Epileptic encephalopathies secondary to hypothalamic hamartomas treated with radiosurgery: A case series.

OBJECTIVE: Hypothalamic hamartomas are congenital lesions that typically present with gelastic seizures, refractory epilepsy, neurodevelopmental delay, and severe cognitive impairment. Surgical procedures have been reported to be effective in removing the hamartomas, however, they are associated with significant morbidity. Therefore, it is not considered a safe therapeutic modality. Image-guided robotic radiosurgery (CyberKnife® Radiosurgery System) has been shown to provide good outcomes without lasting complications. METHODS: This series of cases describes the clinical, radiological, radiotherapeutic, and postsurgical outcomes of five patients with epileptic encephalopathies secondary to hypothalamic hamartomas who were treated with CyberKnife®. RESULTS: All patients exhibited refractory epilepsy with gelastic seizures and were unsuitable candidates for surgical resection The prescribed dose ranged between 16 and 25 Gy, delivered in a single fraction for four patients and five fractions for one patient while adhering strictly to visual pathway constraints. After radiosurgery, four patients maintained seizure control (one with an Engel class Ia, three with an Engel class 1d), and another presented sporadic, nondisabling gelastic seizures (with an Engel class IIa). After 24-26 months of follow-up, in three patients, their intelligence quotient scores increased. No complications were reported. SIGNIFICANCE: This report suggests that Cyberknife may be a good option for treating hypothalamic hamartoma, particularly in cases where other noninvasive alternatives are unavailable. Nevertheless, additional studies are essential in order to evaluate the effectiveness of the technique in these cases.

The multispecies microbial cluster of Fusobacterium, Parvimonas, Bacteroides and Faecalibacterium as a precision biomarker for colorectal cancer diagnosis.

The incidence of colorectal cancer (CRC) has increased worldwide, and early diagnosis is crucial to reduce mortality rates. Therefore, new noninvasive biomarkers for CRC are required. Recent studies have revealed an imbalance in the oral and gut microbiomes of patients with CRC, as well as impaired gut vascular barrier function. In the present study, the microbiomes of saliva, crevicular fluid, feces, and non-neoplastic and tumor intestinal tissue samples of 93 CRC patients and 30 healthy individuals without digestive disorders (non-CRC) were analyzed by 16S rRNA metabarcoding procedures. The data revealed that Parvimonas, Fusobacterium, and Bacteroides fragilis were significantly over-represented in stool samples of CRC patients, whereas Faecalibacterium and Blautia were significantly over-abundant in the non-CRC group. Moreover, the tumor samples were enriched in well-known periodontal anaerobes, including Fusobacterium, Parvimonas, Peptostreptococcus, Porphyromonas, and Prevotella. Co-occurrence patterns of these oral microorganisms were observed in the subgingival pocket and in the tumor tissues of CRC patients, where they also correlated with other gut microbes, such as Hungatella. This study provides new evidence that oral pathobionts, normally located in subgingival pockets, can migrate to the colon and probably aggregate with aerobic bacteria, forming synergistic consortia. Furthermore, we suggest that the group composed of Fusobacterium, Parvimonas, Bacteroides, and Faecalibacterium could be used to design an excellent noninvasive fecal test for the early diagnosis of CRC. The combination of these four genera would significantly improve the reliability of a discriminatory test with respect to others that use a single species as a unique CRC biomarker.

Alumina-Hydroxyapatite Millimetric Spheres for Cadmium(II) Removal in Aqueous Medium.

Heavy metals can act as selective agents in the development and proliferation of antibiotic-resistant bacteria through a process called coselection. In the year 2050, an estimated 10 million deaths will be caused by antibiotic-resistant bacteria; therefore, the presence of heavy metals in bodies of water represents an environmental and sanitary threat that requires efficient treatment processes and/or materials for their removal. In the present study, the effect of the hydroxyapatite coating on the adsorbent capacity of cadmium in alumina spheres was evaluated. The hydroxyapatite coating on the alumina sphere increased the surface area from 0.66 to 0.96 m2/g and the number of acid sites from 0.064 to 0.306 meq/g and displaced the IEP of hydroxyapatite from 5.37 to 4.2, increasing the Cd2+ adsorbing capacity from 59.87 mg/g to 89.37 mg/g and promoting adsorption by surface complexation. Alumina-hydroxyapatite spheres stand out for their improved adsorbent properties and easy handling, which positioned this material as a potential alternative in adsorption processes.

Use or abuse of antibiotics as prophylactic therapy in oral surgery: A systematic review.

