Subaltern Modernity: Kerala, the Eastern Theatre of Resistance in the Global South

In engaging with the debate on modernity, this article constructs the notion of a ‘subaltern modernity’ as a process of epistemological – spatial/temporal/agential – coalescence constituting a transverse solidarity politics. This is empirically informed by the narratives of the livelihood-environmental resistance launched by subalterns in the Indian state of Kerala, known for its twin legacies – of communist government and social development – which have proved to be a direct challenge to the state/corporate-led developmentalism in the region. The article thus attempts to contribute to the debate on modernity more from the perspective of resisting subjects and agents, with their particular subjective experience and understandings of science and reasoning. However, their resistance generates transformative events of universal relevance and thereby global issues of epistemology. As such, the article develops a theory of knowledge that takes subaltern resistance itself as modernity

Use of Disease-Modifying Therapies in Pediatric MS

Pediatric multiple sclerosis (PedMS) is a rare disease with a more severe prognosis compared to adult-onset MS. It remains a challenging condition to treat because of the highly inflammatory nature of the disease, the prominent cognitive issues, and the limited knowledge about the efficacy and safety of current available disease-modifying therapies. Over the past decade, there has been a dramatic increase in the number of drugs licensed for adult-onset MS and several of them, although not tested in PedMS, are currently being used off-label in this population. To date, interferon-beta and glatiramer acetate are the most commonly used first-line treatments in children, although the efficacy and safety of these drugs have only been studied in observational cohorts and in unblinded randomized controlled trials. For children with breakthrough disease, escalation to higher efficacious second-line therapies, such as natalizumab, fingolimod, dimethyl fumarate, mitoxantrone, cyclophosphamide, rituximab, and daclizumab may be considered. Large observational studies showed natalizumab is an effective treatment with safety and efficacy comparable to those in adult populations. The safety, efficacy, and tolerability of the other second-line treatments in PedMS have been reported only in small size retrospective case series. Large phase III studies are underway which will provide important information regarding the efficacy and safety of fingolimod, teriflunomide, and dimethyl fumarate in PedMS. Symptomatic treatments for fatigue, spasticity, depression, bladder and bowel dysfunction, and neuropathic pain should be considered in PedMS, especially when these symptoms impact the quality of life. Further work is needed to ensure that new trials best address treatment outcomes tailored to PedM

Cross-feeding and interkingdom communication in dual-species biofilms of Streptococcus mutans and Candida albicans.

Polymicrobial biofilms are of large medical importance, but relatively little is known about the role of interspecies interactions for their physiology and virulence. Here, we studied two human pathogens co-occuring in the oral cavity, the opportunistic fungus Candida albicans and the caries-promoting bacterium Streptococcus mutans. Dual-species biofilms reached higher biomass and cell numbers than mono-species biofilms, and the production of extracellular polymeric substances (EPSs) by S. mutans was strongly suppressed, which was confirmed by scanning electron microscopy, gas chromatography-mass spectrometry and transcriptome analysis. To detect interkingdom communication, C. albicans was co-cultivated with a strain of S. mutans carrying a transcriptional fusion between a green fluorescent protein-encoding gene and the promoter for sigX, the alternative sigma factor of S. mutans, which is induced by quorum sensing signals. Strong induction of sigX was observed in dual-species biofilms, but not in single-species biofilms. Conditioned media from mixed biofilms but not from C. albicans or S. mutans cultivated alone activated sigX in the reporter strain. Deletion of comS encoding the synthesis of the sigX-inducing peptide precursor abolished this activity, whereas deletion of comC encoding the competence-stimulating peptide precursor had no effect. Transcriptome analysis of S. mutans confirmed induction of comS, sigX, bacteriocins and the downstream late competence genes, including fratricins, in dual-species biofilms. We show here for the first time the stimulation of the complete quorum sensing system of S. mutans by a species from another kingdom, namely the fungus C. albicans, resulting in fundamentally changed virulence properties of the caries pathogen