Low frequency of AIP mutations in patients with young-onset sporadic pituitary macroadenomas.

PURPOSE: Mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene cause familial isolated pituitary adenomas (FIPA). AIP mutations have also been found in patients with apparently sporadic pituitary adenomas, particularly in young patients with large adenomas. The aim of this study was to determine the frequency of AIP germline mutations in patients with young-onset sporadic pituitary macroadenomas. METHODS: The AIP gene was sequenced in 218 Portuguese patients with sporadic pituitary macroadenomas diagnosed before the age of 40 years. RESULTS: Heterozygous rare sequence variants in AIP were identified in 18 (8.3%) patients. However, only four (1.8%) patients had pathogenic or likely pathogenic variants. These consisted of two already known mutations (p.Arg81* and p.Leu115Trpfs*41) and two novel mutations (p.Glu246*, p.Ser53Thrfs*36). All four patients had GH-secreting adenomas diagnosed between the ages of 14 and 25 years. The frequency of AIP pathogenic or likely pathogenic variants in patients under the age of 30 and 18 years was 3.4% and 5.0%, respectively. CONCLUSION: The frequency of AIP mutations in this cohort was lower than in other studies. Previous reports may have overestimated the contribution of AIP mutations due to the inclusion of genetic variants of uncertain significance. The identification of novel AIP mutations expands the known spectrum of genetic causes of pituitary adenomas and may help understand the role of AIP mutations in the molecular mechanisms underlying pituitary tumorigenesis.

The influence of simultaneous pancreas-kidney transplantation on the evolution of diabetic foot lesions and peripheral arterial disease.

PURPOSE: Simultaneous pancreas-kidney transplantation (SPKT) remains the best treatment option in patients with type 1 diabetes and chronic kidney failure. There are only a few studies addressing the potential ischemic deterioration of peripheral arterial disease (PAD) due to blood diverting from the iliac artery to the kidney graft. We aimed to evaluate diabetic foot lesions and PAD evolution in SPKT recipients and investigate if they are more frequent in ipsilateral lower limb of kidney graft. METHODS: We developed a retrospective cohort, including patients submitted to SPKT in our tertiary center, between 2000 and 2017. Diabetic foot lesions and PAD frequencies were compared in the period before and after transplantation. RESULTS: Two hundred and eleven patients were included, 50.2% (n = 106) female, with a median age at transplantation of 35 years (IQR 9). After a median follow-up period of 10 years (IQR 7), patient, kidney, and pancreatic graft survival were 90.5% (n = 191), 83.4% (n = 176), and 74.9% (n = 158), respectively. Before transplant, 2.8% (n = 6) had PAD and 5.3% (n = 11) had history of foot lesions. In post-transplant period, 17.1% (n = 36) patients presented PAD and 25.6% (n = 54) developed diabetic foot ulcers, 47.6% (n = 35) of which in the ipsilateral and 53.3% (n = 40) in the contralateral lower limb of the kidney graft (p = 0.48). Nine patients (4.3%) underwent major lower limb amputation, 3 (30%) ipsilateral and 7 (70%) contralateral to the kidney graft (p = 0.29). CONCLUSIONS: Diabetic foot lesions were not more frequent in the ipsilateral lower limb of the kidney graft, therefore downgrading the 'steal syndrome' role in these patients.

Zap1 is required for Candida glabrata response to fluconazole.

The increasing prevalence of fluconazole-resistant clinical isolates of Candida spp. strongly hinders the widespread use of the drug. To tackle this problem, great efforts have been made to fully understand the fungal response to fluconazole. In this work, we show that the role of Zap1 in Candida glabrata goes beyond regulating yeast adaptation to zinc deficiency. In line with our previous observation that deletion of ZAP1 makes yeast cells more sensitive to fluconazole, we found that the mutant CgΔzap1 accumulates higher levels of the drug, which correlates well with its lower levels of ergosterol. Surprisingly, Zap1 is a negative regulator of the drug efflux transporter gene CDR1 and of its regulator, PDR1. The apparent paradox of drug accumulation in cells where genes encoding transporters relevant for drug extrusion are being overexpressed led us to postulate that their activity could be impaired. In agreement, Zap1-depleted cells present, in addition to decreased ergosterol levels, an altered composition of membrane phospholipids, which together should impact membrane function and impair the detoxification of fluconazole. Overall, our study brings to light Zap1 as an important hub in Candida glabrata response to fluconazole.

