Corrigendum to "Treatment of textile wastewater using the Co(II)/NaHCO3/H2O2 oxidation system" [Heliyon 9(12) December 2023 e22444].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e22444.].

Treatment of textile wastewater using the Co(II)/NaHCO3/H2O2 oxidation system.

Textile wastewater (TWW) is one of the most hazardous wastewaters for ecosystems when it is discharged directly into water streams without adequate treatment. Some organic pollutants, such as dyes in TWW, are considered refractory compounds that are difficult to degrade using conventional chemical and biological methods. The bicarbonate-activated peroxide (BAP) system is an advanced oxidation process (AOP) based on applying H2O2, which has been demonstrated to be a clean and efficient technology for dye degradation, with the advantage of operating under slightly alkaline pH conditions. In this study, response surface methodology (RSM) based on a central composite design (CCD) was used to optimize the degradation of TWW contaminated with the azo dye Acid Black 194 using the BAP system catalyzed with cobalt ions in solution (Co2+). The analysis of variance (ANOVA) technique was applied to identify significant variables and their individual and interactive effects on the degradation of TWW. The optimum reagent concentrations for degrading TWW at 25 °C and with 45 µM Co2+ were 787.61 and 183.34 mM for H2O2 and NaHCO3, respectively. Under these conditions, complete decolorization (≥99.40), 32.20 % mineralization, and 52.02 % chemical oxygen demand removal were achieved. Additionally, the acute toxicity of textile wastewater before and after oxidation was evaluated with guppy fish (Poecilia reticulata), showing a total reduction in mortality after treatment with the Co2+-BAP system. The Co2+-BAP oxidation system is a potential method for textile wastewater treatment, which, in addition to achieving complete decolorization and partial mineralization, improves biodegradability and reduces the toxicity of the treated water.

Effect of the historic Spanish heatwave over glycemic control in adult patients with type 1 diabetes.

AIM: To evaluate the effect of the historic Spanish heatwave (9th-26th July 2022) over glycemic control in adults with type 1 diabetes (T1D). METHODS: Cross-sectional retrospective analysis of adult patients with T1D in Castilla-La Mancha (south-central Spanish region) using intermittently scanned continuous glucose monitoring (isCGM) during and after the heatwave. Primary outcome was change in time in range (TIR) 3.0-10 mmol/L (70-180 mg/dL) of interstitial glucose in the two weeks following the heatwave. RESULTS: A total of 2701 T1D patients were analyzed. We detected a TIR reduction of 4.0 % (95 % CI -3.4, -4.6; P < 0.001) in the two weeks following the heatwave. Patients in the highest daily scan frequency quartile (>13 scans/day) during the heatwave showed the greatest deterioration in TIR after it concluded (-5.4 % [95 % CI -6.5, -4.3; P < 0.001]). The percentage of patients meeting all the recommendations of the International Consensus of Time in Range was greater during the heatwave than after it ended (10.6 % vs. 8.4 %, P < 0.001). CONCLUSIONS: Adults with T1D had better glycemic control during the historic Spanish heatwave compared to the following period.

Metabolic control and treatment regimens in patients with type 1 diabetes in Castilla-La Mancha, 10 years later: The 2020 DIACAM1 study.

