Biography:

Romila Gopalan has completed his PhD in 2012 from Monash University. She is currently a sSnior Lecturer at The University of the South Pacific- a regional institution governed by twelve South Pacific Countries. Her research is mainly in the areas of Functional Foods, Medicinal Chemistry and Natural Products Chemistry. She has published in reputed journals. She also is involved in Research Skill Development and Science Edication at The University of the South Pacific.

Abstract:

Traditional and alternative medicine is the indigenous healthcare method that is still widely in the developing countries. Traditional medicine has been part of the Fijian culture due to its safety and effectiveness to illnesses. However, this knowledge is restricted to only the traditionalvillage healers. In a survey carried out recently in Fiji, thirteen traditional medicinal plants were selected those that were used by Itaukei village healers to cure headache, depression and related sickness. Since the traditional method for medicine preparation is extraction in water, the plant samples used in the study were extracted with water and ethanol. The crude extracts were then analysed for Acetylcholinesterase inhibition (AChEI) using Ellman‘s assay. Method: Thirteen plant species belonging to Melastomataceae, Asteraceae, Apiaceae, Rutaceae, Goodeniaceae, Loganiaceae, Araliaceae, Solanaceae, Polygonaceae, Zingiberaceae and Anacardiaceae families were tested at 0.2 mg/mL, 0.4 mg/mL, 0.6 mg/mL, 0.8 mg/mL, 1.0 mg/mL, 1.5 mg/mL and 2.0 mg/mL concentrations. Results and Discussions: The most active plants showed AChEI activity between IC50 = 4.57 mg/mL to IC50 = 9.24 mg/mL indicating the effectiveness of the compounds present in the extracts against the Acetylcholinesterase, the enzyme that plays a key role in normal cognition and memory. Conclusion: The plant extracts used in this study were crude extracts, thus the concentration of the active phytochemicals present may be of avery low concentration. These thirteen plants could prove leads to safer and better candidates for the future selection of acetylcholinesterase inhibitors and potenially in treatment of Alzheimer’s disease and related

Biography:

Dr. Sandeep Chavan is a Homoeopathic doctor, postgraduate in public health administration from Tata institute of Social Sicences, Mumbai, India. He has total 8 years of professional experience and is working with India’s biggest philanthropic organization – Tata Trusts since past 4.5 years as a Program Officer for Healthcare initiatives. His area of experience is across maternal and child health, vector borne diseases, mental health and primary healthcare. Dr. Sandeep is passionated towards promoting and mainstreaming Homoeopathy for better public health outcomes.

Abstract:

Homoeopathy is a system of medicine originated in Germany, founded by a modern medicine physician – Dr. Samuel Hahnemann, is thriving alternative system of medicine in India, most popular in northern states. Homoeopathic medicines are proven to be effective in treating large number of acute as well as chronic ailments and have nil side effects. The successful treatment ensues when a physician understands dimensions of the disease in the holistic Homoeopathic perspective and accordingly prescribes. Despite cost effectiveness, Homoeopathy offers promising public health benefits to maintain as well as restore health in most natural ways by helping to avoid overuse of antibiotics, eventually boosting individual’s immunity.  Hence integrating Homoeopathy with modern medicine is critical to mitigate huge unmet needs of primary healthcare in India, especially where accessibility of healthcare provider is key concerns for rural masses.

India relies on a three-tier public health system, the first one being Health Sub-Centers (HSC). HSCs, manned by a trained nurse, are meant to cater to a population of 5,000. Consulting a doctor is through a Primary Health Center (PHC) exists for every 30,000 people. Hence patients need to travel to seek a doctor’s consultation. Further, challenges related to infrastructure and competent paramedical personnel at peripheral health facilities still exist. Despite proven efficacy, availability of alternative medicine practitioner such as a Homoeopath is only at the block level, typically for a population of 1 lakh. In such a scenario rural people have no choice but to seek care from local quacks who provide service at the villagers’ doorsteps. To fulfill villagers’ primary healthcare needs, guided women collectives in villages of Uttar Pradesh state in India initiated Gaon Dawakhana (A village Clinic) with 1,000 families in January 2017. It is a community funded integrated primary healthcare service delivery platform through a Homoeopathic doctor – visiting weekly twice and a Modern Medicine doctor – visiting monthly twice to provide medical services at doorsteps for villagers. Unit of one clinic is a collective of 500 families, each contributing 50/-INR per family per month to seek services of a clinic. Except for the administrative cost (which is being funded by Tata Trusts), entire operational cost of clinics (including doctors’ fees, medicines’ cost, etc.) is met through the monthly subscription fees. Since January 2017, total 31,919 patients are treated across 10 clinic locations benefitting to more than 5,000 families. Through 15 quarterly health camps for non communicable diseases, child health issues, etc 3,132 patients are treated.