Omega-3 Supplementation Prevents Short-Term High-Fat Diet Effects on the α7 Nicotinic Cholinergic Receptor Expression and Inflammatory Response.

The study is aimed at investigating if PUFA supplementation could prevent the effects of a short-term HFD on α7nAChR expression and on the severity of sepsis. Swiss mice were used for the in vivo experiments. For the in vitro experiments, we used a microglia cell line (BV-2) and a hepatoma cell line (Hepa-1c1c7) derived from mice. The animals were either fed standard chow, fed a short-term HFD (60%), or given supplementation with omega-3 fatty acid (2 g/kg or 4 g/kg bw) for 17 days, followed by a short-term HFD. Endotoxemia was induced with an intraperitoneal (i.p.) lipopolysaccharide injection (LPS, 5 or 12 mg/kg), and sepsis was induced by subjecting the animals to cecal ligation and puncture (CLP). BV-2 and Hepa-1c1c7 cells were treated with LPS (100 and 500 ng/mL, respectively) for 3 hours. RT-PCR or Western blotting was used to evaluate α7nAChR expression, inflammatory markers, DNMT1, and overall ubiquitination. LPS and HFD reduced the expression of α7nAChR and increased the expression of inflammatory markers. Omega-3 partially prevented the damage caused by the HFD to the expression of α7nAChR in the bone marrow and hypothalamus, decreased the inflammatory markers, and reduced susceptibility to sepsis-induced death. Exposing the BV-2 cells to LPS increased the protein content of DNMT1 and the overall ubiquitination and reduced the expression of α7nAChR. The inflammation induced by LPS in the BV-2 cell decreased α7nAChR expression and concomitantly increased DNMT1 expression and the ubiquitinated protein levels, indicating the participation of pre- and posttranscriptional mechanisms.

Electrochemical dissolution of nickel-titanium instrument fragments in root canals of extracted human maxillary molars using a small reservoir of electrolyte.

AIM: To evaluate the viability of the electrochemical dissolution of fragments of fractured NiTi instruments in root canals of extracted human maxillary molars, using two electrodes and the solution restricted to a small reservoir coupled to the pulp chamber. The primary hypothesis was that this method enables the reduction of fragment volume and re-establishment of the root canal path with a size 08 K-file, both in simulated canals and in extracted human maxillary molars. METHODOLOGY: Fragments of F1 ProTaper instruments were polarized in simulated root canals and in distobuccal root canals of extracted maxillary molars using a new method, with the solution restricted to a small acrylic microcell coupled to each resin block or pulp chamber. Two electrodes were used, where one was kept in contact with the intracanal fragment and another was positioned in the solution present in the acrylic microcell. After the tests, a size 08 K-file was used passively to verify the possibility of bypassing the fragment, which was also confirmed by radiographic analysis. Micro-CT analysis of the teeth was used before and after fragment dissolution to evaluate the volume, length and porosity of the fragments. The D'Agostino-Pearson normality test was used to verify the distribution of the data. A paired t-test (P < 0.05) was used to compare the volume, length and porosity of the fragments before and after the dissolution tests. RESULTS: After dissolution, all fragments could be bypassed with a size 08 K-file in both simulated canals and in extracted teeth. The dissolution process did not result in significant reduction of neither the fragment length nor the fragment porosity. However, it resulted in a significant reduction of fragment volume (paired t-test, P < 0.05). CONCLUSION: The electrochemical dissolution of fragments of NiTi files in root canals of extracted human maxillary molars using two electrodes, and the solution restricted to a small reservoir coupled to the pulp chamber resulted in a significant reduction of fragment volume. The re-establishment of the root canal path with the passive insertion of size 08 K-files was possible in all samples after the tests, both in simulated canals and in extracted teeth.

