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Background and purpose: Functional neuroimaging studies have suggested a dysfunction of prefrontal regions in clinically pre-symptomatic individuals with the Huntington’s disease (HD) gene mutation (pre-HD) during cognitive processing. The objective of this study was to test the impact of cognitive demand on prefrontal connectivity in pre-HD individuals. Methods: Sixteen healthy controls and sixteen pre-HD subjects were studied using functional MRI and a verbal working memory task with increasing cognitive load. Load-dependent functional connectivity of the left dorsolateral prefrontal cortex (DLPFC) was investigated by means of psychophysiological interactions. Results: In pre-HD subjects, aberrant functional connectivity of the left DLPFC was found at high working memory load levels only. Compared with healthy controls, pre-HD individuals exhibited lower connectivity strength in the left putamen, the right anterior cingulate and the left medial prefrontal cortex. Pre-HD individuals close to the onset of motor symptoms additionally exhibited lower connectivity strength in the right putamen and the left superior frontal cortex. The connectivity strength in the left putamen was associated with several clinical measures including CAG repeat length, Unified Huntington's Disease Rating Scale motor score and predicted years to manifest symptom onset. Conclusion: These findings suggest that early prefrontal connectivity abnormalities in pre-HD individuals are modulated by cognitive demand. [ABSTRACT FROM AUTHOR]

Simple Summary: Triple-negative breast cancer (TNBC) is a clinically, phenotypically, and molecularly heterogeneous disease. This heterogeneity is a factor that negatively impacts therapy response. To analyze evolutionary patterns and the genomic alterations in patients with clinically aggressive disease who did not respond to treatment, we performed whole-exome sequencing in multiple longitudinal samples from diagnosis to distant metastasis. We found an extensive intrapatient and interpatient genetic heterogeneity, mutational signature composition at different stages, and, interestingly, an early lymph node metastasis formation during the evolution of aggressive TNBC. This study provides detailed insights into the genomic complexity, and the phylogenetic and evolutionary development of TNBC, as well as identifying specific mutations associated with targeted treatments in TNBC. In triple-negative breast cancer (TNBC), only 30% of patients treated with neoadjuvant chemotherapy achieve a pathological complete response after treatment and more than 90% die due to metastasis formation. The diverse clinical responses and metastatic developments are attributed to extensive intrapatient genetic heterogeneity and tumor evolution acting on this neoplasm. In this work, we aimed to evaluate genomic alterations and tumor evolution in TNBC patients with aggressive disease. We sequenced the whole exome of 16 lesions from four patients who did not respond to therapy, and took several follow-up samples, including samples from tumors before and after treatment, as well as from the lymph nodes and skin metastases. We found substantial intrapatient genetic heterogeneity, with a variable tumor mutational composition. Early truncal events were MCL1 amplifications. Metastatic lesions had deletions in RB1 and PTEN, along with TERT, AKT2, and CCNE1 amplifications. Mutational signatures 06 and 12 were mainly detected in skin metastases and lymph nodes. According to phylogenetic analysis, the lymph node metastases occurred at an early stage of TNBC development. Finally, each patient had three to eight candidate driving mutations for targeted treatments. This study delves into the genomic complexity and the phylogenetic and evolutionary development of aggressive TNBC, supporting early metastatic development, and identifies specific genetic alterations associated with a response to targeted therapies. [ABSTRACT FROM AUTHOR]

Abstract: In clinically presymptomatic individuals with the Huntington''s disease (HD) gene mutation, functional neuroimaging data have suggested a dysfunction of multiple cortical and subcortical regions including the prefrontal and parietal cortex, as well as the striatum. Although it has been hypothesized that these activation differences most likely reflect aberrant corticostriatal circuits, the functional coupling of neural networks associated with cognitive performance has not been investigated so far. In this study, we used functional magnetic resonance imaging (fMRI) and multivariate analytic techniques to investigate memory-related patterns of functional connectivity in healthy controls (n =16) and pre-HD individuals (n =16). Independent component analyses (ICA) revealed distinct bilateral frontostriatal and frontoparietal networks that were activated during a verbal working memory paradigm in both healthy controls and pre-HD subjects. Compared with healthy controls, pre-HD individuals exhibited lower functional connectivity in left lateral prefrontal and parietal regions as well as in the bilateral putamen. Functional connectivity indices in the left putamen were negatively correlated with the CAG repeat size and the UHDRS behavioral score, and positively correlated with the predicted years to manifest symptom onset. The connectivity of the right putamen was negatively correlated with the UHDRS motor score. In pre-HD individuals, these results suggest an early frontostriatal and frontoparietal deficit of dissociable functional networks associated with executive processing. [Copyright &y& Elsevier]

Hypoxia inhibits Na-K-ATPase activity and leads to its degradation in mammalian cells. Von Hippel Lindau protein (pVHL) and hypoxia inducible factor (HIF) are key mediators in cellular adaptation to hypoxia; thus, we set out to investigate whether pVH and HIF participate in the hypoxia-mediated degradation of plasma membrane Na-K-ATPase. We found that in the presence of pVHL hypoxia decreased Na-KATPase activity and promoted the degradation of plasma membrane Na-K-ATPase. In pVHL-deficient cells, hypoxia did not decrease the Na-K-ATPase activity and the degradation of plasma membrane Na-K-ATPase was prevented, pVHL-mediated degradation of Na-K-ATPase required the functional pVHL E3 ligase and Ubc5 since pVI-IL mutants and dominant-negative Ubc5 prevented Na-K-ATPase from degradation. The generation of reactive oxygen species was necessary for pVHL-mediated Na-K-ATPase degradation during hypoxia. Desferrioxamine, which stabilizes HIF1/2α, did not affect the half-life of plasma membrane Na-K-ATPase. In addition, stabilizing HIF1/2α by infecting mammalian cells with adenoviruses containing the oxygen-dependent degradation domain of HIF1α did not affect the plasma membrane Na-K-ATPase degradation. In cells with suppression of pVHL by short hairpin RNA, the Na-K-ATPase was not degraded during hypoxia, whereas cells with knockdown of HIF1/2α retained the ability to degrade plasma membrane Na-K-ATPase. These findings suggest that pVHL participates in the hypoxia-mediated degradation of plasma membrane Na-K-ATPase in a HIF-independent manner. [ABSTRACT FROM AUTHOR]

Hypercapnia (elevated CO(2) levels) occurs as a consequence of poor alveolar ventilation and impairs alveolar fluid reabsorption (AFR) by promoting Na,K-ATPase endocytosis. We studied the mechanisms regulating CO(2)-induced Na,K-ATPase endocytosis in alveolar epithelial cells (AECs) and alveolar epithelial dysfunction in rats. Elevated CO(2) levels caused a rapid activation of AMP-activated protein kinase (AMPK) in AECs, a key regulator of metabolic homeostasis. Activation of AMPK was mediated by a CO(2)-triggered increase in intracellular Ca(2+) concentration and Ca(2+)/calmodulin-dependent kinase kinase-beta (CaMKK-beta). Chelating intracellular Ca(2+) or abrogating CaMKK-beta function by gene silencing or chemical inhibition prevented the CO(2)-induced AMPK activation in AECs. Activation of AMPK or overexpression of constitutively active AMPK was sufficient to activate PKC-zeta and promote Na,K-ATPase endocytosis. Inhibition or downregulation of AMPK via adenoviral delivery of dominant-negative AMPK-alpha(1) prevented CO(2)-induced Na,K-ATPase endocytosis. The hypercapnia effects were independent of intracellular ROS. Exposure of rats to hypercapnia for up to 7 days caused a sustained decrease in AFR. Pretreatment with a beta-adrenergic agonist, isoproterenol, or a cAMP analog ameliorated the hypercapnia-induced impairment of AFR. Accordingly, we provide evidence that elevated CO(2) levels are sensed by AECs and that AMPK mediates CO(2)-induced Na,K-ATPase endocytosis and alveolar epithelial dysfunction, which can be prevented with beta-adrenergic agonists and cAMP. [ABSTRACT FROM AUTHOR]

Focuses on a case of Wilson's disease in psychiatric patients. Patient case background. Inherited disorder of copper metabolism; Complications of Wilson's disease; Hypersomnia in major depression.

Abstract: Localization of cognitive processes is a strength of functional neuroimaging. However, information about functional interactions between brain areas is crucial for a deeper understanding of brain function. We applied vector autoregressive modeling in the context of Granger causality as a method to analyze directed connectivity in a standard event-related fMRI study using a simple auditory–motor paradigm. The basic idea is to use temporal information in stochastic time series of a brain region in order to predict signal time courses in other brain regions. Thus, we predicted that the method should demonstrate causal influence of the auditory cortex and the supplementary motor area (SMA) on primary motor cortex. Eleven right-handed healthy female subjects were instructed to press a ball with either their left or their right hand when hearing the command “left” or “right” in the scanner. Influence to the left motor cortex was found from bilateral auditory cortex as well as from the SMA in 9 of 11 subjects. Granger causality to the right motor cortex existed from bilateral auditory cortex in 5 and from SMA in 6 subjects. Granger causality to the SMA existed from right auditory cortex in 7 subjects and from left auditory cortex in 8 subjects. Our findings in a simple task show that even under suboptimal circumstances (a relatively long TR of 2440 ms), Granger causality can be a useful tool to explore effective connectivity. Temporally optimized scanning should increase that potential. [Copyright &y& Elsevier]