OBJECTIVE: To evaluate degree of metabolic control and treatment regimens in patients with type 1 diabetes mellitus (T1DM) enrolled in the DIACAM1 study, after 10 years of follow-up under routine clinical practice conditions. PATIENTS AND METHODS: A total of 1,465 patients enrolled in the DIACAM1 study, a multicentre, cross-sectional study conducted in Castilla-La Mancha in 2010, were analysed. Of these patients, 58 (4%) died during the 10-year follow-up period. Anthropometric, clinical, laboratory and treatment data were reviewed for 1,121 (76.5%) patients in active follow-up. RESULTS: Mean glycosylated haemoglobin (HbA1c) levels were 7.66% lower than in 2010 (p<0.001), 26% of patients achieved HbA1c levels <7%, 24.4% were obese, 51.7% had dyslipidaemia and 33.6% had hypertension. The following were found to be predictive factors for good glycaemic control (HbA1c<7%): good glycaemic control in 2010 (odds ratio [OR] 4.8); the use of intensified insulin regimens, including the Institute for Clinical Systems Improvement (ICSI) guideline and glucose monitoring (OR 2.8); no hyperlipidaemia (OR 1.97); and higher levels of education (OR 1.4). The recommended targets for lipid and blood pressure control were met by 76% of patients; 40% of the patients enrolled required drug treatment. CONCLUSIONS: Glycaemic control in patients with T1DM in Castilla-La Mancha improved after 10 years of follow-up. The use of intensified insulin regimens and technology applied to diabetes care appear to be determining factors in achieving this improvement. Despite the increase in the prevalence of cardiovascular risk factors, the majority of the patients achieved good lipid and blood pressure control.

Research Trends on Pillared Interlayered Clays (PILCs) Used as Catalysts in Environmental and Chemical Processes: Bibliometric Analysis.

Over the last four decades, a large number of studies have been published on pillared interlayered clays (PILCs) used as adsorbent materials and catalysts or supports for transition metals in heterogeneous catalysis. Particularly, PILCs have been used for water treatment through advanced oxidation processes (AOPs) to remove organic pollutants. They have also been studied in various chemical and environmental processes. Because of the growing interest in PILCs, this article is focused on analyzing scientific publications such as research/review articles and book chapters from the last four decades (from 1980 to 2019) through a bibliometric analysis (BA) to visualize and describe research trends on PILCs. By narrowing the bibliographic search to titles, keywords, and abstracts of publications related to PILCs, using Scopus and Web of Science (WoS) (the two scientific databases), a total of 3425 documents have been retrieved. The bibliometric dataset was analyzed by VantagePoint®. The main research trends identified in the last four decades were the use of PILCs in environmental processes (34.4% of total publications) along with chemical processes (petrochemical reactions 17.5%, SCR NOx 10.8%, and decomposition 8.2%). In environmental processes, PILCs have been used in photo-oxidation (32%), CWPO (21.1%), and heterogeneous catalysis (19.4%). Phenols, dyes, and VOCs have been the main pollutants studied using PILCs as catalysts. Fe, Ti, Zr, Cu, and Co are the most supported active phases in PILCs. Other research trends grouped by characterization techniques, countries, research areas, institutes, scientific journals that have published the most on this topic, number of publications per 5-year period, and most frequently used keywords through the last four decades have been identified. It was determined that the number of publications on PILCs has increased since 1980 and the countries with the highest number of publications are China, Spain, and The United States of America.

"Clinical status and mortality in older adults with type 1 diabetes: Results from a public health system".

AIM: To evaluate clinical status and mortality in older adults with long-standing type 1 diabetes mellitus (T1D). METHODS: Cross-sectional analysis of all patients with T1D for 50 years or more from a cohort followed since 2010 at Castilla-La Mancha Public Health Service (Spain). Primary outcome was HbA1c change during the follow-up (2010-2020 period). Secondary outcomes included evaluation of insulin and continuous glucose monitoring (CGM) use, cardiovascular risk factors (CVRF), diabetes chronic complications and mortality. RESULTS: A total of fifty-five T1D patients were analysed. Mean age was 69.5 ± 8.3 yrs. and T1D duration of 54.7 ± 4.7 yrs. We detected a HbA1c reduction of -0.5% (-6 mmol/mol) [95% CI -0.1, -0.9 (-2, -10); P = 0.016]. CGM was used by 26% of the patients. More patients suffered from hypertension and obesity in 2020 (66% vs. 78%, P = 0.016; and 26% vs. 31%, P = 0.016; respectively). An increase of diabetic polyneuropathy was detected (45% vs. 67%, P = 0.008). Rate of mortality was higher among patients with long-standing T1D (26% vs. 3.5%, P < 0.001), due to cardiovascular disease (57%). CONCLUSIONS: Older adults with long-standing T1D patients improved glycemic control although a worsening of CVRF and higher mortality rateweredetected.

