Testis-specific actin-like 7A (ACTL7A) is an indispensable protein for subacrosomal-associated F-actin formation, acrosomal anchoring, and male fertility.

Formation of the acrosome during spermiogenesis is an essential process for creating fertilization-competent sperm. Of the numerous aspects required for acrosome biogenesis, adherence of the acrosomal outer membrane to the nuclear surface is mediated by the subacrosomal perinuclear theca. However, the cellular dynamics and congruent functions pertaining to these acrosomal anchoring factors are not well understood despite many of them being implicated as potential causes for human male infertility. Actin-like 7A (ACTL7A) is one such factor for which deleterious polymorphisms have recently been shown to cause human male infertility. It is thought that acrosomal attachment is coordinated by cytoskeletal associations between the acrosome and nucleus via the acroplaxome. To further illuminate the mechanistic underpinnings of ACTL7A for essential acrosome associations, in this study, we investigated its dynamic localization in the developing germline, molecular associations with other cytoskeletal components, and the cellular consequences of ablation. Our intracellular localization data show ACTL7A to be dynamically present within the nucleus and subacrosomal space and later associated with postacrosomal regions of developing spermatids. Through the generation of an Actl7a knock-out mouse model, we consistently observed disruption of acrosomal biogenesis with abnormal migration of the acrosomal granule and peeling acrosomes during spermatid elongation. Significantly, we found a complete loss of subacrosomal filamentous actin (F-actin) structures in knock-out spermatids suggesting a regulatory role for subacrosomal F-actin. Considering our reported data together with existing literature, we propose a mechanistic model explaining the essential role of ACTL7A for acroplaxome-associated F-actin, acrosomal attachment integrity, and male fertility.

The impact of replacing barley by dehydrated orange pulp in finishing pig diets on performance, carcass quality, and gaseous emissions from slurry.

Using agricultural by-products such as dehydrated orange pulp (DOP) in animal feeds is of interest to increase pig sector sustainability. With this aim, an assay was carried out to assess the effects of increasing inclusion levels of DOP in pig diets regarding animal performance, carcass quality, and environmental impact. Four experimental diets were designed, a control diet (T1) and three more diets with increasing levels of DOP with 80, 160, and 240 g/kg of DOP for diets T2, T3, and T4, respectively. One hundred and sixty growing pigs were used in the experiment. Growth performance (average daily gain, ADG; average daily feed intake, ADFI and feed conversion ratio, FCR) and in vivo backfat thickness (BF) and loin depth (LD) gain were recorded during the finishing phase (from 70 to 130 kg BW). Faecal samples were incubated for bacteria enumeration. At slaughter, carcass characteristics and meat quality traits were measured, and subcutaneous fat was sampled to analyse the fatty acid (FA) profile. Additionally, the slurry excreted by the animals was measured, characterised and subjected to a gaseous emission assay during its storage. The final BW and overall ADFI, ADG and FCR were similar among treatments. In vivo final LD and BF gain decreased (P ≤ 0.10) as the inclusion level of DOP increased. No differences were observed in carcass characteristics with the inclusion of DOP, except carcass weight that decreased linearly (P = 0.05) with DOP. Regarding the FA profile of the subcutaneous fat, the ratio of total monounsaturated to saturated FA increased with the inclusion level of DOP. Neither slurry excretion and characterisation nor bacterial counts from faeces showed any significant difference among treatments. The inclusion of DOP led to greater CH4 emissions in mg per L of slurry and hour, whereas these differences disappeared when expressed in mg per animal and day. In all, it has been demonstrated that the inclusion of DOP up to 240 mg/kg in pig diets had minor effects on growth performance, carcass quality traits or gaseous emissions from slurry, favouring the circular economy strategy and pig sector sustainability.

Is it important to achieve physical activity recommendations at early stages of life to improve bone health?

