Genome-wide screen to identify genetic loci associated with cognitive decline in late-life depression.

OBJECTIVE: This study sought to conduct a comprehensive search for genetic risk of cognitive decline in the context of geriatric depression. DESIGN: A genome-wide association study (GWAS) analysis in the Neurocognitive Outcomes of Depression in the Elderly (NCODE) study. SETTING: Longitudinal, naturalistic follow-up study. PARTICIPANTS: Older depressed adults, both outpatients and inpatients, receiving care at an academic medical center. MEASUREMENTS: The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery was administered to the study participants at baseline and a minimum of twice within a subsequent 3-year period in order to measure cognitive decline. A GWAS analysis was conducted to identify genetic variation that is associated with baseline and change in the CERAD Total Score (CERAD-TS) in NCODE. RESULTS: The GWAS of baseline CERAD-TS revealed a significant association with an intergenic single-nucleotide polymorphism (SNP) on chromosome 6, rs17662598, that surpassed adjustment for multiple testing (p = 3.7 × 10-7; false discovery rate q = 0.0371). For each additional G allele, average baseline CERAD-TS decreased by 8.656 points. The most significant SNP that lies within a gene was rs11666579 in SLC27A1 (p = 1.1 × 10-5). Each additional copy of the G allele was associated with an average decrease of baseline CERAD-TS of 4.829 points. SLC27A1 is involved with processing docosahexaenoic acid (DHA), an endogenous neuroprotective compound in the brain. Decreased levels of DHA have been associated with the development of Alzheimer's disease. The most significant SNP associated with CERAD-TS decline over time was rs73240021 in GRXCR1 (p = 1.1 × 10-6), a gene previously linked with deafness. However, none of the associations within genes survived adjustment for multiple testing. CONCLUSIONS: Our GWAS of cognitive function and decline among individuals with late-life depression (LLD) has identified promising candidate genes that, upon replication in other cohorts of LLD, may be potential biomarkers for cognitive decline and suggests DHA supplementation as a possible therapy of interest.

The affect of personality traits and decision-making style on postoperative quality of life and distress in patients undergoing pelvic exenteration.

AIM: Our aim was to identify whether personality traits and decision-making styles affect quality of life (QoL) outcomes and levels of psychological distress following pelvic exenteration (PE). METHOD: Patients undergoing PE between 2008 and 2015 were identified from a prospectively maintained database at a single quaternary referral centre. Patients were invited to complete two validated questionnaires, with the Big Five inventory being used to assess personality traits and the Melbourne Decision Making Questionnaire to determine decision-making style. Data on QoL outcomes and distress from the prospectively established database were utilized. QoL with respect to both physical and mental health components was measured using Short Form 36 version 2 (SF-36v2) and the Functional Assessment of Cancer Therapy - Colorectal (FACT-C). Distress was measured using the Distress Thermometer. Postoperative pain scores were also measured using SF-36v2. RESULTS: Of the 93 patients eligible for participation, 42 returned the study questionnaire. On multivariate analysis, neuroticism was the most significant predictor of poorer QoL and increased levels of distress, consistent across all of the measures utilized and at the different time points used. Other personality traits showed an isolated statistically significant impact upon QoL. There were no significant findings with respect to decision-making style. Apart from neuroticism, the most significant predictor of QoL was the number of major complications for the patient. CONCLUSION: Patients demonstrating neurotic personality traits show poorer QoL outcomes and higher levels of distress following PE. Identification of these patients would allow targeted pre- and postoperative intervention to improve outcomes following PE.

Quality of life and functional outcomes following pelvic exenteration and sacrectomy.

