Micro-computed tomographic assessment of dentinal microcrack formation in straight and curved root canals in extracted teeth prepared with hand, rotary and reciprocating instruments.

AIM: To compare microcrack formation in roots of extracted teeth after the shaping of straight and curved root canals with hand, rotary and reciprocating files using micro-computed tomographic (micro-CT) analysis. METHODOLOGY: Thirty straight mandibular incisors and 30 severely curved mesial roots of mandibular molars were randomly divided into 6 experimental groups (n = 10) according to the systems used for the root canal preparation and the root canal curvature: ProTaper Universal for Hand Use (Dentsply Sirona, Ballaigues, Switzerland), HyFlex EDM (Coltene-Whaledent, Altstätten, Switzerland) and Reciproc Blue (VDW, Munich, Germany) files used in mandibular incisors (straight canals) and mesial roots of mandibular molars (curved canals). The roots were imaged with micro-CT scanning at an isotropic resolution of 14 µm before and after root canal preparation, and the cross-sectional images generated were assessed to detect microcracks. RESULTS: All dentinal defects identified after root canal preparation were already present before instrumentation, and no new microcracks were detected. Dentinal microcracks were present in 19% (ProTaper Universal for Hand Use), 11% (Hyflex EDM) and 23% (Reciproc Blue) of the cross-sections when the instrumentation was performed in mandibular incisors. Instrumentation of mandibular molars revealed microcracks in 15% (ProTaper Universal for Hand Use), 16% (Hyflex EDM) and 17% (Reciproc Blue) of the cross-sections. CONCLUSIONS: Preparation of straight and curved root canals with ProTaper Universal for Hand Use, HyFlex EDM and Reciproc Blue systems did not produce microcracks in extracted teeth when evaluated with micro-CT.

Rituximab use in pediatric lupus anticoagulant hypoprothrombinemia syndrome - report of three cases and review of the literature.

Lupus anticoagulant hypoprothrombinemia syndrome (LA-HPS) is a rare condition that may predispose both to thrombosis and bleeding due to positive lupus anticoagulant (LA) and factor II (FII) deficiency. It can be seen in association with infections or systemic lupus erythematosus (SLE) and may require glucocorticoids (GCs) and/or immunosuppressive medications. Pediatric LA-HPS cases in the literature and three cases that received only rituximab (RTX) for LA-HPS (in addition to GCs) at two institutions between January 2010 and June 2017 were analyzed descriptively. Pediatric LA-HPS cases (≤18 years) with bleeding or thrombotic events were included. Information obtained included demographics, presenting symptoms, diagnoses, treatments, pre-/post-treatment prothrombin time (PT)/partial thromboplastin time (PTT)/LA/FII levels, and outcomes. In addition to three LA-HPS cases identified at our institutions, as of June 2017, 37 articles reported 54 pediatric LA-HPS cases (mean age: 8 years (0.9-17 years); female/male: (2:1); viral illness 27 (50%), SLE 20 (37%), and other six (11%)). All cases had a positive LA and FII deficiency (range: 0%-40%). All cases presented with bleeding diathesis and were treated with various regimens, but there was no reported use of RTX. The purpose of this report is to describe the novel use of RTX as a steroid-sparing agent in three pediatric SLE cases and to systematically review the literature on pediatric cases of LA-HPS.

Effector memory CD4(+) T cells differentially express activation associated molecules depending on the duration of American cutaneous leishmaniasis lesions.

