Socioeconomic inequalities in dental visits among high school students in Chile, years 2013 and 2017.

OBJECTIVE: To analyze prevalence changes in dental visits and socioeconomic inequalities among high school students in Chile, years 2013 and 2017. METHODS: Analysis of nationally representative data from 2013 and 2017 waves of the Chilean National Socioeconomic Characterization Survey (CASEN). In a sample of high school students aged 14 to 20 years old (n=12699 in 2013; n=11122 in 2017) we investigated prevalence of dental visits in the last 3 months, by urban-rural residence, sex, type of health insurance, type of school, income level and benefit of dental care at school. For inequality analysis we estimated prevalence ratio of dental visits in the last 3 months according to study variables. RESULTS: There was a significant increase in the prevalence of dental visits in the last 3 months and the receipt of dental care at school between years 2013 and 2017. The highest prevalence of dental visits in the last 3 months was found among students living in urban residence, women, with private insurance, in the highest income level, that attended private schools. Inequalities persist but the gap associated with type of residence, health insurance and between the lowest income quintiles decreased over the years. CONCLUSIONS: The Comprehensive Dental Care for senior year high school students, a public policy that began in 2015 in Chile, could have aided the gap reduction and the increase in visits to the dentist in the last 3 months in this group.

Evaluation of the Antimicrobial Effect on Enterococcus Faecalis of Bioceramic Cements with and without Silver Nanoparticles.

OBJECTIVE: To compare the antimicrobial effect of bioceramic endodontic cements with and without silver nanoparticles on Enterococcus faecalis. MATERIALS AND METHODS: Six groups were evaluated (n=8), and divided according to the materials: MTA Flow + AgNP ; MTA Flow Group; Bio C Repair + AgNP; Bio C Repair; PBS Cimmo + AgNP; PBS Cimmo. The groups were maintained for 72 h in the suspension of Enterococcus faecalis in Simulated Body Fluid (SBF). Samples of 100 µL were removed from the suspension at 0, 24, 48 and 72 h and seeded in triplicate in a Petri dish. Colony forming units (CFU) were counted using a colony counter. All procedures described were performed in a laminar flow chamber. Two-way ANOVA followed by Tukey's post hoc test and paired t-test were used for statistical analyses (α = 0.05). RESULTS: The addition of silver nanoparticles resulted in a statistically significant difference for MTA and CIMMO PBS cements (p⟨0.05), with the lowest bacterial growth being shown by the MTA group. For all groups, only the times of 48 and 72 h presented results without differences. CONCLUSION: The addition of silver nanoparticles to bioceramic cements was efficient to promote an acceleration of bacterial death.

Maternofetal outcomes in early-onset gestational diabetes: does weight gain matter?

AIM: Women with early-onset gestational diabetes mellitus (GDM) have overall lower gestational weight gain (GWG) compared to those with later-onset GDM, albeit with usually worse maternofetal outcomes. We intent to investigate the association between inadequate GWG and maternofetal outcomes in pregnant women with early-onset GDM. METHODS: We performed a retrospective study of women with early-onset GDM based on the National Registry of GDM. Three study groups were defined according to the recommendations of the Institute of Medicine for GWG: excessive GWG (eGWG), adequate (aGWG) or insufficient (iGWG). RESULTS: A total of 8040 pregnant women were included: 27% (n = 2170) eGWG, 31% (n = 2492) aGWG and 42% (n = 3378) iGWG. Preeclampsia (4.3 vs 3 vs 1.6%, p < 0.001), polyhydramnios (3.1 vs 2.3 vs 1.8%, p = 0.008) and cesarean section (37.4 vs 34.1 vs 29.5%, p < 0.001) were significantly more frequent among women with eGWG. Additionally, there was a higher frequency of macrosomia (8.1 vs 3.6 vs 2.4%, p < 0.001), large-for-gestational-age (8.2 vs 3.7 vs 2.6%, p < 0.001) and birth trauma (2.6 vs 1.5 vs 1.1%, p < 0.001) in this group. On the other hand, fetal death (0.2 vs 0.2 vs 0.5%, p = 0.04), small-for-gestational-age (9 vs 10.3 vs 14.9, p < 0.001) and preterm delivery (5.6 vs 7.1 vs 7.5%, p = 0.03) were more frequent in iGWG group. CONCLUSIONS: Over two-thirds of pregnant women with early-onset GDM had inappropriate GWG, which was significantly associated with adverse maternofetal outcomes. Weight management must be a focus of special attention in women with early-onset GDM, beyond glycemic control, to achieve healthy pregnancy outcomes.

