Pheochromocytoma: A Rare Cause of Secondary Hypertension

  Introduction: Pheochromocytoma is a rare tumor, originating from the chromaffin tissue. Its frequency is approximately 1/100,000. The clinical manifestation is due to catecholamine excess, which includes high blood pressure, palpitation, headache, sweating, nausea, vomiting, trembling, weakness, irritation, abdominal and chest pain, dyspnea, red warm face, constipation, polyuria, and polydipsia.   Case Report: We present a case of 53 years old male, hospitalized for hypertensive crisis following the manipulation of left sided frozen shoulder. He had labile blood pressure ranging from 220/120 systolic- 90/60 diastolic, profuse sweating and tachycardia. Findings of Contrast enhanced CT of abdomen was consistent with right adrenal pheochromocytoma and 24 hours urinary VMA was 17 mg /24 hr (Normal <13.6 mg /24hr). After the clinical, paraclinical investigations and radiological tests, it was proved to be a pheochromocytoma. The surgical intervention was planned. But due to unavailability of required antihypertensive drugs in Nepal (alpha-blockers like phentolamine and phenoxybenzamine), surgeons were reluctant to operate, although blood pressure was well controlled with use of sodium nitroprusside during hypertensive crisis and prazosin, a selective alpha blocker as maintainance therapy. The use of prazosin to control hypertension secondary to pheochromocytoma is limited to case report and case series.   Conclusion: Although rare, pheochromocytoma is a treatable surgical cause of secondary hypertension

Metabolic signaling directs the reciprocal lineage decisions of αβ and γδ T cells

Wiring metabolic signaling circuits in thymocytes Cell differentiation is often accompanied by metabolic changes. Yang et al. report that generation of double-positive (DP) thymocytes from double-negative (DN) cells coincides with dynamic regulation of glycolytic and oxidative metabolism. Given the central role of mechanistic target of rapamycin complex 1 (mTORC1) signaling in regulating metabolic changes, they examined the role of mTORC1 pathway in thymocyte development by conditionally deleting RAPTOR, the key component of the mTORC1 complex, in thymocytes. Loss of RAPTOR impaired the DN-to-DP transition, but unexpectedly also perturbed the balance between αβ and γδ T cells and promoted the generation of γδ T cells. Their studies highlight an unappreciated role for mTORC1-dependent metabolic changes in controlling thymocyte fates. The interaction between extrinsic factors and intrinsic signal strength governs thymocyte development, but the mechanisms linking them remain elusive. We report that mechanistic target of rapamycin complex 1 (mTORC1) couples microenvironmental cues with metabolic programs to orchestrate the reciprocal development of two fundamentally distinct T cell lineages, the αβ and γδ T cells. Developing thymocytes dynamically engage metabolic programs including glycolysis and oxidative phosphorylation, as well as mTORC1 signaling. Loss of RAPTOR-mediated mTORC1 activity impairs the development of αβ T cells but promotes γδ T cell generation, associated with disrupted metabolic remodeling of oxidative and glycolytic metabolism. Mechanistically, we identify mTORC1-dependent control of reactive oxygen species production as a key metabolic signal in mediating αβ and γδ T cell development, and perturbation of redox homeostasis impinges upon thymocyte fate decisions and mTORC1-associated phenotypes. Furthermore, single-cell RNA sequencing and genetic dissection reveal that mTORC1 links developmental signals from T cell receptors and NOTCH to coordinate metabolic activity and signal strength. Our results establish mTORC1-driven metabolic signaling as a decisive factor for reciprocal αβ and γδ T cell development and provide insight into metabolic control of cell signaling and fate decisions. Development of αβ and γδ T cells requires coupling of environmental signals with metabolic and redox regulation by mTORC1. Development of αβ and γδ T cells requires coupling of environmental signals with metabolic and redox regulation by mTORC1

Facilitating corals in an early Silurian deep‐water assemblage

Corals are powerful ecosystem engineers and can form reef communities with extraordinary biodiversity through time. Understanding the processes underlying the spatial distribution of corals allows us to identify the key biological and physical processes that structure coral communities and how these processes and interactions have evolved. However, few spatial ecology studies have been conducted on coral assemblages in the fossil record. Here we use spatial point process analysis (SPPA) to investigate the ecological interactions of an in situ tabulate and rugose coral community (n = 199), preserved under volcanic ash in the Silurian of Ireland. SPPA is able to identify many different sorts of interactions including dispersal limitation and competition within and between taxa. Our SPPA found that the spatial distribution of rugose corals were best modelled by Thomas clusters (pd = 0.834), indicating a single dispersal episode and that the tabulate corals were best modelled by double Thomas clusters (pd = 0.820), indicating two dispersal episodes. Further, the bivariate distribution was best modelled by linked double clusters (pd = 0.970), giving significant evidence of facilitation between the tabulate and rugose populations, and identifying the facilitators in this community to be the tabulate corals. This interaction could be an important ecological driver for enabling the aggregation of sessile organisms over long temporal periods and facilitation may help to explain trends in reef diversity and abundance during the Ordovician biodiversification and in the early Silurian

