An overview of Neem (Azadirachta indica) and its potential impact on health

Global health and medical practice seek to merge alternative medicine with evidence-based medicine for a better understanding of the metabolic process and its effects in the human body. An example is the use of complementary medicine like phytotherapy. Azadirachta indica (Neem), a tree originally from India and Myanmar, called by many “The village pharmacy” or “Divine tree” because of its many health properties. In recent times, Neem-derived extracts have been shown to work from anywhere from insect repellent, to supplements to lower inflammation, diabetic control, and even to combat cancer. Herein, we state the health benefits found in diverse compounds and extracts derived from Neem, highlighting the mechanisms and pathways in which Neem compounds produce their effects, while warning that the improper and unstandardized conditions to produce extracts can lead to health issues, particularly certain compounds might have damaging effects on the liver and kidneys

The unfinished agenda of communicable diseases among children and adolescents before the COVID-19 pandemic, 1990-2019: a systematic analysis of the Global Burden of Disease Study 2019

BACKGROUND: Communicable disease control has long been a focus of global health policy. There have been substantial reductions in the burden and mortality of communicable diseases among children younger than 5 years, but we know less about this burden in older children and adolescents, and it is unclear whether current programmes and policies remain aligned with targets for intervention. This knowledge is especially important for policy and programmes in the context of the COVID-19 pandemic. We aimed to use the Global Burden of Disease (GBD) Study 2019 to systematically characterise the burden of communicable diseases across childhood and adolescence. METHODS: In this systematic analysis of the GBD study from 1990 to 2019, all communicable diseases and their manifestations as modelled within GBD 2019 were included, categorised as 16 subgroups of common diseases or presentations. Data were reported for absolute count, prevalence, and incidence across measures of cause-specific mortality (deaths and years of life lost), disability (years lived with disability [YLDs]), and disease burden (disability-adjusted life-years [DALYs]) for children and adolescents aged 0-24 years. Data were reported across the Socio-demographic Index (SDI) and across time (1990-2019), and for 204 countries and territories. For HIV, we reported the mortality-to-incidence ratio (MIR) as a measure of health system performance. FINDINGS: In 2019, there were 3·0 million deaths and 30·0 million years of healthy life lost to disability (as measured by YLDs), corresponding to 288·4 million DALYs from communicable diseases among children and adolescents globally (57·3% of total communicable disease burden across all ages). Over time, there has been a shift in communicable disease burden from young children to older children and adolescents (largely driven by the considerable reductions in children younger than 5 years and slower progress elsewhere), although children younger than 5 years still accounted for most of the communicable disease burden in 2019. Disease burden and mortality were predominantly in low-SDI settings, with high and high-middle SDI settings also having an appreciable burden of communicable disease morbidity (4·0 million YLDs in 2019 alone). Three cause groups (enteric infections, lower-respiratory-tract infections, and malaria) accounted for 59·8% of the global communicable disease burden in children and adolescents, with tuberculosis and HIV both emerging as important causes during adolescence. HIV was the only cause for which disease burden increased over time, particularly in children and adolescents older than 5 years, and especially in females. Excess MIRs for HIV were observed for males aged 15-19 years in low-SDI settings. INTERPRETATION: Our analysis supports continued policy focus on enteric infections and lower-respiratory-tract infections, with orientation to children younger than 5 years in settings of low socioeconomic development. However, efforts should also be targeted to other conditions, particularly HIV, given its increased burden in older children and adolescents. Older children and adolescents also experience a large burden of communicable disease, further highlighting the need for efforts to extend beyond the first 5 years of life. Our analysis also identified substantial morbidity caused by communicable diseases affecting child and adolescent health across the world. FUNDING: The Australian National Health and Medical Research Council Centre for Research Excellence for Driving Investment in Global Adolescent Health and the Bill & Melinda Gates Foundation

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background Disorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021. Methods We estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined. Findings Globally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer. Interpretation As the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed. Funding Bill & Melinda Gates Foundation

Cortical hyperactivity beyond immune attack : pivotal role of TNF-alpha in early Multiple Sclerosis