Acquired hepatocerebral degeneration and hepatic encephalopathy: one or two entities?

BACKGROUND AND PURPOSE: Acquired hepatocerebral degeneration (AHD) and hepatic encephalopathy (HE) are neurological complications of chronic liver disease (CLD) with portosystemic shunt. While HE is common, AHD is a rare entity, and the clinical imaging relationships observed in small series lack validation in large patient cohorts. The aim of this study was to characterize a cohort of AHD patients and to explore possible associations with HE coexistence. METHODS: We performed a retrospective analysis of patients with a working AHD diagnosis, between 2008 and 2019. Clinical, laboratory, imaging and neuropsychological results at first neurological observation were reviewed and compared between the 'AHD' group and the 'AHD with HE' group. RESULTS: A total of 76 patients were recruited. The most frequent neurological manifestations were neuropsychiatric (93.4%) and extrapyramidal (84.2%). Only 38% of patients had hypermanganesemia. Compared with the AHD group, the AHD with HE group had more hyperkinetic movement disorders (71.4% vs. 38.5%; P = 0.05), a higher number of patients on the dementia spectrum (57.7% vs. 20%; P = 0.04), higher median ammonia levels (P = 0.014) and more widespread cortico-subcortical and pyramidal involvement on brain magnetic resonance imaging. Nineteen patients underwent liver transplantation, with significantly improved survival (P = 0.006). DISCUSSION: Hepatic encephalopathy and AHD often coexist in the same patient. Seventy-six patients with CLD and AHD were evaluated, making this one of the largest reported AHD cohorts. Blood manganese level was a weak diagnostic marker in AHD. Early liver function restoration through liver transplantation improved survival. Our report provides a detailed description of the phenotype and long-term outcome of AHD, with relevance for diagnosis and treatment.

Comprehensive germline mutation analysis and clinical profile in a large cohort of Brazilian xeroderma pigmentosum patients.

BACKGROUND: Xeroderma pigmentosum (XP) patients present a high risk of developing skin cancer and other complications at an early age. This disease is characterized by mutations in the genes related to the DNA repair system. OBJECTIVES: To describe the clinical and molecular findings in a cohort of 32 Brazilian individuals who received a clinical diagnosis of XP. METHODS: Twenty-seven families were screened for germline variants in eight XP-related genes. RESULTS: All patients (N = 32) were diagnosed with bi-allelic germline pathogenic or potentially pathogenic variants, including nine variants previously undescribed. The c.2251-1G>C XPC pathogenic variant, reported as the founder mutation in Comorian and Pakistani patients, was observed in 15 cases in homozygous or compound heterozygous. Seven homozygous patients for POLH/XPV variants developed their symptoms by an average age of 7.7 years. ERCC2/XPD, DDB2/XPE and ERCC5/XPG variants were found in a few patients. Aside from melanoma and non-melanoma skin tumours, a set of patients developed skin sebaceous carcinoma, leiomyosarcoma, angiosarcoma, mucoepidermoid carcinoma, gastric adenocarcinoma and serous ovarian carcinoma. CONCLUSIONS: We reported a high frequency of XPC variants in 32 XP Brazilian patients. Nine new variants in XP-related genes, unexpected non-skin cancer lesions and an anticipation of the clinical manifestation in POLH/XPV cases were also described.

Front propagation steered by a high-wavenumber modulation: Theory and experiments.

