Real-world persistence of initial targeted therapy strategy in monotherapy versus combination therapy in patients with chronic inflammatory arthritis.

OBJECTIVE: The persistence of biologic (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs(DMARDs) in monotherapy versus in combination with conventional synthetic (cs) DMARDs is still a controversial topic in rheumatic diseases. To clarify this issue, the retention of the initial treatment strategy of b/tsDMARD in combination with csDMARD versus monotherapy in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients under real-life conditions was evaluated. Factors associated with maintenance of the initial strategy were analysed. METHODS: Nested cohort study within the Spanish BIOBADASER III registry. Bivariate comparisons and multivariate Cox proportional hazards models were used for the analyses. RESULTS: A total of 2521 patients were included in the study. In the multivariate model, the initial strategy of combination therapy was associated with shorter persistence in patients with RA (hazard ratio [HR] 1.58;95% confidence interval [CI] 1.00-2.50; p = .049), PsA (HR 2.48; 95% CI 1.65-3.72) and AS (HR 16.77; 95% CI 7.37-38.16; p < .001), regardless of sex, time of disease progression, baseline disease activity, glucocorticoid use or type of b/tsDMARD. Overall, the combination strategy was associated with an increased incidence of adverse events (incidence rate ratio [IRR] 1.13; 95% CI 1.05-1.21). CONCLUSIONS: In this real-life study, the strategy of combining a b/tsDMARD with a csDMARD is associated with lower persistence and worse safety profile compared to monotherapy in RA and especially in PsA and AS, suggesting that combination therapy should be rethought as first choice in RA patients, but especially in PsA and AS patients.

"Pray Observe How Time Slips By:" Collaborators, Assistants, and the Background Dynamics in the Publication of Darwin's Cirripedia Project.

This study investigates nineteenth century natural history practices through the lens of the Actor-Network Theory, which posits that scientific practice is shaped by an intricate network of interactions between human and non-human actors. At the core of this research is the analysis of correspondence between Charles Darwin and his collaborators during the Cirripedia Project, which unveils a complex landscape of negotiations with illustrators, funders, specimen owners, and translators, among other stakeholders and interested parties. The study goes beyond the final outcomes of scientific research, delving into behind-the-scenes interactions, and hidden constructions, shedding light on the complex dynamics and actors that conventional scientific narratives often overlook. In general, this approach provides a detailed and insightful view of the underlying processes of nineteenth-century scientific practice, underscoring the importance of epistolary correspondence as a central element in producing scientific knowledge at the time, and in particular it reveals to us how much Darwin was himself involved in the production of his famous work on barnacles. By emphasizing the intricacies of research, this study enriches our understanding of Darwin's work as well as natural history practices in the 19th century, highlighting the complexity and diversity of actors and agents involved in shaping scientific knowledge.

Molecular Basis of the Schuurs-Hoeijmakers Syndrome: What We Know about the Gene and the PACS-1 Protein and Novel Therapeutic Approaches.

The Schuurs−Hoeijmakers syndrome (SHMS) or PACS1 Neurodevelopment Disorder (PACS1-NDD) is a rare autosomal dominant disease caused by mutations in the PACS1 gene. To date, only 87 patients have been reported and, surprisingly, most of them carry the same variant (c.607C>T; p.R203W). The most relevant clinical features of the syndrome include neurodevelopment delay, seizures or a recognizable facial phenotype. Moreover, some of these characteristics overlap with other syndromes, such as the PACS2 or Wdr37 syndromes. The encoded protein phosphofurin acid cluster sorting 1 (PACS-1) is able to bind to different client proteins and direct them to their subcellular final locations. Therefore, although its main function is protein trafficking, it could perform other roles related to its client proteins. In patients with PACS1-NDD, a gain-of-function or a dominant negative mechanism for the mutated protein has been suggested. This, together with the fact that most of the patients carry the same genetic variant, makes it a good candidate for novel therapeutic approaches directed to decreasing the toxic effect of the mutated protein. Some of these strategies include the use of antisense oligonucleotides (ASOs) or targeting of its client proteins.

Emergence of linezolid-resistance in vancomycin-resistant Enterococcus faecium ST117 associated with increased linezolid-consumption.