Prevalence of transactive response DNA-binding protein 43 (TDP-43) proteinopathy in cognitively normal older adults: systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review and meta-analysis on the prevalence of transactive response DNA-binding protein 43 (TDP-43) proteinopathy in cognitively normal older adults. METHODS: We systematically reviewed and performed a meta-analysis on the prevalence of TDP-43 proteinopathy in older adults with normal cognition, evaluated by the Mini-Mental State Examination or the Clinical Dementia Rating. We estimated the overall prevalence of TDP-43 using random-effect models, and stratified by age, sex, sample size, study quality, antibody used to assess TDP-43 aggregates, analysed brain regions, Braak stage, Consortium to Establish a Registry for Alzheimer's Disease score, hippocampal sclerosis and geographic location. RESULTS: A total of 505 articles were identified in the systematic review, and 7 were included in the meta-analysis with 1196 cognitively normal older adults. We found an overall prevalence of TDP-43 proteinopathy of 24%. Prevalence of TDP-43 proteinopathy varied widely across geographic location (North America: 37%, Asia: 29%, Europe: 14%, and Latin America: 11%). Estimated prevalence of TDP-43 proteinopathy also varied according to study quality (quality score >7: 22% vs. quality score <7: 42%), antibody used to assess TDP-43 proteinopathy (native: 18% vs. hyperphosphorylated: 24%) and presence of hippocampal sclerosis (without 24% vs. with hippocampal sclerosis: 48%). Other stratified analyses by age, sex, analysed brain regions, sample size and severity of AD neuropathology showed similar pooled TDP-43 prevalence. CONCLUSIONS: Different methodology to access TDP-43, and also differences in lifestyle and genetic factors across different populations could explain our results. Standardization of TDP-43 measurement, and future studies about the impact of genetic and lifestyle characteristics on the development of neurodegenerative diseases are needed.

Influence of clinical use on physical-structural surface properties and electrochemical potential of NiTi endodontic instruments.

AIM: To investigate the surface morphology and electrochemical potential of superelastic (SE), M-Wire (MW) and shape memory technology (SMT) NiTi instruments before and after single clinical use in vivo. METHODOLOGY: A total of 60 ProTaper Universal F2 (PTU-SE), ProTaper Next X2 (PTN-MW), Typhoon (TYP), Hyflex (HF) and Vortex Blue (VB), the last three SMT, and size 25, .06 taper (n = 6 of each type) files were examined. Scanning electron microscopy (SEM), X-ray energy-dispersive spectroscopy (EDS) and electrochemical potential analysis were employed before and after clinical use. Statistical analysis was performed with one-way analysis of variance and Bonferroni's post hoc test. Significance was determined at the 95% confidence level for both tests. RESULTS: SEM observations of new instruments indicated the presence of marks left by the machining process during manufacturing and EDS revealed the existence of an oxide coating on shape memory instruments. After clinical use, the five types were associated with propagation of transverse cracks 3 mm from the tip. The surface oxide layer of TYP, HF and VB instruments had microcracks in multiple directions, whilst TYP and HF had fragmentation in chip form of the oxide layer. EDS analysis demonstrated a significant reduction of the oxide layer in shape memory instruments, except for VB. Electrochemical potentials were higher for shape memory instruments than for M-Wire and superelastic NiTi instruments, respectively (P < 0.05). CONCLUSIONS: It appears that shape memory technology NiTi instruments have a dysfunctional oxide layer after clinical use. Additionally, they featured higher electrochemical potential relative to NiTi instruments manufactured from M-Wire, and conventional superelastic NiTi alloy.

Evaluation of the effects of the solution used for electrochemical dissolution of nickel-titanium endodontic files on dentine structure, microhardness and cell viability.