One of the important challenges faced is overcrowding at clinics and difficulty to maintain stock of key Homoeopathic medicine owing to its availability at remote places. Major learning from the initiative is, Homoeopathy as an alternative system, can be integrated with Modern Medicine to mitigate unmet needs of primary health care of rural masses because of its efficacy and cost effectiveness. Continuous community contribution is sign of acceptability towards Homoeopathy and it also ensures sustainability for the initiative. Further it demystifices the common notion that rural poor are always in need of free services. It is appreciated that, though economically vulnerable, families are willing to pay, if they perceive value in services. Both the initiative itself and the Homoepathy has got promising potential to meet primary healthcare needs for rural masses.

Biography:

Professor Prem P. Rai, PhD served in the University of Papua New Guinea for over 20 years.  He is currently Dean of the School of Natural Resources & Applied Sciences at Solomon Islands National University. His speciality includes pharmacognosy and quality control aspects of herbal medicine. Dr. Rai headed the traditional medicine program of the National Department of Health in Papua New Guinea for over 15 years. He is an active researcher and has published more than 98 papers and authored number of technical books including one on Medicinal Plants in Papua New Guinea, published by the World Health Organization. Dr. Rai serves as an advisor and member on editorial board of number of local and international scientific journals.

Abstract:

HIV/AIDS is not only a regional but global challenge and a major public health problem. Globally, about 36.7 million people are living with HIV/AIDS, with a particular burden on developing countries. Despite active control measures and series of programs initiated by government an estimated 34,100 people are still living with HIV infection in Papua New Guinea (PNG). High cost and scarcity of antiretroviral and other drugs make it difficult to provide health care needs for this group of patients. Traditional healers in PNG are treating patients with HIV and AIDS symptoms, and herbal preparations are being promoted specifically for this use. In a cross sectional pilot study conducted in Milne Bay and Oro provinces of PNG, the study showed the positive role played by traditional healers in providing treatment for HIV/AIDS-related sicknesses. Their main contribution is in alleviating suffering from opportunistic infections and providing advice on diet and healthy life style, and improving the quality of life by effectively treating the symptoms of the disease. People living with HIV (PLHIV) infection responded better to herbal treatments for cconditions such as chronic diarrhea, loss of appetite and nausea, skin infections, sores and panful blisters, persistent fever and cough, thrush, weight loss and weakened immunity.  Psidium guajava, Acalypha wilkesiana, Syzygium malaccense, Ficus copiosa, Eleusine indica, Codiaeum variegatum, Calophyllum inophyllum were most commonly used medicinal plants by healers. Specific uses, preparations and mode of applications of these plants will be presented. It is concluded that traditional healers are potential key to scaling up comprehensive care for PLHIV in PNG as in many other countries in Africa and Asia.

Biography:

Professor Supayang P. Voravuthikunchai received both B.Sc. (Hons) and Ph.D. in Microbiology from the University of New South Wales, Australia. She is currently a Professor at Department of Microbiology, Faculty of Science and Director of Natural Product Research Center of Excellence, Prince of Songkla University, Thailand. 150 articles have been published, together with 17 patents. National Invention Awards were given by National Research Council of Thailand (NRCT) in 2003 and 2014. In 2015, prototypes won a silver medal from Inventions  Geneva  and a gold medal from Brussels Innova. She received Research Excellence Awards at Thailand National Research Universities Summit in 2013 and 2014. She was named by NRCT as National Outstanding Researcher (Agriculture and Biology) in 2014. In 2015, she was honoured as Thailand Research Fund Senior Research Scholar (Medical Microbiology). In 2016, she was awarded as National Outstanding University Professor by the Council of University Faculty Senate of Thailand.