Research in bone health during childhood is limited and important to prevent future diseases, particularly, osteoporosis. Bone parameters using DXA and pQCT in 295 Spanish children were evaluated and we found a benefit of meeting the World Health Organization physical activity recommendations in bone composition in childhood. PURPOSE: To investigate the association between physical activity (PA) and bone health in a Spanish paediatric cohort, considering the influence of meeting/not meeting the current World Health Organization (WHO) PA recommendations and to elucidate if there are differences between boys and girls. METHODS: In a cohort of children born in the region of Aragon (Spain) in 2009, followed until the age of 7 years, bone parameters were assessed using dual-energy X-ray absorptiometry (DXA) (whole body scan) and peripheral quantitative computed tomography (pQCT) (tibia scanned at the 8% (distal) and 38% (diaphyseal) of the total tibia length) in 295 7-year-old children (154 boys) in the last evaluation performed between 2016 and 2017. PA was assessed using GT3X Actigraph accelerometers. RESULTS: Boys had significantly higher areal bone mineral density (aBMD), higher total bone mineral content (BMC) at the diaphyseal site and higher trabecular BMC and vBMD, and higher total bone area at the distal site than girls (p<0.01 for all of them). Both boys and girls complying with the WHO PA recommendations had significantly higher trabecular BMC than their inactive counterparts. CONCLUSIONS: Meeting WHO PA recommendations has a beneficial effect in bone composition in childhood both in boys and in girls.

Placental chemical elements concentration in small fetuses and its relationship with Doppler markers of placental function.

INTRODUCTION: In this study, we aimed at quantifying placental concentrations of 22 chemical elements in small fetuses (SGA) as compared with normally grown fetuses (AGA), and to assess the relationship with Doppler markers of placental function. METHODS: Prospective cohort study, including 71 SGA fetuses (estimated fetal weight < 10th percentile) and 96 AGA fetuses (estimated fetal weight > 10th percentile), recruited in the third trimester of gestation. The placental concentration of 22 chemical elements was determined by inductively coupled plasma optical emission spectrophotometer (ICP-OES, ICAP 6500 Duo Thermo): aluminum (Al), beryllium (Be), bismuth (Bi), calcium (Ca), cadmium (Cd), cobalt (Co), chrome (Cr), copper (Cu), magnesium (Mg), manganese (Mn), molybdenum (Mo), nickel (Ni), phosphorus (P), lead (Pb), rubidium (Rb), sulfur (S), strontium (Sr), titanium (Ti), thallium (Tl), antimony (Sb), selenium (Se), and zinc (Zn). Placental function was assessed by measuring the following fetal-maternal parameters: Uterine artery Pulsatility Index (UtA PI), Umbilical artery Pulsatility Index (UA PI) and Middle Cerebral artery Pulsatility Index (MCA PI). The association between the chemical elements concentration and study group and the association with Doppler measures were evaluated. RESULTS: SGA was associated with significantly (p < 0.05) lower concentrations of Al (AGA 21.14 vs SGA 0.51 mg/kg), Cr (AGA 0.17 vs SGA 0.12 mg/kg), Cu (AGA 0.89 vs SGA 0.81 mg/kg), Mg (AGA 0.007 vs SGA 0.006 g/100g), Mn (AGA 0.60 vs SGA 0.47 mg/kg), Rb (AGA 1.68 vs SGA 1.47 mg/kg), Se (AGA 0.02 vs SGA 0.01 mg/kg), Ti (AGA 0.75 vs SGA 0.05 mg/kg) and Zn (AGA 9.04 vs SGA 8.22 mg/kg). Lower placental concentrations of Al, Cr, Mn, Se, Ti were associated with abnormal UtA, UA and MCA Doppler. DISCUSSION: Lower placental concentrations of Al, Cr, Cu, Mn, Rb, Se, Ti and Zn are associated with SGA fetuses and abnormal fetal-maternal Doppler results. Additional studies are required to further understand how chemical elements affect fetal growth and potentially find strategies to prevent SGA.