BACKGROUD: Antibiotics are a type of medication routinely prescribed by dental professionals; however, it is very common that the administration is not justified. Around 15% of dentists admit that they have administered antibiotics unnecessarily more than once a week. The objective of this project is to identify the effectiveness of the use of antibiotics as prophylactic therapy in oral surgery, and to carry out an analysis of the alternatives to pharmacological therapy. METHODS: The search strategy was carried out in the PubMed, Scopus, and ScienceDirect databases. For study selection, a first filter was carried out by title and abstract, which mentioned the use of prophylactic antibiotics in some type of oral surgery. To establish the risk of bias, the JBI Critical Appraisal Checklist for Randomized Controlled Trials was utilized. RESULTS: The type of antibiotics most prescribed as prophylactic therapy were beta-lactams, which were indicated in 100% of the studies. Penicillins predominated, observing amoxicillin as the most indicated drug in 54.1% of the studies (n = 13) followed by the use of amoxicillin in conjunction with clavulanic acid in 33.3% of the studies (n = 8). Of the 21 studies included, 17 mention that there is insufficient evidence to support the use of antibiotics as prophylactic therapy in patients who will undergo some type of oral surgery. CONCLUSIONS: Without a doubt, the biggest challenge is to develop academic update strategies aimed at dentists with active clinical practice and dental students from educational and government institutions to provide updated information about the correct use of prescription drugs.

Parvimonas micra can translocate from the subgingival sulcus of the human oral cavity to colorectal adenocarcinoma.

Oral and intestinal samples from a cohort of 93 colorectal cancer (CRC) patients and 30 healthy controls (non-CRC) were collected for microbiome analysis. Saliva (28 non-CRC and 94 CRC), feces (30 non-CRC and 97 CRC), subgingival fluid (20 CRC), and tumor tissue samples (20 CRC) were used for 16S metabarcoding and/or RNA sequencing (RNAseq) approaches. A differential analysis of the abundance, performed with the ANCOM-BC package, adjusting the P-values by the Holm-Bonferroni method, revealed that Parvimonas was significantly over-represented in feces from CRC patients (P-value < 0.001) compared to healthy controls. A total of 11 Parvimonas micra isolates were obtained from the oral cavity and adenocarcinoma of CRC patients. Genome analysis identified a pair of isolates from the same patient that shared 99.2% identity, demonstrating that P. micra can translocate from the subgingival cavity to the gut. The data suggest that P. micra could migrate in a synergistic consortium with other periodontal bacteria. Metatranscriptomics confirmed that oral bacteria were more active in tumor than in non-neoplastic tissues. We suggest that P. micra could be considered as a CRC biomarker detected in non-invasive samples such as feces.

Efecto del compuesto N-2,6-dicloro-aralquil-2-Aminoindano en la conducta estereotipada de ratas. Acción dopaminérgica selectiva central sobre los ganglios basales más que en las estructuras límbicas / Effect of the compound N-2,6-dichloro-aralkyl-2-aminoindane on the stereotyped behavior of rats. Selective action on the central dopaminergic system in the basal ganglia over limbic structures

Resumen La dopamina 1, está implicada en trastornos neurodegenerativos que afectan al sistema nervioso central (SNC) tales como la enfermedad de Parkinson, entre otros. Aunque no se dispone aún de ningún fármaco capaz de prevenir, detener o curar la progresión de estas enfermedades, son numerosos los compuestos que han sido diseñados, sintetizados y evaluados farmacológicamente, que han aportado las generalizaciones farmacofóricas del receptor dopaminérgico, necesarias para la búsqueda de un fármaco capaz de mejorar o curar estas patologías. Los derivados 2-aminoindano-N-aralquílicos han mostrado tener actividad selectiva en el sistema dopaminérgico central, de modo tal que los compuestos clorhidratos de N-[(2,4-diclorofenil)-1-metil- etil]-2-aminoindano 2 y N-[(3,4-diclorofenil)-1-metil-etil]-2-aminoindano 3 demostraron tener actividad agonística mediada por mecanismos dopaminérgicos centrales. Con el propósito de contribuir en la búsqueda de nuevos fármacos que permitan restablecer la homeostasis de la transmisión dopaminérgica en la enfermedad de Parkinson, el compuesto N-2,6-dicloro-aralquil-2-aminoindano 4 fue diseñado a través de estrategias de la química medicinal, que contienen las aproximaciones farmacofóricas de los profármacos. La evaluación farmacológica del compuesto 4, en la conducta estereotipada en ratas macho de la cepa Sprague Dawley, demostró tener actividad agonística a través de la activación de los mecanismos dopaminérgicos centrales y mostró mayor selectividad en las respuestas de conductas estereotipadas propias de los ganglios basales sobre las respuestas conductuales propias de las estructuras límbicas.