OBJECTIVE: We aim to describe the epidemiological, clinical and microbiological characteristics of the linezolid- and vancomycin- resistant Enterococcus faecium (LVRE) in a tertiary care hospital in Germany. METHODS: We conducted a retrospective analysis of 196 LVRE cases observed from 1st January 2012 to 31th December 2018. Patients' medical charts were reviewed and available LVRE (n = 102) were subjected to whole-genome-sequencing. Antibiotic consumption was measured in defined daily dose (DDD)/100 bed-days (BD). RESULTS: The prevalence of LVRE isolates among VRE was 6.3 % in 2018. Most patients had an onco-hematological disease (134/196, 68.4 %). From 2012-2018 an increase of +356.7 % of linezolid defined daily dose/100 bed-days was observed. In 71.4 % (90/126, 70 missing values) of the patients, linezolid was prescribed in the previous 6 months. The median exposure to linezolid was 15 days (Interquartile, IQR 9-23). 42/196 (21.4 %) patients had an LVRE-related infection with an overall 30-day mortality rate of 33 %. In 121/196 (61.7 %) patients, linezolid-susceptible VREfm were isolated before LVRE, suggesting secondary acquisition of linezolid resistance. Genetic analysis revealed that most isolates belonged to ST117 (64/102 available isolates, 62.7 %). The G2576T 23S rDNA mutation was identified as the most common resistance mechanism (96/102, 94.1 %). poxtA was identified in two isolates, while cfr, and optrA were not detected. CONCLUSIONS: Incidence of LVRE related to 23S rDNA mutations is rising and probably associated with antibiotic consumption. Restrictions in the use of linezolid may be needed in order to retain therapeutic options in VRE.

Monocenter study on epidemiology, outcomes, and risk factors of infections in recipients of 166 allogeneic stem cell transplantations during 1 year.

OBJECTIVES: During allogeneic hematopoietic stem cell transplantation (allo-SCT), infections significantly contribute to morbidity and mortality. A monocentric prospective analysis was performed to assess epidemiology, risk factors, and outcomes of infections during the peri-transplant period. METHODS: Data were recorded prospectively using a predefined questionnaire. RESULTS: In 2015, 163 consecutive patients, 37.4% female, median age 59 (range 18-79) years received 166 allo-SCT. Median duration of leukopenia <109 /L was 14.5 days (range 4-43 days). Fever of unknown origin (FUO) occurred in 118/166 patients (71.1%). Severe sepsis developed in 95, and septic shock developed in 26 patients. Intensive diagnostic workup helped to identify causative microorganisms only in a small number of infectious courses. All but 13 patients needed antibiotic therapy, each according to the standard operating procedures of the department. Cumulative incidence of death by infection after 1 year was 16.6% (95% CI: 11.3-22.7). The only risk factor for FUO in neutropenia was duration of neutropenia

Evaluating Face2Gene as a Tool to Identify Cornelia de Lange Syndrome by Facial Phenotypes.

Characteristic or classic phenotype of Cornelia de Lange syndrome (CdLS) is associated with a recognisable facial pattern. However, the heterogeneity in causal genes and the presence of overlapping syndromes have made it increasingly difficult to diagnose only by clinical features. DeepGestalt technology, and its app Face2Gene, is having a growing impact on the diagnosis and management of genetic diseases by analysing the features of affected individuals. Here, we performed a phenotypic study on a cohort of 49 individuals harbouring causative variants in known CdLS genes in order to evaluate Face2Gene utility and sensitivity in the clinical diagnosis of CdLS. Based on the profile images of patients, a diagnosis of CdLS was within the top five predicted syndromes for 97.9% of our cases and even listed as first prediction for 83.7%. The age of patients did not seem to affect the prediction accuracy, whereas our results indicate a correlation between the clinical score and affected genes. Furthermore, each gene presents a different pattern recognition that may be used to develop new neural networks with the goal of separating different genetic subtypes in CdLS. Overall, we conclude that computer-assisted image analysis based on deep learning could support the clinical diagnosis of CdLS.

More Than One HMG-CoA Lyase: The Classical Mitochondrial Enzyme Plus the Peroxisomal and the Cytosolic Ones.

There are three human enzymes with HMG-CoA lyase activity that are able to synthesize ketone bodies in different subcellular compartments. The mitochondrial HMG-CoA lyase was the first to be described, and catalyzes the cleavage of 3-hydroxy-3-methylglutaryl CoA to acetoacetate and acetyl-CoA, the common final step in ketogenesis and leucine catabolism. This protein is mainly expressed in the liver and its function is metabolic, since it produces ketone bodies as energetic fuels when glucose levels are low. Another isoform is encoded by the same gene for the mitochondrial HMG-CoA lyase (HMGCL), but it is located in peroxisomes. The last HMG-CoA lyase to be described is encoded by a different gene, HMGCLL1, and is located in the cytosolic side of the endoplasmic reticulum membrane. Some activity assays and tissue distribution of this enzyme have shown the brain and lung as key tissues for studying its function. Although the roles of the peroxisomal and cytosolic HMG-CoA lyases remain unknown, recent studies highlight the role of ketone bodies in metabolic remodeling, homeostasis, and signaling, providing new insights into the molecular and cellular function of these enzymes.