AIM: To evaluate the effects of the [NaF 12 g L-1  + NaCl 1 g L-1 ] solution used in the electrochemical dissolution process of fractured endodontic files, as well as its NiTi-containing product, on dentine hardness, topography and human fibroblast viability. METHODOLOGY: Sixty single-rooted human teeth were evaluated for dentine microhardness using the Vickers hardness test and the area and number of dentinal tubules by scanning electron microscopy. The samples were divided according to the dentine surface treatment: distilled water; 17% EDTA; [NaF 12 g L-1  + NaCl 1 g L-1 ]; and 17% EDTA + [NaF 12 g L-1  + NaCl 1 g L-1 ]. Thirty-six single-rooted human teeth were divided according to the irrigation protocol: Dulbecco's Modified Eagle's Medium + 10% foetal bovine serum; 5.25% NaOCl; [NaF 12 g L-1  + NaCl 1 g L-1 ]; and [NaF 12 g L-1  + NaCl 1 g L-1  + NiTi]. The extracts in contact with the apical foramen were used in the MTT assay to evaluate human fibroblast viability, with dilutions of 100%, 50%, 25% and 12.5%. Statistical tests used were paired t-tests, one-way anova, Tukey's test, Kruskal-Wallis test and Dunn's post-test. RESULTS: The [NaF 12 g L-1  + NaCl 1 g L-1 ] solution did not modify dentine microhardness or the average dentinal tubule area. However, EDTA induced changes in dentine structure and microhardness (P < 0.05). The [NaF 12 g L-1  + NaCl 1 g L-1 ] solution, and its NiTi-containing product had lower cytotoxicity than NaOCl at dilutions of 25% and 50% (P < 0.01). CONCLUSIONS: The [NaF 12 g L-1  + NaCl 1 g L-1 ] solution did not alter dentine microhardness or damage the dentine structure. It also demonstrated lower cytotoxicity than NaOCl.

Anandamide oxidative metabolism-induced endoplasmic reticulum stress and apoptosis.

The Endocannabinoid System (ECS) has been recognized as a crucial player in human reproduction. Changes in the levels of anandamide (AEA), the main endocannabinoid (eCB), negatively affect reproductive events, such as implantation, decidualization and placentation. Cyclooxygenase-2 (COX-2) is a major enzyme expressed in the endometrium and its involvement in female reproductive system has evolved over the last few years. Currently, COX-2 oxidative metabolism is emerging as a key mediator of AEA-induced actions. In this study, we aimed to disclose the mechanisms underlying the effects of AEA in human endometrial stromal cell fate, using a human-derived endometrial cell line (St-T1b). We found that AEA has an anti-proliferative activity through a direct effect on cell cycle progression by inducing G2/M arrest. Moreover, high levels of AEA increased COX-2 activity, triggering apoptotic cell death, with loss of mitochondrial membrane potential, induction of caspase -9 and -3/-7 activities, and cleavage of poly (ADP-ribose) polymerase (PARP). In addition, the involvement of intracellular reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress was verified. These effects were prevented by pre-incubation with a selective COX-2 inhibitor. Therefore, we hypothesize that, in response to altered levels of this eCB, COX-2 oxidative metabolism of AEA may deregulate endometrial cell turnover and, consequently, interfere with cellular events crucial for implantation and decidualization, with a negative impact on human fertility.

A diabetic foot ulcer treated with hydrogel and hyperbaric oxygen therapy: a case study.

This study reports on the case of an elderly patient, with diabetes, and a bullous wound on the left big toe that led to an amputation of the first and second left toes. The amputation was because of deep injury as it was not able to heal with a conventional treatment. After completing the normal treatment and the removal of a bacterial infection in the lesion, the patient underwent a treatment that was based on a hydrogel gel (0.9% saline solution) and hyperbaric oxygen therapy (HBOT). After 60 sessions of the therapy, almost complete closure of the wound was observed. There were no reports of discomfort or infection during the treatment. After seven months of treatment almost complete healing was observed with no infection. This treatment appears to be effective and should be recommended for the treatment of DFUs.

The endocannabinoid anandamide impairs in vitro decidualization of human cells.

Endocannabinoids (eCBs) are endogenous mediators that along with the cannabinoid receptors (CB1 and CB2), a membrane transporter and metabolic enzymes form the endocannabinoid system (ECS). Several eCBs have been discovered with emphasis on anandamide (AEA). They are involved in several biological processes such as energy balance, immune response and reproduction. Decidualization occurs during the secretory phase of human menstrual cycle, which involves proliferation and differentiation of endometrial stromal cells into decidual cells and is crucial for the establishment and progression of pregnancy. In this study, a telomerase-immortalized human endometrial stromal cell line (St-T1b) and non-differentiated primary cultures of human decidual fibroblasts from term placenta were used to characterize the ECS using immunoblotting and qRT-PCR techniques. It was shown that St-T1b cells express CB1, but not CB2, and that both receptors are expressed in HdF cells. Furthermore, the expression of fatty acid amide hydrolase (FAAH), the main degrading enzyme of AEA, increased during stromal cell differentiation. AEA inhibited cell proliferation, through deregulation of cell cycle progression and induced polyploidy. Moreover, through CB1 binding receptor, AEA also impaired cell differentiation. Therefore, AEA is proposed as a modulator of human decidualization. Our findings may provide wider implications, as deregulated levels of AEA, due to Cannabis sativa consumption or altered expression of the metabolic enzymes, may negatively regulate human endometrial stromal cell decidualization with an impact on human (in)fertility.Free Portuguese abstract: A Portuguese translation of this abstract is freely available at http://www.reproduction-online.org/content/152/4/351/suppl/DC1.