Bibliometric analysis of advanced oxidation processes (AOPs) in wastewater treatment: global and Ibero-American research trends.

Advanced oxidation processes (AOPs) constitute a developing area of particular interest for researchers in different fields due to their broad range of applications. However, there are few studies dedicated to the bibliometric analysis of AOPs. Hence, a systematic literature review of research publications (research articles, review articles, and book chapters) from 1980 to 2018 was carried out to visualize and evaluate research trends on AOPs around the world and, especially in Ibero-America (IA), on the field of wastewater treatment. Using the most extensive databases in literature search, Scopus and Web of Science (WoS), which encompass 95% of the publications in the world, a total of 18,751 records were retrieved by limiting the search results to words associated with AOPs in the titles, keyword, and abstracts. Raw data were manually organized and filtered, standardizing authors and institution names, publication titles, and keywords for the purpose of eliminating double-counted entries. Similarly, homonymous authors and institutions were identified for all records retrieved. The bibliometric dataset was processed using the VantagePoint software. The research trends visualized about AOPs were as follows: number of publications per triennium, publications by country, participation by continent, most important journals and authors, most referenced institutions, global network of co-authors, and keywords network visualization, highlighting the Ibero-American contribution to global research.

Experimental data of a catalytic decolorization of Ponceau 4R dye using the cobalt (II)/NaHCO3/H2O2 system in aqueous solution.

The treatment by Advanced Oxidation Processes (AOPs) of wastewater polluted with dyes is of particular interest in the field of environmental engineering, especially for the removal azo-dyes, representing over 50% of the global annual production of dyes. Unfortunately, most azo-dyes are non-biodegradable and can be toxic to aquatic organisms. This is the first data article that applies the methodology of response surface for the optimization of decolorization of an azo-compound using cobalt in a homogeneous medium as the catalyst of a bicarbonate activated hydrogen peroxide (BAP) system which, in turn, is an emerging technology for wastewater treatment. The Response Surface Methodology (RSM) based on a Central Composite Design (CCD) was used to evaluate and optimize the influence of three experimental variables (stoichiometric dosage of H2O2, molar ratio H2O2/NaHCO3 and cobalt concentration) on the decolorization of Ponceau 4R. Reactions were performed at 25 °C, pH 8.3 with a reaction time of 2 h. Analysis of variance (ANOVA) showed values of R2 and adjusted-R2 of 0.9815 and 0.9648, and experimental data were fit to a second-order regression model. The optimal conditions to achieve a maximum decolorization (96.31%) of a Ponceau 4R aqueous solution of 20 mg/l were: 4.73 times stoichiometric dosage of H2O2, molar ratio H2O2/NaHCO3 of 1.70 and cobalt concentration of 11.16 µM. Under the optimal reaction conditions, the influence of temperature (20, 25, 30 and 35 °C) on decolorization was evaluated and data were adjusted to second order kinetics. To verify the efficiency of the BAP system on the decolorization of Ponceau 4R, under the optimal conditions of reaction, UV-Vis spectra, at different reaction times, were measured. Additionally, blank experiments in order to evaluate the effect of individual factors in the Ponceau 4R decolorization, using BAP system, were carried out. Data showed that the Co(II)-NaHCO3-H2O2 system is a suitable technology for the decolorization of azo-dyes aqueous solutions.

Adsorption of Cr(VI) in Aqueous Solution Using a Surfactant-Modified Bentonite.

