Search

Histone demethylase LSDl (KDMlA) belongs to the flavin adenine dinucleotide (FAD) dependent family of monoamine oxidases and is vital in regulation of mammalian biology. Dysregulation and overexpression of LSD1 are hallmarks of a number of human diseases, particularly cancers that are characterized as morphologically poorly differentiated. As such, inhibitors of LSD1 have potential to be beneficial as a cancer therapy. The most clinically advanced inhibitors of LSDl are covalent inhibitors derived from tranylcypromine (TCP). Herein, we report the discovery of a novel series of reversible and selective LSDl inhibitors. Exploration of structure-activity relationships (SARs) and optimization of ADME properties resulted in the identification of clinical candidate CC-90011. CC-90011 exhibits potent on-target induction of cellular differentiation in acute myeloid leukemia (AML) and small cell lung cancer (SCLC) cell lines, and antitumor efficacy in patient-derived xenograft (PDX) SCLC models. CC-90011 is currently in phase 2 trials in patients with first line, extensive stage SCLC (ClinicalTrials.gov identifier: NCT03850067).

Biorefineries provide a platform for different industries to produce multiple bio-products enhancing the economic value of the system. The production of these biorefineries has led to an increase in the generation of biowaste. To minimize the risk of environmental pollution, numerous studies have focused on a variety of strategies to mitigate these concerns reflected in the vast amount of literature written on this topic. This paper aims to systematically analyze and review the enormous body of scientific literature in the biowaste and biorefinery field for establishing an understanding and providing a direction for future works. A bibliometric analysis is first performed using the CorTexT Manager platform on a corpus of 1488 articles written on the topic of biowaste. Popular and emerging topics are determined using a terms extraction algorithm. A contingency matrix is then created to study the correlation of scientific journals and key topics from this field. Then, the connection and evolution of these terms were analyzed using network mapping, to determine relationships among key terms and analyze notable trends in this research field. Finally, a critical review of articles was presented across three main categories of biowaste management such as mitigation, sustainable utilization, and cleaner disposal from the perspective of the biorefinery concept. Operational and technological challenges are identified for the integration of anaerobic digestion in biorefineries, especially in developing nations. Moreover, logistical challenges in the biorefinery supply-chain are established based on the economics and collection aspect of handling biowaste.

The authors applied a one group pretest-posttest quasi-experimental research design to one section of GVAHS with 45 students to look into the effectiveness of journal writing in mathematics performance consequently preparing the students to technical subjects in the STEM track of the K to 12 curricula. The findings of the study revealed that journals in mathematics produce better and improved scores for students in problem solving tasks. Likewise, journal writing helped the students communicate with their Math Teacher. It can improve their abilities on how to use mathematical tools, symbols and numbers, use math models, analyze, understand and solve problems preparing them for higher mathematics and other related sciences. Also, journal writing helped students to learn how to transfer ideas clearly and convey their feelings and thoughts effectively. Likewise, it enhanced different characteristics that they can use in pursuing the STEM track andin living in the globally competitive world of work.

Tracking mechanisms were found to improve the performance of solar renewable energy systems that contribute to energy sustainability and security. However, the commonly used closed-loop solar trackers require sophisticated equipment that leads to high upfront costs and energy consumption. The literature suggests that simpler open-loop trackers can be sought as a feasible alternative for small-scale applications. In this study, an open-loop solar tracking mechanism was designed through the kinematic synthesis of a Watt II six-bar linkage using Freudenstein’s method and analytical position method. The desired motion of the mechanism was obtained using the solar apparent motion trajectory model. A finite number of precision points were selected using Chebyshev’s spacing to simplify the synthesis while minimizing the error. The design was validated through kinematic analysis using loop closure equations and complex number analysis. The position, velocity, and acceleration behaviors obtained from the numerical method done in MATLAB was compared to that of the graphical method done in MechAnalyzer. The synthesis results hint the special considerations needed in the physical implementation of the design, while the validation results show a general agreement between the results of the numerical and graphical kinematic analyses, implying the effectiveness of the presented methodology.

The rise of mixed-use buildings contributes to the sustainable development of cities but are still met with challenges in energy management due to the lack of energy efficiency and sustainability guidelines. The use of integrated renewable-storage energy systems is a more beneficial solution to this problem over individual solutions; however, most design studies in the literature only focus on single-type of buildings or solutions. Thus, this study aims to develop an optimization model to determine the design capacities of an integrated energy system for mixed-use buildings. The objective is to minimize net present costs, subject to sizing, energy balances, and operational constraints. The case study considered a mixed-use building in a tropical area, with solar photovoltaic system as the renewable energy source and Lithium-ion battery as the energy storage system technology. The model was developed in HOMER Grid software, and economic metrics were used to evaluate and compare the proposed system to the following design cases: business-as-usual, stand-alone renewable source, and standalone energy storage. The results show that the integrated system has the lowest equivalent annual costs despite its high capital costs. Still, it has the most attractive economic case based on the evaluation metrics compared to other design cases.