Abstract:

A talk will present a successful story on the transformation of scientific discoveries into patented inventions. Extraction method of  Rhodomyrtus tomentosa  leaf was developed. Semi-purified fractions as well as a principle compound, rhodomyrtone, was isolated. Forty five scientific papers are available in ISI. Top quality natural products were then designed based on strong scientific evidence (in vitro and in vivo) on their biological activities.  Advanced pharmaceutical technology was used to develop products. Clinical trials were performed for cosmetics and pharmaceutical products. Field trials in agricultural field and aquaculture system have been shown to prevent bovine mastitis and streptococcosis in fish of economic importance such as tilapia and rainbow trout, respectively. For applications as food additive. It was demonstrated that it could effectively prevent food from spoilage. In addition, sensory test in food models demonstrated that all samples rinsed with the extract attained acceptance limit for overall acceptability. Two patents and 7 petty patents are being pending in Thailand, together with six prototypes available.

Biography:

Connie Kam Yuen Ching is a registered Chinese medicine practitioner and registered nurse in Hong Kong. Now, she is continuing her PhD study in an university in Hong Kong. Also, she is a Senior Lecturer in the Open University of Hong Kong. She has published several papers in international conference.  

Abstract:

Obesity is an important risk factor of causing many health problems. Catgut embedding therapy (CMT) is one of the Chinese medicine intervention developed based on the theory of acupuncture. A piece of catgut is placed on the acupoints by using a fine needle and syringe and the catgut will stay there until it is being absorbed. The effects are similar to acupuncture but the duration of stimulation through the acupoint is longer. Objective: The study aims to examine the effectiveness of CMT at acupoints in reducing body weight (BW) for obesity. Methodology: A pilot study with 5 subjects was recruited. The length of catgut with 1-2 cm long and 12-16 threads of catgut were inserted into the selected acupoints in abdomen and 4 limbs of the subjects. It was absorbed in the body in 14 – 21 days and the next treatment was implemented on 21 days after the last treatment.  Each subject was received 3 consecutive treatments. Outcomes: It found that 0.3 – 1.2 kg BW reduction in 4 subjects with only one subject with no significant BW changes. Also, it found that 1 – 3.5 cm waist circumference reduction in 3 subjects and 1-3 cm arm circumference reduction in 4 subjects.  Significance:  The outcome of the study showed this intervention maybe effective on weight reduction.  It could be an alternative approach on reducing body weight and in scientific manner. Discussion:  It was a pilot study with limited sample size, a further large scale study is required for proving its effectiveness.  

Biography:

Nor Hidayah Abu Bakar has completed her MD and Master of Pathology (Anatomic Pathology from Universiti Sains Malaysia. She is now a senior medical lecturer of Universiti Sultan Zainal Abidin, Terengganu, Malaysia. She has a special interest in addiction medicine since 2005 and has been joining the Centre of Research in Addiction, UNISZA since a few years ago.  She has published several papers on addiction in a few indexed journals.

Abstract:

Honey has been  used traditionally as a remedy as well as a food supplement.

Honey is said to be able to cure many diseases. However, its influences on opioid tolerance

and dependence have not yet been clarified. Objective: To determine the effect of honey on the development of morphine tolerance and dependence.  Materials and Methods: Adult male Sprague-Dawley rats were rendered tolerant to the analgesic effect of morphine by injection of morphine (10 mg/kg, i.p.) twice daily for 14 days. To develop morphine dependence, the rats were given  chronic escalating doses of morphine. To determine the effect of stingless bee honey on the development of morphine tolerance and dependence, the hotplate and naloxone precipitation tests were used for the assessment. Results: Our results showed that chronic morphine-injected rats displayed tolerance to the analgesic effect of morphine as well as morphine dependence. Methadone+morphine (MetM), methadone+morphine+honey (MetMH) and morphine+Honey (MH) significantly lower the development of morphine tolerance with p-value p<0.05. In addition, a concomitant treatment of morphine with MH and MetMH attenuated almost all of the naloxone-induced withdrawal signs which include abdominal contraction, diarrhea, pertussis, teeth chattering, and jumping. Conclusion: The data indicate that honey has a potential to reduce tolerance and dependence in chronic morphine exposure.