Clay minerals can be modified organically by a cationic surfactant resulting in materials known as organoclays. The organoclays have been used as adsorbents of most of the organic contaminants in the aqueous solution and oxyanions of the heavy metal. In this study, a Colombian bentonite was modified with hexadecyltrimethylammonium bromide to obtain an organobentonite, and its capacity to adsorb Cr(VI) oxyanions in the aqueous solution was evaluated. The effect of pH, stirring speed, adsorbent amount, contact time, and ionic strength were investigated at 25°C. Stirring speeds above 200 rpm, contact times greater than 120 min, and the addition of NaCl (0.1 to 2.0 mM) did not have a significant effect on Cr(VI) removal. The influence of the adsorbent amount and pH on Cr(VI) adsorption was studied by the response surface methodology (RSM) approach based on a complete factorial design 32. Results proved that the Cr(VI) adsorption follows a quadratic model with high values of coefficient of determination (R 2 = 95.1% and adjusted R 2 = 93.9%). The optimal conditions for removal of Cr(VI) from an aqueous solution of 50 mg/L were pH of 3.4 and 0.44 g amount of the adsorbent. The adsorption isotherm data were fitted to the Langmuir and Freundlich adsorption isotherm models, and the model parameters were evaluated. The maximum adsorption capacity of Cr(VI) onto organobentonite calculated from the Langmuir model equation was 10.04 ± 0.34 mg/g at 25°C. The results suggest that organobentonite is an effective adsorbent for Cr(VI) removal, with the advantage of being a low-cost material.

Resultados del seguimiento de pacientes con carcinoma diferenciado de tiroides en Castilla-La Mancha (2001-2015). Estudio CADIT-CAM / Follow-up and results in patients with differentiated thyroid carcinoma in Castilla-La Mancha (2001-2015). The CADIT-CAM study

Objetivo: El estudio CADIT-CAM es un estudio retrospectivo diseñado para analizar las características clínicas, el tratamiento y los resultados finales de los pacientes con cáncer diferenciado de tiroides (CDT) en Castilla-La Mancha. Pacientes y métodos: Se ha incluido a 1.434 pacientes diagnosticados en 7 hospitales castellano-manchegos, entre 2001 y 2015. Resultados: El 77% eran mujeres, con una edad media al diagnóstico de 48 años, y el tipo histológico principal fue carcinoma papilar en el 93%. El tamaño el tumor fue descendiendo de forma significativa a lo largo de los 15 años (p <0,05). El tratamiento con radioyodo se ha utilizado en el 84% de la serie, habiendo disminuido su utilización a lo largo del estudio, sobre todo en los de bajo riesgo de recurrencia. Existió recurrencia en el 22% de los pacientes, siendo los factores relacionados con la misma: sexo masculino, mayor tamaño tumoral, multifocalidad, presencia de metástasis linfáticas o a distancia o de afectación extratiroidea así como la presencia de anticuerpos antitiroglobulina con evolución desfavorable. Al final del seguimiento, el 76,2% de los casos estaban libres de enfermedad y el 2,4% de los pacientes habían fallecido por CDT, siendo la supervivencia global de la cohorte del 95,1% a los 15 años de seguimiento. Conclusiones: Las características del CDT de la cohorte de Castilla-La Mancha son similares a las de otras series españolas. Los resultados finales son excelentes y las tendencias del tratamiento se han ido adaptando al riesgo de recurrencia de los pacientes

Objective: The CADIT-CAM study was designed to retrospectively analyze the clinical characteristics, treatments, and outcomes of patients with differentiated thyroid carcinoma (DTC) in Castilla La Mancha. Patients and methods: A total of 1434 patients from 7 hospitals in Castilla La Mancha were enrolled into the study from 2001 to 2015. Results: Seventy-seven percent of patients were female, with a mean age at diagnosis of 48 years. Papillary thyroid carcinoma accounted for 93% of cases. Mean tumor size was significantly smaller at final follow-up (P<.05). Radioiodine ablation (RA) was performed in 84% of patients, and its use decreased during the study, especially in tumors with low recurrence risk. Recurrence occurred in 22% of patients and was associated to male gender, greater tumor size, multifocality, lymph node metastases, extrathyroid involvement, distant metastases and increasing thyroglobulin antibody titers. At the end of follow-up 76.2% of patients were alive and free of disease, 2.4% had died from DTC. Overall survival of the cohort was 95.1% at 15 years of follow-up. Conclusions: Characteristics of DTC in this Spanish cohort are similar to those reported in other studies in our country. Final results were excellent and use of treatment (RA) was consistent with risk-stratified recommendations

