Dyskeratosis congenita: clinical report and review of the literature

Abstract:  Dyskeratosis congenita (DKC) is an inherited disorder that usually presents in males, consisting of the triad of leukoplakia of the mucous membranes, nails dystrophy and skin pigmentation. Oral and dental abnormalities may also be present. Most cases are X-linked autosomal dominant, but recessive forms have also been reported. This study describes herein a case in which the classic triad of signs was present, along with the development of leukoplakia in the buccal mucosa. Our patient, a 25-year-old man, presented with several characteristic systemic features of this condition, together with the following oral features: hypodontia, delayed dental eruption, short blunt roots, extensive caries, gingival inflammation and bleeding, loss of alveolar bone and buccal mucosa with leukoplakia and irregular ulcers. The patient was given full preventive care. The primary teeth were extracted under local anaesthesia. After establishing optimal oral health, oral hygiene instructions were given to the patient and he was rehabilitated with fixed and removable partial denture. Prosthetic treatments were carried out after establishing optimal oral health. This treatment option appears beneficial in this patient, resulting in rehabilitation of occlusion and less mechanical irritation to the oral mucosa.     

Combination reperfusion therapy with eptifibatide and reduced-dose tenecteplase for ST-elevation myocardial infarction: results of the integrilin and tenecteplase in acute myocardial infarction (INTEGRITI) Phase II Angiographic Trial

OBJECTIVES: The goal of this study was to evaluate combinations of eptifibatide with reduced-dose tenecteplase (TNK) in ST-elevation myocardial infarction (STEMI). BACKGROUND: Glycoprotein IIb/IIIa inhibitors enhance thrombolysis. The role of combination therapy in clinical practice remains to be established. METHODS: Patients (n = 438) with STEMI <6 h were enrolled. In dose-finding, 189 patients were randomized to different combinations of double-bolus eptifibatide and reduced-dose TNK. In dose-confirmation, 249 patients were randomized 1:1 to eptifibatide 180 microg/kg bolus, 2 microg/kg/min infusion, and 180 microg/kg bolus 10 min later (180/2/180) plus half-dose TNK (0.27 mg/kg) or standard-dose (0.53 mg/kg) TNK monotherapy. All patients received aspirin and unfractionated heparin (60 U/kg bolus; infusion 7 U/kg/h [combination], 12 U/kg/h [monotherapy]). The primary end point was Thrombolysis In Myocardial Infarction (TIMI) grade 3 epicardial flow at 60 min. RESULTS: In dose-finding, TIMI grade 3 flow rates were similar across groups (64% to 68%). Arterial patency was highest for eptifibatide 180/2/180 plus half-dose TNK (96%, p = 0.02 vs. eptifibatide 180/2/90 plus half-dose TNK). In dose-confirmation, this combination, compared with TNK monotherapy, tended to achieve more TIMI 3 flow (59% vs. 49%, p = 0.15), arterial patency (85% vs. 77%, p = 0.17), and ST-segment resolution (median 71% vs. 61%, p = 0.08) but was associated with more major hemorrhage (7.6% vs. 2.5%, p = 0.14) and transfusions (13.4% vs. 4.2%, p = 0.02). Intracranial hemorrhage occurred in 1.0%, 0.6%, and 1.7% of patients treated with any combination, eptifibatide 180/2/180 and half-dose TNK, and TNK monotherapy, respectively. CONCLUSIONS: Double-bolus eptifibatide (180/2/180) plus half-dose TNK tended to improve angiographic flow and ST-segment resolution compared with TNK monotherapy but was associated with more transfusions and non-cerebral bleeding. Further study is needed before this combination can be recommended for general use.     

Risk factors for nosocomial imipenem-resistant Acinetobacter baumannii infections.

