Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanisms of interaction between obesity and ischaemic stroke

Obesity is an independent risk factor for ischaemic stroke and may worsen stroke outcome. Therefore, the objective of this thesis was to identify potential interactions between obesity and stroke, with particular focus on inflammatory mechanisms.Ischaemic stroke was surgically induced in obese (ob/ob) and control (ob/-) mice by middle cerebral artery occlusion (MCAO). Outcome was worse in ob/ob mice, which showed rapid and severe ischaemic and vascular damage, characterised by blood vessel haemorrhage as early as 30 minutes post-stroke. The early vascular damage is likely an important driver of subsequent ischaemic damage by exacerbating inflammation in the brain. Assessment of systemic inflammation in ob/ob mice found that stroke had triggered a deregulated inflammatory response in the plasma, spleen, liver and bone marrow, and increased adipose tissue inflammation.Increased vascular damage was hypothesised to mediate the worse outcome found in obese rodents. The structural and inflammatory state of the vasculature was therefore assessed in ob/ob mice prior to and after stroke. Prior to stroke, increased vascular inflammation was found in ob/ob mice, though no differences in tight junction expression or structural alterations were noted. Stroke resulted in vascular damage that was similar on structural and molecular levels between genotypes, though ob/ob mice showed an increase in transcytosis in endothelial cells which may mediate their enhanced blood-brain barrier breakdown.Some studies have found obese patients have better outcome after stroke, perhaps because they are protected from detrimental post-stroke weight loss. The metabolic response to MCAO was therefore assessed, with ob/ob mice showing altered lipid metabolism post-stroke, such as increased fatty acid release from adipose tissue into the plasma. The potential role of fatty acid release in triggering adipose inflammation was also assessed in adipose tissue explants, though limited evidence for an inflammatory response to lipolysis was found.Overall, these findings suggest rapid and enhanced vascular damage may drive worse stroke outcome in ob/ob mice, as may their altered immunological and metabolic states.
Intracellular Cannabinoid Type 1 (CB1) Receptors Are Activated by Anandamide*

Recent studies have demonstrated that the majority of endogenous cannabinoid type 1 (CB1) receptors do not reach the cell surface but are instead associated with endosomal and lysosomal compartments. Using calcium imaging and intracellular microinjection in CB1 receptor-transfected HEK293 cells and NG108-15 neuroblastoma × glioma cells, we provide evidence that anandamide acting on CB1 receptors increases intracellular calcium concentration when administered intracellularly but not extracellularly. The calcium-mobilizing effect of intracellular anandamide was dose-dependent and abolished by pretreatment with SR141716A, a CB1 receptor antagonist. The anandamide-induced calcium increase was reduced by blocking nicotinic acid-adenine dinucleotide phosphate- or inositol 1,4,5-trisphosphate-dependent calcium release and abolished when both lysosomal and endoplasmic reticulum calcium release pathways were blocked. Taken together, our results indicate that, in CB1 receptor-transfected HEK293 cells, intracellular CB1 receptors are functional; they are located in acid-filled calcium stores (endolysosomes). Activation of intracellular CB1 receptors releases calcium from endoplasmic reticulum and lysosomal calcium stores. In addition, our results support a novel role for nicotinic acid-adenine dinucleotide phosphate in cannabinoid-induced calcium signaling.
A neural net screening of psychiatric patients

Describes a method for screening psychiatric patients based on a questionnaire consisting of simple yes/no questions relating to physical, mental conditions and subjective symptoms which is provided at their first visit to the hospital. The analysis of the questionnaire is important to understand patients' background. One hundred filled out questionnaires were utilized for constructing and evaluating a neural net classifier which classifies patients into three categories i.e. schizophrenic, emotional and neurotic disorders with average correct prediction rate of 74.7%. The rate was 18.0% higher than the result given by experienced medical doctors and the method will be a useful mean for automatic screening the psychiatric patients.
Molecular and clinical description of a girl with a 46,X,t(Y;4)(q11.2;p16)/45,X,der(4)t(Y;4)(q11.2;p16) karyotype and a small cryptic 4p subtelomeric deletion