A high number of Leishmania-responder T cells is found in cutaneous leishmaniasis lesions, suggesting that important immunological events occur at the site of infection. Although activated, cytotoxic and regulatory T cells infiltrating into lesions may influence disease pathogenesis, the role of the T cell differentiation pattern of lymphocytes in lesions is unknown. Our aim was to investigate whether the phase of lesion development (early or late) is influenced by the functional status of cells present in inflammatory infiltrate. Activation, cytotoxity and T cell differentiation molecules were evaluated in lesion mononuclear cells by flow cytometry. The frequency of T cells was correlated with the lesion area (r = 0·68; P = 0·020). CD4(+) CD25(+) T cells predominated over CD4(+) CD69(+) T cells in early lesions (less than 30 days), whereas late lesions (more than 60 days) exhibited more CD4(+) CD69(+) T cells than CD4(+) CD25(+) T cells. The duration of illness was correlated positively with CD4(+) CD69(+) (r = 0·68; P = 0·005) and negatively with CD4(+) CD25(+) T cells (r = -0·45; P = 0·046). Most CD8(+) T cells expressed cytotoxic-associated molecules (CD244(+) ), and the percentages were correlated with the lesion area (r = 0·52; P = 0·04). Both CD4(+) and CD8(+) effector memory T cells (TEM -CD45RO(+) CCR7(-) ) predominated in CL lesions and were significantly higher than central memory (TCM -CD45RO(+) CCR7(+) ) or naive T cells (CD45RO(-) CCR7(+) ). An enrichment of TEM cells and contraction of naive T cells were observed in lesions in comparison to blood (P = 0·006) for both CD4(+) and CD8(+) T cells. Lesion chronicity is associated with a shift in activation phenotype. The enrichment of TEM and activated cytotoxic cells can contribute to immune-mediated tissue damage.

The role of tenofovir alafenamide in future HIV management.

HIV infection has become a chronic condition rather than an acute life-threatening disease in developed countries, thanks to consistent innovation and evolution of effective interventions. This has altered HIV management and created new challenges. People living with HIV (PLWHIV) are living longer and so encounter comorbidities linked not only with their disease, but also with ageing, lifestyle and chronic exposure to antiretroviral therapy (ART). Although longevity, viral suppression and the prevention of viral transmission remain key goals, more needs to be achieved to encompass the vision of attaining an optimum level of overall health. Treatment choices and management practices should ensure patients' long-term health with minimal comorbidity. Treatments that balance optimal efficacy with the potential for improved long-term safety are needed for all patients. In this review, we consider the evolution and development of tenofovir alafenamide (TAF), a novel prodrug of tenofovir which offers high antiviral efficacy at doses over ten times lower than that of tenofovir disoproxil fumarate (TDF). Emerging clinical data suggest that elvitegravir, cobicistat, emtricitabine and TAF (E/C/F/TAF) as a single-tablet regimen offers highly effective viral suppression in treatment-naïve and treatment-experienced patients with an improved renal and bone safety profile compared with TDF, this having been demonstrated in diverse groups including patients with existing renal impairment and adolescents. The profile of TAF identifies it as an agent with a promising role within future ART regimens that aim to deliver the vision of undetectable viral load, while requiring less monitoring and having a safety profile designed to minimize comorbid risks while supporting good long-term health.

Effect of the combination of metformin hydrochloride and melatonin on oxidative stress before and during pregnancy, and biochemical and histopathological analysis of the livers of rats after treatment for polycystic ovary syndrome.

The aim of the present study was to analyze the effect of a combination of metformin hydrochloride and melatonin on oxidative stress together with a biochemical and histopathological analysis of the livers of Wistar rats induced with PCOS. The results indicated that a combination of the drugs was more effective in the reduction of plasmatic levels of liver enzyme alanine aminotransferase, nitric oxide and total glutathione, and decreased the inflammatory response and histopathological damage, producing results that were significantly similar to animals from the control group. A mixture of the drugs produced more effective results against liver toxicity caused by PCOS, encouraging the normalization of biochemical parameters. During pregnancy, there was reduced oxidative stress compared to monotherapeutic use of these drugs. Interestingly, the combination of the drugs caused a physiological reaction similar to responses identified in healthy rats without induction of the PCOS control group. However, the clinical and physiological effectiveness of the combination should be further explored, especially with respect to the possible side effects on offspring.

