Evaluation of thyroid functions in leprosy. III. Circulating auto-antibodies against thyroid and nuclear components.

Sera from twenty six patients of various types of leprosy were tested for the detection of circulating auto-antibodies and nuclear components against thyroid using various methods. Four patients of lepromatous leprosy had higher levels of thyroid auto-antibodies by latex agglutination. Three patients showed the presence of anti-nuclear antibodies, two belonged to the TT and one to the LL group.     

Can nutrition rehabilitation centers address severe malnutrition in India?

Madhya Pradesh has made remarkable progress in facility based management of severe acute malnutrition, and has developed a model that is being replicated in many states. India has uniquely high prevalence of both stunting and wasting, implying that both severe acute malnutrition and severe chronic malnutrition co-exist. This study sought to explore design issues of nutritional rehabilitation centers in order to inform its effectiveness in settings where the prevalence of chronic poverty and malnutrition is high. Our analysis attributes the limited success (marked by poor cure rates and high non-responder rates) to high prevalence of chronic malnutrition, particularly in nutritional rehabilitation centers located in pheripheral areas. There is a failure to recognize severe chronic malnutrition as an epidemiological entity and gear wide-ranging programmatic and social interventions.     

Diverse innate stimuli activate basophils through pathways involving Syk and IκB kinases

Mature basophils play critical inflammatory roles during helminthic, autoimmune, and allergic diseases through their secretion of histamine and the type 2 cytokines interleukin 4 (IL-4) and IL-13. Basophils are activated typically by allergen-mediated IgE cross-linking but also by endogenous “innate” factors. The aim of this study was to identify the innate stimuli (cytokines, chemokines, growth factors, hormones, neuropeptides, metabolites, and bacterial products) and signaling pathways inducing primary basophil activation. Basophils from naïve mice or helminth-infected mice were cultured with up to 96 distinct stimuli and their influence on basophil survival, activation, degranulation, and IL-4 or IL-13 expression were investigated. Activated basophils show a heterogeneous phenotype and segregate into distinct subsets expressing IL-4, IL-13, activation, or degranulation markers. We find that several innate stimuli including epithelial derived inflammatory cytokines (IL-33, IL-18, TSLP, and GM-CSF), growth factors (IL-3, IL-7, TGFβ, and VEGF), eicosanoids, metabolites, TLR ligands, and type I IFN exert significant direct effects on basophils. Basophil activation mediated by distinct upstream signaling pathways is always sensitive to Syk and IκB kinases-specific inhibitors but not necessarily to NFAT, STAT5, adenylate cyclase, or c-fos/AP-1 inhibitors. Thus, basophils are activated by very diverse mediators, but their activation seem controlled by a core checkpoint involving Syk and IκB kinases.

Basophils are rare circulating granulocytes activated by immunoglobulin E (IgE)-mediated cross-linking of the high affinity receptor for IgE (FcεRI), which induces their degranulation and synthesis of the type 2 cytokines, interleukin 4 (IL-4) and IL-13 in autoimmune, allergic diseases and helminthiases (1). Basophils are also sensitive to innate signals, including the cytokine IL-3, the alarmins IL-18, IL-33, and Thymic stromal Lymphopoietin (TSLP), the prostaglandin D2 (PGD2), ATP, and various chemokines or growth factors (1–4). Some of these stimuli might regulate basophil immunoregulatory functions during homeostasis (5). Secretion of IL-4 and histamine release by human basophils is sensitive to FK506 (a calcineurin inhibitor), while secretion of IL-13 is not affected, indicating that distinct signaling pathways regulate the expression of these type 2 cytokines (6–8). By contrast, activation of basophils by IgE or IL-18/33 involves distinct receptors and upstream signaling pathways but results in expression of both IL-4 and IL-13 (5, 7, 9–11). Despite common evolutionary ancestry, it is currently thought that IL-4 and IL-13 show divergent functions in immunity and physiology (12, 13). Basophil IL-4 secretion has been implicated in T helper type 2 (Th2) differentiation and M2 skewing. Basophils are an important source of IL-13 in the lungs, where they control the phenotype of alveolar macrophages during development (1, 5).The Il4/13 locus is subject to a differential regulation between distinct cell types but has been mostly studied in T cells. The locus contains elements regulated by cAMP, c-fos/AP-1, NFAT, NF-κB, GATA3, STAT5, and STAT6 that have been associated with the regulation of Il4/13 expression (6, 14–19). Basophils produce IL-4 and IL-13 after the cross-linking of their surface-bound IgE by antigen or by exposure to IL-3. IgE- or IL-3-mediated basophil activation are both controlled by the tyrosine kinase Syk (6, 20, 21). IgE-induced cytokine expression is also promoted by IκB kinase (IKK) through NF-κB-dependent or -independent signals (22, 23).To date, studies of murine basophils have focused on cultured bone marrow-derived basophils (BMBa) or primary bone marrow (BM) basophils, with circulating mature basophils too few in number for useful studies (6). We used B8 × 4C13R IL-4/IL-13 triple reporter mice (24) to follow and compare the ex vivo responses of primary mature basophils to 96 common stimuli and found that basophils were highly sensitive to type 2 and epithelial-derived cytokines and growth factors. Single-cell analysis revealed that basophils displayed distinct phenotypes upon stimulation with IL-3, expressing IL-4, and/or IL-13, Ly6C, or the degranulation marker CD63 (25). During helminth infection, basophils were found to be hyper- and hyporeactive to distinct stimuli (“Hp-basophils”). Purified Hp-basophils were also sensitive to homeostatic growth factors and antiviral response elements. Basophil reactivity was always sensitive to Syk and IKKs specific inhibitors. In conclusion, we found basophils to be sensitive to a complex array of distinct innate stimuli that worked through core common signaling pathways.     