The central nervous system (CNS) is the primary target in both multiple sclerosis (MS) and the animal model of experimental autoimmune encephalomyelitis (EAE). The disease is mainly driven by infiltrating myelin specific T cells that are peripherally activated by antigen presenting cells (APCs), yet little known about how the disease itself affects neuronal activity patterns in the different cortices in vivo. In the last decades, growing advancement in functional imaging has been successfully applied in several other CNS diseases but its real-time application in CNS autoimmunity has not been achieved. Here, we employed in vivo two-photon Ca2+ imaging to study the activity patterns of neurons in the visual cortex of mice with different phases of the EAE. By using this method, we identified spontaneous activity of the network in the visual cortex that had drastically increased followed by increased hyperactive cells in remission (disease phase with no or mild symptoms present) rather than in relapse where the disease symptoms were less prominent. In addition, frontal cortex also displayed similar activity pattern supporting that it is a cortex-wide phenomenon and such alteration of activity is independent of demyelination or cellular infiltration. Furthermore, cortical TNF-α level had significantly elevated throughout the cortex in remission mice and a reversal of increased cortex activity was achieved by intraventricular injections of infliximab, a monoclonal antibody specific against TNF-α. CamKII+ excitatory neurons were found to be surrounded by soluble TNF-α. Taken together, this thesis furnishes advances of two-photon microscopy to enable functional studies of visual and frontal cortices neuronal activity in vivo in different disease states of EAE.Das zentrale Nervensystem (ZNS) ist sowohl bei Multipler Sklerose (MS) als auch im Tiermodel der experimentellen autoimmunen Encephalomyelitis (EAE) das primäre Ziel. Die Krankheit wird vor allem durch myelin-spezifische T-Zellen, die in der Peripherie durch Antigen-präsentierende Zellen (APZ) aktiviert werden, vorangetrieben. Dennoch ist relativ wenig darüber bekannt, wie das die neuronalen Aktivitätsmuster in den verschiedenen Kortizes in vivo beeinflusst. Die Fortschritte im funktionellen Imaging in den letzten Jahrzehnten konnten erfolgreich in anderen Erkrankungen des ZNS angewandt werden, jedoch wurde der Einsatz dieser „real-time“ Methoden bei Autoimmunerkrankungen des ZNS noch nicht umgesetzt. Hier haben wir in vivo 2-Photonen-Kalzium-Imaging eingesetzt um das Aktivitätsmuster der Neuronen im visuellen Kortex der Mäuse in den verschiedenen Phasen der EAE zu untersuchen. Durch diese Technik war es uns möglich eine drastische Erhöhung der spontanen Aktivität des neuronalen Netzwerkes im visuellen Kortex festzustellen, gefolgt von einem Anstieg hyperaktiver Zellen während der Remissions-Phase (Krankheitsphase mit keinen oder sehr schwachen Symptomen). Im Gegensatz dazu traten die Krankheitssymptome in der Relaps-Phase weniger auf. Zusätzlich zeigte auch der frontale Kortex ein ähnliches Aktivitätsmuster. Dies unterstützt die Annahme, dass es sich um ein Phänomen handelt, welches im gesamten Kortex auftritt und dass die Änderung der Aktivität unabhängig von der Demyelinisierung oder der zellulären Infiltration ist. Außerdem war das kortikale TNF-α bei Mäusen in der Remission im gesamten Kortex signifikant erhöht und die gesteigerte kortikale Aktivität konnte durch eine intraventrikuläre Gabe von Infliximab, ein monoklonaler Antikörper gegen TNF-α, rückgängig gemacht werden. Besonders außergewöhnlich war, dass CamKII+ exzitatorische Neuronen von löslichem TNF-α umgeben waren. Zusammengenommen zeigt diese Arbeit neue Wege der 2-Photonen-Mikroskopie auf, die es ermöglichen funktionelle Studien der neuronalen Aktivität in frontalen und visuellen Kortizes in den unterschiedlichen Krankheitsstadien der EAE durchzuführen

Preparation of formed-coke using devolatilized inferior coal and its mechanical properties

Coke plays multiple roles in blast furnace operation. Preparation of formed coke from inferior coal provides an alternate way to utilize inferior coal for metallurgical uses. In this process briquettes of coal, char were prepared to produce similar properties to the conventional coke and sufficient strength to maintain the shape during transport, storage and utilization. In this study formed coke was prepared using devolatilized coal at different temperature. The effect of use of this devolatilized coal was studied in terms of point crushing strength. In general, it was observed that higher devolatilization temperature (550 °C) and longer duration (3 hr) increases the point crushing strength and fixed carbon. Fast volatilization process during carbonization significantly decreases the coke mechanical strength. The use of devolatilized coal reduces the volatile matter content and in turn reduces the fast volatilization which increase the point crushing strength

Plant reproductive traits mediate tritrophic feedback effects within an obligate brood-site pollination mutualism