A pediatric case of gluten sensitivity with severe neurological presentation.

UNLABELLED: Neurologic manifestations are present in a reasonable proportion of adult celiac patients and can be the first sign of gluten sensitivity. In children, the risk of neurological complications is lower, and gluten sensitivity with neurological presentation seems to be rare. We report a case of gluten sensitivity with severe neurological presentation in a 3-year-old girl. In the absence of gastrointestinal symptoms, the presence of white matter lesions in cerebral magnetic resonance imaging suggested an acute disseminated encephalomyelitis. Recurrence of neurologic symptoms and cerebral lesions over a long period of time made the authors consider an autoimmune/inflammatory systemic disease. IgA anti-transglutaminase (TG) 2 was elevated and duodenal biopsy confirmed the presence of enteropathy. A gluten-free diet led to complete resolution of neurological manifestations and arrest of white matter lesions progression. CONCLUSION: In children with unclear neurologic manifestations with probable autoimmune etiology, anti-TG2 autoantibody titers should be determined considering the possibility of gluten sensitivity. Gluten-free diet remains the only effective treatment reported to date and, therefore, should be recommended to all patients with gluten sensitivity despite the type of manifestations. More studies, focusing on neurological manifestations and its response to gluten-free diet, are needed.

Electronic and structural properties of Möbius boron-nitride and carbon nanobelts.

For the development of nanofilters and nanosensors, we wish to know the impact of size on their geometric, electronic, and thermal stabilities. Using the semiempirical tight binding method as implemented in the xTB program, we characterized Möbius boron-nitride and carbon-based nanobelts with different sizes and compared them to each other and to normal nanobelts. The calculated properties include the infrared spectra, the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO), the energy gap, the chemical potential, and the molecular hardness. The agreement between the peak positions from theoretical infrared spectra compared with experimental ones for all systems validates the methodology that we used. Our findings show that for the boron-nitride-based nanobelts, the calculated properties have an opposite monotonic relationship with the size of the systems, whereas for the carbon-based nanobelts, the properties show the same monotonic relationship for both types of nanobelts. Also, the torsion presented on the Möbius nanobelts, in the case of boron-nitride, induced an inhomogeneous surface distribution for the HOMO orbitals. High-temperature molecular dynamics also allowed us to contrast carbon-based systems with boron-nitride systems at various temperatures. In all cases, the properties vary with the increase in size of the nanobelts, indicating that it is possible to choose the desired values by changing the size and type of the systems. This work has many implications for future studies, for example our results show that carbon-based nanobelts did not break as we increased the temperature, whereas boron-nitride nanobelts had a rupture temperature that varied with their size; this is a meaningful result that can be tested when the use of more accurate simulation methods become practical for such systems in the future.

Risks and benefits of sharing patient information on social media: a digital dilemma.

Social media (SoMe) has witnessed remarkable growth and emerged as a dominant method of communication worldwide. Platforms such as Facebook, X (formerly Twitter), LinkedIn, Instagram, TikTok, and YouTube have become important tools of the digital native generation. In the field of medicine, particularly, cardiology, attitudes towards SoMe have shifted, and professionals increasingly utilize it to share scientific findings, network with experts, and enhance teaching and learning. Notably, SoMe is being leveraged for teaching purposes, including the sharing of challenging and intriguing cases. However, sharing patient data, including photos or images, online carries significant implications and risks, potentially compromising individual privacy both online and offline. Privacy and data protection are fundamental rights within European Union treaties, and the General Data Protection Regulation (GDPR) serves as the cornerstone of data protection legislation. The GDPR outlines crucial requirements, such as obtaining 'consent' and implementing 'anonymization', that must be met before sharing sensitive and patient-identifiable information. Additionally, it is vital to consider the patient's perspective and prioritize ethical and social considerations when addressing challenges associated with sharing patient information on SoMe platforms. Given the absence of a peer-review process and clear guidelines, we present an initial approach, a code of conduct, and recommendations for the ethical use of SoMe. In conclusion, this comprehensive review underscores the importance of a balanced approach that ensures patient privacy and upholds ethical standards while harnessing the immense potential of SoMe to advance cardiology practice and facilitate knowledge dissemination.

