Palliative Care

Pharmacogenomics in palliative medicine Mahadev Rao Indian Journal of Palliative Care 2019 25(2):169-171

A survey of medical professionals in an apex tertiary care hospital to assess awareness, interest, practices, and knowledge in palliative care: A descriptive cross-sectional study Anuradha Patel, SVS Deo, Sushma Bhatnagar Indian Journal of Palliative Care 2019 25(2):172-180 Background: Medical discipline in India focuses on cure rather than comfort care. Palliative care is concerned with improving quality of life and relieving sufferings in patients with advanced incurable terminal diseases. Palliative care in India is still in infancy stage due to lack of knowledge, attitude and skills among health care providers. The reason being lack of training in under graduate as well as postgraduate teaching curriculum and lack of sensitization among policy makers. Aims and Objectives: To assess the awareness, interest, practices and knowledge in palliative care among medical professionals working in a tertiary care hospital. Materials and Methods: All participants were mailed proforma to be filled in a fixed format including details of their qualification, demographic data, their field of work, their training in palliative care and multiple choice questions regarding awareness interest, practices and knowledge of palliative care. Results: Out of 186 respondents, 56% had not received any basic training in palliative care. 81% wanted palliative care education to be included in undergraduate curriculum. Poor program was identified as the most common barrier in learning palliative care. 77% respondents had no idea about home based palliative care services. 50.8% patients dies in hospital in their terminal stage. 88% were interested in learning safe opioid practices. Although 89.8% were aware of the need of palliative care in metastatic cancer but less than 50% were aware of the fact that palliative care is also required in MDR-TB and mental illness. Conclusion: This study reflects data of an apex cancer institute of the country. The result of awareness is not very encouraging despite a dedicated palliative care department. So, we can assume what will be the palliative care status in other parts of India where there is no palliative care at all. Recommendation: We strongly recommends that palliative care teaching should be incorporated in undergraduate curriculum to sensitize the students from the beginning. Budding residents in their learning phase can play an important role by learning and providing palliative care as the first person to come into contact with the patients are residents. There is a strong need of spreading palliative care awareness all over the country.

A qualitative evaluation of a home-based palliative care program utilizing community health workers in India Maryellen Potts, Kathleen B Cartmell, Lynne S Nemeth, Suparna Qanungo Indian Journal of Palliative Care 2019 25(2):181-189 Aim: In India, the need for rural palliative care is increasing with the rising number of people diagnosed with late-stage cancers. Rural areas also have a shortage of trained medical personnel to deliver palliative care. To address these needs, a home-based palliative care program using community health workers (CHWs) to facilitate care delivery was developed to extend the reach of a cancer center's palliative care services outside of Kolkata, India. The research question guiding this qualitative study was, how feasible, useful, and acceptable was this program from the perspectives of the clinical team and CHWs who delivered the intervention? Methods: This qualitative descriptive study used a grounded theory approach and the iterative constant comparative method to collect and analyze data from the key stakeholder interviews. Ten qualitative interviews took place at the Saroj Gupta Cancer Center and Research Institute and were conducted with the CHWs who delivered the home-based palliative care intervention (n = 3) and the clinical team who provided them with training, support, and supervision (n = 7). Results: Three major themes emerged (a) CHWs' desire and need for more training, (b) the need for tailoring of existing intervention protocols and modifying expectations of stakeholders, and (c) the need for considerations for ensuring program sustainability. Conclusions: The study provided evidence that the utilization of CHWs to facilitate delivery of palliative care is a feasible model worthy of consideration and further research testing in low-resource settings.

The correlation between respecting the dignity of cancer patients and the quality of nurse-patient communication Zoleikha Avestan, Vahid Pakpour, Azad Rahmani, Robab Mohammadian, Amin Soheili Indian Journal of Palliative Care 2019 25(2):190-196 Context: Nurse–patient communication is one of the important factors affects the promotion and maintenance of the dignity of cancer patients in the hospital settings. Aims: This study aimed to determine the perceptions of cancer patients regarding respecting their dignity and its correlation with nurse–patient communication in the hospital settings. Subjects and Methods: This correlational study was conducted on 250 cancer patients admitted to the Oncology Departments of Tabriz Shahid Ghazi University Hospital, Iran. These patients were selected using a convenience sampling method. The Patient Dignity Inventory and Nurse Quality of Communication with Patient Questionnaire were used for collecting the data. Statistical Analysis Used: Descriptive and inferential statistics were applied to the data. Results: The score of nurse–patient relationship is significantly correlated with patient's dignity score (R = −0.21, P = 0.001). Conclusions: Due to the importance of nurse–patient communication on maintenance of the dignity of cancer patients, it is a necessary requirement to take proper actions in this area, particularly by promoting “nurse's communication skills.”

Functional status of older adults with dementia at the end of life: Is there still anything to do? Mehmet Ilkin Naharci, Oznur Buyukturan, Umit Cintosun, Huseyin Doruk, Ilker Tasci Indian Journal of Palliative Care 2019 25(2):197-202 Aims: There is a lack of data on physical functional status near death of patients with different types of dementia that can contribute to decisions about what kind of care is needed. The aim of this study was to investigate the course of functional status along with the documented reasons for death in participants with dementia who had regularly been followed at a geriatric outpatient unit. Setting and Design: A retrospective observational cohort study was done using the database of a geriatric outpatient clinic. Subjects and Methods: Sociodemographic and medical records of patients with Alzheimer's disease (AD), vascular dementia, mixed dementia, and dementia with Lewy bodies (DLB)/Parkinson's disease dementia (PDD) who had received routine care in a geriatrics outpatient setting for a minimum of 12 months before death were analyzed. Scores for activities of daily living and documented probable causes of death were recorded. Results: Of the 258 participants, 111 (42 female and 69 male) were included in this study. AD was the leading cause of dementia (51.8%). The median duration of survival with dementia was 4 years. The leading causes of death were cardiovascular disease (CVD) (27.0%) and dementia (27.0%) followed by infections (21.6%) and stroke (10.8%). Disability was the highest in patients with DLB/PDD. Conclusions: This study found relatively shorter survival after the diagnosis of dementia when compared to other populations. CVD still appeared as a major cause of that in this particular disease. Most debilitating type of dementia was DLB/PDD.

Barriers to effective use of palliative care services in the acute care setting with emphasis on terminal noncancer diseases Randol Kennedy, Nabilah Abdullah, Rhajarshi Bhadra, Nana Osei Bonsu, Mojtaba Fayezizadeh, Harold Ickes Indian Journal of Palliative Care 2019 25(2):203-209 Introduction: This study assessed the views of nurses, resident doctors, and attending physicians of the use of a readily available pain and palliative care specialty at their institution while assessing their ability to recognize terminal noncancer illnesses. Methodology: In community hospital consisting of an in-patient pain and palliative specialty, attending physicians, residents, and nurses participate in a survey highlighting the following: parameters for referral/consultation, definition of noncancer-related terminal illnesses, role of pain and palliative care in acute care, consult/referral delay, barriers to effective referral, recognition and withdrawal of futile care, and opioid prescription. Patterns of responses by each professional group were compared and contrasted. Results: The most common accepted reasons for referral were that of hospice care, terminal cancer, and uncontrolled pain, while reasons related to terminal noncancer illnesses were less accepted. A majority of approved physical and social parameters to define terminal noncancer illnesses were not universally accepted among the groups-especially among attendings and residents. While most participants agreed that the best time to refer to palliative care specialty was at the point of diagnosis of a terminal illness, >25% of participants from each group felt that referrals should be done later in the course of the illness. The most highlighted reasons expressed by attendings and residents for the delay in consult were either that of excessive withdrawal of modalities of care or interference with ongoing management that may benefit the patient. Most residents and nurses agreed that attendings' reluctance to consult is a major barrier to its utilization. Conclusion: Barriers to effective utilization are multifactorial, mostly relating to perceptions of the specialty as well as ineffective communication within specialties.

The effect of positive psychotherapy on the meaning of life in patients with cancer: A randomized clinical trial Batool Saeedi, Zohreh Khoshnood, Mahlagha Dehghan, Farokh Abazari, Ali Saeedi Indian Journal of Palliative Care 2019 25(2):210-217 Background and Aim: Cancer, as a social phenomenon, disrupts the daily functions and social activities of a person and changes his ability to perform roles and responsibilities and reach the meaning of life. The purpose of this study was to investigate the effect of positive psychotherapy on understanding the meaning of life in patients with cancer. Materials and Methods: This was a randomized clinical trial study. Sixty-one patients with cancer were selected by convenience sampling method and were assigned randomly into two positive psychotherapeutic (n = 30) and control (n = 31) groups. Positive psychotherapy included eight 90-min sessions held weekly in group form. The life attitude profile-Gary Reker was completed before and after the intervention. Results: The results showed that there was no significant difference between the mean scores of meaning of life and all its dimensions (purposes, existential vacuum, death acceptance, goal seeking, coherence and responsibility choice) before intervention, but there was a significant difference between the two groups after intervention (P < 0.05). Also in the control group, the mean score was reduced after the intervention. Conclusion: The positive psychotherapy is effective in increasing the level of meaningful life, enjoyable and committed life of people with cancer. Therefore, based on the results of this study, health-care managers can plan to train and increase the empowerment of nurses in providing these interventions to patients in need.