Plants, herbivores and parasitoids affect each other directly and indirectly; however, feedback effects mediated by host plant traits have rarely been demonstrated in these tritrophic interactions. Brood-site pollination mutualisms (e.g. those involving figs and fig wasps) represent specialised tritrophic communities where the progeny of mutualistic pollinators and of non-mutualistic gallers (both herbivores) together with that of their parasitoids develop within enclosed inflorescences called syconia (hence termed brood-sites or microcosms). Plant reproductive phenology (which affects temporal brood-site availability) and inflorescence size (representing brood-site size) are plant traits that could affect reproductive resources, and hence relationships between trees, pollinators and non-pollinating wasps. Analysing wasp and seed contents of syconia, we examined direct, indirect, trophic and non-trophic relationships within the interaction web of the fig-fig wasp community of Ficus racemosa in the context of brood site size and availability. We demonstrate that in addition to direct resource competition and predator-prey (host-parasitoid) interactions, these communities display exploitative or apparent competition and trait-mediated indirect interactions. Inflorescence size and plant reproductive phenology impacted plant-herbivore and plant-parasitoid associations. These plant traits also influenced herbivore-herbivore and herbivore-parasitoid relationships via indirect effects. Most importantly, we found a reciprocal effect between within-tree reproductive asynchrony and fig wasp progeny abundances per syconium that drives a positive feedback cycle within the system. The impact of a multitrophic feedback cycle within a community built around a mutualistic core highlights the need for a holistic view of plant-herbivore-parasitoid interactions in the community ecology of mutualisms

Path diagrams representative of the best-fit models for each season.

<p>These path models describe the relationships between various factors for: (a) Season 1 (winter), (b) Season 2 (hot days and cold nights), (c) Season 3 (summer) and (d) Season 4 (wet). Measures of syconium volume, number of pollinators, parasites and seeds per syconium for the path analyses were obtained from 237 syconia in season 1, 340 in season 2, 427 in season 3 and 405 in season 4. The intra-crop variations in syconium inhabitants and syconium volume were described using the standard deviation (SD) in numbers of that inhabitant and syconium volumes amongst syconia within a tree during a particular reproductive episode. All arrows indicate direct relationships between factors. Solid arrows indicate positive relationships and dotted arrows indicate negative relationships. Numbers next to these arrows indicate standardised path coefficients for direct effects. *** p<0.001, ** p<0.01 and >0.001, *p<0.05 and >0.01, n.s.</p

High Temperatures Result in Smaller Nurseries which Lower Reproduction of Pollinators and Parasites in a Brood Site Pollination Mutualism

<div><p>In a nursery pollination mutualism, we asked whether environmental factors affected reproduction of mutualistic pollinators, non-mutualistic parasites and seed production via seasonal changes in plant traits such as inflorescence size and within-tree reproductive phenology. We examined seasonal variation in reproduction in <i>Ficus racemosa</i> community members that utilise enclosed inflorescences called syconia as nurseries. Temperature, relative humidity and rainfall defined four seasons: winter; hot days, cold nights; summer and wet seasons. Syconium volumes were highest in winter and lowest in summer, and affected syconium contents positively across all seasons. Greater transpiration from the nurseries was possibly responsible for smaller syconia in summer. The 3–5°C increase in mean temperatures between the cooler seasons and summer reduced fig wasp reproduction and increased seed production nearly two-fold. Yet, seed and pollinator progeny production were never negatively related in any season confirming the mutualistic fig–pollinator association across seasons. Non-pollinator parasites affected seed production negatively in some seasons, but had a surprisingly positive relationship with pollinators in most seasons. While within-tree reproductive phenology did not vary across seasons, its effect on syconium inhabitants varied with season. In all seasons, within-tree reproductive asynchrony affected parasite reproduction negatively, whereas it had a positive effect on pollinator reproduction in winter and a negative effect in summer. Seasonally variable syconium volumes probably caused the differential effect of within-tree reproductive phenology on pollinator reproduction. Within-tree reproductive asynchrony itself was positively affected by intra-tree variation in syconium contents and volume, creating a unique feedback loop which varied across seasons. Therefore, nursery size affected fig wasp reproduction, seed production and within-tree reproductive phenology via the feedback cycle in this system. Climatic factors affecting plant reproductive traits cause biotic relationships between plants, mutualists and parasites to vary seasonally and must be accorded greater attention, especially in the context of climate change.</p></div

Average daily maximum and minimum values of: (a) Temperature; (b) Relative humidity for each month.

<p>Based on these values, months were grouped into 4 seasons, with 1 denoting the cold season, 2 denoting the season with hot days and cold nights, 3 denoting the hot season and 4 denoting the wet season.</p