Efficacy of introducing a checklist to reduce central venous line associated bloodstream infections in the ICU caring for adult patients.

BACKGROUND: Central line-associated bloodstream infections (CLABSI) are a major source of sepsis in modern intensive care medicine. Some years ago bundle interventions have been introduced to reduce CLABSI. The use of checklists may be an additional tool to improve the effect of these bundles even in highly specialized institutions. In this study we investigate if the introduction of a checklist reduces the frequency of CLABSI. METHODS: During the study period from October 2011 to September 2012, we investigated the effect of implementing a checklist for the placement of central venous lines (CVL). Patients were allocated either to the checklist group or to the control group, roughly in a 1:2 ratio. The frequency of CLABSI was compared between the two groups. RESULTS: During the study period 4416 CVL were inserted; 1518 in the checklist group and 2898 in the control group. The use of the checklist during CVL placement resulted in a lower CLABSI frequency. The incidence in the checklist group was 3.8 per 1000 catheter days as compared to 5.9 per 1000 catheter days in the control group (IRR = 0.57; p = 0.001). The use of the checklist also reduced the frequency of catheter colonisation significantly, 36.3 per 1000 catheter days in the checklist group vs 21.2 per 1000 catheter days in the control group, respectively (IRR = 0.58; p < 0.001). CONCLUSION: The introduction of a checklist to improve the adherence to hygiene standards while placement of central venous lines reduced the frequency of infections significantly.

Neonatal hyperglycemia induces cell death in the rat brain.

Several studies have examined neonatal diabetes, a rare disease characterized by hyperglycemia and low insulin levels that is usually diagnosed in the first 6 month of life. Recently, the effects of diabetes on the brain have received considerable attention. In addition, hyperglycemia may perturb brain function and might be associated with neuronal death in adult rats. However, few studies have investigated the damaging effects of neonatal hyperglycemia on the rat brain during central nervous system (CNS) development, particularly the mechanisms involved in the disease. Thus, in the present work, we investigated whether neonatal hyperglycemia induced by streptozotocin (STZ) promoted cell death and altered the levels of proteins involved in survival/death pathways in the rat brain. Cell death was assessed using FluoroJade C (FJC) staining and the expression of the p38 mitogen-activated protein kinase (p38), phosphorylated-c-Jun amino-terminal kinase (p-JNK), c-Jun amino-terminal kinase (JNK), protein kinase B (Akt), phosphorylated-protein kinase B (p-Akt), glycogen synthase kinase-3ß (Gsk3ß), B-cell lymphoma 2 (Bcl2) and Bcl2-associated X protein (Bax) protein were measured by Western blotting. The main results of this study showed that the metabolic alterations observed in diabetic rats (hyperglycemia and hypoinsulinemia) increased p38 expression and decreased p-Akt expression, suggesting that cell survival was altered and cell death was induced, which was confirmed by FJC staining. Therefore, the metabolic conditions observed during neonatal hyperglycemia may contribute to the harmful effect of diabetes on the CNS in a crucial phase of postnatal neuronal development.

Genetic and biochemical characterization of HMB-1, a novel subclass B1 metallo-ß-lactamase found in a Pseudomonas aeruginosa clinical isolate.

Objectives: To characterize a novel subclass B1 metallo-ß-lactamase (MBL) found in an MDR Pseudomonas aeruginosa clinical isolate. Methods: The isolate P. aeruginosa NRZ-03096 was recovered in 2012 from an anal swab from a patient hospitalized in Northern Germany and showed high MICs of carbapenems. MBL production was analysed by several phenotypic tests. Genetic characterization of the novel bla gene and MLST was performed by WGS. The novel bla gene was expressed in Escherichia coli TOP10 and the enzyme was subjected to biochemical characterization to determine the kinetic parameters K m and k cat . Results: P. aeruginosa NRZ-03096 was resistant to all tested ß-lactams and showed an MBL phenotype. Shotgun cloning experiments yielded a clone producing a novel subclass B1 enzyme with only 74.3% identity to the next nearest relative, KHM-1. The novel MBL was named HMB-1 (for Hamburg MBL). Analysis of WGS data showed that the bla HMB-1 gene was chromosomally located as part of a Tn 3 family transposon that was named Tn 6345 . Expression of bla HMB-1 in E. coli TOP10 led to increased resistance to ß-lactams. Determination of K m and k cat revealed that HMB-1 had different hydrolytic characteristics compared with KHM-1, with lower hydrolytic rates for cephalosporins and a higher rate for imipenem. Conclusions: The identification of HMB-1 further underlines the ongoing spread and diversification of carbapenemases in Gram-negative human pathogens and especially in P. aeruginosa .

