We assessed the efficacy and safety of biologic therapy in severe and refractory Peripheral Ulcerative Keratitis (PUK).
Open-label multicenter study of biologic-treated patients with severe PUK ...refractory to conventional immunosuppressive drugs.
We studied 34 patients (44 affected eyes) (24 women/10 men; mean age, 55.26±17.4 years). PUK was associated with a well-defined condition in 29 of them (rheumatoid arthritis n = 20, psoriatic arthritis n = 2, inflammatory bowel disease n = 2, Behçet disease n = 1, granulomatosis with polyangiitis n = 1, microscopic polyangiitis n = 1, systemic lupus erythematosus n = 1 and axial spondyloarthritis n = 1). Besides topical and oral systemic glucocorticoids, patients had received: methylprednisolone pulses n = 9, and conventional immunosuppressive drugs, mainly methotrexate n = 18, and leflunomide n = 7. Eleven patients had required ocular surgery prior to biologic therapy.
Following biologic therapy, baseline main outcomes were compared with those found at 1st week, 1st and 6th months and 1st year.
Efficacy and safety of biologic therapy. Efficacy was analyzed by the assessment of corneal inflammation (corneal thinning, central keratolysis and ocular perforation); other causes of ocular surface inflammation (scleritis, episcleritis); intraocular inflammation (uveitis); visual acuity and glucocorticoid sparing effect.
The first biologic agents used were anti-TNFα drugs (n = 25); adalimumab (n = 16), infliximab (n = 8), etanercept (n = 1), and non-TNFα agents (n = 9); rituximab (n = 7), tocilizumab (n = 1) belimumab (n = 1) and abatacept (n = 1). During the follow-up, switching to a second biologic agent was required in 12 of the 25 (48%) patients treated with anti-TNFα drugs. However, no switching was required in those undergoing biologic therapy different from anti-TNFα agents. The main outcome variables showed a rapid and maintained improvement after a mean follow-up of 23.7 ± 20 months. Major adverse effects were tachyphylaxis, relapsing respiratory infections, supraventricular tachycardia, pulmonary tuberculosis and death, one each.
Biologic therapy is effective and relatively safe in patients with severe and refractory PUK. Non-anti-TNFα agents appear to be effective in these patients.
Summary
Fruit ripening is divided into climacteric and non‐climacteric types depending on the presence or absence of a transient rise in respiration rate and the production of autocatalytic ethylene. ...Melon is ideal for the study of fruit ripening, as both climacteric and non‐climacteric varieties exist. Two introgressions of the non‐climacteric accession
PI
161375, encompassed in the
QTL
s
ETHQB
3.5
and
ETHQV
6.3
, into the non‐climacteric ‘Piel de Sapo’ background are able to induce climacteric ripening independently. We report that the gene underlying
ETHQV
6.3
is
MELO
3C016540
(
Cm
NAC
‐
NOR
), encoding a
NAC
(
N
AM
,
A
TAF
1,2,
C
UC
2) transcription factor that is closely related to the tomato
NOR
(
non‐ripening
) gene.
Cm
NAC
‐
NOR
was functionally validated through the identification of two
TILLING
lines carrying non‐synonymous mutations in the conserved
NAC
domain region. In an otherwise highly climacteric genetic background, both mutations provoked a significant delay in the onset of fruit ripening and in the biosynthesis of ethylene. The
PI
161375 allele of
ETHQV
6.3
is similar to that of climacteric lines of the
cantalupensis
type and, when introgressed into the non‐climacteric ‘Piel de Sapo’, partially restores its climacteric ripening capacity.
Cm
NAC
‐
NOR
is expressed in fruit flesh of both climacteric and non‐climacteric lines, suggesting that the causal mutation may not be acting at the transcriptional level. The use of a comparative genetic approach in a species with both climacteric and non‐climacteric ripening is a powerful strategy to dissect the complex mechanisms regulating the onset of fruit ripening.