Homogeneously driven dynamical systems exhibit multistability. Depending on the initial conditions, fronts present a rich dynamical behavior between equilibria. Qualitatively, this phenomenology is persistent under spatially modulated forcing. However, the understanding of equilibria and front dynamics organization is not fully established. Here, we investigate these phenomena in the high-wavenumber limit. Based on a model that describes the reorientation transition of a liquid crystal light valve with spatially modulated optical forcing and the homogenization method, equilibria and fronts as a function of forcing parameters are studied. The forcing induces patterns coexisting with the uniform state in regions where the system without forcing is monostable. The front dynamics is characterized theoretically and numerically. Experimental results verify these phenomena and the law describing bistability, showing quite good agreement.

[Evaluation of HIV epidemic in Chile. A statement of the Chilean Academy of Medicine]. / Evaluación de la infección por VIH en Chile: pronunciamiento del Comité VIH de la Academia Chilena de Medicina.

The Chilean Academy of Medicine convened a commission to evaluate the status of HIV epidemic and the national response to it, regarding its achievements, gaps and challenges, aiming to recommend actions to optimize assessment quality and national response. This publication summarizes the agreed upon opinion of its members. The epidemic is overwhelmingly sexually transmitted, predominant in homo/bisexual men. Vertical transmission is very low. An increasing number of new diagnoses is occurring, with relative over representation of foreign people lately. There is a legal guarantee of confidentiality, nondiscrimination and treatment for those affected, both in the private and public sector. All public health services have active HIV care units. Modern antiviral drugs and monitoring tests are also available. Despite these clear achievements, insufficient, occasionally inadequate public policies and certain rigid regulations thwart optimal effectivity and efficiency of the programs, contributing to the slow and incomplete compliance with international commitments. Shortcomings worth highlighting are: suboptimal educational and preventive programs directed to youngsters, vulnerable and general population; persistent underdiagnosis of infected population; cumbersome requirements to request and inform diagnostic tests, thus discouraging testing; excessive centralization and long latency of diagnosis confirmation and monitoring tests; incomplete epidemiologic analysis and public reporting of findings; non flexibility and slow updating of therapeutic guidelines; insufficient adaptation of care and drug delivery modalities to patients' needs; excessive administrative requirements at care centers and restrictive legislation for outcome and interventional clinical research. Recommendations to deal with these issues were proposed.

[Acute perforated appendicitis with pre-surgical diagnosis and bilateral inguinal hernia in preterm infants]. / Apendicitis aguda perforada con diagnóstico prequirúrgico y hernia inguinal bilateral en recién nacido de pretérmino.

INTRODUCTION: Acute neonatal appendicitis is a rare pathology, with few reports in the last 30 years. Since its clinical presentation and imaging studies are non-specific, most cases are diagnosed during a surgical pro cedure. OBJECTIVE: To describe a neonatal case of acute perforated appendicitis associated with later appearance of inguinal hernia, with pre-surgical diagnosis and treated through laparoscopy. CLINICAL CASE: A 17-day-old preterm female newborn presented with fever, irritability, and increased milk intolerance. Physical examination showed abdominal distention, tenderness and both, abdominal X- ray and ultrasound showed compatible images with acute perforated appendicitis. Once the diagnosis was confirmed, we performed an appendicectomy through laparoscopy. Two weeks later, during an outpatient visit, we observed a bilateral inguinal hernia which was confirmed by ultrasound, and then it was surgically corrected. CONCLUSION: Acute appendicitis should be considered within the differential diagnosis in neonates with acute abdominal symptoms, mainly in premature infants. In this case, ultrasound scan allowed us to make the pre-operative diagnosis. The possible association with inguinal hernias should motivate to examine inguinal ducts during imaging assessment and surgical procedure.

Immunohistochemical evaluation of Sonic Hedgehog signaling pathway proteins (Shh, Ptch1, Ptch2, Smo, Gli1, Gli2, and Gli3) in sporadic and syndromic odontogenic keratocysts.

