Retinal function after intravitreal injection of autologous bone marrow-derived mesenchymal stromal cells in advanced glaucoma.

PURPOSE: To report electroretinographic (ERG) findings in advanced glaucoma treated with a single intravitreal injection of bone marrow-derived mesenchymal stem cells (MSCs). METHODS: Intravitreal injection of autologous MSCs (1 × 106 cells) was performed in 2 eyes from 2 patients with open-angle glaucoma in advanced stage of optic neuropathy (ClinicalTrials.gov, NCT02330978, 01.05.2015): cup/disk ratio worse than 0.9, visual field mean deviation index lower than - 15 dB, visual acuity of light perception, but controlled intraocular pressure. ERG tests were recorded at baseline and week 1, 4 and 48 after injection, using DTL electrodes following the ISCEV standard: After dark adaptation, ERG was elicited using white flashes of 0.01 cd.s/m2 and 3.0 cd.s/m2, followed by 10-min light adaptation (30 cd/m2) and stimuli of 3.0 cd.s/m2 and 30 Hz flicker. RESULTS: Patients did not show improvement on visual acuity or visual field after treatment. At baseline, ERG responses showed typical findings for advanced glaucoma, with a- and b-wave amplitude and latency within normative range, but reduced photopic negative responses. No noteworthy changes were observed on ERG responses for both cases up to 1 week after treatment, but at day 15, one patient showed retinal detachment with proliferative vitreoretinopathy and was removed from the trial. The other patient kept ERG responses stable throughout study period. CONCLUSION: Although no ERG response changes were observed after MSCs injection in one case, the complication observed on the second one, along with the lack of visual function improvement, warrants further studies involving modified MSCs to treat ocular disorders, including glaucoma. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02330978- missed in pdf.

Impact of farnesol and Corsodyl® on Candida albicans forming dual biofilm with Streptococcus mutans.

OBJECTIVE: This work studied the biofilm formed by Candida albicans and Streptococcus mutans on a hydroxyapatite surface after exposure to the quorum-sensing molecule farnesol (200 µM) in comparison with the diluted mouthwash Corsodyl® (0.0001% chlorhexidine digluconate). MATERIALS AND METHODS: The cytotoxicity of farnesol was evaluated by Galleria mellonella surviving assay. The viability of biofilm cells after exposure to farnesol and Corsodyl® was determined by colony-forming units. The morphology and structure of a dual-species biofilm was evaluated by scanning electron microscopy. RESULTS: Farnesol did not exhibit a toxic effect on larval survival. While 200 µM farnesol effectively reduced the yeast-to-hyphae transition in the dual biofilm, it did not affect the growth of S. mutans. Additionally, despite the presence of farnesol, many blastospores were observed. Corsodyl® reduced S. mutans in the dual biofilm, but did not influence C. albicans. CONCLUSION: This study showed that 200 µM farnesol modulated C. albicans in a dual-species biofilm with S. mutans, but did not exhibit antimicrobial activity against S. mutans. Moreover, it seems that S. mutans provides conditions that support the growth of the yeast form of C. albicans. The mouthwash Corsodyl® reduces S. mutans, but was not effective against C. albicans.

MRI Findings of Desmoplastic Infantile Ganglioglioma: A Case Report and Analysis.

Desmoplastic infantile gangliogliomas (DIG) are rare intracranial tumors that predominantly affect children. They are characterized by a mixture of glial and neuronal components interspersed with abundant fibrous stroma and are typically located on the surface of the cerebral hemispheres. In this case report, we present a seven-year-old male child with a late presentation of DIG, which is typically diagnosed between zero and 60 months of age. We discuss the MRI findings, clinical symptoms, and differential diagnosis of DIG in patients with this central nervous system tumor.

Insights on catheter-related bloodstream infections: a prospective observational study on the catheter colonization and multidrug resistance.

