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Background: Forensic DNA phenotyping (FDP) consists of the use of methodologies for predicting externally visible characteristics (EVCs) from the genetic material of biological samples found in crime scenes and has proven to be a promising tool in aiding human identification in police activities. Currently, methods based on multiplex assays and statistical models of prediction of EVCs related to hair, skin, and iris pigmentation using panels of SNP and INDEL biomarkers have already been developed and validated by the forensic scientific community. As well as traces of pigmentation, an individual's perceived age (PA) can also be considered an EVC and its estimation in unknown individuals can be useful for the progress of investigations. Liu and colleagues (2016) were pioneers in evidencing that, in addition to lifestyle and environmental factors, the presence of SNP and INDEL variants in the MC1R gene - which encodes a transmembrane receptor responsible for regulating melanin production - seems to contribute to an individual's PA. The group highlighted the association between these MC1R gene polymorphisms and the PA in the European population, where carriers of risk haplotypes appeared to be up to 2 years older in comparison to their chronological age (CA)., Purpose: Understanding that genotype-phenotype relationships cannot be extrapolated between different population groups, this study aimed to test this hypothesis and verify the applicability of this variant panel in the Rio Grande do Sul admixed population., Methods: Based on genomic data from a sample of 261 volunteers representative of gaucho population and using a multiple linear regression (MLR) model, our group was able to verify a significant association among nine intronic variants in loci adjacent to MC1R (e.g., AFG3L1P, TUBB3, FANCA) and facial age appearance, whose PA was defined after age heteroclassification of standard frontal face images through 11 assessors., Results: Different from that observed in European populations, our results show that the presence of effect alleles (R) of the selected variants in our sample influenced both younger and older face phenotypes. The influence of each variant on PA is expressed as β values., Conclusions: There are important molecular mechanisms behind the effects of MC1R locus on PA, and the genomic background of each population seems to be crucial to determine this influence., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Objectives: Primary progressive aphasia (PPA) is a neurodegenerative condition that predominantly impairs language. Most investigations of how focal atrophy affects language consider 1 time point compared with healthy controls. However, true atrophy quantification requires comparing individual brains over time. In this observational cohort study, we identified areas where focal atrophy was associated with contemporaneous decline in naming in the same individuals., Methods: Cross-sectional analyses-related Boston Naming Test (BNT) performance and volume in 22 regions of interests (ROIs) at each time point using Least Absolute Shrinkage and Selection Operator (LASSO) regression. Longitudinal analysis evaluated changes in BNT performance and change in volume in the same ROIs., Results: Participants (N = 62; 50% female; mean age = 66.8 ± 7.4 years) with PPA completed the BNT and MRI twice (mean = 343.9 ± 209.0 days apart). In cross-sectional left inferior frontal gyrus pars opercularis, superior temporal pole, middle temporal gyrus, and inferior temporal gyrus were identified as critical for naming at all time points. Longitudinal analysis revealed that increasing atrophy in the left supramarginal gyrus and middle temporal pole predicted greater naming decline, as did female sex and longer intervals between time points., Discussion: Although cross-sectional analyses identified classic language areas that were consistently related to poor performance at multiple time points, it was not increasing atrophy in these areas that lead to further decline: longitudinal analysis of each person's atrophy over time instead identified nearby but distinct regions where increased atrophy was related to decreasing performance. The results demonstrate that directly examining atrophy (in each individual) over time furthers understanding of decline in PPA and reveal the importance of left supramarginal gyrus and middle temporal pole in maintaining naming when areas normally critical for language degenerate. The novel results provide insight into how the underlying disease progresses to result in the clinical decline in naming, the deficit most common among