Peripheral brain-derived neurotrophic factor levels in alzheimer's disease and mild cognitive impairment: A comprehensive systematic review and meta-analysis

Alzheimer's disease (AD) is becoming a growing global problem, and there is an urgent need to identify reliable blood biomarkers of the risk and progression of this condition. A potential candidate is the brain-derived neurotrophic factor (BDNF), which modulates major trophic effects in the brain. However, findings are apparently inconsistent regarding peripheral blood BDNF levels in AD patients vs. healthy people. We thus performed a systematic review and meta-analysis of the studies that have examined peripheral BDNF levels in patients with AD or mild cognitive impairment (MCI) and healthy controls. We searched articles through PubMed, EMBASE, and hand searching. Over a total pool of 2061 potential articles, 26 met all inclusion criteria (including a total of 1584 AD patients, 556 MCI patients, and 1294 controls). A meta-analysis of BDNF levels between early AD and controls showed statistically significantly higher levels (SMD [95 % CI]: 0.72 [0.31, 1.13]) with no heterogeneity. AD patients with a low (<20) mini-mental state examination (MMSE) score had lower peripheral BDNF levels compared with controls (SMD [95 % CI]: -0.33 [-0.60, -0.05]). However, we found no statistically significant difference in blood (serum/plasma) BDNF levels between all AD patients and controls (standard mean difference, SMD [95 % CI]: -0.16 [-0.4, 0.07]), and there was heterogeneity among studies (P < 0.0001, I 2 = 85.8 %). There were no differences in blood BDNF levels among AD or MCI patients vs. controls by subgroup analyses according to age, sex, and drug use. In conclusion, this meta-analysis shows that peripheral blood BDNF levels seem to be increased in early AD and decreased in AD patients with low MMSE scores respectively compared with their age- and sex-matched healthy referents. At present, however, this could not be concluded from individual studies.

Pelvic-Floor Rehabilitation, Part 1 : Comparison of Two Surface Electrode Placements During Stimulation of the Pelvic-Floor Musculature in Women Who Are Continent Using Bipolar Interferential Currents

Background and Purpose. Electrical stimulation of the pelvic floor is used as an adjunct in the conservative treatment of urinary incontinence. No consensus exists, however, regarding electrode placements for optimal stimulation of the pelvic-floor musculature. The purpose of this study was to compare two different bipolar electrode placements, one suggested by Laycock and Green (L2) the other by Dumoulin (D2), during electrical stimulation with interferential currents of the pelvic-floor musculature in continent women, using a two-group crossover design. Subjects. Ten continent female volunteers, ranging in age from 20 to 39 years (X̅=27.3, SD=5.6), were randomly assigned to one of two study groups. Methods. Each study group received neuromuscular electrical stimulation (NMES) of the pelvic-floor musculature using both electrode placements, the order of application being reversed for each group. Force of contraction was measured as pressure (in centimeters of water [cm H2O]) exerted on a vaginal pressure probe attached to a manometer. Data were analyzed using a two-way, mixed-model analysis of variance. Results. No difference in pressure was observed between the two electrode placements. Differences in current amplitude were observed, with the D2 electrode placement requiring less current amplitude to produce a maximum recorded pressure on the manometer. Subjective assessment by the subjects revealed a preference for the D2 electrode placement (7 of 10 subjects). Conclusion and Discussion. The lower current amplitudes required with the D2 placement to obtain recordings comparable to those obtained with the L2 technique suggest a more comfortable stimulation of the pelvic-floor muscles. The lower current amplitudes required also suggest that greater increases in pressure might be obtained with the D2 placement by increasing the current amplitude while remaining within the comfort threshold. These results will help to define treatment guidelines for a planned clinical study investigating the effects of NMES and exercise in the treatment of urinary stress incontinence in women postpartum.

Growth and survival of Sclerolobium paniculatum vogel and the relationship between rainfall and the increment in diameter at different planting spacings.

Sclerolobium paniculatum Vogel is a species that has good potential for reclamation of degraded soils. The aim of the investigation was to evaluate the growth and survival of the species and the influence of rainfall on growth in diameter as a function of different spacings (4 m x 2 m, 4 m x 3 m, and 4 m x 4 m). The results indicate that the temporal analysis (period from November 2007 to August 2013) detected significant differences (p ? 0.05) in height between the 4 m x 2 m and 4 m x 4 m spacings, while no significant difference in diameter was found between the 4 m x 2 m and 4 m x 3 m spacings. However, the statistical differences did not persist when the data was analyzed at seven and half years old. Regarding survival, a significant difference was observed only between the 4 m x 4 m spacing and the others, with superiority to the former. A strong correlation was found between rainfall and the increment in diameter of individuals in the broader spacings (R = 0.80 in the 4 m x 3 m spacing and R = 0.77 in the 4 m x 4 m spacing), while in the denser spacing the correlation was moderate (R = 0.56 in the 4 m x 2 m spacing). Since the spacings adopted did not influence tree growth by the end of the period, the choice will depend on other factors such as survival and costs of implementation and forestry management. Plantations in regions with larger rainfall amplitude may benefit the productivity of the species.

