A20 deficiency in myeloid cells protects mice from diet-induced obesity and insulin resistance due to increased fatty acid metabolism

Obesity-induced inflammation is a major driving force in the development of insulin resistance, type 2 diabetes (T2D), and related metabolic disorders. During obesity, macrophages accumulate in the visceral adipose tissue, creating a low-grade inflammatory environment. Nuclear factor kappa B (NF-kappa B) signaling is a central coordinator of inflammatory responses and is tightly regulated by the anti-inflammatory protein A20. Here, we find that myeloid-specific A20-deficient mice are protected from diet-induced obesity and insulin resistance despite an inflammatory environment in their metabolic tissues. Macrophages lacking A20 show impaired mitochondrial respiratory function and metabolize more palmitate both in vitro and in vivo. We hypothesize that A20-deficient macrophages rely more on palmitate oxidation and metabolize the fat present in the diet, resulting in a lean phenotype and protection from metabolic disease. These findings reveal a role for A20 in regulating macrophage immunometabolism

Mapping 123 million neonatal, infant and child deaths between 2000 and 2017

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations

Nations within a nation: variations in epidemiological transition across the states of India, 1990–2016 in the Global Burden of Disease Study

18% of the world's population lives in India, and many states of India have populations similar to those of large countries. Action to effectively improve population health in India requires availability of reliable and comprehensive state-level estimates of disease burden and risk factors over time. Such comprehensive estimates have not been available so far for all major diseases and risk factors. Thus, we aimed to estimate the disease burden and risk factors in every state of India as part of the Global Burden of Disease (GBD) Study 2016

DNA Interaction Studies of an Anticancer Plant Alkaloid, Vincristine, Using Fourier Transform Infrared Spectroscopy

The binding of vincristine with DNA has been investigated using Fourier transform infrared spectroscopy. Various changes in the double helical structure of DNA after addition of vincristine have been examined. It is evident from Fourier transform infrared results that vincristine–DNA interaction occurs through guanine and cytosine base pairs. External binding of vincristine with phosphate backbone of the DNA is also observed. Vincristine perturbs guanine band at 1714 cm−1, cytosine band at 1488 cm−1, and the phosphate vibrations at 1225 and 1086 cm−1. The UV–visible spectra of vincristine–DNA complex show hypochromic and bathochromic shifts, indicating the intercalation of vincristine into the double helical structure of DNA. Both intercalative and external binding modes are observed for vincristine binding with DNA, with an estimated binding constant K = 1.0 × 103 M−1

Drugging the efferocytosis process : concepts and opportunities

Aberrations in efferocytosis are associated with numerous inflammatory pathologies, including atherosclerosis, cancer and infections. Here, Mehrotra and Ravichandran discuss the mechanisms of efferocytosis and the role of this physiological process in disease, and assess strategies and agents for therapeutic intervention. The daily removal of billions of apoptotic cells in the human body via the process of efferocytosis is essential for homeostasis. To allow for this continuous efferocytosis, rapid phenotypic changes occur in the phagocytes enabling them to engulf and digest the apoptotic cargo. In addition, efferocytosis is actively anti-inflammatory and promotes resolution. Owing to its ubiquitous nature and the sheer volume of cell turnover, efferocytosis is a point of vulnerability. Aberrations in efferocytosis are associated with numerous inflammatory pathologies, including atherosclerosis, cancer and infections. The recent exciting discoveries defining the molecular machinery involved in efferocytosis have opened many avenues for therapeutic intervention, with several agents now in clinical trials.The daily removal of billions of apoptotic cells in the human body via the process of efferocytosis is essential for homeostasis. To allow for this continuous efferocytosis, rapid phenotypic changes occur in the phagocytes enabling them to engulf and digest the apoptotic cargo. In addition, efferocytosis is actively anti-inflammatory and promotes resolution. Owing to its ubiquitous nature and the sheer volume of cell turnover, efferocytosis is a point of vulnerability. Aberrations in efferocytosis are associated with numerous inflammatory pathologies, including atherosclerosis, cancer and infections. The recent exciting discoveries defining the molecular machinery involved in efferocytosis have opened many avenues for therapeutic intervention, with several agents now in clinical trials

Necrobiosis Lipoidica through the Microscope

Background: Necrobiosis lipoidica (NL) is a rare, idiopathic granulomatous dermatitis, known for its strong association with diabetes mellitus (DM). Most of the literature available is based on the western population, and studies focusing on histopathology are few. The largest series from India reported so far comprised six cases. Purpose: The objective of this study was to highlight the histopathologic spectrum and presentations of NL in Indian patients. Methods: We reviewed eight cases diagnosed as NL over 10 years. Clinical features were recorded, and various histopathologic parameters were reassessed. Results: The age ranged from 26 to 77 years with a mean of 42, with a female preponderance of 3:1. Clinical presentations included erythematous indurated plaques, painful nodules, and ulcers on the legs. Only one patient had DM. Provisional diagnosis ranged from granuloma annulare to mycosis fungoides. One patient had generalized involvement, with nodules on the upper limbs, trunk, and face. His DM was detected after the onset of lesions. Histopathologic features common to all cases were altered collagen, tiered arrangement of necrobiosis, myointimal hyperplasia and luminal narrowing of blood vessels, and perivascular lymphohistiocytic infiltrate. The upper dermis was involved in five cases and subcutis in four cases. The patterns of granulomas were mixed (6/8), tuberculoid (1/8), and palisading (1/8). Plasma cells were predominant in only one case. Perineural inflammation was seen in one case. A perforating variant was seen in one case. None of the cases had dermal mucin. Conclusion: Diagnosis of NL relies on clinicopathologic correlation. Our series highlights variations in histopathology compared to classically described findings such as involvement of upper dermis, striking vascular changes, rarity of palisading granulomas, perineural inflammation, and paucity of plasma cells. It is important to be aware of these in order to avoid misdiagnosis

Direct determination of moisture in powder milk using near infrared spectroscopy

Moisture content in commercially available milk powder was investigated using near infrared (NIR) diffuse reflectance spectroscopy with an Indian low-cost dispersive NIR spectrophotometer. Different packets of milk powder of the same batch were procured from the market. Forty-five samples with moisture range 4–10 % were prepared in the laboratory. Spectra of the samples were collected in the wavelength region 800–2500 nm. Moisture values of all the samples were simultaneously determined by Karl Fischer (KF) titration. These KF values were used as reference for developing calibration model using partial least squares regression (PLSR) method. The calibration and validation statistics are R 2 cal: 0.9942, RMSEC: 0.1040, and R 2 val: 0.9822, RMSEV: 0.1730. Five samples of unknown moisture contents were taken for NIR prediction using developed calibration model. The agreement between NIR predicted results and those of Karl Fischer values is appreciable. The result shows that the instrument can be successfully used for the determination of moisture content in milk powder. Copyright © 2006 R. Nagarajan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 1