Mitochondrial DNA variability in populations of Centris aenea (Hymenoptera, Apidae), a crop-pollinating bee in Brazil.

Centris spp are oil-collecting solitary bees that are valuable pollinators of crops such as Brazil nut, cashew, and acerola. We investigated the genetic variability of populations of C. aenea in the northeastern region of Brazil. Total DNA was extracted from 59 individuals from 6 locations in the States of Pernambuco and Bahia and a 600-650-bp fragment of the mitochondrial COI/COII region amplified by PCR, followed by digestion with the restriction enzymes DraI and SspI. PCR-RFLP analysis revealed eight different haplotypes among the populations. Haplotype A1, revealed by DraI, was the most frequent (50%), and haplotypes A3 and A4 were exclusive to Feira de Santana, Bahia and Morro do Chapéu, Bahia, respectively. Among the haplotypes revealed by SspI, B2 was the most frequent (37%) and B3 was exclusive to Feira de Santana. This information revealing high haplotype diversity will be useful for developing management strategies for Centris, especially because of increasing interest in the rearing and/ or relocation of these bees for crop pollination.

Möbius carbon nanobelts interacting with heavy metal nanoclusters.

CONTEXT: The interaction between carbon nanostructures and heavy metal clusters is of great interest due to their potential applications as sensors and filters to remove the former from environment. In this work, we investigated the interaction between two types of carbon nanobelts (Möbius-type nanobelt and simple nanobelt) and nickel, cadmium, and lead nanoclusters. Our aim was to determine how both systems interact which would shed light on the potential applications of the carbon nanostructures as pollutant removal and detecting devices. METHODS: To investigate the interaction between carbon nanostructures and heavy metal nanoclusters, we utilized the semiempirical tight binding framework provided by xTB software with the GFN2-xTB Hamiltonian. We performed calculations to determine the best interaction site, lowest energy geometries, complexes stability (using molecular dynamics at 298K), binding energy, and electronic properties. We also carried out a topological study to investigate the nature and intensity of the bonds formed between the metal nanoclusters and the nanobelts. Our results demonstrate that heavy metal nanoclusters have a favorable binding affinity towards both nanobelts, with the Möbius-type nanobelt having a stronger interaction. Additionally, our calculations reveal that the nickel nanocluster has the lowest binding energy, displaying the greatest charge transfer with the nanobelts, which was nearly twice that of the cadmium and lead nanoclusters. Our combined results lead to the conclusion that the nickel nanoclusters are chemisorbed, whereas cadmium and lead nanoclusters are physisorbed in both nanobelts. These findings have significant implications for the development of sensor and filtering devices based on carbon and heavy metal nanoclusters.

Effectiveness of the ProTaper Universal Retreatment™ system for removing a 10-year-old filling material.

AIM: The aim of the present study was to evaluate the effectiveness of the ProTaper Universal Retreatment™ system and the manual technique for removing a 10-year-old filling material. METHODS: Twenty mesiobuccal canals of mandibular first molars with curvature degrees ranging from 20° to 35° were instrumented by the Double-Flared Instrumentation Technique with the NitiFlex files. The root canals were dried with sterile paper points and filled with gutta-percha and a zinc oxide-eugenol-based sealer using a cold lateral condensation technique. Accesses to the cavities were temporarily sealed with Cavit. The teeth were embedded in gauze containing saline solution, which was renewed every 2 weeks, and were stored at 37 °C in 100% humidity for 10 years. Buccolingual and mesiodistal radiographs were taken to evaluate the quality of the root canal filling. The radiographs were mounted in slide frames to allow them to be evaluated by the three examiners, who were specialists in endodontics. Only the specimens in whom there was agreement between the three evaluators were included in the study. The specimens were divided into 2 groups with 10 root canals each, according to gutta-percha removal techniques: Group 1: ProTaper Universal Retreatment™ system; Group 2: Hedström and K-files. Buccolingual and mesiodistal radiographs were taken and evaluated by three examiners who determined the effectiveness of the removal of the filling material. The presence of material was measured according to a score scale. Data were analyzed statistically by Fisher's exact test at 5% significance level. RESULTS: There were no statistical differences between the two methods in the coronal (P=0.211), and middle (P=0.266) thirds, but there were statistical differences between the two methods in the apical third (P=0.038). CONCLUSION: Not one of the experimental techniques promoted complete removal of the filling materials. The manual technique with K-file and Hedström files achieved better results than the ProTaper Universal Retreatment™ system.