Background: Alterations in epigenetic control can cause defective post-translational histone modification and dysregulation of gene activity leading to cancer development. Overexpression of KDM4, a demethylase of histone lysine 9 methyl 2/3 and lysine 36 methyl 2/3 (H3K9me2/3 and H3K36me2/3), is documented in a variety of cancers and is linked to aggressive disease and poor clinical outcomes. TACH101 is a novel first-in-class, selective and potent pan KDM4 inhibitor with favorable pharmacologic properties. Methods: TACH101 was evaluated using in vitro and in vivo studies including cell-proliferation assays in multiple cancer cell lines and patient-derived organoid models, apoptotic and cell cycle analyses, pharmacology studies in various animal species, and efficacy studies in xenograft tumor models. Results: Inhibition mechanism studies demonstrated TACH101 to be a reversible, α-ketoglutarate competitive, selective and potent inhibitor of KDM4 isoforms A-D with IC50 values less than 0.100 μM for all four isoforms. In vitro, TACH101 demonstrated potent increase of H3K36me3 levels (EC50 Conclusions: TACH101 is a potent pan inhibitor of KDM4 that is suggestive of broad potential in cancer treatment. Further preclinical evaluation is ongoing to advance the molecule into clinical trials. Citation Format: Sanghee Yoo, Chandtip Chandhasin, Joselyn R. Del Rosario, Young K. Chen, Jeff Stafford, Stephen Quake, Frank Perabo, Michael F. Clarke. TACH101, a first-in-class pan inhibitor of KDM4 histone lysine demethylases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2128.

e15067 Background: The histone Lysine (K) Demethylase 4 family, KDM4 family, is involved in nuclear functions such as programming development, activation or repression of transcription, timing and control of the cell cycle, and initiating DNA replication and repair through chromatin remodeling. Overexpression of KDM4 leading to mistakes in post-translational histone modification has been associated with many cancer types and is being investigated as a potential therapeutic drug target. TACH101 is a novel potent and small molecule inhibitor of the KDM4 family. It demonstrated strong efficacy in multiple cancer types in vitro and in vivo and favorable pharmacokinetics (PK) and safety profiles in preclinical models. Methods: The target interaction properties of TACH101 were evaluated using purified enzymes for biochemical, biophysical, and inhibition mechanism studies. For PK parameter measurements, Sprague-Dawley rats and Beagle dogs were used for intravenous or oral administration of TACH101. Hepatocytes or liver microsomes were used to measure cytochrome P450 (CYP) inhibition and induction studies. Cell lines expressing cardiac channels were used for radioligand displacement assays and patch clamping. Results: Biochemical, biophysical, and inhibition mechanism studies using purified enzymes showed TACH101 is a reversible, alpha-KG (co-factor) competitive, and slow-binding inhibitor with IC50 values less than 100 nM. Pharmacologic studies showed plasma protein binding of TACH101 to be ≥99% bound in mouse, rat, dog, and human. TACH101 appeared to be selective in off-target panel assays of receptors, ion channels and transporters. TACH101 did not show any significant binding displacement activity against cardiac ion channels or any effect on hERG in CHO cells using manual patch clamp techniques. In rats and dogs, TACH101 exhibited low systemic clearance, a moderate volume of distribution in rats and dogs, linear exposure profiles with a terminal half-life (̃ 6-hour) and high bioavailability (46-100%). In repeated dose studies in rats and dogs, mean Cmax and AUC values increased in a dose-related manner over the dose range evaluated. There was no significant impact of food on systemic exposure in dogs. TACH101 did not show inhibition or induction of CYP enzymes tested. Conclusions: TACH101 is a potent KDM4 specific inhibitor without significant off-target activity in in vitro and in vivo studies. It did not show inhibition or induction of CYP enzymes suggesting low probability of CYP mediated drug-drug interaction. The exposure from oral administration in rats and dogs was dose proportional and was not significantly affected by food intake in dogs. Given the favorable target activity, PK properties and safety profile, a Phase 1 study is being planned to advance TACH101 for patients with advanced cancer.