Understanding the organization of hospital-based palliative care in a Nigerian Hospital: An ethnographic study David A Agom, Helen Poole, Stuart Allen, Tonia C Onyeka, Jude Ominyi Indian Journal of Palliative Care 2019 25(2):218-223 Context: Organization and delivery of palliative care (PC) services vary from one country to another. In Nigeria, PC has continued to develop, yet the organization and scope of PC is not widely known by most clinicians and the public. Objectives: The aim of the study is to identify PC services available in a Nigerian Hospital and how they are organized. Methods: This ethnographic study, utilized documentary analysis, participant observation, and ethnographic interviews (causal chat during observation and individual interviews) to gather data from members of PC team comprising doctors (n = 10), nurses (n = 4), medical social workers (n = 2), a physiotherapist, and a pharmacist, as well nurses from the oncology department (n = 3). Data were analyzed using Spradley's framework for ethnographic data analysis. Results: PC was found to be largely adult patient-centered. A hospital-based care delivery model, in the forms of family meetings, in- and out-patients' consultation services, and a home-based delivery model which is primarily home visits conducted once in a week, were the two models of care available in the studied hospital. The members of the PC team operated two shift patterns from 7:00 am to 2.00 pm and a late shift from 2:00 pm to 7:00 pm instead of 24 h service provision. Conclusions: Although PC in this hospital has made significant developmental progress, the organization and scope of services are suggestive of the need for more development, especially in manpower and collaborative care. This study provided knowledge that could be used to improve the clinical practice of PC in various cross-cultural Nigerian societies and other African context, as well as revealing areas for PC development.

End-of-life practices in rural South India: SocioCultural determinants Sudha Ramalingam, Subhashini Ganesan Indian Journal of Palliative Care 2019 25(2):224-227 Introduction: End of life care of terminally ill is a sensitive topic in our socio cultural ethos. In a country where Euthanasia policies are widely debated, dignified death is a desired form of death. Euthanasia literally means “good death”. In India the debate still continues on practices related to euthanasia and its legalization until recently when the verdict on the passive euthanasia has been passed by the supreme court. In addition, lack of an effective palliative care system has led to complex situations towards the end of life. Globally, it is estimated that palliative care is needed in 40-60% of all deaths. However there is no training or facility to meet this demand. Methodology: A focus group discussion (FGD) was carried out among 22 residents in a rural area of Tamilnadu to identify the social and cultural determinants of end of life care practices. A FGD guide was prepared and after an informed consent the study was undertaken. An in depth interview was carried out among a sub group of participants. Results: The FGD and the IDI revealed several end of life practices in the rural areas such as Thalaikoothal, Feeding the ill with holy water and sand etc. The study also revealed the major determinants leading to such practices such as the social, and cultural beliefs in addition to economical and emotional factors. Conclusion: Several factors determine the end of life decisions in a family ranging from economical to social and cultural factors. While we are examining these factors, it is important to strengthen the palliative care provision in the country by building capacity and integrating it in primary care.

Assessment of caregivers' strain during radiation therapy of head-and-neck cancer patients: An institutional report using modified caregivers' strain index scale Kazi S Manir, Sourav Ghosh Indian Journal of Palliative Care 2019 25(2):228-231 Aims: Very little works have been reported on the issues of burden perceived by the caregivers of head-and-neck cancer (HNC) patients. Job of the caregiver is complex, and it limits their social, psychological, and economical well-being. Our study aims at assessing caregivers' strain during radiation therapy (RT) of HNC patients using the Modified Caregivers' Strain Index (MCSI) Scale. Materials and Methods: In this single-institutional cross-sectional study, we interviewed caregivers of HNC patients undergoing curative RT. Along with MCSI, a 13-point questionnaire, which was self-administered in local languages; we collected baseline data of patients and their caregivers. Scores were evaluated. For each question, score varies 0–2. Higher the Median Hazard Score (H Score), more was the level of the strain. Results: We interviewed 24 participants. Response rate was 100%. About 45.8% of patients were in Stage III. The median age of caregivers was 40 years; 58.3% were male, 79.2% were employed, and 58.3% were belonging to the upper-lower class. Nearly 66.6% were spouse of the patients and 70.8% belong to joint family. In MCSI score analysis, H Score was 22 (range 14) with a minimum score of 14 and maximum score of 26. The most common score was 20. About 65.1% of participants responded Score 2 in all aspects of strain indices. Travel time had a significant positive association with total H Scores (Pearson's r = 0.663, P < 0.05). Conclusion: Majority of the caregivers was suffering from severe physical, personal, emotional, and social/financial strain. This issue must be addressed in holistic cancer care.

Medical Issues

Overview of nuclear medicine Julie Hephzibah Current Medical Issues 2018 16(4):121-130 Nuclear medicine is a medical speciality that uses radioactive materials for diagnostic and therapeutic purposes. The various techniques have made inroads into several other medical and surgical specialities. This article aims to provide an overview of the various diagnostic and therapeutic techniques available in the nuclear medicine armamentarium.

Overview of role of nuclear medicine in differentiated thyroid cancers Saumya Sara Sunny Current Medical Issues 2018 16(4):131-139 There has been a rising trend in the incidence of differentiated thyroid cancers. Diagnostic and therapeutic modalities using Radioiodine are employed in these conditions. This article aims to provide an overview of the types, staging, evaluation, treatment and follow up of thyroid cancers with focus on the nuclear medicine techniques.

Brief overview of the role of nuclear medicine in evaluation of hyperthyroidism David Mathew Current Medical Issues 2018 16(4):140-142 Excessive production of thyroid hormones from the thyroid gland leads to hyperthyroidism. The role of radioiodine uptake study has been well established in the evaluation of hyperthyroidism. This article aims to delineate the nuances involved in the diagnosis and treatment of hyperthyroidism using radioiodine.

Neuroendocrine tumors and role of nuclear medicine in diagnosis and management Junita Rachel John Current Medical Issues 2018 16(4):143-147 Neuroendocrine tumours are a heterogenous group of tumours. They arise from the neuroendocrine cells and can occur in several organs including lung and GIT. This article aims to provide an overview of the nuclear medicine techniques that can be used for diagnosis and treatment of these tumours.

Role of nuclear medicine in evaluation of renal system Julie Hephzibah Current Medical Issues 2018 16(4):148-154 The aim of this article is to highlight the importance of Nuclear Medicine imaging in the diagnosis and management of common renal conditions. Nuclear Medicine procedures provide useful information on renal blood flow and individual kidney functions and drainage. The advantages of these procedures are that there is low radiation burden, no sedation or no special pre-procedural preparations are required and are easy to perform and interpret. It is a valuable asset in the imaging of renal system in both adults and children. Renal radiopharmaceuticals are categorized by their uptake and clearance mechanisms for studying glomerular filtration, tubular secretion, or cortical binding.

Rifampicin-induced thrombocytopenia Sultan Nawahirsha, Sohini Das, G Karthik, I Ramya Current Medical Issues 2018 16(4):155-157 The discovery of rifampicin in 1965 ushered in the era of short-course antituberculosis (TB) chemotherapy. The duration of anti-TB therapy was reduced from 12–24 months to 6 months. Thrombocytopenia is an uncommon but severe side effect of rifampicin, which needs a high clinical index of suspicion for diagnosis. It reverses completely on stopping the drug. Re-challenge is not advised because thrombocytopenia will recur on re-initiation of the drug. We present the case of a patient with rifampicin-induced thrombocytopenia who presented with purpuric rash all over the body. Investigations revealed a low platelet count which resolved completely on stopping the drug. This case highlights the importance of diagnosis of a rare adverse drug reaction and prompts management, which leads to a good outcome.

Potassium dichromate poisoning Ramya Iyyadurai, Sowmya Sathyendra Current Medical Issues 2018 16(4):158-160 Chromium compounds are used as oxidizing agents in leather industries. Acute dichromate poisoning is rare. Ingestion of potassium dichromate is often fatal with rapidly progressive renal and hepatic failure. We report a case of potassium dichromate poisoning in a young girl with a successful outcome. The patient had presented with features of acute renal injury without hepatic involvement.