We report on a 13‐year‐old female with short stature, minimal axillary and pubic hair, no breast development, absence of uterus and ovaries, with the following karyotype on lymphocyte cultures: 46,X,t(Y;4)(q11.2;p16)[40]/45,X,der(4)t(Y;4)(q11.2;p16)[10]. Loss of the small derivative Y chromosome in 20% of the cells was also confirmed in skin fibroblast cultures. FISH analyses using Y centromere, SRY, subtelomere XpYp/XqYq, Y and 4 painting probes, confirmed the cytogenetic findings. High‐resolution STS analyses using 40 markers covering the Y chromosome did not identify any deletion on the Y. However, de novo absence of the 4p subtelomeric region was noted by FISH, although this deletion was not revealed by Array‐CGH at 1 Mb resolution, the last array clone being 0.35 or 1 Mb distal to the 4p FISH probe. The female phenotype of this patient must be due to the loss of the derivative Y chromosomes in some of her cells, especially the gonads, while the 4p subtelomeric deletion does not seem to contribute to her phenotype. © 2008 Wiley‐Liss, Inc.
Effect of acid-etching procedure on selected physical properties of mineral trioxide aggregate.

AIM To evaluate the effect of acid-etch procedures on the compressive strength and surface microhardness of tooth-coloured mineral trioxide aggregate (MTA). METHODOLOGY White ProRoot MTA (Dentsply Tulsa Dental) was mixed and packed into cylindrical tubes of 4 mm in diameter and 6 mm in height. Three groups, each of 15 specimens were subjected to an acid-etch procedure either 4, 24 or 96 h after mixing. The compressive strength was measured and compared with unetched control groups. Differences between groups were analysed using the Kruskall-Wallis test. A further batch of cylindrical specimens of 6 mm in diameter and 12 mm in height were prepared for testing surface microhardness. Three groups of 15 specimens were subjected to the acid-etch procedure at either 4, 24 or 96 h following mixing. Data were subjected to one-way anova. Changes in the surface microstructure before and after the acid-etch procedures were analysed using a scanning electron microscope (SEM). RESULTS There was a general trend for the compressive strength and surface microhardness of specimens to increase with time. In terms of compressive strength, the increase was significant between 4 h and the other time periods for both experimental and control groups (P < 0.0001); however, there was no significant difference between 24 and 96 h. The increase in surface microhardness was significant between 4, 24 and 96 h (P < 0.0001). In addition, there was a significant difference between experimental and control groups at all time periods (P < 0.0001). SEM examination revealed morphological differences between the intact and the etched MTA surfaces. CONCLUSIONS Acid-etch procedures affected the compressive strength and surface microhardness of ProRoot MTA. This indicates that it may be better to postpone restorative procedures for at least 96 h after mixing MTA. Etching created surface changes that might have the potential to enhance bonding of resinous materials.
Selective Activation of the Transcription Factor NFAT1 by Calcium Microdomains near Ca2+ Release-activated Ca2+ (CRAC) Channels*

NFATs are a family of Ca2+-dependent transcription factors that play a central role in the morphogenesis, development, and physiological activities of numerous distinct cell types and organ systems. Here, we visualize NFAT1 movement in and out of the nucleus in response to transient activation of store-operated Ca2+ release-activated Ca2+ (CRAC) channels in nonexcitable cells. We show that NFAT migration is exquisitely sensitive to Ca2+ microdomains near open CRAC channels. Another Ca2+-permeable ion channel (TRPC3) was ineffective in driving NFAT1 to the nucleus. NFAT1 movement is temporally dissociated from the time course of the Ca2+ signal and remains within the nucleus for 10 times longer than the duration of the trigger Ca2+ signal. Kinetic analyses of each step linking CRAC channel activation to NFAT1 nuclear residency reveals that the rate-limiting step is transcription factor exit from the nucleus. The slow deactivation of NFAT provides a mechanism whereby Ca2+-dependent responses can be sustained despite the termination of the initial Ca2+ signal and helps explain how gene expression in nonexcitable cells can continue after the primary stimulus has been removed.
Ex vivo performance of five methods for root canal length determination in primary anterior teeth.

