Immune checkpoint inhibitor-induced inflammatory arthritis: a novel clinical entity with striking similarities to seronegative rheumatoid arthritis

Clinical Rheumatology - To determine the clinical and serologic similarities and differences between inflammatory arthritis induced by immune checkpoint inhibitors (IA-irAE) and rheumatoid...     

Oral polio vaccine response in breast fed infants with malnutrition and diarrhea

Oral vaccines for polio (OPV) and rotavirus are less effective in children in the developing world. The reasons for this are not well understood. We tested for risk factors for poor response to OPV in infants from an urban slum of Dhaka, Bangladesh. Diminished serum neutralizing response to OPV, but not failure of intramuscularly administered vaccines, was associated with malnutrition, diarrhea, and shorter breastfeeding duration. Children with malnutrition (WAZ <−2) had significantly lower OPV 3 titers (p = 0.029). Children who had 2 or more diarrhea episodes during the 1st months of life were more than twice as likely to experience OPV failure as those who had 1 diarrhea episode or no diarrhea (p = 0.0245). In contrast, each additional month in exclusive breastfeeding was associated with an increase in OPV 3 titer by 0.41 (p = 0.0072) and 0.16 (p = 0.0065) at the 25th and 50th percentiles of OPV 3 titers respectively. These data are consistent with a defect in induction of immunity in the gut for OPV but not parenteral vaccines, a defect that may be amenable to intervention in part via promotion of exclusive breastfeeding.     

Associations of perceived prenatal stress and adverse pregnancy outcomes with perceived stress years after delivery

Archives of Women's Mental Health - Maternal stress is a risk factor for adverse pregnancy outcomes (APOs). This study evaluates the associations of prenatal stress and APOs with maternal...     

Cytological diagnosis of bilateral primary adrenal lymphoma with cutaneous involvement

Primary adrenal lymphoma (PAL) is an extremely rare condition. We describe here, a case of bilateral adrenal lymphoma in a 62‐year‐old man. He later developed subcutaneous masses on the hand and the leg. Fine‐needle aspiration cytology from the adrenals and the soft tissue swellings led to a diagnosis of non‐Hodgkin's lymphoma (NHL). Histopathological examination from the lesion on the leg, confirmed the diagnosis to be B‐cell NHL. The case highlights the cytomorphological findings of this unusual case. Awareness of this entity is essential to differentiate it from other common causes of adrenal enlargement and formulate an appropriate treatment.     

Cytological diagnosis of amyloidosis presenting as a supraclavicular swelling

Amyloidosis is a well‐recognized entity, that can present as a systemic disease, or, uncommonly, as a localized mass. We report here, a rare presentation of amyloidosis presenting as a supraclavicular swelling, diagnosed on fine‐needle aspiration cytology. Subsequent bone marrow examination led to the diagnosis of multiple myeloma. This case highlights the need to be aware of cytological characteristics of amyloidosis, which can have unusual presentation posing a diagnostic dilemma.     

Oral Administration of Nicotinamide Mononucleotide Increases Nicotinamide Adenine Dinucleotide Level in an Animal Brain

As a redox-sensitive coenzyme, nicotinamide adenine dinucleotide (NAD⁺) plays a central role in cellular energy metabolism and homeostasis. Low NAD⁺ levels are linked to multiple disease states, including age-related diseases, such as metabolic and neurodegenerative diseases. Consequently, restoring/increasing NAD⁺ levels in vivo has emerged as an important intervention targeting age-related neurodegenerative diseases. One of the widely studied approaches to increase NAD⁺ levels in vivo is accomplished by using NAD⁺ precursors, such as nicotinamide mononucleotide (NMN). Oral administration of NMN has been shown to successfully increase NAD⁺ levels in a variety of tissues; however, it remains unclear whether NMN can cross the blood–brain barrier to increase brain NAD⁺ levels. This study evaluated the effects of oral NMN administration on NAD⁺ levels in C57/B6J mice brain tissues. Our results demonstrate that oral gavage of 400 mg/kg NMN successfully increases brain NAD⁺ levels in mice after 45 min. These findings provide evidence that NMN may be used as an intervention to increase NAD⁺ levels in the brain.     

GBT440 increases haemoglobin oxygen affinity,reduces sickling and prolongs RBC half‐life in a murine model of sickle cell disease

A major driver of the pathophysiology of sickle cell disease (SCD) is polymerization of deoxygenated haemoglobin S (HbS), which leads to sickling and destruction of red blood cells (RBCs) and end‐organ damage. Pharmacologically increasing the proportion of oxygenated HbS in RBCs may inhibit polymerization, prevent sickling and provide long term disease modification. We report that GBT440, a small molecule which binds to the N‐terminal α chain of Hb, increases HbS affinity for oxygen, delays in vitro HbS polymerization and prevents sickling of RBCs. Moreover, in a murine model of SCD, GBT440 extends the half‐life of RBCs, reduces reticulocyte counts and prevents ex vivo RBC sickling. Importantly, oral dosing of GBT440 in animals demonstrates suitability for once daily dosing in humans and a highly selective partitioning into RBCs, which is a key therapeutic safety attribute. Thus, GBT440 has the potential for clinical use as a disease‐modifying agent in sickle cell patients.     

Potential applications of lactic acid bacteria and bacteriocins in antimycobacterial therapy

Tuberculosis(TB) is a communicable disease caused by Mycobacterium tuberculosis(M. tuberculosis). WHO estimated that 10.4 million new(incident) TB cases worldwide in year 2016. The increased prevalence of drug resistant strains and side effects associated with the current anti-tubercular drugs make the treatment options more complicated. Hence, there are necessities to identify new drug candidates to fight against various sub-populations of M. tuberculosis with less or no toxicity/side effects and shorter treatment duration. Bacteriocins produced by lactic acid bacteria(LAB) attract attention of researchers because of its "Generally recognized as safe" status. LAB and its bacteriocins possess an effective antimicrobial activity against various bacteria and fungi. Interestingly bacteriocins such as nisin and lacticin 3147 have shown antimycobacterial activity in vitro. As probiotics, LAB plays a vital role in promoting various health benefits including ability to modulate immune response against various infectious diseases. LAB and its metabolic products activate immune system and thereby limiting the M. tuberculosis pathogenesis. The protein and peptide engineering techniques paved the ways to obtain hybrid bacteriocin derivatives from the known peptide sequence of existing bacteriocin. In this review, we focus on the antimycobacterial property and immunomodulatory role of LAB and its metabolic products. Techniques for large scale synthesis of potential bacteriocin with multifunctional activity and enhanced stability are also discussed.