A brief history of some medications used in modern medicine Current Medical Issues 2018 16(4):161-163

Drug Dialogues – Medication news and new medications Current Medical Issues 2018 16(4):164-165

Medical news – from around the World Current Medical Issues 2018 16(4):166-166

Oncology

The new IJMPO: The phoenix is ready to fly Padmaj S Kulkarni, Jyoti Bajpai Indian Journal of Medical and Paediatric Oncology 2019 40(1):1-1

The "Phoenix" rises from its ashes Gouri Shankar Bhattacharyya Indian Journal of Medical and Paediatric Oncology 2019 40(1):2-2

What should I Do? What should my patients Do? Purvish M Parikh, Padmaj Kulkarni Indian Journal of Medical and Paediatric Oncology 2019 40(1):3-4

Liquid biopsy when MEAT is not the treat K Govind Babu Indian Journal of Medical and Paediatric Oncology 2019 40(1):5-6

Editorial - T790M mutation and clinical outcomes with genuine osimertinib Purvish M Parikh Indian Journal of Medical and Paediatric Oncology 2019 40(1):7-8

Indian council of medical research consensus document for the management of pancreatic cancer Shailesh V Shrikhande, Savio G Barreto, Bhawna Sirohi, Munita Bal, Raj Kumar Shrimali, Raju T Chacko, Vikram Chaudhari, Vikram Bhatia, Suyash Kulkarni, Tanvir Kaur, RS Dhaliwal, Goura Kishor Rath Indian Journal of Medical and Paediatric Oncology 2019 40(1):9-14

Selective cyclin-dependent kinase 4/6 inhibitors as anticancer drugs: Moving beyond hormone receptor-positive breast cancer Tamojit Chaudhuri, K Govind Babu, KC Lakshmaiah, Lokanatha Dasappa, Linu Abraham Jacob, MC Suresh Babu, AH Rudresha, KN Lokesh, LK Rajeev Indian Journal of Medical and Paediatric Oncology 2019 40(1):15-20 The cyclin D-cyclin-dependent kinase (CDK) 4/6 pathway controls the cell cycle machinery by regulating the G1-to-S-phase transition. Dysregulation of this pathway, resulting in increased cellular proliferation, is frequently observed in a variety of human cancers. Activation of cyclin D-CDK 4/6 pathway can occur through different mechanisms, including gene amplification/rearrangement, loss of negative regulatory factors, epigenetic modifications, and point mutations of different components of this pathway. Quite conspicuously, CDK 4/6 inhibitors have emerged as promising anticancer agents in various tumors in which CDK 4/6 has a pivotal role in the G1-to-S-phase cell cycle transition. The clinical use of first-generation, nonselective pan-CDK inhibitors was not progressed beyond early phase trials, due to unacceptable toxicity and lack of efficacy noted with these agents. The emergence of selective CDK 4/6 inhibitors, including ribociclib, abemaciclib, and palbociclib, has enabled us to effectively target cyclin D-CDK 4/6 pathway, at the cost of acceptable toxicity. The results of landmark Phase III trials investigating palbociclib and ribociclib in advanced hormone receptor (HR)-positive breast cancer have demonstrated a substantial clinical benefit with a well-tolerated toxicity profile. Mechanisms of acquired resistance to selective CDK 4/6 inhibitors are beginning to emerge. Clearly, a detailed understanding of these resistance mechanisms is very much essential for the rational development of post-CDK 4/6 inhibitor therapeutic strategies. Extending the use of selective CDK 4/6 inhibitors beyond HR-positive breast cancer is a challenging task and will likely require identification of clinically meaningful biomarkers to predict response and the use of combination approaches to optimize CDK 4/6 targeting.

Role of pretreatment fluorodeoxyglucose positron emission tomography quantitative parameters in prognostication of head-and-neck squamous cell carcinoma Narayana Subramaniam, Deepak Balasubramanian, P Shanmuga Sundaram, Samskruthi Murthy, Krishnakumar Thankappan, Subramania Iyer Indian Journal of Medical and Paediatric Oncology 2019 40(1):21-27 In spite of the good organ preservation strategies available for locally advanced head-and-neck squamous cell carcinoma (HNSCC), failure rates have been reported to be as high as 35%–50%. There has been an increasing interest in predicting response to treatment, to aid early intervention and better outcomes. Fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) is a standard modality for posttreatment evaluation; however, it is still underutilized as a pretreatment investigative modality. Several articles have described quantitative parameters in pretreatment FDG-PET to prognosticate patients and determine the likelihood of response to treatment; however, they are still not used commonly. This article was a review of the literature available on pretreatment FDG-PET quantitative parameters and their value in predicting failure. A thorough review of literature from MEDLINE and EMBASE was performed on pretreatment quantitative parameters in HNSCC. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were reliable parameters to predict response to organ preservation therapy, disease-free survival, and overall survival. Maximum SUV (SUVmax) was an inconsistent parameter. MTV and TLG may help predict poor response to organ preservation to initiate early surgical salvage or modify therapeutic decisions to optimize clinical outcomes. Routine use may provide additional information over SUVmax alone.

The prevalence of BRAF V600E mutation in hairy cell leukemia: A systematic review and meta-analysis study Mehrdad Payandeh, Masoud Sadeghi, Edris Sadeghi, Nasrin Iranshahi Indian Journal of Medical and Paediatric Oncology 2019 40(1):28-31 Background: BRAF V600E mutations were recently identified in the leukemic cells from patients with hairy cell leukemia (HCL) that this mutation in exon 15 is considered the disease-defining mutation in HCL. Objectives: This meta-analysis aimed to report the prevalence of BRAF V600E mutation in HCL patients. Methods: Three databases including PubMed, Scopus, and Web of Science up to 2017 were searched for the prevalence of BRAF mutation in HCL patients. A random effects meta-analysis was performed using the Comprehensive Meta-Analysis software version 2.0 with the event rate (ER) and 95% confidence interval (95% CI). Results: Out of 552 articles identified from the search, 11 were included included and were analyzed for meta-analysis study. The studies in meta-analysis included 437 patients with HCL, of which 353 (80.8%) patients had BRAF V600E mutation. The pooled ER of the studies was 81.5% (95% CI: 69.5%–89.5%). The Begg's test did not show publication bias, but the Egger's test showed publication bias. Conclusions: With regard to the mentioned limitations, the prevalence of BRAF mutation in HCL patients was >80%. In future studies, considering sex, age, and other variables can exactly show the correlation between these variables with the detection of BRAF mutation.

Human leukocyte antigen-matched unrelated donor search experience for hematological disorder patients requiring transplant: scenario for Indian patients Vikash Chandra Mishra, Pranav Dorwal, Hina Solanki, Tarun Kohli, Aseem Kumar Tiwari, Vimarsh Raina, Girish Sharma Indian Journal of Medical and Paediatric Oncology 2019 40(1):32-34 Introduction: Human leukocyte antigen (HLA)-matched unrelated donor (MUD) is the source of MUD transplantation (MUDT) for about 70% of patients who do not have matched related donor. To facilitate MUD search globally, there are 75 stem cell registries with more than 28 million donors registered (as of January 2017). Out of these donors, India has an insignificant representation of approximately 0.23 million. Further, Indians express high genetic variations, making it difficult to find MUD for an Indian patient. Aims and Objectives: The aim of this study is to analyze the MUD search for hematological disorder patients requiring transplant. An attempt was made to observe the MUD scenario for Indian patients requiring MUDT from accessible stem cell registries. Methods: A total of 558 patients approached Genebandhu registry and Chimera Transplant Research Foundation for MUD search over a period of 4 years requiring MUDT were included in this study. High resolution of HLA-A, -B, -C, -DRB1, and -DQB1 was used to perform MUD search through proprietary software called Prometheus and Bone Marrow Donors Worldwide (BMDW) search tool. Results: Out of 558 patients, MUD was located only for 135 (24.19%) patients. Out of these 135 patients, 91 (16.30%) patients found an MUD in global database and only 44 (7.88%) patients within India. Conclusion: This study demonstrates that building a large Indian database will not only help in increasing the chances of finding an MUD for maximum number of patients within India but also provide cost-effective treatment, in a society where cost is a vital factor.

Preventive Medicine

Masthead Publication date: April 2019 Source: American Journal of Preventive Medicine, Volume 56, Issue 4 Author(s):

Kenneth W. Kizer, MD, MPH. Advancing Tobacco Control Among Medicaid Beneficiaries: A Historical Perspective and Call to Action. Am J Prev Med. 2018;55(6S2):S222–S226. Publication date: April 2019 Source: American Journal of Preventive Medicine, Volume 56, Issue 4 Author(s):

Acknowledgments for AJPM Volumes 54 and 55 Publication date: April 2019 Source: American Journal of Preventive Medicine, Volume 56, Issue 4 Author(s):

The Association Between E-cigarette Use and Myocardial Infarction Is What One Would Expect Based on the Biological and Clinical Evidence Publication date: April 2019 Source: American Journal of Preventive Medicine, Volume 56, Issue 4 Author(s): Talal Alzahrani, Stanton A. Glantz

E-cigarette Use and Myocardial Infarction: Association Versus Causal Inference Publication date: April 2019 Source: American Journal of Preventive Medicine, Volume 56, Issue 4 Author(s): Konstantinos Farsalinos, Raymond Niaura

Harnessing the Power of Food Labels for Public Health Publication date: April 2019 Source: American Journal of Preventive Medicine, Volume 56, Issue 4 Author(s): Jennifer L. Pomeranz, Peter G. Lurie

The Emerging Identity of the Preventive Medicine Specialty: A Model for the Population Health Transition Publication date: April 2019 Source: American Journal of Preventive Medicine, Volume 56, Issue 4 Author(s): Yuri T. Jadotte, Heather B. Leisy, Kimberly Noel, Dorothy S. Lane

Urban–Rural Differences in Older Adult Depression: A Systematic Review and Meta-analysis of Comparative Studies Publication date: April 2019 Source: American Journal of Preventive Medicine, Volume 56, Issue 4 Author(s): Jonathan Purtle, Katherine L. Nelson, Yong Yang, Brent Langellier, Ivana Stankov, Ana V. Diez Roux Context Depression among older adults (aged 60 years or older) is a problem that could be exacerbated by global trends in urbanization and population aging. The study purpose was to assess whether urban, relative to rural, residence is associated with depression among older adults and whether associations differ in countries with developed versus developing economies. Evidence acquisition In 2017, the authors identified and extracted information from comparative studies of urban–rural depression prevalence among older adults. Studies were identified in PubMed, PsychINFO, and Web of Science and limited to English language articles published after 1985. Eighteen studies met inclusion criteria. Random effects meta-analysis was conducted to produce weighted pooled ORs estimating the association between urban–rural residence and depression for all study participants (N=31,598) and sub-analyses were conducted for developed (n=12,728) and developing (n=18,870) countries. Evidence synthesis Depression prevalence was significantly higher among urban residents in ten studies and significantly higher among rural residents in three studies (all three conducted in China). Associations between urban–rural residence and depression generally remained significant after adjusting for covariates. In developed countries, the odds of depression were significantly higher among urban than rural residents (pooled OR=1.44, 95% CI=1.10, 1.88). However, in developing countries, this association was not observed (pooled OR=0.91, 95% CI=0.46, 1.77). Conclusions Converging trends of urbanization and population aging could increase the global burden of depression among older adults. The pathways through which urban–rural residence influences depression risk among older adults might differ by country context. Future research should focus on measuring variation in these contexts.

