Risk factors and outcomes of immune and non-immune causes of diffuse alveolar hemorrhage: a tertiary-care academic single-center experience.

Diffuse alveolar hemorrhage (DAH) is a rare but potentially life-threatening emergency that has both immune and non-immune etiologies. The objective of this investigation was to compare the risk factors and outcomes of immune and non-immune causes of DAH at a tertiary-care academic center. This was a retrospective observational study conducted at a University center. We reviewed all chest radiographs spanning 12 years (2007-2019) at our institute with the words "diffuse alveolar hemorrhage" in the body of their report, and ascertained cases of DAH through a detailed chart review. We used Chi-squared test to determine the differences in risk factors and outcomes between immune versus non-immune causes of DAH. We performed logistic regressions to assess whether baseline demographics and clinical features influence four critical outcomes: death, shock, renal failure, and severe anemia requiring transfusions. Over the 12-year period, there were 88 patients with DAH, 55 with non-immune and 33 with immune etiologies. Among immune causes of DAH, granulomatosis with polyangiitis (GPA) (10.2%), microscopic polyangiitis (MPA) (9%) and systemic lupus erythematosus (SLE) (9%) were most common. Among non-immune causes of DAH, coagulopathy (6.8%), decompensated heart failure (4.5%) and infection (3.4%) were most common. Patients with non-immune causes of DAH were 45.8% more likely to die and 20.7% less likely to experience sustained remission (p = 0.001). Patient with immune causes of DAH were 21% more likely to have extra-pulmonary findings and 23.7% more likely to have received hemodialysis (HD). The presence of extra-pulmonary findings was statistically significantly correlated with the number of blood products received, the need for HD and non-statistically significantly correlated with likelihood of death. Patients with immune causes of DAH were 71.5% more likely to receive multimodal therapy including corticosteroids. Immune-mediated DAH is associated with a better prognosis than non-immune DAH, despite its greater association with extra-pulmonary findings and requirement for hemodialysis.

Influenza A(H1N1)pdm09 outbreak detected in inter-seasonal months during the surveillance of influenza-like illness in Pune, India, 2012-2015.

An outbreak of influenza A(H1N1)pdm09 was detected during the ongoing community-based surveillance of influenza-like illness (ILI). Among reported 119 influenza A(H1N1)pdm09 cases (59 cases in the year 2012 and 60 cases in 2015) in summer months, common clinical features were fever (100%), cough (90·7%), sore throat (85·7%), nasal discharge (48·7%), headache (55·5%), fatigue (18·5%), breathlessness (3·4%), and ear discharge (1·7%). Rise in ILI cases were negatively correlated with the seasonal factors such as relative humidity (Karl Pearson's correlation coefficient, i.e. r = -0·71 in the year 2012 and r = -0·44 in the year 2015), while rise in ILI cases were positively correlated with the temperature difference (r = 0·44 in the year 2012 and r = 0·77 in the year 2015). The effective reproduction number R, was estimated to be 1·30 in 2012 and 1·64 in 2015. The study highlights the rise in unusual influenza activity in summer month with high attack rate of ILI among children aged ⩽9 years. Children in this age group may need special attention for influenza vaccination. Influenza A(H1N1)pdm09 outbreak was confirmed in inter-seasonal months during the surveillance of ILI in Pune, India, 2012-2015.

RLIM inhibits functional activity of LIM homeodomain transcription factors via recruitment of the histone deacetylase complex.

LIM domains are required for both inhibitory effects on LIM homeodomain transcription factors and synergistic transcriptional activation events. The inhibitory actions of the LIM domain can often be overcome by the LIM co-regulator known as CLIM2, LDB1 and NLI (referred to hereafter as CLIM2; refs 2-4). The association of the CLIM cofactors with LIM domains does not, however, improve the DNA-binding ability of LIM homeodomain proteins, suggesting the action of a LIM-associated inhibitor factor. Here we present evidence that LIM domains are capable of binding a novel RING-H2 zinc-finger protein, Rlim (for RING finger LIM domain-binding protein), which acts as a negative co-regulator via the recruitment of the Sin3A/histone deacetylase corepressor complex. A corepressor function of RLIM is also suggested by in vivo studies of chick wing development. Overexpression of the gene Rnf12, encoding Rlim, results in phenotypes similar to those observed after inhibition of the LIM homeodomain factor LHX2, which is required for the formation of distal structures along the proximodistal axis, or by overexpression of dominant-negative CLIM1. We conclude that Rlim is a novel corepressor that recruits histone deacetylase-containing complexes to the LIM domain.

Efficacy of external cold and a vibrating device in reducing pain and anxiety during local anaesthesia.

BACKGROUND AND AIM: To evaluate and compare the efficacy of external cold and a vibrating device in reducing the pain and anxiety amidst children receiving maxillary infiltration anaesthesia over conventional methods. METHOD: A sum of thirty subjects aged between 5 and 10 years who had undergone dental procedures requiring maxillary infiltration were enrolled in the current split-mouth randomised control study. The control intervention constitutes infiltration of 1.8 mL of 2% lignocaine in addition to 1:100,000 adrenaline (Lox, Neon Laboratories Mumbai, India) whereas, the experimental group used external cold and a vibrating device (Buzzy®, MMJ Labs, Atlanta, GA, USA) in annexation to the control protocol. Simultaneous to LA administration, pulse rate was employed as an objective measure and the subjective measure was recorded using RMS Pictorial Scale (RMS-PS) for the child's discomfort. To document the child's pain as anticipated by the dentist the revised face, limbs, arms, cry and consolability (FLACC-R) scale was employed. RESULT: Lower pain sensation and anxiety was recorded in the experimental group using Buzzy when compared to control. CONCLUSION: External cold in adjacent with vibrations might be efficient in lowering pain as well as anxiety in children experiencing infiltration dental anaesthesia though further research work is requisite with a larger sample size.