Guía de actuación para el manejo de la infección por COVID-19 durante en el embarazo / A clinical management protocol for COVID-19 infection in pregnant women

La infección causada por el nuevo coronavirus SARS-CoV-2 (COVID-19) representa actualmente una de las mayores emergencias sanitarias a nivel mundial. La aparición de una nueva infección potencialmente grave y la situación de pandemia actual ha implicado importantes ajustes en la práctica clínica en medicina materno-fetal. Aunque no parece existir una mayor afectación o susceptibilidad al virus de las mujeres embarazadas respecto la población general, existen aspectos específicos ligados a la gestación que deben tenerse en cuenta de cara al diagnóstico y manejo de la COVID-19 en pacientes embarazadas. En el siguiente documento se exponen las recomendaciones y el protocolo de actuación ante la infección por COVID-19 durante el embarazo desarrollado en nuestro centro, basado en la evidencia científica disponible hasta la fecha y las principales recomendaciones internacionales

The severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) disease (COVID-19) has caused a large global outbreak and has had a major impact on health systems and societies worldwide. The generation of knowledge about the disease has occurred almost as fast as its global expansion. Very few studies have reported on the effects of the infection on maternal health, since its onset. The mother and foetus do not seem to be at particularly high risk. Nevertheless, obstetrics and maternal-foetal medicine practice have made profound changes in order to adapt to the pandemic. In addition, there are aspects specific to COVID-19 and gestation that should be known by specialists. In this review an evidenced-based protocol is presented for the management of COVID-19 in pregnancy

[A clinical management protocol for COVID-19 infection in pregnant women]. / Guía de actuación para el manejo de la infección por COVID-19 durante en el embarazo.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) has caused a large global outbreak and has had a major impact on health systems and societies worldwide. The generation of knowledge about the disease has occurred almost as fast as its global expansion. Very few studies have reported on the effects of the infection on maternal health, since its onset. The mother and foetus do not seem to be at particularly high risk. Nevertheless, obstetrics and maternal-foetal medicine practice have made profound changes in order to adapt to the pandemic. In addition, there are aspects specific to COVID-19 and gestation that should be known by specialists. In this review an evidenced-based protocol is presented for the management of COVID-19 in pregnancy.

Partially defatted olive cake in finishing pig diets: implications on performance, faecal microbiota, carcass quality, slurry composition and gas emission.

One of the key factors to improve swine production sustainability is the use of agro-industrial by-products in feeds, such as olive by-products. However, it is necessary to assess its effects on the overall production process, including the animal and the environment. With this aim, an experiment was conducted to determine the effects of including a partially defatted olive cake (PDOC) in pig diets on growth performance, faecal microbiota, carcass quality and gas emission from the slurry. Two finishing diets were formulated, a control (C) diet and a diet with PDOC included at 120 g/kg. Eighty finishing male pigs Duroc-Danbred × (Landrace × Large White) of 60.4 ± 7.00 kg BW were divided between these two treatments. During the finishing period (60 to 110 kg BW, 55 days) average daily gain, average daily feed intake and feed conversion ratio were recorded. Faecal samples from the rectum of 16 animals per treatment were incubated for bacteria enumeration. At the end of finishing period, backfat thickness and loin depth (LD) were measured. Animals were slaughtered to obtain carcass weight and carcass composition parameters, and subcutaneous fat was sampled to analyse the fatty acid (FA) profile. In addition greenhouse gas and ammonia emissions were measured during pig slurry storage using the methodology of dynamic flux chambers. An initial slurry characterisation and biochemical methane potential (B0) were also determined. No significant differences between treatments were found in performance, carcass quality and microbial counts with the exception of LD, which was lower in PDOC compared with C animals (45.5 v. 47.5 mm, SEM: 0.62; P = 0.020). The FA profile of the subcutaneous fat did not differ between treatments, but the monounsaturated FA (MUFA) concentration was higher and the polyunsaturated FA was lower in the animals fed PDOC (50.9 v. 48.3, SEM: 0.48, P < 0.001; 17.6 v. 19.3, SEM: 0.30, P < 0.001 in mg/100 g of Total FA, for PDOC and C animals, respectively). The initial pig slurry characterisation only showed differences in ADF concentration that was higher (P < 0.05) in the slurry from PDOC treatment. Regarding gas emission, slurries from both treatments emitted similar amounts of ammonia (NH3), carbon dioxide (CO2), methane (CH4) and nitrous oxide (N2O), as well as B0 values. The results obtained suggest that PDOC may be included in balanced pig diets at rates of up to 120 g/kg without negative effects on performance, carcass quality, gut microflora and slurry gas emission, while improving the MUFA concentration of subcutaneous fat.