AIMS: The aim of this study was to compare the clinical and demographic features of 62 patients presenting sporadic odontogenic keratocysts (OKCs) or OKCs associated with nevoid basal cell carcinoma syndrome (NBCCS). In conjunction with this, we also evaluated the immunohistochemical expression of Shh, Ptch1, Ptch2, Smo, Gli1, Gli2 and Gli3 proteins in 86 OKCs. By doing this, we add to the understanding of the biology of this type of lesion, providing tools that will help facilitate the early diagnosis of NBCCS in those patients where the first manifestation is that of OKCs. METHODS: This is a retrospective study; patients were classified into two groups: group 1 which consisted of those who were not affected by NBCCS (49 patients and 57 OKCs) and group 2 which consisted of those who were diagnosed with NBCCS (13 patients and 29 OKCs). The clinical and demographic features were studied and the immunohistochemical expression of Sonic Hedgehog proteins (Shh, Ptch1, Ptch2, Smo, Gli1, Gli2, and Gli3) was analyzed in all samples. RESULTS: There was an increase in the expression of three proteins in the syndromic OKC, when compared to that of sporadic cysts. Shh and Gli1 showed higher cytoplasmic expression, while Smo revealed stronger nuclear and cytoplasmic expressions. CONCLUSION AND CLINICAL RELEVANCE: Our findings suggest that the expression patterns of important Shh pathway proteins can represent valuable markers for early diagnosis of NBCCS-associated OKCs, as the major criterion for the diagnosis of NBCCS is currently based on the late appearance of basal cellular carcinomas. Thus, standardizing a new diagnostic tool for diagnosis of NBCCS could be of great importance in the identification of therapeutic targets. We therefore suggest, as based on our findings, that OKCs showing high expression of Shh, Smo, and Gli1 are potentially associated with NBCCS.

Ineffectiveness of information and access to health services: vulnerability to human papillomavirus.

AIM: To examine situations of vulnerability to human papillomavirus in the social representations of young women. BACKGROUND: Human papillomavirus is one of the most frequent sexually transmitted infections among women and constitutes a serious health problem among youth. This problem is embedded in psychosocial issues that promote situations of vulnerability and affect attitudes and behaviour in relation to prevention. METHODS: Qualitative study based on the theory of social representations, conducted among 64 female students in a high school in the city of Rio de Janeiro, Brazil. The study used personal semi-structured interviews, with a lexical analysis by Alceste 2010 software. FINDINGS: The inefficacy of information on the human papillomavirus pointed out individual and social vulnerabilities, and showed relationships between the difficulty of access and the perception of low quality in public health services, which also promotes institutional vulnerability. DISCUSSION: The representation of vulnerability to human papillomavirus infection is associated, not only with individual behaviours related to sexuality and gender identity but also to social and institutional conditions involving insufficient information and low quality of and ineffective access to public health services. CONCLUSION: Situations of vulnerability of young women to human papillomavirus infection influence ways of thinking and acting, when they generate feelings and behaviours that put them at risk. The social representations provided knowledge about how the participants appropriated consensual and reified universes in relation to vulnerability, influencing care and awareness of prevention. IMPLICATION FOR NURSING AND HEALTH POLICY: Situations of vulnerability, whether individual, social or institutional, warrant the attention of nurses and should be prioritized as public health policy goals to reduce the number of cases of human papillomavirus infection among younger women.

The anti-thrombotic effects of vitamin D and their possible relationship with antiphospholipid syndrome.

The importance of the immunomodulatory effects of vitamin D has recently been associated with autoimmune and chronic inflammatory diseases. Vitamin D deficiency has been linked to the development of autoimmune conditions. Antiphospholipid syndrome is an autoimmune disease characterized by thrombotic events and obstetric complications in patients with antiphospholipid antibodies. Current data show that patients with antiphospholipid syndrome have a high prevalence of vitamin D deficiency even without classic risk factors. Several studies have suggested vitamin D may have anti-thrombotic functions. In antiphospholipid syndrome, low vitamin D serum levels have been associated with thrombotic manifestations, suggesting a possible protective role of vitamin D in antiphospholipid syndrome. This literature review presents current evidence on the haemostatic functions of vitamin D and their possible relationship with the clinical manifestations of antiphospholipid syndrome.

Prevalence of functional gastrointestinal disorders in adults with systemic lupus erythematosus.