Human Papillomavirus Vaccine Interventions in the U.S.: A Systematic Review and Meta-analysis Publication date: April 2019 Source: American Journal of Preventive Medicine, Volume 56, Issue 4 Author(s): Ana M. Rodriguez, Thuy Quynh N. Do, Michael Goodman, Kathleen M. Schmeler, Sapna Kaul, Yong-Fang Kuo Context Despite current recommendations, human papillomavirus vaccine uptake remains low. A systematic review and meta-analysis assessed the effectiveness of interventions targeting human papillomavirus vaccine initiation and completion among children, adolescents, and young adults aged 9–26 years. Evidence acquisition Three electronic databases (CINAHL, OVID, and Web of Science) were searched for articles published in English peer-reviewed journals between January 2006 and January 2017 of U.S. studies that evaluated intervention strategies and reported post-intervention human papillomavirus vaccine initiation or completion rates among individuals aged 9–26 years. Study characteristics and outcomes were extracted. Data were collected in 2016 and analyzed in 2017. Evidence synthesis Reviewers screened 983 unique titles and abstracts, read 241 full-text articles, and extracted data from 30 articles meeting the inclusion criteria (12 behavioral, ten environmental, four informational, and four combination strategies). Published EQUATOR (Enhancing the Quality and Transparency of Health Research) guidelines were used to assess study quality. Random effects meta-analyses were conducted. The meta-analyses included 17 RCTs and quasi-experiments involving 68,623 children, adolescents, and young adults. The pooled relative incidence estimates were 1.84 (95% CI=1.36, 2.48) for human papillomavirus vaccine initiation and 1.50 (95% CI=1.23, 1.83) for completion. Behavioral and informational interventions doubled human papillomavirus vaccine initiation (relative incidence estimate=2.04, 95% CI=1.36, 3.06 and relative incidence estimate=1.92, 95% CI=1.27, 2.91, respectively). Behavioral interventions increased completion by 68% (relative incidence estimate=1.68, 95% CI=1.25, 2.27). Conclusions Evidence supports behavioral interventions for increasing human papillomavirus vaccine initiation and completion. Future studies are needed to assess the effectiveness of interventions in reaching diverse populations and reducing missed opportunities for human papillomavirus vaccination.

The Relationship Between Hearing Loss and Substance Use Disorders Among Adults in the U.S. Publication date: April 2019 Source: American Journal of Preventive Medicine, Volume 56, Issue 4 Author(s): Michael M. McKee, Michelle A. Meade, Philip Zazove, Haylie J. Stewart, Mary L. Jannausch, Mark A. Ilgen Introduction Hearing loss is common and associated with poorer health and impeded communication. Little is known about the association between hearing loss and substance use disorders in the general population. The objective of this study was to assess substance use disorder prevalence among individuals with hearing loss, versus those without hearing loss, in a nationally representative sample of adults. Methods Two years (2015 and 2016) of National Survey on Drug Use and Health (unweighted N=86,186) were combined to compare substance use disorders among adults with and without self-reported hearing loss. Statistical analysis included descriptive frequencies, chi-square tests, and multiple logistic regressions. Analyses were performed in 2018. Results Hearing loss prevalence across all age groups was 5.2%. Among younger age groups, after adjusting for sociodemographics, hearing loss was independently associated with an increased likelihood of experiencing a substance use disorder (ages 18–34 years, AOR=1.34, 95% CI=1.10, 1.64 vs 35–49 years, AOR=1.87, 95% CI=1.39, 2.53). Hearing loss was also associated with a greater likelihood of a prescription opioid use disorder (AOR=2.85, 95% CI=1.86, 4.39) in the group aged 18–34 years and, for the group aged 35–49 years, hearing loss increased the likelihood of both an alcohol use disorder (AOR=1.87, 95% CI=1.39, 2.53) and a prescription opioid use disorder (AOR=1.99, 95% CI=1.01, 3.91). Conclusions Hearing loss is independently associated with substance use disorders among those aged 49 years and younger; these associations are particularly pronounced for prescription opioid use disorders in the group aged 18–34 years. Given the concern of inappropriate use of prescription opioids, this information may have implications for healthcare providers' pain management for patients with hearing loss.

Neurology and Neurosurgery

A descriptive study of clinical and radiological profile of longitudinal extensive myelitis in a tertiary hospital in Rajasthan, India Publication date: June 2019 Source: Clinical Neurology and Neurosurgery, Volume 181 Author(s): Arti Devi, K.K. Singh, Suresh Gupta, Neeraj Bhutani, Priya Agarwal Abstract Objectives To explore the aetiological, clinical and radiological profiles of patients with LETM presenting to this tertiary care hospital in North India. Patients and methods All eligible LETM patients presenting to our hospital between April 2015 and Jan 2016 were prospectively studied. A total of 37 patients were included and after thorough history, examination, relevant laboratory and radiological investigation, were profiled according to the various aetiologies of LETM. Results Our study included 37 patients (62% males and 38% females). Most patients were young (21–30 years). Main aetiologies of LETMp were NMO (8), inflammatory (9), idiopathic (6), NMOSD (4), Vitamin B12 deficiency (4) and others (6). Most patients (62%) had acute onset of symptoms except NMOSD and B12 deficient patients who presented subacutely too. NMO group was most disabled (poor Rankin and MRC assessments) at presentation; prognostically no (87%) or minimal improvement (13%) at discharge was seen in this group compared to other aetiologies. Forty point five percent patients had thoracic sensory complaints. CSF (pleocytosis 62%) and raised protein (81%) and brain abnormalities on MRI were seen in 11% patients. Bladder and optic nerve involvement (75.7% and 35% patients respectively). Seventy five percent NMO and 67% probable inflammatory aetiology patients also had B12 deficiency. Conclusion This study concludes that LETMp has varied aetiologies with NMO having more disability and poorer outcomes. Thoracic cord segment is most commonly involved. Vitamin B12 deficiency may predispose patients to inflammatory LETM including NMO syndromes.

Retrospective analysis of accuracy and positive predictive value of preoperative lumbar MRI grading after successful outcome following outpatient endoscopic decompression for lumbar foraminal and lateral recess stenosis Publication date: June 2019 Source: Clinical Neurology and Neurosurgery, Volume 181 Author(s): Anthony T. Yeung, Kai-Uwe Lewandrowski

Trending serial CSF samples to guide treatment of refractory coccidioidal meningitis with intrathecal liposomal amphotericin Publication date: June 2019 Source: Clinical Neurology and Neurosurgery, Volume 181 Author(s): Brian Fiani, Alvin Nguyen, Syed A. Quadri, Mudassir Farooqui, Atif Zafar, Ajeet Sodhi, Shubha Kerkar, David Nacionales, Glenn M. Fischberg Abstract Intrathecal amphotericin B deoxycholate (AmB-d) can be prescribed as an adjunct to systemic therapy for severe or recalcitrant cases coccidioidal meningitis. Recently intravenous (IV) Liposomal amphotericin B (L-AmB) has been recommended as monotherapy therapy for refractory coccidioidal meningitis based on its advantages over (AmB-d), however, its intrathecal use has not been reported. Moreover, there is nothing in the literature quantifying clinical improvement with objective laboratory data in human patients. Consequently, there are no guidelines on how to monitor regularly for improvement of coccidioidal meningitis with treatment of intrathecal L-AmB. The present case addresses both of these. We report intrathecal use of L-AmB for refractory coccidioidal meningitis. Our data demonstrate that there is a correlation between clinical improvement and a decrease in cerebrospinal fluid (CSF) white blood cells (WBC's), protein, and coccidioidal titers with treatment of intrathecal L-AmB with serial collection of CSF studies at the same site, in our case via collection through an external ventricular drain (EVD). As a result, one may postulate that serial CSF collection can be used to monitor the treatment of coccidioidal meningitis; however this case also addresses the risk of developing ventriculitis with sustained EVD placement.