AIM: The aim was to compare postoperative quality of life (QOL) between patients undergoing pelvic exenteration (PE) and pelvic exenteration with sacrectomy (PES), and to investigate the influence of high (L5-S2) vs low (≤ S3) sacrectomy on QOL and functional outcomes. METHOD: Patients undergoing en bloc sacrectomy as part of a PE and PE alone from 2008 to 2015 were identified from a prospectively maintained database. QOL and functional outcomes were assessed using the 36-Item Short Form Survey, the European Organization for Research and Treatment of Cancer Colorectal Cancer questionnaire and Quality of Life questionnaire, the Revised Musculoskeletal Tumour Scale, the Lower Extremity Functional Scale, the Sexual Health Inventory for Men and the Female Sexual Function Index. RESULTS: Of the 344 patients identified, data were available for 116 patients who underwent PE alone and 140 patients who underwent PES. PES patients had significantly poorer physical component scores (P < 0.001) but not mental component scores (P = 0.17). Of the 140 PES patients, 55 were eligible and were invited to participate in a second functional survey, with 30 patients returning the study questionnaire. High sacrectomy patients, compared with low sacrectomy, had significantly worse lower limb motor function (P = 0.03) and poorer physical (P = 0.001) and mental health component scores (P = 0.02). No differences were found in sexual, bladder and bowel function between high and low sacrectomy patients. CONCLUSIONS: Patients undergoing PES had worse physical component scores compared with PE alone, whereas high sacrectomy patients had significantly worse lower limb motor function and physical and mental component scores but comparable bowel, bladder and sexual functional outcomes compared with low sacrectomy patients.

Pushing the boundaries of pelvic exenteration by maintaining survival at the cost of morbidity.

BACKGROUND: Pelvic exenteration (PE) provides a potentially curative option for advanced or recurrent malignancy confined to the pelvis. A clear (R0) resection margin is the strongest prognostic factor predicting long-term survival, driving most technical advances in PE surgery. The aim of this cohort study was to describe changing trends in extent of resection, postoperative complications, mortality and overall survival after PE surgery. METHODS: Consecutive patients who underwent PE for advanced or recurrent pelvic malignancy at a single institution in Sydney, Australia, were identified. The cohort was divided into three groups based on time periods reflecting annual surgical volume: 1994-2006 (20 or fewer procedures per year), 2007-2013 (21-50 procedures per year) and 2014-2017 (over 50 procedures per year). Primary outcomes were extent of resection, postoperative complications, 60-day mortality and 3-year overall survival. Secondary outcomes were patient characteristics, receipt of neoadjuvant therapy and duration of hospital stay. RESULTS: There were increases over time in rates of lateral and posterior compartment resections (P < 0·001), and bony pelvis (P = 0·002) and neurovascular (P < 0·001) excision. For patients undergoing reconstruction, the proportion receiving vertical rectus abdominus myocutaneous flaps increased significantly (P = 0·005). Rates of wound infection, dehiscence, and abdominal and pelvic collections increased over the study interval. Short-term mortality decreased, and 1- and 3-year survival rates improved. CONCLUSION: Technical and surgical advancements have led to more complex PE resections, with R0 and mortality rates improving with higher annual volume. There were associated increases in intraoperative blood loss and postoperative morbidity.

ANTECEDENTES: La exenteración pélvica (pelvic exenteration, PE) ofrece una opción potencialmente curativa para el cáncer localmente avanzado o la recidiva de la neoplasia limitada a la pelvis. Un margen de resección libre (R0) es el factor pronóstico más importante que predice la supervivencia a largo plazo, lo que ha impulsado la mayoría de los avances técnicos en la cirugía de la PE. El objetivo de este estudio de cohortes fue describir el cambio en la tendencia relativa a la extensión de la resección, las complicaciones postoperatorias, la mortalidad y la supervivencia global después de la cirugía de la PE. MÉTODOS: Se identificaron pacientes intervenidos de forma consecutiva a los que se practicó una PE por neoplasia pélvica avanzada o recidivante en una sola institución en Sydney, Australia. La cohorte se dividió en tres grupos según períodos de tiempo que reflejan el volumen quirúrgico anual: 1994-2006 (≤ 20 casos por año), 2007-2013 (21-50 casos por año) y 2014-2017 (> 50 casos por año). Los criterios de valoración principal fueron la extensión de la resección, las complicaciones postoperatorias, la mortalidad a los 60 días y la supervivencia a los tres años. Los criterios de valoración secundarios fueron las características del paciente, la administración de tratamiento neoadyuvante y la duración de la estancia hospitalaria. Las tendencias se evaluaron mediante pruebas de χ2 o ANOVA de una vía. RESULTADOS: Los porcentajes de resección de los compartimentos lateral y posterior, pelvis ósea así como de escisión neurovascular aumentaron con el tiempo (P < 0,01). Entre los pacientes en los que se hizo una reconstrucción, el porcentaje de colgajos miocutáneos verticales del recto del abdomen aumentó significativamente (P = 0,005). Las tasas de infección de herida, dehiscencia y colecciones abdominales y pélvicas aumentaron durante el período de estudio. La mortalidad a corto plazo disminuyó y la supervivencia a 1 y 3 años mejoró durante el período de estudio. CONCLUSIÓN: Los avances técnicos y quirúrgicos han permitido realizar resecciones de PE más complejas, mejorando las tasas de resección R0 y de mortalidad al aumentar el volumen anual de intervenciones. Al mismo tiempo se han observado incrementos en las pérdidas intraoperatorias de sangre, en las reconstrucciones y en la morbilidad postoperatoria.