OBJECTIVES: To identify the risk factors for nosocomial imipenem-resistant Acinetobacter baumannii (IRAB) infections. METHODS: A prospective case-control study, set in an 1100-bed referral and tertiary-care hospital, of all patients who had nosocomial A. baumannii infections between January 1 and December 31, 2004. Only the first isolation of A. baumannii was considered. RESULTS: IRAB was isolated from 66 (53.7%) patients and imipenem-sensitive Acinetobacter baumannii (ISAB) was isolated from 57 (46.3%) patients during the study period. The mean duration of hospital stay until A. baumannii isolation was 20.8+/-13.6 days in IRAB infections, whereas it was 15.4+/-9.4 days in ISAB infections. Of the patients, 65.2% with IRAB infections and 40.4% with ISAB infections were followed at the intensive care unit (ICU). Previous carbapenem use was present in 43.9% of the patients with IRAB and 12.3% of the patients with ISAB infection. In univariate analysis female sex, longer duration of hospital stay until infection, ICU stay, emergent surgical operation, total parenteral nutrition, having a central venous catheter, endotracheal tube, urinary catheter or nasogastric tube, previous antibiotic use, and previous administration of carbapenems were significant risk factors for IRAB infections (p<0.05). In multivariate analysis, longer duration of hospital stay until A. baumannii isolation (odds ratio (OR) 1.043; 95% confidence interval (CI) 1.003-1.084; p=0.032), previous antibiotic use (OR 5.051; 95% CI 1.004-25.396; p=0.049), and ICU stay (OR 3.100; 95% CI 1.398-6.873; p=0.005) were independently associated with imipenem resistance. CONCLUSIONS: Our results suggest that the nosocomial occurrence of IRAB is strongly related to an ICU stay and duration of hospital stay, and that IRAB occurrence may be favored by the selection pressure of previously used antibiotics.     

Turkey Handwashing Survey: suggestion for taking the ecological model into better consideration

Objectives

This study is aimed to find out the handwashing habits and their relations to the socio-economic variables.

Methods

The sampling is determined regarding the address-based population registration system of the country. The multi-staged stratified cluster sampling method was used. It is conducted by a face to face questionnaire with 6854 persons. 22 questions are asked whether they are washing their hands or not related to different situations, the results are graded and the “Handwashing Habits Score” (HHS) is obtained. The reasons for not handwashing were evaluated by categorizing as individual, environmental and combined reasons.

Results

The HHS is increasing in the older age groups (β = 0.148, p < 0.001), females (β = 0.306, p < 0.001), citizens of urban settlement (β = 0.061, p < 0.001), higher education levels (β = 0.191, p < 0.001). The reasons for not handwashing were found as 53.3 % individual, 39.2 % environmental, 7.5 % combined. The frequency of mentioning not washing hands because of the environmental reasons is getting higher in the older age groups, in the urban side, and in the higher education level (p < 0.001).

Conclusions

The handwashing habits are shaped by the determinant networks which form a complex structure by intertwining individual, socio-economic and environmental factors in different sub-groups with various weights. This result might contribute to the efforts of conceptualizing the health behaviors with ecological model.     

Tear in mitral anterior leaflet as a complication of Manouguian's procedure in a woman with an aortic valve prosthesis

Complications of valve replacement are diverse. In addition to morbidity due to the prosthetic valve itself (e.g. endocarditis, thrombosis), complications due to operative technique may occur in complex cases, as in aortic valve replacement with annular enlargement. Postoperative echocardiography is a simple, non-invasive method to evaluate patients with prosthetic valves. Detailed knowledge of the surgical technique employed and of probable complications is necessary to make an accurate diagnosis. The case is reported of a woman with aortic valve replacement and annular enlargement who had mitral regurgitation due to a tear in the anterior mitral leaflet as a complication of Manouguian's annulus enlargement.     