Abstract Dopamine 1 is involved in neurodegenerative disorders affecting the central nervous system (CNS), such as Parkinson's disease. Despite the absence of some available drugs capable of preventing, stopping or curing the progression of such diseases, there are numerous compounds designed, synthesized, and pharmacologically tested which give rise to pharmacophoric generalizations about the dopaminergic receptor required for the search of a drug able to improve or cure those pathologies. N-aralkyl-2-aminoindane derivatives have shown selective activity in the central dopaminergic system. Both the N-[(2,4-dichlorophenyl)-1-methyl-ethyl]-2-aminoindane hydrochloride 2 and N-[(3,4-dichlorophenyl)-1-methyl-ethyl]-2-aminoindane hydrochloride 3 showed an agonistic activity mediated by central dopaminergic mechanisms. To contribute to the search of new drugs able to re-establish homeostasis in the dopaminergic transmission in Parkinson's disease, the compound N-2,6- dichloro-aralkyl-2-aminoindane 4 was designed through medicinal chemistry strategies that contain pharmacophoric approximations of prodrugs. The pharmacological evaluation of compound 4 in the stereotyped behavior of male Sprague Dawley rats showed agonistic activity through the activation of central dopaminergic mechanisms and a higher selectivity in the responses of stereo- typed behavior characteristic of the basal ganglia over the typical responses from limbic structures.

Synthesis and Characterization of α-Al2O3/Ba-ß-Al2O3 Spheres for Cadmium Ions Removal from Aqueous Solutions.

The search for adsorbent materials with a certain chemical inertness, mechanical resistance, and high adsorption capacity, as is the case with alumina, is carried out with structural or surface modifications with the addition of additives or metallic salts. This research shows the synthesis, characterization, phase evolution and Cd(II) adsorbent capacity of α-Al2O3/Ba-ß-Al2O3 spheres obtained from α-Al2O3 nanopowders by the ion encapsulation method. The formation of the Ba-ß-Al2O3 phase is manifested at 1500 °C according to the infrared spectrum by the appearance of bands corresponding to AlO4 bonds and the appearance of peaks corresponding to Ba-O bonds in Raman spectroscopy. XRD determined the presence of BaO·Al2O3 at 1000 °C and the formation of Ba-ß-Al2O3 at 1600 °C. Scanning electron microscopy revealed the presence of spherical grains corresponding to α-Al2O3 and hexagonal plates corresponding to ß-Al2O3 in the spheres treated at 1600 °C. The spheres obtained have dimensions of 4.65 ± 0.30 mm in diameter, weight of 43 ± 2 mg and a surface area of 0.66 m2/g. According to the curve of pH vs. zeta potential, the spheres have an acid character and a negative surface charge of -30 mV at pH 5. Through adsorption studies, an adsorbent capacity of Cd(II) of 59.97 mg/g (87 ppm Cd(II)) was determined at pH 5, and the data were fitted to the pseudo first order, pseudo second order and Freundlich models, with correlation factors of 0.993, 0.987 and 0.998, respectively.

Caffeine Restores Neuronal Damage and Inflammatory Response in a Model of Intraventricular Hemorrhage of the Preterm Newborn.

Germinal matrix-intraventricular hemorrhage (GM-IVH) is the most frequent intracranial hemorrhage in the preterm infant (PT). Long-term GM-IVH-associated sequelae include cerebral palsy, sensory and motor impairment, learning disabilities, or neuropsychiatric disorders. The societal and health burden associated with GM-IVH is worsened by the fact that there is no successful treatment to limit or reduce brain damage and neurodevelopment disabilities. Caffeine (Caf) is a methylxanthine that binds to adenosine receptors, regularly used to treat the apnea of prematurity. While previous studies support the beneficial effects at the brain level of Caf in PT, there are no studies that specifically focus on the role of Caf in GM-IVH. Therefore, to further understand the role of Caf in GM-IVH, we have analyzed two doses of Caf (10 and 20 mg/kg) in a murine model of the disease. We have analyzed the short (P14) and long (P70) effects of the treatment on brain atrophy and neuron wellbeing, including density, curvature, and phospho-tau/total tau ratio. We have analyzed proliferation and neurogenesis, as well as microglia and hemorrhage burdens. We have also assessed the long-term effects of Caf treatment at cognitive level. To induce GM-IVH, we have administered intraventricular collagenase to P7 CD1 mice and have analyzed these animals in the short (P14) and long (P70) term. Caf showed a general neuroprotective effect in our model of GM-IVH of the PT. In our study, Caf administration diminishes brain atrophy and ventricle enlargement. Likewise, Caf limits neuronal damage, including neurite curvature and tau phosphorylation. It also contributes to maintaining neurogenesis in the subventricular zone, a neurogenic niche that is severely affected after GM-IVH. Furthermore, Caf ameliorates small vessel bleeding and inflammation in both the cortex and the subventricular zone. Observed mitigation of brain pathological features commonly associated with GM-IVH also results in a significant improvement of learning and memory abilities in the long term. Altogether, our data support the promising effects of Caf to reduce central nervous system complications associated with GM-IVH.

