The role of mesolimbic system and lateral habenular molecular targets (CB₁, GluA₁ and NK₁ receptors) in mitragyna speciosa korth (ketum) addiction in the mitragynine-sensitised swiss albino mice

There is a growing trend to use the leaves of Malaysian folklore medicinal plant Mitragyna speciosa Korth. (or ketum) for recreational high and as a self-medication alternative to traditional opiates, hence subjecting it to addictive liabilities. Mitragynine (ketum major alkaloid) is an atypical opioid agonist exhibiting complex psychostimulant and morphine-like analgesic effects, although the exact mechanisms remain unclear. In recent years, studies demonstrated a wide array of overlapping and integrated neuronal circuits in addiction, including the opioid-cannabinoid-glutamate AMPA-neurokinin-dopaminergic systems. This study aimed to demonstrate the involvement of the cannabinoid (CB1), glutamate (GluA1) and neurokinin (NK1) receptors in the hippocampus, ventral tegmental area (VTA) and lateral habenula (LHb) brain regions as the neurobiological bases of ketum abuse potential through its interaction with mitragynine. One hundred and twenty (n=120) male Swiss albino mice were subjected to 28-days (chronic) regimen with untreated and Tween-20 vehicle control, morphine sulphate, THC or mitragynine, either with/without coadministration with CB1, GluA1 or NK1 receptor antagonists (i.e. NIDA-41020, PhTx- 74 or RP-67580, respectively). The IntelliCage® system was used as the behavioural sensitisation setting to assess mice cognitive performances and addiction-like behaviours following chronic drug treatment. Findings revealed that chronic mitragynine exposure (incremental doses of 5 to 25 mg/kg) resulted in hyperlocomotion (p < 0.05), potentiated preference and persistence for natural reward (i.e. 10% sucrose) (p < 0.01), resistance to punishment (p < 0.05), and spatial learning memory deficit (p < 0.05), comparable to those observed in morphine- and THCsensitised mice (p > 0.05). The mitragynine-, morphine- and THC-induced spatial learning and memory impairments were attenuated by NIDA-41020 (p < 0.05), PhTx- 74 (p < 0.05) and RP-67580 (p < 0.05), suggesting the CB1, GluA1 and NK1 receptors putative role in the drugs’ mechanism of actions. The underlying adaptations in mice key brain mesolimbic areas, with regards to CB1, GluA1 and NK1 receptors, were investigated using immunohistochemistry, Western Blot and quantitative real-time PCR (qPCR) studies. Mitragynine-sensitised mice demonstrated enhanced CB1 receptor proteins and genes expression at hippocampus CA1 (p < 0.001) and VTA regions (p < 0.001). GluA1 receptor proteins and genes were also up-regulated at hippocampus CA1 regions (p < 0.001), whereas NK1 were up-regulated at the LHb (p < 0.05). These mitragynine-induced receptor up-regulations resembled those observed with chronic morphine (p > 0.05). Neuronal changes as seen in mitragynine- and morphine-sensitised mice appeared to be absent in drug paired with respective receptor antagonist groups, thus providing affirmative clues to the behavioural changes observed. Taken together, these findings demonstrate the seeming integrated role of brain CB1, GluA1 and NK1 receptors in mitragynine/ketum addictive liabilities, leading to behavioural and probable adaptive changes in the brain mesolimbic reward pathway. However, the extent and nature of these receptor interactions in ketum misuse remain unclear. The study findings lend the first correlative relationship that implicates drug molecular targets not previously known (i.e. cannabinoid-glutamate AMPA-neurokinin systems) in relation to chronic mitragynine misuse. This may also provide new insight to inform the phytomedicinal potentials that are linked to this plant

Integration of Sensing Framework with a Decision Support System for Monitoring Water Quality in Agriculture

Water is an essential element for every plant to survive, absorb nutrients, and perform photosynthesis and respiration. If water is polluted, plant growth can be truncated. The aim of this research is to develop a water quality monitoring system for agriculture purposes based on integration of sensing framework with a smart decision support method. This research consists of three stages: (1) the first stage: developing sensing framework which has four different water quality parameter sensors such as potential hydrogen (pH), electrical conductivity (EC), temperature, and oxidation-reduction potential (ORP), (2) the second stage: developing a hardware platform that uses an Arduino for sensor array of data processing and acquisition, and finally (3) the third stage: developing soft computing framework for decision support which uses python applications and fuzzy logic. The system was tested using water from many sources such as rivers, lakes, tap water, and filtered machine. Filtered water shows the highest value of pH as the filtered machine produces alkaline water, whereas tap water shows the highest value of temperature because the water is trapped in a polyvinyl chloride (PVC) pipe. Lake water depicts the highest value of EC due to the highest amount of total suspended solids (TSS) in the water, whereas river water shows the highest value of ORP due to the highest amount of dissolved oxygen. The system can display three ranges of water quality: not acceptable (NA), adequate (ADE) and highly acceptable (HACC) ranges from 0 to 9. Filtered water is in HACC condition (ranges 7–9) because all water quality parameters are in highly acceptable ranges. Tap water shows ADE condition (ranges 4–7) because one of the water quality parameters is in adequate ranges. River and lake water depict NA conditions (ranges 0–4) as one of the water quality parameters is in not acceptable ranges. The research outcome shows that filtered water is the most reliable water source for plants due to the absence of dissolved solids and contaminants in the water. Filtered water can improve pH and reduce the risk of plant disease. This research can help farmers to monitor the quality of irrigated water which eventually prevents crop disease, enhances crop growth, and increases crop yield