Follow-up and results in patients with differentiated thyroid carcinoma in Castilla-La Mancha (2001-2015). The CADIT-CAM study. / Resultados del seguimiento de pacientes con carcinoma diferenciado de tiroides en Castilla-La Mancha (2001-2015). Estudio CADIT-CAM.

OBJECTIVE: The CADIT-CAM study was designed to retrospectively analyze the clinical characteristics, treatments, and outcomes of patients with differentiated thyroid carcinoma (DTC) in Castilla La Mancha. PATIENTS AND METHODS: A total of 1434 patients from 7 hospitals in Castilla La Mancha were enrolled into the study from 2001 to 2015. RESULTS: Seventy-seven percent of patients were female, with a mean age at diagnosis of 48 years. Papillary thyroid carcinoma accounted for 93% of cases. Mean tumor size was significantly smaller at final follow-up (P<.05). Radioiodine ablation (RA) was performed in 84% of patients, and its use decreased during the study, especially in tumors with low recurrence risk. Recurrence occurred in 22% of patients and was associated to male gender, greater tumor size, multifocality, lymph node metastases, extrathyroid involvement, distant metastases and increasing thyroglobulin antibody titers. At the end of follow-up 76.2% of patients were alive and free of disease, 2.4% had died from DTC. Overall survival of the cohort was 95.1% at 15 years of follow-up. CONCLUSIONS: Characteristics of DTC in this Spanish cohort are similar to those reported in other studies in our country. Final results were excellent and use of treatment (RA) was consistent with risk-stratified recommendations.

Characterization of Colombian Clay and Its Potential Use as Adsorbent.

This paper presents a mineralogical and physicochemical characterization of a Colombian clay found in an area with the greatest exploitation potential of smectites and possible use as an adsorbent for the removal of chromium. The clay was characterized by using X-ray diffraction (XRD), cation exchange capacity (CEC), X-ray fluorescence (XRF), Fourier transform infrared spectroscopy (FT-IR), thermal analysis (TGA/DSC), and nitrogen adsorption at 77 K. The homoionized clay was used as an adsorbent for the removal of Cr(III) in an aqueous solution. The homoionized clay was modified with hexadecyltrimethylammonium bromide (HDTMA-Br), and the organoclay obtained was evaluated for the adsorption of Cr(VI) in aqueous solution. The XRD analysis showed that the clay from Armero-Guayabal is primarily constituted by smectite (48 wt%) followed by quartz mineral (21 wt%). The chemical analysis of bulk clay showed that the predominant oxides are SiO2 (55.81 wt%), Al2O3 (16.25 wt%), and Fe2O3 (7.51 wt%), and the nitrogen adsorption indicated that the bulk clay has a specific surface area of 45.1 m2/g. Homoionized clay and organoclay achieved Cr(III) and Cr(VI) removals greater than 85.05 ± 2.04% (pH between 3 and 4) and 82.93 ± 1.03% (pH between 3 and 5), respectively, proving the potential of these materials for the removal of heavy metals in an aqueous solution.