all 3 PPA variants., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Tailings from iron mining are characterized by high concentrations of iron and manganese oxides, as well as high pH values. With these characteristics, most of the potentially toxic elements (PTE) contained in the tailings are somewhat unavailable. The aim of the present study was to evaluate how a reduction in the pH of iron mine tailings may affect PTE availabilities. The tailings were collected on the banks of the Gualaxo do Norte River (Mariana, MG, Brazil), one of the main areas impacted by the rupture of the Fundão Dam (Barragem de Fundão). A completely randomized experimental design was used, including five pH values (6.4, 5.4, 4.3, 3.7, and 3.4) and five replications. The concentrations of the PTE (Ba, Cr, Cd, Co, Cu, Fe, Mn, Pb, Ni, and Zn) were determined after extraction following different methodologies: USEPA 3051A, DTPA, Mehlich-1, Mehlich-3, and distilled water. A comparison of the available concentrations of the elements in the tailings with those in a soil not impacted by tailings shows that Cr, Cd, Cu, Fe, Mn, Ni, Ba, and Co were higher in the soil impacted by the tailings. The different methods used for evaluating the availability of PTE in the tailings at various pH exhibited the following decreasing order in relation to the quantity extracted: Mehlich-3 > Mehlich-1 > DTPA > distilled water. However, regarding sensitivity to change in pH, the order was DTPA > water > Mehlich-1 > Mehlich-3. The increases in the concentrations of PTE due to the reduction in the pH of the tailings did not lead to concentrations that exceed the limits of Brazilian regulations. The DTPA extractant exhibited higher coefficients of correlation between the PTE concentrations and the pH of the tailings, proving to be suitable for use in areas affected by the deposition of iron mine tailings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Objectives: It is widely agreed that primary progressive aphasia (PPA) is a clinical syndrome with at least 3 distinct variants that differ in phenotype, areas of atrophy, and most common underlying neurodegenerative disease. The distinction between logopenic variant PPA (lvPPA) and other variants is important for prognosis and medical management. However, differentiating logopenic from nonfluent agrammatic variant can be difficult. We aimed to identify a novel behavioral assessment that (1) distinguishes logopenic from the other variants with a high degree of accuracy and (2) correlates with left superior temporal-inferior parietal atrophy (previously shown to be associated with this variant). The location of atrophy was measured using a novel, clinically useful imaging analysis., Methods: In this observational cohort study of 227 individuals with PPA, participants were administered sentence reading and repetition subtests from a standard battery. A subset of 41 participants were administered enhanced reading and repetition subtests with 5 longer sentences, of which 13 had brain imaging. Ratios of word-level and sentence-level accuracy in reading:repetition were calculated. We used one-way analysis of variance (ANOVA) to determine whether either or both ratios of reading:repetition independently discriminated between variants and t test to determine whether the ratios distinguished between nonfluent and logopenic variants. We identified receiver operating characteristics and Pearson correlations between the reading:repetition ratios and ratio of left:right superior temporal-inferior parietal volume., Results: The sentence reading:repetition ratio using the new stimuli significantly differed across the 3 variants ( p < 0.00001) and differed between nonfluent and logopenic variants (t(27) = 4.1; p = 0.0003). The area under the curve for distinguishing logopenic from other variants was 0.85 (0.71-0.99), and the diagnostic accuracy was 87.5%. The sentence reading:repetition ratio correlated with left:right superior temporal-inferior parietal volume ( r = 0.69; p = 0.0087), but not with left:right volume of regions of interest associated with other variants., Discussion: Results provide an efficient and reliable clinical assessment, and a novel imaging analysis, to distinguish the clinical syndrome of logopenic variant from other variants of PPA. Results also support the proposal that lvPPA reflects a defect in phonological short-term memory caused by atrophy in the superior temporal-inferior parietal cortex., Classification of Evidence: This study provides Class III evidence that the sentence reading:repetition ratio distinguished logopenic PPA from other PPA variants., (© 2022 American Academy of Neurology.)