Lung ultrasound score has better diagnostic ability than NT-proBNP to predict moderate-severe bronchopulmonary dysplasia.

The N-terminal end of B-type natriuretic peptide (NT-proBNP) and lung ultrasound (LUS) score have been proven to be adequate early biomarkers of bronchopulmonary dysplasia (BPD) in preterm infants. Our aim was to study if the predictive capacity of each one is increased by analyzing them together. We included infants born before 32 weeks with NT-proBNP and LUS scores on the first day of life (DOL) and on the 3rd, 7th, and 14th DOL and compared the diagnostic ability for moderate-severe BPD (msBPD) of each biomarker and in combination. We also compared them with a multivariate model of msBPD using only clinical variables. The sample size was 133 patients, and twenty-seven (20%) developed msBPD. The LUS score on the 7th DOL had better performance than NT-proBNP at the same moment: area under the receiver operating characteristic curve (AUC) 0.83 (0.75-0.89) versus 0.66 (0.56-0.75), p = 0.003, without differences in the rest of the times studied. These values did not increase when using the combination of both. A multivariate regression model that included only clinical variables (birth weight and invasive mechanical ventilation (IMV) at the 7th DOL) predicted msBPD with the same AUC as after the addition of any of these biomarkers, neither together. CONCLUSION: The LUS score is a better predictor of msBPD on the 7th DOL than NT-proBNP in preterm infants born before 32 weeks, although they have similar diagnostic accuracy on the 1st, 3rd, and 14th DOL. Neither of them, nor together, have a better AUC for msBPD than a clinical model with birthweight and the need for IMV at the 7th DOL. WHAT IS KNOWN: • NT-proBNP and LUS score are early predictors of moderate-severe bronchopulmonary dysplasia (msBPD). WHAT IS NEW: • The combination of both NT-proBNP and LUS score does not increase the predictive ability of each separately.

Data for the synthesis, characterization, and use of xerogels as adsorbents for the removal of fluoride and bromide in aqueous phase.

Groundwater with high fluoride concentrations has been recognized as one of the serious concerns worldwide. Besides, the fluoride released into the groundwater by slow dissolution of fluoride-containing rocks, various industries also contribute to fluoride pollution [1]. Excess intake of fluoride leads to various health problems such as dental and skeletal fluorosis, cancer, infertility, brain damage, thyroid diseases, etc. [2]. On the other hand, bromide is naturally present in surface and groundwater sources. However, during the chlorination process, bromide can be oxidized to HOBr, which can react with natural organic matter in water to form brominated organic disinfection byproducts, which are very harmful to human health [3]. Among various methods for water treatment, the adsorption process has been widely used and seems to be an efficient and attractive method for the removal of many contaminants in water, such as anions, in terms of cost, simplicity of design, and operation [4], [5]. In the past years, xerogels and carbon xerogels, a new type of adsorbents, which are synthesized by the sol-gel polycondensation of resorcinol and formaldehyde, have gained attention due to their moldable texture and chemical properties [6]. Moreover, melamine addition in resorcinol and formaldehyde xerogels adds basic groups on its surface, favouring Lewis acid-base interactions between xerogels and other components by adsorption [7]. In this data article, the synthesis of three resorcinol-formaldehyde (R/F) xerogels with an increasing amount of melamine (M) was carried out by colloidal polymerization (molar ratios of M/R = 0.5, M/R = 1.0, and M/R = 2.0). Additionally, samples of M/R = 0.5 xerogel were carbonized at 400, 450, and 550 °C under an inert atmosphere to increase their specific area. Organic and carbon xerogels obtained were characterized by FTIR, TGA, SEM, Physisorption of N2, and the pH at the point of zero charge (pHPZC). All organic xerogels were also tested as adsorbents on the removal of fluoride and bromide ions from aqueous phase. The Freundlich, Langmuir, and Radke-Prausnitz isotherm models were applied to interpret the experimental data from adsorption equilibrium. Additionally, the data of the mass of the xerogel needed to remove fluoride and bromide from groundwater and fulfill the maximum concentration levels are also included.