Evaluation Of The Radiopacity Of Esthetic Root Canal Posts.

The radiopacity of esthetic root canal posts may impair the assessment of their fit to the root canal when using radiographic images. This study determined in vitro the radiographic density of esthetic root canal posts using digital images. Thirty-six roots of human maxillary canines were assigned to six groups (N=6 per group): Reforpost (RP); Aestheti-Plus (AP); Reforpost MIX (RPM); D.T. Light Post (LP); Reforpost Radiopaque (RPR); and White Post DC (WP). Standardized digital images of the posts were obtained in different conditions: outside the root canal, inside the canal before and after cementation using luting material, and with a tissue simulator. Analysis of variance was used to compare the radiopacity mean values among the posts outside the root canal and among the posts under the other conditions, and the t unpaired test to compare the radiopacity between the posts and the dentin, and between the posts and the root canal space. There was no statistically significant difference in radiopacity between RP and RPM, and LP and WP. AP posts showed radiopacity values significantly lower than those for dentin. No statistically significant difference was found between posts (RP and AP) and the root canal space. A statistically significant difference was observed between the luted and non-luted posts; additionally, luted posts with and without tissue simulator showed no significant differences. Most of the cement-luted posts analyzed in this study were distinguishable from the density of adjacent dentin surfaces, allowing radiographic confirmation of the fit of the post in the canal. The success of using esthetic root canal posts depends mainly on the fit of the post within the canal.[1] The radiopacity of a post allows for radiographic imaging to be used to determine the fit, an important factor in a clinical perspective.

Microbial Evaluation Of Traumatized Teeth Treated With Triple Antibiotic Paste Or Calcium Hydroxide With 2% Chlorhexidine Gel In Pulp Revascularization.

Revascularization outcome depends on microbial elimination because apical repair will not happen in the presence of infected tissues. This study evaluated the microbial composition of traumatized immature teeth and assessed their reduction during different stages of the revascularization procedures performed with 2 intracanal medicaments. Fifteen patients (7-17 years old) with immature teeth were submitted to the revascularization procedures; they were divided into 2 groups according to the intracanal medicament used: TAP group (n = 7), medicated with a triple antibiotic paste, and CHP group (n = 8), dressed with calcium hydroxide + 2% chlorhexidine gel. Samples were taken before any treatment (S1), after irrigation with 6% NaOCl (S2), after irrigation with 2% chlorhexidine (S3), after intracanal dressing (S4), and after 17% EDTA irrigation (S5). Cultivable bacteria recovered from the 5 stages were counted and identified by means of polymerase chain reaction assay (16S rRNA). Both groups had colony-forming unit counts significantly reduced after S2 (P < .05); however, no significant difference was found between the irrigants (S2 and S3, P = .99). No difference in bacteria counts was found between the intracanal medicaments used (P = .95). The most prevalent bacteria detected were Actinomyces naeslundii (66.67%), followed by Porphyromonas endodontalis, Parvimonas micra, and Fusobacterium nucleatum, which were detected in 33.34% of the root canals. An average of 2.13 species per canal was found, and no statistical correlation was observed between bacterial species and clinical/radiographic features. The microbial profile of infected immature teeth is similar to that of primarily infected permanent teeth. The greatest bacterial reduction was promoted by the irrigation solutions. The revascularization protocols that used the tested intracanal medicaments were efficient in reducing viable bacteria in necrotic immature teeth.

Comparison Of The Solution Of Histidine-tryptophan-alfacetoglutarate With Histidine-tryptophan-glutamate As Cardioplegic Agents In Isolated Rat Hearts: An Immunohistochemical Study.