Improving the optical and thermoelectric properties of Cs2InAgCl6 with heavy substitutional doping: a DFT insight

The next-generation indium-based lead-free halide material Cs₂InAgCl₆ is promising for photovoltaic applications due to its good air stability and non-toxic behavior. However, its wide bandgap (>3 eV) is not suitable for the solar spectrum and hence reduces its photoelectronic efficiency for device applications. Here we report a significant bandgap reduction from 2.85 eV to 0.65 eV via substitutional doping and its effects on the optoelectronic and opto-thermoelectric properties from a first-principles study. The results predict that Sn/Pb and Ga and Cu co-doping will enhance the density of states significantly near the valence band maximum (VBM) and thus reduce the bandgap via shifting the VBM upward, while alkali metals (K/Rb) slightly increase the bandgap. A strong absorption peak near the Shockley–Queisser limit is observed in the co-doped case, while in the Sn/Pb-doped case, we notice a peak in the middle of the visible region of the solar spectrum. The nature of the bandgap is indirect with Cu–Ga/Pb/Sn doping, and a significant reduction in the bandgap, from 2.85 eV to 0.65 eV, is observed in the case of Ga–Cu co-doping. We observe a significant increase in the power factor (PF) (2.03 mW m⁻¹ K⁻²) for the n-type carrier after Pb-doping, which is ∼3.5 times higher than in the pristine case (0.6 mW m ⁻¹ K⁻²) at 500 K.

The next-generation indium-based lead-free halide material Cs₂InAgCl₆ is promising for photovoltaic applications due to its good air stability and non-toxic behavior while it shows good thermoelectric properties when doped with Pb.     

Flavonoids of Korean Citrus aurantium L. Induce Apoptosis via Intrinsic Pathway in Human Hepatoblastoma HepG2 Cells

Korean Citrus aurantium L. has long been used as a medicinal herb for its anti‐inflammatory, antioxidant, and anticancer properties. The present study investigates the anticancer role of flavonoids extracted from C. aurantium on human hepatoblastoma cell, HepG2. The Citrus flavonoids inhibit the proliferation of HepG2 cells in a dose‐dependent manner. This result was consistent with the in vivo xenograft results. Apoptosis was detected by cell morphology, cell cycle analysis, and immunoblot. Flavonoids decreased the level of pAkt and other downstream targets of phosphoinositide‐3‐kinase/Akt pathway – P‐4EBP1 and P‐p70S6K. The expressions of cleaved caspase 3, Bax, and Bak were increased, while those of Bcl‐2 and Bcl‐xL were decreased with an increase in the expression of Bax/Bcl‐xL ratio in treated cells. Loss of mitochondrial membrane potential was also observed in flavonoid‐treated HepG2 cells. It was also observed that the P‐p38 protein level was increased both dose and time dependently in flavonoid‐treated cells. Collectively, these results suggest that flavonoid extracted from Citrus inhibits HepG2 cell proliferation by inducing apoptosis via an intrinsic pathway. These findings suggest that flavonoids extracted from C. aurantium L. are potential chemotherapeutic agents against liver cancer. Copyright © 2015 John Wiley & Sons, Ltd.     