Neuroactive venom compounds obtained from Phlogiellus bundokalbo as potential leads for neurodegenerative diseases: insights on their acetylcholinesterase and beta-secretase inhibitory activities in vitro

Spider venom is a rich cocktail of neuroactive compounds designed to prey capture and defense against predators that act on neuronal membrane proteins, in particular, acetylcholinesterases (AChE) that regulate synaptic transmission through acetylcholine (ACh) hydrolysis - an excitatory neurotransmitter - and beta-secretases (BACE) that primarily cleave amyloid precursor proteins (APP), which are, in turn, relevant in the structural integrity of neurons. The present study provides preliminary evidence on the therapeutic potential of Phlogiellus bundokalbo venom against neurodegenerative diseases. Methods Spider venom was extracted by electrostimulation and fractionated by reverse-phase high-performance liquid chromatography (RP-HPLC) and characterized by matrix-assisted laser desorption ionization-time flight mass spectrometry (MALDI-TOF-MS). Neuroactivity of the whole venom was observed by a neurobehavioral response from Terebrio molitor larvae in vivo and fractions were screened for their inhibitory activities against AChE and BACE in vitro. Results The whole venom from P. bundokalbo demonstrated neuroactivity by inducing excitatory movements from T. molitor for 15 min. Sixteen fractions collected produced diverse mass fragments from MALDI-TOF-MS ranging from 900-4500 Da. Eleven of sixteen fractions demonstrated AChE inhibitory activities with 14.34% (± 2.60e-4) to 62.05% (± 6.40e-5) compared with donepezil which has 86.34% (± 3.90e-5) inhibition (p > 0.05), while none of the fractions were observed to exhibit BACE inhibition. Furthermore, three potent fractions against AChE, F1, F3, and F16 displayed competitive and uncompetitive inhibitions compared to donepezil as the positive control. Conclusion The venom of P. bundokalbo contains compounds that demonstrate neuroactivity and anti-AChE activities in vitro, which could comprise possible therapeutic leads for the development of cholinergic compounds against neurological diseases.(AU)

Lung ultrasound score and diuretics in preterm infants born before 32 weeks: A pilot study.

OBJECTIVE: To describe if weekly determined lung ultrasound (LU) scores in preterm infants born before 32 weeks (PTB32W) change with diuretic therapy. DESIGN: We included infants who received diuretics and compared LU scores according to their evolution on respiratory support (RS) before and after diuretics. RESULTS: We included 18 PTB32W divided into two groups. Both groups were similar in terms of median gestational age: 26 weeks (interquartile range [IQR]: 25-28) in the responders' group and 27 weeks (IQR: 24-28) in the other. They differed, however, in the median number of days on invasive mechanical ventilation: 27 (IQR: 11-43) versus 76 (IQR: 35-117), p = .03; in addition to the number of infants with moderate-severe bronchopulmonary dysplasia: 3 (33%) versus 8 (89%), p = .025. The responders' group showed lower LU scores 2 days after diuretics, with a median LU score of 6 (IQR: 3-12) versus 14 (IQR: 12-17) in the nonresponders group, p = .03; 1 week after (3 [IQR: 0-10] versus 12 [12-12], p = .04); and 3 weeks after (5 [IQR: 3-6] versus 12 [10-15], p = .01). RS also decreased at the same time: 7 out of 9 (78%) were extubated in the responders' group, and 1 out of 9 (11%) in the nonresponders group, p = .02, and these differences remained throughout the entire follow-up. CONCLUSIONS: There is a group of PTB32W patients whose LU score improves after diuretics. This change appears only in those patients that can be weaned off from RS, and at the same period of time as the administration of diuretics.

The Venom of Philippine Tarantula (Theraphosidae) Contains Peptides with Pro-Oxidative and Nitrosative-Dependent Cytotoxic Activities against Breast Cancer Cells (MCF-7) In Vitro.

