Complete response of skull base inverted papilloma to chemotherapy: Case report.

BackgroundInverted papilloma (IP) is the most common benign sinonasal neoplasm. Endoscopic techniques, improved understanding of pathophysiology, and novel surgical approaches have allowed rhinologists to treat IPs more effectively, with surgery being the mainstay of therapy. Frontal sinus IP poses a challenge for surgical therapy due to complex anatomy and potentially difficult surgical access.ObjectivesWe reported a unique case of a massive frontal sinus IP that presented with intracranial and orbital extension, with near resolution after chemotherapy.MethodsA retrospective case review of a patient with a frontal sinus IP treated at a tertiary academic medical center.ResultsA 75-year-old male patient presented with nasal obstruction, purulent nasal discharge, and a growing left supraorbital mass. Endoscopy demonstrated a mass that filled both frontal and ethmoid sinuses, with orbital invasion. There also was substantial erosion of the posterior table, which measured 1.73 × 1.40 cm. A biopsy specimen demonstrated IP with carcinoma in situ. The patient was deemed unresectable on initial evaluation and, subsequently, underwent chemotherapy (carboplatin and paclitaxel). The tumor had a dramatic response to chemotherapy, and the patient elected for definitive surgery to remove any residual disease. During surgery, only a small focus of IP was found along the superior wall of the frontal sinus. No tumor was found elsewhere, including at the site of skull base erosion. The final pathology was IP without carcinoma in situ or dysplasia.ConclusionThis was the first reported case of chemotherapeutic "debulking" of IP, which facilitated surgical resection, despite substantial intracranial and orbital involvement. Although nearly all IPs can be treated surgically, rare cases, such as unresectable tumors, may benefit from systemic chemotherapy

Millimagnitude Photometry for Transiting Extrasolar Planetary Candidates III: Accurate Radius and Period for OGLE-TR-111-b

We present accurate V-band photometry for a planetary transit of OGLE-TR-111 acquired with VIMOS at the ESO Very Large Telescope. The measurement of this transit allows to refine the planetary radius, obtaining R_p= 1.01 +/- 0.06 R_J. Given the mass of M_p = 0.53 M_J previously measured from radial velocities, we confirm that the density is rho_p= 0.6 +/- 0.2 g/cm^3. We also revise the ephemeris for OGLE-TR-111-b, obtaining an accurate orbital period P= 4.014484 +/- 0.000014 days, and predicting that the next observable transits would occur around December 2006, and after that only in mid-2008. Even though this period is different from previously published values, we cannot yet rule out a constant period.Comment: 16 pages (including figures), 5 figures, 1 table. Accepted for publication in the Astrophysical Journa

Loop 1 modulates the fidelity of DNA polymerase λ

Differences in the substrate specificity of mammalian family X DNA polymerases are proposed to partly depend on a loop (loop 1) upstream of the polymerase active site. To examine if this is the case in DNA polymerase λ (pol λ), here we characterize a variant of the human polymerase in which nine residues of loop 1 are replaced with four residues from the equivalent position in pol β. Crystal structures of the mutant enzyme bound to gapped DNA with and without a correct dNTP reveal that the change in loop 1 does not affect the overall structure of the protein. Consistent with these structural data, the mutant enzyme has relatively normal catalytic efficiency for correct incorporation, and it efficiently participates in non-homologous end joining of double-strand DNA breaks. However, DNA junctions recovered from end-joining reactions are more diverse than normal, and the mutant enzyme is substantially less accurate than wild-type pol λ in three different biochemical assays. Comparisons of the binary and ternary complex crystal structures of mutant and wild-type pol λ suggest that loop 1 modulates pol λ’s fidelity by controlling dNTP-induced movements of the template strand and the primer-terminal 3′-OH as the enzyme transitions from an inactive to an active conformation

T-cell epitopes of the major peach allergen, Pru p 3: Identification and differential T-cell response of peach-allergic and non-allergic subjects

