Intussusception after Rotavirus Vaccine Introduction in India.

BACKGROUND: A three-dose, oral rotavirus vaccine (Rotavac) was introduced in the universal immunization program in India in 2016. A prelicensure trial involving 6799 infants was not large enough to detect a small increased risk of intussusception. Postmarketing surveillance data would be useful in assessing whether the risk of intussusception would be similar to the risk seen with different rotavirus vaccines used in other countries. METHODS: We conducted a multicenter, hospital-based, active surveillance study at 27 hospitals in India. Infants meeting the Brighton level 1 criteria of radiologic or surgical confirmation of intussusception were enrolled, and rotavirus vaccination was ascertained by means of vaccination records. The relative incidence (incidence during the risk window vs. all other times) of intussusception among infants 28 to 365 days of age within risk windows of 1 to 7 days, 8 to 21 days, and 1 to 21 days after vaccination was evaluated by means of a self-controlled case-series analysis. For a subgroup of patients, a matched case-control analysis was performed, with matching for age, sex, and location. RESULTS: From April 2016 through June 2019, a total of 970 infants with intussusception were enrolled, and 589 infants who were 28 to 365 days of age were included in the self-controlled case-series analysis. The relative incidence of intussusception after the first dose was 0.83 (95% confidence interval [CI], 0.00 to 3.00) in the 1-to-7-day risk window and 0.35 (95% CI, 0.00 to 1.09) in the 8-to-21-day risk window. Similar results were observed after the second dose (relative incidence, 0.86 [95% CI, 0.20 to 2.15] and 1.23 [95% CI, 0.60 to 2.10] in the respective risk windows) and after the third dose (relative incidence, 1.65 [95% CI, 0.82 to 2.64] and 1.08 [95% CI, 0.69 to 1.73], respectively). No increase in intussusception risk was found in the case-control analysis. CONCLUSIONS: The rotavirus vaccine produced in India that we evaluated was not associated with intussusception in Indian infants. (Funded by the Bill and Melinda Gates Foundation and others.).

Nuclear receptor Nr1d1 alleviates asthma by abating GATA3 gene expression and Th2 cell differentiation.

Nuclear receptors are a unique family of transcription factors that play cardinal roles in physiology and plethora of human diseases. The adopted orphan nuclear receptor Nr1d1 is a constitutive transcriptional repressor known to modulate several biological processes. In this study, we found that Nr1d1 plays a decisive role in T helper (Th)-cell polarization and transcriptionally impedes the formation of Th2 cells by directly binding to the promoter region of GATA binding protein 3 (GATA3) gene. Nr1d1 interacts with its cellular companion, the nuclear receptor corepressor and histone deacetylase 3 to form a stable repression complex on the GATA3 promoter. The presence of Nr1d1 also imparts protection against associated inflammatory responses in murine model of asthma and its ligand SR9011 eased disease severity by suppressing Th2 responses. Moreover, Chip-seq profiling uncovered Nr1d1 interactions with other gene subsets that impedes Th2-linked pathways and regulates metabolism, immunity and brain functions, therefore, providing empirical evidence regarding the genetic link between asthma and other comorbid conditions. Thus, Nr1d1 emerges as a molecular switch that could be targeted to subdue asthma.

Expatiating the molecular approaches of HMGB1 in diabetes mellitus: Highlighting signalling pathways via RAGE and TLRs.

Diabetes mellitus (DM) has become one of the major healthcare challenges worldwide in the recent times and inflammation being one of its key pathogenic process/mechanism affect several body parts including the peripheral and central nervous system. High-mobility group box 1 (HMGB1) is one of the major non-histone proteins that plays a key role in triggering the inflammatory response. Upon its release into the extracellular milieu, HMGB1 acts as an "alarmin" for the immune system to initiate tissue repair as a component of the host defense system. Furthermore, HMGB1 along with its downstream receptors like Toll-like receptors (TLRs) and receptors for advanced glycation end products (RAGE) serve as the suitable target for DM. The forthcoming research in the field of diabetes would potentially focus on the development of alternative approaches to target the centre of inflammation that is primarily mediated by HMGB1 to improve diabetic-related complications. This review covers the therapeutic actions of HMGB1 protein, which acts by activating the RAGE and TLR molecules to constitute a functional tripod system, in turn activating NF-κB pathway that contributes to the production of mediators for pro-inflammatory cytokines associated with DM. The interaction between TLR2 and TLR4 with ligands present in the host and the activation of RAGE stimulates various immune and metabolic responses that contribute to diabetes. This review emphasizes to elucidate the role of HMGB1 in the initiation and progression of DM and control over the inflammatory tripod as a promising therapeutic approach in the management of DM.