Clinical analysis of syringomyelia resulting from spinal hemangioblastoma in a single series of 38 consecutive patients Publication date: June 2019 Source: Clinical Neurology and Neurosurgery, Volume 181 Author(s): Dingkang Xu, Mengzhao Feng, Vigneyshwar Suresh, Guoqing Wang, Fang Wang, Laijun Song, Fuyou Guo Abstract objective Syringomyelia was predominantly caused by Chiari malformation or intramedullary ependymoma. The goal of this study was to identify factors related to clinical outcomes and spinal hemangioblastoma (SH)-induced syringomyelia formation in a single series of patients. Patient and methods Thirty-eight patients with SH were treated with microsurgery from January 2013 to December 2018. Clinical features and related factors were retrospectively analyzed in SH patients with and without syringomyelia. Results Out of the total number of SH patients, 21 presented with remarkable syringomyelia, resulting in an incidence of 55.26% (21/38).Gross total resection was achieved in 36 cases (94.73%), and subtotal resection was obtained in 2 patients (5.27%). Neurological symptoms improved in 34 patients, remained stable in 2 patients and were aggravated in 2 cases during follow-up. In addition, there was a notable difference between the location of tumors and syringomyelia (P < 0.05). Syringomyelia occurred more frequently in the cervical segment than in any other spinal segment. Moreover, there was an association between symptom duration and clinical prognosis (P < 0.05). Ordinal regression analysis showed that the prognosis of middle duration groups (6–12 months) was better than early groups (0–6 months, p < 0.05, OR 20.21, 95%CI 2.34–336.97) and late groups (>12 months, p < 0.05, OR 11.54, 95%CI 1.30–102.21). Syringomyelia collapse or reduction occurred between two weeks and 15 months after surgery. An improvement of spinal function grade after surgery was more significant in syringomyelia reduction groups (p < 0.05). Conclusions The prevalence of syringomyelia due to SH is considerably high, and the initial clinical presentation of syringomyelia resulting from SH should be emphasized. Satisfactory outcomes were achieved by effective surgery in affected patients.

Migraine in patients with fibromyalgia and outcomes of greater occipital nerve blockage Publication date: June 2019 Source: Clinical Neurology and Neurosurgery, Volume 181 Author(s): Volkan Yilmaz, Berke Aras, Fatma Avsar Erturk, Fatma Aytul Cakcı, Ebru Umay Abstract Objectives The aim of this study is to evaluate the efficacy of greater occipital nerve (GON) blockage in patients with migraine and fibromyalgia (FM) comorbidity. Patients and method 20 patients who were diagnosed as FM according to 2010 American College of Rheumatology (ACR) diagnostic criteria and migraine according to International Classification of Headache Disorers II criteria and did not recieve any medication or GON block for both disorders were included for the study. GON blocks were repeated every week in the first month and repeated montly for the following 2 months. The frequency and duration of the migraine attacks, pain severity with visual analogue scale (VAS), quality of life (QoL) with revised fibromyalgia impact questionnaire (FIQR) and migraine disability assesment questionnaire (MIDAS) before,1 st month and 3rd months after treatment were recorded and compared. Results 95% of 20 patients were female (n = 19) and 5% was male (n = 1). The affected site was left in 60% of the patients (n = 12) and 40% was right (n = 8). There was significant improvement in terms of all evaluation parameters both at 1 st month and 3rd months after treatment compared to the baseline. Likely, all parameters were significantly improved at 3rd month compared to the 1 st month. Conclusions GON blockage reduces pain severity, headache frequency and duration and increases QoL in patients with migraine and FM comorbidity.

Association between perioperative stroke and 30-day mortality in carotid endarterectomy: A meta-analysis Publication date: June 2019 Source: Clinical Neurology and Neurosurgery, Volume 181 Author(s): Rajiv P. Reddy, Tejas Karnati, Robyn E. Massa, Parthasarathy D. Thirumala Abstract Objectives Perioperative stroke is a known complication of carotid endarterectomy (CEA) for patients with symptomatic and asymptomatic carotid stenosis. The Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) has shown that stroke following CEA is associated with nearly a 3-fold increase in the 4-year mortality compared to patients without such an event. However, no studies to date can establish whether the stroke was the cause of the short term mortality. Thus, our objective is to evaluate if perioperative stroke after CEA increases the risk of 30-day mortality. Patients and Methods We performed a meta-analysis of the literature from PubMed and the World Science Database on studies reporting perioperative strokes and 30-day mortality in symptomatic and asymptomatic CEA patients. 3400 articles were retrieved, and abstracts were further screened using the inclusion criteria to obtain a final set of 83 randomized controlled trials and retrospective/prospective studies. Results A total of 123,507 CEA procedures were included among the 83 studies. The 30-day perioperative stroke rate for all included studies was 2.15%. The 30-day all-cause mortality rate was 0.93%. In patients with perioperative strokes, the 30-day mortality rate was found to be 17.01%. Among patients without perioperative strokes, the 30-day mortality rate was much lower at 0.57%. The summary odds ratio of perioperative stroke and 30-day mortality was 39.86 (95% CI, 29.30–54.23, p < 0.001). Conclusion Patients with perioperative stroke have an almost 40 times increased risk of 30-day stroke-related mortality. This study highlights the importance of developing a preoperative risk assessment and neuroprotective treatment trial for perioperative stroke.

Response Letter Regarding "Utility of CT angiography in screening for traumatic cerebrovascular injury" Publication date: June 2019 Source: Clinical Neurology and Neurosurgery, Volume 181 Author(s): Hilary L.P. Orlowski, Akash P. Kansagra, Michelle M. Miller-Thomas, Katie D. Vo, Manu S. Goyal

Frameless stereotactic neuronavigated biopsy: A retrospective study of morbidity, diagnostic yield, and the potential of fluorescence: A single-center clinical investigation Publication date: June 2019 Source: Clinical Neurology and Neurosurgery, Volume 181 Author(s): Andreas M. Æbelø, Victor R. Noer, Mette K. Schulz, Bjarne W. Kristensen, Christian B. Pedersen, Frantz R. Poulsen Abstract Objective The primary objective of this retrospective study was to evaluate the diagnostic yield and morbidity/mortality associated with frameless stereotactic neuronavigated intracranial biopsies with and without the use of fluorescein. Patients and methods Patient cases from January 2007 to December 2017 were identified using the ICD-10 procedure code AAG00. Relevant clinical data, including histological diagnosis, were collected retrospectively from the electronic patient charts and independently reviewed by two authors. Results 111 biopsies obtained from 103 patients were identified. Of these, 109 biopsies yielded a diagnosis and resulted in a diagnostic yield of 98.2%. Fluorescein was used in 13 biopsies (11.7%). Twelve patients (10.8%) experienced postoperative complications, and the mortality attributed to the surgery was 1.8%. In 12.6% of cases, the biopsies showed inflammation or nonspecific reactive changes. No statistically significant differences were observed in diagnostic yield or number and severity of complications according to whether intraoperative histological examination was used or not. Conclusion Although direct comparisons between studies are difficult due to lack of consensus about the definition of diagnostic yield, the present study reports a similar diagnostic yield to other studies. Intraoperative histopathological analysis appeared to give little extra benefit.

Prognostic value of preoperative neutrophil to lymphocyte ratio is superior to systemic immune inflammation index for survival in patients with Glioblastoma Publication date: June 2019 Source: Clinical Neurology and Neurosurgery, Volume 181 Author(s): Yajuan Lv, Shaohua Zhang, Zhen Liu, Yuan Tian, Ning Liang, Jiandong Zhang Abstract Objective This study evaluated the prognostic value of preoperative neutrophil to lymphocyte ratio(NLR), platelet to lymphocyte ratio(PLR), and systemic immune inflammation index(SII) in patients with Glioblastoma(GBM). Patients and methods The peripheral blood indexes and other clinical data were obtained within 1 week before surgery. Receiving operating characteristics(ROC) curve was used to find the optimal cut-off value of NLR, SII and PLR, respectively. Kaplan-Meier (KM) analysis and cox proportional hazard models were used to assess the prognostic value of SII and other indexes. Results The optimal cut-off values for NLR, SII, PLR were 2.7, 718, 87, respectively. The high NLR group has a higher proportion of Ki67 expression than the low NLR group. KM survival curves revealed that patients with high NLR (>2.7) or high SII (>718) had worse overall survival. Multivariable Cox analysis revealed NLR, adjuvant therapy and age were prognostic factors for overall survival(OS). The AUC area (the area under the receiver operating characteristics curves) of the NLR was higher than the area of PLR or SII. Conclusion Preoperative NLR was superior to SII in prognostic value of patients with glioblastoma.

Determinants of reoperation after decompressive craniectomy in patients with traumatic brain injury: A comparative study Publication date: June 2019 Source: Clinical Neurology and Neurosurgery, Volume 181 Author(s): Hosseinali Khalili, Fariborz Ghaffarpasand, Amin Niakan, Nasim Golestani, Iman Ahrari, Hamid Reza Abbasi, Ali Rasti Abstract Objectives: Reoperation after decompressive craniectomy (DC) in patients with traumatic brain injury (TBI) remains a dilemma and the risk factors are to be identified. The aim of the current study was to determine the determinants and risk factors of reoperation after DC in patients with TBI. Patients and methods: This retrospective case-controlled study was conducted during a 4-year period from September 2013 to October 2017 in a level I trauma center affiliated with Shiraz University of Medical Sciences in southern Iran. We included all the adult (≥18 years) patients with TBI who underwent primary or secondary DC in our center during the study period. Those who underwent reoperation were compared to those who underwent DC only regarding the demographic findings, clinical features and neuroimaging findings. A univariate and multivariate logistic regression analysis was performed to determine the determining factors of reoperation. Results: Overall we included 371 patients with mean age of 36.45 ± 14.18 years. Among the patients there were 325 (87.6%) men and 46 (12.4%) women. The reoperation in patients undergoing DC due to TBI was associated with primary DC (p = 0.039) and higher Marshall grade (p = 0.027). Those who underwent reoperation after DC for TBI had significantly higher ICU (p = 0.007) and hospital LOS (p = 0.001) and lower 6-month GOSE (p = 0.010). Age (p < 0.001), GCS (p < 0.001) and pupils (p = 0.027) were predictors of outcome in reoperation group. Reoperation in primary DC group was associated with pupil reactivity (p = 0.002) and number of episodes with INR above 1.5 (p = 0.037) Conclusion: Reoperation after DC for TBI is associated with primary DC, and Marshall grade. The reoperation after DC is associated with worse outcome and longer ICU and hospital stay. The age, GCS and pupil reactivity are the main predictors of outcome in those with reoperation after DC for TBI.