Biography:

Assistant Professor (Soils), Rajasthan Agril. University, Bikaner, 1982-87; Commonwealth Fellow (Rothamsted, UK) 1983-84; Scientist-C, 1987-92, Scientist EI, 1992-97, Scientist E II, 1997-2002, and Scientist F 2002-07, Central Institute of Medicinal and Aromatic Plants (CIMAP), Lucknow; STA-JISTEC Fellow (Visiting Scientist), HNAES, Japan, 1999; Chief Scientist (Head, Agrotechnology), CSIR-Central Institute of Medicinal and Aromatic Plants (CIMAP), Lucknow, 2007-16.

Awards/Honours: FAI Silver Jubilee Award, 1980; FAI Gold Medal, 1983; Mint Technology Award, 1999; PPIC-FAI Gold Medal, 2000; 12th International Congress Commemoration Award, 2005; UPCAR Eminent Scientist Award (NRM), 2006; Golden Peacock Eco-innovation Award, 2008; ISCA Platinum Jubilee Award, 2008; CSIR S&T Innovation Award for Rural Development, 2008; VASVIK Award, 2010.

Fellow: National Academy of Sciences, India; Indian Society of Soil Science), New Delhi.

Research Areas: Soil Science & Agricultural Chemistry, Isotope technique, Agrotechnology of medicinal and aromatic plants, waste land utilization.

Abstract:

Phytotherapy has emerged as a new concept of health aid and consumption of plant mediated nutraceuticals has become very popular because of their less or no side effect. Risk of toxicity or adverse effect of drugs, led us to consider safer nutraceuticals, and functional food based approaches for health management. 

Nutraceutical is a term to define substances, which are non-traditionally recognized nutrients but have positive physiological effects on human body.  The active ingredients are phytochemicals, such as lycopene in tomatoes, allicin in garlic, isoflavones in soyabeans, glucosamine in ginseng, Omega-3 fatty acids in linseeds, epigallocatechin gallate in green tea, etc.  These phytochemicals, also called functional food, may be extracted and consumed as food supplements or may have therapeutic value when consumed in whole food. 

Promise of nutraceuticals is considered in two ways, viz. potential nutraceuticals and established nutraceuticals.  Similarly, the food products used as nutraceuticals are categorized as (i) Prebiotic, (ii) Dietary fibre (iii) Omega-3 fatty acid, and (iv) antioxidant.

This development in this area is propelling expansion in the nutraceuticals market globally.  The emerging nutraceutical industry seems destined to occupy the landscape in the new millennium.  Its tremendous growth has implications for the food, pharmaceuticals, healthcare and agricultural industries. 

Fermentation technology using microbes to create new food products also has great potentials.   The interaction of nutraceuticals with food and drugs is another area, which should be taken into consideration.  The effect of different processing methods on biological availability and effectiveness of nutraceuticals remains to be determined.

Biography:

Nasir Mohamad has completed his MD, Master of Medicine and PhD from Universiti Sains Malaysia. He is the director of Centrena, the centre for research in addiction,  in a community public University of Sultan Zainal Abidin, Terengganu, Malaysia. He has an interest in researches related to application of traditional herbs in the treatment of drugs and substances addiction. He is currently working to focus on integrating bio-psychosocio and spiritual components to empower the primary prevention with the secondary and tertiary management of addiction in the community for a better therapy. He has published more than 100 papers and books.

Abstract:

3,4-methylenedioxymethamphetamine (MDMA; “ecstasy”) is an illicit drug grouped under the amphetamine-type stimulants (ATS). The long-term effects of MDMA include depletion of extracellular serotonin or 5-hydroxytryptamine (5-HT). Hence, the aim of this study was to investigate the protective effect of thymoquinone (TQ) in preventing the 5-HT depletion induced by a single MDMA exposure. This study was conducted by dividing the rats randomly into four groups i.e: i) Control group, receiving 0.1 ml/kg saline, ii) MDMA group, receiving a single administration of 20 mg/kg MDMA, iii) MDMA-TQ group, receiving a single administration of 20 mg/kg MDMA and treated with 40 mg/kg TQ for one week and, iv) TQ group, receiving 40 mg/kg TQ for one week.  All compounds were administered to the rats through oral gavage. Percentage of weight gain was measured, and at the end of the experiment, cerebrospinal fluid was collected from the cisterna magna of the rats for evaluation of the 5-HT neurotransmitter level. Our results demonstrated a significant increased in 5-HT level from the CSF of the MDMA-TQ group as compared to the MDMA group. MDMA-TQ group also showed a higher percentage of weight gain as compared to the MDMA group. Our study suggests that the subsequent long-term 5-HT depletion induced by MDMA can be prevented by thymoquinone.