3105 Background: The KDM4 family of histone lysine demethylases consists of four main isoforms (KDM4A, B, C, D), all of which have been identified as key oncogenic drivers. They function as epigenetic regulators and control transitions between transcriptionally silent and active chromatin states via removal of methyl marks on histone H3K9 and histone H3K36. KDM4 isoforms play an important role in the epigenetic dysregulation in various cancers and is linked to more aggressive disease and poorer clinical outcomes. Functional redundancy and cross-activity have been observed across KDM4 family members, thus, selective inhibition of one isoform appears to not be effective. TACH101 is a novel, first-in-class pan inhibitor of KDM4 that simultaneously targets multiple isoforms of KDM4. Here we present data that show TACH101 has promising pre-clinical and pharmacologic properties as a cancer therapeutic. Methods: TACH101 was evaluated in in vitro and in vivo studies including cell-proliferation assays in multiple cancer cell lines, apoptotic and cell cycle analyses, and efficacy studies in various xenograft tumor models and patient-derived organoid models. Results: In vitro, TACH101 was broadly effective in killing 67% (200 out of 300) of cancer cell lines screened. TACH101 demonstrated potent increase of H3K36me3 levels (EC50 < 0.001 mM, HTRF) in KYSE-150 cell line engineered to overexpress KDM4C and potent anti-proliferative activity in multiple cell lines in OncoPanel. TACH101 treatment increased cancer cell population in S-phase in multiple cancer cell lines indicating cell-cycle arrest. TACH101 induced apoptosis in human colorectal (HT-29), esophageal (KYSE-150), and triple negative breast cancer (MDA-MB-231) cell lines with EC50s ranging from 0.033-0.092 µM. In vivo, TACH101 triggered effective tumor control in xenograft models including colorectal, esophageal, gastric, breast, and lymphoma with tumor growth inhibition of up to 100%. Further evaluation using a panel of patient-derived colorectal models and patient-derived organoids showed a strong correlation of TACH101 sensitivity with MSI-H status (IC50 ranges 1-150 nM). TACH101 also reduced tumorigenic potential by 4.4-fold as determined by FACS analysis using sorted CD44High EpCAM+ population in Limiting Dilution Assays in vivo, suggesting that reduction of cancer stem cells by TACH101 may be effective in therapy-resistant settings. Pharmacologic studies showed TACH101 demonstrated favorable cell permeability, good oral bioavailability, and high metabolic stability. Conclusions: Extensive preclinical work on TACH101 KDM4 inhibitor shows compelling data and broad applicability as a potential anti-cancer agent. Further evaluation is ongoing to advance the molecule into clinical trials.

América Latina, a grandes rasgos, es un continente con varios niveles contextuales, dependientes de las características históricas, económicas, políticas y sociales. Con todo, hay aspectos que –como la brecha tecnológica- se reproducen en mayor o menor medida en los distintos países. Dicha brecha promueve unas sociedades parcialmente desconectadas –y, por tanto, invisibilizadas- y tiende a aminorar las posibilidades de innovación y desarrollo del periodismo digital. Metodología: En este estudio, y a partir de un análisis de contenido, hemos analizado la gestión de la interactividad en 87 cibermedios de Colombia, México y Ecuador durante 2016. Resultados y conclusiones: Los resultados muestran una baja implementación general de las opciones de interactividad en los ecosistemas digitales de estos tres países latinoamericanos.

Background Checkpoint blockade immunotherapy has improved metastatic cancer patient survival, but response rates remain low. There is an unmet need to identify mechanisms and tools to circumvent resistance. In human patients, responses to checkpoint blockade therapy correlate with tumor mutation load, and intrinsic resistance associates with pre-treatment signatures of epithelial mesenchymal transition (EMT), immunosuppression, macrophage chemotaxis and TGFβ signaling. Methods To facilitate studies on mechanisms of squamous cell carcinoma (SCC) evasion of checkpoint blockade immunotherapy, we sought to develop a novel panel of murine syngeneic SCC lines reflecting the heterogeneity of human cancer and its responses to immunotherapy. We characterized six Kras-driven cutaneous SCC lines with a range of mutation loads. Following implantation into syngeneic FVB mice, we examined multiple tumor responses to α-PD-1, α-TGFβ or combinatorial therapy, including tumor growth rate and regression, tumor immune cell composition, acquired tumor immunity, and the role of cytotoxic T cells and Tregs in immunotherapy responses. Results We show that α-PD-1 therapy is ineffective in establishing complete regression (CR) of tumors in all six SCC lines, but causes partial tumor growth inhibition of two lines with the highest mutations loads, CCK168 and CCK169. α-TGFβ monotherapy results in 20% CR and 10% CR of established CCK168 and CCK169 tumors respectively, together with acquisition of long-term anti-tumor immunity. α-PD-1 synergizes with α-TGFβ, increasing CR rates to 60% (CCK168) and 20% (CCK169). α-PD-1 therapy enhances CD4 + Treg/CD4 + Th ratios and increases tumor cell pSmad3 expression in CCK168 SCCs, whereas α-TGFβ antibody administration attenuates these effects. We show that α-TGFβ acts in part through suppressing immunosuppressive Tregs induced by α-PD-1, that limit the anti-tumor activity of α-PD-1 monotherapy. Additionally, in vitro and in vivo, α-TGFβ acts directly on the tumor cell to attenuate EMT, to activate a program of gene expression that stimulates immuno-surveillance, including up regulation of genes encoding the tumor cell antigen presentation machinery. Conclusions We show that α-PD-1 not only initiates a tumor rejection program, but can induce a competing TGFβ-driven immuno-suppressive program. We identify new opportunities for α-PD-1/α-TGFβ combinatorial treatment of SCCs especially those with a high mutation load, high CD4+ T cell content and pSmad3 signaling. Our data form the basis for clinical trial of α-TGFβ/α-PD-1 combination therapy (NCT02947165). Electronic supplementary material The online version of this article (10.1186/s40425-018-0493-9) contains supplementary material, which is available to authorized users.

