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1.

Background

Scientific guidelines consider atrial fibrillation (AF) complicating degenerative mitral regurgitation (DMR) a debated indication for surgery.

Objectives

This study analyzed the prognostic/therapeutic implications of AF at DMR diagnosis and long-term.

Methods

Patients were enrolled in the MIDA (Mitral Regurgitation International Database) registry, which reported the consecutive, multicenter, international experience with DMR due to flail leaflets echocardiographically diagnosed.

Results

Among 2,425 patients (age 67 ± 13 years; 71% male, 67% asymptomatic, ejection fraction 64 ± 10%), 1,646 presented at diagnosis with sinus rhythm (SR), 317 with paroxysmal AD, and 462 with persistent AF. Underlying clinical/instrumental characteristics progressively worsened from SR to paroxysmal to persistent AF. During follow-up, paroxysmal and persistent AF were associated with excess mortality (10-year survival in SR and in paroxysmal and persistent AF was 74 ± 1%, 59 ± 3%, and 46 ± 2%, respectively; p < 0.0001), that persisted 20 years post-diagnosis and independently of all baseline characteristics (p values <0.0001). Surgery (n = 1,889, repair 88%) was associated with better survival versus medical management, regardless of all baseline characteristics and rhythm (adjusted hazard ratio: 0.26; 95% confidence interval: 0.23 to 0.30; p < 0.0001) but post-surgical outcome remained affected by AF (10-year post-surgical survival in SR and in paroxysmal and persistent AF was 82 ± 1%, 70 ± 4%, and 57 ± 3%, respectively; p < 0.0001).

