Search results for: curative
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 82

Search results for: curative

22 Women Writing Group as a Mean for Personal and Social Change

Authors: Michal Almagor, Rivka Tuval-Mashiach

Abstract:

This presentation will explore the main processes identified in women writing group, as an interdisciplinary field with personal and social effects. It is based on the initial findings of a Ph.D. research focus on the intersection of group processes with the element of writing, in the context of gender. Writing as a therapeutic mean has been recognized and found to be highly effective. Additionally, a substantial amount of research reveals the psychological impact of group processes. However, the combination of writing and groups as a therapeutic tool was hardly investigated; this is the contribution of this research. In the following qualitative-phenomenological study, the experiences of eight women participating in a 10-sessions structured writing group were investigated. We used the meetings transcripts, semi-structured interviews, and the texts to analyze and understand the experience of participating in the group. The two significant findings revealed were spiral intersubjectivity and archaic level of semiotic language. We realized that the content and the process are interwoven; participants are writing, reading and discussing their texts in a group setting that enhanced self-dialogue between the participants and their own narratives and texts, as well as dialogue with others. This process includes working through otherness within and between while discovering and creating a multiplicity of narratives. A movement of increasing shared circles from the personal to the group and to the social-cultural environment was identified, forming what we termed as spiral intersubjectivity. An additional layer of findings was revealed while we listened to the resonance of the group-texts, and discourse; during this process, we could trace the semiotic level in addition to the symbolic one. We were witness to the dominant presence of the body, and primal sensuality, expressed by rhythm, sound and movements, signs of pre-verbal language. Those findings led us to a new understanding of the semiotic function as a way to express the fullness of women experience and the enabling role of writing in reviving what was repressed. The poetic language serves as a bridge between the symbolic and the semiotic. Re-reading the group materials, exposed another layer of expression, an old-new language. This approach suggests a feminine expression of subjective experience with personal and social importance. It is a subversive move, encouraging women to write themselves, as a craft that every woman can use, giving voice to the silent and hidden, and experiencing the power of performing 'my story'. We suggest that women writing group is an efficient, powerful yet welcoming way to raise the awareness of researchers and clinicians, and more importantly of the participants, to the uniqueness of the feminine experience, and to gender-sensitive curative approaches.

Keywords: group, intersubjectivity, semiotic, writing

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21 Phage Therapy as a Potential Solution in the Fight against Antimicrobial Resistance

Authors: Sanjay Shukla

Abstract:

Excessive use of antibiotics is a main problem in the treatment of wounds and other chronic infections and antibiotic treatment is frequently non-curative, thus alternative treatment is necessary. Phage therapy is considered one of the most effective approaches to treat multi-drug resistant bacterial pathogens. Infections caused by Staphylococcus aureus are very efficiently controlled with phage cocktails, containing a different individual phages lysate infecting a majority of known pathogenic S. aureus strains. The aim of current study was to investigate the efficiency of a purified phage cocktail for prophylactic as well as therapeutic application in mouse model and in large animals with chronic septic infection of wounds. A total of 150 sewage samples were collected from various livestock farms. These samples were subjected for the isolation of bacteriophage by double agar layer method. A total of 27 sewage samples showed plaque formation by producing lytic activity against S. aureus in double agar overlay method out of 150 sewage samples. In TEM recovered isolates of bacteriophages showed hexagonal structure with tail fiber. In the bacteriophage (ØVS) had an icosahedral symmetry with the head size 52.20 nm in diameter and long tail of 109 nm. Head and tail were held together by connector and can be classified as a member of the Myoviridae family under the order of Caudovirale. Recovered bacteriophage had shown the antibacterial activity against the S. aureus in vitro. Cocktail (ØVS1, ØVS5, ØVS9 and ØVS 27) of phage lysate were tested to know in vivo antibacterial activity as well as the safety profile. Result of mice experiment indicated that the bacteriophage lysate was very safe, did not show any appearance of abscess formation which indicates its safety in living system. The mice were also prophylactically protected against S. aureus when administered with cocktail of bacteriophage lysate just before the administration of S. aureus which indicates that they are good prophylactic agent. The S. aureus inoculated mice were completely recovered by bacteriophage administration with 100% recovery which was very good as compere to conventional therapy. In present study ten chronic cases of wound were treated with phage lysate and follow up of these cases was done regularly up to ten days (at 0, 5 and 10 d). Result indicated that the six cases out of ten showed complete recovery of wounds within 10 d. The efficacy of bacteriophage therapy was found to be 60% which was very good as compared to the conventional antibiotic therapy in chronic septic wounds infections. Thus, the application of lytic phage in single dose proved to be innovative and effective therapy for treatment of septic chronic wounds.

Keywords: phage therapy, phage lysate, antimicrobial resistance, S. aureus

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20 Medicinal Plants: An Antiviral Depository with Complex Mode of Action

Authors: Daniel Todorov, Anton Hinkov, Petya Angelova, Kalina Shishkova, Venelin Tsvetkov, Stoyan Shishkov

Abstract:

Human herpes viruses (HHV) are ubiquitous pathogens with a pandemic spread across the globe. HHV type 1 is the main causative agent of cold sores and fever blisters around the mouth and on the face, whereas HHV type 2 is generally responsible for genital herpes outbreaks. The treatment of both viruses is more or less successful with antivirals from the nucleoside analogues group. Their wide application increasingly leads to the emergence of resistant mutants In the past, medicinal plants have been used to treat a number of infectious and non-infectious diseases. Their diversity and ability to produce the vast variety of secondary metabolites according to the characteristics of the environment give them the potential to help us in our warfare with viral infections. The variable chemical characteristics and complex composition is an advantage in the treatment of herpes since the emergence of resistant mutants is significantly complicated. The screening process is difficult due to the lack of standardization. That is why it is especially important to follow the mechanism of antiviral action of plants. On the one hand, it may be expected to interact with its compounds, resulting in enhanced antiviral effects, and the most appropriate environmental conditions can be chosen to maximize the amount of active secondary metabolites. During our study, we followed the activity of various plant extracts on the viral replication cycle as well as their effect on the extracellular virion. We obtained our results following the logical sequence of the experimental settings - determining the cytotoxicity of the extracts, evaluating the overall effect on viral replication and extracellular virion.During our research, we have screened a variety of plant extracts for their antiviral activity against both virus replication and the virion itself. We investigated the effect of the extracts on the individual stages of the viral replication cycle - viral adsorption, penetration and the effect on replication depending on the time of addition. If there are positive results in the later experiments, we had studied the activity over viral adsorption, penetration and the effect of replication according to the time of addition. Our results indicate that some of the extracts from the Lamium album have several targets. The first stages of the viral life cycle are most affected. Several of our active antiviral agents have shown an effect on extracellular virion and adsorption and penetration processes. Our research over the last decade has shown several curative antiviral plants - some of which are from the Lamiacea family. The rich set of active ingredients of the plants in this family makes them a good source of antiviral preparation.