BACKGROUND: Central venous catheter-related bloodstream infection (CRBSI) is a huge public health concern with considerable impact on mortality and health costs. AIM: A three-year observational study enrolling three tertiary hospitals located in Lisbon, Portugal, was designed to identify the major aetiological agents of CRBSI, their ability to colonize central venous catheters and their antimicrobial resistance profiles. METHODS: Aetiological agents of CRBSI were identified by Vitek 2. Whole-genome sequencing was used to confirm CRBSI by the most prevalent aetiological agents and characterize their resistome. Central venous catheter colonization (namely by biofilm assembly) was monitored by scanning electron microscopy. FINDINGS: Staphylococci were the most prevalent causative agent (36/58, 62.0%), with S. aureus and coagulase-negative S. epidermidis accounting for 24.1% and 36.2% of CRBSIs, respectively. Fifty-nine of 72 staphylococci isolates were meticillin resistant. Comparative genomic analysis of central venous catheters/haemoculture pairs of isolates revealed genomic matches for 35 of 36 pairs and a good correlation between antibiotic susceptibility phenotype and the presence of antimicrobial resistance genetic determinants. Biofilms were present on 48.6% of the central venous catheters; nevertheless, no statistically significant association was established between biofilm assembly and CRBSI, and the presence/absence of ica operon and agr groups did not correlate with biofilm phenotypes, highlighting the need for further studies to elucidate biofilms' role on this healthcare-associated infection. CONCLUSION: Whole-genome sequencing was shown to be a valuable tool to confirm CRBSI. Although more than 42.3% of the central venous catheters were colonized by staphylococci, no statistically significant association was found between CRBSI and biofilms.

Quality of education and adolescents' oral health-related behaviours: a multilevel analysis.

PURPOSE: The school environment may positively influence student health behaviours and learning. This study aimed to investigate the association between cities' quality of education and adolescent students' oral health-related behaviours. METHODS: Cross-sectional study using data of the 2015 Brazilian National Adolescent School-Based Health Survey and other public databases. The sample was composed of adolescents (N = 23,674) from public schools of the 27 Brazilian state capitals. Outcomes were four oral health-related behaviours: toothbrushing, sweets and soft-drink consumption, and dental visits. The explanatory variable was the cities' quality of education, measured by the Brazilian Basic Education Development Index. Covariates were individual (sociodemographic) and contextual (socioeconomic, oral health coverage and oral health-promoting schools). Multilevel logistic regression was performed considering two levels: individual (adolescents) and contextual (city). RESULTS: The prevalence of the outcomes were: low daily toothbrushing frequency 6.7% (95% CI 6.0-7.4); high weekly sweets consumption 41.5% (95% CI 40.3-42.7); high weekly soft-drink consumption 28.5% (95% CI 27.2-29.9); and low frequency of annual dental visits 31.2% (95% CI 30.1-32.3). In the adjusted models, cities whose schools had higher scores of education quality were more likely to have students with low toothbrushing frequency and high frequency of sweets consumption. CONCLUSION: The cities' quality of education was associated with unhealthy oral health-related behaviours, particularly the frequency of toothbrushing and sweets consumption. Therefore, appropriate health promotion strategies as well as high-quality education are needed in schools.

Isolation of Histoplasma capsulatum from bats in the urban area of São Paulo State, Brazil.

The presence of bats in caves, attics, ceilings, and roofs is important epidemiologically as they can increase the chance of human acquisition of pathogens, including Histoplasma capsulatum. Brazilian urban areas contain many species of bats, especially insectivorous bats, that are attracted by a wide range of readily available food and shelter. From August 2003 to December 2008, we analysed 2427 bats in the São Paulo State region. Homogenates of the livers and spleens of the bats were plated on specific medium to identify animals infected with H. capsulatum. The fungus was isolated from 87 bats (3·6%). The infected bats were identified as Molossus molossus (74), Nyctinomops macrotis (10), Tadarida brasiliensis (1), Molossus rufus (1) and Eumops glaucinus (1), all insectivorous species. The data presented are a relevant contribution to the epidemiology of H. capsulatum in densely populated urban areas such as in São Paulo State, especially since histoplasmosis is not included in the mandatory disease notification system.

Untreated sewage contamination of beach sand from a leaking underground sewage system.

Thirty people (mostly children) experienced an episode of skin rash days after a sand sifting beach operation at Porto Pim Beach in Faial, Azores during June 2019. An environmental and epidemiologic investigation was conducted to identify the cause of the outbreak of skin rash. The epidemiologic investigation found that some of the patients experiencing symptoms had never entered the beach water. During the pollution period and throughout the epidemiologic investigation, faecal indicator bacteria levels (94 CFU/100 ml for intestinal enterococci and 61 CFU/100 ml for Escherichia coli) in water remained under the limits used for the ninety-five percentile calculation of an Excellent coastal and transitional bathing water defined in the Portuguese Legislation (100 CFU/100 ml for intestinal enterococci and 250 CFU/100 ml for Escherichia coli). Thus sand contact was considered as a likely primary exposure route. Sand microbiological analysis for faecal indicator organisms and electron microscopy strongly suggested faecal contamination. Chemical analysis of the sand also revealed a concomitant substance compatible with sodium-hypochlorite as analysed using gas chromatography and subsequently confirmed by free chlorine analysis. Inspection of the toilet facilities and sewage disposal system revealed a leaking sewage distribution box. Collectively, results suggest that the cause of the outbreak was the leaking underground sewage distribution box that serviced the beach toilet facilities (40 m from beach), where sodium-hypochlorite was used for cleaning and disinfection. This sewage then contaminated the surficial sands to which beach goers were exposed. Chlorine being an irritant substance, was believed to have been the cause of the symptoms given the sudden presentation and dissipation of skin rashes. No gastro-intestinal illness was reported during this episode and during the following 30 days. Like water, beach sand should also be monitored for safety, especially for areas serviced by aged infrastructure.

