Validity of the dental operating microscope and selective dentin removal with ultrasonic tips for locating the second mesiobuccal canal (MB2) in maxillary first molars: An in vivo study.

Background: Several investigations have determined whether the use of a dental operating microscope (DOM) in combination with selective dentine removal with ultrasonic tips increases the percentage of location of the Mesiobuccal 2 (MB2) root canal in maxillary first molars (MFM). However, these studies did not report the performance of in vivo measurements with the comparison with a gold standard. The aim of this study was to determine the validity of the DOM and selective dentin removal with ultrasonic tips to locate the MB2 root canal in MFM using Cone Beam Computed Tomography (CBCT) as the gold standard. Material and Methods: The initial sample size was 91 patients, but 7 were excluded, so the sample size was 84 patients who signed the informed consent. Inclusion criteria: MFM indicated for root canal treatment. An expert blinded observer identified the MB2 in the CBCT. Two standardized examiners (Kappa=91%) performed the clinical assessment in three stages: Stage 1, canal location with an endodontic explorer and a mirror; Stage 2, use of DOM and Stage 3, use of DOM plus selective dentine removal with ultrasonic tips. The validity of each stage was calculated. Results: The prevalence of MB2 using CBCT was 79%, by clinical location was 68%. Sensitivity was 79%, 82%, 86% for stage 1, 2 and 3, respectively. Specificity and Positive Predictive Values were 100% for all methods. Negative Predictive Value was 56%, 60%, 67%, respectively. Positive Likelihood Ratio tends to infinity for all methods, Negative Likelihood Ratio= 0.21, 0.18 and 0.14 and Accuracy= 83%, 86% and 89%, respectively. Conclusions: The use of DOM with selective dentine removal with ultrasonic tips is the most valid method for locating MB2 canal in MFM. There was an increase in the location of the MB2 root canal with the DOM and ultrasonic tips, which definitely help the clinician. Key words:Cone beam computed tomography, microscopy, second mesiobuccal canal, sensitivity and specificity, validity.

Electronic complementarity permits hindered butenolide heterodimerization and discovery of novel cGAS/STING pathway antagonists.

sp3-hybridized attached-rings are common motifs in secondary metabolites and represent tetrahedral equivalents to the biaryl substructures that overpopulate synthetic libraries. Few methods are available that can link fully substituted carbon atoms of two rings with stereocontrol. Here we have developed a stereoselective, heteroselective butenolide coupling that exhibits an unusually fast rate of C-C bond formation driven by exquisite complementarity of the reacting π systems. Heterodimerization generates a compound collection with topological complexity and diverse principal moments of inertia. The special status of the sp3-sp3 attached-ring motif is demonstrated in a high-throughput screen for inhibitors of the cyclic GMP-AMP synthase/stimulator of interferon genes pathway, which recruited these butenolide heterodimers from a field of 250,000 compounds. The driving forces underlying this general attached-ring coupling identify a novel paradigm for the accession of wider natural product chemical space, accelerating the discovery of selective lead compounds.

Utilizing Native Directing Groups: Mechanistic Understanding of a Direct Arylation Leads to Formation of Tetracyclic Heterocycles via Tandem Intermolecular, Intramolecular C-H Activation.

A mechanistic study on a direct arylation using a native picolylamine directing group is reported. Kinetic studies determined the concentration dependence of substrates and catalysts, as well as catalyst degradation, which led to the development of a new set of reaction conditions capable of affording a robust kinetic profile. During reaction optimization, a small impurity was observed, which was determined to be a dual C-H activation product. A second set of conditions were found to flip the selectivity of the C-H activation to form this tetracycle in high yield. A catalytic cycle is proposed for the intermolecular/intramolecular C-H activation pathway.

Abnormal pulmonary function tests predict the development of radiation-induced pneumonitis in advanced non-small cell lung Cancer.