BACKGROUND: Breast cancer is a multifactorial disease that affects women worldwide. Its progression is likely to be executed by oxidative stress wherein elevated levels of reactive oxygen and nitrogen species drive several breast cancer pathologies. Spider venom contains various pharmacological peptides which exhibit selective activity to abnormal expression of ion channels on cancer cell surface which can confer potent anti-cancer activities against this disease. METHODS: Venom was extracted from a Philippine tarantula by electrostimulation and fractionated by reverse phase-high performance liquid chromatography (RP-HPLC). Venom fractions were collected and used for in vitro analyses such as cellular toxicity, morphological assessment, and oxidative stress levels. RESULTS: The fractionation of crude spider venom generated several peaks which were predominantly detected spectrophotometrically and colorimetrically as peptides. Treatment of MCF-7 cell line of selected spider venom peptides induced production of several endogenous radicals such as hydroxyl radicals (•OH), nitric oxide radicals (•NO), superoxide anion radicals (•O2-) and lipid peroxides via malondialdehyde (MDA) reaction, which is comparable with the scavenging effects afforded by 400 µg/mL vitamin E and L-cysteine (p<0.05). Concomitantly, the free radicals produced decrease the mitochondrial membrane potential and metabolic activity as detected by rhodamine 123 and tetrazolium dye respectively (p>0.05). This is manifested by cytotoxicity in MCF-7 cells as seen by increase in membrane blebbing, cellular detachment, caspase activity and nuclear fragmentation. CONCLUSION: These data suggest that the Philippine tarantula venom contains peptide constituents exhibiting pro-oxidative and nitrosative-dependent cytotoxic activities against MCF-7 cells and can indicate mechanistic insights to further explore its potential application as prooxidants in cancer therapy.
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In-office endoscopic nasal polypectomy: prospective analysis of patient tolerability and efficacy.

PURPOSE: In-office rhinologic procedures have become popularised in the last decade, especially in North America. Endoscopic nasal polypectomy under local anaesthesia offers instant relief in selected patients with obstructive chronic rhinosinusitis with nasal polyps. We aimed to analyse patient tolerability during the procedure while measuring its effectiveness. METHODS: A prospective study of patients who underwent in-office microdebrider-assisted polypectomy under local anaesthetic from September 2018 to November 2019 in a Spanish tertiary hospital was performed. The tolerability was measured by monitoring vital signs during the procedure and using a visual analogue scale posteriorly. The effectiveness was calculated through patient-reported outcomes (SNOT-22) and endoscopic evaluation 1 and 6 months follow-up. RESULTS: Forty-four patients were included, with a mean age of 60.7 years. The mean visual analogue scale score was 2.76 out of 10 points. Vital signs were steady overall, with a statistically significant reduction (p < 0.001) in systolic pressure during the procedure. Presyncope and epistaxis were among the few mild complications. However, we registered one major complication that required intensive care admission. There was a 64% reduction in the SNOT-22 score in the first month, with a maintained effect after 6 months. Patients with asthma and a higher polyp load were the subgroups that required more time to achieve significant improvement. CONCLUSIONS: In-office polypectomy is a very effective technique that alleviates obstructive symptoms in patients with nasal polyposis, and it is generally safe and well tolerated when performed by an expert. However, rhinologists must be aware of potentially severe complications.

Anticancer potential of new 3-nitroaryl-6-(N-methyl)piperazin-1,2,4-triazolo[3,4-a]phthalazines targeting voltage-gated K+ channel: Copper-catalyzed one-pot synthesis from 4-chloro-1-phthalazinyl-arylhydrazones.

A series of six 3-aryl-6-(N-methylpiperazin)-1,2,4-triazolo[3,4-a]phthalazines were prepared through a facile and efficient one-pot copper-catalyzed procedure from 4-chloro-1-phthalazinyl-arylhydrazones with relatively good yields (62-83%). The one-pot copper-catalytic procedure consists of two simultaneous reactions: (i) a direct intramolecular dehydrogentaive cyclization between ylidenic carbon and adjacent pyrazine nitrogen to form 1,2,4-triazolo ring and, (ii) a direct N-amination on carbon-chlorine bond. Then, an in vitro anticancer evaluation was performed for the synthesized compounds against five selected human cancer cells (A549, MCF-7, SKBr3, PC-3 and HeLa). The nitro-derivatives were significantly more active against cancer strains than against the rest of tested compounds. Specifically, compound 8d was identified as the most promising anticancer agent with significant biological responses and low relative toxicities on human dermis fibroblast. The cytotoxic effect of compound 8d was more significant on PC3, MCF-7 and SKBr3 cancer cells with low-micromolar IC50 value ranging from 0.11 to 0.59 µM, superior to Adriamycin drug. Mechanistic experimental and theoretical studies demonstrated that compounds 8d act as a K+ channel inhibitor in cancer models. Further molecular docking studies suggest that the EGFR Tyrosine Kinase enzyme may be a potential target for the most active 3-aryl-6-(N-methylpiperazin)-1,2,4-triazolo[3,4-a]phthalazines.