Analysis of maternal and newborn training curricula and approaches to inform future trainings for routine care, basic and comprehensive emergency obstetric and newborn care in the low- and middle-income countries: Lessons from Ethiopia and Nepal

Program managers routinely design and implement specialised maternal and newborn health trainings for health workers in low- and middle-income countries to provide better-coordinated care across the continuum of care. However, in these countries details on the availability of different training packages, skills covered in those training packages and the gaps in their implementation are patchy. This paper presents an assessment of maternal and newborn health training packages to describe differences in training contents and implementation approaches used for a range of training packages in Ethiopia and Nepal. We conducted a mixed-methods study. The quantitative assessment was conducted using a comprehensive assessment questionnaire based on validated WHO guidelines and developed jointly with global maternal and newborn health experts. The qualitative assessment was conducted through key informant interviews with national stakeholders involved in implementing these training packages and working with the Ministries of Health in both countries. Our quantitative analysis revealed several key gaps in the technical content of maternal and newborn health training packages in both countries. Our qualitative results from key informant interviews provided additional insights by highlighting several issues with trainings related to quality, skill retention, logistics, and management. Taken together, our findings suggest four key areas of improvement: first, training materials should be updated based on the content gaps identified and should be aligned with each other. Second, trainings should address actual health worker performance gaps using a variety of innovative approaches such as blended and self-directed learning. Third, post-training supervision and ongoing mentoring need to be strengthened. Lastly, functional training information systems are required to support planning efforts in both countries

Extensive Spectroscopy and Photometry of the Type IIP Supernova 2013ej

We present extensive optical ($UBVRI$, $g'r'i'z'$, and open CCD) and near-infrared ($ZYJH$) photometry for the very nearby Type IIP SN ~2013ej extending from +1 to +461 days after shock breakout, estimated to be MJD $56496.9\pm0.3$. Substantial time series ultraviolet and optical spectroscopy obtained from +8 to +135 days are also presented. Considering well-observed SNe IIP from the literature, we derive $UBVRIJHK$ bolometric calibrations from $UBVRI$ and unfiltered measurements that potentially reach 2\% precision with a $B-V$ color-dependent correction. We observe moderately strong Si II $\lambda6355$ as early as +8 days. The photospheric velocity ($v_{\rm ph}$) is determined by modeling the spectra in the vicinity of Fe II $\lambda5169$ whenever observed, and interpolating at photometric epochs based on a semianalytic method. This gives $v_{\rm ph} = 4500\pm500$ km s$^{-1}$ at +50 days. We also observe spectral homogeneity of ultraviolet spectra at +10--12 days for SNe IIP, while variations are evident a week after explosion. Using the expanding photosphere method, from combined analysis of SN 2013ej and SN 2002ap, we estimate the distance to the host galaxy to be $9.0_{-0.6}^{+0.4}$ Mpc, consistent with distance estimates from other methods. Photometric and spectroscopic analysis during the plateau phase, which we estimated to be $94\pm7$ days long, yields an explosion energy of $0.9\pm0.3\times10^{51}$ ergs, a final pre-explosion progenitor mass of $15.2\pm4.2$~M$_\odot$ and a radius of $250\pm70$~R$_\odot$. We observe a broken exponential profile beyond +120 days, with a break point at +$183\pm16$ days. Measurements beyond this break time yield a $^{56}$Ni mass of $0.013\pm0.001$~M$_\odot$.Comment: 29 pages, 23 figures, 15 tables, Published in The Astrophisical Journa

SN~2012cg: Evidence for Interaction Between a Normal Type Ia Supernova and a Non-Degenerate Binary Companion

We report evidence for excess blue light from the Type Ia supernova SN 2012cg at fifteen and sixteen days before maximum B-band brightness. The emission is consistent with predictions for the impact of the supernova on a non-degenerate binary companion. This is the first evidence for emission from a companion to a SN Ia. Sixteen days before maximum light, the B-V color of SN 2012cg is 0.2 mag bluer than for other normal SN~Ia. At later times, this supernova has a typical SN Ia light curve, with extinction-corrected M_B = -19.62 +/- 0.02 mag and Delta m_{15}(B) = 0.86 +/- 0.02. Our data set is extensive, with photometry in 7 filters from 5 independent sources. Early spectra also show the effects of blue light, and high-velocity features are observed at early times. Near maximum, the spectra are normal with a silicon velocity v_{Si} = -10,500$ km s^{-1}. Comparing the early data with models by Kasen (2010) favors a main-sequence companion of about 6 solar masses. It is possible that many other SN Ia have main-sequence companions that have eluded detection because the emission from the impact is fleeting and faint.Comment: accepted to Ap

Mechanisms of goethite dissolution in the presence of desferrioxamine B and Suwannee River fulvic acid at pH 6.5