BACKGROUND: Radiation pneumonitis (RP) is a frequent complication of concurrent chemoradiotherapy (CCRT) and is associated with severe symptoms that decrease quality of life and might result in pulmonary fibrosis or death. The aim of this study is to identify whether pulmonary function test (PFT) abnormalities may predict RP in non-small cell lung cancer (NSCLC) patients. METHODS: A prospective multi-institutional study was conducted with locally advanced and oligometastatic NSCLC patients. All participants were evaluated at baseline, end of CCRT, week 6, 12, 24, and 48 post-CCRT. They completed forced spirometry with a bronchodilator, body plethysmography, impulse oscillometry, carbon monoxide diffusing capacity (DLCO), molar mass of CO2, six-minute walk test and exhaled fraction of nitric oxide (FeNO). Radiation pneumonitis was assessed with RTOG and CTCAE. The protocol was registered in www.clinicaltrials.gov (NCT01580579), registered April 19, 2012. RESULTS: Fifty-two patients were enrolled; 37 completed one-year follow-up. RP ≥ Grade 2 was present in 11/37 (29%) for RTOG and 15/37 (40%) for CTCAE. Factors associated with RP were age over 60 years and hypofractionated dose. PFT abnormalities at baseline that correlated with the development of RP included lower forced expiratory volume in one second after bronchodilator (p = 0.02), DLCO (p = 0.02) and FeNO (p = 0.04). All PFT results decreased after CCRT and did not return to basal values at follow-up. CONCLUSIONS: FEV1, DLCO and FeNO prior to CCRT predict the development of RP in NSCLC. This study suggests that all patients under CCRT should be assessed by PFT to identify high-risk patients for close follow-up and early treatment.

Dynamic Ligand Exchange as a Mechanistic Probe in Pd-Catalyzed Enantioselective C-H Functionalization Reactions Using Monoprotected Amino Acid Ligands.

A new tool for probing enantioselective reaction mechanisms is introduced. Monitoring the temporal change in product enantiomeric excess after addition of the opposite enantiomer of the ligand during the reaction provides a means of probing dynamic ligand exchange in enantioselective C-H iodination catalyzed by Pd with monoprotected amino acid ligands (MPAAs). This work has general potential to provide insights about the dynamics of catalyst and ligand molecularity and exchange.

A Role for Pd(IV) in Catalytic Enantioselective C-H Functionalization with Monoprotected Amino Acid Ligands under Mild Conditions.

Kinetic and mechanistic studies of the desymmetrization of benzhydrylamine using Pd/monoprotected amino acid ligands (Pd/MPAA) via C-H functionalization with molecular iodine provide mechanistic insight into the rate-determining step and the oxidation state of Pd in the C-H functionalization step. Enantiomeric excess is strikingly insensitive to temperature from ambient temperature up to over 70 °C, and reaction rate is insensitive to the electronic characteristics of the ligand's benzoyl protecting group. The reaction is highly robust with no evidence of catalyst deactivation. Intriguingly, C-H bond breaking does not occur prior to the addition of I2 to the reaction mixture. Electrochemical experiments demonstrate the viability of oxidative addition of I2 to Pd(II). Together with 19F NMR studies, these observations suggest that iodine oxidizes Pd prior to addition of the amine substrate. This work may lead to a better general understanding of the subtle variations in the reaction mechanisms for C-H functionalization reactions that may be extant for this ligand class depending on substrate, amino acid ligand and protecting group, and reaction conditions.

Mono-Oxidation of Bidentate Bis-phosphines in Catalyst Activation: Kinetic and Mechanistic Studies of a Pd/Xantphos-Catalyzed C-H Functionalization.

Kinetic, spectroscopic, crystallographic, and computational studies probing a Pd-catalyzed C-H arylation reaction reveal that mono-oxidation of the bis-phosphine ligand is critical for the formation of the active catalyst. The bis-phosphine mono-oxide is shown to be a hemilabile, bidentate ligand for palladium. Isolation of the oxidative addition adduct, with structural elucidation by X-ray analysis, showed that the mono-oxide was catalytically competent, giving the same reaction rate in the productive reaction as the Pd(II)/xantphos precursor. A dual role for the carboxylate base in both catalyst activation and reaction turnover was demonstrated, along with the inhibiting effect of excess phosphine ligand. The generality of the role of phosphine mono-oxide complexes in Pd-catalyzed coupling processes is discussed.

A case study of the mechanism of alcohol-mediated Morita Baylis-Hillman reactions. The importance of experimental observations.