AIM To evaluate in a laboratory setting the performance of five methods for the determination of root canal length in primary anterior teeth. METHODOLOGY Twenty extracted primary incisors, with at least two-thirds of the root, were used. After access cavity preparation, the teeth were embedded in alginate mixed with 0.9% sodium chloride solution. One operator determined root canal length using tactile sense (T), conventional radiography (RAD), tactile sense and conventional radiography (T + RAD), digital radiography (RDIG) and Root ZX electronic apex locator (EAL) methods. Next, the actual length (AL) was visually determined using a K-file from the coronal reference to the apical foramen or apical resorption level. The measurements obtained through each method were compared to the AL using the intraclass correlation coefficient (ICC) with the limits of agreement calculated with Bland and Altman analysis. The measurements were classified as acceptable (+/-1 mm from the AL) or not (>1 mm shorter or longer), and the McNemar test was employed for method comparison. RESULTS Differences, limits of agreement and ICCs for each method were respectively EAL = -0.29; -1.02 to 0.44; 0.990; T + RAD = 0.17; -2.18 to 2.51; 0.929; RAD = 0.50; -3.41 to 4.41; 0.818; RDIG = 0.95; -3.76 to 5.65; 0.700; and T = -0.48; -5.59 to 4.64; 0.499. The most accurate and acceptable method was the EAL, followed by the T + RAD. : The EAL method performed best for root canal length determination in primary teeth.
Progressive and symmetric supraorbital hyperostosis with bony and soft tissue overgrowth in an Ethiopian female: A newly recognized overgrowth syndrome?

We report on an Ethiopian female with generalized overgrowth of postnatal onset accompanied by progressive and symmetric overgrowth of skeletal and soft tissues. Her phenotype consisted of progressive and symmetric overgrowth of the supraorbital ridges, glabella, occiput, cervical spine, and distal phalanges of all extremities, but particularly the 3rd and 4th digits. She also has overgrowth of soft tissues of the posterior neck (thought to be fatty in origin), alveolar hyperplasia, and overgrowth of the skin comprising the areola and umbilicus. Other clinical findings included obstructive sleep apnea and normal intelligence. A genetic workup of extended banding chromosome analysis and chromosomal microarray were normal, as were PTEN and FNLA mutation analyses. Histologic examination of the excised supraorbital ridges demonstrated normal bone. However, the bone began to regrow in a symmetric fashion within 3 months of removal. This patient's phenotype is at variance with any known overgrowth syndrome. © 2008 Wiley‐Liss, Inc.
Temporal relationship between cancer and myositis identifies two distinctive subgroups of cancers: impact on cancer risk and survival in patients with myositis.

OBJECTIVES The aim was to compare standardized incidence ratios (SIRs) of cancers temporally related and unrelated to active myositis in patients with myositis. METHODS Fifty-two cancer cases were identified in 281 myositis patients. SIRs of cancers having temporal overlap with the active phase of myositis [cancers concurrent with active myositis (CAM), n = 30] and cancers not having such temporal overlap [cancers non-concurrent with active myositis (CNM), n = 22] were compared in 281 patients. RESULTS Patients with CAM were older at diagnosis of myositis, had a greater tendency to be male, more frequent dysphagia and less frequent interstitial lung disease than patients with CNM. CAM SIR (95% CI) was 1.78 (1.19, 2.56) and CNM SIR 1.23 (0.75, 1.90). The peak SIR was observed in the seventh decade of life for CAM and in the third decade for CNM. When stratified by myositis-cancer intervals, CAM SIR was 9.94 (6.43, 14.67) within 1 year of myositis diagnosis, whereas no temporal relationship was found for CNM. Elevated SIRs were observed for oesophageal cancer [57.77 (11.91, 168.82)], non-Hodgkin's lymphoma [41.43 (13.45, 96.69)], adenocarcinoma of unknown primary origin [67.6 (18.42, 173.07]), lung cancer [7.27 (1.98, 18.61)] and ovarian cancer [19.15 (2.32, 69.17)] within 3 years of CAM diagnosis. The cancer stage at the time of diagnosis was more advanced in CAM than CNM (P < 0.001), with a correspondingly increased hazard ratio of mortality [4.3 (1.5, 12.7)] in patients with CAM vs CNM. CONCLUSION A significantly elevated SIR was found for CAM, whereas there was a comparable SIR for CNM relative to the general population. Multiple types of cancers showed elevated SIRs among CAM, but none among CNM. Given that cancer stages in CAM were far advanced at diagnosis, mortality risk was greater in patients with CAM.
Notch- and Transducin-like Enhancer of Split (TLE)-dependent Histone Deacetylation Explain Interleukin 12 (IL-12) p70 Inhibition by Zymosan*