Introducción: El tabaco, además de ser la causa singular de mortalidad más prevenible, genera desigualdades en salud sociales y de género. Los colectivos social y económicamente menos favorecidos son los que mayor consumo presentan. Respecto a su prevalencia, entre los hombres el tabaquismo ha disminuido en los últimos años, siendo estable entre las mujeres desde 2002 incluso con ligeros ascensos en ciertos sectores de edad. Está demostrada la repercusión del tabaquismo en el entorno humano (fumadores pasivos) y ambiental (humo de tercera y cuarta mano). Objetivos: General: Sensibilizar la población para conseguir una Tolosaldea libre de humo y colillas de tabaco Específicos: Difundir las ventajas de una vida sin tabaco tanto a modo individual como social. Promocionar la oferta de deshabituación de Osakidetza y Asociación contra el Cáncer (AECC) Evitar la incorporación de los jóvenes tabaquismo Sensibilizar a la población de la toxicidad de las colillas. Población diana Población de Tolosaldea. Entidades organizadoras Osakidetza, AECC, Salud Pública, Ayuntamientos de la comarca, Clínica Asunción. Cronología 2016: Diseño de la campaña y preparación del material de apoyo (Osakidetza y Salud Pública). Búsqueda de colaboradores (AECC, Ayuntamientos, Clínica Asunción) 2017: Difusión: reunión con farmacéuticos y odontólogos de Tolosaldea, trípticos informativos y carteles en todos los centros de salud de Osakidetza, clínica Asunción, farmacias y consultas de odontología, entrevistas en radio, televisión y prensa locales. Oferta de grupos de deshabituación a todas las empresas de la zona Envío de cartas a todos los establecimientos hosteleros solicitándoles su colaboración con el cumplimiento de la ley. Oferta de talleres a centros educativos Actividades: talleres con alumnado de ESO, concurso fotográfico "¿Dónde están las colillas?", mesa informativa. 2018: Actividades: talleres con alumnado de ESO, concurso fotográfico "¿Cuáles son tus razones para no fumar?", exposición, mesa informativa. Innovación: Aúna agentes sanitarios y sociales en la lucha contra el tabaco Aborda el impacto negativo de las colillas en el medioambiente y pretende sensibilizar a la población Impacto y resultados: Difusión: Reuniones realizadas: 11; asistentes /personas convocadas: 60 / 106 Envío de documentación: 235 cartas a establecimientos hosteleros y 700 a empresas Entrevistas divulgativas en medios de Comunicación: 8 Actividades preventivas: Talleres con alumnado de ESO, participantes: 212 en 2017 y 513 en 2018 Concursos fotográficos, fotografías recibidas 27 en 2017 y 38 en 2018; personas que interactúan en Instagram 800 y 1.000 respectivamente Exposición realizada en 4 centros educativos y una sala de cine. Asistentes 1336 personas Acción de calle participantes: 250 en 2017 y 200 en 2018. Oferta de deshabituación: Grupos formados: 3 en Osakidetza, 2 en AECC. Sostenibilidad y transferibilidad: Aunar recursos evita duplicidades y mejora resultados. Consideramos que puede ser transferible a otras comunidades. Conclusiones, discusión y lecciones aprendidas: La implicación de múltiples organismos proporciona un abordaje integral. Campaña dinámica, todavía en activo que va aumentando su repercusión en la sociedad. Ha tenido una amplia repercusión mediática y muy buena aceptación por los centros escolares. Instagram resulta muy útil para difundir fotografías, a la hora de recibir fotografías WhatsApp fue la opción preferida. [ABSTRACT FROM AUTHOR]

Abstract: This paper reports novel experimental results derived through field testing of a part load solar energized cooling system for typical Spanish houses in Madrid during the summer period of 2003. Solar hot water was delivered by means of a 49.9m2 array of flat-plate collectors to drive a single-effect (LiBr/H2O) absorption chiller of 35kW nominal cooling capacity. Thermal energy was stored in a 2m3 stratified hot water storage tank during hours of bright sunshine. Chilled water produced at the evaporator was supplied to a row of fan coil units and the heat of condensation and absorption was rejected by means of a forced draft cooling tower. Instantaneous, daily and period energy flows and energy balance in the installation is presented. System and absorption machine temperature profiles are given for a clear, hot and dry day''s operation. Daily and period system efficiencies are given. Peak insolation of 969Wm−2 (at 12:30 solar time on 08/08/03) produced 5.13kW of cooling at a solar to cooling conversion efficiency of 11%. Maximum cooling capacity was 7.5kW. Cooling was provided for 8.67h and the chiller required a threshold insolation of 711Wm−2 for start-up and 373Wm−2 for shut-down. A minimum hot water inlet temperature to the generator of 65°C was required to commence cold generation, whereas at 81°C, 6.4kW of cooling (18.3% of nominal capacity) was produced. The absorption refrigeration machine operated within the generation and absorption temperature ranges of 57–67 and 32–36°C, respectively. The measured maximum instantaneous, daily average and period average COP were 0.60 (at maximum capacity), 0.42 and 0.34, respectively. Energy flows in the system are represented on a novel area diagram. The results clearly demonstrate that the technology works best in dry and hot climatic conditions where large daily variations in relative humidity and dry bulb temperature prevail. This case study provides benchmark data for the assessment of other similar prototypes and for the validation of mathematical models. [Copyright &y& Elsevier]

Mechanical ventilation is a valuable treatment regimen for respiratory failure. However, mechanical ventilation (especially with high tidal volumes) is implicated in the initiation and/or exacerbation of lung injury. Hence, it is important to understand how the cells that line the inner surface of the lung [alveolar epithelial cells (AECs)] sense cyclic stretching. Here, we tested the hypothesis that matrix molecules, via their interaction with surface receptors, transduce mechanical signals in AECs. We first determined that rat AECs secrete an extracellular matrix (ECM) rich in anastamosing fibers composed of the α3 laminin subunit, complexed with β1 and γ1 laminin subunits (i.e. laminin-6), and perlecan by a combination of immunofluorescence microscopy and immunoblotting analyses. The fibrous network exhibits isotropic expansion when exposed to cyclic stretching (30 cycles per minute, 10% strain). Moreover, this same stretching regimen activates mitogen-activated-protein kinase (MAPK) in AECs. Stretch-induced MAPK activation is not inhibited in AECs treated with antagonists to α3 or β1 integrin. However, MAPK activation is significantly reduced in cells treated with function-inhibiting antibodies against the α3 laminin subunit and dystroglycan, and when dystroglycan is knocked down in AECs using short hairpin RNA. In summary, our results support a novel mechanism by which laminin-6, via interaction with dystroglycan, transduces a mechanical signal initiated by stretching that subsequently activates the MAPK pathway in rat AECs. These results are the first to indicate a function for laminin-6. They also provide novel insight into the role of the pericellular environment in dictating the response of epithelial cells to mechanical stimulation and have broad implications for the pathophysiology of lung injury. [ABSTRACT FROM AUTHOR]