Diversity of rotavirus genotypes circulating in children < 5 years of age hospitalized for acute gastroenteritis in India from 2005 to 2016: analysis of temporal and regional genotype variation.

BACKGROUND: From 2016, the Government of India introduced the oral rotavirus vaccine into the national immunization schedule. Currently, two indigenously developed vaccines (ROTAVAC, Bharat Biotech; ROTASIIL, Serum Institute of India) are included in the Indian immunization program. We report the rotavirus disease burden and the diversity of rotavirus genotypes from 2005 to 2016 in a multi-centric surveillance study before the introduction of vaccines. METHODS: A total of 29,561 stool samples collected from 2005 to 2016 (7 sites during 2005-2009, 3 sites from 2009 to 2012, and 28 sites during 2012-2016) were included in the analysis. Stools were tested for rotavirus antigen using enzyme immunoassay (EIA). Genotyping was performed on 65.8% of the EIA positive samples using reverse transcription- polymerase chain reaction (RT-PCR) to identify the G (VP7) and P (VP4) types. Multinomial logistic regression was used to quantify the odds of detecting genotypes across the surveillance period and in particular age groups. RESULTS: Of the 29,561 samples tested, 10,959 (37.1%) were positive for rotavirus. There was a peak in rotavirus positivity during December to February across all sites. Of the 7215 genotyped samples, G1P[8] (38.7%) was the most common, followed by G2P[4] (12.3%), G9P[4] (5.8%), G12P[6] (4.2%), G9P[8] (4%), and G12P[8] (2.4%). Globally, G9P[4] and G12P[6] are less common genotypes, although these genotypes have been reported from India and few other countries. There was a variation in the geographic and temporal distribution of genotypes, and the emergence or re-emergence of new genotypes such as G3P[8] was seen. Over the surveillance period, there was a decline in the proportion of G2P[4], and an increase in the proportion of G9P[4]. A higher proportion of mixed and partially typed/untyped samples was also seen more in the age group 0-11 months. CONCLUSIONS: This 11 years surveillance highlights the high burden of severe rotavirus gastroenteritis in Indian children < 5 years of age before inclusion of rotavirus vaccines in the national programme. Regional variations in rotavirus epidemiology were seen, including the emergence of G3P[8] in the latter part of the surveillance. Having pre-introduction data is important to track changing epidemiology of rotaviruses, particularly following vaccine introduction.

Rotavirus gastroenteritis in Indian children < 5 years hospitalized for diarrhoea, 2012 to 2016.

BACKGROUND: In 2016, the Government of India introduced the oral rotavirus vaccine (ROTAVAC, Bharat Biotech, India) in 4 states of India as part of the Universal Immunization Programme, and expanded to 5 more states in 2017. We report four years of data on rotavirus gastroenteritis in hospitalized children < 5 years of age prior to vaccine introduction. METHODS: Children from 7 sites in southern and northern India hospitalized for diarrhoea were recruited between July 2012 and June 2016. Stool samples were screened for rotavirus using enzyme immunoassay (EIA). The EIA positive samples were genotyped by reverse-transcription polymerase chain reaction. RESULTS: Of the 5834 samples from the 7 sites, 2069 (35.5%) were positive for rotavirus by EIA. Genotyping was performed for 2010 (97.1%) samples. G1P[8](56.3%), G2P[4](9.1%), G9P[4](7.6%), G9P[8](4.2%), and G12P[6](3.7%) were the common genotypes in southern India and G1P[8](36%), G9P[4](11.4%), G2P[4](11.2%), G12P[6](8.4%), and G3P[8](5.9%) in northern India. CONCLUSIONS: The study highlights the high prevalence of rotavirus gastroenteritis in India and the diversity of rotavirus genotypes across different geographical regions. Pre- vaccine surveillance data is necessary to evaluate the potential change in admission rates for gastroenteritis and circulating rotavirus genotypes after vaccine introduction, thus assessing impact.

Safety monitoring of ROTAVAC vaccine and etiological investigation of intussusception in India: study protocol.