Effects of donor age on patient survival in liver transplantation: short-and long-term analysis.

BACKGROUND/AIMS: This study aim was to investigate an association between donor age and lower recipient survival in liver transplantation. METHODOLOGY: A total of 178 consecutive patients underwent liver transplantation between 1999 and 2007. Among these patients, 172 liver transplants (donor age: 32.04 +/- 16.66) and 167 recipients were included in the analysis. Mean recipient age was 39.16 +/- 21.61 years (range: 6 mo-71 years) and 90 (53.89%) were males. RESULTS: Among 172 transplants, 32.9% recipients died during follow-up. Mean follow-up time was 34.37 +/- 20.50 mo. A lower mean recipient survival prevailed from donors older than 50 years (p = .01) at 7-year patient survival. At 6-month and 1-year recipient survival, cut-offs were 50 and 55 years, respectively (p < .05). A significant difference was observed in graft survival from donors older than 30 years (p = .02) and at 6-month and 1-year, cutoffs were 35 and 50 years, respectively (p < .05). CONCLUSIONS: Although the utilization of donors with increased age in liver transplantation offers a new option to increase the number of liver transplants it presents lower survivals. Other factors related to graft loss such as MELD score > 15 and longer CIT (cold ischemia time) should be avoided to reduce the risk of using elderly donor grafts.

Trick-or-treat: dietary lipids and host resistance to infectious disease.

The increased intake of omega-6 fatty acids together with the widely use of omega-3 supplements in Western diets can affect the host defence against infectious diseases. In the present review we focused on the impact of these fatty acids on salmonella and mycobacteria infection models in animals or in cell cultures. Particular attention was given to the molecular mechanisms involved.

Cytocompatibility, biofilm assembly and corrosion behavior of Mg-HAP composites processed by extrusion.

In this work the cytocompatibility of pure magnesium and Mg-xHAP composites (x=5, 10 and 15wt%) fabricated by powder metallurgy routes has been investigated. The materials were produced from raw HAP powders with particle mean sizes of 6µm (S-xHAP) or 25µm (L-xHAP). The biocompatibility study has been performed for MC3T3 cells (osteoblasts/osteoclasts) and L929 fibroblasts. The results indicate that S-Mg (pure magnesium), S-10HAP and L-10HAP composites are the materials with the best biocompatibility. The ability of S. aureus bacteria to assemble biofilms was also evaluated. Biofilm formation assays showed that these materials are not particular prone to colonization and biofilm assembly is strain dependent. The corrosion resistance of S-Mg, S-10HAP and L-10HAP materials immersed in the media used for the cells culture has also been analyzed. Different trends in the corrosion resistance have been found: S-Mg and S-10HAP show a very high resistance to corrosion whereas the corrosion of L-10HAP steadily increases with time.

Disturbance chemical cues determine changes in spatial occupation by the convict cichlid Archocentrus nigrofasciatus.

I studied the effect of disturbance chemical cues on fish that make trade-offs between foraging in an open area and remaining in a safe refuge. I used convict cichlids Archocentrus nigrofasciatus that were either visually exposed to a predator (n = 8) or exposed to water conditioned by chemical cues from disturbed conspecifics (n = 8). Fish visually exposed to a predator decreased their ingestion rate and spent more time in the refuge than in the foraging area, while fish receiving water from frightened conspecifics did not alter their ingestion rate or time spent in the refuge and foraging site, but increased their spatial occupation (i.e., motion). These results suggest that convict cichlids recognized the predator by visual cues. Moreover, disturbance cues are a form of threatening public information that may increase fish spatial occupation due to increased exploring behaviour; but is not sufficiently alarming to alter feeding or increase refuge use.