Study of antidepressant use in 5 European settings. Could economic, sociodemographic and cultural determinants be related to their use?

BACKGROUND: We aimed at describing the trends in antidepressants use (AD) by age and sex, during 2007-2011, in 5 European settings (Sweden, Norway, Denmark, Catalonia and Veneto), and to assess whether the differences found across settings could be related to economic, social and cultural determinants. METHODS: We collected data of AD use expressed in defined daily doses (DDD). Data were retrieved from population-based databases. We calculated DDD/1000 inhabitants/day. We analysed which economic, social, and cultural covariates determined between-settings differences in AD consumption. RESULTS: The use of AD showed an increasing trend during the study period, being Selective Serotonin Reuptake Inhibitors the most consumed, followed "others AD". Women and the elderly showed the highest AD consumption. Between-settings variability in AD consumption showed a positive correlation with pharmaceutical expenditure and a negative one with general practitioner's rate. After adjusting by pharmaceutical expenditure and general practitioners rate Masculinity, Long-Term Orientation and Individualism cultural dimensions were associated with AD use by using the Hofstede´s cultural dimensions model. LIMITATIONS: This study has been conducted in administrative databases, with no information on AD use by indication; differences among AD use could be related to their prescription for other disorders. Analyses were based on a small dataset and none of the results reached statistical significance. CONCLUSIONS: AD use increased through 2007-2011. Pharmaceutical expenditure and General Practitioners rate, Masculinity, Long-Term Orientation and Individualism explained the differences in AD use between countries. People's attitude should be considered when designing national campaigns to improve antidepressant use.

Size determination and quantification of engineered cerium oxide nanoparticles by flow field-flow fractionation coupled to inductively coupled plasma mass spectrometry.

Facing the lack of studies on characterization and quantification of cerium oxide nanoparticles (CeO2 NPs), whose consumption and release is greatly increasing, this work proposes a method for their sizing and quantification by Flow Field-flow Fractionation (FFFF) coupled to Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). Two modalities of FFFF (Asymmetric Flow- and Hollow Fiber-Flow Field Flow Fractionation, AF4 and HF5, respectively) are compared, and their advantages and limitations discussed. Experimental conditions (carrier composition, pH, ionic strength, crossflow and carrier flow rates) are studied in detail in terms of NP separation, recovery, and repeatability. Size characterization of CeO2 NPs was addressed by different approaches. In the absence of feasible size standards of CeO2 NPs, suspensions of Ag, Au, and SiO2 NPs of known size were investigated. Ag and Au NPs failed to show a comparable behavior to that of the CeO2 NPs, whereas the use of SiO2 NPs provided size estimations in agreement to those predicted by the theory. The latter approach was thus used for characterizing the size of CeO2 NPs in a commercial suspension. Results were in adequate concordance with those achieved by transmission electron microscopy, X-ray diffraction and dynamic light scattering. The quantification of CeO2 NPs in the commercial suspension by AF4-ICP-MS required the use of a CeO2 NPs standards, since the use of ionic cerium resulted in low recoveries (99 ± 9% vs. 73 ± 7%, respectively). A limit of detection of 0.9 µg L(-1) CeO2 corresponding to a number concentration of 1.8 × 1012 L(-1) for NPs of 5 nm was achieved for an injection volume of 100 µL.