Emergence of ceftazidime/avibactam non-susceptibility in an MDR Klebsiella pneumoniae isolate.

Background: Avibactam is a novel broad-range ß-lactamase inhibitor active against Ambler class A (including ESBL and KPC) and some Ambler class C and D (e.g. OXA-48) enzymes. We here report on the emergence of ceftazidime/avibactam resistance in clinical, multiresistant, OXA-48 and CTX-M-14-producing Klebsiella pneumoniae isolate DT12 during ceftazidime/avibactam treatment. Methods and results: Comparative whole-genome sequence analysis identified two SNPs in the CTX-M-14-encoding gene leading to two amino acid changes (P170S and T264I). Compared with WT CTX-M-14, expression of the CTX-M-14Δ170Δ264 isoform in Escherichia coli led to a >64- and 16-fold increase in ceftazidime and ceftazidime/avibactam MICs, respectively, functionally linking the observed SNPs and elevated MICs. The mutated CTX-M-14 isoform exhibited augmented ceftazidime hydrolytic activity, which was a reasonable cause for impaired susceptibility to avibactam inhibition. The P170S exchange in CTX-M-14 was found in association with elevated ceftazidime/avibactam MICs for independent K. pneumoniae isolates, but was not sufficient for full resistance. Apparently, additional CTX-M-independent mechanisms contribute to ceftazidime/avibactam resistance in K. pneumoniae DT12. Conclusions: This study on the molecular basis of ceftazidime/avibactam resistance in clinical K. pneumoniae emerging in vivo underscores the need for continuous monitoring of ceftazidime/avibactam susceptibility during therapy. Despite sustained inhibition of OXA-48, rapid development of CTX-M-14 isoforms exhibiting augmented ceftazidime hydrolytic activity may limit the usefulness of ceftazidime/avibactam monotherapies in infections caused by isolates carrying blaCTX-M-14 and blaOXA-48.

Effect of Free and Nanoencapsulated Copaiba Oil on Monocrotaline-induced Pulmonary Arterial Hypertension.

Copaiba oil comes from an Amazonian tree and has been used as an alternative medicine in Brazil. However, it has not been investigated yet in the treatment of cardiovascular diseases. This study was designed to test whether copaiba oil or nanocapsules containing this oil could modulate monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). Male Wistar rats (170 ± 20 g) received oil or nanocapsules containing this oil (400 mg/kg) by gavage daily for 1 week. At the end of this period, a single injection of MCT (60 mg/kg i.p.) was administered and measurements were performed after 3 weeks. The animals were divided into 6 groups: control, copaiba oil, nanocapsules with copaiba oil, MCT, oil + MCT, and nanocapsules + MCT. Afterward, echocardiographic assessments were performed, and rats were killed to collect hearts for morphometry and oxidative stress. MCT promoted a significant increase in pulmonary vascular resistance, right ventricle (RV) hypertrophy, and RV oxidative stress. Both oil and copaiba nanocapsules significantly reduced RV hypertrophy and oxidative stress. Pulmonary vascular resistance was reduced by copaiba oil in natura but not by nanocapsules. In conclusion, copaiba oil seems to offer protection against MCT-induced PAH. Our preliminary results suggest that copaiba oil may be an important adjuvant treatment for PAH.

NP-59 test for preoperative localization of primary hyperaldosteronism.