Electrochemical-induced dissolution of stainless steel files.

AIM: To investigate the effectiveness of the dissolution process when hand stainless steel files are polarized in solutions containing chloride and fluoride to promote their dissolution. METHODOLOGY: Redox curves and anodic polarization curves were obtained to determine the conditions necessary for the dissolution of stainless steel endodontic files. Anodic polarization of sizes 20 and 30 files was performed, and a t-test (P < 0.05) was used to compare the weight loss, the time of dissolution and the electrical charge generated by both groups of files. Fragments were polarized in simulated root canals to evaluate the dissolution process. After the tests, a size 10 K-file was used to verify the possibility of bypassing the fragment. Radiographic analysis of the simulated canals was used before and after the tests to verify fragment dissolution. RESULTS: A progressive consumption of the sizes 20 and 30 files was observed with total polarization times of 7.0 and 9.0 min, respectively. Files with the larger diameters exhibited greater weight loss, longer times of dissolution and generated a greater electrical charge during the active dissolution process (t-test, P < 0.05). After 60 min, the anodic polarization of file fragments in simulated root canals resulted in their partial dissolution. CONCLUSION: A 60-min anodic polarization of stainless steel K-file fragments in simulated root canals resulted in their partial dissolution. The fragments could be bypassed after the test.

Assumed infectiousness, treatment adherence and sexual behaviours: applying the Swiss Statement on infectiousness to HIV-positive alcohol drinkers.

OBJECTIVES: The success of antiretroviral therapy (ART) for treating HIV infection is now being turned towards HIV prevention. The Swiss Federal Commission for HIV/AIDS has declared that HIV-positive persons who are treated with ART, have an undetectable viral load, and are free of co-occurring sexually transmitted infections (STIs) should be considered noninfectious for sexual transmission of HIV. This study examined the implications of these assumptions in a sample of HIV-positive individuals who drink alcohol. METHODS: People living with HIV/AIDS (n = 228) were recruited through community sampling. They completed confidential computerized interviews and underwent monthly unannounced pill counts for ART adherence. HIV viral loads were obtained from medical records. RESULTS: One hundred and eighty-five HIV-positive drinkers were currently receiving ART and 43 were untreated. Among those receiving ART, one in three were not virally suppressed and one in five had recently been diagnosed with an STI. Adherence was generally suboptimal, including among those assumed to be less infectious. As many as one in four participants reported engaging in unprotected intercourse with an HIV-uninfected partner in the past 4 months. There were few associations between assumed infectiousness and sexual practices. CONCLUSIONS: Less than half of people who drank alcohol and took ART met the Swiss criteria for noninfectiousness. Poor adherence and prevalent STI threaten the long-term potential of using ART for prevention. In the absence of behavioral interventions, the realities of substance use and other barriers call into question the use of ART as prevention among alcohol drinkers.

Thermal Performance of Multifunctional Facade Solution Containing Phase Change Materials: Experimental and Numerical Analysis.