Mitochondrial uncoupling proteins (UCPs) are specialized proteins capable of dissipating the proton electrochemical gradient generated in respiration independent of ATP synthesis. Three UCP coding genes with distinct expression patterns have been identified in Arabidopsis thaliana (namely UCP1, UCP2 and UCP3). Here, we generated T-DNA double-insertion mutants (ucp1 ucp2, ucp1 ucp3 and ucp2 ucp3) to investigate the functionality of the Arabidopsis UCP isoforms. A strong compensatory effect of the wild-type UCP gene was found in the double-knockdown lines. Higher levels of reactive oxygen species (ROS) were observed in vegetative and reproductive organs of double mutant plants. This exacerbated oxidative stress in plants also increased lipid peroxidation but was not compensated by the activation of the antioxidant system. Alterations in O 2 consumption and ADP/ATP ratio were also observed, suggesting a change in mitochondrial energy-generating processes. Deficiencies in double-mutants were not limited to mitochondria and also changed photosynthetic efficiency and redox state. Our results indicate that UCP2 and UCP3 have complementary function with UCP1 in plant reproductive and vegetative organ/tissues, as well as in stress adaptation. The partial redundancy between the UCP isoforms suggests that they could act separately or jointly on mitochondrial homeostasis during A. thaliana development., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Compared to unilateral cerebral palsy (CP), less is known about brain reorganization and plasticity in bilateral CP especially in relation or response to motor training. The few trials that reported brain imaging results alongside functional outcomes include a handful of studies in unilateral CP, and one pilot trial of three children with bilateral CP. This study is the first locomotor training randomized controlled trial (RCT) in bilateral CP to our knowledge reporting brain imaging outcomes., Methods: Objective was to compare MRI brain volumes, resting state connectivity and white matter integrity using DTI in children with bilateral CP with PVL and preterm birth history (<34 weeks), to age-related controls, and from an RCT of intensive 12 week rapid-reciprocal locomotor training using an elliptical or motor-assisted cycle. We hypothesized that connectivity in CP compared to controls would be greater across sensorimotor-related brain regions and that functional (resting state) and structural (fractional anisotropy) connectivity would improve post intervention. We further anticipated that baseline and post-intervention imaging and functional measures would correlate., Results: Images were acquired with a 3T MRI scanner for 16/27 children with CP in the trial, and 18 controls. No conclusive evidence of training-induced neuroplastic effects were seen. However, analysis of shared variance revealed that greater increases in precentral gyrus connectivity with the thalamus and pons may be associated with larger improvements in the trained device speed. Exploratory analyses also revealed interesting potential relationships between brain integrity and multiple functional outcomes in CP, with functional connectivity between the motor cortex and midbrain showing the strongest potential relationship with mobility. Decreased posterior white matter, corpus callosum and thalamic volumes, and FA in the posterior thalamic radiation were the most prominent group differences with corticospinal tract differences notably not found., Conclusions: Results reinforce the involvement of sensory-related brain areas in bilateral CP. Given the wide individual variability in imaging results and clinical responses to training, a greater focus on neural and other mechanisms related to better or worse outcomes is recommended to enhance rehabilitation results on a patient vs. group level., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Damiano, Pekar, Mori, Faria, Ye, Stashinko, Stanley, Alter, Hoon and Chin.)