Cardiac arrest during heart surgery is a common procedure and allows the surgeon to perform surgical procedures in an environment free of blood and movement. Using a model of isolated rat heart, the authors compare a new cardioplegic solution containing histidine-tryptophan-glutamate (group 2) with the histidine-tryptophan-alphacetoglutarate (group 1) routinely used by some cardiac surgeons. To assess caspase, IL-8 and KI-67 in isolated rat hearts using immunohistochemistry. 20 Wistar male rats were anesthetized and heparinized. The chest was opened, cardioctomy was performed and 40 ml/kg of the appropriate cardioplegic solution was infused. The hearts were kept for 2 hours at 4ºC in the same solution, and thereafter, placed in the Langendorff apparatus for 30 minutes with Ringer-Locke solution. Immunohistochemistry analysis of caspase, IL-8, and KI-67 were performed. The concentration of caspase was lower in group 2 and Ki-67 was higher in group 2, both P<0.05. There was no statistical difference between the values of IL-8 between the groups. Histidine-tryptophan-glutamate solution was better than histidine-tryptophan-alphacetoglutarate solution because it reduced caspase (apoptosis), increased KI-67 (cell proliferation), and showed no difference in IL-8 levels compared to group 1. This suggests that the histidine-tryptophan-glutamate solution was more efficient than the histidine-tryptophan-alphacetoglutarate for the preservation of hearts of rat cardiomyocytes.

Nebivolol Reduces Central Blood Pressure In Stage I Hypertensive Patients: Experimental Single Cohort Study.

Assessment of central blood pressure (BP) has grown substantially over recent years because evidence has shown that central BP is more relevant to cardiovascular outcomes than peripheral BP. Thus, different classes of antihypertensive drugs have different effects on central BP despite similar reductions in brachial BP. The aim of this study was to investigate the effect of nebivolol, a β-blocker with vasodilator properties, on the biochemical and hemodynamic parameters of hypertensive patients. Experimental single cohort study conducted in the outpatient clinic of a university hospital. Twenty-six patients were recruited. All of them underwent biochemical and hemodynamic evaluation (BP, heart rate (HR), central BP and augmentation index) before and after 3 months of using nebivolol. 88.5% of the patients were male; their mean age was 49.7 ± 9.3 years and most of them were overweight (29.6 ± 3.1 kg/m2) with large abdominal waist (102.1 ± 7.2 cm). There were significant decreases in peripheral systolic BP (P = 0.0020), diastolic BP (P = 0.0049), HR (P < 0.0001) and central BP (129.9 ± 12.3 versus 122.3 ± 10.3 mmHg; P = 0.0083) after treatment, in comparison with the baseline values. There was no statistical difference in the augmentation index or in the biochemical parameters, from before to after the treatment. Nebivolol use seems to be associated with significant reduction of central BP in stage I hypertensive patients, in addition to reductions in brachial systolic and diastolic BP.

Biochemical, Anthropometric And Body Composition Indicators As Predictors Of Hepatic Steatosis In Obese Adolescents.

To describe the prevalence of hepatic steatosis and to assess the performance of biochemical, anthropometric and body composition indicators for hepatic steatosis in obese teenagers. Cross-sectional study including 79 adolecents aged from ten to 18 years old. Hepatic steatosis was diagnosed by abdominal ultrasound in case of moderate or intense hepatorenal contrast and/or a difference in the histogram ≥7 on the right kidney cortex. The insulin resistance was determined by the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) index for values >3.16. Anthropometric and body composition indicators consisted of body mass index, body fat percentage, abdominal circumference and subcutaneous fat. Fasting glycemia and insulin, lipid profile and hepatic enzymes, such as aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase and alkaline phosphatase, were also evaluated. In order to assess the performance of these indicators in the diagnosis of hepatic steatosis in teenagers, a ROC curve analysis was applied. Hepatic steatosis was found in 20% of the patients and insulin resistance, in 29%. Gamma-glutamyltransferase and HOMA-IR were good indicators for predicting hepatic steatosis, with a cutoff of 1.06 times above the reference value for gamma-glutamyltransferase and 3.28 times for the HOMA-IR. The anthropometric indicators, the body fat percentage, the lipid profile, the glycemia and the aspartate aminotransferase did not present significant associations. Patients with high gamma-glutamyltransferase level and/or HOMA-IR should be submitted to abdominal ultrasound examination due to the increased chance of having hepatic steatosis.

Urinary Tract Infection In Renal Transplant Recipients: Incidence, Risk Factors, And Impact On Graft Function.