Solvent assisted size effect on AuNPs and significant inhibition on K562 cells

Herein, the synthesis and characterization of ideal size (∼10 and 40 nm, in diameter) AuNPs (gold nanoparticles) were reported. Two different organic solvents such as DMF (dimethyl formamide) and NMPL (N-methyl-2-pyrrolidone) were used to synthesize AuNPs along with agents reducing agents such as NaBH₄ (sodium borohydrate) and Na₃C₆H₅O₇ (sodium citrate). The combination of [(HAuCl₄)–(DMF)–(NaBH₄)] gives AuNPs with an avg. size of 10.2 nm. Similarly, the combination of [(HAuCl₄)–(NMPL)–(Na₃C₆H₅O₇)] gives AuNPs with an avg. size of 40.4 nm. The morphology of these nanoscale AuNPs has been characterized through TEM and HRTEM imaging followed by SAED for lattice parameters such as d-spacing value (2.6 Å/0.26 nm) of crystalline metal (Au) nanoparticles. Further, these unique and ideal nanoscale AuNPs were used to evaluate the potential working efficacy by using in vitro cell based studies on K562 (leukaemia) blood cancer cells. From the MTT assay results around 88% cell inhibition was measured for ∼10 nm sized AuNPs. The treated cells were stained with different fluorescent dyes such as FITC, DAPI, Rho-6G and their ruptured morphology has been reported in the respective sections. These types of ideal sized metal (Au) nanoparticles are recommended for various theranostics such as to cure breast, colon, lung and liver cancers.

Herein, the synthesis and characterization of ideal size (∼10 and 40 nm, in diameter) AuNPs (gold nanoparticles) were reported.     

Rapid survey of wasting and stunting in children: What’s new,what’s old and what’s the buzz?

Nationwide Rapid Survey on Children (RSoC), conducted by the Ministry of Women and Child Development and UNICEF in 2013-14 showed a marked improvement in the status of the child malnutrition over the third National Family Health Survey (NFHS-3) that was conducted in 2005-06. Despite some impressive gains in the anthropometric indicators of malnutrition, the absolute levels remain high, and of concern. Despite these gains, the feeding indicators remain stagnant. The programmatic responses need to adopt a multi-sectoral comprehensive approach with regular and comprehensive nutrition surveillance and recognize the epidemiological diversity.     

Functional status of auditory pathways in hypothyroidism: evoked potential study

Hypothyroidism is known to be associated with mental retardation, motor dysfunction, memory deficits and hearing impairment. In the present study, the functional integrity of the thalamocortical projections to the primary auditory cortex and association cortex has been assessed by using Auditory Evoked Responses i.e Auditory Brainstem (ABR), Mid Latency Response (MLR) and Slow Vertex Response (SVR). Thirty newly diagnosed hypothyroid patients and thirty healthy controls were taken for the study and ABR, MLR and SVR were recorded on computerized evoked potential recorder using 10-20 system of electrode placement. The second recordings for the hypothyroid patients were done 3 months after treatment with attainment of euthyroid states. The present study revealed a slight increase in absolute latency of wave III of ABR in hypothyroid patients and significant decrease in absolute latency of wave III and interpeak latency of I-III after treatment. There was a significant decrease in amplitude of wave V in hypothyroid patients and significant increase in amplitudes of ABR wave I and wave V after treatment. There was a significant increase in latency of wave Na of MLR and wave P2 of SVR in hypothyroid patients. The latencies of waves Na, Pa, Nb of MLR and waves PI and N2 of SVR showed significant improvement with thyroid hormone treatment. The results of the present study indicates that in hypothyroid state there might be slow conduction at the periphery and with treatment there is better recruitment of neuronal pool of the generators of the waves of ABR in the brainstem. We can also conclude that the thalamocortical projections of the auditory pathways are adversely affected in the hypothyroid state and this improves after treatment.     

Evaluation of thyroid functions in leprosy. I. Thyroid function tests

Twenty six patients of different types of leprosy were studied for radio active iodine uptake (I131) and serum levels of triiodothyronine (T3), thyroxine (T4) and thyroid stimulating hormone (TSH). None of the patients had clinical evidence of thyroid involvement. No significant difference was found between the values obtained in patients and normals and in different varieties of leprosy.