable values when VI was applied because dried product with low moisture content and low density was obtained at shorter process time compared with the control. There were not found significant differences between reconstitutional properties (rehydration for MS and solubility for MPM) of freeze dried mango resulting from controls, and VI treatments.

Keywords: drying time, lyophilization, mango, vacuum induced freezing

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Authors: S. Haque, M. Kanapathy, E. Bollen, I. Younis, A. Mosahebi

Abstract:

Background: Implant loss due to infection is the most devastating complication of implant-based breast reconstruction. The use of negative pressure wound therapy with instillation (NPWTi) for salvage of infected implant-based breast reconstructions has shown promising results to allow early reinsertion of a new implant as an alternative to current management of delayed reinsertion. This study compares the cost implication of NPWTi against current management of delayed reinsertion of infected breast implants. Methods: 20 cases of an infected breast implant treated with NPWTi (V.A.C. VERAFLO™ Therapy) followed by early re-insertion of a new implant were compared with 20 cases who had delayed reinsertion (non-NPWTi). Average cost per person was calculated using total operative expenses, cost of inpatient stay, cost of investigations, cost of antibiotics, and cost of outpatient visits. Results: Treatment with NPWTi allowed for earlier re-insertion of a new implant (NPWTi: 9.04 ± 2.92 days vs. non-NPWTi: 236.25 ± 123.89 days). The average cost per patient for NPWTi and non-NPWTi was £14,343.13 ± £2,786.70 and £8,920.31 ± £3,005.73 respectively. All patients treated with NPWTi had one admission and spent 11.9 ± 4.1days as an inpatient while non-NPWTi patients had 2.1 ± 0.3 admissions with total length of inpatient stay of 7.1 ± 5.8days. Patients treated with NPWTi had more surgeries (NPWTi: 3.35 ± 0.81 vs. non-NPWTi: 2.2 ± 0.41), however 3 non-NPWTi cases required flap reconstruction. Patients treated with NPWTi had fewer total outpatient visits (NPWTi: 12 ± 6 vs. non-NPWTi: 14.2 ± 6.3). Conclusion: Patients treated with NPWTi incurred higher average cost per patient, longer inpatient stay, and more procedures; however, had early re-insertion of new implants and fewer admissions and outpatient visits. A further study on patient-reported outcome is essential to compare cost against patient benefit.

Keywords: breast reconstruction, cost evaluation, infection, negative pressure wound therapy

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