Potassium-induced decrease in cytosolic Na+ alleviates deleterious effects of salt stress on wheat (Triticum aestivum L.).

Accumulation of NaCl in soil causes osmotic stress in plants, and sodium (Na+ ) and chloride (Cl- ) cause ion toxicity, but also reduce the potassium (K+ ) uptake by plant roots and stimulate the K+ efflux through the cell membrane. Thus, decreased K+ /Na+ ratio in plant tissue lead us to hypothesise that elevated levels of K+ in nutrient medium enhance this ratio in plant tissue and cytosol to improve enzyme activation, osmoregulation and charge balance. In this study, wheat was cultivated at different concentrations of K+ (2.2, 4.4 or 8.8 mm) with or without salinity (1, 60 or 120 mm NaCl) and the effects on growth, root and shoot Na+ and K+ distribution and grain yield were determined. Also, the cytosolic Na+ concentration was investigated, as well as photosynthesis rate and water potential. Salinity reduced fresh weight of both shoots and roots and dry weight of roots. The grain yield was significantly reduced under Na+ stress and improved with elevated K+ fertilisation. Elevated K+ level during cultivation prevented the accumulation of Na+ into the cytosol of both shoot and root protoplasts. Wheat growth at vegetative stage was transiently reduced at the highest K+ concentration, perhaps due to plants' efforts to overcome a high solute concentration in the plant tissue, nevertheless grain yield was increased at both K+ levels. In conclusion, a moderately elevated K+ application to wheat seedlings reduces tissue as well as cytosolic Na+ concentration and enhances wheat growth and grain yield by mitigating the deleterious effects of Na+ toxicity.

Cohort study of long-term survival and quality of life following pelvic exenteration.

BACKGROUND: Pelvic exenteration (PE) is the preferred treatment available for selected patients diagnosed with locally advanced or recurrent cancer confined to the pelvis. Currently, the majority of the literature reports only on short-term survival and quality-of-life (QoL) outcomes. The aim of this prospective cohort study was to describe long-term survival and QoL outcomes following PE. METHODS: This was a cohort study of consecutive patients undergoing PE from 1994 to 2016 at a major teaching hospital in Sydney, Australia. From 2008, consenting patients were also included in a prospective QoL study. Main outcomes were long-term survival and QoL assessed with SF-36® and FACT-C questionnaires. Survival was estimated using the Kaplan-Meier method. RESULTS: Some 515 patients underwent PE for locally advanced or recurrent cancer. The cumulative 5- and 10-year overall survival rates were 48·6 and 37·8 per cent respectively. The survival estimates were significantly higher for patients with advanced primary rectal cancer (P = 0·045) and those in whom a clear resection margin was achieved (P < 0·001). Some 287 patients were enrolled into the QoL study. Response rates at baseline, 6 months and 5 years were 92·0, 70·0 and 33 per cent respectively. Patients had recovered to their preoperative QoL status by 6 months and, among survivors, QoL remained essentially unchanged during the 5-year follow-up. CONCLUSION: Patients who underwent PE owing to advanced primary rectal cancer or achieved a clear resection margin had a greater chance of survival. Overall, QoL returned to baseline within 6 months after surgery.

Development of VEGF-loaded PLGA matrices in association with mesenchymal stem cells for tissue engineering.