Objective (a) to assess the prevalence of functional gastrointestinal disorders (FGIDs) in female Mexican systemic lupus erythematosus (SLE) patients using the Rome III criteria and (b) to examine the effect of disease duration on FGID prevalence. Methods Female SLE outpatients aged ≥18 years with no organic gastrointestinal disorder were included. Participants were invited to upper gastrointestinal endoscopy screening and a faecal immunochemical test. FGID symptoms were evaluated using the Rome III questionnaire. Results Eighty-six SLE patients with median age of 45 (interquartile range 34-54) years were included. At least one FGID was found in 76.7% (66/88) of patients with SLE. The most prevalent domains of FGID diagnosed were functional oesophageal, gastroduodenal disorders and bowel disorders, of which functional dyspepsia (72.7%), functional heartburn (68.1%) and bloating (63.8%) were the most frequent. Fifty-nine per cent of patients had overlapping FGIDs. The most prevalent overlap was the combination of functional dyspepsia and functional heartburn. Patients with longer disease duration had a higher prevalence of FGID than those with shorter disease duration. Conclusions There was a high prevalence of FGIDs in Mexican SLE women with low disease activity. Overlapping FGIDs were frequent. Longer disease duration may be associated with FGIDs in SLE patients.

Factors of the epidemiological triad that influence the persistence of human papilloma virus infection in women with systemic lupus erythematosus.

We studied the epidemiologic triad-related factors influencing human papilloma virus (HPV) persistence in Mexican women with systemic lupus erythematosus (SLE). Patients aged ≥18 years with SLE (American College of Rheumatology criteria), with and without HPV persistence, were selected. Groups were analyzed by (1) host: clinical disease characteristics; (2) agent: (I) infectious (prevalence, incidence, HPV genotype and co-infections (≥2 HPV genotypes or mycoplasmas)), (II) chemical (contraceptives and immunosuppressive drugs) and (III) physical (vitamin D deficiency) and (3) environment. A total of 121 SLE patients were selected over a two-year period. (1) Host: mean age 45.8 years and disease duration 12.7 years. (2) Agent: (I) infectious. HPV infection prevalence in the second sample was 26.4%, high-risk HPV genotypes 21.5% and co-infections 7.4%. HPV infection incidence was 13.2%, persistence 13.2% and clearance 15.7%. (II) Chemical: use of oral hormonal contraceptives 5% and immunosuppressive treatment 97.5%. (III) Physical: Vitamin D levels were similar in both groups. (3) Environment: (I) natural. A total of 60.6% of patients were residents of Puebla City. (II) Social: The mean education level was 10.9. Poverty levels were: III degree 52.4%, IV degree 28% and II degree 17%. (III) Cultural behavioral: Onset of sexual life was 20.5 years, 10% had ≥3 sexual partners and 51.2% were postmenopausal. In conclusion, no factor of the epidemiologic triad was associated with HPV infection prevalence.

Dissipative structures induced by photoisomerization in a dye-doped nematic liquid crystal layer.

Order-disorder phase transitions driven by temperature or light in soft matter materials exhibit complex dissipative structures. Here, we investigate the spatio-temporal phenomena induced by light in a dye-doped nematic liquid crystal layer. Experimentally, for planar anchoring of the nematic layer and high enough input power, photoisomerization processes induce a nematic-isotropic phase transition mediated by interface propagation between the two phases. In the case of a twisted nematic layer and for intermediate input power, the light induces a spatially modulated phase, which exhibits stripe patterns. The pattern originates as an instability mediated by interface propagation between the modulated and the homogeneous nematic states. Theoretically, the phase transition, emergence of stripe patterns and front dynamics are described on the basis of a proposed model for the dopant concentration coupled with the nematic order parameter. Numerical simulations show quite a fair agreement with the experimental observations.This article is part of the theme issue 'Dissipative structures in matter out of equilibrium: from chemistry, photonics and biology (part 2)'.

A brief psychological intervention for mothers of children with food allergy can change risk perception and reduce anxiety: Outcomes of a randomized controlled trial.