The growing global energy demand and continuous dependency on fossil fuels have triggered concerns over energy security and global warming. This issue has led to the prioritization of renewable sources in order to achieve sustainable development in the energy sector. The use of hybrid renewable sources and polygeneration systems to develop a sustainable energy system have also been emphasized in the literature. Thus, this study aims to optimize the design of a hybrid renewable energy-water system for tropical buildings. A fuzzy quadratic programming model was developed from a system architecture utilizing solar and biomass sources to meet electricity, cooling, heating, and water demands. The objective is to maximize the degree of satisfaction, which is based on multiple objectives of meeting the projected demand and minimizing the economic and environmental impacts. Technical, economic, and environmental constraints are included in the model based on fuzzy membership functions. The model was demonstrated using a case study considering a tropical commercial hotel building. The optimized system design yields a degree of satisfaction of 0.9999, compared to 0.1351 for a system with solar energy as the only source. These results highlight the benefit of renewable source hybridization and polygeneration to design a sustainable energy system.

The histone demethylase LSD1 is a key enzyme in the epigenetic regulation of gene transcription. Here we present our efforts to discover small molecule reversible inhibitors of LSD1 as an attractive approach to treat hematologic malignancies and certain solid tumors. Using structure-based drug design, we designed and synthesized a novel series of heteroaromatic imidazole inhibitors that demonstrate potent inhibition of the demethylase activity and low nanomolar cell-based activity. This novel LSD1 inhibitor series was further optimized by attenuating the hERG inhibition and improving oral bioavailability.

Background Neurocutaneous melanosis is a rare phakomatosis characterized by large or multiple pigmented nevi and melanosis of the leptomeninges. It is often complicated by hydrocephalus due to melanotic deposits interfering with cerebrospinal fluid reabsorption in the basal cisterns or causing foraminal or aqueductal obstruction. In 10% of cases, it will be associated with the Dandy-Walker complex. Case Description We present the case of a 6-year-old girl with multiple congenital hairy nevi presenting with generalized tonic-clonic seizures, headache, and vomiting. Neuroimaging showed a communicating hydrocephalus associated with the Dandy-Walker variant, melanotic deposits in the amygdalae, thalami, and cortical sulci, and abnormal leptomeningeal enhancement. After undergoing ventriculoperitoneal shunt insertion, the symptoms of increased intracranial pressure abated. However, she again showed deterioration 1 month postoperatively due to progressive leptomeningeal spread suspicious for malignant degeneration. Conclusion The results of the present case and the findings from a review of related data suggest that shunt insertion (ventriculoperitoneal or cystoperitoneal) is an effective palliative measure for patients with neurocutaneous melanosis with associated hydrocephalus. Despite treatment, however, the prognosis of these patients remains poor owing to malignant progression and leptomeningeal spread of lesions, in particular, in cases associated with the Dandy-Walker complex.

OBJETIVO: Comparar el grado de aceptación de dos registros de los movimientos fetales percibidos por la gestante en una población de riesgo bajo. Lugar: Hospital San Bartolomé. MATERIAL Y MÉTODOS: Entre octubre 1998 y marzo 1999, se seleccionó aleatoriamente a 350 gestantes para el registro de movimientos fetales en la gráfica propuesta por el Centro Latino Americano de Perinatología (CLAP) y 350 para el registro en una gráfica alterna (“Conteo hasta 10 "). Se evaluó la dificultad para el llenado, el cumplimiento del mismo, y se comparó el grado de aceptación de ambas cartillas. Los resultados fueron sometidos a valoración estadística con la prueba del x2, aceptándose un valor de p

Histone lysine demethylases (KDMs) play a vital role in the regulation of chromatin-related processes. Herein, we describe our discovery of a series of potent KDM4 inhibitors that are both cell permeable and antiproliferative in cancer models. The modulation of histone H3K9me3 and H3K36me3 upon compound treatment was verified by homogeneous time-resolved fluorescence assay and by mass spectroscopy detection. Optimization of the series using structure-based drug design led to compound 6 (QC6352), a potent KDM4 family inhibitor that is efficacious in breast and colon cancer PDX models.