Lipid transfer proteins (LTPs), particularly peach Pru p 3, are the most relevant plant food allergens in the South of Europe, and, therefore, their allergic properties have been extensively studied. However, neither T-cell epitopes nor their effect on the patients’ T-cell response has been investigated in any member of the LTP panallergen family. The objective of the present study was to map the major T-cell epitopes of Pru p 3, as well as to evaluate their induced T-cell response in peach-allergic versus control subjects. Thus, peripheral blood mononuclear cells (PBMCs) from 18 peach-allergic patients and Pru p 3-specific T-cell lines (TCLs) from 9 of them were cultured with Pru p 3 and with a panel of 17 derived peptides (10-mer overlapping in 5 amino acids representing the full sequence of Pru p 3). Proliferation in 5-day assays was carried out via tritiated-thymidine incorporation, while IL4 and IFNγ production was assessed via sandwich enzyme-linked immunosorbent tests (ELISA) of TCL culture supernatants. The results were compared to those obtained from 10 non-peach allergic control volunteers. Two consecutive peptides showed the highest activation capacity. About 74% of PBMCs and TCLs recognized them, forming a single T-epitope: Pru p 365–80. Additionally, other specific T-cell epitopes were observed. Pru p 325–35 was detected by more than 60% of TCLs from peach-allergic patients, and Pru p 345–55 only activated PBMCs from control subjects. Interestingly, TCLs from patients were associated with a Th2-type, whereas control TCLs presented a Th1-type cytokine response. The major immunogenic T-cell epitope identified in Pru p 3, Pru p 365–80, is a good candidate to develop new vaccines for hypersensitivity reactions associated with LTP allergens from Rosaceae fruits

Climate change and the kidney

The worldwide increase in temperature has resulted in a marked increase in heat waves (heat extremes) that carries a markedly increased risk for morbidity and mortality. The kidney has a unique role not only in protecting the host from heat and dehydration but also is an important site of heat-associated disease. Here we review the potential impact of global warming and heat extremes on kidney diseases. High temperatures can result in increased core temperatures, dehydration, and blood hyperosmolality. Heatstroke (both clinical and subclinical whole-body hyperthermia) may have a major role in causing both acute kidney disease, leading to increased risk of acute kidney injury from rhabdomyolysis, or heat-induced inflammatory injury to the kidney. Recurrent heat and dehydration can result in chronic kidney disease (CKD) in animals and theoretically plays a role in epidemics of CKD developing in hot regions of the world where workers are exposed to extreme heat. Heat stress and dehydration also has a role in kidney stone formation, and poor hydration habits may increase the risk for recurrent urinary tract infections. The resultant social and economic consequences include disability and loss of productivity and employment. Given the rise in world temperatures, there is a major need to better understand how heat stress can induce kidney disease, how best to provide adequate hydration, and ways to reduce the negative effects of chronic heat exposure.Published versio

Determination of heat wave definition temperatures in Spain at an isoclimatic level: time trend of heat wave duration and intensity across the decade 2009–2018