This work focuses on the development and analysis of a new multifunctional facade panel incorporating PCM in foam layers. The thermal performance was analysed recurring to a hotbox heat flux meter method to determine the thermal transmittance (U-value) and the main findings are presented. The experimental setup was based on the steady-state approach, using climatic chambers, assuring a stable thermal environment. Even small fractions of PCM achieved a small reduction in thermal amplitude. Numerical simulations using Ansys Fluent were developed to evaluate the performance of PCM use over a wide range of temperature boundary conditions and operating modes. These numerical models were calibrated and validated using the results of experimental tests, achieving a correlation factor of 0.9674, and, thus, accurately representing a real-world scenario. The decrement factor (f) was used to analyse the data. It was identified that the efficiency of the panel and size of the optimum region increased with the PCM fraction growth. The results showed the significant potential of the multi-layered panel, with the thermal regulator effect of the PCM incorporated, on indoor space temperature so as to reach good thermal comfort levels. The efficiency of the panel can be improved by nearly 50% depending on the input boundary conditions. The efficiency of the panel and the size of the optimum region increase with growth in the PCM fraction. The simulated behaviour was at an optimum when the input mean temperature was 20 °C for a room temperature of between 18-20 °C.

Hypertension favors the inflammatory process in rats with experimentally induced periodontitis.

BACKGROUND AND OBJECTIVE: Cardiovascular diseases are significantly correlated with chronic periodontitis. The aim of this study was to evaluate bone-loss level, neutrophil migration, CXCL2/CINC-2α, CXCL5/LIX, CCL20/MIP-3α and tumor necrosis factor-α (TNF-α) production, inducible nitric oxide synthase (iNOS) expression and C-reactive protein (CRP) release in spontaneously hypertensive rats (SHRs) and normotensive (WTK) rats after experimental induction of periodontal disease. MATERIAL AND METHODS: Periodontitis was induced by placement of silk yarn ligatures around the first molar counterparts. The levels of CRP, CCL20/MIP-3α and CXCL5/LIX were evaluated in the peripheral blood, and bone-loss level, neutrophil recruitment, the production of myeloperoxidase, CXCL2, CXCL5, CCL20 and TNF-α, and the expression of iNOS were evaluated in the gingival tissue. Histological sections were taken to evaluate and measure bone resorption and neutrophil recruitment in the furcation region. RESULTS: Rats with periodontitis had alveolar bone resorption. SHRs with periodontitis showed marked bone loss and increased neutrophil infiltration in comparison with WTK rats. SHRs with periodontitis showed increased levels of TNF-α and CXCL2, and a slight tendency for increased levels of CXCL5, in the gingival tissue but no increase in the level of CCL20. In SHRs, even without periodontitis, the levels of TNF-α, CXCL2, CXCL5 and CCL20 showed a slight tendency to increase. In the WTK rats, TNF-α, CXCL2 and CXCL5 levels were increased with periodontitis, but the level of CCL20 was not. iNOS was expressed in the gingival tissue of WTK rats and SHRs with periodontitis; however, SHRs appeared to express a higher level of iNOS than did WKT rats. The CRP level was elevated in both types of rats with periodontitis; however, the CRP level was higher in SHRs with periodontitis than in WTK rats with periodontitis. CONCLUSION: In SHRs, the hypertensive condition per se seems to favor the inflammatory processes that become potentiated with periodontitis, when compared with WKT rats.

Frequency of human papillomavirus types 16, 18, 31, and 33 and sites of cervical lesions in gynecological patients from Recife, Brazil.

Human papilloma virus (HPV) is a well-established cause of cervical cancer. While many studies have been performed so far on HPV viral biology, mode of infection and prevention measures, scanty information is available on lesion sites of infected women and the incidence of viral types at specific locations. We looked for a possible relationship between the most common viral types (HPVs 16, 18, 31, 33) found in Recife, PE, Brazil, and lesion sites. We examined 396 HPV-positive women at the Gynecological Unit of the IMIP at Recife; 288 women were positive for HPV 16, 18, 31, or 33, present as a single-virus type or as co-infection. HPV 16 was the most frequent virus type found in the vulva, vagina, uterine cervix-vagina, and uterine cervix. HPV 31 was the second prevalent virus type in vulva, vagina, uterine cervix-vagina, uterine cervix, and mole. HPVs 18 and 33 were present with similar frequencies in the mole-vulva region. Among the co-infections, HPV 16/18 and HPV16/31 were the most frequent in our study group, followed by HPV 16/33.

Metformin and atorvastatin combination further protect the liver in type 2 diabetes with hyperlipidaemia.