La displasia fibrosa es una enfermedad ósea benigna que cambia el tejido óseo normal por una proliferación de tejido conectivo. Se piensa que la alteración del gen Gsalfa es la principal razón de la enfermedad. La hemofilia C es una enfermedad sanguínea, hereditaria rara, que provoca hemorragias en pacientes afectos. Es autonómica recesiva, por lo que hombres y mujeres pueden estar afectos. Paciente de 13 años que desarrolla una displasia fibrosa en maxilar superior derecho que empieza con dolor durante la masticación de alimentos duros. Presenta abombamiento de vestíbulo y enrojecimiento de paladar derecho. Presenta un déficit discreto de factor XI (heterocigoto). Por ello, necesita una preparación especial antes de extirpar la lesión debido a su déficit. Se ha descubierto que la razón de la displasia fibrosa es la mutación del gen Gsalfa (GNAS1) que está en el cromosoma 20q. La causa de la hemofilia C es el déficit del factor XI debido a una mutación del gen FXI en el cromosoma 4. Quizás estas dos raras enfermedades tengan una relación, porque ambas se presentan en el mismo paciente.Fibrous Dysplasia is a benign bone disease that changes normal bone tissue for a proliferation of connective fibrous tissue. It is thought that an alteration of the Gsalpha gene is the main cause of the disease. Hemophilia C is a rare inherited blood disease leading to abnormal hemorrhages in affected patients. They have a factor XI deficiency. It is the least frequent of all hemophilias. It is a recessive autosomal disease, affecting both men and women. A 13 year-old patient developed fibrous dysplasia in right upper maxilla. The patient started with pain on chewing hard food. She had vestibular swelling and reddening of the right side of the palate. She had a discrete factor XI deficiency (heterozygotic). She needed special preparation before the lesion could be removed because of her deficiency. It has been discovered that the mutation of gene Gsalpha (GNAS1) is the reason for fibrous dysplasia. This gene is in chromosome 20q. The cause of hemophilia C is a factor XI deficiency due to a mutation in the FXI gene in chromosome 4. Perhaps these two rare diseases are related, because both are unusual diseases and both are in the same patient.

Summary This study was conducted to determine the effects of temperature, time and concentration of acids on the hydrolysis of coconut and soybean meals. Using 6∼ hydrochloric acid (HCl), the complete hydrolysis of soybean meal was reached after 36 hr at 95°C, while it took only 24 hr to complete the process when 18 N sulphuric acid (H2SO2) was used at the same temperature. Coconut protein exhibited some degree of resistance to hydrolysis. Using 10 N HC1 and 18 N H2SO2 in two separate tests, it took 48 hr to complete hydrolysis at 95°C. Sulphuric acid caused a considerably greater decomposition of amino acids than HCl during longer periods of reaction with high acid concentration and temperature. Flavour development is a function of the free amino acids released which in turn is a function of acid concentration, reaction time and temperature.

Presentamos tres pacientes con defectos genianos complejos, que fueron reconstruidos mediante tres combinaciones diferentes de colgajos cutáneos y suspensiones dinámicas de músculo temporal. Los defectos comprendían amplias pérdidas de piel y musculatura facial, pudiendo incluir o no la mucosa geniana. En dos de los casos se trataba de una lesión indurada a nivel geniano con histología compatible con dermatofibrosarcoma protuberans, que no habían recibido ningún tratamiento previo. En el otro paciente se trataba de un carcinoma epidermoide, intervenido en dos ocasiones y que había recibido radioterapia. Para la reconstrucción del defecto cutáneo usamos el colgajo libre compuesto radial, un colgajo de rotación cervicofacial y un colgajo de músculo temporal. Todos los pacientes curaron sin complicaciones y los resultados estéticos y funcionales fueron buenos.We present three patients whose genian complex defects were reconstructed with several cutaneous flaps and dynamic suspension of the temporal muscle. Complex genian defects are those that involve major skin and facial muscle loss, which can also include genian mucous or not. Two cases involved a nodular lesion in the genian region with biopsy reports that indicated dermatofibrosarcoma protuberans, without previous treatment; the other patient had an epidermoide carcinoma, which had been operated twice, and she had received radiotherapy. For the cutaneous reconstruction a composite free radial forearm flap, a cervicofacial flap and a temporal muscle flap were used. Primary healing with no complications was achieved in all patients together with good aesthetic and functional results.

Introducción. La parótida es primer escalón ganglionar en la diseminación regional de los melanomas cutáneos de región frontal, orbitaria y nasal. Aunque la linfografía se ha convertido en una prueba diagnóstica estándar en el estudio del melanoma, no está exenta de inconvenientes. Material y método. Presentamos el caso de un paciente con melanoma frontal y ganglios centinela parotídeos y discutimos las particularidades, ventajas y desventajas de la técnica en dicha región. Conclusiones. Aunque se ha demostrado que la afectación del ganglio centinela es el factor predictor más importante de recurrencia y supervivencia, creemos que es una técnica en estudio cuyo efecto en la supervivencia debe ser demostrado frente a la alternativa de seguimiento clínico y que por tanto debe indicarse en casos seleccionados con mayor probabilidad de metástasis.Introduction. The parotid gland is the first lymph node echelon in the regional dissemination of frontal, orbital and nasal cutaneous melanomas. Although the lymphoscintigraphy has been become a standard diagnostic technique for studying melanomas, it is not exempt of inconveniences. Material and methods. We present the case of a patient with frontal melanoma and sentinel nodes in the parotid region, and we discuss the peculiarities, advantages and disadvantages of using this technique in this region. Conclusions. Although it has been proved that an affected sentinel lymph node is the most important prognostic factor for recurrence and survival, we believe that this is a technique under study, and that its influence on survival should be demonstrated with regard to the alternative of clinical monitoring. It should therefore be indicated in specific cases with greater probabilities of metastases.