BACKGROUND: ROTAVAC, an indigenous rotavirus vaccine, was introduced in the universal immunization program of India in four states in 2016 and expanded to five more states in 2017. The clinical trial on efficacy of ROTAVAC did not detect an increased risk of intussusception, but the trial was not large enough to detect a small risk. This protocol paper describes the establishment and implementation of a surveillance system to monitor the safety of rotavirus vaccine and investigate the potential infectious etiologies of intussusception. METHODS: This is a multi-centric hospital-based active surveillance being conducted at 28 hospitals in nine states of India. Data gathered from surveillance will be used to assess the risk of intussusception after ROTAVAC administration and to determine the infectious etiologies of intussusception. For safety assessment of ROTAVAC vaccine, children aged less than two years with intussusception admitted at the sentinel hospitals are enrolled into surveillance, a case report form completed, and a copy of the vaccination card obtained. The risk of intussusception following rotavirus vaccination will be assessed using a self-controlled case-series design. The investigation for potential infectious etiologies of intussusception is through a matched case-control design. Children enrolled for the safety assessment serve as cases and for each case, an age, gender and location matched control is enrolled within 30 days of case enrollment. Stool specimens are obtained from cases and controls. All forms and specimens are sent to the referral laboratory for data entry, analysis, multiplexed molecular testing, and storage. DISCUSSION: Anticipated public health benefits of this surveillance include the generation of information useful to national government on safety of vaccine and to make future decisions on vaccine use through risk-benefit analysis. Investigating infectious agents may help to determine the potential infectious etiologies of intussusception.

HIV-malaria interactions in North-East India: A prospective cohort study.

BACKGROUND & OBJECTIVES: The interactions between HIV and malaria co-infection have been shown to influence each other in their clinical outcomes in Sub-Saharan Africa. This study was carried out in the two States of north east India endemic for both HIV and malaria infections, to study the interactions between the two diseases in the HIV-infected population. METHODS: In this prospective study, a total of 333 HIV-infected individuals were followed up for a period of 6-18 months in Mizoram and Manipur during 2010-2011. The study assessed the changes in viral load and also the therapeutic efficacy of artesunate plus sulphadoxine-pyrimethamine (AS+SP) combination therapy in HIV-infected and HIV-uninfected individuals with Plasmodium falciparum malaria. RESULTS: Viral load in HIV-infected malaria patients on day zero (D0) ranged from 1110 to 147,000 copies/ml. The log transformation of the geometric means of HIV viral loads revealed no significant difference on different days of follow up. There was 100 per cent adequate clinical and parasitological response (ACPR) after treating with artemisinin based combination therapy (ACT) both in HIV-infected and HIV-uninfected P. falciparum-positive individuals. Similarly, chloroquine showed 100 per cent ACPR in P. vivax HIV-infected individuals. INTERPRETATION & CONCLUSION: The study showed no significant increase in HIV viral load in malaria cases. All HIV-infected and HIV-uninfected P. falciparum malaria-positive cases responded to the treatment with 100 per cent ACPR.

DHR-ICMR Guidelines for diagnosis & management of Rickettsial diseases in India.

Rickettsial diseases, caused by a variety of obligate intracellular, gram-negative bacteria from the genera Rickettsia, Orientia, Ehrlichia, Neorickettsia, Neoehrlichia, and Anaplasma, belonging to the Alphaproteobacteria, are considered some of the most covert emerging and re-emerging diseases and are being increasingly recognized. Among the major groups of rickettsioses, commonly reported diseases in India are scrub typhus, murine flea-borne typhus, Indian tick typhus and Q fever. Rickettsial infections are generally incapacitating and difficult to diagnose; untreated cases have case fatality rates as high as 30-45 per cent with multiple organ dysfunction, if not promptly diagnosed and appropriately treated. The vast variability and non-specific presentation of this infection have often made it difficult to diagnose clinically. Prompt antibiotic therapy shortens the course of the disease, lowers the risk of complications and in turn reduces morbidity and mortality due to rickettsial diseases. There is a distinct need for physicians and health care workers at all levels of care in India to be aware of the clinical features, available diagnostic tests and their interpretation, and the therapy of these infections. Therefore, a Task Force was constituted by the Indian Council of Medical Research (ICMR) to formulate guidelines for diagnosis and management of rickettsial diseases. These guidelines include presenting manifestations, case definition, laboratory criteria (specific and supportive investigations) and treatment.