Advancements in Monitoring Water Quality Based on Various Sensing Methods: A Systematic Review

Nowadays, water pollution has become a global issue affecting most countries in the world. Water quality should be monitored to alert authorities on water pollution, so that action can be taken quickly. The objective of the review is to study various conventional and modern methods of monitoring water quality to identify the strengths and weaknesses of the methods. The methods include the Internet of Things (IoT), virtual sensing, cyber-physical system (CPS), and optical techniques. In this review, water quality monitoring systems and process control in several countries, such as New Zealand, China, Serbia, Bangladesh, Malaysia, and India, are discussed. Conventional and modern methods are compared in terms of parameters, complexity, and reliability. Recent methods of water quality monitoring techniques are also reviewed to study any loopholes in modern methods. We found that CPS is suitable for monitoring water quality due to a good combination of physical and computational algorithms. Its embedded sensors, processors, and actuators can be designed to detect and interact with environments. We believe that conventional methods are costly and complex, whereas modern methods are also expensive but simpler with real-time detection. Traditional approaches are more time-consuming and expensive due to the high maintenance of laboratory facilities, involve chemical materials, and are inefficient for on-site monitoring applications. Apart from that, previous monitoring methods have issues in achieving a reliable measurement of water quality parameters in real time. There are still limitations in instruments for detecting pollutants and producing valuable information on water quality. Thus, the review is important in order to compare previous methods and to improve current water quality assessments in terms of reliability and cost-effectiveness

Nanotechnology-based approaches for antitubercular drug delivery

Tuberculosis (TB) is an old disease that may have coexisted with humans for at least 15,000 years before the Neolithic [1]. TB is a communicable disease caused by Mycobac- terium tuberculosis and it remains the deadliest infectious disease killing 60 million people since 2000 [2,3]. The disease can be spread through the respiratory route, such as coughing from an infected person or gastrointestinal route possibly by drinking milk contaminated by bovine tubercle bacillus (M. bovis) by infecting the lung (pulmonary TB) and other sites (extrapulmonary TB) [1]. Almost a quarter of the world population is infected with TB [3] affecting more men than women. However, the treatment of TB has a fundamental issue that the long duration of the therapy which induce patient non-compliance, treatment failure and development of drug resistant by the pathogen [4]. Therefore, innovative strategy in the delivery of TB drugs such as in nanotechnology approach particularly in nanoparticle delivery would be more effective than conventional antibiotic treatment regimens via oral delivery. Nanoparticles which are administered via pulmonary inhalation gains special interest due to their intrinsic antimicrobial activity which acts directly to the lungs and avoiding first-pass metabolism reduction of dose and user-friendly administration (Fig. 10.1A) [5]. Nanoparticle is a small molecule sized less than 1000 nm that can encapsulate drugs and works efficiently in terms of improving physicochemical, stability and effectiveness of a drug. Nanoparticles can be made from different materials such as organic and polymer based nanocarriers (e.g polymer, solid lipid (SLNs), liquid crystal (LC), liposomes (LIP), micro- emulsions (MEs), carbon, and nanomicelles (NMs)) as well as inorganic nanocarriers (e.g gold, silver, and iron oxide) [6,7]. There are different methods available to produce nanopar- ticles resulting in different structures and sizes [5]. Some composition of different types of nanoparticles that have been tested for activity against Mycobacterium tuberculosis, such as those encapsulations first-or second-line anti-TB drugs, alone or in combination, as well as other potentially useful particles such as antimicrobial peptide and other therapeutic agents. Different properties of nanoparticles may influence their absorption, distribution, and efficacy in nanoparticle-based therapeutics as shown in Fig. 10.1B [5]

Neuroscience 101 for school pupils: 'The Brain Apprentice' project

Community engagement efforts in brains and neurosciences projects involving higher education institutions are currently sporadic in Malaysia and likely to contribute the apparent lack of neuroscience awareness in the society. In this paper, we highlight 'The Brain Apprentice' project as a knowledge transfer effort to raise neuroscience awareness using school-centred neuroscience clubs. These groups promote the appreciation of neuroscience beyond conventional classroom approaches and the training of neuroscience graduate interns as student facilitators in the teaching and learning of neuroscience. The Brain Apprentice was delivered through the establishment of two school-based neuroscience clubs, Sekolah Kebangsaan Kubang Kerian 3 (primary level) and Sekolah Menengah Sains Tengku Muhammad Faris Petra (secondary level). The teaching and learning of neuroscience was delivered through practical sessions and competitions. Questionnaires were collected from the students based on the following four domains: general satisfaction, impact of knowledge transfer, satisfaction with graduate interns, and knowledge and practical relevance of neuroscience. The National Brain Bee championship has resulted in the first Malaysia representative competing at the International Brain Bee 2012. Students, who had participated as neuroscience club members were exposed to the basic principles of neuroscience, which boosted their interest in science and neuroscience. The graduate interns had also been provided with opportunities to hone in their soft skills and be involved in community-engagement efforts. This project offered a suitable model of community-engagement in raising awareness about and the profile of neuroscience both in terms of knowledge exposure and from the perspective of career options in the field.</p

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially