Central nervous system mast cells in peripheral inflammatory nociception

<p>Abstract</p> <p>Background</p> <p>Functional aspects of mast cell-neuronal interactions remain poorly understood. Mast cell activation and degranulation can result in the release of powerful pro-inflammatory mediators such as histamine and cytokines. Cerebral dural mast cells have been proposed to modulate meningeal nociceptor activity and be involved in migraine pathophysiology. Little is known about the functional role of spinal cord dural mast cells. In this study, we examine their potential involvement in nociception and synaptic plasticity in superficial spinal dorsal horn. Changes of lower spinal cord dura mast cells and their contribution to hyperalgesia are examined in animal models of peripheral neurogenic and non-neurogenic inflammation.</p> <p>Results</p> <p>Spinal application of supernatant from activated cultured mast cells induces significant mechanical hyperalgesia and long-term potentiation (LTP) at spinal synapses of C-fibers. Lumbar, thoracic and thalamic preparations are then examined for mast cell number and degranulation status after intraplantar capsaicin and carrageenan. Intradermal capsaicin induces a significant percent increase of lumbar dural mast cells at 3 hours post-administration. Peripheral carrageenan in female rats significantly increases mast cell density in the lumbar dura, but not in thoracic dura or thalamus. Intrathecal administration of the mast cell stabilizer sodium cromoglycate or the spleen tyrosine kinase (Syk) inhibitor BAY-613606 reduce the increased percent degranulation and degranulated cell density of lumbar dural mast cells after capsaicin and carrageenan respectively, without affecting hyperalgesia.</p> <p>Conclusion</p> <p>The results suggest that lumbar dural mast cells may be sufficient but are not necessary for capsaicin or carrageenan-induced hyperalgesia.</p

Retraction.

This is a retraction of 'Gradual emergence followed by exponential spread of the SARS-CoV-2 Omicron variant in Africa' 10.1126/science.add873

Gradual emergence followed by exponential spread of the SARS-CoV-2 Omicron variant in Africa.

The geographic and evolutionary origins of the SARS-CoV-2 Omicron variant (BA.1), which was first detected mid-November 2021 in Southern Africa, remain unknown. We tested 13,097 COVID-19 patients sampled between mid-2021 to early 2022 from 22 African countries for BA.1 by real-time RT-PCR. By November-December 2021, BA.1 had replaced the Delta variant in all African sub-regions following a South-North gradient, with a peak Rt of 4.1. Polymerase chain reaction and near-full genome sequencing data revealed genetically diverse Omicron ancestors already existed across Africa by August 2021. Mutations, altering viral tropism, replication and immune escape, gradually accumulated in the spike gene. Omicron ancestors were therefore present in several African countries months before Omicron dominated transmission. These data also indicate that travel bans are ineffective in the face of undetected and widespread infection

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Antibacterial, antioxidant activity and chemical composition of some medicinal plants from Albania.

The antibacterial activity of six Albanian plants were studied. Essential oils of: Juniperus communis, Laurus nobilis, Lavandula angustifolia, Myrtus communis, Origanum vulgare and Salvia officinalis were tested in-vitro against three selected Gram negative and Gram positive microorganisms: Staphylococcus aureus ATCC 6538, Pseudomonas aeruginosa ATCC 9027 and Escherichia coli ATCC 8739, by the agar diffusion method. The essential oil of oregano demonstrated the highest antibacterial activity, against Staphylococcus aureus, followed by Lavandula angustifolia and Juniperus communis essential oils. Essential oil of oregano demonstrated the highest antimicrobial activity, against Pseudomonas aeruginosa. P.aeruginosa was resistant against all investigated essential oils except Origanum vulgare. The essential oil of oregano demonstrated the highest antimicrobial activity, against Escherichia coli, followed by Salvia officinalis. The essential oils of Origanum vulgare, from three different locations in Albania, were chemically characterized by GC/FID. Carvacrol was the main component. The second major constituent was thymol and the third one was p-cymene. The other main constituents were caryophyllene, limonene and γ-terpinene. A rapid evaluation for antioxidants of Origanum vulgare essential oil, using TLC screening methods, showed that carvacrol and thymol and other component have interesting radical scavenging property

Feeding practices and malnutrition at the Princess Marie Louise Children’s hospital, Accra: what has changed after 80 years?