The mechanism of the Morita Baylis-Hillman reaction has been heavily studied in the literature, and a long series of computational studies have defined complete theoretical energy profiles in these reactions. We employ here a combination of mechanistic probes, including the observation of intermediates, the independent generation and partitioning of intermediates, thermodynamic and kinetic measurements on the main reaction and side reactions, isotopic incorporation from solvent, and kinetic isotope effects, to define the mechanism and an experimental mechanistic free-energy profile for a prototypical Morita Baylis-Hillman reaction in methanol. The results are then used to critically evaluate the ability of computations to predict the mechanism. The most notable prediction of the many computational studies, that of a proton-shuttle pathway, is refuted in favor of a simple but computationally intractable acid-base mechanism. Computational predictions vary vastly, and it is not clear that any significant accurate information that was not already apparent from experiment could have been garnered from computations. With care, entropy calculations are only a minor contributor to the larger computational error, while literature entropy-correction processes lead to absurd free-energy predictions. The computations aid in interpreting observations but fail utterly as a replacement for experiment.

Melanoma angiomatoide: reporte de un caso / Angiomatoid melanoma: a case report

El melanoma es una neoplasia originada en el melanocito y su localización más frecuente es la piel. Existen cuatro formas comunes de melanomamaligno y varias formas infrecuentes. Se presenta el caso de una paciente con melanoma angiomatoide una variante inusual de esta entidad (AU)

Melanoma is a neoplasm in the melanocyte and the most common site is the skin. There are four common forms of malignant melanoma and variousforms rare. A case of a patient with melanoma angiomatoid an unusual variant of this entity (AU)

Conventional and surgical treatment of a two-rooted maxillary central incisor.

Conventional and surgical endodontic management were performed on a two-rooted maxillary central incisor with a periapical lesion. Anatomical complexity of the tooth lead to perforation in the distal root during conventional treatment, thus a surgical approach was taken. A 4-month postoperative radiograph shows repair.

The first clinical and epidemiological programme on renal disease in Bolivia: a model for prevention and early diagnosis of renal diseases in the developing countries.

BACKGROUND: The prevalence and incidence of renal diseases in developing countries are not known. This lack of knowledge is an obstacle to the adoption of preventive measures which may be of great value in a social and economic environment where treatment options for end-stage renal failure are simply not available to the vast majority of the population. Urinalysis, a simple and inexpensive test, remains a cornerstone in the evaluation of the kidney and may also be easily employed in mass screening for renal abnormalities in a developing country. METHODS: An educational campaign on renal diseases was conducted in three selected areas of Bolivia. Urine samples were collected and sent to one of 21 participating clinical centers. Fresh urine specimens were screened using a dipstick for chemical analysis and by microscopic urinalysis after centrifugation. In those patients in whom urinary abnormalities were found, further investigations were carried out in order to define the diagnosis; these patients were enrolled in a 3-year follow-up program. RESULTS: Apparently healthy subjects (n = 14,082) were referred to the First Clinical and Epidemiological Program of Renal Diseases from rural and metropolitan areas in Bolivia. Urinary abnormalities were detected in 4261 subjects at first screening. The most common form of urinary abnormality was hematuria, which was found in 2010 (47% of positively screened subjects). Other renal abnormalities were leukocyturia (41%) and proteinuria (11%). Confirmatory tests and further clinical studies were then carried out in 1019 people. On a second screening 35% of the subjects had no urinary abnormalities; in the remaining people the following diagnosis were made: asymptomatic urinary-tract infection (48.4%), isolated benign hematuria (43.9%), chronic renal failure (1.6%), renal tuberculosis (1.6%). Other diagnosis were: renal stones 1.3%, diabetic nephropathy 1% and polycystic kidney diseases 1.9%. CONCLUSIONS: This study helped define for the first time the frequency of asymptomatic renal diseases in Bolivia. It shows that it is possible to screen a large population of patients at relatively low cost, providing the framework for further action that may help in the prevention and timely diagnosis of renal diseases.

[Specular bilateral lenticular hematomas]. / Hematomas lenticulares bilaterales en espejo.

A 49-year-old right-handed hypertensive female developed two consecutive putaminal hemorrhages in the left and right hemispheres within one month. Recurrent specular hypertensive hematomas are rare, even though the underlying pathological changes in the arterial wall occur bilaterally. This may be explained by the spontaneous decrease in blood pressure occurring in patients after an acute stroke. In this patient, a new abrupt increase in blood pressure may account for the second hemorrhage. While lowering the blood pressure during an acute stroke may be in principle unadvisable, it seems reasonable to prevent a new increase in blood pressure with adequate therapy.