The association of bioactive molecules, such as vascular endothelial growth factor (VEGF), with nanofibers facilitates their controlled release, which could contribute to cellular migration and differentiation in tissue regeneration. In this research, the influence of their incorporation on a polylactic-co-glycolic acid (PLGA) scaffold produced by electrospinning on cell adhesion and viability and cytotoxicity was carried out in three groups: 1) PLGA/BSA/VEGF; 2) PLGA/BSA, and 3) PLGA. Morphology, fiber diameter, contact angle, loading efficiency and controlled release of VEGF of the biomaterials, among others, were measured. The nanofibers showed smooth surfaces without beads and with interconnected pores. PLGA/BSA/VEGF showed the smallest water contact angle and VEGF released for up to 160 h. An improvement in cell adhesion was observed for the PLGA/BSA/VEGF scaffolds compared to the other groups and the scaffolds were non-toxic for the cells. Therefore, the scaffolds were shown to be a good strategy for sustained delivery of VEGF and may be a useful tool for tissue engineering.

Incidence of MRI-detected brain lesions and neurocognitive function after electrical cardioversion in anticoagulated patients with persistent atrial fibrillation.

BACKGROUND: After electrical cardioversion (eCV) in patients with atrial fibrillation (AF), the risk for clinically apparent cerebral thromboembolism is increased in the subsequent weeks. To date, there is little evidence on the incidence of acute brain lesions (ABL) detected with cerebral magnetic resonance imaging (MRI) after eCV, in particular in patients treated with the Non-Vitamin K Antagonist oral anticoagulants (NOAC). AIMS: The aim of this pilot study was to evaluate the incidence of MRI-detected ABL, as well as the neuro-cognitive function after eCV in patients with persistent AF using NOACs as compared to phenprocoumon. METHODS AND RESULTS: 50 consecutive patients with persistent AF (mean age 69.6±3.5years, 26 male) were evaluated in this prospective study. Cerebral 3Tesla MRI and neuro-cognitive assessment using the National Institutes of Health Stroke Scale (NIHSS) score and the Montreal Cognitive Assessment Test (MoCA) were performed in all patients within 24h before eCV and after a median follow-up duration of 14days (Q1: 13, Q3: 19days). Patients were treated with an OAC for at least 4weeks after eCV and according to the CHA2DS2-Vasc-score thereafter. Thirty-nine patients were treated with NOACs (Dabigatran 10/50 [20%], Apixaban 21/50 [42%] and Rivaroxaban 8/50 [16]) and 11/50 patients with Phenprocoumon (22%). No patient developed ABL on cerebral MRI at the 2-week follow-up. Neurological as well as cognitive function were similar before and 2weeks after eCV (NIHSS-score: p=0.35; MoCa score: p=0.21). CONCLUSION: Electrical CV in patients with persistent AF, in particular when treated with NOACs, carries a low risk for the development of MRI-detected ABL or neurocognitive decline. CLINICAL TRIALS REGISTRATION: GermanClinicalTrialsRegister number: DRKS00010460.

Development of VEGF-loaded PLGA matrices in association with mesenchymal stem cells for tissue engineering

The association of bioactive molecules, such as vascular endothelial growth factor (VEGF), with nanofibers facilitates their controlled release, which could contribute to cellular migration and differentiation in tissue regeneration. In this research, the influence of their incorporation on a polylactic-co-glycolic acid (PLGA) scaffold produced by electrospinning on cell adhesion and viability and cytotoxicity was carried out in three groups: 1) PLGA/BSA/VEGF; 2) PLGA/BSA, and 3) PLGA. Morphology, fiber diameter, contact angle, loading efficiency and controlled release of VEGF of the biomaterials, among others, were measured. The nanofibers showed smooth surfaces without beads and with interconnected pores. PLGA/BSA/VEGF showed the smallest water contact angle and VEGF released for up to 160 h. An improvement in cell adhesion was observed for the PLGA/BSA/VEGF scaffolds compared to the other groups and the scaffolds were non-toxic for the cells. Therefore, the scaffolds were shown to be a good strategy for sustained delivery of VEGF and may be a useful tool for tissue engineering.

Evaluating the effectiveness of a home-based exercise programme delivered through a tablet computer for preventing falls in older community-dwelling people over 2†years: study protocol for the Standing Tall randomised controlled trial.