Análisis de los resultados del tratamiento de la enfermedad de Cushing en los hospitales de Castilla-La Mancha / Assessment of the outcomes of the treatment of Cushing's disease in the hospitals of Castilla-La Mancha

OBJETIVO: El tratamiento de la enfermedad de Cushing plantea interesantes dilemas en la práctica clínica. Nuestro objetivo es analizar los resultados y complicaciones de los distintos tratamientos de esta enfermedad. MATERIAL Y MÉTODOS: Se recopilaron datos mediante revisión de las historias clínicas de 22 pacientes (86,4% mujeres), mayores de 18 años, diagnosticados de enfermedad de Cushing entre los años 2000 y 2012, con seguimiento en el Complejo Hospitalario Universitario de Albacete, Hospital Virgen de la Salud (Toledo), Hospital General de Ciudad Real, Hospital Virgen de la Luz (Cuenca), Hospital Nuestra Señora del Prado (Talavera de la Reina) y en el Complejo Hospitalario la Mancha Centro (Alcázar de San Juan). RESULTADOS: En todos los casos el tratamiento de elección fue el quirúrgico. Se consiguió la curación bioquímica en el 72,7%. Nueve pacientes desarrollaron diabetes insípida en el perioperatorio, de las que 2 resultaron permanentes. Tres pacientes desarrollaron diabetes insípida permanente, que no había sido identificada en el perioperatorio. Aparecieron nuevos déficits hormonales adenohipofisarios posquirúrgicos en 7 pacientes. Diecisiete pacientes recibieron tratamiento médico prequirúrgico con ketoconazol (5 también postoperatorio), consiguiéndose la normalización del cortisol libre urinario en el 70%. Tres pacientes se irradiaron por persistencia de hipersecreción y, tras una mediana de seguimiento de 85,8 meses, se ha conseguido la curación en todos; ninguno de ellos ha desarrollado tumores, alteraciones vasculares ni otra complicación. CONCLUSIONES: Nuestro estudio presenta los resultados del manejo de la enfermedad de Cushing en centros que no son de referencia nacional para esta enfermedad, lo que posiblemente refleja la práctica clínica habitual en esta enfermedad

OBJECTIVE: Treatment of Cushing's disease poses interesting dilemmas in clinical practice. The aim of our study was to analyze the outcomes of the different treatments, the control and recurrence rates, and the complications derived from them. MATERIAL AND METHODS: Data were collected from the clinical records of 22 patients over 18 years of age (86.4% women). They had been diagnosed with Cushing's disease between 2000 and 2012, and were monitored at Complejo Hospitalario Universitario-Albacete, Hospital Virgen de la Salud-Toledo Hospital General Universitario de Ciudad Real, Hospital Virgen de la Luz-Cuenca, Hospital Nuestra Señora del Prado-Talavera de la Reina, and Complejo Hospitalario la Mancha Centro-Alcázar de San Juan. RESULTS: Surgery was the treatment of choice in all patients. Biochemical cure was achieved in 72.2% of patients. Nine patients developed in the early postoperative period diabetes insipidus, which became in 2 patients only. Surprisingly, 3 patients with normal postoperative neurohypophyseal function later developed permanent diabetes insipidus. New hormone deficiencies occurred in 7 patients. Seventeen patients received ketoconazole before surgery (5 of them after surgery also), and 70% of them achieved normal urinary free cortisol levels. Three patients also received radiotherapy, and all of them were cured after a median follow-up of 85.5 months; they developed no tumors or other complications. CONCLUSIONS: Our study reports the outcomes of management of Cushing's disease in non-reference centers for this disease, possibly giving a realistic picture of standard clinical practice for the condition in Spain

Assessment of the outcomes of the treatment of Cushing's disease in the hospitals of Castilla-La Mancha.