Keywords: human herpes virus, antiviral activity, Lamium album, Nepeta nuda

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19 Bacteriophage Is a Novel Solution of Therapy Against S. aureus Having Multiple Drug Resistance

Authors: Sanjay Shukla, A. Nayak, R. K. Sharma, A. P. Singh, S. P. Tiwari

Abstract:

Excessive use of antibiotics is a major problem in the treatment of wounds and other chronic infections, and antibiotic treatment is frequently non-curative, thus alternative treatment is necessary. Phage therapy is considered one of the most promising approaches to treat multi-drug resistant bacterial pathogens. Infections caused by Staphylococcus aureus are very efficiently controlled with phage cocktails, containing a different individual phages lysate infecting a majority of known pathogenic S. aureus strains. The aim of the present study was to evaluate the efficacy of a purified phage cocktail for prophylactic as well as therapeutic application in mouse model and in large animals with chronic septic infection of wounds. A total of 150 sewage samples were collected from various livestock farms. These samples were subjected for the isolation of bacteriophage by the double agar layer method. A total of 27 sewage samples showed plaque formation by producing lytic activity against S. aureus in the double agar overlay method out of 150 sewage samples. In TEM, recovered isolates of bacteriophages showed hexagonal structure with tail fiber. In the bacteriophage (ØVS) had an icosahedral symmetry with the head size 52.20 nm in diameter and long tail of 109 nm. Head and tail were held together by connector and can be classified as a member of the Myoviridae family under the order of Caudovirale. Recovered bacteriophage had shown the antibacterial activity against the S. aureus in vitro. Cocktail (ØVS1, ØVS5, ØVS9, and ØVS 27) of phage lysate were tested to know in vivo antibacterial activity as well as the safety profile. Result of mice experiment indicated that the bacteriophage lysate were very safe, did not show any appearance of abscess formation, which indicates its safety in living system. The mice were also prophylactically protected against S. aureus when administered with cocktail of bacteriophage lysate just before the administration of S. aureuswhich indicates that they are good prophylactic agent. The S. aureusinoculated mice were completely recovered by bacteriophage administration with 100% recovery, which was very good as compere to conventional therapy. In the present study, ten chronic cases of the wound were treated with phage lysate, and follow up of these cases was done regularly up to ten days (at 0, 5, and 10 d). The result indicated that the six cases out of ten showed complete recovery of wounds within 10 d. The efficacy of bacteriophage therapy was found to be 60% which was very good as compared to the conventional antibiotic therapy in chronic septic wounds infections. Thus, the application of lytic phage in single dose proved to be innovative and effective therapy for the treatment of septic chronic wounds.

Keywords: phage therapy, S aureus, antimicrobial resistance, lytic phage, and bacteriophage

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18 A Case of Prosthetic Vascular-Graft Infection Due to Mycobacterium fortuitum

Authors: Takaaki Nemoto

Abstract:

Case presentation: A 69-year-old Japanese man presented with a low-grade fever and fatigue that had persisted for one month. The patient had an aortic dissection on the aortic arch 13 years prior, an abdominal aortic aneurysm seven years prior, and an aortic dissection on the distal aortic arch one year prior, which were all treated with artificial blood-vessel replacement surgery. Laboratory tests revealed an inflammatory response (CRP 7.61 mg/dl), high serum creatinine (Cr 1.4 mg/dL), and elevated transaminase (AST 47 IU/L, ALT 45 IU/L). The patient was admitted to our hospital on suspicion of prosthetic vascular graft infection. Following further workups on the inflammatory response, an enhanced chest computed tomography (CT) and a non-enhanced chest DWI (MRI) were performed. The patient was diagnosed with a pulmonary fistula and a prosthetic vascular graft infection on the distal aortic arch. After admission, the patient was administered Ceftriaxion and Vancomycine for 10 days, but his fever and inflammatory response did not improve. On day 13 of hospitalization, a lung fistula repair surgery and an omental filling operation were performed, and Meropenem and Vancomycine were administered. The fever and inflammatory response continued, and therefore we took repeated blood cultures. M. fortuitum was detected in a blood culture on day 16 of hospitalization. As a result, we changed the treatment regimen to Amikacin (400 mg/day), Meropenem (2 g/day), and Cefmetazole (4 g/day), and the fever and inflammatory response began to decrease gradually. We performed a test of sensitivity for Mycobacterium fortuitum, and found that the MIC was low for fluoroquinolone antibacterial agent. The clinical course was good, and the patient was discharged after a total of 8 weeks of intravenous drug administration. At discharge, we changed the treatment regimen to Levofloxacin (500 mg/day) and Clarithromycin (800 mg/day), and prescribed these two drugs as a long life suppressive therapy. Discussion: There are few cases of prosthetic vascular graft infection caused by mycobacteria, and a standard therapy remains to be established. For prosthetic vascular graft infections, it is ideal to provide surgical and medical treatment in parallel, but in this case, surgical treatment was difficult and, therefore, a conservative treatment was chosen. We attempted to increase the treatment success rate of this refractory disease by conducting a susceptibility test for mycobacteria and treating with different combinations of antimicrobial agents, which was ultimately effective. With our treatment approach, a good clinical course was obtained and continues at the present stage. Conclusion: Although prosthetic vascular graft infection resulting from mycobacteria is a refractory infectious disease, it may be curative to administer appropriate antibiotics based on the susceptibility test in addition to surgical treatment.

Keywords: prosthetic vascular graft infection, lung fistula, Mycobacterium fortuitum, conservative treatment

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17 Nutritional Education in Health Resort Institutions in the Face of Demographic and Epidemiological Changes in Poland

Authors: J. Woźniak-Holecka, T. Holecki, S. Jaruga

Abstract:

Spa treatment is an important area of the health care system in Poland due to the increasing needs of the population and the context of historical conditions for this form of therapy. It extends the range of financing possibilities of the outlets and increases the potential of spa services, which is very important in the context of demographic and epidemiological changes. The main advantages of spa treatment services include its relatively wide availability, low risk of side effects, good patient tolerance, long-lasting curative effect and a relatively low cost. In addition, patients should be provided with a proper diet and enable participation in health education and health promotion classes aimed at health problems consistent with the treatment profile. Challenges for global health care systems include a sharp increase in spending on benefits, dynamic development of health technologies and growing social expectations. This requires extending the competences of health resort facilities for health promotion. Within each type of health resort institutions in Poland, nutritional education services are implemented, aimed at creating and consolidating proper eating habits. Choosing the right diet can speed up recovery or become one of the methods to alleviate the symptoms of chronic diseases. During spa treatment patient learns the principles of rational nutrition and adequate dietotherapy to his diseases. The aim of the project is to assess the frequency and quality of nutritional education provided to patients in health resort facilities in a nationwide perspective. The material for the study will be data obtained as part of an in-depth interview conducted among Heads of Nutrition Departments of selected institutions. The use of nutritional education in a health resort may be an important goal of implementing the state health policy as a useful tool to reduce the risk of diet-related diseases. Recognizing nutritional education in health resort institutions as a type of full-value health service can be effective system support for health policy, including seniors, due to demographic changes currently occurring in the Polish population. Furthermore, it is necessary to increase the interest and motivation of patients to follow the recommendations of nutritional education, because it will bring tangible benefits for the long-term effects of therapy and care should be taken for the form and methodology of nutrition education implemented in health resort institutions. Finally it is necessary to construct an educational offer in terms of selected groups of patients with the highest health needs: the elderly and the disabled. In conclusion, it can be said that the system of nutritional education implemented in polish health resort institutions should be subjected to global changes and strong systemic correction.