BACKGROUND: non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes are associated with dyslipidaemia, inflammation and oxidative stress. However, the pathophysiology of NAFLD in type 2 diabetes with hyperlipidaemia is not fully known, as well as the utility of the commonly prescribed anti-diabetic and lipid-lowering drugs in ameliorating liver injury markers. METHODS: hepatic complications of type 2 diabetes with hyperlipidaemia and the effects of atorvastatin and metformin, isolated and in association, in systemic and hepatic inflammatory and oxidative stress markers were tested using genetic type 2 diabetic Goto-Kakizaki rats fed with a high-fat diet. RESULTS: the high-fat diet aggravated the overall metabolic state and the hepatic markers of injury. All treatments decreased fasting glycaemia, insulin resistance and free fatty acid levels. Combined treatment further decreased C-reactive protein (CRP), adiponectin, liver tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6), systemic and hepatic oxidative stress and portal inflammation. CONCLUSIONS: our data provides evidence of a greater benefit with a combination of atorvastatin and metformin in improving liver injury in type 2 diabetes with hyperlipidaemia.

Erratum to "Gastroenteropancreatic Neuroendocrine Neoplasia Characterization in Portugal: Results from the NETs Study Group of the Portuguese Society of Endocrinology, Diabetes and Metabolism".

[This corrects the article DOI: 10.1155/2019/4518742.].

Incidence of stroke subtypes, prognosis and prevalence of risk factors in Joinville, Brazil: a 2 year community based study.

BACKGROUND: There have been few population based studies on stroke risk factors and prognosis conducted in Brazil. The objective of this study was to evaluate, over a 2 year period, the incidence of the subtypes of first ever stroke, the prevalence of cardiovascular risk factors and functional prognosis in a city located in the south of Brazil. METHODS: The period from January 2005 to December 2006 was evaluated prospectively by compiling data on first ever stroke cases, medications used prior to the morbidity and the incidence of traditional risk factors. The annual incidence was adjusted for age using the direct method. Patients were monitored for at least 6 months following the event. RESULTS: Of 1323 stroke cases, 759 were first ever stroke cases. Of these, 610 were classified as infarctions, 94 as intracerebral haemorrhage and 55 as subarachnoid haemorrhage. The crude incidence rate per 100 000 inhabitants was 61.8 for infarction (95% CI 57.0 to 66.9), 9.5 for intracerebral haemorrhage (95% CI 7.7 to 11.6) and 5.6 for subarachnoid haemorrhage (95% CI 4.2 to 7.3). The 30 day case fatality was 19.1%. The most prevalent cardiovascular risk factor was arterial hypertension. By post-stroke month 6, 25% had died (95% CI 21.4 to 29.1) whereas 61.5% had regained their independence (95% CI 56.2 to 68.3). CONCLUSIONS: Case fatality rate, prognosis and incidence adjusted for stroke subtypes were similar to those found in other population based studies. The prevalence rates of ischaemic heart disease, dyslipidaemia, arterial hypertension and diabetes suggest that Joinville presents a mixed pattern of cardiovascular risk, a pattern seen in developed and developing countries alike.

Trends in stroke incidence, mortality and case fatality rates in Joinville, Brazil: 1995-2006.

BACKGROUND: Studying stroke rates in a whole community is a rational way to assess the quality of patient care and primary prevention. However, there are few studies of trends in stroke rates worldwide and none in Brazil. OBJECTIVE: Established study methods were used to define the rates for first ever stroke in a defined population in Brazil compared with similar data obtained and published in 1995. METHODS: All stroke cases occurring in the city of Joinville during 2005-2006 were prospectively ascertained. Crude incidence and mortality rates were determined, and age adjusted rates and 30 day case fatality were calculated and compared with the 1995 data. RESULTS: Of the 1323 stroke cases registered, 759 were first ever strokes. The incidence rate per 100 000 was 105.4 (95% CI 98.0 to 113.2), mortality rate was 23.9 (95% CI 20.4 to 27.8) and the 30 day case fatality was 19.1%. Compared with the 1995 data, we found that the incidence had decreased by 27%, mortality decreased by 37% and the 30 day case fatality decreased by 28%. CONCLUSIONS: Using defined criteria we showed that in an industrial southern Brazilian city, stroke rates are similar to those from developed countries. A significant decrease in stroke rates over the past decade was also found, suggesting an improvement in primary prevention and inpatient care of stroke patients in Joinville.