Significance Statement
Regulatory mechanisms common to climacteric and non‐climacteric fruit ripening are not fully understood. Melon is a unique model species presenting both climacteric and non‐climacteric types. ETHQV6.3 QTL allele introgressed into a non‐climacteric background partially restores climacteric ripening. We show that ETHQV6.3 is encoded by the NAC‐domain transcription factor MELO3C016540 (CmNAC‐NOR). Mutations in CmNAC‐NOR in a climacteric genetic background delay fruit ripening and biosynthesis of ethylene, confirming its role in this process.
Designing a new astronomical instrument typically challenges the available cameras on the market. In many cases, no camera can fulfill the requirements of the instrument in terms of photon budget, ...speed, and even interfaces with the rest of the instrument. In this situation, the only options are to either downgrade the performance of the instrument or design new cameras from scratch, provided it is possible to identify a compliant detector. The latter is the case of the SPGCams, the cameras developed to be used with the Tunable Magnetograph (TuMag) and the Sunrise Chromospheric Infrared spectroPolarimeter (SCIP) for the
Sunrise iii
mission. SPGCams have been designed, developed, and built entirely in-house by the Solar Physics Group (SPG) at the Instituto de Astrofísica de Andalucía (IAA-CSIC). We report here on the scientific rationale and system engineering requirements set by the two instruments that drove the development, as well as on the technical details and trade-offs used to fulfill the specifications. The cameras were fully verified before the flight, and results from the assembly and verification campaign are presented as well. SPGCams share the design, although some parametric features differentiate the visible cameras (for TuMag) and the IR ones (for SCIP). Even though they were specifically developed for the
Sunrise iii
mission, the robust and careful design makes them suitable for different applications in other astronomical instruments.
Resumo Este artigo analisa o comportamento do setor bancário no ciclo recente de crédito no Brasil (2003-2016), caraterizado pelo boom e a desaceleração, a partir da abordagem pós-keynesiana de ...preferência pela liquidez desenvolvida por Keynes e Cardim de Carvalho e da hipótese de fragilidade financeira de Minsky. Sustenta-se que o comportamento dos bancos e o ciclo de crédito seguiram, grosso modo, o padrão estabelecido por essa teoria. Contudo, a aplicação dessa abordagem à realidade dos bancos no Brasil impõe que se levem em conta especificidades institucionais e macroeconômicas que desempenharam um papel destacado no período analisado, tais como inovações financeiras, spreads elevados, existência de um circuito de overnight e importância dos bancos públicos.
Abstract This paper analyzes the behavior of the banking sector in the recent cycle of credit in Brazil (2003-2016), boom and bust, taking as a starting point, the post-Keynesian liquidity preference approach developed by Keynes and Cardim de Carvalho and Minsky’s financial fragility hypothesis. It argues that the behavior of banks and the credit cycle broadly followed the pattern established by this theory. However, the application of this approach to the reality of banks in Brazil requires taking into account institutional and macroeconomic specificities that played a major role in the analyzed period, such as financial innovations, high spreads, the presence of an overnight circuit, and the importance of state-owned banks.
Sleeve gastrectomy(SG) is a restrictive bariatric surgery technique that was first used as part of restrictive horizontal gastrectomy in the original Scopinaro type biliopancreatic diversion. Its ...good results as a single technique have led to a rise in its use, and it is currently the second most performed technique worldwide. SG achieves clearly better results than other restrictive techniques and is comparable in some aspects to the Roux-en-Y gastric bypass, the current gold standard in bariatric surgery. These benefits have been associated with different pathophysiologic mechanisms unrelated to weight loss such as increased gastric emptying and intestinal transit, and activation of hormonal mechanisms such as increased GLP-1 hormone and decreased ghrelin. The aim of this review was to highlight the salient aspects of SG regarding its historical evolution, pathophysiologic mechanisms, main results, clinical applications and perioperative complications.
The objective of this study was to identify molecular alterations in the human blood serum related to bipolar disorder, using nuclear magnetic resonance (NMR) spectroscopy and chemometrics.
...Metabolomic profiling, employing
H-NMR,
H-NMR T
-edited, and 2D-NMR spectroscopy and chemometrics of human blood serum samples from patients with bipolar disorder (n = 26) compared with healthy volunteers (n = 50) was performed.