Rotavirus vaccines at the threshold of implementation in India.

India is poised to introduce rotavirus vaccines into its routine childhood immunization programme. Substantial data ara available on disease and economic burden of rotavirus gastroenteritis and on circulating strains in India, which highlight the public health need for a rotavirus vaccine. A locally manufactured oral rotavirus vaccine has been licensed in India and it has been shown to be effective against severe rotavirus gastroenteritis in Indian children. The Government of India has announced that the vaccine will be included in the universal immunization n programme. Careful planning and preparation for post-licensure impact and safety evaluations will ensure that additional high quality benefit-risk data will be available for India.

Unleashing the power of silk-based proteins as biomaterials for cutting-edge drug delivery: a comprehensive review.

Silk proteins, viz., sericin, fibroin and their modified forms etc., have been thoroughly researched as natural biopolymers for the development of varied nanomaterials exhibiting diverse biomedical applications. The silk proteins are extracted from the cocoons by degumming and treatment with soaps, followed by dissolution and dialysis against water. These proteins exhibit distinct mechanical and physicochemical characteristics including biocompatibility, controlled biodegradability, self-assembling traits, chemical modifiability, and adaptability, thus making it an ideal drug delivery vehicle. In this regard, silk protein-derived drug delivery systems have been reported as efficient carrier to encapsulate and stabilize the wide variety of pharmacological molecules, enzymes, proteins, vaccines, and even DNA, allowing them to remain active for a longer period of time. Further, different delivery carriers researched employing these proteins for multitude of applications include hydrogels, sponges, fibres, scaffolds and particulate delivery systems. Additionally, the chemical modification of silk proteins has further opened avenues for development of other modified silk proteins with improved physicochemical traits and hence exhibiting enormous potential in development of varied bioenhanced carrier systems. The current article thus provides the holistic information of characteristics, types of silk protein-based delivery carriers, and their fabrication techniques, while emphasizing the applications of different silk proteins in biomedicine and drug delivery.

Nr1h4 and Thrb ameliorate ER stress and provide protection in the MPTP mouse model of Parkinson's.

Elevated ER stress has been linked to the pathogenesis of several disease conditions including neurodegeneration. In this study, we have holistically determined the differential expression of all the nuclear receptors (NRs) in the presence of classical ER stress inducers. Activation of Nr1h4 and Thrb by their cognate ligands (GW4064 and T3) ameliorates the tunicamycin (TM)-induced expression of ER stress genes. A combination of both ligands is effective in mitigating cell death induced by TM. Further exploration of their protective effects in the Parkinson's disease (PD) model shows that they reduce MPP+-induced dissipation of mitochondrial membrane potential and ROS generation in an in vitro PD model in neuronal cells. Furthermore, the generation of an experimental murine PD model reveals that simultaneous treatment of GW4064 and T3 protects mice from ER stress, dopaminergic cell death, and functional deficits in the MPTP mouse model of PD. Thus, activation of Nr1h4 and Thrb by their respective ligands plays an indispensable role in ER stress amelioration and mounts protective effects in the MPTP mouse model of PD.

Unveiling the phyto-restorative potential of ethereal distillates for atopic dermatitis: an advanced therapeutic approach.

Atopic dermatitis is acknowledged as a vital inflammatory disorder associated with the integumentary system of the body and is characterized by the formation of thick reddish-grey scars and erythema formation on skin, prevalent amidst the populace. Numerous synthetic drugs are available for treatment like antihistamines, immunosuppressants, glucocorticoids etc., but contrarily, essential oil therapy is exclusively lime lighted to favour the purpose. The utilization of available engineered drugs, possess the marked adverse effects owing to prolonged duration of therapy and therefore, essential oils are explored well and proved to exhibit the anti-eczematic, anti-inflammatory and antipruritic properties. Ethereal distillates own the assorted and selective therapeutic properties attributable to presence of bioactive compounds liable to treat this torturous and integumentary disorder, likely lavender oil, patchouli oil, frankincense oil etc., have been found to exert their pharmacological actions by impeding the liberation and action of inflammatory mediators and immunological hyperactivities that are engaged in exacerbating this idiopathic illness. The current attempt provided the update with the aim to bring forth the naturally originated treatment that is pertinent to provide the invulnerable therapy by circumventing the noxious symptoms i.e. erythema formation and inflamed lesions.