Urinary tract infection (UTI) is the most common infection posttransplant. However, the risk factors for and the impact of UTIs remain controversial. The aim of this study was to identify the incidence of posttransplant UTIs in a series of renal transplant recipients from deceased donors. Secondary objectives were to identify: (1) the most frequent infectious agents; (2) risk factors related to donor; (3) risk factors related to recipients; and (4) impact of UTI on graft function. This was a retrospective analysis of medical records from renal transplant patients from January to December 2010. Local ethics committee approved the protocol. The incidence of UTI in this series was 34.2%. Risk factors for UTI were older age, (independent of gender), biopsy-proven acute rejection episodes, and kidneys from deceased donors (United Network for Organ Sharing criteria). For female patients, the number of pretransplant pregnancies was an additional risk factor. Recurrent UTI was observed in 44% of patients from the UTI group. The most common infectious agents were Escherichia coli and Klebsiella pneumoniae, for both isolated and recurrent UTI. No difference in renal graft function or immunosuppressive therapy was observed between groups after the 1-year follow-up. In this series, older age, previous pregnancy, kidneys from expanded criteria donors, and biopsy-proven acute rejection episodes were risk factors for posttransplant UTI. Recurrence of UTI was observed in 44%, with no negative impact on graft function or survival.

Frequency Of The Allelic Variant C.1150t > C In Exon 10 Of The Fibroblast Growth Factor Receptor 3 (fgfr3) Gene Is Not Increased In Patients With Pathogenic Mutations And Related Chondrodysplasia Phenotypes.

Mutations in the FGFR3 gene cause the phenotypic spectrum of FGFR3 chondrodysplasias ranging from lethal forms to the milder phenotype seen in hypochondroplasia (Hch). The p.N540K mutation in the FGFR3 gene occurs in ∼70% of individuals with Hch, and nearly 30% of individuals with the Hch phenotype have no mutations in the FGFR3, which suggests genetic heterogeneity. The identification of a severe case of Hch associated with the typical mutation c.1620C > A and the occurrence of a c.1150T > C change that resulted in a p.F384L in exon 10, together with the suspicion that this second change could be a modulator of the phenotype, prompted us to investigate this hypothesis in a cohort of patients. An analysis of 48 patients with FGFR3 chondrodysplasia phenotypes and 330 healthy (control) individuals revealed no significant difference in the frequency of the C allele at the c.1150 position (p = 0.34). One patient carrying the combination `pathogenic mutation plus the allelic variant c.1150T > C' had a typical achondroplasia (Ach) phenotype. In addition, three other patients with atypical phenotypes showed no association with the allelic variant. Together, these results do not support the hypothesis of a modulatory role for the c.1150T > C change in the FGFR3 gene.

Effect Of Sodium Hypochlorite And Peracetic Acid On The Surface Roughness Of Acrylic Resin Polymerized By Heated Water For Short And Long Cycles.

To evaluate the surface roughness of acrylic resin submitted to chemical disinfection via 1% sodium hypochlorite (NaClO) or 1% peracetic acid (C2H4O3). The disc-shaped resin specimens (30 mm diameter ×4 mm height) were polymerized by heated water using two cycles (short cycle: 1 h at 74°C and 30 min at 100°C; conventional long cycle: 9 h at 74°C). The release of substances by these specimens in water solution was also quantified. Specimens were fabricated, divided into four groups (n = 10) depending on the polymerization time and disinfectant. After polishing, the specimens were stored in distilled deionized water. Specimens were immersed in 1% NaClO or 1% C2H4O3 for 30 min, and then were immersed in distilled deionized water for 20 min. The release of C2H4O3 and NaClO was measured via visual colorimetric analysis. Roughness was measured before and after disinfection. Roughness data were subjected to two-way ANOVA and Tukey's test. There was no interaction between polymerization time and disinfectant in influencing the average surface roughness (Ra, P = 0.957). Considering these factors independently, there were significant differences between short and conventional long cycles (P = 0.012), but no significant difference between the disinfectants hypochlorite and C2H4O3 (P = 0.366). Visual colorimetric analysis did not detect release of substances. It was concluded that there was the difference in surface roughness between short and conventional long cycles, and disinfection at acrylic resins polymerized by heated water using a short cycle modified the properties of roughness.

Pain Threshold And Sleep Quality In Women With Endometriosis.

Pain is a common complaint in women with endometriosis and can be influenced by many variables, including sleep disorders; however, no data are available on the sleep quality of women with endometriosis or on the correlation between sleep quality and pain. The 510 volunteers included in this study were divided into two groups: 257 women with a laparoscopic and histopathological diagnosis of endometriosis and 253 women with no history of endometriosis and no endometriosis-related symptoms. The volunteers answered two questionnaires: the Post-Sleep Inventory to evaluate sleep quality and the International Physical Activity Questionnaire to assess their level of physical activity. Pain was evaluated using a visual analogue scale (VAS) and women were also submitted to a physical examination, during which their pain threshold was assessed at 20 different body sites. Sleep quality was significantly poorer in women with endometriosis compared to women without the disease. The pain threshold was significantly lower in the greater trochanter and abdomen in women with endometriosis when compared to women without the disease; however, there was no difference in VAS pain score between the groups. The higher the VAS pain score, the lower the Post-Sleep Inventory score. Additionally, there was a significant positive correlation between the pain threshold at some body sites and sleep quality. Sleep quality was poorer and the pain threshold at certain body sites was lower in the group of women with endometriosis.