La cirugía de las deformidades maxilofaciales ha evolucionado de manera importante en las últimas décadas y el número de pacientes que reciben este tipo de tratamiento ha aumentado de forma considerable. Uno de los temas más debatidos en la literatura reciente se refiere a la necesidad de autodonación sanguinea preoperatoria. hacemos una revisión de las publicaciones relevantes en años recientes, que demuestran puntos de vista opuestos.Surgery for maxillofacial deformities has seen important developments over the last decades and the number of patients undergoing these types of treatment has increased considerably. One of the most debated issues in the recent literature concerns the need for preoperative autologous blood donation. A revision of the relevant publications of recent years reveals opposite views.

La osteomielitis esclerosante difusa (OED) es una enfermedad de etiología desconocida, con dificultades para el diagnóstico y tratamiento ya que la literatura existente al respecto es confusa, con un gran desconocimiento respecto a su causa y evolución natural. Existen de dos teorías para explicar su origen: Infecciosa: difícil de confirmar mediante los datos bacteriológicos. Hiperplasia ósea derivada de una tendoperiostitis crónica, por una disfunción muscular y hábitos parafuncionales. Se caracteriza por dolor recurrente y tumefacción hemimandibular, aunque puede presentar otras localizaciones, acompañada habitualmente de trismus, presión y parestesia y adenopatías regionales, cursa de forma episódica. El tratamiento de la OED es complejo, debido a que se han intentado múltiples terapias sin que ninguna haya dado un resultado satisfactorio a largo plazo.Tras revisar el tema, a propósito de un caso clínico, recomendamos roxitromicina a largo plazo como una línea de tratamiento a tener en cuenta en la OED por la eficacia que viene demostrando y los tolerables efectos secundarios, si bien cada caso debido a la complejidad de la enfermedad debe ser revisado individualmente, pero teniendo en cuenta esta opción terapéutica.Diffuse sclerosing osteomyelitis (DSO) is a disease of unknown etiology which is difficult to diagnose and treat as the literature available on the subject is confused, and there is a considerable lack of knowledge with regards to what causes it and its natural evolution. There are two theories explaining its origin. One suggests an infectious origin, but this is difficult to confirm by means of bacteriological data. The other suggests an osseous hyperplasia origin derived from chronic tendoperiostitis as a result of muscular dysfunction and parafunctional habits. The disease is characterized by recurrent pain and hemimandibular tumefaction, although it can present in other locations. It is accompanied normally by trismus, pressure and paresthesia and regional adenopathy. It has an episodic clinical course. Treating DSO is complex due to the fact that many therapies have been tried but with no long-term success. After reviewing the subject as a result of a clinical case, we recommend considering roxithromycin in the long term as a line of treatment for DSO in view of its efficacy and its tolerable secondary effects. Needless to say, each case should be reviewed individually given the complexity of the disease, while taking into account this therapeutic option.

We assessed the validity of a syndromic case management approach for reproductive tract infections (RTIs) among 371 pregnant women attending antenatal care facilities in Kingston, Jamaica, using an algorithm previously validated in high-risk Jamaican women. For our antenatal attenders, the algorithm had low sensitivities for all RTIs (66.7% for cervicitis, 35.4% for trichomoniasis, 11.1% for bacterial vaginosis (BV) and 24% for candidiasis). Specificities for BV (88.9%) and candidiasis (81.1%) were higher than for cervicitis (62.8%) and trichomoniasis (68.5%). The positive predictive values were lower than 36% for all diagnoses, especially BV (6.9%). Syndromic management of RTIs in pregnant women was problematic using a clinical algorithm that had worked well for high-risk women. Syndromic management for RTIs in Jamaican antenatal clinics is only a temporary solution until more simple and affordable diagnostic tests for RTIs are developed and/or until laboratory support and clinical care can be upgraded at antenatal clinics.