[Predictive factors of hospital and 6-month morbidity and mortality in hospitalized elderly patients]. / Factores preditivos de morbilidade e mortalidade hospitalar e aos seis meses em doentes idosos hospitalizados.

This article presents the results of a prospective multivariable study of elderly patients aged over 70 years, hospitalized in an Internal Medicine Department of a Central Lisbon Hospital. The study aimed to identify, at the beginning of hospital admission (HA), predictive factors of hospital mortality (HM) and mortality at 6 months, of duration of HA, of admission to a nursing home at the time of discharge and during a period of 6 months thereafter and of hospital readmission during the 6 months following discharge. The study included 158 patients with a mean hospital stay of 15 days and a hospital mortality of 12%. The main pathologies responsible for hospital admission were cerebrovascular accident (22%), heart failure (20%) and pneumonia (16%). Mortality at 6 months was 29% and hospital readmission in the 6 months thereafter was 24%. When the patient was cared for by the spouse there was a statistically significant correlation with a shorter duration of admission (p = 0.006). Mean hospital stay was not significantly associated with any other variable. A subjective medical evaluation (SME) at the start of HA (p = 0.001), a low Barthel score prior to and at the time of HA, low serum albumin (p = 0.001) and a high leucocyte count (p = 0.005) were correlated with a higher HM. Nursing home admission was only positively correlated with cerebrovascular pathology. Mortality at 6 months was significantly correlated with the SME (p = 0.001), a low Barthel score prior to admission (p < 0.008) and at the time of HA (p < 0.001), nursing home residency (p < 0.005) and a low mental test score (p < 0.01). Hospital readmission at 6 months was influenced by the SME (p < 0.04) and by the reduction in the Barthel score caused by the illness and HA (p = 0.004). These correlations enabled the development of mathematical models that predict HM and mortality at 6 months and admission to a nursing home at the time of discharge and during a period of 6 months thereafter. They could be important in identifying elderly patients' needs early in the hospital admission and in the improvement of the strategy necessary for a successful and dignified hospital discharge.

GidB mutation as a phylogenetic marker for Q1 cluster Mycobacterium tuberculosis isolates and intermediate-level streptomycin resistance determinant in Lisbon, Portugal.

Development of streptomycin resistance in Mycobacterium tuberculosis is usually associated with mutations in rpsL and rrs genes, although up to 50% of clinical streptomycin-resistant isolates may present no mutation in either of these genes. In the present report we investigate the role of gidB gene mutations in streptomycin resistance. We have analyzed 52 streptomycin-resistant and 30 streptomycin-susceptible Mycobacterium tuberculosis clinical isolates by sequencing and endonuclease analysis of the gidB and rpsL genes. All clinical isolates were genotyped by 12-loci MIRU-VNTR. The gidB gene of 18 streptomycin-resistant isolates was sequenced and four missense mutations were found: F12L (1/18), L16R (18/18), A80P (4/18) and S100F (18/18). The remaining isolates were screened by endonuclease analysis for mutations A80P in the gidB gene and K43R in the rpsL gene. Overall, mutation A80P in the gidB gene was found in eight streptomycin-resistant isolates and 11 streptomycin-susceptible multidrug-resistant isolates. Also noteworthy, is the fact that gidB mutations were only present in isolates without rpsL and rrs mutations, all from genetic cluster Q1. Streptomycin quantitative drug susceptibility testing showed that isolates carrying the gidB A80P mutation were streptomycin intermediate-level resistant and that standard drug susceptibility testing yielded inconsistent results, probably due to borderline resistance. We conclude that gidB mutations may explain the high number of streptomycin-resistant strains with no mutation in rpsL or rrs. These mutations might occasionally confer low-level streptomycin resistance that will go undetected in standard susceptibility testing.

First isolation and genotyping of Toxoplasma gondii from bats (Mammalia: Chiroptera).