Head and neck cancer screening in patients eligible for liver transplantation. / Cribado de cáncer de cabeza y cuello en pacientes candidatos a trasplante hepático.

INTRODUCTION: Liver transplantation is the only alternative treatment in patients in end-stage liver function. In many cases the need for liver transplantation is a consequence of the toxic effects of alcohol. The aim of our study was to determine if patients who are candidates for a liver transplant require a systematic exploration of the head and neck to rule out malignant lesions in this area. PATIENTS AND METHODS: All the candidates for a liver transplant, between 2011 and 2017, were included in our study. All of them underwent a systematic exploration of the head and neck by an otolaryngologist to rule out malignancy of the head and neck. RESULTS: A total of 141 patients were included in our study. In 2 of them (1.3%) a carcinoma of the head and neck was detected (one of the oropharynx and the other of the larynx). Both patients were asymptomatic from an ENT point of view. They were treated with chemoradiotherapy. One of them died during follow-up due to the appearance of a metachronous lung tumour. The other is free of disease 2 years after diagnosis but without having been transplanted. Both patients had a history of smoking and high alcohol intake. CONCLUSIONS: In patients who are candidates for a liver transplant who have a history of smoking and / or high alcohol intake, a pretransplant head and neck study including pharyngo-laryngeal fibroscopy is indicated.

Efficacy of growth factors for the treatment of peri-implant diseases: a systematic review and meta-analysis.

OBJECTIVES: The aim of this study was to conduct a systematic review and meta-analysis on the efficacy of growth factors (GF) on clinical outcomes after treatment (surgical/non-surgical) of peri-implant diseases (peri-implant mucositis and peri-implantitis). MATERIALS AND METHODS: A protocol was developed to answer the following focused question: Is there any difference for the use of GF for treatment of peri-implant diseases versus comparative GF treatment or without GF? Electronic database and manual searches were independently conducted to identify randomized controlled trials (RCTs). Publications were selected based on eligibility criteria and then assessed for risk-of-bias using the Cochrane Handbook. The primary outcome was probing depth (PD) and bleeding on probing (BOP) reduction along with changes in vertical defect depth (VDD). Changes in clinical attachment level, gingival recession, and plaque index, among others, were studied as secondary outcomes. Based on primary outcomes, random-effects meta-analysis was conducted. RESULTS: A total of five RCTs were included. GF enhance the reduction of PD (standardized mean difference (SMD) = - 1.28; 95% confidence interval (CI) - 1.75, - 0.79; p = < 0.0001) and BOP (SMD = - 1.23; 95% CI - 1.70, - 0.76; p = < 0.0001) in the management of peri-implant mucositis. For the treatment of peri-implantitis, the use of GF yielded to significantly greater improvement in VDD (SMD = 0.68; 95% CI 0.22, 1.14; p = 0.004); however, there were no significant differences in terms of PD (SMD = 0.08; 95% CI - 1.08, 1.26; p = 0.887) and BOP (SMD = 0.211; 95% CI - 0.20, 0.63; p = 0.317). The overall risk of bias of the included studies was low to unclear. CONCLUSION: The results of the present systematic review suggest that the addition of GF might enhance the outcomes in the treatment of peri-implant mucositis. However, there is a lack of evidence for supporting additional benefit of GF managing peri-implantitis. CLINICAL RELEVANCE: Within the limitations of the current systematic review and based on the meta-analyses, (1) the addition of GF for the treatment peri-implant mucositis might be associated with better outcomes in terms of PD and BOP, and (2) an additional benefit of GF for the treatment peri-implantitis could not be determined on the basis of the selected evidence.

Evaluación de la adhesión de sistemas adhesivos de grabado total en esmalte dental bovino usando un agente desproteinizante: un estudio in vitro / Evaluation of adhesion of total etch adhesive systems on bovine dental enamel using a deproteinizing agent: an in vitro study