Marine-derived Compounds: A Powerful Platform for the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a debilitating form of dementia that primarily affects cholinergic neurons in the brain, significantly reducing an individual's capacity for learning and creative skills and ultimately resulting in an inability to carry out even basic daily tasks. As the elderly population is exponentially increasing, the disease has become a significant concern for society. Therefore, neuroprotective substances have garnered considerable interest in addressing this universal issue. Studies have shown that oxidative damage to neurons contributes to the pathophysiological processes underlying AD progression. In AD, tau phosphorylation and glutamate excitotoxicity may play essential roles, but no permanent cure for AD is available. The existing therapies only manage the early symptoms of AD and often come with numerous side effects and toxicities. To address these challenges, researchers have turned to nature and explored various sources such as plants, animals, and marine organisms. Many historic holy books from different cultures emphasize that adding marine compounds to the regular diet enhances brain function and mitigates its decline. Consequently, researchers have devoted significant time to identifying potentially active neuroprotective substances from marine sources. Marine-derived compounds are gaining recognition due to their abundant supply of diverse chemical compounds with biological and pharmacological potential and unique mechanisms of action. Several studies have reported that plants exhibit multitarget potential in treating AD. In light of this, the current study focuses on marine-derived components with excellent potential for treating this neurodegenerative disease.

Rev-erbα regulate neurogenesis through suppression of Sox2 in neuronal cells to regenerate dopaminergic neurons and abates MPP+ induced neuroinflammation.

Parkinson's disease is a progressive neurodegenerative disease that affects the motor and non-motor circuits of the brain. Currently, there are no promising therapeutic measures for Parkinson's disease, and most strategies designed to alleviate the Parkinson's disease are palliative. The dearth of therapeutic interventions in Parkinson's disease has driven attention in the search for targets that may augment dopamine secretion, promote differentiation towards dopaminergic neuronal lineage, or aid in neuroprotection from neuronal stress and inflammation, and prevent Parkinson's disease associated motor impairment and behavioural chaos. The study first reports that Rev-erbα plays an important role in regulating the differentiation of undifferentiated neuronal cells towards dopaminergic neurons through abating Sox2 expression in human SH-SY5Y cells. Rev-erbα directly binds to the human Sox2 promoter region and represses their expression to promote differentiation towards dopaminergic neurons. We have reported a novel mechanism of Rev-erbα which effectively abrogates 1-methyl-4-phenylpyridinium induced cytotoxicity, inflammation, and oxidative stress, exerted a beneficial effect on transmembrane potential, and suppressed apoptosis in the neuronal in vitro model of Parkinson's disease. Rev-erbα ligand SR9011 was observed to ease the disease severity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induced mouse model of Parkinson's disease. Rev-erbα alleviates the locomotor behavioural impairment, prevents cognitive decline and promotes motor coordination in mice. Administration of Rev-erbα ligand also helps in replenishing the dopaminergic neurons and abrogating the neurotoxin mediated toxicity in an in vitro and in vivo Parkinson's disease model. We conclude that Rev-erbα emerges as a moonlighting nuclear receptor that could be targeted in the treatment and alleviation of Parkinson disease.

Exploring the Intersection of Geophysics and Diagnostic Imaging in the Health Sciences.

To develop diagnostic imaging approaches, this paper emphasizes the transformational potential of merging geophysics with health sciences. Diagnostic imaging technology improvements have transformed the health sciences by enabling earlier and more precise disease identification, individualized therapy, and improved patient care. This review article examines the connection between geophysics and diagnostic imaging in the field of health sciences. Geophysics, which is typically used to explore Earth's subsurface, has provided new uses of its methodology in the medical field, providing innovative solutions to pressing medical problems. The article examines the different geophysical techniques like electrical imaging, seismic imaging, and geophysics and their corresponding imaging techniques used in health sciences like tomography, magnetic resonance imaging, ultrasound imaging, etc. The examination includes the description, similarities, differences, and challenges associated with these techniques and how modified geophysical techniques can be used in imaging methods in health sciences. Examining the progression of each method from geophysics to medical imaging and its contributions to illness diagnosis, treatment planning, and monitoring are highlighted. Also, the utilization of geophysical data analysis techniques like signal processing and inversion techniques in image processing in health sciences has been briefly explained, along with different mathematical and computational tools in geophysics and how they can be implemented for image processing in health sciences. The key findings include the development of machine learning and artificial intelligence in geophysics-driven medical imaging, demonstrating the revolutionary effects of data-driven methods on precision, speed, and predictive modeling.