The transforming growth factor beta type II receptor can replace the activin type II receptor in inducing mesoderm.

The type II receptors for the polypeptide growth factors transforming growth factor beta (TGF-beta) and activin belong to a new family of predicted serine/threonine protein kinases. In Xenopus embryos, the biological effects of activin and TGF-beta 1 are strikingly different; activin induces a full range of mesodermal cell types in the animal cap assay, while TGF-beta 1 has no effects, presumably because of the lack of functional TGF-beta receptors. In order to assess the biological activities of exogenously added TGF-beta 1, RNA encoding the TGF-beta type II receptor was introduced into Xenopus embryos. In animal caps from these embryos, TGF-beta 1 and activin show similar potencies for induction of mesoderm-specific mRNAs, and both elicit the same types of mesodermal tissues. In addition, the response of animal caps to TGF-beta 1, as well as to activin, is blocked by a dominant inhibitory ras mutant, p21(Asn-17)Ha-ras. These results indicate that the activin and TGF-beta type II receptors can couple to similar signalling pathways and that the biological specificities of these growth factors lie in their different ligand-binding domains and in different competences of the responding cells.

Cationic surfactants and other factors that affect enzymatic activities and transport.

Surfactants influence functions of proteins in cell signalling. Because molecular mechanisms of surfactants are poorly understood, the cationic surfactant effect on three metabolically important enzymes--L-glutamate dehydrogenase, L-lactate dehydrogenase, and L-malate dehydrogenase--were investigated at a physiologically relevant pH range (6.5-7.4). How a cationic, a non-ionic, and an anionic surfactant could differentially influence these enzymes, and how these surfactants could influence the interfacial mass transport of these enzymes across a polycarbonate membrane in a separation cell were also investigated. Provided the charge density was the same, cationic surfactants affected enzymatic activities similarly, regardless of their molecular masses. Hence, a cationic surfactant behaved similarly to a hydrophilic anionic surfactant; however, the cationic surfactant also enhanced enzymatic activity at pH 6.5 and a moderately high concentration (150 ppm). The hydrophilic surfactant enhanced enzymatic activity and the hydrophobic surfactant depressed enzymatic activity. Addition of 0.1 ppm of the hydrophilic anionic surfactant decreased the amount of enzyme permeation through the membrane, but 0.1 ppm of the non-ionic surfactant had no effect, whereas 0.1 ppm of the hydrophobic surfactant increased enzyme permeation. These results have physiological and signalling implications in nanobiotechnology.

Autocrine production of interleukin 6 causes multidrug resistance in breast cancer cells.

It has been shown that serum levels of interleukin (IL)-6 are elevated in patients with various types of cancer. However, the exact source of IL-6 in these patients and its role in tumor progression remain unclear. Here we demonstrate that the autocrine production of IL-6 by tumor cells promotes resistance of the cells to chemotherapy, a novel function of IL-6 in cancer biology. Breast cancer cells that are sensitive to drug treatment do not express IL-6, whereas high levels of IL-6 are produced by multidrug-resistant breast cancer cells. Expression of the IL-6 gene in drug-sensitive breast cancer cells increases their resistance to drug treatment by activating the CCAAT enhancer-binding protein family of transcription factors and inducing mdr1 gene expression. Thus, the autocrine production of IL-6 by tumor cells is an important factor in determining the susceptibility or resistance of these cells to drug treatment. Because tumors from some breast cancer patients contain IL-6-producing cells, it is possible that IL-6 could potentially be used as a prognostic factor for chemotherapy resistance.

Differential scanning calorimetry and Fourier transform infrared analysis of lipid-protein interactions involving the nicotinic acetylcholine receptor.

Lipid-protein interactions were studied using Torpedo californica acetylcholine receptor (AChR) as a model system by reconstituting purified AChR into dielaidoylphosphatidylcholine (DEPC, 18:1 trans-9,10) membranes. The structural and thermodynamic behavior of lipids in the vicinity of the protein were studied by differential scanning calorimetry and Fourier transform infrared spectroscopy. The effects of AChR on the thermodynamic parameters associated with lipid phase transitions were to reduce the enthalpy change, lower the transition temperature and reduce the cooperative behavior of the lipid molecules. A stoichiometry of approx. 95 lipids per AChR molecule was found by simulating the decrease in enthalpy in terms of a simple model in which a fixed number of lipid molecules are prevented from undergoing a cooperative phase transition. In parallel, the vibrational spectra of pure DEPC and AChR reconstituted in DEPC membranes at various lipid to protein ratios were examined. Profiles of the 3000-2800 cm-1 C-H stretching region and 1350-950 cm-1 characteristic of the headgroup region of the lipid exhibit little sensitivity to protein/lipid ratio reflecting weak interaction of AChR with DEPC. The lipid carbonyl on the other hand appear to be increasingly hydrogen bonded in the presence of AChR. The results provide new information about the size and physical state of the motionally restricted lipid environment that surrounds the acetylcholine receptor. The results are discussed in the context of lipid-mediated alterations in acetylcholine receptor function.