Introducción: Hoy en día, la mayoría de los pacientes requieren tratamiento de ortodoncia fija convencional, la cual utiliza procedimientos adhesivos afines con la superficie amelodentinaria. Aunque existen diferentes técnicas adhesivas que pueden ofrecer adecuados niveles de resistencia al desalojo, el uso del hipoclorito de sodio (NaClO) como agente desproteinizante no ha sido bien definido en materiales de cementación en aparatología ortodóncica convencional. Objetivo: El objetivo de este estudio fue determinar los niveles de resistencia al desalojo con pruebas de microtensión y análisis topográfico con microscopia electrónica de barrido. Material y métodos: 20 bloques de esmalte bovino fueron expuestos superficialmente a soluciones acondicionadoras (ácido ortofosfórico al 37%) con y sin agente desproteinizante (NaClO al 5.25%); finalmente, brackets individuales de ortodoncia fueron cementados con sistemas adhesivos y resinas compuestas de casas comerciales (Ormco y 3M). Las pruebas de resistencia al desalojo fueron realizadas con una máquina de fuerzas universales y el análisis topográfico con microscopia electrónica de barrido. Resultados: El uso del NaClO al 5.25% y la marca Ormco tuvieron estadísticamente los mejores niveles de adhesión que el grupo sin desproteinización y la casa comercial 3M, respectivamente. La topografía adamantina expuesta al agente desproteinizante mostró características de superficie relacionadas con el patrón de grabado tipo I. Conclusión: El uso de un agente desproteinizante (NaClO 5.25%) así como una marca comercial (Ormco) en particular podrían definir el aumento en los niveles de adhesión en superficies adamantinas con aparatología ortodóncica convencional (AU)

Introduction: Nowadays, patients require conventional fixed orthodontic treatment, which uses adhesive procedures related to the dentinal denture surface. Although there are different adhesive techniques that can offer adequate levels of bonding resistance, the use of NaClO as a deproteinizing agent has not been well defined in cementing materials in conventional orthodontic appliances. Objective: The objective of this study was to determine the levels of bond resistance using micro tension tests and topographic analysis with scanning electron microscopy. Material and methods: Twenty-blocks of bovine enamel were exposed superficially to conditioning solutions (37% orthophosphoric acid) with and without deproteinizing agent (5.25% NaClO); finally, individual orthodontic brackets were cemented with adhesive systems and resin composites of different trademarks (Ormco and 3M). Bonding resistance tests were performed with a universal force machine and topographic analysis was made with scanning electron microscopy. Results: The use of 5.25% NaClO and the Ormco brand had statistically better levels of adhesion than the group without deproteinization and the 3M brand, respectively. Adamantine topography exposed to the deproteinizing agent showed surface characteristics related to the type I etching pattern. Conclusion: The use of a deproteinizing agent (NaClO 5.25%) as well as a trademark (Ormco) in particular conditions could define the increase in adhesion levels on adamantine surfaces with conventional orthodontic appliances (AU)

Primary maxillary chondrosarcoma: A case report.

BACKGROUND: Sarcomas of the head and neck region are rare tumors, constituting less than 1% of malignant neoplasms in this area, of which few cases (20%) originate from bone or cartilage. Chondrosarcoma is a malignant neoplasm that develops in bone, with a predilection for the pelvis, chest wall, and scapula, and is uncommon in the maxilla and jaw. Although this type of lesion has locally aggressive behavior, destroying the affected bone, it can metastasize when it is not diagnosed early and compromise the patient's life. CASE SUMMARY: On intraoral examination of a 32-year-old female with a tumor in the middle third of the face, a well-defined rise in volume of approximately 3 cm in diameter was observed. Computed tomography with 3-dimensional reconstruction was performed, and we observed that the osteolytic lesion affected the vestibular cortex as the palatal bone. Hematoxylin and eosin staining revealed an appearance that was similar to mature hyaline cartilage, hypercellularity, nuclear and cellular pleomorphism, and multinucleated cells, with significant vacuolization. CONCLUSION: Determination of the clinical and histopathological characteristics of rare neoplasms in the maxillofacial region, such as chondrosarcomas, allows the pathologist and surgeon to make the appropriate therapeutic decisions, optimizing the patient's prognosis.

Hyalinizing clear cell carcinoma-a rare entity in the oral cavity: A case report.

BACKGROUND: Hyalinizing clear cell carcinoma (HCCC) is an uncommon tumor that originates in the salivary glands. This neoplasia constitutes less than 1% of minor salivary gland tumors. CASE SUMMARY: A 67-year-old female visited the maxillofacial surgery department owing to a smooth, slightly yellowish protruding mass on the left side of the floor of the mouth, at the level of the molars; the tumor mass had a soft consistency on palpation and did not adhere to deep planes. The microscopical analysis of the excisional biopsy showed that the lesion was composed of sheets and cords of clear cells separated by thick eosinophilic bands of hyaline collagen. Normal glandular tissue was absent, periodic acid-Schiff with and without diastase stains, and immunohistochemical reactions were performed to confirm the diagnosis. This is the second case reported in the literature of HCCC arising in the floor of the mouth. CONCLUSION: HCCC is a rare salivary gland tumor that has not been studied extensively. Its diagnosis is usually challenging, because clinically, it can be confused with a benign neoplasm.