Mitochondrial uncoupling proteins (UCPs) are mitochondrial inner membrane proteins that dissipate the proton electrochemical gradient generated by the respiratory chain complexes. In plants, these proteins are crucial for maintaining mitochondrial reactive oxygen species (ROS) homeostasis. In this study, single T-DNA insertion mutants for two (AtUCP1 and AtUCP2) out of the three UCP genes present in Arabidopsis thaliana were employed to elucidate their potential roles in planta. Our data revealed a significant increase in the Adenosine triphosphate (ATP)/Adenosine diphosphate (ADP) ratios of both mutants, indicating clear alterations in energy metabolism, and a reduced respiratory rate in atucp2. Phenotypic characterization revealed that atucp1 and atucp2 plants displayed reduced primary root growth under normal and stressed conditions. Moreover, a reduced fertility phenotype was observed in both mutants, which exhibited an increased number of sterile siliques and a lower seed yield compared with wild-type plants. Reciprocal crosses demonstrated that both male fertility and female fertility were compromised in atucp1, while such effect was exclusively observed in the male counterpart in atucp2. Most strikingly, a pronounced accumulation of hydrogen peroxide in the reproductive organs was observed in all mutant lines, indicating a disturbance in ROS homeostasis of mutant flowers. Accordingly, the atucp1 and atucp2 mutants exhibited higher levels of ROS in pollen grains. Further, alternative oxidase 1a was highly induced in mutant flowers, while the expression profiles of transcription factors implicated in gene regulation during female and male reproductive organ/tissue development were perturbed. Overall, these data support the important role for AtUCP1 and AtUCP2 in flower oxidative homeostasis and overall plant fertility., (© The Author(s) 2021. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The production of industrial waste has increased in the last decades along with world population. Wastes are used in agriculture as fertilizers and soil amendments depending on their composition, dynamics in soil and effects on plant growth. The aim of this study was to assess the effect of industrial saline wastewater from heparin production on soil chemistry and plant yield in a subtropical soil in Brazil. Five rates of industrial saline wastewater (0, 10, 20, 40 and 60 m 3  ha -1 year -1 ) were applied as fertilizer in a corn -soybean rotation on an Oxisol with limited nutrient availability. Five soils sampling were done: before and after the first application of the industrial wastewater (2017, corn), before and after the second application of wastewater (2018, soybean) and two years after the first application (2019). Soil K, Ca, Mg, Na content and CEC increased immediately after the application of wastewater but they returned to former values with time due to plant uptake and lixiviation. Wastewater application significantly increased corn (all rates) and soybean (only with the highest rate) yields around 103-250% and 50%, respectively, in comparison with no wastewater application. However, the highest rate temporally increased soil Na content and electrical conductivity (up to 650 and 800%, respectively). Although nutrient uptake, chlorophyll content and corn and soybean yields were enhanced, the use of high rates of industrial saline wastewater could cause soil salinization (mainly in locations with low rainfall), affecting soil chemistry and physical parameters due to clay dispersion, and pollution or water bodies., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: Toilet training (TT) is an important marker in a child's physical and psychosocial development. The present study aimed to evaluate aspects associated to delayed TT., Material and Methods: We interviewed 372 parents of children who had completed TT up to 48 months before the interview. The questionnaires were applied at school exits when parents went to pick their children up and at public parks. Questions included demographics, aspects related to TT, dysfunction voiding symptom score and evaluation of constipation., Results: The interviews were performed at a mean of 15.3±10.4 (0 to 47) months after the end of TT. Girls accounted for 53% of the sample. The mean age at finishing TT was 31.6±9.3 months and similar in both genders (p=0.77). TT occurred before school entry in 45.7% of the children and medical advice for TT was sought only by 4.8% of the parents. No association was observed of age at completing TT and presence of lower urinary tract symptoms (LUTS) (p=0.57) and/or constipation (p=0.98). In the univariate analysis, prematurity (OR=2.7 [95% CI 2.3-3.1], p <0.0001) and mothers who work outside their household (OR=1.8 [95% CI 1.4-2.3], p <0.0001) were associated to delayed TT., Conclusion: Children completed TT at a mean of 2 years and 7 months of age. The age of completing TT was not related to LUTS and/or constipation. Premature children and those whose mothers work outside the home finish TT later., Competing Interests: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Transcranial direct current stimulation (tDCS) is an innovative technique recently shown to improve language outcomes even in neurodegenerative conditions such as primary progressive aphasia (PPA), but the underlying brain mechanisms are not known. The present study tested whether the additional language gains with repetitive tDCS (over sham) in PPA are caused by changes in functional connectivity between the stimulated area (the left inferior frontal gyrus (IFG)) and the rest of the language network. We scanned 24 PPA participants (11 female) before and after language intervention (written naming/spelling) with a resting-state fMRI sequence and compared changes before and after three weeks of tDCS or sham coupled with language therapy. We correlated changes in the language network as well as in the default mode network (DMN) with language therapy outcome measures (letter accuracy in written naming). Significant tDCS effects in functional connectivity were observed between the stimulated area and other language network areas and between the language network and the DMN. TDCS over the left IFG lowered the connectivity between the above pairs. Changes in functional connectivity correlated with improvement in language scores (letter accuracy as a proxy for written naming) evaluated before and after therapy. These results suggest that one mechanism for anodal tDCS over the left IFG in PPA is a decrease in functional connectivity (compared to sham) between the stimulated site and other posterior areas of the language network. These results are in line with similar decreases in connectivity observed after tDCS over the left IFG in aging and other neurodegenerative conditions., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To compare postoperative changes in retinal nerve fiber layer thickness in patients with macular holes treated with vitrectomy with Brilliant Blue-assisted internal limiting membrane peeling., Methods: Twenty-two eyes of 20 patients with macular holes were studied. Each eye was selected to undergo Brilliant Blue-assisted internal limiting membrane peeling. The circumferential retinal nerve fiber layer thickness was determined using spectral domain optical coherence tomography preoperatively and 2 months postoperatively. Mean overall and sectoral retinal nerve fiber layer thicknesses were obtained for each patient., Results: There was no statistically significant difference (p≥0.05) between the pre- and post-treatment measurements in relation to each CFN variable, i.e., on average, pre-treatment measures were the same as post-treatment measures. Furthermore, despite the differences between the pre- and post-treatment measures always being positive (pre-post >0), they are not statistically significant., Conclusions: This study showed no significant decrease in retinal nerve fiber layer thickness measurements after macular holes surgery, regardless of age or sex.