Siderophores are Fe3+ specific low MW chelating ligands secreted by microorganisms in response to Fe stress. Low MW organic acids such as oxalate have been shown to enhance siderophore mediated dissolution of Fe3+ oxides. However, the effect of fulvic acid presence on siderophore function remains unknown. We used batch dissolution experiments to investigate Fe release from goethite in the goethite-fulvic acid desferrioxamine B (goethite-SRFA-DFOB) ternary system. Experiments were conducted at pH 6.5 while varying reagent addition sequence. FTIR and UV-Vis spectroscopy were employed to characterise the Fe-DFOB, Fe-SRFA and DFOB–SRFA complexes. Iron released from goethite in the presence of SRFA alone was below detection limit. In the presence of both SRFA and DFOB, dissolved Fe increased with reaction time, presence of the DFOB-SRFA complex, and where SRFA was introduced prior to DFOB. FTIR data show that in the ternary system, Fe3+ is complexed primarily to oxygen of the DFOB hydroxamate group, whilst the carboxylate C=O of SRFA forms an electrostatic association with the terminal NH3+ of DFOB. We propose that SRFA sorbed to goethite lowers the net positive charge of the oxide surface, thus facilitating adsorption of cationic DFOB and subsequent Fe3+ chelation and release. Furthermore, the sorbed SRFA weakens Fe-O bonds at the goethite surface, increasing the population of kinetically labile Fe. This work demonstrates the positive, though indirect role of SRFA in increasing the bioavailability of Fe3+

Extensive Spectroscopy and Photometry of the Type IIP Supernova 2013ej

We present extensive optical (UBVRI, g′r′i′z′, and open CCD) and near-infrared (ZYJH) photometry for the very nearby Type IIP SN ~2013ej extending from +1 to +461 days after shock breakout, estimated to be MJD 56496.9±0.3. Substantial time series ultraviolet and optical spectroscopy obtained from +8 to +135 days are also presented. Considering well-observed SNe IIP from the literature, we derive UBVRIJHK bolometric calibrations from UBVRI and unfiltered measurements that potentially reach 2\% precision with a B−V color-dependent correction. We observe moderately strong Si II λ6355 as early as +8 days. The photospheric velocity (vph) is determined by modeling the spectra in the vicinity of Fe II λ5169 whenever observed, and interpolating at photometric epochs based on a semianalytic method. This gives vph=4500±500 km s−1 at +50 days. We also observe spectral homogeneity of ultraviolet spectra at +10--12 days for SNe IIP, while variations are evident a week after explosion. Using the expanding photosphere method, from combined analysis of SN 2013ej and SN 2002ap, we estimate the distance to the host galaxy to be 9.0+0.4−0.6 Mpc, consistent with distance estimates from other methods. Photometric and spectroscopic analysis during the plateau phase, which we estimated to be 94±7 days long, yields an explosion energy of 0.9±0.3×1051 ergs, a final pre-explosion progenitor mass of 15.2±4.2~M⊙ and a radius of 250±70~R⊙. We observe a broken exponential profile beyond +120 days, with a break point at +183±16 days. Measurements beyond this break time yield a 56Ni mass of 0.013±0.001~M⊙

Sub-inhibitory fosmidomycin exposures elicits oxidative stress in Salmonella enterica Serovar typhimurium LT2

Fosmidomycin is a time-dependent nanomolar inhibitor of methylerythritol phosphate (MEP) synthase, which is the enzyme that catalyzes the first committed step in the MEP pathway to isoprenoids. Importantly, fosmidomycin is one of only a few MEP pathway-specific inhibitors that exhibits antimicrobial activity. Most inhibitors identified to date only exhibit activity against isolated pathway enzymes. The MEP pathway is the sole route to isoprenoids in many bacteria, yet has no human homologs. The development of inhibitors of this pathway holds promise as novel antimicrobial agents. Similarly, analyses of the bacterial response toward MEP pathway inhibitors provides valuable information toward the understanding of how emergent resistance may ultimately develop to this class of antibiotics. We have examined the transcriptional response of Salmonella enterica serovar typhimurium LT2 to sub-inhibitory concentrations of fosmidomycin via cDNA microarray and RTPCR. Within the regulated genes identified by microarray were a number of genes encoding enzymes associated with the mediation of reactive oxygen species (ROS). Regulation of a panel of genes implicated in the response of cells to oxidative stress (including genes for catalases, superoxide dismutases, and alkylhydrogen peroxide reductases) was investigated and mild upregulation in some members was observed as a function of fosmidomycin exposure over time. The extent of regulation of these genes was similar to that observed for comparable exposures to kanamycin, but differed significantly from tetracycline. Furthermore, S. typhimurium exposed to sub-inhibitory concentrations of fosmidomycin displayed an increased sensitivity to exogenous H2O2 relative to either untreated controls or kanamycin-treated cells. Our results suggest that endogenous oxidative stress is one consequence of exposures to fosmidomycin, likely through the temporal depletion of intracellular isoprenoids themselves, rather than other mechanisms that have been proposed to facilitate ROS accumulation in bacteria (e.g. cell death processes or the ability of the antibiotic to redox cycle)