The investigated groups presented distinct metabolic profiles, in which the main differential metabolites found in the serum sample of bipolar disorder patients compared with those from controls were lipids, lipid metabolism-related molecules (choline, myo-inositol), and some amino acids (N-acetyl-L-phenyl alanine, N-acetyl-L-aspartyl-L-glutamic acid, L-glutamine). In addition, amygdalin, α-ketoglutaric acid, and lipoamide, among other compounds, were also present or were significantly altered in the serum of bipolar disorder patients. The data presented herein suggest that some of these metabolites differentially distributed between the groups studied may be directly related to the bipolar disorder pathophysiology.
The strategy employed here showed significant potential for exploring pathophysiological features and molecular pathways involved in bipolar disorder. Thus, our findings may contribute to pave the way for future studies aiming at identifying important potential biomarkers for bipolar disorder diagnosis or progression follow-up.
The objective of this study was to identify molecular alterations in the human blood serum related to bipolar disorder, using nuclear magnetic resonance (NMR) spectroscopy and chemometrics. ...Metabolomic profiling, employing 1H-NMR, 1H-NMR T2-edited, and 2D-NMR spectroscopy and chemometrics of human blood serum samples from patients with bipolar disorder (n = 26) compared with healthy volunteers (n = 50) was performed. The investigated groups presented distinct metabolic profiles, in which the main differential metabolites found in the serum sample of bipolar disorder patients compared with those from controls were lipids, lipid metabolism-related molecules (choline, myo-inositol), and some amino acids (N-acetyl-l-phenyl alanine, N-acetyl-l-aspartyl-l-glutamic acid, l-glutamine). In addition, amygdalin, α-ketoglutaric acid, and lipoamide, among other compounds, were also present or were significantly altered in the serum of bipolar disorder patients. The data presented herein suggest that some of these metabolites differentially distributed between the groups studied may be directly related to the bipolar disorder pathophysiology. The strategy employed here showed significant potential for exploring pathophysiological features and molecular pathways involved in bipolar disorder. Thus, our findings may contribute to pave the way for future studies aiming at identifying important potential biomarkers for bipolar disorder diagnosis or progression follow-up.
A set of near-isogenic lines (NILs) of melon (
Cucumis melo L.) was used to test the relationship between the climacteric pattern and postharvest disorders at harvest and after 30 days at 8
°C. The ...NILs contained different chromosome introgressions in the linkage group III from the non-climacteric exotic Korean accession
PI 161375 transferred into the genetic background of the non-climacteric Spanish cultivar ‘Piel de Sapo’ (PS). A quantitative trait locus (QTL) in this linkage group induced climacteric behavior in eight NILs accompanied by a peak of ethylene production and fruit dehiscence to different degrees. The cultivar ‘Nicolás’ and one NIL showed a non-climacteric pattern of respiration rate and ethylene production. The climacteric NILs were used to test the relationship between this pattern and postharvest disorders. The reference climacteric lines ‘Fado’ and ‘Védrantais’ were more sensitive to CI and associated Cladosporium rot than the NILs or PS. In general, a more intense climacteric behavior was accompanied by fruit dehiscence, and higher total losses and greater skin scald after storage, than in PS. A higher incidence of chilling injury (CI) in the climacteric NILs was found compared with the non-climacteric ones, although with exceptions (one NIL for CI in the form of scald; the same NIL and one more for pitting). The climacteric onset and netting scald were not related, and CI in the form of skin spots was only found in climacteric NILs and was positively correlated with the maximum peak of ethylene production. Some climacteric NILs did not follow the rule of a higher susceptibility to other disorders and decay after storage compared with PS, such as for example in fruit over-ripening (detected externally or internally), Cladosporium rot at the peduncle and Alternaria rot. Mealiness was independent of climacteric behavior. Three climacteric NILs obtained better flavor scores after storage than PS, although the maximum peak of ethylene production was positively correlated with off-flavor. Genotypic correlation between disorder data and the physiological data of climacteric fruit revealed positive (flavor index) or negative postharvest consequences (skin injuries, rots or off-flavors). At least one QTL can be assigned to most of the quality traits analyzed.
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