Sediments are formed by deposition of organic and inorganic particles on depth of water bodies, being an important role in aquatic ecosystems, including destination and potential source of essential nutrients and heavy metals, which may be toxic for living organisms. The Lake Guaíba supplies water for approximately two million people and it is located in the metropolitan region of Porto Alegre, Rio Grande do Sul State, Brazil. Thus, the aim of this study was to evaluate the sediment pollution in the margins of Lake Guaíba in the vicinity of Porto Alegre city. Surface sediment was sampled in 12 sites to assess the concentration of several elements (C, N, P, Fe, Al, Ca, Mg, Na, K, Mn, Ba, Zn, V, Pb, Cu, Cr, Ni, Cd, Mo, and Se) and the mineralogical composition. Sediment in margins of Lake Guaíba presented predominantly (> 95%) sandy fraction in all samples, but with significant differences between evaluated sites. Sediments in the margins of Lake Guaíba showed indications of punctual water pollution with Pb, Cu, Cr, Ni, TOC, TKN, and P, mainly derived from urban streams that flow into the lake. In order to solve these environmental liabilities, public actions should not focus only on Guaíba, but also in the streams that flow into the lake.

Williams syndrome is a developmental disorder with a genetic basis, which results in an uneven cognitive profile with relatively strong language skills and severely impaired visuospatial abilities. To better understand the brain structure underlying this profile, we compared individuals with Williams syndrome with controls using multimodal neuroimaging data and new analytic methods (diffeomorphic mapping and atlas-based analysis). People with Williams syndrome had basal ganglia atrophy, while the fusiform, the medium temporal gyri, and the cerebellar cortex were relatively preserved. The right superior longitudinal fasciculus, the left frontooccipital fasciculus, the caudate, and the cingulum demonstrated increased fractional anisotropy, whereas the corticospinal tract revealed decreased values. These findings may be linked to the uneven cognitive profile evident in Williams syndrome.