The fungal analog zymosan induces IL-23 and low amounts of IL-12 p70. This study addresses the molecular mechanisms underlying this cytokine pattern in human monocyte-derived dendritic cells. The transcriptional regulation of il23a, one of the chains of IL-23, depended on the activation of c-Rel and histone H3 phosphorylation, as judged from the association of c-Rel with the il23a promoter and the correlation between IL-23 production and Ser-10-histone H3 phosphorylation. Consistent with its reduced ability to produce IL-12 p70, zymosan induced a transient occupancy of the il12a promoter by c-Rel, blocked the production of IL-12 p70 and the transcription of il12a induced by other stimuli, and triggered the expression and nuclear translocation of the transcriptional repressors of the Notch family hairy and enhancer of split (Hes)-1, Hes5, hairy/enhancer-of-split related with YRPW motif protein (Hey)-1, and transducin-like enhancer of split (TLE). Zymosan also induced the interaction of Hes1 and TLE with histone H3 phosphorylated on Ser-10 and deacetylated on Lys-14. Inhibition of class III histone deacetylases increased the production of IL-12 p70 and partially blunted the inhibitory effect of zymosan on the production of IL-12 p70 elicited by LPS and IFN-γ. These results indicate that the selective induction of IL-23 by β-glucans is explained by the activation of c-Rel associated with Ser-10-histone H3 phosphorylation in the il23a promoter mediated by mitogen- and stress-activated kinase and/or protein kinase A and inhibition of il12a transcription by a mechanism involving activation of several corepressors with the ability to bind TLE and to promote histone deacetylation.
Fracture resistance of incisor teeth restored using fibre-reinforced posts and threaded metal posts: effect of post length, location, pretreatment and cementation of the final restoration.

OBJECTIVE The hypothesis of this study was that the fracture load of incisor teeth restored using short, threaded, parallel-sided posts (TMP) is, under special conditions, not inferior to that of teeth restored using long TMPs or fibre-reinforced posts (FRP). METHODOLOGY Seventy-two maxillary incisors and 72 mandibular incisors were collected. Sixty-four in each group were root filled; in half of these FRPs were cemented, and in the other half TMPs were used. Half of the FRPs were pretreated; the others were not pretreated. In the TMP-group, half of the teeth received a long post (10 mm), the other half a short post (3 mm). Crowns were fabricated and cemented with Ketac-cem or Panavia. Eight maxillary incisors and eight mandibular incisors with intact natural crowns were used as control groups. All specimens were loaded until fracture. RESULTS Fracture loads were higher for pretreated FRPs than for untreated FRPs. If the FRPs were not pretreated, fracture loads for maxillary incisors after use of short metal posts were significantly higher (248 N compared with 133 N, P = 0.027). Fracture loads for teeth restored using long TMPs were not higher than for teeth restored using short TMPs (277 N compared with 266 N). Fracture loads for mandibular incisors restored using long (10 mm) pretreated FRP were higher than for mandibular incisors restored using short (3 mm) metal posts (436 N compared with 285 N). Cementation of the crowns using an adhesive resin cement did not increase the fracture load for mandibular incisors, whereas for maxillary incisors, this cementation technique tended to increase fracture loads in teeth restored with FRP, although this increase was not significant at the P < 0.05 level (P = 0.06). In both groups, fracture loads were higher for mandibular incisors. CONCLUSIONS Short, threaded, parallel-sided metal posts might be an alternative to fibre- reinforced posts for maxillary incisors, for teeth with short roots or when FRP cannot be pretreated.
Interferon-α as a Treatment Modality for Colchicine-Resistant Familial Mediterranean Fever