BACKGROUND: Mothers of children with food allergy have increased anxiety, which may be influenced by healthcare professionals' communication of risk. OBJECTIVE: To evaluate a brief psychological intervention for reducing anxiety in mothers of children with food allergy. METHODS: Two hundred mothers of children with food allergy were recruited from allergy clinics. A computer-generated randomization list was used to allocate participants to a single-session cognitive behavioural therapy intervention including a risk communication module, or standard care. Anxiety and risk perception were assessed at 6 weeks and 1 year. Primary outcome was state anxiety at 6 weeks. Secondary outcomes included state anxiety at 1 year, risk perception at 6 weeks and 1 year, and salivary cortisol response to a simulated anaphylaxis scenario at 1 year. RESULTS: We found no significant difference in the primary outcome state anxiety at 6 weeks, with mean 31.9 (SD 10.2) intervention, 34.0 (10.2) control; mean difference 2.1 (95% CI -0.9, 5.0; P=.17). There was significantly reduced state anxiety at 6 weeks in the intervention group, in the subgroup of participants with moderate/high anxiety at enrolment (103/200, 52%), with mean 33.0 (SD 9.3) intervention, 37.8 (SD 10.0) control; mean difference 4.8 (95% CI 0.9, 8.7; P=.016; Cohen's d effect size 0.50). The psychological intervention also reduced risk perception and salivary cortisol response (P=.032; effect size 0.36). CONCLUSION: We found evidence that a brief psychological intervention which incorporates accurate risk information may impact on anxiety, risk perception and physiological stress response in mothers of children with food allergy.

Incidence of cervical human papillomavirus infection in systemic lupus erythematosus women.

Objectives Our objective was to study the incidence, persistence and clearance of human papillomavirus infection in systemic lupus erythematosus women and assess risk factors for persistence of human papillomavirus infection. Methods We carried out a prospective, observational cohort study of 127 systemic lupus erythematosus women. Patients were evaluated at baseline and at three years. Traditional and systemic lupus erythematosus women-related disease risk factors were collected. Gynaecological evaluations and cervical cytology screening were made. Human papillomavirus detection and genotyping were made by polymerase chain reaction and linear array. Results The cumulative prevalence of human papillomavirus infection increased from 22.8% at baseline to 33.8% at three years; p = < 0.001: 20.1% of patients experienced 43 incident infections. The risk of any human papillomavirus infection was 10.1 per 1000 patient-months. At three years, 47 (88.6%) prevalent infections were cleared. Independent risk factors associated with incident human papillomavirus infection included more lifetime sexual partners (odds ratio = 1.8, 95% confidence interval = 1.11-3.0) and cumulative cyclophosphamide dose (odds ratio = 3.9, 95% confidence interval = 1.2-12.8). Conclusions In systemic lupus erythematosus women, the cumulative prevalence of human papillomavirus infection, including high risk-human papillomavirus and multiple human papillomavirus infections, may increase over time. Most persistent infections were low risk-human papillomavirus. The number of lifetime sexual partners and the cumulative cyclophosphamide dose were independently associated with incident human papillomavirus infection.

Determinants of percent mammographic density in women with premature ovarian insufficiency.

OBJECTIVE: To evaluate the determinants of breast density in women with premature ovarian insufficiency (POI). METHODS: In a cross-sectional study of 163 women with POI undergoing mammography, percent mammographic density (PMD) was evaluated by digitizing the image. PMD was correlated with age, age at menarche, age at POI, time since POI, body mass index (BMI), gestational history and hormone therapy (HT) use (duration, dose, regimen). RESULTS: POI was diagnosed at a mean age of 32.3 ± 5.9 years. The mean age of the women at mammography was 41.3 ± 5.4 years; mean BMI was 27.4 ± 5.4 kg/m2 and mean PMD was 24.3 ± 18.5. Mean PMD did not differ between the different age groups evaluated (29-39, 40-49 and 50-55 years) or between users and non-users of HT. Mean duration of HT use was 5.6 ± 4.7 years. PMD was higher in nulligravidas compared to women who had been pregnant (p = 0.0016); however, POI occurred earlier in nulligravidas (p < 0.0001). PMD correlated negatively with BMI (r = -0.27; p = 0.0005). CONCLUSION: In women with POI, HT use had no effect on PMD, irrespective of the duration of use, dose or regimen. Pregnancy and BMI were consistently associated with PMD, with density being greater in nulligravidas and in women with lower BMI.

Gestational trophoblastic disease in Campinas, Brazil and persistency predictors.