PURPOSE: Adrenal venous sampling is generally considered the gold standard to identify unilateral hormone production in cases of primary hyperaldosteronism. The aim of this study is to evaluate whether the iodine-131-6-ß-iodomethyl-19-norcholesterol (NP-59) test may represent an alternative in selected cases. METHODS: Patients submitted to laparoscopic adrenalectomy for suspected primary hyperaldosteronism (n = 27) were retrospectively reviewed. When nuclear medicine tests were preoperatively performed, their results were compared with the histopathologic findings and clinical improvement. RESULTS: Nuclear medicine tests were realized in 13 patients. In 11 (84.6%), a planar anterior and posterior NP-59 scintigraphy was performed and a SPECT/TC in two (15.4%). Scintigraphy indicated a preoperative lateralization in 12 out of 13 patients (92.3%). When the value of NP-59 tests was based on pathologic results, it showed a sensitivity of 90.9% and a positive predictive value of 83.3%. When the nuclear medicine test's performance was based on postoperative blood pressure control, both sensitivity and positive predictive value were 91.6%. CONCLUSIONS: Nuclear medicine tests represent a useful tool in the preoperative localisation of primary hyperaldosteronism with a high sensitivity and positive predictive value. In patients with contraindications to adrenal venous sampling like contrast allergies, or when it is inconclusive, scintigraphy can represent a useful and non-invasive alternative.

Molecular analysis of the ramRA locus in clinical Klebsiella pneumoniae isolates with reduced susceptibility to tigecycline.

Mutations in ramR, a negative regulator of ramA which stimulates transcription of acrA/-B encoding the multidrug efflux pump AcrAB-TolC, were recently shown to result in reduced susceptibility to tigecycline in Klebsiella pneumoniae. We analysed six non-duplicate K. pneumoniae isolates with elevated MICs to tigecycline. All isolates showed transcriptional up-regulation of ramA and acrB as demonstrated by Northern blot and quantitative real-time PCR. Sequencing of the ramR gene revealed deletions in five of the isolates and a premature stop codon in one isolate. Transformation of the wild-type ramR gene but not of any of the detected mutant ramR genes into a ramR-mutant K. pneumoniae strain restored tigecycline susceptibility and repressed ramA and acrB transcription to wild type levels. Thus, our study confirms the role of inactivating mutations in the ramR gene in tigecycline resistance.

Thyroid hormones improve cardiac function and decrease expression of pro-apoptotic proteins in the heart of rats 14 days after infarction.

Apoptosis is a key process associated with pathological cardiac remodelling in early-phase post-myocardial infarction. In this context, several studies have demonstrated an anti-apoptotic effect of thyroid hormones (TH). The aim of this study was to evaluate the effects of TH on the expression of proteins associated with the apoptotic process 14 days after infarction. Male Wistar rats (300-350 g) (n = 8/group) were divided into four groups: Sham-operated (SHAM), infarcted (AMI), sham-operated + TH (SHAMT) and infarcted + TH (AMIT). For 12 days, the animals received T3 and T4 [2 and 8 µg/(100 g day)] by gavage. After this, the rats were submitted to haemodynamic and echocardiographic analysis, and then were sacrificed and the heart tissue was collected for molecular analysis. Statistical analyses included two-way ANOVA with Student-Newman-Keuls post test. Ethics Committee number: 23262. TH administration prevented the loss of ventricular wall thickness and improved cardiac function in the infarcted rats 14 days after the injury. AMI rats presented an increase in the pro-apoptotic proteins p53 and JNK. The hormonal treatment prevented this increase in AMIT rats. In addition, TH administration decreased the Bax:Bcl-2 ratio in the infarcted rats. TH administration improved cardiac functional parameters, and decreased the expression of pro-apoptotic proteins 14 days after myocardial infarction.

Extended spectrum beta-lactamase producing Enterobacteriaceae causing bloodstream infections in rural Ghana, 2007-2012.

BACKGROUND: High prevalence of Extended Spectrum Beta-Lactamase (ESBL) producing Enterobacteriaceae threatens treatment options for invasive bloodstream infections in sub-Saharan Africa. OBJECTIVES: To explore the frequency and genotype distribution of ESBL producing Enterobacteriaceae causing bloodstream infections in a primary health care setting in rural Ghana. METHODS: Blood cultures from all patients with fever ≥38°C within 24h after admission (community-acquired) and from all neonates with suspected neonatal sepsis (hospital-acquired) were obtained. ESBL-producing isolates were characterized by combined disc test and by amplifying the blaCTX-M, blaTEM and blaSHV genes. Multilocus sequence typing (MLST) was performed for all ESBL-producing Klebsiella pneumoniae and Escherichia coli isolates, and all K. pneumoniae isolates were differentiated by pulsed-field gel electrophoresis (PFGE). RESULTS: Among 426 Enterobacteriaceae isolated from blood cultures, non-typhoid Salmonella (n=215, 50.8%), S. Typhi (n=110, 26.0%), E. coli (n=50, 11.8%) and K. pneumoniae (n=41, 9.7%) were the most frequent. ESBL-producing isolates were restricted to the CTX-M-15 genotype and the species K. pneumoniae (n=34, 82.9%), Enterobacter cloacae complex (n=2, 66.7%) and E. coli (n=5, 10.0%). The rates of ESBL-producers in K. pneumoniae were 55.6% and 90.6% in community-acquired and neonatal bloodstream infections, respectively. MLST and PFGE analysis identified four outbreak clusters among neonates. CONCLUSIONS: Considering the rural primary health care study setting, the high proportion of ESBL-producing Klebsiella pneumoniae is worrisome and might be devastating in the absence of second line antibiotics. Therefore, enhanced diagnostic laboratories for surveillance purposes and sustainable hospital hygiene measures must be considered to prevent further spread of multidrug resistant bacteria within rural communities.