Keywords: health care system, nutritional education, public health, spa and treatment

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16 Bio-Medical Equipment Technicians: Crucial Workforce to Improve Quality of Health Services in Rural Remote Hospitals in Nepal

Authors: C. M. Sapkota, B. P. Sapkota

Abstract:

Background: Continuous developments in science and technology are increasing the availability of thousands of medical devices – all of which should be of good quality and used appropriately to address global health challenges. It is obvious that bio medical devices are becoming ever more indispensable in health service delivery and among the key workforce responsible for their design, development, regulation, evaluation and training in their use: biomedical technician (BMET) is the crucial. As a pivotal member of health workforce, biomedical technicians are an essential component of the quality health service delivery mechanism supporting the attainment of the Sustainable Development Goals. Methods: The study was based on cross sectional descriptive design. Indicators measuring the quality of health services were assessed in Mechi Zonal Hospital (MZH) and Sagarmatha Zonal Hospital (SZH). Indicators were calculated based on the data about hospital utilization and performance of 2018 available in Medical record section of both hospitals. MZH had employed the BMET during 2018 but SZH had no BMET in 2018.Focus Group Discussion with health workers in both hospitals was conducted to validate the hospital records. Client exit interview was conducted to assess the level of client satisfaction in both the hospitals. Results: In MZH there was round the clock availability and utilization of Radio diagnostics equipment, Laboratory equipment. Operation Theater was functional throughout the year. Bed Occupancy rate in MZH was 97% but in SZH it was only 63%.In SZH, OT was functional only 54% of the days in 2018. CT scan machine was just installed but not functional. Computerized X-Ray in SZH was functional only in 72% of the days. Level of client satisfaction was 87% in MZH but was just 43% in SZH. MZH performed all (256) the Caesarean Sections but SZH performed only 36% of 210 Caesarean Sections in 2018. In annual performance ranking of Government Hospitals, MZH was placed in 1st rank while as SZH was placed in 19th rank out of 32 referral hospitals nationwide in 2018. Conclusion: Biomedical technicians are the crucial member of the human resource for health team with the pivotal role. Trained and qualified BMET professionals are required within health-care systems in order to design, evaluate, regulate, acquire, maintain, manage and train on safe medical technologies. Applying knowledge of engineering and technology to health-care systems to ensure availability, affordability, accessibility, acceptability and utilization of the safer, higher quality, effective, appropriate and socially acceptable bio medical technology to populations for preventive, promotive, curative, rehabilitative and palliative care across all levels of the health service delivery.

Keywords: biomedical equipment technicians, BMET, human resources for health, HRH, quality health service, rural hospitals

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15 Approaching a Tat-Rev Independent HIV-1 Clone towards a Model for Research

Authors: Walter Vera-Ortega, Idoia Busnadiego, Sam J. Wilson

Abstract:

Introduction: Human Immunodeficiency Virus type 1 (HIV-1) is responsible for the acquired immunodeficiency syndrome (AIDS), a leading cause of death worldwide infecting millions of people each year. Despite intensive research in vaccine development, therapies against HIV-1 infection are not curative, and the huge genetic variability of HIV-1 challenges to drug development. Current animal models for HIV-1 research present important limitations, impairing the progress of in vivo approaches. Macaques require a CD8+ depletion to progress to AIDS, and the maintenance cost is high. Mice are a cheaper alternative but need to be 'humanized,' and breeding is not possible. The development of an HIV-1 clone able to replicate in mice is a challenging proposal. The lack of human co-factors in mice impedes the function of the HIV-1 accessory proteins, Tat and Rev, hampering HIV-1 replication. However, Tat and Rev function can be replaced by constitutive/chimeric promoters, codon-optimized proteins and the constitutive transport element (CTE), generating a novel HIV-1 clone able to replicate in mice without disrupting the amino acid sequence of the virus. By minimally manipulating the genomic 'identity' of the virus, we propose the generation of an HIV-1 clone able to replicate in mice to assist in antiviral drug development. Methods: i) Plasmid construction: The chimeric promoters and CTE copies were cloned by PCR using lentiviral vectors as templates (pCGSW and pSIV-MPCG). Tat mutants were generated from replication competent HIV-1 plasmids (NHG and NL4-3). ii) Infectivity assays: Retroviral vectors were generated by transfection of human 293T cells and murine NIH 3T3 cells. Virus titre was determined by flow cytometry measuring GFP expression. Human B-cells (AA-2) and Hela cells (TZMbl) were used for infectivity assays. iii) Protein analysis: Tat protein expression was determined by TZMbl assay and HIV-1 capsid by western blot. Results: We have determined that NIH 3T3 cells are able to generate HIV-1 particles. However, they are not infectious, and further analysis needs to be performed. Codon-optimized HIV-1 constructs are efficiently made in 293T cells in a Tat and Rev independent manner and capable of packaging a competent genome in trans. CSGW is capable of generating infectious particles in the absence of Tat and Rev in human cells when 4 copies of the CTE are placed preceding the 3’LTR. HIV-1 Tat mutant clones encoding different promoters are functional during the first cycle of replication when Tat is added in trans. Conclusion: Our findings suggest that the development of an HIV-1 Tat-Rev independent clone is challenging but achievable aim. However, further investigations need to be developed prior presenting our HIV-1 clone as a candidate model for research.

Keywords: codon-optimized, constitutive transport element, HIV-1, long terminal repeats, research model

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14 Health and Disease, Sickness and Well Being: Depictions in the Vinaya Pitaka and Jataka Narratives

Authors: Abhimanyu Kumar

Abstract:

The relationship between religion and medicine is much evident in the context of Buddhism. This paper is an attempt to look at the processes of social and cultural evolution of scientific creativity in the field of medicine and institutionalization of medical practices. The objective of the paper is to understand the Buddhist responses towards health as understood from the Vinaya Piṭaka and the Jātaka. This work is a result of the analysis of two important Buddhist texts: the Vinaya Piṭaka and the Jātaka. Broadly the Vinaya Piṭaka is concerned with the growth of Buddhist monasticism. The Vinaya Piṭaka is considered one of the most important sacred texts of the Buddhists, and contains rules for monastic life. These rules deal with such aspects as formal meetings of the saṃgha (monastery), expiation, confession, training, and legal questions. The Jātaka stories, on the other hand, are in the form of folk narratives, and provide a major source of medical consultation for all classes. These texts help us to ascertain the ‘proficiency and perceptions’ of the prevailing medical traditions. The Jātakas are a collection of 547 stories about the past lives of the Buddha, who is represented in anthropomorphic and animal form. The Jātaka connects itself between existing cognitive environments related to ethics and Buddhist didacticism. These stories are a reflection of the connection between the past and contemporary times (in the sense of time of creation of the story) as well. This is visible through the narrative strategy of the text, where every story is sub-divided into the story of the past and story of the present, and there is a significant identification element or connection that established at the end of each story. The minimal presence of philosophical content and the adoption of a narrative strategy make it possible for more of everyday life. This study gives me an opportunity to raise questions about how far were the body and mind closely interrelated in the Buddhist perceptions, and also did the society act like a laboratory for the Buddhists to practice healing activities? How far did religious responses to afflictions, be they leprosy or plague or anger, influence medical care; what impact did medical practitioners, religious authorities and the regulation of medical activity and practice have on healing the body and the mind; and, how has the healing environment been viewed. This paper is working with the idea that medical science in early India was not only for the curative purpose of diseases, but it fulfilled a greater cause of promoting, maintaining and restoring human health. In this regard, studying these texts gives an insight regarding religious responses to epidemics, from leprosy to plague, as well as to behavioral disorder such as anger. In other words, it deals with the idea about healing the body and healing the soul from a religious perspective.