OBJECTIVE: Treatment of Cushing's disease poses interesting dilemmas in clinical practice. The aim of our study was to analyze the outcomes of the different treatments, the control and recurrence rates, and the complications derived from them. MATERIAL AND METHODS: Data were collected from the clinical records of 22 patients over 18 years of age (86.4% women). They had been diagnosed with Cushing's disease between 2000 and 2012, and were monitored at Complejo Hospitalario Universitario-Albacete, Hospital Virgen de la Salud-Toledo Hospital General Universitario de Ciudad Real, Hospital Virgen de la Luz-Cuenca, Hospital Nuestra Señora del Prado-Talavera de la Reina, and Complejo Hospitalario la Mancha Centro-Alcázar de San Juan. RESULTS: Surgery was the treatment of choice in all patients. Biochemical cure was achieved in 72.2% of patients. Nine patients developed in the early postoperative period diabetes insipidus, which became in 2 patients only. Surprisingly, 3 patients with normal postoperative neurohypophyseal function later developed permanent diabetes insipidus. New hormone deficiencies occurred in 7 patients. Seventeen patients received ketoconazole before surgery (5 of them after surgery also), and 70% of them achieved normal urinary free cortisol levels. Three patients also received radiotherapy, and all of them were cured after a median follow-up of 85.5 months; they developed no tumors or other complications. CONCLUSIONS: Our study reports the outcomes of management of Cushing's disease in non-reference centers for this disease, possibly giving a realistic picture of standard clinical practice for the condition in Spain.

NTS-Polyplex: a potential nanocarrier for neurotrophic therapy of Parkinson's disease.

Nanomedicine has focused on targeted neurotrophic gene delivery to the brain as a strategy to stop and reverse neurodegeneration in Parkinson's disease. Because of improved transfection ability, synthetic nanocarriers have become candidates for neurotrophic therapy. Neurotensin (NTS)-polyplex is a "Trojan horse" synthetic nanocarrier system that enters dopaminergic neurons through NTS receptor internalization to deliver a genetic cargo. The success of preclinical studies with different neurotrophic genes supports the possibility of using NTS-polyplex in nanomedicine. In this review, we describe the mechanism of NTS-polyplex transfection. We discuss the concept that an effective neurotrophic therapy requires a simultaneous effect on the axon terminals and soma of the remaining dopaminergic neurons. We also discuss the future of this strategy for the treatment of Parkinson's disease. FROM THE CLINICAL EDITOR: This review paper focuses on nanomedicine-based treatment of Parkinson's disease, a neurodegenerative condition with existing symptomatic but no curative treatment. Neurotensin-polyplex is a synthetic nanocarrier system that enables delivery of genetic cargo to dopaminergic neurons via NTS receptor internalization.

Heterogeneity in ventricular zone neural precursors contributes to neuronal fate diversity in the postnatal neocortex.

The recent discovery of short neural precursors (SNPs) in the murine neocortical ventricular zone (VZ) challenges the widely held view that radial glial cells (RGCs) are the sole occupants of this germinal compartment and suggests that precursor variety is an important factor of brain development. Here, we use in utero electroporation and genetic fate mapping to show that SNPs and RGCs cohabit the VZ but display different cell cycle kinetics and generate phenotypically different progeny. In addition, we find that RGC progeny undergo additional rounds of cell division as intermediate progenitor cells (IPCs), whereas SNP progeny generally produce postmitotic neurons directly from the VZ. By clearly defining SNPs as bona fide VZ residents, separate from both RGCs and IPCs, and uncovering their unique proliferative and lineage properties, these results demonstrate how individual neural precursor groups in the embryonic rodent VZ create diversity in the overlying neocortex.

Neurotensin polyplex as an efficient carrier for delivering the human GDNF gene into nigral dopamine neurons of hemiparkinsonian rats.