### Objective Previous reports on interferon-α (IFN-α) were conflicting with respect to its efficacy in familial Mediterranean fever (FMF) refractory to colchicine treatment. We investigated the effect of IFN-α in patients with colchicine-resistant FMF. ### Methods In a prospective, patient self-controlled, open-label study evaluating the safety and efficacy of IFN-α in patients with FMF with a severe phenotype, refractory to intensified (oral plus intravenous) colchicine therapy, we advised patients to subcutaneously inject IFN-α, 3 million international units, at the onset of the FMF attack. Attacks not treated with IFN-α of the same patients and in the same sites served as control attacks. Features of each attack were recorded in a questionnaire, eventually used to compare between IFN-α-treated and non-treated attacks. ### Results Ten patients with a total of 80 attacks were recruited. Compared to 22 untreated attacks, a >20% and > 50% reduction in the duration of the attacks was noted in 100% and 90% of the 58 IFN-α-treated attacks, respectively (p 20% and > 50% in 88% and 49% of these attacks, respectively (p < 0.001 for both). The most common drug-related adverse events were chills and fatigue. ### Conclusion Early intervention with IFN-α injections was associated with reduced attack length and/or severity in a substantial number of bouts, with an acceptable cost of adverse events.
Non-surgical management of a large periapical lesion using a simple aspiration technique: a case report.

AIM To report the non-surgical management of a large periapical lesion. SUMMARY Surgical treatment of large periapical lesions is often subject to various complications. Hence, a non-surgical approach should be considered for the management of these lesions. The traditional aspiration technique involves creation of buccal and palatal wounds that can cause considerable discomfort for the patient. This case report describes a simple aspiration technique achieved through the root canal space, which might hasten osseous regeneration, whilst eliminating the need for periapical surgery. KEY LEARNING POINTS Non-surgical techniques can aid in healing of periapical lesions. Non-surgical approaches should be considered before resorting to surgery.
The cytotoxic effects of resin-based sealers on dental pulp stem cells.

AIM To evaluate the effect of four current resin-based adhesives on expanded ex vivo human dental pulp mesenchymal stem cells (DP-MSCs). METHODOLOGY Dental pulp mesenchymal stem cells were derived from dental pulps of ten donors. After in vitro isolation, dental pulp stem cells were analysed using flow cytometry. The immunophenotype of DP-MSCs disclosed the homogeneous expression of the mesenchymal-related antigens CD29, CD44, CD73, CD90, CD105, CD166. DP-MSCs were exposed to four different commercially available bonding systems (CMF Bond, Prime&Bond NT, Clearfil S(3) Bond, XP Bond), and after 24, 48 and 72 h of incubation the morphological features and the cell growth were analysed. Moreover, the cell viability was evaluated at the same times by MTT assay. Data were statistically analysed using a two-way anova and Holm-Sidak method (alpha set at 0.05). RESULTS Significant differences were observed between the four groups when comparing DP-MSCs appearance. DP-MSCs survived and proliferated without inhibition in the presence of CMF Bond adhesive. On the contrary, microscopic evaluation of the other three groups revealed extensive cytotoxic effects from the dentine bonding agents. The MTT assay revealed no statistically significant differences in cell viability after 72 h between the control group and CMF Bond group. All the other experimental groups had statistically lower optical density values. CONCLUSIONS CMF Bond adhesive allowed human dental pulp stem cells to survive and proliferate. All of the other dentine bonding agents had extensive cytotoxic effects.
Regulation of the Action of Early Mitotic Inhibitor 1 on the Anaphase-promoting Complex/Cyclosome by Cyclin-dependent Kinases*

Cell cycle regulation is characterized by alternating activities of cyclin-dependent kinases (CDKs) and of the ubiquitin ligase anaphase promoting complex/cyclosome (APC/C). During S-phase APC/C is inhibited by early mitotic inhibitor 1 (Emi1) to allow the accumulation of cyclins A and B and to prevent re-replication. Emi1 is degraded at prophase by a Plk1-dependent pathway. Recent studies in which the degradation pathway of Emi1 was disrupted have shown that APC/C is activated at mitotic entry despite stabilization of Emi1. These results suggested the possibility of additional mechanisms other than degradation of Emi1, which release APC/C from inhibition by Emi1 upon entry into mitosis. In this study we report one such mechanism, by which the ability of Emi1 to inhibit APC/C is negatively regulated by CDKs. We show that in Plk1-inhibited cells Emi1 is stabilized and phosphorylated, that Emi1 is phosphorylated by CDKs in mitotic but not S-phase cell extracts, and that Emi1 phosphorylation by mitotic cell extracts or purified CDKs markedly reduces the ability of Emi1 to bind and to inhibit APC/C. Finally, we show that the addition of extracts from S-phase cells to extracts from mitotic cells protects Emi1 from CDK-mediated inactivation.