Applied Microbiology and Biotechnology

Role of β-oxidation and de novo fatty acid synthesis in the production of rhamnolipids and polyhydroxyalkanoates by Pseudomonas aeruginosa Abstract Pseudomonas aeruginosa are ubiquitous γ-proteobacteria capable of producing the biosurfactant rhamnolipids (RL) and the polymer polyhydroxyalkanoate (PHA). RL are glycolipids with high biotechnological potential, whereas PHA is used for the production of biodegradable plastics. It has been proposed that the β-oxidation pathway provides intermediates for RL biosynthesis, even when using a non-fatty acid carbon source for growth, while an intermediate of de novo fatty acid biosynthesis (FASII) pathway [(R)-3-hydroxyacyl-ACP] is used for PHA biosynthesis. The aim of this work is to study the inter-relationship of the RL and PHA biosynthetic pathways in a culture medium with a non-fatty acid carbon source, focusing on the role of FASII and β-oxidation in supplying the substrates for the first step in RL and PHA synthesis, carried out by the RhlA and PhaG enzymes, respectively. The PHA synthases (PhaC1 and PhaC2) are only able to use CoA-linked 3-hydroxy acids and the PhaG enzyme catalyzes the conversion of (R)-3-hydroxyacyl-ACP to (R)-3-hydroxyacyl-CoA, the substrate of PhaC1 and PhaC2. RhlA in turn catalyzes the synthesis of the RL precursor 3-(3-hydroxyalkanoyloxy) alkanoic acids (HAA) by the dimerization of two 3-hydroxyalkanoic acid molecules (that have been shown to be also (R)-3-hydroxyacyl-ACP). In this work, we show that RhlA can produce both RL and PHA precursors (presumably CoA-linked HAA), that the blockage of carbon flux through β-oxidation pathway does not decrease RL titer, and that the enoyl-CoA hydratase RhlY and enoyl-CoA hydratase/isomerase RhlZ produce the main fatty acids precursor of RL using as substrate also a FASII intermediate (presumably (S)-3-hydroxyacyl-CoA).

The antitumor antibiotic rebeccamycin—challenges and advanced approaches in production processes Abstract Rebeccamycin is an antibiotic and antitumor substance isolated from the filamentous bacterium Lentzea aerocolonigenes. After its discovery, investigations of rebeccamycin focused on elucidating its structure, biological activity, and biosynthetic pathway. For potential medical application, a sufficient drug supply has to be ensured, meaning that the production process of rebeccamycin plays a major role. In addition to the natural production of rebeccamycin in L. aerocolonigenes, where the complex cell morphology is an important factor for a sufficient production, rebeccamycin can also be heterologously produced or chemically synthesized. Each of these production processes has its own challenges, and first approaches to production often lead to low final product concentrations, which is why process optimizations are performed. This review provides an overview of the production of rebeccamycin and the different approaches used for rebeccamycin formation including process optimizations.

Identification of genes involved in shea butter biosynthesis from Vitellaria paradoxa fruits through transcriptomics and functional heterologous expression Abstract Shea tree (Vitellaria paradoxa) is one economically important plant species that mainly distributes in West Africa. Shea butter extracted from shea fruit kernels can be used as valuable products in the food and cosmetic industries. The most valuable composition in shea butter was one kind of triacylglycerol (TAG), 1,3-distearoyl-2-oleoyl-glycerol (SOS, C18:0–C18:1–C18:0). However, shea butter production is limited and little is known about the genetic information of shea tree. In this study, we tried to reveal genetic information of shea tree and identified shea TAG biosynthetic genes for future shea butter production in yeast cell factories. First, we measured lipid content, lipid composition, and TAG composition of seven shea fruits at different ripe stages. Then, we performed transcriptome analysis on two shea fruits containing obviously different levels of SOS and revealed a list of TAG biosynthetic genes potentially involved in TAG biosynthesis. In total, 4 glycerol-3-phosphate acyltransferase (GPAT) genes, 8 lysophospholipid acyltransferase (LPAT) genes, and 11 diacylglycerol acyltransferase (DGAT) genes in TAG biosynthetic pathway were predicted from the assembled transcriptome and 14 of them were cloned from shea fruit cDNA. Furthermore, the heterologous expression of these 14 potential GPAT, LPAT, and DGAT genes in Saccharomyces cerevisiae changed yeast fatty acid and lipid profiles, suggesting that they functioned in S. cerevisiae. Moreover, two shea DGAT genes, VpDGAT1 and VpDGAT7, were identified as functional DGATs in shea tree, showing they might be useful for shea butter (SOS) production in yeast cell factories.

Highly thermostable GH51 α-arabinofuranosidase from Hungateiclostridium clariflavum DSM 19732 Abstract Arabinofuranosidase plays an essential role in the process of hydrolysis of arabinoxylan (AX). Thermostable, versatile, and efficient arabinofuranosidase is thus of great interest for the biorefinery industry. A GH51 arabinofuranosidase, Abf51, from Hungateiclostridium clariflavum DSM 19732 was heterogeneously expressed in Escherichia coli. Abf51 was found to have an optimal pH and temperature of 6.5 and 60 °C, respectively, with very high thermostability. At the optimal working temperature (60 °C), Abf51 retained over 90% activity after a 2-day incubation and over 60% activity after a 6-day incubation. Abf51 could effectively remove the arabinofuranosyls from three kinds of AX oligosaccharides [23-α-l-arabinofuranosyl-xylotriose (A2XX), 32-α-l-arabinofuranosyl-xylobiose (A3X), and 2333-di-α-l-arabinofuranosyl-xylotriose (A2 + 3XX)], which characterized as either single substitution or double substitution by arabinofuranosyls on terminal xylopyranosyl units. The maximal catalytic efficiency (Kcat/Km) was observed using p-nitrophenyl-α-l-arabinofuranoside (pNPAF) as a substrate (205.0 s−1 mM−1), followed by using A3X (22.8 s−1 mM−1), A2XX (6.9 s−1 mM−1), and A2 + 3XX (0.5 s−1 mM−1) as substrates. Moreover, the presence of Abf51 significantly stimulated the saccharification level of AX (18.5 g L−1) up to six times along with a β-xylanase as well as a β-xylosidase. Interestingly, in our survey of top thermostable arabinofuranosidases, most members were found from GH51, probably due to their owning of (β/α)8-barrel architectures. Our results suggested the great importance of GH51s as candidates for thermostable, versatile, and efficient arabinofuranosidases toward industry application.

Haloferax volcanii as immobilised whole cell biocatalyst: new applications for halophilic systems Abstract Enzyme-mediated synthesis of pharmaceutical compounds is a 'green' alternative to traditional synthetic chemistry, and microbial engineering opens up the possibility of using whole cells as mini-factories. Whole-cell biocatalysis reduces cost by eliminating expensive enzyme purification and cofactor addition steps, as well as resulting in increased enzyme stability. Haloferax volcanii is a model halophilic archaeon encoding highly salt and organic solvent tolerant enzymes such as alcohol dehydrogenase (HvADH2), which catalyses the reduction of aldehydes and ketone in the presence of NADPH/NADH cofactor. A H. volcanii strain for constitutive HvADH2 expression was generated using a strong synthetic promoter (p.syn). The strain was immobilised in calcium alginate beads and repeatedly used as a whole-cell biocatalyst. The reduction of acetophenone, used as test substrate, was very successful and high yields were detected from immobilised whole cells over repeated biotransformation cycles. The immobilised H. volcanii retained stability and high product yields after 1 month of storage at room temperature. This newly developed system offers halophilic enzyme expression in its native environment, high product yield, stability and reusability without the addition of any expensive NADPH/NADH cofactor. This is the first report of whole cell–mediated biocatalysis by the halophilic archaeon H. volcanii.

Function, essentiality, and expression of cytochrome P450 enzymes and their cognate redox partners in Mycobacterium tuberculosis: are they drug targets? Abstract This review covers the current knowledge of the cytochrome P450 enzymes (CYPs) of the human pathogen Mycobacterium tuberculosis (Mtb) and their endogenous redox partners, focusing on their biological function, expression, regulation, involvement in antibiotic resistance, and suitability for exploitation as antitubercular targets. The Mtb genome encodes twenty  CYPs and nine associated redox partners required for CYP catalytic activity. Transposon insertion mutagenesis studies have established the (conditional) essentiality of several of these enzymes for in vitro growth and host infection. Biochemical characterization of a handful of Mtb CYPs has revealed that they have specific physiological functions in bacterial virulence and persistence in the host. Analysis of the transcriptional response of Mtb CYPs and redox partners to external insults and to first-line antibiotics used to treat tuberculosis showed a diverse expression landscape, suggesting for some enzymes a potential role in drug resistance. Combining the knowledge about the physiological roles and expression profiles indicates that, at least five Mtb CYPs, CYP121A1, CYP125A1, CYP139A1, CYP142A1, and CYP143A1, as well as two ferredoxins, FdxA and FdxC, can be considered promising novel therapeutic targets.