Keywords: food for health, folk narratives, human body, materia medica, social sickness

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13 The Different Effects of Mindfulness-Based Relapse Prevention Group Therapy on QEEG Measures in Various Severity Substance Use Disorder Involuntary Clients

Authors: Yu-Chi Liao, Nai-Wen Guo, Chun‑Hung Lee, Yung-Chin Lu, Cheng-Hung Ko

Abstract:

Objective: The incidence of behavioral addictions, especially substance use disorders (SUDs), is gradually be taken seriously with various physical health problems. Mindfulness-based relapse prevention (MBRP) is a treatment option for promoting long-term health behavior change in recent years. MBRP is a structured protocol that integrates formal meditation practices with the cognitive-behavioral approach of relapse prevention treatment by teaching participants not to engage in reappraisal or savoring techniques. However, considering SUDs as a complex brain disease, questionnaires and symptom evaluation are not sufficient to evaluate the effect of MBRP. Neurophysiological biomarkers such as quantitative electroencephalogram (QEEG) may improve accurately represent the curative effects. This study attempted to find out the neurophysiological indicator of MBRP in various severity SUD involuntary clients. Participants and Methods: Thirteen participants (all males) completed 8-week mindfulness-based treatment provided by trained, licensed clinical psychologists. The behavioral data were from the Severity of Dependence Scale (SDS) and Negative Mood Regulation Scale (NMR) before and afterMBRP treatment. The QEEG data were simultaneously recorded with executive attention tasks, called comprehensive nonverbal attention test(CNAT). The two-way repeated-measures (treatment * severity) ANOVA and independent t-test were used for statistical analysis. Results: Thirteen participants regrouped into high substance dependence (HS) and low substance dependence (LS) by SDS cut-off. The HS group showed more SDS total score and lower gamma wave in the Go/No Go task of CNAT at pretest. Both groups showed the main effect that they had a lower frontal theta/beta ratio (TBR) during the simple reaction time task of CNAT. The main effect showed that the delay errors of CNAT were lower after MBRP. There was no other difference in CNAT between groups. However, after MBRP, compared to LS, the HS group have resonant progress in improving SDS and NMR scores. The neurophysiological index, the frontal TBR of the HS during the Go/No Go task of CNATdecreased than that of the LS group. Otherwise, the LS group’s gamma wave was a significant reduction on the Go/No Go task of CNAT. Conclusion: The QEEG data supports the MBRP can restore the prefrontal function of involuntary addicts and lower their errors in executive attention tasks. However, the improvement of MBRPfor the addict with high addiction severity is significantly more than that with low severity, including QEEG’s indicators and negative emotion regulation. Future directions include investigating the reasons for differences in efficacy among different severity of the addiction.

Keywords: mindfulness, involuntary clients, QEEG, emotion regulation

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12 Retrospective Assessment of the Safety and Efficacy of Percutaneous Microwave Ablation in the Management of Hepatic Lesions

Authors: Suang K. Lau, Ismail Goolam, Rafid Al-Asady

Abstract:

Background: The majority of patients with hepatocellular carcinoma (HCC) are not suitable for curative treatment, in the form of surgical resection or transplantation, due to tumour extent and underlying liver dysfunction. In these non-resectable cases, a variety of non-surgical therapies are available, including microwave ablation (MWA), which has shown increasing popularity due to its low morbidity, low reported complication rate, and the ability to perform multiple ablations simultaneously. Objective: The aim of this study was to evaluate the validity of MWA as a viable treatment option in the management of HCC and hepatic metastatic disease, by assessing its efficacy and complication rate at a tertiary hospital situated in Westmead (Australia). Methods: A retrospective observational study was performed evaluating patients that underwent MWA between 1/1/2017–31/12/2018 at Westmead Hospital, NSW, Australia. Outcome measures, including residual disease, recurrence rates, as well as major and minor complication rates, were retrospectively analysed over a 12-months period following MWA treatment. Excluded patients included those whose lesions were treated on the basis of residual or recurrent disease from previous treatment, which occurred prior to the study window (11 patients) and those who were lost to follow up (2 patients). Results: Following treatment of 106 new hepatic lesions, the complete response rate (CR) was 86% (91/106) at 12 months follow up. 10 patients had the residual disease at post-treatment follow up imaging, corresponding to an incomplete response (ICR) rate of 9.4% (10/106). The local recurrence rate (LRR) was 4.6% (5/106) with follow-up period up to 12 months. The minor complication rate was 9.4% (10/106) including asymptomatic pneumothorax (n=2), asymptomatic pleural effusions (n=2), right lower lobe pneumonia (n=3), pain requiring admission (n=1), hypotension (n=1), cellulitis (n=1) and intraparenchymal hematoma (n=1). There was 1 major complication reported, with pleuro-peritoneal fistula causing recurrent large pleural effusion necessitating repeated thoracocentesis (n=1). There was no statistically significant association between tumour size, location or ablation factors, and risk of recurrence or residual disease. A subset analysis identified 6 segment VIII lesions, which were treated via a trans-pleural approach. This cohort demonstrated an overall complication rate of 33% (2/6), including 1 minor complication of asymptomatic pneumothorax and 1 major complication of pleuro-peritoneal fistula. Conclusions: Microwave ablation therapy is an effective and safe treatment option in cases of non-resectable hepatocellular carcinoma and liver metastases, with good local tumour control and low complication rates. A trans-pleural approach for high segment VIII lesions is associated with a higher complication rate and warrants greater caution.

Keywords: hepatocellular carcinoma, liver metastases, microwave ablation, trans-pleural approach

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11 Sustainable Biostimulant and Bioprotective Compound for the Control of Fungal Diseases in Agricultural Crops

Authors: Geisa Lima Mesquita Zambrosi, Maisa Ciampi Guillardi, Flávia Rodrigues Patrício, Oliveiro Guerreiro Filho

Abstract:

Certified agricultural products are important components of the food industry. However, certifiers have been expanding the list of restricted or prohibited pesticides, limiting the options of products for phytosanitary control of plant diseases, but without offering alternatives to the farmers. Soybean and coffee leaf rust, brown eye spots, and Phoma leaf spots are the main fungal diseases that pose a serious threat to soybean and coffee cultivation worldwide. In conventional farming systems, these diseases are controlled by using synthetic fungicides, which, in addition to intensify the occurrence of fungal resistance, are highly toxic to the environment, farmers and consumers. In organic, agroecological, or regenerative farming systems, product options for plant protection are limited, being available only copper-based compounds, biodefensives or non-standard homemade products. Therefore, there is a growing demand for effective bioprotectors with low environmental impact for adoption in more sustainable agricultural systems. Then, to contribute with the covering of such a gap, we have developed a compound based on plant extracts and metallic elements for foliar application. This product has both biostimulant and bioprotective action, which promotes sustainable disease control, increases productivity as well as reduces the dependence on imported technologies the damages to the environment. The product's components have complementary mechanisms that promote protection against the disease by directly acting on the pathogens and activating the plant's natural defense system. The protective ability of the product against three coffee diseases (coffee leaf rust, brown eye spot, and Phoma leaf spot) and against soybean rust disease was evaluated, in addition to its ability to promote plant growth. Our goal is to offer an effective alternative to control the main coffee fungal diseases and soybean fungal diseases, with a biostimulant effect and low toxicity. The proposed product can also be part of the integrated management of coffee and soybean diseases in conventional farming associated with chemical and biological pesticides, offering the market a sustainable coffee and soybean with high added value and low residue content. Experiments were carried out under controlled conditions to evaluate the effectiveness of the product in controlling rust, phoma, and cercosporiosis in comparison to a control-inoculated plants that did not receive the product. The in vitro and in vivo effects of the product on the pathogen were evaluated using light microscopy and scanning electron microscopy, respectively. The fungistatic action of the product was demonstrated by a reduction of 85% and 95% in spore germination and disease symptoms severity on the leaves of coffee plants, respectively. The formulation had both a protective effect, acting to prevent infection by coffee leaf rust, and a curative effect, reducing the rust symptoms after its establishment.

Keywords: plant disease, natural fungicide, plant health, sustainability, alternative disease management

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10 Modeling Taxane-Induced Peripheral Neuropathy Ex Vivo Using Patient-Derived Neurons

Authors: G. Cunningham, E. Cantor, X. Wu, F. Shen, G. Jiang, S. Philips, C. Bales, Y. Xiao, T. R. Cummins, J. C. Fehrenbacher, B. P. Schneider

Abstract:

Background: Taxane-induced peripheral neuropathy (TIPN) is the most devastating survivorship issue for patients receiving therapy. Dose reductions due to TIPN in the curative setting lead to inferior outcomes for African American patients, as prior research has shown that this group is more susceptible to developing severe neuropathy. The mechanistic underpinnings of TIPN, however, have not been entirely elucidated. While it would be appealing to use primary tissue to study the development of TIPN, procuring nerves from patients is not realistically feasible, as nerve biopsies are painful and may result in permanent damage. Therefore, our laboratory has investigated paclitaxel-induced neuronal morphological and molecular changes using an ex vivo model of human-induced pluripotent stem cell (iPSC)-derived neurons. Methods: iPSCs are undifferentiated and endlessly dividing cells that can be generated from a patient’s somatic cells, such as peripheral blood mononuclear cells (PBMCs). We successfully reprogrammed PBMCs into iPSCs using the Erythroid Progenitor Reprograming Kit (STEMCell Technologiesᵀᴹ); pluripotency was verified by flow cytometry analysis. iPSCs were then induced into neurons using a differentiation protocol that bypasses the neural progenitor stage and uses selected small-molecule modulators of key signaling pathways (SMAD, Notch, FGFR1 inhibition, and Wnt activation). Results: Flow cytometry analysis revealed expression of core pluripotency transcription factors Nanog, Oct3/4 and Sox2 in iPSCs overlaps with commercially purchased pluripotent cell line UCSD064i-20-2. Trilineage differentiation of iPSCs was confirmed with immunofluorescent imaging with germ-layer-specific markers; Sox17 and ExoA2 for ectoderm, Nestin, and Pax6 for mesoderm, and Ncam and Brachyury for endoderm. Sensory neuron markers, β-III tubulin, and Peripherin were applied to stain the cells for the maturity of iPSC-derived neurons. Patch-clamp electrophysiology and calcitonin gene-related peptide (CGRP) release data supported the functionality of the induced neurons and provided insight into the timing for which downstream assays could be performed (week 4 post-induction). We have also performed a cell viability assay and fluorescence-activated cell sorting (FACS) using four cell-surface markers (CD184, CD44, CD15, and CD24) to select a neuronal population. At least 70% of the cells were viable in the isolated neuron population. Conclusion: We have found that these iPSC-derived neurons recapitulate mature neuronal phenotypes and demonstrate functionality. Thus, this represents a patient-derived ex vivo neuronal model to investigate the molecular mechanisms of clinical TIPN.

Keywords: chemotherapy, iPSC-derived neurons, peripheral neuropathy, taxane, paclitaxel

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9 Anti-tuberculosis, Resistance Modulatory, Anti-pulmonary Fibrosis and Anti-silicosis Effects of Crinum Asiaticum Bulbs and Its Active Metabolite, Betulin

Authors: Theophilus Asante, Comfort Nyarko, Daniel Antwi

Abstract:

Drug-resistant tuberculosis, together with the associated comorbidities like pulmonary fibrosis and silicosis, has been one of the most serious global public health threats that requires immediate action to curb or mitigate it. This prolongs hospital stays, increases the cost of medication, and increases the death toll recorded annually. Crinum asiaticum bulb (CAE) and betulin (BET) are known for their biological and pharmacological effects. Pharmacological effects reported on CAE include antimicrobial, anti-inflammatory, anti-pyretic, anti-analgesic, and anti-cancer effects. Betulin has exhibited a multitude of powerful pharmacological properties ranging from antitumor, anti-inflammatory, anti-parasitic, anti-microbial, and anti-viral activities. This work sought to investigate the anti-tuberculosis and resistant modulatory effects and also assess their effects on mitigating pulmonary fibrosis and silicosis. In the anti-tuberculosis and resistant modulatory effects, both CAE and BET showed strong antimicrobial activities (31.25 ≤ MIC ≤ 500) µg/ml against the studied microorganisms and also produced significant anti-efflux pump and biofilm inhibitory effects (ρ < 0.0001) as well as exhibiting resistance modulatory and synergistic effects when combined with standard antibiotics. Crinum asiaticum bulbs extract and betulin were shown to possess anti-pulmonary fibrosis effects. There was an increased survival rate in the CAE and BET treatment groups compared to the BLM-induced group. There was a marked decrease in the levels of hydroxyproline and collagen I and III in the CAE and BET treatment groups compared to the BLM-treated group. The treatment groups of CAE and BET significantly downregulated the levels of pro-fibrotic and pro-inflammatory cytokine concentrations such as TGF-β1, MMP9, IL-6, IL-1β and TNF-alpha compared to an increase in the BLM-treated groups. The histological findings of the lungs suggested the curative effects of CAE and BET following BLM-induced pulmonary fibrosis in mice. The study showed improved lung functions with a wide focal area of viable alveolar spaces and few collagen fibers deposition on the lungs of the treatment groups. In the anti-silicosis and pulmonoprotective effects of CAE and BET, the levels of NF-κB, TNF-α, IL-1β, IL-6 and hydroxyproline, collagen types I and III were significantly reduced by CAE and BET (ρ < 0.0001). Both CAE and BET significantly (ρ < 0.0001) inhibited the levels of hydroxyproline, collagen I and III when compared with the negative control group. On BALF biomarkers such as macrophages, lymphocytes, monocytes, and neutrophils, CAE and BET were able to reduce their levels significantly (ρ < 0.0001). The CAE and BET were examined for anti-oxidant activity and shown to raise the levels of catalase (CAT) and superoxide dismutase (SOD) while lowering the level of malondialdehyde (MDA). There was an improvement in lung function when lung tissues were examined histologically. Crinum asiaticum bulbs extract and betulin were discovered to exhibit anti-tubercular and resistance-modulatory properties, as well as the capacity to minimize TB comorbidities such as pulmonary fibrosis and silicosis. In addition, CAE and BET may act as protective mechanisms, facilitating the preservation of the lung's physiological integrity. The outcomes of this study might pave the way for the development of leads for producing single medications for the management of drug-resistant tuberculosis and its accompanying comorbidities.