Formation of titanium monoxide (001) single-crystalline thin film induced by ion bombardment of titanium dioxide (110).

A plethora of technological applications justify why titanium dioxide is probably the most studied oxide, and an optimal exploitation of its properties quite frequently requires a controlled modification of the surface. Low-energy ion bombardment is one of the most extended techniques for this purpose and has been recently used in titanium oxides, among other applications, to favour resistive switching mechanisms or to form transparent conductive layers. Surfaces modified in this way are frequently described as reduced and defective, with a high density of oxygen vacancies. Here we show, at variance with this view, that high ion doses on rutile titanium dioxide (110) induce its transformation into a nanometric and single-crystalline titanium monoxide (001) thin film with rocksalt structure. The discovery of this ability may pave the way to new technical applications of ion bombardment not previously reported, which can be used to fabricate heterostructures and interfaces.

Switching from zidovudine/lamivudine to tenofovir/emtricitabine improves fat distribution as measured by fat mass ratio.

OBJECTIVES: Fat mass ratio (FMR) has been suggested as an objective indicator of abnormal body fat distribution in HIV infection. Although it could provide more comprehensive information on body fat changes than limb fat mass, FMR has scarcely been used in clinical trials examining body fat distribution in HIV-infected patients. METHODS: A subanalysis of a controlled, randomized clinical trial in virologically suppressed HIV-1-infected men switching from zidovudine (ZDV)/lamivudine (3TC) to emtricitabine (FTC)/tenofovir (TDF) versus continuing on ZDV/3TC was carried out. FMR was assessed by dual X-ray absorptiometry (DEXA) for a period of 72 weeks. Lipoatrophy was defined as FMR ≥ 1.5. Multivariate linear regression models for the change in FMR from baseline were fitted. RESULTS: Sixty-five men were randomized and treated (28 in the FTC/TDF arm and 37 in the ZDV/3TC arm), and 57 completed the study (25 and 32 in each arm, respectively). In the FTC/TDF arm, adjusted mean FMR decreased by 0.52 at week 72 (P = 0.014), and in the ZDV/3TC arm it increased by 0.13 (P = 0.491; P between arms = 0.023). Among subjects with lipoatrophy (baseline FMR ≥ 1.5), adjusted FMR decreased by 0.76 (P = 0.003) in the FTC/TDF arm and increased by 0.21 (P = 0.411; P between arms = 0.009) in the ZDV/3TC arm. Baseline FMR and treatment group were significant predictors (P < 0.05) of post-baseline changes in FMR. CONCLUSIONS: Switching from ZDV/3TC to FTC/TDF led to an improvement in FMR, compared with progressive worsening of FMR in subjects receiving ZDV/3TC, showing that fat mass not only increased but was also distributed in a healthier way after the switch.

Prevalence of R5 and X4 HIV variants in antiretroviral treatment experienced patients with virologic failure.