Cobalamin is produced by Acetobacter pasteurianus DSM 3509 Abstract Only a few cobalamin-producing bacterial species are known which are suitable for food fermentations. The strain of Acetobacter pasteurianus DSM 3509 was found to have the capability to synthesize cobalamin. A survival test and a preliminary genetic study of the gene of uroporphyrinogen-III synthase indicated the ability to synthesize cobalamin. By a modified microbiological assay based on Lactobacillus delbrueckii ssp. lactis DSM 20355, 4.57 ng/mL of cyanocorrinoids and 0.75 ng/mL of noncorrinoid growth factors were detected. The product extracted and isolated by immunoaffinity chromatography in its cyanide form had the similar UV spectrum as standard cyanocobalamin and Coα-[α-(7-adenyl)]-(Coβ-cyano) cobamide also known as pseudovitamin B12 produced by Lactobacillus reuteri DSM 20016. The chromatographically separated product of A. pasteurianus was subjected to mass spectrometrical analysis. There, its fragmentation pattern turned out to be equivalent to that of cyanocobalamin also produced by Propionibacterium freudenreichii ssp. freudenreichii DSM 20271 and clearly differs from pseudovitamin B12. Due to the presence of this species in several food applications, there might be cobalamin residues in food fermented with these bacteria.

Directed aryl sulfotransferase evolution toward improved sulfation stoichiometry on the example of catechols Abstract Sulfation is an important way for detoxifying xenobiotics and endobiotics including catechols. Enzymatic sulfation occurs usually with high chemo- and/or regioselectivity under mild reaction conditions. In this study, a two-step p-NPS-4-AAP screening system for laboratory evolution of aryl sulfotransferase B (ASTB) was developed in 96-well microtiter plates to improve the sulfate transfer efficiency toward catechols. Increased transfer efficiency and improved sulfation stoichiometry are achieved through the two-step screening procedure in a one-pot reaction. In the first step, the p-NPS assay is used (detection of the colorimetric by-product, p-nitrophenol) to determine the apparent ASTB activity. The sulfated product, 3-chlorocatechol-1-monosulfate, is quantified by the 4-aminoantipyrine (4-AAP) assay in the second step. Comparison of product formation to p-NPS consumption ensures successful directed evolution campaigns of ASTB. Optimization yielded a coefficient of variation below 15% for the two-step screening system (p-NPS-4-AAP). In total, 1760 clones from an ASTB-SeSaM library were screened toward the improved sulfation activity of 3-chlorocatechol. The turnover number (kcat = 41 ± 2 s−1) and catalytic efficiency (kcat/KM = 0.41 μM−1 s−1) of the final variant ASTB-M5 were improved 2.4- and 2.3-fold compared with ASTB-WT. HPLC analysis confirmed the improved sulfate stoichiometry of ASTB-M5 with a conversion of 58% (ASTB-WT 29%; two–fold improvement). Mass spectrometry (MS) and nuclear magnetic resonance spectroscopy (NMR) confirmed the chemo- and regioselectivity, which yielded exclusively 3-chlorocatechol-1-monosulfate. For all five additionally investigated catechols, the variant ASTB-M5 achieved an improved kcat value of up to 4.5-fold and sulfate transfer efficiency was also increased (up to 2.3-fold).

Different behaviors of cyclic dipeptide prenyltransferases toward the tripeptide derivative ardeemin fumiquinazoline and its enantiomer Abstract In nature, cyclic dipeptide prenyltransferases catalyze regioselective Friedel-Crafts alkylations of tryptophan-containing cyclic dipeptides. This enzyme class, belonging to the dimethylallyl tryptophan synthase superfamily, is known to be flexible toward aromatic prenyl acceptors, while mostly retaining its typical regioselectivity. Ardeemin fumiquinazoline (FQ) (1), a tryptophan-containing cyclic tripeptide derivative, is assembled in Aspergillus fischeri by the non-ribosomal peptide synthetase ArdA and modified by the prenyltransferase ArdB, leading to the pharmaceutically active hexacyclic ardeemin. Therefore, 1 and its enantiomer ent-ardeemin FQ (2) constitute potential substrates for aromatic prenyltransferases. In this study, we investigated the acceptance of both enantiomers by two cyclic dipeptide C2-prenyltransferases BrePT and FtmPT1 and three C3-prenyltransferases CdpNPT, CdpC3PT, and AnaPT. LC-MS analysis of the incubation mixtures and NMR analysis of the isolated products revealed that the stereochemistry at C11 and C14 in 1 and 2 has a strong influence on their acceptance by these enzymes and the regioselectivity of the prenylation reactions. 1 was very well accepted by BrePT, FtmPT1, and CdpNPT, with C2- or C3-prenylated derivatives as predominant products, which fills the prenylation gaps by tryptophan prenyltransferases reported in a previous study. 2 was a poor substrate for all the enzymes and converted with low regioselectivity and mainly prenylated at C6 and C7 of the indole moiety.

Shape of gastrointestinal immunity with non-genetically modified Lactococcus lactis particles requires commensal bacteria and myeloid cells-derived TGF-β1 Abstract Heat-killed probiotics or microbial autologous components show multiple activities on modulating host immune responses towards tolerance or vice versus aggressiveness. Gram-positive enhancer matrix particles (GEMs), the non-genetically modified particles which composed of the cell wall derived from Lactococcus lactis (L. lactis), were used as a typical microbial molecule to investigate the mechanism of opposite immune responses generated in disparate scenarios. The results of stool 16S rRNA Illumina sequencing suggested that the overwhelming number of mice pre-administered with GEMs showed the expansion of Bacteroidetes but contraction of Verrucomicrobia. Co-administration GEMs and antibiotics could preserve the microbial diversity, even though the abundance of gut microbes was largely depleted by antibiotics. Additionally, dendritic cells (DCs) from mice receiving GEMs rather than DCs that in vitro treated with GEMs induced the expansion of regulatory T cells (Tregs), witnessing the critical role of gut flora alteration. Importantly, this alteration provided protection to alleviate dextran sulfate sodium (DSS)-induced intestinal inflammation. On the other hand, in the context of Helicobacter felis (H. felis) infection, the mice pre-administrated with GEMs exhibited a comparably potent gastric immunity with the elevated expression of IFN-γ, IL-17, and multiple anti-microbial factors, leading to the reduced burden of H. felis. However, tolerance for both DSS-induced intestinal inflammation and immunity against H. felis was depleted in a mice model lacking of transforming growth factor-β1 (TGF-β1) in myeloid cells. These findings suggest that GEMs can modulate host immune responses bidirectionally according to context, and may serve as a supplement for antibiotic treatment.

Anaesthesiology Clinical Pharmacology,Truview evo2 and Macintosh laryngoscope for ease of orotracheal intubation in children,I-gel is comparable to endotracheal intubation in terms of adequacy of ventilation. The increase in peak airway pressures is less with I-gel. In addition, postoperative complications are fewer with I-gel,oral dexmedetomidine and oral midazolam as premedicants in children,ropivacaine with ultrasound-guided ISB with multiple injection technique, without clinical deterioration in block onset and duration of analgesia,

Medication errors: They continue Rashmi Salhotra, Asha Tyagi Journal of Anaesthesiology Clinical Pharmacology 2019 35(1):1-2

Anesthetic implications in hyperthermic intraperitoneal chemotherapy Nishkarsh Gupta, Vinod Kumar, Rakesh Garg, Sachidanand Jee Bharti, Seema Mishra, Sushma Bhatnagar Journal of Anaesthesiology Clinical Pharmacology 2019 35(1):3-11 Patients with peritoneal carcinomatosis were considered incurable with dismal survival rates till hyperthermic intraperitoneal chemotherapy after optimal cytoreductive surgery evolved. Perioperative management for these procedures is complex and involves an optimal cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy. In this article we highlight the perioperative concerns in these patients including anesthetic challenges, such as optimal fluid management, maintaining blood pressure, control of body temperature, coagulation and electrolyte derangement and renal toxicity of chemotherapeutic drugs. We have also discussed the postoperative problems and their management.

Monitoring cerebral vasospasm: How much can we rely on transcranial Doppler Navneh Samagh, Hemant Bhagat, Kiran Jangra Journal of Anaesthesiology Clinical Pharmacology 2019 35(1):12-18 Cerebral vasospasm leading to delayed cerebral ischaemia is one of the major concerns following subarachnoid haemorrhage (SAH). Various modalities are present for evaluation and detection of cerebral vasospasm that occurs following SAH. They include transcranial Doppler (TCD), computed tomographic angiography (CTA), computed tomographic (CT) perfusion and digital subtraction angiography (DSA). The recent guidelines have advocated the use of TCD and have described it as a reasonable technique for monitoring the development of vasospasm. This review describes the functioning of TCD, the cerebral haemodynamic changes during vasospasm and TCD-based detection of vasospasm. The review shall highlight as to how the TCD derived values are relevant in the settings of neurocritical care. The data in the review have been consolidated based on our search of literature from year 1981 till 2016 using various data base.