Increased segregation of structural brain networks underpins enhanced broad cognitive abilities of cognitive training

A major challenge in the cognitive training field is inducing broad, far‐transfer training effects. Thus far, little is known about the neural mechanisms underlying broad training effects. Here, we tested a set of competitive hypotheses regarding the role of brain integration versus segregation underlying the broad training effect. We retrospectively analyzed data from a randomized controlled trial comparing neurocognitive effects of vision‐based speed of processing training (VSOP) and an active control consisting of mental leisure activities (MLA) in older adults with MCI. We classified a subset of participants in the VSOP as learners, who showed improvement in executive function and episodic memory. The other participants in the VSOP (i.e., VSOP non‐learners) and a subset of participants in the MLA (i.e., MLA non‐learners) served as controls. Structural brain networks were constructed from diffusion tensor imaging. Clustering coefficients (CCs) and characteristic path lengths were computed as measures of segregation and integration, respectively. Learners showed significantly greater global CCs after intervention than controls. Nodal CCs were selectively enhanced in cingulate cortex, parietal regions, striatum, and thalamus. Among VSOP learners, those with more severe baseline neurodegeneration had greater improvement in segregation after training. Our findings suggest broad training effects are related to enhanced segregation in selective brain networks, providing insight into cognitive training related neuroplasticity.     

PD1 expression and correlation with its ligands in oral cancer specimens and peripheral blood

ObjectivesThis study analyzed the expression of the PD1 receptor in tumor tissue and peripheral blood of oral squamous cell carcinoma (OSCC) patients, and correlated it with the PD1 ligands PD-L1 and PD-L2. The currently low response rates of checkpoint inhibitor treatment in OSCC could be increased by a better understanding of immune checkpoint biology. Despite evidence in the literature for upregulation of PD1 checkpoint ligands in OSCC tissue, there has been no correlation analysis of the PD1 receptor with its ligands in tissue specimens and peripheral blood of OSCC patients.Materials and methodsAn RT-qPCR analysis of PD1 mRNA expression was performed in oral cancer specimens, healthy mucosa, and corresponding blood samples. A cut-off point (COP) was determined and a chi-square (χ²) test was carried out. PD1 expression was correlated with previously reported PD-L1 and PD-L2 expression values using the Spearman test.ResultsTissue and blood specimens of 48 OSCC patients and 26 healthy individuals were analyzed. PD1 expression in OSCC specimens was significantly increased (p = 0.006) compared with healthy oral mucosa. PD1 overexpression in tissue samples showed a significant association with the presence of malignancy (p = 0.006). PD1 expression in tissue samples showed a significant positive correlation (p < 0.001) with the ligands PD-L1 and PD-L2. In contrast, there was no correlation between PD1 and its ligands in blood samples. However, there was a significant positive correlation (p < 0.001) between the ligands PD-L1 and PD-L2, both in tissue and blood samples.ConclusionsIncreased PD1 expression might be a manifestation of T-cell exhaustion in OSCC specimens, leading to immune tolerance. PD-L1/PD-L2-PD1 interaction may be a major mediator of local immunosuppression in OSCC, requiring advanced multimodal treatment protocols.     

Fe3O4@SiO2@Au nanoparticles for MRI-guided chemo/NIR photothermal therapy of cancer cells

Novel functionalized (biofunctionalization followed by cisplatin immobilization) Fe₃O₄@SiO₂@Au nanoparticles (NPs) were designed. The encapsulation of Fe₃O₄ cores inside continuous SiO₂ shells preserves their initial structure and strong magnetic properties, while the shell surface can be decorated by small Au NPs, and then cisplatin (cPt) can be successfully immobilized on their surface. The fabricated NPs exhibit very strong T₂ contrasting properties for magnetic resonance imaging (MRI). The functionalized Fe₃O₄@SiO₂@Au NPs are tested for a potential application in photothermal cancer therapy, which is simulated by irradiation of two colon cancer cell lines (SW480 and SW620) with a laser (λ = 808 nm, W = 100 mW cm⁻²). It is found that the functionalized NPs possess low toxicity towards cancer cells (∼10–15%), which however could be drastically increased by laser irradiation, leading to a mortality of the cells of ∼43–50%. This increase of the cytotoxic properties of the Fe₃O₄@SiO₂@Au NPs, due to the synergic effect between the presence of cPt plus Au NPs and laser irradiation, makes these NPs perspective agents for potential (MRI)-guided stimulated chemo-photothermal treatment of cancer.

Novel functionalized nanoparticles, with toxicity controlled by laser irradiation, are perspective agents for potential (MRI)-guided stimulated chemo-photothermal treatment of cancer.