Recently we showed that the neurotensin polyplex is a nanoparticle carrier system that targets reporter genes in nigral dopamine neurons in vivo. Herein, we report its first practical application in experimental parkinsonism, which consisted of transfecting dopamine neurons with the gene coding for human glial cell line-derived neurotrophic factor (hGDNF). Hemiparkinsonism was induced in rats by a single dose of 6-hydroxydopamine (30 microg) into the ventrolateral part of the striatum. We showed that transfection of the hGDNF gene into the substantia nigra of rats 1 week after the neurotoxin injection produced biochemical, anatomical, and functional recovery from hemiparkinsonism. RT-PCR analysis showed mRNA expression of exogenous hGDNF in the transfected substantia nigra. Western blot analysis verified transgene expression by recognizing the flag epitope added at the C-terminus of the hGDNF polypeptide, which was found mainly in dopamine neurons by double immunofluorescence techniques. These data indicate that the neurotensin polyplex holds great promise for the neuroprotective therapy of Parkinson disease.

Postnatal cellular contributions of the hippocampus subventricular zone to the dentate gyrus, corpus callosum, fimbria, and cerebral cortex.

The rodent dentate gyrus (DG) is formed in the embryo when progenitor cells migrate from the dentate neuroepithelium to establish a germinal zone in the hilus and a secondary germinal matrix, near the fimbria, called the hippocampal subventricular zone (HSVZ). The developmental plasticity of progenitors within the HSVZ is not well understood. To delineate the migratory routes and fates of progenitors within this zone, we injected a replication-incompetent retrovirus, encoding the enhanced green fluorescent protein (EGFP), into the HSVZ of postnatal day 5 (P5) mice. Between P6 and P45, retrovirally-infected EGFP(+) of progenitors migrated into the DG, established a reservoir of progenitor cells, and differentiated into neurons and glia. By P6-7, EGFP(+) cells were observed migrating into the DG. Subsets of these EGFP(+) cells expressed Sox2 and Musashi-1, characteristic of neural stem cells. By P10, EGFP(+) cells assumed positions within the DG and expressed immature neuronal markers. By P20, many EGFP(+) cells expressed the homeobox prospero-like protein Prox1, an early and specific granule cell marker in the CNS, and extended mossy fiber projections into the CA3. A subset of non-neuronal EGFP(+) cells in the dentate gyrus acquired the morphology of astrocytes. Another subset included EGFP(+)/RIP(+) oligodendrocytes that migrated into the fimbria, corpus callosum, and cerebral cortex. Retroviral injections on P15 labeled very few cells, suggesting depletion of HSVZ progenitors by this age. These findings suggest that the early postnatal HSVZ progenitors are multipotent and migratory, and contribute to both dentate gyrus neurogenesis as well as forebrain gliogenesis.

Biophysical characteristics of neurotensin polyplex for in vitro and in vivo gene transfection.

Previously we improved the neurotensin (NT)-polyplex by the coupling of HA2 fusogenic peptide (FP) and Vp1 SV40 karyophilic peptide (KP). We now report the proportion of [(125)I]-NT, [(3)H]-FP, and poly-l-lysine (PLL) in the NT-polyplex, and some of its biophysical properties. We concluded that the most efficient NT-polyplex comprised 1 NT, 4 FP, and 2 PLL molecules. Electrophoresis revealed that high acidity is detrimental for NT-polyplex stability. Electron microscopy and electrophoresis studies showed that 6 muM KP and 1% serum condensed the plasmid DNA (pDNA) before the appearance of toroid structures. Four plasmids were used to evaluate the transfection efficiency. In vitro, maximum expression was produced at molar ratios (pDNA : [(125)I]-NT-[(3)H]-FP-PLL conjugate) of 1:34 for pEGFP-N1 and 1:27 for pECFP-Nuc. Cotransfection of those plasmids was attained at their optimum molar ratios. In vivo, maximum expression of the pDAT-BDNF-flag in dopamine neurons was produced at a 1:45 molar ratio, whereas that of pDAT-EGFP was at 1:20. The NT-polyplex in the presence of 1 muM SR-48692, an NT-receptor specific antagonist, and untargeted polyplex did not cause transfection in vivo demonstrating the specificity of gene transfer via NT-receptor endocytosis. This information is essential for synthesizing an efficient NT-polyplex that can provide a useful tool for specific gene transfection.