PURPOSE: To determine the prevalence of the gestational trophoblastic disease (GTD) and to evaluate the risk factors for persistence of the disease. MATERIALS AND METHODS: A retrospective study with 152 women diagnosed with GTD at University of Campinas from 2006 to 2013. Frequencies, average, and standard deviation were evaluated for each variable and an exact Fisher test was utilized to study persistent disease risk factors. RESULTS: The women were on average 25.81 ± 8.02 years old. The most prevalent blood type was O positive (49.6%). The diagnosis of complete mole was found in 64.8%, followed by partial mole in 32%, and choriocarcinoma in 3%. Complete mole developed invasive mole in 12.3%, the same occurred with 7.5% of the partial moles. No significant association was found between age, number of gestations, race, BMI or blood type and persistent mole. CONCLUSION: The complete mole is the most fre- quent GTD, and is at high risk for developing malignant forms.

Evaluation of helper-dependent canine adenovirus vectors in a 3D human CNS model.

Gene therapy is a promising approach with enormous potential for treatment of neurodegenerative disorders. Viral vectors derived from canine adenovirus type 2 (CAV-2) present attractive features for gene delivery strategies in the human brain, by preferentially transducing neurons, are capable of efficient axonal transport to afferent brain structures, have a 30-kb cloning capacity and have low innate and induced immunogenicity in preclinical tests. For clinical translation, in-depth preclinical evaluation of efficacy and safety in a human setting is primordial. Stem cell-derived human neural cells have a great potential as complementary tools by bridging the gap between animal models, which often diverge considerably from human phenotype, and clinical trials. Herein, we explore helper-dependent CAV-2 (hd-CAV-2) efficacy and safety for gene delivery in a human stem cell-derived 3D neural in vitro model. Assessment of hd-CAV-2 vector efficacy was performed at different multiplicities of infection, by evaluating transgene expression and impact on cell viability, ultrastructural cellular organization and neuronal gene expression. Under optimized conditions, hd-CAV-2 transduction led to stable long-term transgene expression with minimal toxicity. hd-CAV-2 preferentially transduced neurons, whereas human adenovirus type 5 (HAdV5) showed increased tropism toward glial cells. This work demonstrates, in a physiologically relevant 3D model, that hd-CAV-2 vectors are efficient tools for gene delivery to human neurons, with stable long-term transgene expression and minimal cytotoxicity.

Bacterial vaginosis, aerobic vaginitis, vaginal inflammation and major Pap smear abnormalities.

The purpose of this investigation was to evaluate the impact of the vaginal milieu on the presence of abnormal Pap smears and a positive human papilloma virus (HPV) test. A cross-sectional study was conducted between June 2014 and May 2015, evaluating the vaginal discharge by fresh wet mount microscopy and comparing these data with Pap smear findings. Wet mount slides were scored for bacterial vaginosis (BV), aerobic vaginitis (AV), presence of Candida and Trichomonas vaginalis. Cytologic evaluation was done on all Pap smears according to the Bethesda criteria. The cobas© HPV Test (Roche) was performed for HPV detection. A total of 622 cases were evaluated. The mean age of the patients was 41.6 ± 10.65 years (range 21-75). Eighty-three women (13.3 %) had a cytology result worse than low-grade squamous intraepithelial lesion (LSIL). When comparing this group with the one with normal or minor [atypical squamous cells of undetermined significance (ASC-US) or LSIL] Pap smear abnormalities, there were no differences in the presence of Candida (32.5 % vs. 33.2 %, p = 1.0), absence of lactobacilli (38.6 % vs. 32.5 %, p = 0.32) or BV (20.5 % vs. 13.2 %, p = 0.09). On the other hand, moderate or severe inflammation (msI) (41.0 % vs. 28.8 %, p = 0,04), moderate or severe AV (msAV) (16.9 % vs. 7.2 %, p = 0.009) and msAV/BV (37.3 % vs. 20.0 %, p = 0.001) were more common in women with such major cervical abnormalities. No significant association was found between deviations of the vaginal milieu and high-risk HPV infection. The presence of msI or msAV, but not BV, is independently associated with an increased risk of major cervical cytological abnormalities, but not with HPV infection.