Resumen: El manejo de los cuellos N0 en pacientes con carcinoma epidermoide de cabeza y cuello es controvertido. Objetivo. Demostrar la eficacia diagnóstica de la biopsia del ganglio centinela (GC) en los pacientes con carcinoma epidermoide oral con cuello clinicamente negativo. Metodología. Se realiza un estudio prospectivo de 12 pacientes consecutivos, hasta el momento, con carcinoma epidermoide oral de cualquier tamaño y cuello clinicamente negativo que no habian recibido tratamiento antitumoral, asistidos en el S. de Cirugía Maxilofacial del área del H.U.V.M de Sevilla. A estos pacientes se les realiza una linfografía cervical con nanocoloides -Tc 99 para localizar el GC, y una dosis de recuerdo antes de iniciar el ttº quirúrgico. Durante la cirugía se localiza el GC con la sonda y se extirpa, se completa la disección cervical funcional y la extirpación de la lesión con posteriores estudios histológicos independientes. Resultados. índice de linfolocalización: 91%, índice de radiolocalización 100%, falsos negativos 0%, la sensibilidad y VPN del 100%, cocientes de probabilidades positivo > 10 y negativo < 0,1. Conclusiones. La técnica es eficaz para detectar GC-metástasico y es una guia prometedora para indicar la disección cervical (Subvención FIS 2002).Abstract: IManagement of the N0 neck in patients with head and neck squamous cell carcinoma remains controversial. Objective. To evaluate the feasibility and predictive ability of the sentinel node (SN) localization-biopsy technique for patients with squamous cell carcinoma of the oral cavity and clinically negative necks. Methodology. We realize a prospective study of 12 consecutive patients at present, with squamous cell carcinoma oral and clinically negative necks. These patients had not recived treatment against tumor and they were assited by Maxillofacial Surgery Service of HUVM from Seville. All patients received a cervical Tc99mlymphoscintigraphy to localize the sentinel node and a new dose before surgery. Intraoperatively, the sentinel node is localized and it is removed separately before tumor resection and elective functional neck dissection. The different anatomic specimens are sent for independent histological examination. Results. lympholocalization 91%, radiolocalization 100%, false negative 0%, sensitivity and NPV 100%, likely hood ratios > 10 and likely negative ratios < 0.1. Conclusions. The technique allows identification of SN-metastases and shows promise in guiding functional neck dissection (FIS-2002 subvention)

A case - control study was conducted to assess the risk factors of stillbirth among pregnant women in Jamaica. A total of 314 women participated (160 with stillborn babies and 154 with live-born babies). A questionnaire designed to collect information on sociodemographic characteristics, antenatal care, medical and sexually transmitted disease (STD) history, method of delivery and infant birth and health status was administered to each woman. Medical records were reviewed to verify medical history. Six variables were found to be significant predictors of stillbirth by multivariate logistic regression. Low birth weight (OR = 4.3, CI = 2.4 - 7.7), complications during pregnancy or delivery (OR = .19, CI = 0.09 - 0.41), method of delivery (caesarean section; OR = 7.2, CI = 1.6 - 33.2), number of living children (OR = 0.54, CI = 0.40 - 0.73), number of antenatal visits (less than three; OR = 2.0, CI = 1.3 - 3.1), and presence of unfavourable and /or adverse fetal outcome (OR = 4.0, CI = 1.8 - 9.2) were found to be associated with stillbirth. These findings have important implications in establishing policies for prenatal care in Jamaica.

The objective of this study is to assess the serum concentration and the urinary depletion of vitamin A in patients with AIDS with acute illness (hospitalized) and without acute illness (clinic attenders); and to examine the relationship of serum and urinary retinol levels with weight loss, patient survival, CD4 count, fever, and liver function. Serum and urinary retinol of 26 patients from the AIDS clinic or hospital of the University of Alabama at Birmingham (UAB) were measured using HPLC. Mean serum retinol was lower in hospital patients than in clinic attenders, although the difference was not statistically significant. However, urinary retinol loss was significantly higher in hospital patients than clinic patients (0.09± 0.12 vs. 0.04 ± 0.12, p=0.0193). There were significant correlations between urinary retinol excretion and body weight loss in clinic patients and between urinary retinol loss and high serum bilirubin levels in hospital patients. A significantly higher proportion of hospital than clinic patients lost body weight during the last month before recruitment into the study (p=0.039). Further, a significantly higher proportion of those who lost weight subsequently died than survived (p=0.015). Urinary loss of retinol was significantly predicted by increased body temperature (p=0.0069) and decreased CD4 count (p=0.0454) in clinic patients. No single variable predicted significantly the urinary retinol loss in hospital patients. The presence of acute illness in hospital patients with AIDS appeared to be a risk factor for low serum retinol and increased urinary excretion of retinol. Greater urinary retinol loss and more severe illness are associated with body weight loss and death.

Following a rail accident that spilled the soil fumigant VAPAM into the Sacramento River on 14 July 1991, a special study was carried out to assess the extent of contamination in Lake Shasta. A total of 32 river water samples collected on 18 July and another 316 samples collected from 22 July through 30 August were analyzed. Data obtained clearly showed the presence of the degradation products of Metham, namely, methyl isothiocynate, carbonyl sulfide, methyl sulfide, and traces of methylamine

A high performance liquid chromatographic (HPLC) procedure was developed for the determination of domoic acid (DA) in seafood, including on-line sample purification. Unpurified aqueous methanol extracts of tissue samples were partially purified with a cyano precolumn cartridge. Separation was performed on a reverse-phase C-18 column with gradient elution, and UV detection. UV spectra were acquired for confirmation. Analyte recoveries from 89% to 100% were obtained for a variety of tissues. The detection limit with confirmation by UV spectrum was 0.1 μg/g. The method eliminates the use of a manual sample cleanup step. In contrast to other published procedures, the method is insensitive to NaCl, which maybe present at high concentrations in some seafood samples. Further, tryptophan does not interfere.