In this paper the simultaneous mass and heat transfer processes taking place during the absorption of ammonia vapour by lithium nitrate–ammonia solution droplets is numerically simulated. The low-pressure and high-pressure absorbers of a double-stage absorption system are considered. Results obtained are compared with Newman model for mass transfer. Simulation shows that droplets analysed, with diameter equal to 60 and 100 μm, follow Newman model for mass transfer. Droplets achieve the equilibrium state in an approximate dimensionless time equal to 0.5, that corresponds to times lower than 1 s. Effect of subcooling on absorption is evaluated. Results obtained are important for the design of spray absorbers of absorption refrigeration systems. [Copyright &y& Elsevier]

In the present work the use of low-temperature solar heat is studied to produce cooling at 5°C, using a double-stage LiBr–H2O air-cooled absorption cycle. A solar plant, consisting of flat plate collectors feeding the generators of the absorption machine, has been modeled. Operating conditions of the double-stage absorption machine, integrated in the solar plant without crystallization problems for condensation temperatures up to 53°C, are obtained. Results show that about 80°C of generation temperature are required in the absorption machine when condensation temperature reach 50°C, obtaining a COP equal to 0.38 in the theoretical cycle.A comparative study respect to single-stage absorption cycles is performed. Efficiency gain of the double-stage solar absorption system, over the single-stage one, will increase with higher condensation temperatures and lower solar radiation values. Single-stage cycles cannot operate for condensation temperatures higher than 40°C using heat from flat plate collectors. For higher condensation temperatures (45°C) the generation temperatures required (105°C) are very high and crystallization occurs. Condensation temperatures able to use in double-stage cycles may be increased until 53°C using heat from flat plate collectors without reaching crystallization. [Copyright &y& Elsevier]

Objective: Repetitive transcranial magnetic stimulation (rTMS) is regarded as a potentially new tool to treat depression. In a double-blind, randomized, sham-controlled pilot study we investigated the efficacy of neuronavigated rTMS, guided according to the prefrontal metabolic state determined by positron emission tomography (PET). Methods: 25 patients with major depression were included. Prior to rTMS, PET scans were obtained. For the real stimulation condition, the dorsolateral prefrontal cortex (DLPFC) with lower metabolic activity compared to the contralateral hemisphere was selected, if detected by prior PET. Stimulation parameters were 15 Hz, 110% motor threshold (MT), 3000 stimuli/day, for 10 days. A neuronavigational system was used to place the magnetic coil above each individuals’ selected cortical region (real condition: DLPFC, sham: midline parieto-occipital, intensity 90% of MT). RTMS was administered add-on to medication. Depression-related symptoms were rated with Beck''s, Hamilton''s (HAM-D), and Montgomery–Asberg''s (MADRS) depression rating scales. Results: Real stimulation improved depression according to HAM-D and MADRS moderately but significantly better compared to sham at the end of the stimulation sessions. In the real condition, four out of 13 patients responded with a mean improvement in HAM-D and/or MADRS of at least 50%, whereas none responded to sham. Antidepressant effects of stimulation of the relatively hypometabolic DLPFC were comparable to stimulation in absence of metabolic differences. Conclusions: A moderate improvement of depressive symptoms after rTMS was observed. Our preliminary data show that stimulation of prefrontal hypometabolism may not be advantageous to stimulation irrespective of the metabolic state. [Copyright &y& Elsevier]

Purpose: Children with retinoblastoma that extends into or through the choroid, sclera, or optic nerve are at risk of developing orbital disease, as well as metastases. Previously, these enucleated orbits were treated with external beam radiotherapy in addition to chemotherapy. 125I brachytherapy for tumors in and around the eye was pioneered by Sealy in Cape Town, South Africa, in 1974. In 1983, he developed a technique to irradiate the contents of the orbit while limiting the dose to the bony orbit and eyelids. Methods and Materials: Six nylon tubes containing 125I seeds were implanted through the eyelids around the periphery of the orbit. Each contained a metal gutter that screens the outer part of the seeds from the bony orbit. A seventh unscreened tube was placed in the center, and a metal disc with 125I seeds on its posterior surface was secured beneath the eyelids. Between 1983 and 2000, 57 orbits were treated in 56 children with retinoblastoma. Thirty-six were treated prophylactically and 21, with tumor at the resection line of the nerve, extrascleral tumor, or metastases, were treated therapeutically. They received a median dose of 34 Gy in 70 h; 30 also received chemotherapy. Children with tumor at the resection line of the nerve also received treatment to the craniospinal axis. Results: The median follow-up of the 35 patients treated prophylactically was 35 months (range 0–187). Seven patients died, 6 of metastases, at a median of 10 months (range 4–29) after the implant. Eight of the 13 patients with microscopic extraocular tumor survived a median of 29 months (range 5–156). None of the 8 patients presenting with orbital tumor or metastases survived. No orbital recurrences developed in any of the patients. Cosmesis was considerably improved compared with previous forms of irradiation. Conclusion: Orbital brachytherapy is an effective method of irradiating the orbit to prevent recurrent tumor, the treatment time is short, and the cosmesis is much more acceptable than with other forms of irradiation. No facial atrophy or second nonocular tumors have occurred. [Copyright &y& Elsevier]

Reports that paired-pulse transcranial magnetic stimulation (ppTMS) of the motor cortex can be used to measure intracortical inhibition and facilitation of evoked motor potentials dependent on different interstimulus intervals. Features of ppTMS; Implication of the experiment on the evaluation of the neurophysiological properties of antidepressive medication.

Focuses on the influence of dopamine in the increase of lung liquid clearance during mechanical ventilation. Impairment of active sodium transport; Incidence of alveolar fluid reabsorption; Depolymerization of cellular microtubules.