Maternal anesthesia for EXIT procedure: A systematic review of literature Kamal Kumar, Cristiana Miron, Sudha Indu Singh Journal of Anaesthesiology Clinical Pharmacology 2019 35(1):19-24 The ex utero intrapartum treatment (EXIT) procedure is performed in cases of fetal congenital malformation. The anesthetic management is much more challenging and involves providing profound uterine relaxation, maintenance of Uteroplacental blood flow and fetal anesthesia. The aim of the article is to review the literature and compare the efficacy of both the anesthetic techniques with respect to maternal and fetal outcomes. The literature source for this review was obtained via PubMed, Medline, Google scholar and Cochrane database of systematic reviews until January 2017. In our literature review we found that both GA and Regional anesthesia were successfully described for EXIT procedure but GA was performed in the majority of cases.Consideration for anesthetic technique should be done on a case-by-case basis.

Comparative evaluation of Truview evo2 and Macintosh laryngoscope for ease of orotracheal intubation in children – A prospective randomized controlled trial Neha Pangasa, Jaspal Singh Dali, Kavita Rani Sharma, Mona Arya, Anant Vikram Pachisia Journal of Anaesthesiology Clinical Pharmacology 2019 35(1):25-29 Background and Aims: Truview evo2 has been found to improve the glottic view when compared with the Miller blade in pediatric population. However, there is limited literature comparing it with Macintosh laryngoscope in children. We thus aimed to assess and compare Truview evo2 with the Macintosh laryngoscope for orotracheal intubation in children with regards to time to intubate, laryngoscopic view, ease of intubation, and associated hemodynamic changes. Material and Methods: Fifty ASA I-II children aged 2–8 years for elective surgery requiring general anesthesia with orotracheal intubation participated in this prospective randomized-controlled study. They were randomly allocated to two groups. In group-M (N = 25), laryngoscopy and intubation were performed using Macintosh laryngoscope, and in group-T (N = 25), Truview evo2 laryngoscope was used. Modified Cormack–Lehane grade, time to intubation, intubation difficulty score (IDS), and hemodynamic changes were compared between the groups. Data were analyzed using SPSS statistical software version 17 and P value <0.05 was considered statistically significant. Results: CL grade 1 was found in a larger number of patients of group-T (P = 0.003) and CL grades2a and 2b were found in a larger number of patients of group-M (P = 0.023 and P = 0.037, respectively). The mean time to intubation was significantly longer in group-T (19.0 ± 3.4 seconds) than in group-M (13.1 ± 2.1 seconds), P = 0.00. The over all IDS was lower in group-T than group M [i.e. median (IQR): 0 (0-0) vs 1 (0-2), respectively]. Heart rate, systolic and diastolic blood pressure, and oxygen saturation were comparable between the groups at all times. Conclusion: Truview evo2 provides better laryngeal view and has a lesser IDS, but takes longer for intubation, when compared to the Macintosh laryngoscope in children.

Comparative evaluation of I-gel vs. endotracheal intubation for adequacy of ventilation in pediatric patients undergoing laparoscopic surgeries Megha Kohli, Sonia Wadhawan, Poonam Bhadoria, Simmi K Ratan Journal of Anaesthesiology Clinical Pharmacology 2019 35(1):30-35 Background and Aims: The use of newer supraglottic devices has been extended to laparoscopic procedures. We conducted this study to compare and evaluate the efficacy of these two devices in pediatric laparoscopic surgeries. Material and Methods: Eighty children, 2–8 years of age, scheduled for elective short laparoscopic procedures were randomly allocated to the I-gel or endotracheal tube (ETT) group. Standard anesthesia protocol was followed for inhalational induction. I-gel or ETT was inserted according to the manufacturer's recommendations. Ventilation was set with tidal volume 10 ml/kg and a respiratory rate of 16/min. Carboperitoneum was achieved up to an intra-abdominal pressure of 12 mmHg. Statistical Analysis: The primary outcome variable was adequacy of ventilation (peak airway pressure, end-tidal CO2, minute ventilation, and SPO2). These variables were recorded after securing airway, after carboperitoneum and desufflation of the peritoneal cavity. The oropharyngeal leak pressures were also noted. Statistical analysis was done using SPSS software version 17.0. P <0.05 was considered statistically significant. Results: No significant difference was observed in the heart rate or mean arterial pressure. There was a significant increase in the PECO2and peak airway pressure after creation of carboperitoneum. There was significant increase in minute ventilation in both groups after creation of carboperitoneum. Conclusion: To conclude, I-gel is comparable to endotracheal intubation in terms of adequacy of ventilation. The increase in peak airway pressures is less with I-gel. In addition, postoperative complications are fewer with I-gel.

A comparison of oral dexmedetomidine and oral midazolam as premedicants in children Binu Sajid, Taznim Mohamed, M Jumaila Journal of Anaesthesiology Clinical Pharmacology 2019 35(1):36-40 Background and Aim: Midazolam has been the most popular oral premedicant in children despite its side effects. Dexmedetomidine with its favorable clinical profile is a suitable alternative, but with limited research. The aim of this study was to compare the effectiveness of dexmedetomidine and midazolam as oral premedicants in children. Material and Methods: Eighty children of the American Society of Anesthesiologist physical status I scheduled for elective herniotomy were included in this prospective randomized double-blind study. Patients were randomly assigned to receive either dexmedetomidine 4 μg/kg (Group A, n = 40) or midazolam 0.5 mg/kg (Group B, n= 40) orally 40 min before induction. Pre-operative sedation, response to parental separation and venepuncture, emergence agitation, recovery nurse satisfaction, and side effects were compared between the two groups. Quantitative data were compared using unpaired Student's t-test and categorical variables with Chi-square test. Results: Pre-operative sedation and response to parental separation and venepuncture were similar between the two groups. Group A had a significantly lower incidence and severity of emergence agitation (P = 0.000). Recovery nurse satisfaction was significantly higher in Group A (P = 0.002). However, incidence of hypotension and bradycardia was found to be more in Group A (P = 0.04). Conclusion: Premedication with oral dexmedetomidine is as effective as oral midazolam in providing sedation and anxiolysis in children. Dexmedetomidine in addition reduces the incidence and severity of emergence agitation.

The estimation of minimum effective volume of 0.5% ropivacaine in ultrasound-guided interscalene brachial plexus nerve block: A clinical trial Kailash Mittal, Sarita Janweja, Prateek , Pushpender Sangwan, Deepa Agarwal, Himani Tak Journal of Anaesthesiology Clinical Pharmacology 2019 35(1):41-46 Background and Aims: Interscalene brachial plexus block (ISB) is the most commonly used mode of anesthesia for upper limb surgeries. Higher volume of local anesthetic used in ISB is associated with increased incidence of side effects, particularly phrenic nerve palsy. The aim of this study was to determine the minimum effective volume of 0.5% ropivacaine in 90% patients (MEV90) in ISB. Material and Methods: With target of 45 successful cases, phase 1 clinical trial was conducted based on the principles of biased coin design up-and-down method. After obtaining Ethical Committee's approval and patient's consent, patients with American Society of Anesthesiologist physical status (ASA PS) I and II, aged 18–60 years of either sex, undergoing upper arm surgery were recruited into the study until 45 successful cases. A 7 ml of 0.5% ropivacaine was used as starting dose, with patients receiving a higher or lower dose depending on previous patient's response. R package, SPSS 23, and Microsoft Excel were used for statistical analysis. Results: MEV90 of 0.5% ropivacaine for ISB was determined as 8.64 ml [confidence interval (CI) 95%, 8.28–9.02 ml]. Time for onset of sensory block and motor block was 5 min (5–15 min) and 10 min (5–20 min), respectively, while duration of analgesia was observed as 8.2 (4.8–12.5) h. Conclusions: This study observes that surgical anesthesia can be accomplished with 8.64 ml (95% CI: 8.28–9.02 ml) of 0.5% ropivacaine with ultrasound-guided ISB with multiple injection technique, without clinical deterioration in block onset and duration of analgesia.

Challenges to implement minimum effective volume in regional anesthesia Sudhakar Subramani, Shuchita Garg Journal of Anaesthesiology Clinical Pharmacology 2019 35(1):47-48

Effect of intrathecal catheterisation on incidence of postdural puncture headache after accidental dural puncture in non-obstetric patients Prateek Ahuja, Ranju Singh, Aruna Jain Journal of Anaesthesiology Clinical Pharmacology 2019 35(1):49-52 Background and Aims: After accidental dural puncture (ADP) with large bore epidural needles, postdural puncture headache (PDPH) develops in 16%–86% of patients, which is unpleasant and interferes with activities of daily life of the patient.Hence we aimed to assess the effect of intrathecal catheter insertion after ADP with 18G Tuohy needle on incidence of PDPH. Material and Methods: In all, 173 patients after ADP were enrolled and divided into two groups according to the choice of treating anesthesiologist. Group IC included 74 patients who had intrathecal catheter placed in subarachnoid space. In group NIC, which included 99 patients, one of the following was done: epidural catheter was cited in a different intervertebral space, or the procedure was abandoned and general anesthesia was administered or single-shot spinal anesthesia was administered through the Tuohy needle itself. The catheters were left in situ for 36–48 h. Patients were monitored for the next 7 days after ADP for the incidence of PDPH, its severity and requirement of analgesics, and duration of catheter in situ from the time of ADP. Results: The incidence of PDPH in group IC was 36% in comparison to 59% in group NIC (P = 0.001). The severity of PDPH and requirement of analgesics was significantly less in group IC. Conclusion: Insertion of intrathecal catheter at the site of ADP significantly reduces the incidence and severity of PDPH.