A high performance liquid chromatographic (HPLC) procedure was developed for determination and confirmation of sodium N-methyldithiocarbamate and methyl isothiocyanate (MITC) present in water. Both analytes are separated on a strong anion exchange column (25 cm × 4.6 mm × 5 μm) with a mobile phase of (45+55, V/V) methanol/buffered water (pH 6.9) containing 10mM hexadecyltrimethyl ammonium bromide (CTAB) and are measured by UV using 242 and 284 nm wavelengths. Diode array spectra were acquired for confirmation. Analyte recoveries were 108% and 114%, respectively when both compounds were present in raw surface water. Linear calibration plots from 5 μg/L to 250 mg/L for MITC and 5 mg/L to 250 mg/L for Metham SodiumR with correlation coefficients of >0.99, were obtained. Precision data and analyte UV/VIS spectra for confirmation are shown for both compounds. The detection limit is 2 μg/L for MITC and 2 mg/L for Metham SodiumR

A confirmatory and quantitative technique is developed for domoic acid (DA) in seafood samples which is based on methanol-water extraction, separation by reverse phase liquid chromatography, a ninhydrin post-column derivatization of the acid, and UV detection at 402 nm. Tissue samples containing as low as 0.3 μg DA/g analyzed by a direct method using 242 nm can be confirmed by this technique. The linear range is excellent (1 ng to 4 μg) with a linear correlation coefficient of 0.994. Spike recovery of DA was 93% at a tissue concentration of 10 μg DA/g. The method was applied successfully to mussels, crabs, oysters, razor clams, and anchovies.

This paper describes a direct determination of benomyl and carbendazim in a single analytical run and their confirmation by absorption spectra using diode array detection. A simple technique has been developed for preparation of benomyl calibration standard. Benomyl was dissolved in chloroform prior to a high dilution in water for HPLC. Detection limits, precision, and accuracy of data are presented. The method is simple, rapid, accurate, and precise.

The acceptability and storage stability of a cheese-flavored spread from peanuts were determined. Consumer test involving 416 respondents were conducted at six central locations in the Philippines. The spread was most acceptable to plder respondents in general and least acceptable to those under 20 years of age. Also, respondents earning more than P 24 000 found the spread least acceptable. Consumers were willing to pay a higher price for the cheese-flavoured spread than for peanut butter but lower than that for a dairy-based spread. Results indicate that the color and flavor of the cheese-flavored spread did not significantly change after storage at 30° C for 60 days.

espanolLa displasia fibrosa es una enfermedad osea benigna que cambia el tejido oseo normal por una proliferacion de tejido conectivo. Se piensa que la alteracion del gen Gsalfa es la principal razon de la enfermedad. La hemofilia C es una enfermedad sanguinea, hereditaria rara, que provoca hemorragias en pacientes afectos. Es autonomica recesiva, por lo que hombres y mujeres pueden estar afectos. Paciente de 13 anos que desarrolla una displasia fibrosa en maxilar superior derecho que empieza con dolor durante la masticacion de alimentos duros. Presenta abombamiento de vestibulo y enrojecimiento de paladar derecho. Presenta un deficit discreto de factor XI (heterocigoto). Por ello, necesita una preparacion especial antes de extirpar la lesion debido a su deficit. Se ha descubierto que la razon de la displasia fibrosa es la mutacion del gen Gs? (GNAS1) que esta en el cromosoma 20q. La causa de la hemofilia C es el deficit del factor XI debido a una mutacion del gen FXI en el cromosoma 4. Quizas estas dos raras enfermedades tengan una relacion, porque ambas se presentan en el mismo paciente. EnglishFibrous dysplasia is a benign bone disease that changes normal bone tissue for a proliferation of connective fibrous tissue. It is thought that an alteration of the Gsalpha gene is the main cause of the disease. Hemophilia C is a rare inherited blood disease leading to abnormal hemorrhages in affected patients. They have a factor XI deficiency. It is the least drequent of all hemophilias. It is a recesive autosomal disease, affecting both men and woman. A 13 year-old patient developed fibrous dysplasia in right upper maxila. The patient started with pain on chewing hard food. She had vestibular swelling and reddening of the right side of the palate. She had a discrete factor XI deficiency (heterozygotic). She needed special preparation before the lesion could be removed because of her deficiency. It has been discovered that the mutation of gene Gsalpha (GNAS1) is the reason for fibrous dysplasia. This gene is a chromosome 20q. The cause of hemophilia C is a factor XI deficiency due to a mutation in the FXI gene in chromosome 4. Perhaps these two rare diseases are related, because both are unusual diseases and both are in the same patient.