Background: In line with WHO guidelines for the implementation of public health prevention plans targeted at the impacts of high temperatures, a heat wave defnition temperature (Tthreshold) was calculated for 182 so called “isoclimatic zones” (IZ) in Spain. As the dependent variable for determining this Tthreshold, we analysed daily all-cause mortality data (ICD-10: A00-R99) for each IZ across the period 2009–2018. The independent variable used was the mean value of the maximum daily temperature of the summer months recorded at meteorological observatories in each IZ. We used Box–Jenkins models to ascertain mortality anomalies, and scatterplots to link these anomalies to the temperatures at which they occurred, thereby determining the Tthreshold for each IZ. We then calculated how many heat waves had occurred in each IZ, as well as their intensity, and analysed their time trend over this period. Results: The results showed that in 52.5% of the IZ, the percentile of the maximum temperatures series of the summer months to which Tthreshold corresponded was below the 95th percentile of the meteorological heat wave defnition in Spain: indeed, it only coincided in 30.7% of cases. The geographical distribution of these percentiles displayed great heterogeneity as a consequence of the local factors that infuence the temperature–mortality relationship. The trend in the number of heat waves analysed indicated an overall increase in Spain at a rate of 3.9 heat waves per decade, and a similar rise in mean annual intensity of 9.5 °C/decade. These time-trend values were higher than those yielded by analysing the trend in meteorological heat waves based on the 95th percentile. Conclusions: The results obtained in this study indicate the need to use a heat wave defnition based on epidemiological temperature–mortality studies, rather than on values based on meteorological percentiles. This could be minimising estimated health impacts in analyses of future impacts attributable to heat.Acknowledgements and funding The authors would like to express their gratitude for the following grants from the Carlos III Institute of Health (Instituto de Salud Carlos III/ISCIII) for the ENPY 304/20, and ENPY 436/21 projects.S

Coenzyme Q10 and Cardiovascular Diseases

Coenzyme Q10 (CoQ10), which plays a key role in the electron transport chain by providing an adequate, efficient supply of energy, has another relevant function as an antioxidant, acting in mitochondria, other cell compartments, and plasma lipoproteins. CoQ10 deficiency is present in chronic and age-related diseases. In particular, in cardiovascular diseases (CVDs), there is a reduced bioavailability of CoQ10 since statins, one of the most common lipid-lowering drugs, inhibit the common pathway shared by CoQ10 endogenous biosynthesis and cholesterol biosynthesis. Different clinical trials have analyzed the effect of CoQ10 supplementation as a treatment to ameliorate these deficiencies in the context of CVDs. In this review, we focus on recent advances in CoQ10 supplementation and the clinical implications in the reduction of cardiovascular risk factors (such as lipid and lipoprotein levels, blood pressure, or endothelial function) as well as in a therapeutic approach for the reduction of the clinical complications of CVD

Millimagnitude Photometry for Transiting Extrasolar Planetary Candidates IV: The Puzzle of the Extremely Red OGLE-TR-82 Primary Solved

We present precise new V, I, and K-band photometry for the planetary transit candidate star OGLE-TR-82. Good seeing V-band images acquired with VIMOS instrument at ESO VLT allowed us to measure V=20.6+-0.03 mag star in spite of the presence of a brighter neighbour about 1" away. This faint magnitude answers the question why it has not been possible to measure radial velocities for this object. One transit of this star has been observed with GMOS-S instrument of GEMINI-South telescope in i and g-bands. The measurement of the transit allows us to verify that this is not a false positive, to confirm the transit amplitude measured by OGLE, and to improve the ephemeris. The transit is well defined in i-band light curve, with a depth of A_i=0.034 mag. It is however, less well defined, but deeper (A_g=0.1 mag) in the g-band, in which the star is significantly fainter. The near-infrared photometry obtained with SofI array at the ESO-NTT yields K=12.2+-0.1 and V-K=8.4+-0.1, so red that it is unlike any other transit candidate studied before. Due to the extreme nature of this object, we have not yet been able to measure velocities for this star, but based on the new data we consider two different possible configurations:(1) a nearby M7V star, or (2) a blend with a very reddened distant red giant. The nearby M7V dwarf hypothesis would give a radius for the companion of R_p=0.3+-0.1 R_J, i.e. the size of Neptune. Quantitative analysis of near-IR spectroscopy finally shows that OGLE-TR-82 is a distant, reddened metal poor early K giant. This result is confirmed by direct comparison with stellar templates that gives the best match for a K3III star. Therefore, we discard the planetary nature of the companion. Based on all the new data, we conclude that this system is a main-sequence binary blended with a background red giant.Comment: 26 pages, 9 figures, ApJ accepte