The use of low-temperature heat (between 50 and 90°C) is studied to drive absorption systems in two different applications: refrigeration and heat pump cycles. Double- and triple-stage absorption systems are modelled and simulated, allowing a comparison between the absorbent–refrigerant solutions H2O–NH3, LiNO3–NH3 and NaSCN–NH3. The results obtained for the double-stage cycle show that in the refrigeration cycle the LiNO3–NH3 solution operates with a COP of 0.32, the H2O–NH3 pair with a COP of 0.29 and the NaSCN–NH3 solution with a COP of 0.27, when it evaporates at −15°C, condenses and absorbs refrigerant at 40°C and generates vapour at 90°C. The results are presented for double- and triple-stage absorption systems with evaporation temperatures ranging between −40 and 0°C and condensation temperatures ranging from 15°C to 45°C. The results obtained for the double-stage heat pump cycle show that the LiNO3–NH3 solution reaches a COP of 1.32, the NaSCN–NH3 pair a COP of 1.30 and the H2O–NH3 mixture a COP of 1.24, when it condenses and absorbs refrigerant at 50°C, evaporates at 0°C and generates vapour at 90°C. For the double- and triple-stage cycles, the results are presented for evaporation temperatures ranging between 0 and 15°C. The minimum temperature required in the generators to operate the refrigeration and heat pump cycles are also presented. Copyright © 2002 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objectives: Transcranial magnetic stimulation (TMS) is progressively gaining relevance as a tool in cognitive neuroscience and clinical research. However, most studies in this field do not consider individual anatomy. Neuronavigational devices allow to guide the coil to a specific cortical area, predetermined by functional magnetic resonance imaging (fMRI). Therefore, it is crucial to know whether the area of a certain function as identified by fMRI corresponds to the area where the TMS should be placed in order to influence this function.Methods: We investigated the spatial relation between the cortical area activated by a motor task in fMRI and the area of magnetically evoked motor potentials (MEP) in 8 subjects, using a spacing of 5×5 mm. A neuronavigational system was adapted for coil positioning and for the registration of the stimulation coordinates.Results: A spatial divergence of the centers of gravity from fMRI and MEP was found with a mean distance of about 10 mm, with the MEP centers being, by a mean derivation of 7.5 mm, consistently anterior to the center of fMRI activation. However, regarding MEP areas and fMRI activities, a large overlap was found for stimulation intensities of both 110 and 120% motor threshold.Conclusions: The combination of fMRI and neuronavigated TMS is useful for non-invasive investigation of individual cortical functions predetermined by fMRI. Whereas both are spatially by and large congruent, discrepencies in the exact spatial relation between MEP and fMRI areas should be considered and further studied. [Copyright &y& Elsevier]

The effect of drying temperature and the application of ultrasound on drying kinetics of Lawsonia inermis (henna) leaves and the extraction of lawsone from the dried samples was addressed. Indeed, henna leaves were dried with and without the application of ultrasound (21.7 kHz, 30.8 kW/m3) at 40, 50 and 60 °C with a constant air velocity (1 m/s). As expected, both the increase of temperature and the application of ultrasound decreased the drying time and increased the rate of extraction of the lawsone. The values of the effective diffusion coefficients obtained were used to quantify this influence showing the value increases with higher drying temperature and the application of ultrasound. Moreover, the influence of temperature was quantified by the estimation of the activation energy from an Arrhenius-type equation (46.25 kJ/mol in the case of drying without ultrasound application and 44.06 kJ/mol in the case of ultrasonically-assisted drying). Regarding the influence of studied variables on lawsone extraction yield, the higher is the temperature, the lower is the yield, probably linked with lawsone degradation reaction due to thermal treatment. On the contrary, the application of ultrasound improved the extraction yield mainly at the lower drying temperature tested of 40 °C. [ABSTRACT FROM AUTHOR]

Primary cutaneous mucormycosis is a deep fungal infection, mainly seen in diabetics and immunocomprornised subjects. Rapid diagnosis and therapy are necessary to avoid fatal outcome. We describe the complete histopathological and micro-biological studies of primary cutaneous mucormycosis in a 74-year-old man with several risk factors, such as chronic obstructive pulmonary disease, respiratory acidosis. hemolytic anemia. myelodysplastic syndrome and iatogenic diabetes, due to corticosteroid therapy. He developed two cutaneous necrotic scars on his left leg. Muconniycosis was suspected and specimens from surgical débridement were hisiopathologically and microbiological]y studied conlirmmning the clinical diagnosis. Amphoterkin B was given topically and intravenously resulting in complete healing of the ulcer. Risk factors and microbiological studies are compared with those in the current literature. It is necessary in certain cases to suspect mucormycosis infections in diahetics, immunocompromised subjects and even in healthy individuals. Rapid diagnosis and treatment are important, but they should be based on complete histopatholgical and microbiological studies, to establish the genus of the causal agent. [ABSTRACT FROM AUTHOR]

This study examined whether patients disclosed the same information about suicidal behaviors on a self-report instrument that they conveyed to a clinician in a face-to-face interview. The results indicated a generally high level of agreement between these two forms of suicide assessment. The one exception was the question that concerns recent suicidal ideation, where patients tended to disclose more on the self-report form. [ABSTRACT FROM AUTHOR]

Abstract: To retrieve insights into abuse/dependence of methylphenidate (MPH) in Germany, a query of a pharmacovigilance database was performed (observation interval: 1993 until 2012). From 1190 reports of any ADR related to MPH, n=23 (2%) cases of MPH abuse were identified (mean age 29 years; male sex 78%; mean daily MPH-dosage 111±126.6mg). As oral application was predominant (70%), the majority of reported cases of MPH abuse might be due to pharmacologic neuroenhancement. [Copyright &y& Elsevier]