INTRODUCTION: In order to prevent falls, older people should exercise for at least 2 h per week for 6 months, with a strong focus on balance exercises. This article describes the design of a randomised controlled trial to evaluate the effectiveness of a home-based exercise programme delivered through a tablet computer to prevent falls in older people. METHODS AND ANALYSIS: Participants aged 70 years or older, living in the community in Sydney will be recruited and randomly allocated to an intervention or control group. The intervention consists of a tailored, home-based balance training delivered through a tablet computer. Intervention participants will be asked to complete 2 h of exercises per week for 2 years. Both groups will receive an education programme focused on health-related information relevant to older adults, delivered through the tablet computer via weekly fact sheets. Primary outcome measures include number of fallers and falls rate recorded in weekly fall diaries at 12 months. A sample size of 500 will be necessary to see an effect on falls rate. Secondary outcome measures include concern about falling, depressive symptoms, health-related quality of life and physical activity levels (in all 500 participants); and physiological fall risk, balance, functional mobility, gait, stepping and cognitive performance (in a subsample of 200 participants). Adherence, acceptability, usability and enjoyment will be recorded in intervention group participants over 2 years. Data will be analysed using the intention-to-treat principle. Secondary analyses are planned in people with greater adherence. Economic analyses will be assessed from a health and community care provider perspective. ETHICS AND DISSEMINATION: Ethical approval was obtained from UNSW Ethics Committee in December 2014 (ref number HC#14/266). Outcomes will be disseminated through publication in peer-reviewed journals and presentations at international conferences. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN)12615000138583.

Does magnetic resonance imaging predict future low back pain? A systematic review.

BACKGROUND AND OBJECTIVE: Magnetic resonance imaging (MRI) has the potential to identify pathology responsible for low back pain (LBP). However, the importance of findings on MRI remains controversial. We aimed to systematically review whether MRI findings of the lumbar spine predict future LBP in different samples with and without LBP. DATABASES AND DATA TREATMENT: MEDLINE, CINAHL and EMBASE databases were searched. Included were prospective cohort studies investigating the relationship between baseline MRI abnormalities of the lumbar spine and clinically important LBP outcome at follow-up. We excluded cohorts with specific diseases as the cause of their LBP. Associations between MRI findings and LBP pain outcomes were extracted from eligible studies. RESULTS: A total of 12 studies met the inclusion criteria. Six studies presented data on participants with current LBP; one included a sample with no current LBP, three included a sample with no history of LBP and two included mixed samples. Due to small sample size, poor overall quality and the heterogeneity between studies in terms of participants, MRI findings and clinical outcomes investigated, it was not possible to pool findings. No consistent associations between MRI findings and outcomes were identified. Single studies reported significant associations for Modic changes type 1 with pain, disc degeneration with disability in samples with current LBP and disc herniation with pain in a mixed sample. CONCLUSIONS: The limited number, heterogeneity and overall quality of the studies do not permit definite conclusions on the association of MRI findings of the lumbar spine with future LBP (PROSPERO: CRD42012002342).

A new biomaterial of nanofibers with the microalga Spirulina as scaffolds to cultivate with stem cells for use in tissue engineering.

The association of stem cells (SCs) with biomaterials promises to be the protagonist for future regenerative medicine in the treatment of tissue and organ lesions. Stem cells were cultivated in scaffolds constructed by the electrospinning technique, using poly-D,L-lactic acid (PDLLA) associated or not with Spirulina biomass (PDLLA/Sp), which has bioactive components of interest for tissue engineering (TE). Physicochemical analyses were performed, such as morphology, fiber diameter, degradability, residual solvent, roughness, contact angle with water, among others. SCs adhesion, proliferation and scaffold cytotoxicity were also evaluated. Nanofibers without beads and with characteristics similar to the natural extracellular matrix (ECM) in terms of mechanical and topographical properties were obtained. In biological tests it was found that SCs adhered more and had greater viability in the PDLLA/Sp molds, when compared with the PDLLA scaffolds. The scaffolds were shown to be atoxic for the SCs. It can be concluded that the scaffolds developed in this work have the characteristics to be a new biomaterial suitable for use in TE.