Highly efficient siRNA delivery system into human and murine cells using single-wall carbon nanotubes.

Development of RNA interference (RNAi) technology utilizing short interfering RNA sequences (siRNA) has focused on creating methods for delivering siRNAs to cells and for enhancing siRNA stability in vitro and in vivo. Here, we describe a novel approach for siRNA cellular delivery using siRNA coiling into carboxyl-functionalized single-wall carbon nanotubes (SWCNTs). The CNT-siRNA delivery system successfully demonstrates nonspecific toxicity and transfection efficiency greater than 95%. This approach offers the potential for siRNA delivery into different types of cells, including hard-to-transfect cells, such as neuronal cells and cardiomyocytes. We also tested the CNT-siRNA system in a non-metastatic human hepatocellular carcinoma cell line (SKHep1). In all types of cells used in this work the CNT-siRNA delivery system showed high efficiency and apparent no side effects for various in vitro applications.

ARNIs: balancing "the good and the bad" of neuroendocrine response to HF.

BACKGROUND: A new class of drugs-angiotensin receptor, neprylisin inhibitors, ARNI-has shown to be prognostic superior in HFrEF to the sole inhibition of the renin-angiotensin axes with enalapril. The ultimate mechanism of action of ARNIs is unknown. AIM: We have considered that ARNI exerts a positive modulation of the neuroendocrine balance, with enhancement of the physiological diuresis and dilatation due to neprylisin inhibition by sacubitril. This represents a shift in HF medical therapy always directed to counteract (with inhibitors of the renin-angiotensin system, beta blockers or inhibitors of aldosterone) the so-called "bad" neuroendocrine response. Development of ARNI, on the contrary, has led to consider the neuroendocrine response to HFrEF from a different angle, which is to say that the activation is not always deleterious, but it could also be beneficial. This concept is highlighted by the enhancement of the activity of atrial natriuretic peptide, induced by sacubitril/valsartan in the PARADIGM trial, and found as proof from early studies on untreated patients with constrictive pericarditis. The possibility that sacubitril inhibition of neprylisin acts by enhancing substance P and gene-related calcitonin peptide is also considered, as well as the negative effect of neprylisin inhibition. CONCLUSIONS: The beneficial effects of ARNI are related, in part at least, to a positive modulation of the neuroendocrine response to the disease, resulting in an increase of physiological diuresis and dilatation.

The skin homing receptor cutaneous leucocyte-associated antigen (CLA) is up-regulated by Leishmania antigens in T lymphocytes during active cutaneous leishmaniasis.