Triple-negative breast cancer (TNBC) presents a marked diversity at the molecular level, which promotes a clinical heterogeneity that further complicates treatment. We performed a detailed whole exome sequencing profile of 29 Mexican patients with long follow-up TNBC to identify genomic alterations associated with overall survival (OS), disease-free survival (DFS), and pathologic complete response (PCR), with the aim to define their role as molecular predictive factors of treatment response and prognosis. We detected 31 driver genes with pathogenic mutations in TP53 (53%), BRCA1/2 (27%), CDKN1B (9%), PIK3CA (9%), and PTEN (9%), and 16 operative mutational signatures. Moreover, tumors with mutations in BRCA1/2 showed a trend of sensitivity to platinum salts. We found an association between deficiency in DNA repair and surveillance genes and DFS. Across all analyzed tumors we consistently found a heterogeneous molecular complexity in terms of allelic composition and operative mutational processes, which hampered the definition of molecular traits with clinical utility. This work contributes to the elucidation of the global molecular alterations of TNBC by providing accurate genomic data that may help forthcoming studies to improve treatment and survival. This is the first study that integrates genomic alterations with a long follow-up of clinical variables in a Latin American population that is an underrepresented ethnicity in most of the genomic studies. [ABSTRACT FROM AUTHOR]

In order to summarize current knowledge about the drug 'Krokodil' a systematic review including a literature search of the databases PubMed, Embase, Scopus, and Google was conducted in December 2011. According to information acquired, 'Krokodil' is a mixture of several substances and was first reported to have been used in Russia in 2003. The core agent of 'Krokodil' is desomorphine, an opioid-analogue that can be easily and cheaply manufactured by oneself. Self-production results in a contaminated suspension that is injected intravenously. Due to its pharmacologic features, desomorphine shows a high potential to cause dependence. Against the background of first possible cases of 'Krokodil' use in Western Europe, it appears advisable to provide information regarding the fatal consequences of 'Krokodil.' [ABSTRACT FROM AUTHOR]

Introduction: There are limited treatment options for people with schizophrenia with cytochrome P450 2D6 ultrarapid metabolizer status who do not respond to amisulpride.Furthermore, the literature does not provide evidence-based guidelines for this particular constellation.Case Presentation: We report the case of a 50-year-old Caucasian female patient with schizophrenia and cytochrome P450 2D6 ultrarapid metabolizer status who experienced an insufficient antipsychotic effect with amisulpride. She was successfully treated with melperone-augmented haloperidol.Conclusion: This report yields melperone-augmented haloperidol as a possible pharmacological strategy in the described situation. In addition, our observations support the available evidence for the potential of melperone to act as an inhibitor of cytochrome P450 2D6. [ABSTRACT FROM AUTHOR]

Abstract: In a pilot study, affective components of pain were assessed using repetitive peripheral magnetic stimulation (rPMS) in patients with borderline personality disorder and healthy controls. Significant differences in pain thresholds and in affective components of pain between both groups were found. rPMS was well tolerated and suitable for assessing pain. [Copyright &y& Elsevier]

The article presents a case study of 61-year-old Caucasian female with a history of Parkinson's disease. It examines the implications for the pathophysiology delusional infestation that is induced with Piribedil add-on. It also notes on the mechanism of actions of two drugs including ropinirole and pramipexole.

Second-generation antipsychotics (SGA) are increasingly used in primary and secondary delusional parasitosis (DP) because of their better overall tolerability compared with first-generation antipsychotics (FGA) such as pimozide. Controlled clinical trials with antipsychotics in DP are lacking, owing to difficulties in obtaining informed consent and in securing adherence to a study protocol by patients with DP. We present the case of an 88-year-old man with a 12-year history of DP secondary to leucoencephalopathy. After 9 days of an age-adapted dose of paliperidone, the patient no longer experienced the presence of vermin on his skin and stopped showering at night to get rid off of them. Paliperidone was well tolerated. At follow-up after 2 weeks, the DP was still remitted. Paliperidone appears to expand the therapeutic arsenal in treating DP with modern SGAs; however, this finding needs to be replicated. [ABSTRACT FROM AUTHOR]

Current understanding of the molecular mechanisms underlying ketamine's antidepressant effect remains largely incomplete. Recent imaging studies provide evidence for ketamine effects on amygdalo-hippocampal. This study in mice aimed to investigate acute proteomic changes after ketamine administration in various brain regions including amygdala and hippocampus. One hour after administration of s-ketamine, the brain-region tissues of interest were dissected out and analyzed using label-free shotgun proteomics. The deep proteomic analysis of amygdala and hippocampus identified 89,526 peptides corresponding to 8000 proteins. The analysis revealed a pronounced proteomic signature of the acute ketamine effect in the amygdala. We anticipate that this proteomic dataset will improve understanding of the mechanism of action of ketamine and identification of new drug targets. Major depressive disorder (MDD) is the leading cause of global disability and it presents a significant challenge to human health. S-ketamine has been proposed as a rapid acting antidepressant and, indeed, the FDA recently approved it for treatment of resistant MDD. However, the mechanism of action of s-ketamine as an antidepressant is still elusive. In this context, we investigated the short-term proteomic changes after ketamine administration in mouse brain regions previously related to ketamine effects such as amygdala and hippocampus. We anticipate that this proteomic dataset will provide highly useful information to improve our understanding of the mechanism of action of ketamine and identification of new drug targets. Unlabelled Image • The study investigates s-ketamine induced acute proteomic changes in the murine brain. • It presents a comprehenisve coverage of amygdala and hippocampus proteomes. • It reports on a pronounced rapid effect of s-ketamine on amygdala. • It reveals altered levels of Grm5 and GABA α 1 and ß3. • S-ketamine may affect the balance between excitatory and inhibatory signals. [ABSTRACT FROM AUTHOR]

