Feasibility, safety, and preliminary proof of principles of autologous neural stem cell treatment combined with T-cell vaccination for ALS patients

Uncontrolled activation of the innate immune system promotes the deterioration of neurons in different neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). T-cell vaccination (TCV) was developed by Irun Cohen and coworkers at the Weizmann Institute of Science (Israel) during the late 1970s and has been demonstrated to be an effective treatment for human autoimmune diseases and a regulator of macrophage activation in animal models. We treated seven ALS patients with this cell therapy and were able to slow or stop disease progression in the affected individuals. The median survival, which is 3.5 years, was extended to 6 years. They were also treated with autologous adult neural stem cells associated with effector T cells. The observed neurologic improvements after treatment lasted for at least 1 year. Clinical recovery in the treated ALS patients was confirmed by an independent, skilled neurologist using the ALS Functional Rating Scale-Revised (ALSFRS-R). TCV in conjunction with an autologous neural stem cell treatment might be a feasible, minimally invasive, safe, and effective approach to obtain enduring therapeutic effects in ALS patients.     

Prevalence of lower urinary tract symptoms in school-age children

Epidemiological studies have demonstrated rates of incontinence and enuresis as high as 20% in school-age children. This cross-sectional study aimed to investigate the prevalence of lower urinary tract (LUT) symptoms in 739 children aged 6–12 years enrolled in three government schools with different socioeconomic levels in Minas Gerais, Brazil. Symptoms of LUT were evaluated using a modified version of the Dysfunction Voiding Scoring System in which the cutoff point considered as an indicator of LUT dysfunction is >6 for girls and >9 for boys. Children with a score indicative of symptoms received an educational booklet on the functioning of the LUT and were sent for clinical evaluation. LUT dysfunction symptoms were detected in 161 (21.8%) children. Symptoms were most frequent in girls (p < 0.001), children aged 6–8 (p < 0.028), and attended the school with the lowest social level (p < 0.001). Intestinal constipation was the most prevalent finding (30.7%), independent of LUT score. The most common urinary symptoms in children with an elevated score were diurnal urinary incontinence (30.7%), holding maneuvers (19.1%), and urinary urgency (13.7%). Stress factors were associated in 28.4% of children. Our findings suggest that LUT symptoms must be investigated carefully at routine pediatric visits.     

Time response of rat testicular alterations induced by cryptorchidism and orchiopexy

Cryptorchidism is one of the main risk factors for infertility and testicular cancer. Orchiopexy surgery corrects cryptorchidism effects. Different models of cryptorchidism developed in the rat include surgery. We assessed testicular alterations in rats submitted to surgical cryptorchidism and examined their potential for reversibility at different time points in order to verify time dependency effect(s) on the recovery of the undescended testes. Cryptorchidism was induced in 3‐week‐old rats. Animals were euthanized 3, 6 or 11 weeks after surgery to evaluate the morphological progression of cryptorchidism‐induced germinative epithelial alterations. Other groups underwent orchiopexy 3, 5 or 9 weeks after surgical cryptorchidism, before or after puberty. Animals were euthanized 3 or 8 weeks after orchiopexy. Controls underwent sham surgery at the same time points as the surgical groups. Cryptorchid testes showed decreased weight, germinative epithelial degeneration, apoptosis and vacuolation, corresponding to impairment of spermatogenesis and of Sertoli cells. Some tubules has a Sertoli cell‐only pattern and atrophy. The intensity of damage was related to the duration of cryptorchidism. After orchiopexy, spermatogenesis completely recovered only when testicular relocation occurred before puberty and the interval for recovery was extended. These results indicate that age, sexual maturity and extension of germ cell damage were relevant for producing germ cell restoration and normal spermatogenesis. We provide original observations on the time dependency of testicular alterations induced by cryptorchidism and their restoration using morphologic, morphometric and immunohistochemical approaches. It may be useful to study germ cell impairment, progression and recovery in different experimental settings, including exposure to exogenous chemicals.     

Clinical and magnetic resonance imaging patterns of extensive Chikungunya virus–associated myelitis

Journal of NeuroVirology - Chikungunya fever is an arbovirus infection transmitted by the same mosquito vector of dengue and Zika virus. Besides high fever, common clinical symptoms include...     

Antifolates inhibit Cryptococcus biofilms and enhance susceptibility of planktonic cells to amphotericin B

The Cryptococcus neoformans species complex contains the most important agents of fungal meningoencephalitis. Therapeutic choices are limited and issues related to toxicity and resistance to antifungals have been described. The present study evaluated the inhibitory effect of the antifolate combinations sulfamethoxazole–trimethoprim (SMX/TMP) and sulfadiazine–pyrimethamine (SDZ/PYR) against planktonic cells and biofilms of C. neoformans and C. gattii. The influence of the antifolate combinations on the amphotericin minimum inhibitory concentration (MIC) of planktonic cells was also investigated. In addition, the effect of these combinations on the cellular ergosterol content of planktonic cells was studied. Strains of C. neoformans (n?=?15) and C. gattii (n?=?15) obtained from environmental or clinical sources were evaluated by the broth microdilution method. SMX/TMP and SDZ/PYR showed antifungal activity against free living cells and sessile cells of Cryptococcus spp. Moreover, planktonic cells showed increased susceptibility to amphotericin B after pre-incubation with sub-inhibitory concentrations of SMX/TMP or SDZ/PYR. The drug combinations SMX/TMP and SDZ/PYR were able to prevent the biofilm formation and showed inhibitory effect against mature biofilms of both species. Additionally, the study showed that antifolate drugs reduced the ergosterol content in C. neoformans and C. gattii planktonic cells. Our results highlight the antifungal potential of antifolate drugs.     

Real-Time PCR as a Prognostic Tool for Human Congenital Toxoplasmosis

Real-time PCR (qPCR) was positive in 72/150 (48%) blood samples of newborns with congenital toxoplasmosis. Among infants with active retinochoroiditis, 68% had positive qPCR results, while positivity was 29% (P = 0.009) in the absence of ocular involvement. Positive qPCR was associated with the presence of retinochoroidal lesions, with an odds ratio of 2.8.     

Macrophage polarization following chitosan implantation

Macrophages are a key cell in the host response to implants and can be polarized into different phenotypes capable of inducing both detrimental and beneficial outcomes in tissue repair and remodeling, being important in tissue engineering and regenerative medicine. The objective of this study was to evaluate the macrophage response to 3D porous chitosan (Ch) scaffolds with different degrees of acetylation (DA, 5% and 15%). The M1/M2 phenotypic polarization profile of macrophages was investigated in vivo using a rodent air-pouch model. Our results show that the DA affects the macrophage response. Ch scaffolds with DA 5% induced the adhesion of lower numbers of inflammatory cells, being the M2 the predominant phenotypic profile among the adherent macrophages. In the inflammatory exudates F4/80⁺/CD206⁺ cells (M2 macrophages) appeared in higher numbers then F4/80⁺/CCR7⁺ cells (M1 macrophages), in addition, lower levels of pro-inflammatory cytokines together with higher levels of anti-inflammatory cytokines were found. Ch scaffolds with DA 15% showed opposite results, since M1 were the predominant macrophages both adherent to the scaffold and in the exudates, together with high levels of pro-inflammatory cytokines. In conclusion, Ch scaffolds with DA 5% induced a benign M2 anti-inflammatory macrophage response, whereas Ch scaffolds with DA 15% caused a macrophage M1 pro-inflammatory response.