Viability of mesenchymal stem cells during electrospinning

Tissue engineering is a technique by which a live tissue can be re-constructed and one of its main goals is to associate cells with biomaterials. Electrospinning is a technique that facilitates the production of nanofibers and is commonly used to develop fibrous scaffolds to be used in tissue engineering. In the present study, a different approach for cell incorporation into fibrous scaffolds was tested. Mesenchymal stem cells were extracted from the wall of the umbilical cord and mononuclear cells from umbilical cord blood. Cells were re-suspended in a 10 percent polyvinyl alcohol solution and subjected to electrospinning for 30 min under a voltage of 21 kV. Cell viability was assessed before and after the procedure by exclusion of dead cells using trypan blue staining. Fiber diameter was observed by scanning electron microscopy and the presence of cells within the scaffolds was analyzed by confocal laser scanning microscopy. After electrospinning, the viability of mesenchymal stem cells was reduced from 88 to 19.6 percent and the viability of mononuclear cells from 99 to 8.38 percent. The loss of viability was possibly due to the high viscosity of the polymer solution, which reduced the access to nutrients associated with electric and mechanical stress during electrospinning. These results suggest that the incorporation of cells during fiber formation by electrospinning is a viable process that needs more investigation in order to find ways to protect cells from damage.

Impact of BDNF Val66Met and 5-HTTLPR polymorphism variants on neural substrates related to sadness and executive function.

The brain-derived neurotrophic factor (BDNF) Val(66) Met allelic variation is linked to both the occurrence of mood disorders and antidepressant response. These findings are not universally observed, and the mechanism by which this variation results in increased risk for mood disorders is unclear. One possible explanation is an epistatic relationship with other neurotransmitter genes associated with depression risk, such as the serotonin-transporter-linked promotor region (5-HTTLPR). Further, it is unclear how the coexistence of the BDNF Met and 5-HTTLPR S variants affects the function of the affective and cognitive control systems. To address this question, we conducted a functional magnetic resonance imaging (fMRI) study in 38 older adults (20 healthy and 18 remitted from major depressive disorder). Subjects performed an emotional oddball task during the fMRI scan and provided blood samples for genotyping. Our analyses examined the relationship between genotypes and brain activation to sad distractors and attentional targets. We found that 5-HTTLPR S allele carriers exhibited stronger activation in the amygdala in response to sad distractors, whereas BDNF Met carriers exhibited increased activation to sad stimuli but decreased activation to attentional targets in the dorsolateral prefrontal and dorsomedial prefrontal cortices. In addition, subjects with both the S allele and Met allele genes exhibited increased activation to sad stimuli in the subgenual cingulate and posterior cingulate. Our results indicate that the Met allele alone or in combination with 5-HTTLPR S allele may increase reactivity to sad stimuli, which might represent a neural mechanism underlying increased depression vulnerability.

Transplantation of mononuclear cells from human umbilical cord blood promotes functional recovery after traumatic spinal cord injury in Wistar rats

Cell transplantation is a promising experimental treatment for spinal cord injury. The aim of the present study was to evaluate the efficacy of mononuclear cells from human umbilical cord blood in promoting functional recovery when transplanted after a contusion spinal cord injury. Female Wistar rats (12 weeks old) were submitted to spinal injury with a MASCIS impactor and divided into 4 groups: control, surgical control, spinal cord injury, and one cell-treated lesion group. Mononuclear cells from umbilical cord blood of human male neonates were transplanted in two experiments: a) 1 h after surgery, into the injury site at a concentration of 5 x 10(6) cells diluted in 10 µL 0.9 percent NaCl (N = 8-10 per group); b) into the cisterna magna, 9 days after lesion at a concentration of 5 x 10(6) cells diluted in 150 µL 0.9 percent NaCl (N = 12-14 per group). The transplanted animals were immunosuppressed with cyclosporin-A (10 mg/kg per day). The BBB scale was used to evaluate motor behavior and the injury site was analyzed with immunofluorescent markers to label human transplanted cells, oligodendrocytes, neurons, and astrocytes. Spinal cord injury rats had 25 percent loss of cord tissue and cell treatment did not affect lesion extension. Transplanted cells survived in the injured area for 6 weeks after the procedure and both transplanted groups showed better motor recovery than the untreated ones (P < 0.05). The transplantation of mononuclear cells from human umbilical cord blood promoted functional recovery with no evidence of cell differentiation.