Keywords: fibrosis, crinum, tuberculosis, antiinflammation, drug resistant

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8 Migrant and Population Health, Two Sides of a Coin: A Descriptive Study

Authors: A. Sottomayor, M. Perez Duque, M. C. Henriques

Abstract:

Introduction: Migration is not a new phenomenon; nomads often traveled, seeking better living conditions, including food and water. The increase of migrations affects all countries, rising health-related challenges. In Portugal, we have had migrant movements in the last decades, pairing with economic behavior. Irregular immigrants are detained in Santo António detention center from Portuguese Immigration and Borders Service (USHA-SEF) in Porto until court decision for a maximum of 60 days. It is the only long stay officially designated detention center for immigrants in Portugal. Immigrant health is important for public health (PH). It affects and is affected by the community. The XXVII Portuguese Government considered immigrant integration, including access to health, health promotion, protection and reduction of inequities a political priority. Many curative, psychological and legal services are provided for detainees, but until 2015, no structured health promotion or prevention actions were being held at USHA-SEF. That year, Porto Occidental PH Local Unit started to provide vaccination and health literacy on this theme for detainees and SEF workers. Our activities include a vaccine lecture, a medical consultation with vaccine prescription and administration, along with documented proof of vaccination. All vaccines are volunteer and free of charge. This action reduces the risk of importation and transmission of diseases, contributing to world eradication and elimination programs. We aimed to characterize the demography of irregular immigrant detained at UHSA-SEF and describe our activity. Methods: All data was provided by Porto Occidental Public Health Unit. All paper registers of vaccination were uploaded to MicrosoftExcel®. We included all registers and collected demographic variables, nationality, vaccination date, category, and administered vaccines. Descriptive analysis was performed using MicrosoftExcel®. Results: From 2015 to 2018, we delivered care to 256 individuals (179 immigrants; 77 workers). Considering immigrants, 72% were male, and 8 (16%) women were pregnant. 85% were between 20-54 years (ᵡ=30,8y; 2-71y), and 11 didn’t report any age. Migrants came from 48 countries, and India had the highest number (9%). MMR and Tetanus vaccines had > 90% vaccination rate and Poliomyelitis, hepatitis B and flu vaccines had around 85% vaccination rates. We had a consistent number of refusals. Conclusion: Our irregular migrant population comes from many different countries, which increases the risk of disease importation. Pregnant women are present as a particular subset of irregular migrants, and vaccination protects them and the baby. Vaccination of migrant is valuable for them and for the countries in which they pass. It contributes to universal health coverage, for eradication programmes and accomplishment of the Sustainable Development Goals. Peer influence may present as a determinant of refusals so we must consistently educate migrants before vaccination. More studies would be valuable, particularly on the migrant trajectory, duration of stay, destiny after court decision and health impact.

Keywords: migrants, public health, universal health coverage, vaccination

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7 Comparing Community Health Agents, Physicians and Nurses in Brazil's Family Health Strategy

Authors: Rahbel Rahman, Rogério Meireles Pinto, Margareth Santos Zanchetta

Abstract:

Background: Existing shortcomings of current health-service delivery include poor teamwork, competencies that do not address consumer needs, and episodic rather than continuous care. Brazil’s Sistema Único de Saúde (Unified Health System, UHS) is acknowledged worldwide as a model for delivering community-based care through Estratégia Saúde da Família (FHS; Family Health Strategy) interdisciplinary teams, comprised of Community Health Agents (in Portuguese, Agentes Comunitário de Saude, ACS), nurses, and physicians. FHS teams are mandated to collectively offer clinical care, disease prevention services, vector control, health surveillance and social services. Our study compares medical providers (nurses and physicians) and community-based providers (ACS) on their perceptions of work environment, professional skills, cognitive capacities and job context. Global health administrators and policy makers can leverage on similarities and differences across care providers to develop interprofessional training for community-based primary care. Methods: Cross-sectional data were collected from 168 ACS, 62 nurses and 32 physicians in Brazil. We compared providers’ demographic characteristics (age, race, and gender) and job context variables (caseload, work experience, work proximity to community, the length of commute, and familiarity with the community). Providers perceptions were compared to their work environment (work conditions and work resources), professional skills (consumer-input, interdisciplinary collaboration, efficacy of FHS teams, work-methods and decision-making autonomy), and cognitive capacities (knowledge and skills, skill variety, confidence and perseverance). Descriptive and bi-variate analysis, such as Pearson Chi-square and Analysis of Variance (ANOVA) F-tests, were performed to draw comparisons across providers. Results: Majority of participants were ACS (64%); 24% nurses; and 12% physicians. Majority of nurses and ACS identified as mixed races (ACS, n=85; nurses, n=27); most physicians identified as males (n=16; 52%), and white (n=18; 58%). Physicians were less likely to incorporate consumer-input and demonstrated greater decision-making autonomy than nurses and ACS. ACS reported the highest levels of knowledge and skills but the least confidence compared to nurses and physicians. ACS, nurses, and physicians were efficacious that FHS teams improved the quality of health in their catchment areas, though nurses tend to disagree that interdisciplinary collaboration facilitated their work. Conclusion: To our knowledge, there has been no study comparing key demographic and cognitive variables across ACS, nurses and physicians in the context of their work environment and professional training. We suggest that global health systems can leverage upon the diverse perspectives of providers to implement a community-based primary care model grounded in interprofessional training. Our study underscores the need for in-service trainings to instill reflective skills of providers, improve communication skills of medical providers and curative skills of ACS. Greater autonomy needs to be extended to community based providers to offer care integral to addressing consumer and community needs.

Keywords: global health systems, interdisciplinary health teams, community health agents, community-based care

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6 Single Cell Analysis of Circulating Monocytes in Prostate Cancer Patients

Authors: Leander Van Neste, Kirk Wojno

Abstract:

The innate immune system reacts to foreign insult in several unique ways, one of which is phagocytosis of perceived threats such as cancer, bacteria, and viruses. The goal of this study was to look for evidence of phagocytosed RNA from tumor cells in circulating monocytes. While all monocytes possess phagocytic capabilities, the non-classical CD14+/FCGR3A+ monocytes and the intermediate CD14++/FCGR3A+ monocytes most actively remove threatening ‘external’ cellular materials. Purified CD14-positive monocyte samples from fourteen patients recently diagnosed with clinically localized prostate cancer (PCa) were investigated by single-cell RNA sequencing using the 10X Genomics protocol followed by paired-end sequencing on Illumina’s NovaSeq. Similarly, samples were processed and used as controls, i.e., one patient underwent biopsy but was found not to harbor prostate cancer (benign), three young, healthy men, and three men previously diagnosed with prostate cancer that recently underwent (curative) radical prostatectomy (post-RP). Sequencing data were mapped using 10X Genomics’ CellRanger software and viable cells were subsequently identified using CellBender, removing technical artifacts such as doublets and non-cellular RNA. Next, data analysis was performed in R, using the Seurat package. Because the main goal was to identify differences between PCa patients and ‘control’ patients, rather than exploring differences between individual subjects, the individual Seurat objects of all 21 patients were merged into one Seurat object per Seurat’s recommendation. Finally, the single-cell dataset was normalized as a whole prior to further analysis. Cell identity was assessed using the SingleR and cell dex packages. The Monaco Immune Data was selected as the reference dataset, consisting of bulk RNA-seq data of sorted human immune cells. The Monaco classification was supplemented with normalized PCa data obtained from The Cancer Genome Atlas (TCGA), which consists of bulk RNA sequencing data from 499 prostate tumor tissues (including 1 metastatic) and 52 (adjacent) normal prostate tissues. SingleR was subsequently run on the combined immune cell and PCa datasets. As expected, the vast majority of cells were labeled as having a monocytic origin (~90%), with the most noticeable difference being the larger number of intermediate monocytes in the PCa patients (13.6% versus 7.1%; p<.001). In men harboring PCa, 0.60% of all purified monocytes were classified as harboring PCa signals when the TCGA data were included. This was 3-fold, 7.5-fold, and 4-fold higher compared to post-RP, benign, and young men, respectively (all p<.001). In addition, with 7.91%, the number of unclassified cells, i.e., cells with pruned labels due to high uncertainty of the assigned label, was also highest in men with PCa, compared to 3.51%, 2.67%, and 5.51% of cells in post-RP, benign, and young men, respectively (all p<.001). It can be postulated that actively phagocytosing cells are hardest to classify due to their dual immune cell and foreign cell nature. Hence, the higher number of unclassified cells and intermediate monocytes in PCa patients might reflect higher phagocytic activity due to tumor burden. This also illustrates that small numbers (~1%) of circulating peripheral blood monocytes that have interacted with tumor cells might still possess detectable phagocytosed tumor RNA.

Keywords: circulating monocytes, phagocytic cells, prostate cancer, tumor immune response

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5 Impact of α-Adrenoceptor Antagonists on Biochemical Relapse in Men Undergoing Radiotherapy for Localised Prostate Cancer

Authors: Briohny H. Spencer, Russ Chess-Williams, Catherine McDermott, Shailendra Anoopkumar-Dukie, David Christie

Abstract:

Background: Prostate cancer is the second most common cancer diagnosed in men worldwide and the most prevalent in Australian men. In 2015, it was estimated that approximately 18,000 new cases of prostate cancer were diagnosed in Australia. Currently, for localised disease, androgen depravation therapy (ADT) and radiotherapy are a major part of the curative management of prostate cancer. ADT acts to reduce the levels of circulating androgens, primarily testosterone and the locally produced androgen, dihydrotestosterone (DHT), or by preventing the subsequent activation of the androgen receptor. Thus, the growth of the cancerous cells can be reduced or ceased. Radiation techniques such as brachytherapy (radiation delivered directly to the prostate by transperineal implant) or external beam radiation therapy (exposure to a sufficient dose of radiation aimed at eradicating malignant cells) are also common techniques used in the treatment of this condition. Radiotherapy (RT) has significant limitations, including reduced effectiveness in treating malignant cells present in hypoxic microenvironments leading to radio-resistance and poor clinical outcomes and also the significant side effects for the patients. Alpha1-adrenoceptor antagonists are used for many prostate cancer patients to control lower urinary tract symptoms, due to the progression of the disease itself or may arise as an adverse effect of the radiotherapy treatment. In Australia, a significant number (not a majority) of patients receive a α1-ADR antagonist and four drugs are available including prazosin, terazosin, alfuzosin and tamsulosin. There is currently limited published data on the effects of α1-ADR antagonists during radiotherapy, but it suggests these medications may improve patient outcomes by enhancing the effect of radiotherapy. Aim: To determine the impact of α1-ADR antagonists treatments on time to biochemical relapse following radiotherapy. Methods: A retrospective study of male patients receiving radiotherapy for biopsy-proven localised prostate cancer was undertaken to compare cancer outcomes for drug-naïve patients and those receiving α1-ADR antagonist treatments. Ethical approval for the collection of data at Genesis CancerCare QLD was obtained and biochemical relapse (defined by a PSA rise of >2ng/mL above the nadir) was recorded in months. Rates of biochemical relapse, prostate specific antigen doubling time (PSADT) and Kaplan-Meier survival curves were also compared. Treatment groups were those receiving α1-ADR antagonists treatment before or concurrent with their radiotherapy. Data was statistically analysed using One-way ANOVA and results expressed as mean ± standard deviation. Major findings: The mean time to biochemical relapse for tamsulosin, prazosin, alfuzosin and controls were 45.3±17.4 (n=36), 41.5±19.6 (n=11), 29.3±6.02 (n=6) and 36.5±17.6 (n=16) months respectively. Tamsulosin, prazosin but not alfuzosin delayed time to biochemical relapse although the differences were not statistically significant. Conclusion: Preliminary data for the prior and/or concurrent use of tamsulosin and prazosin showed a positive trend in delaying time to biochemical relapse although no statistical significance was shown. Larger clinical studies are indicated and with thousands of patient records yet to be analysed, it may determine if there is a significant effect of these drugs on control of prostate cancer.

Keywords: alpha1-adrenoceptor antagonists, biochemical relapse, prostate cancer, radiotherapy

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4 Factors Affecting Treatment Resilience in Patients with Oesophago-Gastric Cancers Undergoing Palliative Chemotherapy: A Literature Review

Authors: Kiran Datta, Daniella Holland-Hart, Anthony Byrne

Abstract:

Introduction: Oesophago-gastric (OG) cancers are the fifth commonest in the UK, accounting for over 12,000 deaths each year. Most patients will present at later stages of the disease, with only 21% of patients with stage 4 disease surviving longer than a year. As a result, many patients are unsuitable for curative surgery and instead receive palliative treatment to improve prognosis and symptom burden. However, palliative chemotherapy can result in significant toxicity: almost half of the patients are unable to complete their chemotherapy regimen, with this proportion rising significantly in older and frailer patients. In addition, clinical trials often exclude older and frailer patients due to strict inclusion criteria, meaning there is limited evidence to guide which patients are most likely to benefit from palliative chemotherapy. Inappropriate chemotherapy administration is at odds with the goals of palliative treatment and care, which are to improve quality of life, and this also represents a significant resource expenditure. This literature review aimed to examine and appraise evidence regarding treatment resilience in order to guide clinicians in identifying the most suitable candidates for palliative chemotherapy. Factors influencing treatment resilience were assessed, as measured by completion rates, dose reductions, and toxicities. Methods: This literature review was conducted using rapid review methodology, utilising modified systematic methods. A literature search was performed across the MEDLINE, EMBASE, and Cochrane Library databases, with results limited to papers within the last 15 years and available in English. Key inclusion criteria included: 1) participants with either oesophageal, gastro-oesophageal junction, or gastric cancers; 2) patients treated with palliative chemotherapy; 3) available data evaluating the association between baseline participant characteristics and treatment resilience. Results: Of the 2326 papers returned, 11 reports of 10 studies were included in this review after excluding duplicates and irrelevant papers. Treatment resilience factors that were assessed included: age, performance status, frailty, inflammatory markers, and sarcopenia. Age was generally a poor predictor for how well patients would tolerate chemotherapy, while poor performance status was a better indicator of the need for dose reduction and treatment non-completion. Frailty was assessed across one cohort using multiple screening tools and was an effective marker of the risk of toxicity and the requirement for dose reduction. Inflammatory markers included lymphopenia and the Glasgow Prognostic Score, which assessed inflammation and hypoalbuminaemia. Although quick to obtain and interpret, these findings appeared less reliable due to the inclusion of patients treated with palliative radiotherapy. Sarcopenia and body composition were often associated with chemotherapy toxicity but not the rate of regimen completion. Conclusion: This review demonstrates that there are numerous measures that can estimate the ability of patients with oesophago-gastric cancer to tolerate palliative chemotherapy, and these should be incorporated into clinical assessments to promote personalised decision-making around treatment. Age should not be a barrier to receiving chemotherapy and older and frailer patients should be included in future clinical trials to better represent typical patients with oesophago-gastric cancers. Decisions regarding palliative treatment should be guided by these factors identified as well as patient preference.