Conclusions

AF is a frequent occurrence at DMR diagnosis. Although AF is associated with older age and more severe presentation of DMR, it is independently associated with excess mortality long-term after diagnosis. Surgery is followed by improved survival in each cardiac rhythm subset, but persistence of excess risk is observed for each type of AF. Our study indicates that detection of AF, even paroxysmal, should trigger prompt consideration for surgery.  相似文献   
2.
Poor air quality and related health impacts are still an issue in many cities and regions worldwide. Integrated assessment models (IAMs) can support the design of measures to reduce the emissions of precursors affecting air pollution. In this study, we apply the SHERPA (screening for high emission reduction potentials for air quality) model to compare spatial and sectoral emission reductions, given country-scale emission targets. Different approaches are tested: (a) country ”uniform” emission reductions, (b) emission reductions targeting urban areas, (c) emission reductions targeting preferential sectors. As a case study, we apply the approaches to the implementation of the National Emission Ceiling Directive. Results are evaluated in terms of the reduction in average population exposure to PM2.5 overall in a country and in its main cities. Results indicate that the reduction of population exposure to PM2.5 highly depends on the way emission reductions are implemented. This work also shows the usefulness of the SHERPA model to support national authorities implementing national emission reduction targets while, at the same time, addressing their local air quality issues.  相似文献   
3.
Liposomes are versatile platforms to carry anticancer drugs in targeted drug delivery; they can be surface modified by different strategies and, when coupled with targeting ligands, are able to increase cellular internalisation and organelle-specific drug delivery. An interesting strategy of antitumoral therapy could involve the use of lysosomotropic ligand-targeted liposomes loaded with molecules, which can induce lysosomal membrane permeabilization (LMP), leakage of cathepsins into the cytoplasm and subsequent apoptosis. We have previously demonstrated the ability of liposomes functionalised with a mannose-6-phosphate to reach lysosomes; in this research we compare the behaviour of M6P-modified and non-functionalised liposomes in MCF7 tumour cell and in HDF normal cells. With this aim, we first demonstrated by Western blotting the overexpression of mannose-6-phosphate/insulin-like growth factor (M6P/IGF-II) receptor in MCF7. Then, we prepared calcein-loaded liposomes and we revealed the increased uptake of M6P-functionalised liposomes in MCF7 cells respect to HDF cells by flow cytometry analysis. Finally, we loaded functionalised and not functionalised liposomes with N-hexanoyl-d-erythro-sphingosine (C6Cer), able to initiate LMP-induced apoptosis; after having studied the stability of both vesicles in the presence of serum by Dynamic Light Scattering and Spectrophotometric turbidity measurements, we showed that ceramide-loaded M6P-liposomes significantly increased apoptosis in MCF7 with respect to HDF cells.  相似文献   
4.
OBJECTIVES: The relationship between subgingival dental restorations and periodontal health has been thoroughly investigated for many years. However, longitudinal data on the subgingival microflora features after the placement of well-finished subgingival restorations are still lacking. Therefore, this study compares the short-term clinical and microbiological features occurring in the gingiva after the completion of different subgingival restorations. MATERIAL AND METHODS: Sixteen systemically healthy subjects, 10 males and six females (ages: 31.7-45.8 years; mean age 39.3+/-5.1 years), who were non-smokers and were positive for the presence of three cervical abrasion/erosion defects to be restored in three different adjacent teeth were enrolled in this study. The cervical abrasion/erosion defects were each restored by using one of three different materials: amalgam, glass ionomer cement, or composite resin. Immediately before class V cavity preparations and restorations (baseline), clinical monitoring and subgingival plaque sampling were performed in the mid-buccal aspect of each experimental restored tooth and in one adjacent sound, non-treated, control tooth. These procedures were repeated every 4 months over the following 1 year. RESULTS: Throughout the study, the clinical parameters recorded did not change significantly in any of the experimental groups, and no differences were detected among them at each clinical session. Over this time, no significant changes in the composition of the subgingival microflora were observed in amalgam, glass ionomer cement, and control groups. Conversely, in the composite resin group, there was a significant increase in the total bacterial counts, and a significant (p<0.05) decrease in Gram-positive, aerobic bacteria, which was associated with a significant (p<0.05) increase in the Gram-negative, anaerobic microbiota. CONCLUSIONS: Over a 1-year observation period, amalgam, glass ionomer cement, and composite resin subgingival restorations do not significantly affect the clinical parameters recorded. However, composite resin restorations may have some negative effects on the quantity and quality of subgingival plaque.  相似文献   
5.
BACKGROUND: During orthodontic tooth movement, the early response of periodontal tissues to mechanical stress is an acute inflammatory one. This study uses a longitudinal design to examine lactate dehydrogenase (LDH) activity in gingival crevicular fluid (GCF) to determine if GCF LDH can be used as a diagnostic aid in monitoring tooth movement and tissue response during orthodontic treatment. METHODS: Seventeen patients (mean age: 16.1 years) participated in the study. Each patient was undergoing treatment for distal movement, and an upper first molar served as the test tooth (TT), while the contralateral (CT) and antagonist (AT) teeth were used as controls. The CT was included in the orthodontic appliance, but was not subjected to the distal movement; the AT was free from any orthodontic appliance. The GCF around the experimental teeth was harvested from both mesial and distal tooth sites immediately before appliance activation, and on days 7, 14, and 21. Clinical gingival conditions were also recorded. RESULTS: Gingival crevicular fluid LDH activity was significantly elevated in all sites of the TT and CT, as compared to the AT, where LDH activity remained at the baseline level throughout the study. Enzyme activity levels were also greater in the TT than in the CT, and in the compression sites. CONCLUSIONS: Our results suggest that GCF LDH levels reflect the biological activity that takes place in the periodontium during orthodontic movement, and therefore they can be used as a diagnostic tool for monitoring for correct orthodontic tooth movement in clinical practice.  相似文献   
6.
7.
Identifying frontal impairment in ALS is an important goal albeit disease-dedicated tools are still scarce. For this reason, we decided to consider primitive reflexes (PRs), variably regarded as correlates of frontal release and/or of upper motor neuron (UMN) impairment, often in the setting of dementias. Specifically, the aims of this work consisted in assessing the exact prevalence of the combination of seven PRs in ALS, trying to clarify their role as putative proxies of cognitive impairment or of UMN dysfunction. In this cross-sectional study, 50 consecutive ALS outpatients were evaluated for the presence of: palmomental (PM), corneomandibular (CM), glabella tap (MY), rooting, sucking, snout, and grasping reflexes. Cognitive screening was performed by the Frontal Assessment Battery (FAB) and the Weigl’s Sorting test (WST); UMN dysfunction was concomitantly evaluated. PM, CM and MY were more frequently detected (62, 52, and 44 % of the ALS sample, respectively), while the other reflexes were under-represented. Patients displaying three or more PRs had significantly lower FAB and WST scores. On the other hand, UMN dysfunction was only moderately associated to PRs. In conclusion, PRs’ assessment is a promising complementary tool for screening cognitive impairment in ALS; however, further work will be necessary to establish its added value with respect to already existing ALS-dedicated screening tools for cognition.  相似文献   
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10.
The treatment of premenstrual dysphoric disorder (PMDD) is far from satisfactory, as there is a high proportion of patients who do not respond to conventional treatment. The antidiuretic sulfonamide, acetazolamide, inhibits carbonic anhydrase and potentiates GABAergic transmission; the latter is putatively involved in PMDD. We therefore tried acetazolamide in a series of women with intractable PMDD. Here, we describe a series of eight women diagnosed with DSM-IV-TR PMDD, five of whom had comorbidity with a mood disorder and one with an anxiety disorder, who were resistant to treatment and responded with symptom disappearance after being added-on 125 mg/day acetazolamide for 7-10 days prior to menses each month. Patients were free from premenstrual symptoms at the 12-month follow-up. We suggest that acetazolamide may be used to improve symptoms of PMDD in cases not responding to other treatments. GABAergic mechanisms may be involved in counteracting PMDD symptoms.  相似文献   
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