BACKGROUND: Sub-optimal feeding practices are associated with malnutrition. In 1933, Dr Cecily Williams, while working at Princess Marie Louise Children’s Hospital (PML) in Accra described Kwashiorkor as the disease of children “deposed” from breast feeding who were being fed plain fermented maize diets. Presently, it is not clear how this has changed after 80 years. METHODS: We conducted an unmatched case–control study at PML in 2013 in order to determine faulty feeding practices associated with malnutrition. PML is a 74 bed children’s hospital and the largest centre for treating children with malnutrition in Ghana. Under-fives with Moderate or Severe Acute Malnutrition (SAM or MAM) were selected as cases while the controls were children without SAM or MAM. RESULTS: A total of 182 malnourished and 189 well-nourished under-fives and their mothers were studied. Faulty feeding practices including early weaning, shorter duration of exclusive breastfeeding, mixed feeding, bottle feeding and limited consumption of fruits were found. Though the use of “iced kenkey” a maize-based diet was limited, over one-third of malnourished children (39.1 %) were still being weaned with plain unfortified fermented maize gruel both of which Dr Williams associated with Kwashiorkor. Well-nourished children were more likely to receive solid food (38.0 %), fortified maize gruel (29.2 %), and Cerelac® (24 %) a processed cereal-based complementary food. A child’s refusal to breastfeed was the most common reason for stopping breastfeeding among malnourished children. CONCLUSIONS: More effective nutrition education and new complementary feeding diets that are wholesome yet appeal to a new generation of mothers are needed. The patho-physiology of feeding problems needs further study

Maternal profiles and social determinants of malnutrition and the MDGs: What have we learnt?

Abstract Background Maternal socio-demographic and health profiles are important determinants of malnutrition in children. In the 1990s, malnutrition was associated with low-birth-weight, young mothers and low maternal socio-economic status at Princess Marie Louise Children’s Hospital (PML). It is not known how this has changed by efforts to achieve the Millennium Development Goals. We examined socio-demographic and health profiles of mothers of children with acute malnutrition and those without the condition to identify risk factors for malnutrition and focus on preventive efforts. Methods An unmatched case–control study was conducted in 2013 at PML, the largest facility for treating malnourished children in Ghana in 2013. Mothers of children with moderate and severe acute malnutrition were compared with mothers of well-nourished children. Weight-for-height was used to classify malnutrition. Record forms and a semi-structured questionnaire were used for data collection. An analysis was done with Stata 11.0 software. Results Altogether, 371 mothers were studied consisting of 182 mothers of malnourished children and 189 mothers of well-nourished children. Mothers of malnourished children were more likely to be unmarried or cohabiting, have lower family incomes, HIV infection and chronic disease. They were less likely to stay with or provide alternative care for their child. Awareness and use of social services, health insurance and a cash transfer programme were low. A remarkable reduction in the number of malnourished children occurred when families earned more than $250 USD a month. Over-nutrition was present in both groups of mothers. Conclusion Low family income, unmarried status and type of child care were the main social determinants of malnutrition. There appears to be a reduction in the number of other poor socio-demographic characteristics in both the study and control groups compared to results from a previous study at the same centre, probably because of efforts toward attaining the MDGs. These findings suggest that prevention and optimum management need to involve multidisciplinary teams consisting of health professionals, social workers and/or key workers to enable families at risk to access social care and social protection interventions (MDG 1). This will make the management of malnutrition more effective, prevent relapse, protect the next child and address maternal over-nutrition