Biography:

Cornelius Tony Vulumu at 25 years of age completed his Bachelors in Pharmacy Degree at Fiji National University 2016. Successfully underwent a year of internship and recently in 2018 became a registered Pharmacist at the National Referral Hospital, Honiara, Solomon Islands. He has been appointed to look after clinical pharmacy for pediatric ward in early June 2018.

Abstract:

Type 2 diabetes mellitus (T2DM) has become a major public health issue in Solomon Islands in recent years, with prevalence estimated at 13.5% ± 4.3. Cultural influence on health-seeking behaviors has been documented. There is increasing interest in the use of common medicinal plants for medicinal purposes in chronic diseases due to easy accessibility and availability. There seems to be no evidence of published data on the use of TMPs in the management of T2DM in Solomon Islands. This study investigated the use of TMP by individuals with T2DM. This was a descriptive cross sectional study conducted at the National Diabetic Clinic in Honiara from June 27th to July 22nd 2016. Individuals with T2DM aged 18 years and above were randomly selected and interviewed using a structured questionnaire. Categorical variables were summarized as frequencies and percentages and Chi-Square analysis was used to test relationships between  variables.

A total of 200 individuals with T2DM were interviewed. More than half, 63% (n=126) of the

participants reported using TMPs for the management of T2DM. Common TMPs used include; Annona muricata L. (n=11), Areca Catechu (n=9), Morinda citrifolia (n= 8), Carica papaya (n=8), Zingiber officinale Roscoe (n=6) and Dioscorea. (n=4). Few, 8% (n=16) stated using TMPs concurrently with modern medicines, although 43% (n=86) preferred both TMPs and modern medicines. Some factors influencing use of TMPs included level of education (𝜒2-test, p= 0.001), sex (𝜒2-test, p= 0.034) and years of having T2DM (𝜒2-test, p= 0.021).

It can be concluded that most individuals with T2DM who visit the National Diabetic Clinic in Honiara, Solomon Islands use TMPs for the management of increased blood glucose levels. More research is needed to further investigate the factors influencing the use of TMPs in Solomon Islands.

Biography:

Abdeen Mustafa Omer (BSc, MSc, PhD) is an Associate Researcher at Occupational Health Administration, Ministry of Health and Social Welfare, Khartoum, Sudan. He has been listed in the book WHO’S WHO in the World 2005, 2006, 2007 and 2010. He has published over 300 papers in peer-reviewed journals, 200 review articles, 15 books and 150 chapters in books.

Abstract:

The strategy of price liberalisation and privatisation had been implemented in Sudan over the last decade, and has had a positive result on government deficit. The investment law approved recently has good statements and rules on the above strategy in particular to pharmacy regulations. Under the pressure of the new privatisation policy, the government introduced radical changes in the pharmacy regulations. To improve the effectiveness of the public pharmacy, resources should be switched towards areas of need, reducing inequalities and promoting better health conditions. Medicines are financed either through cost sharing or full private. The role of the private services is significant. A review of reform of financing medicines in Sudan is given in this article. Also, it highlights the current drug supply system in the public sector, which is currently responsibility of the Central Medical Supplies Public Corporation (CMS). In Sudan, the researchers did not identify any rigorous evaluations or quantitative studies about the impact of drug regulations on the quality of medicines and how to protect public health against counterfeit or low quality medicines, although it is practically possible. However, the regulations must be continually evaluated to ensure the public health is protected against by marketing high quality medicines rather than commercial interests, and the drug companies are held accountable for their conducts.

Biography:

Kevin Spelman, Ph.D., MCPP is a researcher, educator and industry consultant that has advised the White House and the Department of Defense on natural products and has been active in several areas of natural products research including immunology at UNC, malaria as a Marie Curie Research Fellow in the European Union, brain cancer, as well as CB1 and CB2 receptor binding at National Institutes of Health where he was the first researcher to elucidate CB2 ligands in Zanthoxylum spp. He has also been a senior executive for multiple companies and has considerable experience in new product development, analytical and QC guidelines and educational curriculums. Dr. Spelman is currently Chief Scientific Officer for Indomira.