The objective of this study was to review magnetic resonance imaging (MRI) findings in patients with vascular involvement of the central nervous system (CNS) associated with systemic diseases. We reviewed the MRI findings in clinically suspected cases of vascular involvement of the CNS associated with systemic diseases. Vascular CNS involvement was considered in the presence of characteristic clinical, MRI and/or MR angiography findings. In order to be included in the study, patients needed to have a complete clinical and laboratory investigation and a follow-up of a minimum of 6 months. Twenty-four patients (17 women and 7 men), with mean age of 29.5 years had diagnosis of CNS vasculitis and were included. The clinical presentation was variable, but the most common complaints were headache in 18, focal deficits in 9, disturbances of consciousness in 9, and seizures in 8 patients. Underlying causes for CNS vasculitis were identified in all patients and included systemic lupus erythematosus in eight, tuberculosis in three, bacterial meningitis in three, Takayasu arteritis in two, polyarteritis nodosa in two, syphilis in two, drug abuse in two, yellow fever in one and varicella in one patient. Nonspecific high intensity T2WI/FLAIR lesions in white matter were the most common finding, present in ten patients. Eight patients had infarctions in large cerebral arteries territory, associated or not with high intensity T2WI/FLAIR small foci. Vascular involvement of the CNS can be found in a great variety of systemic diseases, including rheumatologic, infectious and drug abuse. Clinical findings are unspecific and MRI/MRA may help to establish the correct diagnosis.

We report two patients with bacterial brain abscesses whose etiological diagnosis was correctly proposed by association of diffusion weighted images (DWI) and magnetic resonance spectroscopy (MRS) with conventional MRI. Both patients presented ring enhancing lesions with evidences of restricted diffusion. On MRS, the abscess caused by aerobic bacteria presented lactate and aminoacids peaks and the abscess caused by anaerobic facultative bacteria showed also acetate and succinate peaks. These results are in agreement with an unique previous study that related MRS pattern with bacterial etiology. Conventional MRI, associated with DWI and MRS is effective in diagnosing bacterial abscess and promising in exploring its etiology.

The choroid plexus (CP) produces and secretes numerous biologically active neurotrophic factors into the cerebrospinal fluid (CSF). These circulate throughout the brain and spinal cord, maintaining neuronal networks and associated cells. In neurodegenerative disease and in acute brain injury there is local up-regulation of neurotrophin production close to the site of the lesion. Treatment by direct injection of neurotrophins and growth factors close to these lesion sites has repeatedly been demonstrated to improve recovery. It has therefore been proposed that transplanting viable choroid plexus cells close to the lesion might provide a novel means for continuous delivery of these molecules directly to the site of injury. Recent publications describe how transplanted CP, either free or in an immunoprotected encapsulated form, deliver therapeutic molecules to the desired site. This review briefly describes the accumulated evidence that CP cells support neuronal cells in vitro and have therapeutic properties when transplanted to treat acute and chronic brain disease and injury in animal models.

Cerebellar glioblastoma multiforme (GBM) is a rare tumor. This is the third case published in Brazilian literature and, the last one has been described more than 15 years ago. The aggressive behavior of GBM prompts for fast treatment, which can be hampered by the fact that the diagnosis of GBM requires a high degree of suspicion. We describe a case of GBM in a 46 years old man. In conjunction, we present a literature review including particular issues, clinical data, advances in imaging studies, pathological characteristics, treatment options and the behavior of such malignant tumor.