Hematomas lenticulares bilaterais en espejo / Bilateral specular putaminal hemorrhages

Una paciente diestra e hipertensa de 49 años presentó dos hematomas lenticulares consecutivos en los hemisferios izquierdo y derecho en menos de un mes. Los hematomas recurrentes hipertensivos especulares son raros, aún cuando los cambios patológicos en la pared arterial subyacente se producen en ambos lados. Esto podría explicarse por la reducción espontánea de la tensión arterial que se produce luego de un accidente cerebrovascular agudo. En el presente caso, un nuevo episodio de hipertensión brusca puede explicar la segunda hemorragia. Si bien reducir la tensión arterial durante un accidente cerebrovascular agudo puede ser en principio desaconsejable, parece justificado prevenir nuevos ascensos en al tensión arterial mediante la terapéutica adecuada

Hematomas lenticulares bilaterales en espejo. / [Specular bilateral lenticular hematomas]

A 49-year-old right-handed hypertensive female developed two consecutive putaminal hemorrhages in the left and right hemispheres within one month. Recurrent specular hypertensive hematomas are rare, even though the underlying pathological changes in the arterial wall occur bilaterally. This may be explained by the spontaneous decrease in blood pressure occurring in patients after an acute stroke. In this patient, a new abrupt increase in blood pressure may account for the second hemorrhage. While lowering the blood pressure during an acute stroke may be in principle unadvisable, it seems reasonable to prevent a new increase in blood pressure with adequate therapy.

Hematomas lenticulares bilaterais en espejo / Bilateral specular putaminal hemorrhages

Una paciente diestra e hipertensa de 49 años presentó dos hematomas lenticulares consecutivos en los hemisferios izquierdo y derecho en menos de un mes. Los hematomas recurrentes hipertensivos especulares son raros, aún cuando los cambios patológicos en la pared arterial subyacente se producen en ambos lados. Esto podría explicarse por la reducción espontánea de la tensión arterial que se produce luego de un accidente cerebrovascular agudo. En el presente caso, un nuevo episodio de hipertensión brusca puede explicar la segunda hemorragia. Si bien reducir la tensión arterial durante un accidente cerebrovascular agudo puede ser en principio desaconsejable, parece justificado prevenir nuevos ascensos en al tensión arterial mediante la terapéutica adecuada (AU)

Intentional retention of vital submerged roots in dogs.

In this study, intact and untreated roots of twelve teeth in three dogs were submerged 2 mm. below the alveolar bone crest. On eight regeneration of alveolar bone was seen in 3 weeks, with complete bone coverage in 5 weeks. A complete lamina dura surrounded the buried roots, the original root canal tissue remained vital, and vessels and other structures now entered (or exited) from both ends. Cementum covered the cut end, making the end similar to a normal apex. Bone failed to regenerate completely over four of the twelve roots. Two of these had dentinal spicules which impeded complete bone coverage (Fig 9). Another was a case of delayed healing due to the early loss of sutures and subsequent infection where a sinus tract developed, connecting the oral environment with the resected root. This led to bone resorption and a partial pulp necrosis. In the fourth case the decreased depth of root burial and subsequent lack of bone cover led to external resorption of the cut dentin. Histologic examination after 12 weeks revealed the regeneration of bone, a regenerated periodontal membrane, and a layer of cementoblasts over the cut and exposed root dentin in a typical manner. This study suggests that when healthy bone and roots are present, particularly in an otherwise edentulous mandible retaining only a few nonrestorable anterior teeth, the roots can be retained in a nonpathologic state by means of a simple surgical technique.

Characterization of effector lymphocytes associated with immunity to murine sarcoma virus (MSV) induced tumors. I. Physical properties of cytolytic T lymphocytes generated in vitro and of their immediate progenitors.

Cytolytic T lymphocytes (CTL) were generated in secondary mixed leukocyte-tumor cell cultures (MLTC) with syngeneic RB1-5 tumor cells as stimulating cells and with responding spleen cells from regressor mice that had rejected a murine sarcoma virus (MSV)-induced tumor. CTL precursor cells were found to be exclusively of thymic origin and non-T cells were apparently not required for CTL generation. When the size variations of CTL from syngeneic MLTC were analyzed by velocity sedimentation it appeared that a transition from small precursor cells to larger effector cells occurred during the first 5 days in culture; this change in cell size was then followed by a shift toward small-sized cells. Furthermore, the CTL generated in syngeneic MLTC in the MSV tumor immune system were compared with those CTL obtained in allogeneic mixed leukocyte cultures (MLC) and were shown to exhibit fundamental similarities.