Background: It is repeatedly reported that pregabalin (PRG) and gabapentin feature a potential for abuse/misuse, predominantly in patients with former or active substance use disorder. The most common route of use is oral, though reports of sublingual, intravenous, rectal, and smoking administration also exist. A narrative review was performed to provide an overview of current knowledge about nasal PRG use. Methods: A narrative review of the currently available literature of nasal PRG use was performed by searching the MEDLINE, EMBASE, and Web of Science databases. The abstracts and articles identified were reviewed and examined for relevance. Secondly, a request regarding reports of cases of nasal PRG administration was performed in the worldwide spontaneous reporting system of adverse drug reactions of the European Medicines Agency (EMA, EudraVigilance database). Results: The literature search resulted in two reported cases of nasal PRG use. In the analysis of the EMA-database, 13 reported cases of nasal PRG use (11 male (two not specified), mean age of users = 34.2 years (four not specified)) were found. In two cases fatalities occurred related to PRG nasal use. Conclusions: Even if only little evidence can be found in current literature, the potential for misuse/abuse of PRG via nasal route might be of particular importance in the near future in PRG users who misuse it. Physicians should be aware of these alternative routes of administration. [ABSTRACT FROM AUTHOR]

Transmission of Beijing Mycobacterium tuberculosis can be investigated based on genotypic analysis of clinical isolates. A Beijing strain began to spread on Gran Canaria Island, Spain, at the end of the last century. In 1996, only 3 years after its importation to the island, its frequency had increased to 27.1% of all the isolates. The strain was tracked during the following years, and the most recent data obtained corresponded to 2007-8, when its presence continued to be alarming (21%). In the current study, we updated data on the distribution of this strain 20 years (2013-2014) after it was first detected on the island and extended the analysis for the first time to all the mycobacteriology laboratories covering the population of the Canary Island archipelago. Rapid updating was enabled by means of 2 different strain-specific PCRs: one targeting a peculiar feature of the strain, which was identified based on an IS6110 copy mapping in the Rv2180c gene, and a newly defined strain-specific single nucleotide polymorphism, which was identified by whole-genome sequencing. The results showed that the strain has remained highly prevalent (20.90% of all isolates), has spread throughout the neighbouring islands, and has also reached high representativeness in them (11-32%). [ABSTRACT FROM AUTHOR]

The article presents the case study of a 33-year-old female patient diagnosed with borderline personality disorder. It notes that the study provides only few plausible case reports of pregabalin (PRG) abuse or dependence. It says that further data are needed to identify risk factors for the development of PRG-associated addictive behaviors. It states that the patient showed benzodiazepine (BZP) dependence for several years.

A letter to the editor is presented which is concerned with the case of a 58 year old female patient who was found to have become dependent on the pain relieving drug flupirtine.

Quetiapine hemifumarate (QF) is widely used in psychiatry and is associated with regularly occurring side effects such as dizziness and metabolic problems. Apart from these typical adverse events the agent has attracted attention for several rare phenomena (priapism, cholestasis, rhabdomyolysis) that indeed feature anecdotal character, but are nevertheless indispensable for a comprehensive understanding of the factual risk profile of quetiapine. We present the first report of aseptic gingivitis associated with QF in a patient with mental retardation. [ABSTRACT FROM AUTHOR]

The treatment of psychiatric disorders during pregnancy poses a challenge particularly regarding limited pharmacological possibilities. Repetitive transcranial magnetic stimulation (rTMS) and electroconvulsive therapy (ECT) have been described to be successful in single cases, however, guidelines are lacking. In order to contribute to the pool of empirical data that is necessary to create evidenced-based recommendations we present a case of successful treatment of major depression with ECT in a pregnant patient with previous nonresponse to rTMS. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Female sexual hormones (estrogens and gestagens) may affect neurocognitive functioning and mood. Thus, the use of oral hormonal contraceptives (OHC) bears the risk of psychiatric adverse drug reactions such as depression and psychosis. However, the available empiric evidence regarding this connection is conflicting, and, moreover, female sex hormones seem to feature also mood-stabilizing and antidepressive effects. Hence, individual susceptibility factors and preparation-specific pharmacologic properties might play a pivotal role in the development of mood disturbances related to OHC. Single case reports provide empiric data for further systematic approaches. Methods: A clinical case is presented and discussed. Results: A 36-year-old female patient with recurrent major depressive disorder developed rapid relapse in depression after initialization of OHC with ethinyl estradiol 30 μg/chlormadinone acetate 2 mg. This OHC combination was described to particularly feature positive effects on depressive mood. Conclusions: OHC may induce serious mood disturbances and should be administered with care, particularly in patients with affective disorders. [Copyright &y& Elsevier]