The cutaneous leucocyte-associated antigen receptor (CLA) can direct Leishmania-specific T lymphocytes towards inflamed skin lesions. Homing receptors [CLA, lymphocyte-associated antigen 1 (LFA-1) or CD62L] were analysed in lymphocytes from blood and cutaneous leishmaniasis (CL) lesions. CL patients with active lesions (A-CL) presented lower levels of T lymphocytes expressing the CLA(+) phenotype (T CD4(+) = 10.4% +/- 7.5% and T CD8(+) = 5.8% +/- 3.4%) than did healthy subjects (HS) (T CD4(+) = 19.3% +/- 13.1% and T CD8(+) = 21.6% +/- 8.8%), notably in T CD8(+) (P < 0.001). In clinically cured patients these percentages returned to levels observed in HS. Leishmanial antigens up-regulated CLA in T cells (CLA(+) in T CD4(+) = 33.3% +/- 14.1%; CLA(+) in T CD8(+) = 22.4% +/- 9.4%) from A-CL but not from HS. An enrichment of CLA(+) cells was observed in lesions (CLA(+) in T CD4(+) = 45.9% +/- 22.5%; CLA(+) in T CD8(+) = 46.4% +/- 16.1%) in comparison with blood (CLA(+) in T CD4(+) = 10.4% +/- 7.5%; CLA(+) in T CD8(+) = 5.8% +/- 3.4%). Conversely, LFA-1 was highly expressed in CD8(+) T cells and augmented in CD4(+) T from peripheral blood of A-CL patients. In contrast, CD62L was not affected. These results suggest that Leishmania antigens can modulate molecules responsible for migration to skin lesions, potentially influencing the cell composition of inflammatory infiltrate of leishmaniasis or even the severity of the disease.

Muscarinic acetylcholine neurotransmission enhances the late-phase of long-term potentiation in the hippocampal-prefrontal cortex pathway of rats in vivo: a possible involvement of monoaminergic systems.

The prefrontal cortex is continuously required for working memory processing during wakefulness, but is particularly hypoactivated during sleep and in psychiatric disorders such as schizophrenia. Ammon's horn CA1 hippocampus subfield (CA1) afferents provide a functional modulatory path that is subjected to synaptic plasticity and a prominent monoaminergic influence. However, little is known about the muscarinic cholinergic effects on prefrontal synapses. Here, we investigated the effects of the muscarinic agonist, pilocarpine (PILO), on the induction and maintenance of CA1-medial prefrontal cortex (mPFC) long-term potentiation (LTP) as well as on brain monoamine levels. Field evoked responses were recorded in urethane-anesthetized rats during baseline (50 min) and after LTP (130 min), and compared with controls. LTP was induced 20 min after PILO administration (15 mg/kg, i.p.) or vehicle (NaCl 0.15 M, i.p.). In a separate group of animals, the hippocampus and mPFC were microdissected 20 min after PILO injection and used to quantify monoamine levels. Our results show that PILO potentiates the late-phase of mPFC LTP without affecting either post-tetanic potentiation or early LTP (20 min). This effect was correlated with a significant decrease in relative delta (1-4 Hz) power and an increase in sigma (10-15 Hz) and gamma (25-40 Hz) powers in CA1. Monoamine levels were specifically altered in the mPFC. We observed a decrease in dopamine, 5-HT, 5-hydroxyindolacetic acid and noradrenaline levels, with no changes in 3,4-hydroxyphenylacetic acid levels. Our data, therefore, suggest that muscarinic activation exerts a boosting effect on mPFC synaptic plasticity and possibly on mPFC-dependent memories, associated to monoaminergic changes.

Human periodontal ligament: a niche of neural crest stem cells.