There are currently no reports on the isolation and molecular examination of Toxoplasma gondii from bats. Here, we report the isolation and genotypic characterisation of two T. gondii isolates from bats. A total of 369 bats from different municipalities in São Paulo state, southeastern Brazil, were captured and euthanised, and collected tissues (heart and pectoral muscle) were processed for each bat or in pools of two or three bats and bioassayed in mice (a total of 283 bioassays). Eleven PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) markers were used to genotype positive samples: SAG1, SAG2 (5'-3'SAG2 and alt. SAG2), SAG3, BTUB, GRA6, L358, c22-8, c29-2, PK1, CS3 and Apico. The parasite was isolated from two bats from São Paulo city: an insectivorous bat, the velvety free-tailed bat Molossus molossus, and a hematophagous bat, the common vampire bat Desmodus rotundus. Isolates were designated TgBatBr1 and TgBatBr2, respectively. The genotype of the isolate from M. molossus (TgBatBr1) has been previously described in an isolate from a capybara from São Paulo state, and the genotype from the D. rotundus isolate (TgBatBr2) has already been identified in isolates from cats, chickens, capybaras, sheep, a rodent and a common rabbit from different Brazilian states, suggesting that this may be a common T. gondii lineage circulating in some Brazilian regions. Isolation of T. gondii from a hematophagous species is striking. This study reveals that bats can share the same isolates that are found in domesticated and wild terrestrial animals. This is the first report of the isolation and genotyping of T. gondii in chiropterans.

Donor age as a predictor of risk for short-term outcomes after liver transplant.

OBJECTIVES: To investigate an association between short-term mortality and donor age-associated worst outcomes in liver transplant. MATERIALS AND METHODS: A total of 178 consecutive patients underwent a liver transplant between 1999 and 2007. Among these patients, there were 172 liver transplants (donor age, 32.04 +/- 16.66; range, 2-65 years) and 167 recipients. Mean recipient age was 39.16 +/- 21.61 years (range, 6 months to 71 years), and 90 were males (53.8%). RESULTS: Among 172 transplants, 32.9% recipients died during follow-up (mean, 34.37 +/- 20.50 months). A lower mean recipient and graft survival occurred in donors older than 50 years (P = .01) and 30 years (P = .02) at 7-year patient survival. At 6- month and 1-year recipient survival, cutoffs were 50 and 55 years (P < .05). Log-rank test showed no statistical difference among recipients, and graft survival from donors older/younger 50 and 30 years 1.5 years after liver transplant (P < .565 and P < .259). CONCLUSIONS: Donor age is a key factor in liver transplant that carries prognostic impact in the recipients. Our data suggest that its harmful effects are exclusively elicited during the short-term, postoperative phase. We recommend careful and distinct management of recipients receiving grafts from elderly donors up to 1.5 years after liver transplant. Changes in the current early postoperative management of this selected group are encouraged.

Differential distribution of transforming growth factor beta and receptors in the hyper or hypoproliferative gastric mucosa of developing and adult rats.

Transforming growth factor beta (TGFbeta) isoforms are known for their antiproliferative effect on epithelial cells in vitro, but the role of each isoform in vivo is poorly understood, mainly when non-pathological conditions are considered. We correlated the presence and distribution of isoforms and receptors to physiological changes in gastric cell proliferation in developing and adult rats. We used fasting to induce either the hyper (14-day-old pups) or hypoproliferation (60-day-old rats) of the gastric epithelium. In 14-d-old pups fasting reduced only TGFbeta3 labelling in the gland. Conversely, in 60-d-old rats there was an increase of TGFbeta1 and TGFbeta3 immunolabelled cells. Receptors were detected at both ages. Therefore, the changes induced by fasting in the constitutive TGFbeta expression can be correlated to the differential epithelial proliferation in the stomach of developing and adult rats. These results suggest that one of the functional roles of TGFbeta in vivo is to locally regulate cell proliferation.

Estudo comparativo dos resultados das provas da prono-posiçäo em quarto escuro em indivíduos sentados e em decúbito horizontal ventral / Comparative analysis of the results of dark room prone provocative test of patients in sitting and ventral decubitus positions

Objetivo: Investigar os resultados das provas de prono-posiçäo em quarto escuro (PPQE) em indivíduos sentados e em decúbito horizontal ventral. Material e Métodos: Foram estudados 30 olhos de 15 pacientes portadores de glaucoma. As provas da PPQE foram realizadas nas duas posiçöes (sentado e deitado) com intervalo de 24 horas. Resultados: A média e o desvio padräo da diferença entre as pressöes intra-oculares finais e iniciais, do olho direito na posiçäo sentado foi de 4.13 ñ 1.77 mmHg e na posiçäo de decúbito horizontal ventral foi de 4.40 ñ 1.69 mmHg. No olho esquerdo na posiçäo sentado foi 4.13 ñ 1.69 mmHg e na posiçäo de decúbito horizontal ventral foi de 4.47 ñ 2.07 mmHg. Conclusäo: Näo foram encontradas diferenças estatísticamente significantes, entre as posiçöes sentado e em decúbito horizontal ventral, nos resultados da PPQE.