Introduction: Chronic tinnitus is a frequent disease accompanied in many cases by high morbidity and reduction in quality of life. Despite its high incidence, treatment remains elusive. Aggregated research over the last years has contributed to a deeper understanding of the neurobiological basis of chronic tinnitus and point to the involvement of auditory and non-auditory brain areas. Repetitive transcranial magnetic stimulation (rTMS) is able to non-invasively modulate brain activity. Pilot studies indicate a potential therapeutic effect of rTMS in tinnitus patients, however, sample sizes were small so far. The aim of this study was to evaluate the efficacy and safety of rTMS in tinnitus in a large patient sample. Methods: 7 study centers participated in this randomized, placebo-controlled trial. From February 2008 until May 2011 a total of 154 patients were enrolled and received 10 sessions of either verum or sham 1Hz-rTMS over the left primary auditory cortex. Effects on tinnitus and accompanying psychiatric symptoms were evaluated using a variety of standardized rating scales (tinnitus questionnaire (TQ), tinnitus handicap inventory (THI), beck depression inventory, etc.). Results and conclusions: rTMS treatment was well tolerated in all patients. In the primary outcome (change of the TQ-score baseline vs. day 12) no significant difference between both study arms was observed. During the follow-up period, a trend to superiority of verum rTMS could be observed, which did not reach statistical significance. This study shows, that 1Hz-rTMS over the left primary auditory cortex is not superior to placebo treatment. Therefore, more effective treatment protocols are needed and combined treatment regimes focusing on auditory and non-auditory brain regions may be better as recent studies have demonstrated. [Copyright &y& Elsevier]

Question: Little is known regarding the risks of electroconvulsive therapy (ECT) in patients with clippings of intracerebral aneurysms. Currently, literature merely provides few anecdotal reports (Najiar and Guttmacher, 1998) and manufacturers of such clipping systems (usually made of titanium) refrain from any suggestions concerning the safety during the performance of ECT. Thus, clinicians facing the coincidence of therapy-refractory depression (suggesting performance of ECT) and presence of intracerebral clips have to trade of possible benefits of ECT against theoretical risks in the complete absence of any guidelines or recommendations. Indeed, titanium is principally inert and the application of electric current should therefore not result in significant warming (with the risk of damaging surrounding brain tissue). However, the indication of ECT under these conditions must be confirmed meticulously. Methods: A case report is presented in order to to contribute to the available experience concerning this clinical situation. Results: We present the case of a 55-year old female patient who successfully underwent clipping (Yasargil Titanium Clip, Aesculap®) of the left middle cerebral artery (MCA) due to MCA-aneurysm three years prior. The patient suffered from treatment-refractory major depressive disorder (recurrent type). Taking into account that various pharmacologic treatment attempts failed, ECT was considered. The patient was comprehensively informed about possible risks of the procedure related to the titanium clip. Before ECT CT-angiography was performed showing no re-development of the surgically treated aneurysm or development of new aneurysms. 12 cycles of right-unilateral ECT were performed without any complications despite ECT-related tachycardia. During ECT the patient was treated with esmolol. Subsequently, the patient’s clinical situation significantly improved. Conclusions: Though clear guidelines or suggestions of manufacturers of neurosurgical clips regarding safety during ECT are absent we did not observe any major complications during ECT in a patient with an intracerebral Yasargil titanium clip. However, the material behaviour of titanium during application of electric current remains to be studied systematically in order to rule out problematic warming with the risk of tissue damage. [ABSTRACT FROM AUTHOR]

The treatment of psychiatric disorders during pregnancy poses a challenge particularly regarding limited pharmacological possibilities. Repetitive transcranial magnetic stimulation (rTMS) and electroconvulsive therapy (ECT) have been described to be successful in few single cases but, however, literature lacks of guidelines. In order to contribute to the pool of empirical data that is necessary to create evidenced based recommendations we present a case of successful treatment of major depression with ECT in a 35.year old pregnant patient with non-response to rTMS. [ABSTRACT FROM AUTHOR]

Selfmutilation (SM) is a common phenomenon among patients with psychiatric disorders and has been reported frequently in patients with schizophrenia, personality disorders and occasionally with transsexuality. Several psychotropic agents, as alocohol or amphetamines, are able to induce intoxications during which SM is performed. Though SM related to psychotropic agents is probably a frequent phenomenon, literature lacks of systematic approaches and just provides single case reports. In this context we performed a systematic literature search and identified published cases of psychotropic substance induced selfmutilating behaviour (PSISM). Assessment of these cases shows that the typical patient that is on risk to develop PSISM is male, in the middle age and with a previous history of multiple substance abuse. Most frequent agents involved in PSIMS belong to the amphetamine group. [ABSTRACT FROM AUTHOR]

Introduction: Previous functional neuroimaging studies in schizophrenia have suggested abnormal patterns of functional connectivity during the resting state. However, little is known about the relationship between specific symptom dimensions and resting-state network (RSN) connectivity. Objectives: Using fMRI, this study investigated the relationship between multiple RSN and auditory verbal hallucinations (AVH) in patients with schizophrenia. Methods: Resting state data were acquired from 10 patients with treatment resistant AVH and 14 healthy controls. The data were analyzed using a spatial group independent component analysis, and random effects t-tests were used to compare spatial components between groups (p< 0.001). Results: 16 RSN were identified, from which four networks were selected for further analyses. Within three RSN patients showed increased connectivity of right lateral prefrontal areas and bilateral superior temporal regions as well as decreased connectivity of the anterior cingulate cortex. Correlations were found between measures of AVH severity and functional connectivity of the left anterior cingulate, left superior temporal gyrus and the right lateral prefrontal cortex. Conclusions: These findings indicate that functional changes of multiple RSN associated with language processing, attention and executive control could underlie persistent AVH in patients with schizophrenia. The relationship between AVH severity and functional connectivity measures suggests that distinct cortical loci of dysfunction could contribute to the phenomenological diversity of AVH. [ABSTRACT FROM AUTHOR]

Examines the atypical involvement of the palms and soles in a varicella infection. Characteristics of varicella infection; Presence of fever and widespread pear-shaped vesicles in the face, scalp, trunk and back; Values of the laboratory tests.