BACKGROUND AND OBJECTIVE: The periodontal ligament is a specialized connective tissue, derived from dental follicle and originated from neural crest cells. Recently it has been suggested, based on animal models, that periodontal ligament could be a niche for neural crest stem cells. However, there is still little knowledge on this subject. The identification of neural crest adult stem cells has received much attention based on its potential in tissue regeneration. The objective of the present work was to verify the human periodontal ligament as a niche for neural crest stem cells. MATERIAL AND METHODS: Cells from human periodontal ligament were isolated from 10 teeth of seven individuals (periodontal ligament pool group) and also from four teeth of one individual (periodontal ligament single group), after enzymatic digestion. The cells were cultured in specific inductive medium. Analyses of protein and gene expression were performed through immunocytochemistry and reverse transcription-polymerase chain reaction techniques, respectively. RESULTS: Mesodermal phenotypes (adipogeneic, osteogenic and myofibroblastic) were identified after culture in inductive medium. Immunocytochemistry analyses showed the presence of the nestin marker of neural stem cells and also markers of undifferentiated neural crest cells (HNK1, p75). When cultured in inductive medium that allowed neural differentiation, the cells showed markers for beta-tubulin III, neurofilament M, peripherin, microtubule-associated protein 2 and protein zero. The results were similar between the two study groups (the periodontal ligament pool group and the periodontal ligament single group). CONCLUSION: This research provides evidence that human periodontal ligament, in addition to its mesodermal derivatives, produces neural crest-like cells. Such features suggest a recapitulation of their embryonic state. The human periodontal ligament revealed itself as a viable alternative source for possible primitive precursors to be used in stem-cell therapies.

Heterotic groups in tropical maize germplasm by test crosses and simple sequence repeat markers.

The objectives of the present study were to determine heterotic groups of germplasm lines of tropical maize by test crosses and by simple sequence repeat (SSR) markers and to compare five grouping methods of heterogeneous maize. Sixteen lines of nine populations in the S5 generation were evaluated in test crosses with three testers. The results of four experimental trials over two years were used to group the lines by five methods: evaluation based on the hybrid mean in top-cross tests, hybrid index, genetic diversity by the Mahalanobis distance, genetic diversity by the Euclidean distance, and genetic diversity by SSR markers. The concordance of grouping by the Mahalanobis and Euclidean distance amounted to 87.50%, and the concordance of these methods and grouping by SSR markers was 56.25%. Grouping by SSR markers was consistent with the genealogy of the lines and is a useful procedure for the formation of heterotic groups of tropical maize lines.

Type 2 dens invaginatus in a maxillary lateral incisor: a case report of a conventional endodontic treatment.

Dens invaginatus is a rare malformation of the teeth resulting from the invagination of the tooth crown before biological mineralization occurs. In most cases, the thin or incomplete enamel lining of the invagination cannot prevent the entry of bacteria into the pulp, which leads to pulp necrosis with an eventual periapical inflammatory response. The treatment options include preventive sealing or filling of the invagination, root canal treatment, endodontic apical surgery and extraction. The root canal treatment of such teeth is often complicated because of their anatomical complexity. This case describes a successful non-surgical endodontic treatment of a maxillary lateral incisor with type 2 dens invaginatus with a large periradicular lesion. At follow-up examinations after 6 and 12-months, the tooth was asymptomatic and the healed lesion was evident radiographically

The histamine H3 receptor antagonist thioperamide rescues circadian rhythm and memory function in experimental parkinsonism.

Parkinson's disease (PD) is a common neurodegenerative disorder, characterized by motor impairment and a wide range of non-motor symptoms, including sleep disorders and cognitive and affective deficits. In this study, we used a mouse model of PD based on 6-hydroxydopamine (6-OHDA) to examine the effect of thioperamide, a histamine H3 receptor antagonist, on circadian activity, recognition memory and anxiety. A partial, bilateral 6-OHDA lesion of the striatum reduces motor activity during the active phase of the 24 h cycle. In addition, the lesion disrupts the endogenous circadian rhythm observed when mice are maintained in constant darkness. Administration of thioperamide to 6-OHDA-lesion mice rescues the normal rest/activity cycle. Moreover, thioperamide counteracts the deficit of novel object recognition produced by 6-OHDA. Our experiments show that this memory impairment is accompanied by disrupted gamma oscillations in the hippocampus, which are also rescued by thioperamide. In contrast, we do not observe any modification of the anxiogenic effect of 6-OHDA in response to administration of thioperamide. Our results indicate that thioperamide may act as a multifunctional drug, able to counteract disruptions of circadian rhythm and cognitive deficits associated with PD.