Background: A nonhuman primate model of diabetes is valuable for assessing porcine pancreatic islet transplants that might have clinical benefits in humans., Methods: Neonatal porcine islets, microencapsulated in alginate-polyornithine-alginate, were injected intraperitoneally (10,000 IEQs/kg islets) into eight adult male cynomolgus monkeys rendered diabetic with streptozotocin. Eight diabetic controls were given an equivalent dose of empty placebo capsules. All subjects received a repeat transplant 3 months after the first., Results: The transplant was well tolerated and no adverse or hypoglycemic events occurred. There were two deaths from nontransplant treatment or diabetic complications unrelated to the transplants. After transplantation, the average insulin dose was reduced in the islet-treated group and increased in the control group. At 12 weeks after the first transplant there was a mean 36% (95% CI: 6% to 65%, P = .02) drop in daily insulin dose compared with the control group. After 24 weeks the difference increased to a mean of 43% (95% CI: 12% to 75%, P = .01) without significant differences in blood glucose values between the two groups. Individual responses after islet transplant varied and one monkey was weaned off insulin by 36 weeks. At terminal autopsy, organs appeared normal and there was no visible peritoneal reaction. No animal had polymerase chain reaction (PCR)-amplified signals of porcine endogenous retrovirus or exogenous virus infections in blood or tissues., Conclusion: Repeated intraperitoneal transplantation of microencapsulated neonatal porcine islets is a safe procedure in diabetic primates. It was shown to result in a significant reduction in insulin dose requirement in the majority of animals studied, whereas insulin requirement increased in controls.

The choroid plexuses (CPs) are involved in the most-basic aspects of neural function including maintaining the extracellular milieu of the brain by actively modulating chemical exchange between the CSF and brain parenchyma, surveying the chemical and immunological status of the brain, detoxifying the brain, secreting a nutritive "cocktail" of polypeptides and participating in repair processes following trauma. This diversity of functions may mean that even modest changes in the CP can have far-reaching effects. Indeed, changes in the anatomy and physiology of the CP have been linked to aging and several CNS diseases. It is also possible that replacing diseased or transplanting healthy CP might be useful for treating acute and chronic brain diseases. This review focuses on the wide-ranging and under-appreciated functions of the CP, alterations of these functions in aging and neurodegeneration, and recent demonstrations of the therapeutic potential of transplanted CP for neural trauma., ((c) 2005 Wiley Periodicals, Inc.)

Xenotransplantation of porcine liver cell types may provide a means of overcoming the shortage of suitable donor tissues to treat hepatic diseases characterized by inherited inborn errors of metabolism or protein production. Here we report the successful isolation, culture, and xenotransplantation of liver cells harvested from 7- to 10-day-old piglets. Liver cells were isolated and cultured immediately after harvesting. Cell viability was excellent (>90%) over the duration of the in vitro studies (3 weeks) and the cultured cells continued to significantly proliferate. These cells also retained their normal secretory and metabolic capabilities as determined by continued release of albumin, factor 8, and indocyanin green (ICG) uptake. After 3 weeks in culture, porcine liver cells were loaded into immunoisolatory macro devices (Theracyte devices) and placed into the intraperitoneal cavity of immunocompetant CD1 mice. Eight weeks later, the devices were retrieved and the cells analyzed for posttransplant determinations of survival and function. Post mortem analysis confirmed that the cell-loaded devices were biocompatible, and were well-tolerated without inducing any notable inflammatory reaction in the tissues immediately surrounding the encapsulated cells. Finally, the encapsulated liver cells remained viable and functional as determined by histologic analyses and ICG uptake/release. The successful harvesting, culturing, and xenotransplantation of functional neonatal pig liver cells support the continued development of this approach for treating a range of currently undertreated or intractable hepatic diseases.

Pancreatic islet transplantation into type 1 diabetic patients is currently being performed by intraportal infusion. This method, albeit reproducible, has some disadvantages including potential development of portal hypertension, hemorrhage, and an inability to retrieve or detect the transplanted tissue. Other transplant sites have been examined in animal models including the omentum, peritoneal cavity, and the spleen. A transplant site that has not been successful in supporting functional islet tissue transplantation in humans is the subcutaneous space due primarily to the lack of a well-defined vascular bed. This site has many favorable characteristics such as ease of access for transplantation and potential for removal of the transplanted tissue with a minimally invasive surgical procedure. This report addresses the evaluation of a subcutaneously placed device for the support of rat syngeneic islet transplantation in a streptozocin-induced diabetic model. The data generated support the use of this device for islet engraftment. In addition, beta cell function in this device compared favorably with the function of islets transplanted to the renal subcapsular space as well as islets within the native pancreas.