Keywords: frailty, oesophago-gastric cancer, palliative chemotherapy, treatment resilience

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3 Gis Based Flash Flood Runoff Simulation Model of Upper Teesta River Besin - Using Aster Dem and Meteorological Data

Authors: Abhisek Chakrabarty, Subhraprakash Mandal

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Flash flood is one of the catastrophic natural hazards in the mountainous region of India. The recent flood in the Mandakini River in Kedarnath (14-17th June, 2013) is a classic example of flash floods that devastated Uttarakhand by killing thousands of people.The disaster was an integrated effect of high intensityrainfall, sudden breach of Chorabari Lake and very steep topography. Every year in Himalayan Region flash flood occur due to intense rainfall over a short period of time, cloud burst, glacial lake outburst and collapse of artificial check dam that cause high flow of river water. In Sikkim-Derjeeling Himalaya one of the probable flash flood occurrence zone is Teesta Watershed. The Teesta River is a right tributary of the Brahmaputra with draining mountain area of approximately 8600 Sq. km. It originates in the Pauhunri massif (7127 m). The total length of the mountain section of the river amounts to 182 km. The Teesta is characterized by a complex hydrological regime. The river is fed not only by precipitation, but also by melting glaciers and snow as well as groundwater. The present study describes an attempt to model surface runoff in upper Teesta basin, which is directly related to catastrophic flood events, by creating a system based on GIS technology. The main object was to construct a direct unit hydrograph for an excess rainfall by estimating the stream flow response at the outlet of a watershed. Specifically, the methodology was based on the creation of a spatial database in GIS environment and on data editing. Moreover, rainfall time-series data collected from Indian Meteorological Department and they were processed in order to calculate flow time and the runoff volume. Apart from the meteorological data, background data such as topography, drainage network, land cover and geological data were also collected. Clipping the watershed from the entire area and the streamline generation for Teesta watershed were done and cross-sectional profiles plotted across the river at various locations from Aster DEM data using the ERDAS IMAGINE 9.0 and Arc GIS 10.0 software. The analysis of different hydraulic model to detect flash flood probability ware done using HEC-RAS, Flow-2D, HEC-HMS Software, which were of great importance in order to achieve the final result. With an input rainfall intensity above 400 mm per day for three days the flood runoff simulation models shows outbursts of lakes and check dam individually or in combination with run-off causing severe damage to the downstream settlements. Model output shows that 313 Sq. km area were found to be most vulnerable to flash flood includes Melli, Jourthang, Chungthang, and Lachung and 655sq. km. as moderately vulnerable includes Rangpo,Yathang, Dambung,Bardang, Singtam, Teesta Bazarand Thangu Valley. The model was validated by inserting the rain fall data of a flood event took place in August 1968, and 78% of the actual area flooded reflected in the output of the model. Lastly preventive and curative measures were suggested to reduce the losses by probable flash flood event.

Keywords: flash flood, GIS, runoff, simulation model, Teesta river basin

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2 Enhanced Bioproduction of Moscatilin in Dendrobium ovatum through Hairy Root Culture

Authors: Ipsita Pujari, Abitha Thomas, Vidhu S. Babu, K. Satyamoorthy

Abstract:

Orchids are esteemed as celebrities in cut flower industry globally, due to their long-lasting fragrance and freshness. Apart from splendor, the unique metabolites endowed with pharmaceutical potency have made them one of the most hunted in plant kingdom. This had led to their trafficking, resulting in habitat loss, subsequently making them occupiers of IUCN red list as RET species. Many of the orchids especially wild varieties still remain undiscovered. In view to protect and conserve the wild germplasm, researchers have been inventing novel micropropagation protocols; thereby conserving Orchids. India is overflowing with exclusive wild cultivars of Orchids, whose pharmaceutical properties remain untapped and are not marketed owing to relatively small flowers. However, their germplasm is quite pertinent to be preserved for making unusual hybrids. Dendrobium genus is the second largest among Orchids exists in India and has highest demand attributable to enduring cut flowers and significant therapeutic uses in traditional medicinal system. Though the genus is quite endemic in Western Ghat regions of the country, many species are still anonymous with their unknown curative properties. A standard breeding cycle in Orchids usually takes five to seven years (Dendrobium hybrids taking a long juvenile phase of two to five years reaching maturity and flowering stage) and this extensive life cycle has always hindered the development of Dendrobium breeding. Dendrobium is reported with essential therapeutic plant bio-chemicals and ‘Moscatilin’ is one, found exclusive to this famous Dendrobium genus. Moscatilin is reported to have anti-mutagenic and anti-cancer properties, whose positive action has very recently been demonstrated against a range of cancers. Our preliminary study here established a simple and economic small-scale propagation protocol of Dendrobium ovatum describing in vitro production of Moscatilin. Subsequently for enhancing the content of Moscatilin, an efficient experimental related to the organization of transgenic (hairy) D. ovatum root cultures through infection of Agrobacterium rhizogenes 2364 strain on MS basal medium is being reported in the present study. Hairy roots generated on almost half of the explants used (spherules, in vitro plantlets and calli) maintained through suspension cultures, after 8 weeks of co-cultivation with Agrobacterium rhizogenes. GFP assay performed with isolated hairy roots has confirmed the integrative transformation which was further positively confirmed by PCR using rolB gene specific primers. Reverse phase-high performance liquid chromatography and mass spectrometry techniques were used for quantification and accurate identification of Moscatilin respectively from transgenic systems. A noticeable ~3 fold increase in contents were observed in transformed D. ovatum root cultures as compared to the simple in vitro culture, callus culture and callus regeneration plantlets. Role of elicitors e.g., Methyl jasmonate, Salicylic acid, Yeast extract and Chitosan were tested for elevating the Moscatilin content to obtain a comprehensive optimized protocol facilitating the in vitro production of valuable Moscatilin with larger yield. This study would provide evidence towards the in vitro assembly of Moscatilin within a short time-period through not a so-expensive technology for the first time. It also serves as an appropriate basis for bioreactor scale-up resulting in commercial bioproduction of Moscatilin.

Keywords: bioproduction, Dendrobium ovatum, hairy root culture, moscatilin

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1 Amifostine Analogue, Drde-30, Attenuates Radiation-Induced Lung Injury in Mice

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

Abstract:

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

Keywords: amifostine, fibrosis, inflammation, lung injury radiation

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