BACKGROUND: Antiretroviral therapy (ART) inhibits virus replication. Nevertheless, ART has the disadvantage of generate selective resistance and adverse events. Coreceptor antagonists are a family of antiretroviral drugs that are used with the prior knowledge of patients HIV tropism. OBJECTIVES: The purpose of this work was to estimate the prevalence of R5 and X4 variants among Chilean patients under antiretroviral therapy and virological failure and investigate variables such as plasma viral load (pVL) and CD4 cell count in the population studied. STUDY DESIGN: HIV RNA or proviral DNA was extracted from 454 consecutives patients and tropism testing was performed using a genotypic method performed with Geno2pheno setting a cutoff value for FPR 5.75%. RESULTS: Among 454 individuals analyzed, 299 (66%) harbouring exclusively R5 variants. They not displayed a better clinical profile than individuals harbouring X4 strains (22%). For R5 patients the median of pVL and CD4 cell count were 268,000copies/mL, and 223cells/µL respectively. For X4 samples the values were 368,000copies/mL and 214cells/µL [P>0.05]). Only, 53 patients (12%) could not be analyzed and were categorized as non-reportable. CONCLUSIONS: The genotypic method confirmed that R5 strains were more prevalent despite the fact that patients were treatment-experienced for several years. The genotypic strategy proved to be a faster and cost-effective option as compared to phenotypic assays. According to our results, two of every three patients under antiretroviral therapy and with virologic failure harbour R5 strains, and may be candidates for use of a CCR5 antagonist.

Microbial examination of anaerobic sludge adaptation to animal slurry.

The objective of this study was to evaluate changes in the microbial population of anaerobic sludge digesters during the adaptation to pig slurry (PS) using quantitative real-time polymerase chain reaction (qPCR) and qualitative scanning electron microscopy (SEM). Additionally, the relationship between microbial parameters and sludge physicochemical composition and methane yield was examined. Results showed that the addition of PS to an unadapted thermophilic anaerobic digester caused an increase in volatile fatty acids (VFA) concentration, a decrease in removal efficiency and CH4 yield. Additionally, increases in total bacteria and total archaea were observed using qPCR. Scanning electron micrographs provided a general overview of the sludge's cell morphology, morphological diversity and degree of organic matter degradation. A change in microbial morphotypes from homogeneous cell morphologies to a higher morphological diversity, similar to that observed in PS, was observed with the addition of PS by SEM. Therefore, the combination of qPCR and SEM allowed expanding the knowledge about the microbial adaptation to animal slurry in thermophilic anaerobic digesters.

Environmental influence on Zn-histidine complexes under no-packing conditions.

This paper describes a combined structural analysis of the Zn-histidine complex, using two different and complementary techniques, X-ray absorption spectroscopy (XAS) and surface X-ray diffraction, paying special attention to the environmental conditions. The current procedure for investigating macromolecules consists of examining simple molecules that exhibit properties similar to those of the larger ones, whose functionality is totally related to the atomic structure. The detailed study of the bonding structure formed by zinc and histidine amino acids is motivated by the fact that this material serves as a model for metalloproteins, such as in metalloproteinase, acting as active sites in enzymatic or structural functions. For XAS modeling, Zn-histidine complexes were dissolved in several aqueous solutions, over a wide pH range. Correlations among the degree of protonation, the steric impediment, and the multiple combinations of the histidine amino acid have been found. For the diffraction study, high-quality crystals grown by the seeding method in a supersaturated solution have been studied, and the samples for the surface diffraction study were mounted on a cell specially designed for solid-liquid or solid-gas interface analysis. The surface structural model was built from XAS results. In both cases, the obtained structures are compared with the bulk one, showing atomic differences and highlighting the importance of the environment in which the complex is studied.

Preoperative mapping of fistula-in-ano: a new three-dimensional MRI-based modelling technique.

AIM: We aimed to develop an intuitive, interactive, three-dimensional (3D) MRI modelling technique to produce a 3D image of fistula-in-ano. METHOD: The 3D model was created from standard two-dimensional (2D) MRI sequences to produce an image that is anatomically correct. Individual muscle and soft-tissue layers were extracted from T1-weighted sequences and fistula pathology from short TI inversion recovery (STIR) sequences, to produce two separate volumes. These were then fused using postprocessing software (Vitrea Workstation version 6.3) to generate a 3D model. RESULTS: The final 3D model was incorporated into a PDF file that has an integrated computer aided design (CAD) viewer, allowing the surgeon to rotate it in any direction during preoperative planning or whilst in theatre. CONCLUSION: As an adjunct to 2D MRI images and the associated radiology report, this model communicates the fistula anatomy to the clinician more clearly and should be particularly useful in complex cases.