Efficacy And Safety Of Intravitreal Bevacizumab In Eyes With Neovascular Glaucoma Undergoing Ahmed Glaucoma Valve Implantation: 2-year Follow-up.

To evaluate the efficacy and safety of intravitreal bevacizumab (IVB) in eyes with neovascular glaucoma (NVG) undergoing Ahmed glaucoma valve (AGV) implantation. This was a multicentre, prospective, randomized clinical trial that enrolled 40 patients with uncontrolled neovascular glaucoma that had undergone panretinal photocoagulation and required glaucoma drainage device implantation. Patients were randomized to receive IVB (1.25 mg) or not during Ahmed valve implant surgery. Injections were administered intra-operatively, and 4 and 8 weeks after surgery. After a mean follow-up of 2.25 ± 0.67 years (range 1.5-3 years), both groups showed a significant decrease in IOP (p < 0.05). There was no difference in IOP between groups except at the 18-month interval, when IOP in IVB group was significantly lower (14.57 ± 1.72 mmHg vs. 18.37 ± 1.06 mmHg - p = 0.0002). There was no difference in survival success rates between groups. At 24 months, there was a trend to patients treated with IVB using less antiglaucoma medications than the control group (p = 0.0648). Complete regression of rubeosis iridis was significantly more frequent in the IVB group (80%) than in the control group (25%) (p = 0.0015). Intravitreal bevacizumab may lead to regression of new vessels both in the iris and in the anterior chamber angle in patients with neovascular glaucoma undergoing Ahmed glaucoma valve implantation. There is a trend to slightly lower IOPs and number of medications with IVB use during AGV implantation for neovascular glaucoma.

The Influence Of Body Weight On Sexual Function And Quality Of Life In Women With Polycystic Ovary Syndrome.

To assess sexual function (SF) and quality of life (QOL) in women with polycystic ovary syndrome (PCOS). A cross-sectional study was conducted to assess 56 women with PCOS and 102 control women with regular menstrual cycles. To assess SF and QOL in Brazilian women with PCOS with Female Sexual Function Index (FSFI) and the WHOQOL-bref questionnaires. Women with PCOS had a worse evaluation to arousal, lubrication, satisfaction, pain and total FSFI, and there was no difference in sexual desire and orgasm. Besides, they had a worse evaluation concerning health status than controls. The body mass index was inversely correlated to the QOL, especially to the physical, psychological, environment aspects and self-assessment of QOL, but it did not show correlation to the SF. Women with PCOS had a worse sexual function and self-assessment of health condition in comparison to controls. The body weight as isolated symptom was correlated to the worsening in quality of life, but not with the worsening of sexual function.

P16(ink) (4a) Expression As A Potential Marker Of Low-grade Cervical Intraepithelial Neoplasia Progression.

To evaluate p16(INK) (4a) immunoexpression in CIN1 lesions looking for differences between cases that progress to CIN2/3 maintain CIN1 diagnosis, or spontaneously regress. Seventy-four CIN1 biopsies were studied. In the follow-up, a second biopsy was performed and 28.7% showed no lesion (regression), 37.9% maintained CIN1, and 33.4% progressed to CIN2/3. Immunostaining for p16(INK) (4a) was performed in the first biopsy and it was considered positive when there was strong and diffuse staining of the basal and parabasal layers. Pearson's chi-square was used to compare the groups (p ≤ 0.05). The age of the patients was similar. There was no significant difference in p16(INK) (4a) immunoexpression in the groups, however, statistical analyses showed a significant association when only the progression and regression groups were compared (p = 0.042). Considering p16(INK) (4a) positivity and the progression to CIN2/3, the sensitivity, specificity, positive, and negative predictive values in our cohort were 45%, 75%, 47%, and 94%, respectively. We emphasize that CIN1 with p16(INK) (4a) staining was associated with lesion progression, but the sensitivity was not high. However, the negative predictive value was more reliable (94%) and p16(INK) (4a) may represent a useful biomarker that can identify CIN1 lesions that need particular attention, complementing morphology.