Endoplasmic reticulum (ER)-plasma membrane (PM) junctions form functionally active microdomains that connect intracellular and extracellular environments. While the key role of these interfaces in maintenance of intracellular Ca levels has been uncovered in recent years, the functional significance of ER-PM junctions in non-excitable cells has remained unclear. Here, we show that the ER calcium sensor protein STIM1 (stromal interaction molecule 1) interacts with the plasma membrane-localized adenylyl cyclase 6 (ADCY6) to govern melanogenesis. The physiological stimulus α-melanocyte-stimulating hormone (αMSH) depletes ER Ca stores, thus recruiting STIM1 to ER-PM junctions, which in turn activates ADCY6. Using zebrafish as a model system, we further established STIM1's significance in regulating pigmentation STIM1 domain deletion studies reveal the importance of Ser/Pro-rich C-terminal region in this interaction. This mechanism of cAMP generation creates a positive feedback loop, controlling the output of the classical αMSH-cAMP-MITF axis in melanocytes. Our study thus delineates a signaling module that couples two fundamental secondary messengers to drive pigmentation. Given the central role of calcium and cAMP signaling pathways, this module may be operative during various other physiological processes and pathological conditions.

The steady rise in antimicrobial resistance poses a severe threat to global public health by hindering treatment of an escalating spectrum of infections. We have previously established the potent activity of α-MSH, a 13 residue antimicrobial peptide, against the opportunistic pathogen Staphylococcus aureus. Here, we sought to determine whether an increase in cationic charge in α-MSH could contribute towards improving its staphylocidal potential by increasing its interaction with anionic bacterial membranes. For this we designed novel α-MSH analogues by replacing polar uncharged residues with lysine and alanine. Similar to α-MSH, the designed peptides preserved turn/random coil conformation in artificial bacterial mimic 1,2-dimyristoyl-sn-glycero-3-phosphocholine:1,2-dimyristoyl-sn-glycero-3-phospho-rac-(1-glycerol) (7:3, w/w) vesicles and showed preferential insertion in the hydrophobic core of anionic membranes. Increased cationic charge resulted in considerable augmentation of antibacterial potency against MSSA and MRSA. With ~18-fold better binding than α-MSH to bacterial mimic vesicles, the most charged peptide KKK-MSH showed enhanced membrane permeabilization and depolarization activity against intact S. aureus. Scanning electron microscopy confirmed a membrane disruptive mode of action for KKK-MSH. Overall, increasing the cationic charge improved the staphylocidal activity of α-MSH without compromising its cell selectivity. The present study would help in designing more effective α-MSH-based peptides to combat clinically relevant staphylococcal infections.

A bstract Pancytopenia is a common hematological abnormality encountered in clinical practice. We here report a 36-year-old male who presented to emergency department with complaints of weakness of bilateral lower limbs, burning sensation in all four limbs with history of loose stools, and vomiting 5 days back. The complete blood count of patient showed pancytopenia with no circulating atypical cells. Bone marrow examination performed showed nonspecific but characteristic findings. After excluding the possibility of infective etiology, a possibility of heavy metal toxicity was suspected in multidisciplinary meeting. The urine and blood levels of arsenic done came out very high, and a diagnosis of arsenic poisoning was made. Patient had multisystemic involvement with features characteristic of arsenic poisoning. The present case was a diagnostic challenge in face of nonforthcoming history. This case beautifully highlighted the importance of multidepartmental approach in such cases to arrive at unerring diagnosis and the unique bone marrow findings, although nonspecific were sufficient enough to indicate the possibility of acute insult to the hematopoiesis. How to cite this article: Nair RR, Singh PK, Sharma J, Gambhir I, Khanna S, Jain AK, et al . An Unusual Case of Pancytopenia: The Lessons Learnt. Indian J Crit Care Med 2022;26(1):141–144.

In recent years, the literature on public health interventions and health outcomes in the context of epidemic and pandemic response has grown immensely. However, relatively few of these studies have situated their findings within the institutional, political, organizational, and governmental (IPOG) context in which interventions and outcomes exist. This conceptual mapping scoping study synthesized the published literature on the impact of IPOG factors on epidemic and pandemic response and critically examined definitions and uses of the terms IPOG in this literature. This research involved a comprehensive search of four databases across the social, health, and biomedical sciences as well as multi-level eligibility screening conducted by two independent reviewers. Data on the temporal, geographic, and topical range of studies were extracted, then descriptive statistics were calculated to summarize these data. Hybrid inductive and deductive qualitative analysis of the full-text articles was conducted to critically analyze the definitions and uses of these terms in the literature. The searches retrieved 4,918 distinct articles; 65 met the inclusion criteria and were thus reviewed. These articles were published from 2004 to 2022, were mostly written about COVID-19 (61.5%), and most frequently engaged with the concept of governance (36.9%) in relation to epidemic and pandemic response. Emergent themes related to the variable use of the investigated terms, the significant increase in relevant literature published amidst the COVID-19 pandemic, as well as a lack of consistent definitions used across all four terms: institutions, politics, organizations, and governance. This study revealed opportunities for health systems researchers to further engage in interdisciplinary work with fields such as law and political science, to become more forthright in defining factors which shape responses to epidemics and pandemics, and to develop greater consistency in using these IPOG terms in order to lessen confusion among a rapidly growing body of literature.