Choroid plexus from neonatal pigs was encapsulated in alginate microcapsules and transplanted into the rat striatum. Three days later, the same animals received unilateral injections of quinolinic acid (225 nmol) into the ipsilateral striatum. Choroid plexus transplants ameliorated the weight loss and motor impairments resulting from QA. Histological analysis demonstrated that choroid plexus transplants reduced the volume of striatal damage and protected ChAT-, but not NADPH-diaphorase-positive neurons. These data are the first to demonstrate that transplanted choroid plexus cells can protect striatal neurons from excitotoxic damage and that this strategy may ultimately prove relevant for the treatment of Huntington's disease.

Background and Purpose: Choroid plexus (CP) secretes a cocktail of neurotrophic factors. In the present study, CP from neonatal pigs was encapsulated within alginate microcapsules for in vitro and in vivo neuroprotective studies., Methods: In vitro studies involved serum deprivation of rat embryonic cortical neurons and treatment with a range of concentrations of conditioned media from CP. For in vivo studies, rats received a 1-hour middle cerebral artery occlusion followed by intracranial transplantation of encapsulated or unencapsulated CP, empty capsules, or no transplant. Behavioral testing was conducted on days 1 to 3 after transplantation. Cerebral infarction was analyzed using 2,3,5-triphenyl-tetrazolium chloride staining at 3 days after transplantation., Results: Conditioned media from CP produced a significant dose-dependent protection of serum-deprived cortical neurons. Enzyme-linked immunosorbent assay confirmed secretion of GDNF, BDNF, and NGF from CP. Parallel in vivo studies showed that CP transplants improved behavioral performance and decreased the volume of infarction. Both encapsulated and unencapsulated CP transplants were effective; however, more robust benefits accompanied encapsulated transplants., Conclusions: These data are the first to demonstrate the neuroprotective potential of transplanted CP and raise the intriguing possibility of using these cells as part of the treatment regimen for stroke and other neurological disorders.

The choroid plexus (CP) produces cerebrospinal fluid (CSF) and forms the blood-CSF barrier. However, the CP may have additional functions in the CNS beyond these traditional roles. Preclinical and clinical studies in ageing and neurodegeneration demonstrate anatomical and physiological changes in CP, suggesting roles in normal and pathological conditions and potentially endogenous repair processes following trauma. One of the broadest functions of the CP is establishing and maintaining the extracellular milieu throughout the brain and spinal cord, in part by secreting numerous growth factors into the CSF. The endogenous secretion of growth factors raises the possibility that transplantable CP might enable delivery of these molecules to the brain, while avoiding the conventional molecular and genetic alterations associated with modifying cells to secrete selected products. This review describes some of the anatomical and functional changes of CP in ageing and neurodegeneration, and recent demonstrations of the therapeutic potential of transplanted CP for neural trauma.

The present study examined the neuroprotective effects of choroid plexus isolated from adult rats and encapsulated within alginate microcapsules. In vitro, conditioned media from cultured choroid plexus produced a marked, dose-dependent protection of embryonic cortical neurons against serum deprivation-induced cell death. In vivo studies demonstrated that a one-hour middle cerebral artery occlusion in adult Wistar rats produced profound motor and neurological impairments 1-3 days after stroke. In contrast, stroke animals transplanted with encapsulated choroid plexus cells displayed a significant reduction in both motor and neurological abnormalities. Histological analysis 3 days post-transplantation revealed that choroid plexus transplants significantly decreased the volume of striatal infarction. This is the first report demonstrating the therapeutic potential of transplanted choroid plexus for stroke.

A case of massive Ancylostoma sp. larval infestation is presented in a patient who had received systemic corticosteroid therapy. What attracts attention in this case is the exuberance and rarity of clinical manifestation. Based on the pertinent literature, we discuss the mechanisms of parasital infection, the natural history of the disease and its treatment.