Impact of switching from zidovudine/lamivudine to tenofovir/emtricitabine on lipoatrophy: the RECOMB study.

OBJECTIVES: Lipoatrophy is a long-term adverse effect of some antiretrovirals that affects quality of life, compromises adherence and may limit the clinical impact of HIV treatments. This paper explores the effect of tenofovir/emtricitabine (TDF/FTC) on the amount of limb fat in patients with virological suppression. METHODS: A randomized, prospective clinical trial was performed to compare continuation on a zidovudine/lamivudine (ZDV/3TC)-based regimen with switching to a TDF/FTC-based regimen in terms of the effect on limb fat mass as assessed by DEXA over a 72-week period. RESULTS: Eighty patients were included (39 in the TDF/FTC arm and 41 in the ZDV/3TC arm) and 73 completed the study (37 and 36, respectively). In the switch arm, limb fat increased by a median of 540 g from baseline (P = 0.022), while in the ZDV/3TC arm it decreased by a median of 379 g (P = 0.112; p between groups = 0.007). Subjects with baseline limb fat ≤ 7200 g, previous time on ZDV > 5 years or a body mass index > 25 kg/m(2) experienced higher limb fat gains than other subjects, and these differences were statistically significant. Haemoglobin increased by a median of 1.0 g/dL in the TDF/FTC arm (P < 0.001) and remained unchanged in the ZDV/3TC arm (p between groups = 0.0002). There were no significant differences between groups in other secondary endpoints (body weight, total body and trunk fat content, total body bone mineral density, laboratory parameters, CD4 cell count and viral load). CONCLUSIONS: Switching from a ZDV/3TC-based to a TDF/FTC-based regimen led to a statistically significant improvement in limb fat, in contrast to the progressive loss of limb fat in subjects continuing ZDV/3TC.

Ziprasidone in the treatment of delusional parasitosis.

Delusional parasitosis is characterized by a patient's fixed false belief of being infested with parasites or small creatures. The first-line treatment options are typical antipsychotics such as pimozide. However, the accompanying extrapyramidal side effects might limit their use. We report on a patient with a good response to pimozide combined with ziprasidone. Ziprasidone is an atypical antipsychotic drug with a lower risk of extrapyramidal symptoms; thus, it might be considered a good first or second treatment option for delusional parasitosis.

Activation of glycogen synthase kinase-3 beta mediates ß-amyloid induced neuritic damage in Alzheimer's disease.

ß-Amyloid (Aß) plaques in Alzheimer (AD) brains are surrounded by severe dendritic and axonal changes, including local spine loss, axonal swellings and distorted neurite trajectories. Whether and how plaques induce these neuropil abnormalities remains unknown. We tested the hypothesis that oligomeric assemblies of Aß, seen in the periphery of plaques, mediate the neurodegenerative phenotype of AD by triggering activation of the enzyme GSK-3ß, which in turn appears to inhibit a transcriptional program mediated by CREB. We detect increased activity of GSK-3ß after exposure to oligomeric Aß in neurons in culture, in the brain of double transgenic APP/tau mice and in AD brains. Activation of GSK-3ß, even in the absence of Aß, is sufficient to produce a phenocopy of Aß-induced dendritic spine loss in neurons in culture, while pharmacological inhibition of GSK-3ß prevents spine loss and increases expression of CREB-target genes like BDNF. Of note, in transgenic mice GSK-3ß inhibition ameliorated plaque-related neuritic changes and increased CREB-mediated gene expression. Moreover, GSK-3ß inhibition robustly decreased the oligomeric Aß load in the mouse brain. All these findings support the idea that GSK3ß is aberrantly activated by the presence of Aß, and contributes, at least in part, to the neuronal anatomical derangement associated with Aß plaques in AD brains and to Aß pathology itself.