Magma mixing induced by particle settling.

A time series of experiments at high temperature have been performed to investigate the influence of particle settling on magma mixing. A natural rhyolite glass was held above a natural basalt glass in a platinum crucible. After melting of the glasses at superliquidus temperatures, a platinum sphere was placed on the upper surface of the rhyolitic melt and sank into the experimental column (rhyolitic melt above basaltic melt). Upon falling through the rhyolitic-basaltic melt interface, the Pt sphere entrained a filament of rhyolitic melt in its further fall. The quenched products of the experiments were imaged using X-ray microCT methods. The images of our time series of experiments document the formation of a rhyolite filament as it is entrained into the underlying basalt by the falling platinum sphere. When the Pt particle reached the bottom of the crucible, the entrained rhyolitic filament started to ascend buoyantly up to the initial rhyolitic-basaltic interface. This generated a significant thickness increase of a comingled "melange" layer at the interface due to "liquid rope coiling" and piling up of the filament. As a consequence, the basalt/rhyolite interface was greatly enlarged and diffusive hybridisation greatly accelerated. Further, bubbles, originating at the interface, are observed to have risen into the overlying rhyolite dragging basalt filaments with them. Upon crossing the basalt/rhyolite interface, the bubbles have non-spherical shapes as they adapt to the differing surface tensions of basaltic and rhyolitic melts. Major element profiles, measured across the rhyolite filaments, exhibit asymmetrical shapes from the rhyolite into the basalt. Na and Ti reveal uphill diffusion from the rhyolite towards the interface in the filament cross sections. These results reveal the potential qualitative complexity of the mingling process between rhyolitic and basaltic magmas in the presence of sinking crystals. They imply that crystal-rich magma mingling may be expected to be accelerated with respect to crystal-poor systems. We urge the further fluid dynamic analysis of these phenomena, obtainable for the first time using detailed tomographic imaging.

T3 and T4 decrease ROS levels and increase endothelial nitric oxide synthase expression in the myocardium of infarcted rats.

UNLABELLED: Myocardial infarction leads to a reduction in nitric oxide (NO) bioavailability and an increase in reactive oxygen species (ROS) levels. This scenario has been shown to be detrimental to the heart. Recent studies have shown that thyroid hormone (TH) administration presents positive effects after ischaemic injury. Based on this, the aim of this study was to evaluate the effect of TH on NO bioavailability as well as on endothelial nitric oxide synthase (eNOS) expression after myocardial infarction. Male Wistar rats were divided into three groups: Sham-operated (SHAM), infarcted (AMI) and infarcted + TH (AMIT). During 26 days, the AMIT group received T3 and T4 (2 and 8 µg/100 g/day, respectively) by gavage, while SHAM and AMI rats received saline. After this, the rats underwent echocardiographic analysis were sacrificed, and the left ventricle was collected for biochemical and molecular analysis. STATISTICAL ANALYSIS: one-way ANOVA with Student-Newman-Keuls post test. AMI rats presented a 38% increase in ROS levels. TH administration prevented these alterations in AMIT rats. The AMIT group presented an increase in eNOS expression, in NOS activity and in nitrite levels. TH administration also increased PGC-1α expression in the AMIT group. In conclusion, TH effects seem to involve a modulation of eNOS expression and an improvement in NO bioavailability in the infarcted heart.

Comb sign in intestinal obstruction secondary to desmoplastic reaction due to an ileal neuroendocrine tumor.

This article report the case of an intestinal obstruction secondary to desmoplastic reaction of an ileum neuroendocrine tumor (NET), that was radiologically diagnosed by the comb sign. This is an infrequent clinical manifestation of NETs, often underdiagnosed, related to local overproduction of serotonin.