Nuclear receptor Rev-erbα role in fine-tuning erythropoietin gene expression.

ABSTRACT: The regulation of red blood cell (RBC) homeostasis by erythropoietin (EPO) is critical for O2 transport and maintaining the adequate number of RBCs in vertebrates. Therefore, dysregulation in EPO synthesis results in disease conditions such as polycythemia in the case of excessive EPO production and anemia, which occurs when EPO is inadequately produced. EPO plays a crucial role in treating anemic patients; however, its overproduction can increase blood viscosity, potentially leading to fatal heart failure. Consequently, the identification of druggable transcription factors and their associated ligands capable of regulating EPO offers a promising therapeutic approach to address EPO-related disorders. This study unveils a novel regulatory mechanism involving 2 pivotal nuclear receptors (NRs), Rev-ERBA (Rev-erbα, is a truncation of reverse c-erbAa) and RAR-related orphan receptor A (RORα), in the control of EPO gene expression. Rev-erbα acts as a cell-intrinsic negative regulator, playing a vital role in maintaining erythropoiesis at the correct level. It accomplishes this by directly binding to newly identified response elements within the human and mouse EPO gene promoter, thereby repressing EPO production. These findings are further supported by the discovery that a Rev-erbα agonist (SR9011) effectively suppresses hypoxia-induced EPO expression in mice. In contrast, RORα functions as a positive regulator of EPO gene expression, also binding to the same response elements in the promoter to induce EPO production. Finally, the results of this study revealed that the 2 NRs, Rev-erbα and RORα, influence EPO synthesis in a negative and positive manner, respectively, suggesting that the modulating activity of these 2 NRs could provide a method to target disorders linked with EPO dysregulation.

Impact of Bioactive Compounds in the Management of Various Inflammatory Diseases.

Inflammation is an individual's physiological response to a sequence of physical, chemical, or infectious stressors acting mainly to provide localized protection. Although inflammation is a protective and thus beneficial process, its excess or prolonged action can be harmful to the body. An increasing number of the population worldwide are changing their lifestyles, which leads to a rise in inflammatory diseases, such as atherosclerosis, angina pectoris, myocardial infarction, ulcerative colitis, cancer, and many more. Their treatment is based majorly on the pharmacological approach. However, natural products or bioactive compounds are of great significance in inflammation therapy because they show minimum side effects and maximum bioavailability. Therefore, it is critical to investigate bioactive substances that can modify target functions associated with oxidative stress defense and might be used to achieve various health benefits. This review accentuates the essence of bioactive chemicals used in the treatment of inflammation and other inflammatory illnesses. These bioactive compounds can be of any origin, such as plants, animals, bacteria, fungi, marine invertebrates, etc. Bioactive compounds derived from plant sources, such as glycyrrhizin, lignans, lycopene, resveratrol, indoles, and phenolic and polyphenolic compounds, work mainly by reducing oxidative stress and thereby preventing various inflammatory disorders. A large diversity of these anti-inflammatory bioactive compounds has also been discovered in marine environments, giving rise to an increase in the interest of various scientists in marine invertebrates and microbes. The vast diversity of microbes found in the marine environment represents an enormous supply to extract novel compounds, such as from bacteria, cyanobacteria, fungi, algae, microalgae, tiny invertebrates, etc. In the present review, an attempt has been made to summarize such novel bioactive compounds that help prevent inflammatory responses via different mechanisms of action.

Decoding the Therapeutic Potential of Cannabis and Cannabinoids in Neurological Disorders.

For millennia, Cannabis sativa has served diverse roles, from medicinal applications to recreational use. Despite its extensive historical use, only a fraction of its components have been explored until recent times. The therapeutic potential of Cannabis and its constituents has garnered attention, with suggestions for treating various conditions such as Parkinson's disease, epilepsy, Alzheimer's disease, and other Neurological disorders. Recent research, particularly on animal experimental models, has unveiled the neuroprotective properties of cannabis. This neuroprotective effect is orchestrated through numerous G protein-coupled receptors (GPCRs) and the two cannabinoid receptors, CB1 and CB2. While the capacity of cannabinoids to safeguard neurons is evident, a significant challenge lies in determining the optimal cannabinoid receptor agonist and its application in clinical trials. The intricate interplay of cannabinoids with the endocannabinoid system, involving CB1 and CB2 receptors, underscores the need for precise understanding and targeted approaches. Unravelling the molecular intricacies of this interaction is vital to harness the therapeutic potential of cannabinoids effectively. As the exploration of cannabis components accelerates, there is a growing awareness of the need for nuanced strategies in utilizing cannabinoid receptor agonists in clinical settings. The evolving landscape of cannabis research presents exciting possibilities for developing targeted interventions that capitalize on the neuroprotective benefits of cannabinoids while navigating the complexities of receptor specificity and clinical applicability.