Abstract:

Beyond THC there are at least 60 other cannabinoids in the Cannabis plant. Unfortunately the fascination and politics around THC, have created a potential bias against the pharmacology of other potentially therapeutic cannabidnoids. Cannabidiol (CBD) is the second most plentiful cannabinoid in the Cannabis species. Importantly, this pleiotropic cannabinoid does not induce euphoria but does show some intriguing activity in a number of molecular pathways, tissues and physiological systems. Beyond attenuating the euphoria of THC, anxiolytic, anti-inflammatory, analgesic, anti-seizure, anti-addictive and anti-neoplastic activities are prominent. In addition, it puts other receptors into play besides the the classical cannabinoid receptors (CB1 & CB2). We will examine the evidence base for CBD, which is growing rapidly and offers broad spectrum and potentailly significant therapeutic potential.

Biography:

Dr. Sandeep Chavan is a Homoeopathic doctor, postgraduate in public health administration from Tata institute of Social Sicences, Mumbai, India. He has total 8 years of professional experience and is working with India’s biggest philanthropic organization – Tata Trusts since past 4.5 years as a Program Officer for Healthcare initiatives. His area of experience is across maternal and child health, vector borne diseases, mental health and primary healthcare. Dr. Sandeep is passionated towards promoting and mainstreaming Homoeopathy for better public health outcomes.

Abstract:

Homoeopathy is a system of medicine originated in Germany, founded by a modern medicine physician – Dr. Samuel Hahnemann, is thriving alternative system of medicine in India, most popular in northern states. Homoeopathic medicines are proven to be effective in treating large number of acute as well as chronic ailments and have nil side effects. The successful treatment ensues when a physician understands dimensions of the disease in the holistic Homoeopathic perspective and accordingly prescribes. Despite cost effectiveness, Homoeopathy offers promising public health benefits to maintain as well as restore health in most natural ways by helping to avoid overuse of antibiotics, eventually boosting individual’s immunity.  Hence integrating Homoeopathy with modern medicine is critical to mitigate huge unmet needs of primary healthcare in India, especially where accessibility of healthcare provider is key concerns for rural masses.

India relies on a three-tier public health system, the first one being Health Sub-Centers (HSC). HSCs, manned by a trained nurse, are meant to cater to a population of 5,000. Consulting a doctor is through a Primary Health Center (PHC) exists for every 30,000 people. Hence patients need to travel to seek a doctor’s consultation. Further, challenges related to infrastructure and competent paramedical personnel at peripheral health facilities still exist. Despite proven efficacy, availability of alternative medicine practitioner such as a Homoeopath is only at the block level, typically for a population of 1 lakh. In such a scenario rural people have no choice but to seek care from local quacks who provide service at the villagers’ doorsteps. To fulfill villagers’ primary healthcare needs, guided women collectives in villages of Uttar Pradesh state in India initiated Gaon Dawakhana (A village Clinic) with 1,000 families in January 2017. It is a community funded integrated primary healthcare service delivery platform through a Homoeopathic doctor – visiting weekly twice and a Modern Medicine doctor – visiting monthly twice to provide medical services at doorsteps for villagers. Unit of one clinic is a collective of 500 families, each contributing 50/-INR per family per month to seek services of a clinic. Except for the administrative cost (which is being funded by Tata Trusts), entire operational cost of clinics (including doctors’ fees, medicines’ cost, etc.) is met through the monthly subscription fees. Since January 2017, total 31,919 patients are treated across 10 clinic locations benefitting to more than 5,000 families. Through 15 quarterly health camps for non communicable diseases, child health issues, etc 3,132 patients are treated.

One of the important challenges faced is overcrowding at clinics and difficulty to maintain stock of key Homoeopathic medicine owing to its availability at remote places. Major learning from the initiative is, Homoeopathy as an alternative system, can be integrated with Modern Medicine to mitigate unmet needs of primary health care of rural masses because of its efficacy and cost effectiveness. Continuous community contribution is sign of acceptability towards Homoeopathy and it also ensures sustainability for the initiative. Further it demystifices the common notion that rural poor are always in need of free services. It is appreciated that, though economically vulnerable, families are willing to pay, if they perceive value in services. Both the initiative itself and the Homoepathy has got promising potential to meet primary healthcare needs for rural masses.