Transplantation of mononuclear cells from human umbilical cord blood promotes functional recovery after traumatic spinal cord injury in Wistar rats.

Cell transplantation is a promising experimental treatment for spinal cord injury. The aim of the present study was to evaluate the efficacy of mononuclear cells from human umbilical cord blood in promoting functional recovery when transplanted after a contusion spinal cord injury. Female Wistar rats (12 weeks old) were submitted to spinal injury with a MASCIS impactor and divided into 4 groups: control, surgical control, spinal cord injury, and one cell-treated lesion group. Mononuclear cells from umbilical cord blood of human male neonates were transplanted in two experiments: a) 1 h after surgery, into the injury site at a concentration of 5 x 10(6) cells diluted in 10 µL 0.9% NaCl (N = 8-10 per group); b) into the cisterna magna, 9 days after lesion at a concentration of 5 x 10(6) cells diluted in 150 µL 0.9% NaCl (N = 12-14 per group). The transplanted animals were immunosuppressed with cyclosporin-A (10 mg/kg per day). The BBB scale was used to evaluate motor behavior and the injury site was analyzed with immunofluorescent markers to label human transplanted cells, oligodendrocytes, neurons, and astrocytes. Spinal cord injury rats had 25% loss of cord tissue and cell treatment did not affect lesion extension. Transplanted cells survived in the injured area for 6 weeks after the procedure and both transplanted groups showed better motor recovery than the untreated ones (P < 0.05). The transplantation of mononuclear cells from human umbilical cord blood promoted functional recovery with no evidence of cell differentiation.

Viability of mesenchymal stem cells during electrospinning.

Tissue engineering is a technique by which a live tissue can be re-constructed and one of its main goals is to associate cells with biomaterials. Electrospinning is a technique that facilitates the production of nanofibers and is commonly used to develop fibrous scaffolds to be used in tissue engineering. In the present study, a different approach for cell incorporation into fibrous scaffolds was tested. Mesenchymal stem cells were extracted from the wall of the umbilical cord and mononuclear cells from umbilical cord blood. Cells were re-suspended in a 10% polyvinyl alcohol solution and subjected to electrospinning for 30 min under a voltage of 21 kV. Cell viability was assessed before and after the procedure by exclusion of dead cells using trypan blue staining. Fiber diameter was observed by scanning electron microscopy and the presence of cells within the scaffolds was analyzed by confocal laser scanning microscopy. After electrospinning, the viability of mesenchymal stem cells was reduced from 88 to 19.6% and the viability of mononuclear cells from 99 to 8.38%. The loss of viability was possibly due to the high viscosity of the polymer solution, which reduced the access to nutrients associated with electric and mechanical stress during electrospinning. These results suggest that the incorporation of cells during fiber formation by electrospinning is a viable process that needs more investigation in order to find ways to protect cells from damage.

BDNF Val66Met genotype and 6-month remission rates in late-life depression.

Although not observed in younger adult cohorts, in older individuals the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with major depressive disorder (MDD) risk. It is further associated with subjective social support and magnetic resonance imaging (MRI) hyperintense lesions, clinical features independently related to MDD. We examined the relationship between this polymorphism and antidepressant remission rates in an elderly sample with MDD, while also testing for mediation effects of social support and hyperintensities. A total of 229 elderly Caucasian subjects with MDD completed baseline assessments, 1.5 T MRI, and BDNF genotyping. They received antidepressant medication under a structured treatment algorithm and were evaluated for remission at 3 and 6 months. At the 3-month evaluation, BDNF Val66Met genotype was not associated with remission (Wald's χ²=2.51, P=0.1131). When not controlling for multiple comparisons, Met66 allele carriers were more likely to be remitted at 6 months (χ²=4.32, P=0.0377) with an odds ratio of 1.82 (95% CI: 1.04, 3.22). This effect persisted after controlling for lesion volume and social support, neither of which mediated this relationship. Thus in this exploratory analysis, the Met66 allele may be associated with increased odds of remission in older subjects, but also with increased time to remission as there was no 3-month effect.