Infectious etiology of intussusception in Indian children less than 2 years old: a matched case-control analysis.

BACKGROUND: Enteric infections are hypothesized to be associated with intussusception in children. A small increase in intussusception following rotavirus vaccination has been seen in some settings. We conducted post-marketing surveillance for intussusception following rotavirus vaccine, Rotavac introduction in India and evaluated association of intussusception with enteric pathogens. METHODS: In a case-control study nested within a large sentinel hospital-based surveillance program in India, stool samples from 272 children aged less than 2 years admitted for intussusception and 272 age-, gender- and location-matched controls were evaluated with Taqman array card based molecular assays to detect enteric viruses, bacterial enteropathogens and parasites. Matched case-control analysis with conditional logistic regression evaluated association of enteropathogens with intussusception. Population attributable fractions (PAF) were calculated for enteropathogens significantly associated with intussusception. RESULTS: The most prevalent enteropathogens in cases and controls were enteroaggregative Escherichia coli, adenovirus 40/41, adenovirus C serotypes and enteroviruses. Children with intussusception were more likely to harbor adenovirus C serotypes (adjusted odds-ratio (aOR) = 1.74; 95% confidence interval (CI) 1.06-2.87) and enteroviruses (aOR = 1.77; 95% CI 1.05-2.97) than controls. Rotavirus was not associated with increased intussusception risk. Adenovirus C (PAF = 16.9%; 95% CI 4.7% - 27.6%) and enteroviruses (PAF = 14.7%; 95% CI 4.2% - 24.1%) had the highest population attributable fraction for intussusception. CONCLUSION: Adenovirus C serotypes and enteroviruses were significantly associated with intussusception in Indian children. Rotavirus was not associated with risk of intussusception.

Financing for Sustainable Development Goals (SDGs) in the Era of COVID-19 and Beyond.

The economic and social impact of covid-19 pandemic both on developing and developed countries has been significant. In addition to the impact of the pandemic, the current Ukraine war has also led to severe supply chain disruptions leading to a sharp increase in food and commodity prices globally. Due to a combination of external shocks and the impact of the pandemic global economic growth is expected to slow down from 6.1% in 2021 to 3.2% in 2022 and further to 2.7% in 2023 (IMF in: World economic outlook, International Monetary Fund, 2022). The above factors have led to a sharp increase in government expenditure constraining both developed and developing countries' fiscal capacity. This has further implications for the achievement of SDGs especially for low-income countries. The challenge for developing countries in the current scenario is to mobilise adequate resources both from domestic and international sources, not just for the achievement of SDGs as such, but also to sustain the livelihoods, health, and welfare of people. This special issue aims to examine some of these issues in the context of developing countries.

L'impact économique et social de la pandémie de COVID-19, tant sur les pays en développement que sur les pays développés, a été important. Outre l'impact de la pandémie, la guerre actuelle en Ukraine a également entraîné de graves perturbations de la chaîne d'approvisionnement, entraînant une forte augmentation des prix des denrées alimentaires et des matières premières dans le monde. En raison d'une combinaison entre chocs externes et impact de la pandémie, la croissance économique mondiale devrait ralentir de 6,1 % en 2021 à 3,2 % en 2022, puis à 2,7 % en 2023 (FMI 2022). Les facteurs ci-dessus ont conduit à une forte augmentation des dépenses publiques, limitant la capacité budgétaire des pays développés et en développement. Cela a d'autres implications pour la réalisation des ODD, en particulier pour les pays à faible revenu. Le défi pour les pays en développement dans le scénario actuel est de mobiliser des ressources adéquates provenant de sources nationales et internationales, non seulement pour la réalisation des ODD en tant que tels, mais aussi pour maintenir les moyens de subsistance, la santé et le bien-être des personnes. Ce numéro spécial vise à aborder certaines de ces questions dans le contexte des pays en développement.