No association between periodontitis and preterm low birth weight: a case-control study.

PURPOSE: This study aimed to investigate the association between periodontitis in pregnant women and adverse pregnancy outcomes by heeding confounding risk factors for preterm low birth weight infants. METHODS: This study was reported according to The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement. A case-control study was conducted. Medical records of all pregnant women attending a prenatal care clinic were screened. Those between 21 and 34 years and gestational age of 28-32 weeks were initially enrolled in the study. The exclusion criteria were then applied: diabetes mellitus, genitourinary tract infections, or HIV infection; previous multiple gestations; previous preterm birth/low birth weight infants; in vitro fertilization procedures; placental, cervical/uterine abnormalities; history of infertility; history of drug abuse; and any medical conditions that required antibiotics prophylaxis. Patients' anthropometric, demographic, and behavioral characteristics were collected. The periodontal clinical parameters were obtained from six sites per tooth: clinical attachment level, probing pocket depth, dental plaque index, and gingival bleeding index. Women were then allocated into two groups: mothers of preterm and/or low birth weight newborns (cases) and mothers of full-term and normal birth weight newborns (controls). RESULTS: Periodontal clinical parameters were analyzed and reported separately for each group, and no significant differences were observed (p > 0.05). Logistic regression analysis revealed that periodontal clinical parameters were not associated with the adverse pregnancy outcomes. CONCLUSION(S): After controlling for confounding factors, our results suggest that maternal periodontal disease is not a risk factor associated with preterm low birth weight infants.

The term basal plate of the human placenta as a source of functional extravillous trophoblast cells.

BACKGROUND: Extravillous trophoblast (EVT) cells are of pivotal importance in human embryo implantation and homeostasis of the maternal fetal interface. Invasion of the endometrium by EVT contributes to placental anchorage, spiral artery remodeling, immunological defense, tolerogenic responses, and several collaborative cross talks involved in establishing and maintaining a successful pregnancy. We report here an improved protocol for the isolation of fully differentiated EVT cells from the basal plate of the human term placenta. METHODS: The basal plate was carefully dissected from the villous tissue and the amniochorion membrane prior to enzymatic digestion. Term basal EVT cells were isolated using a 30 and 60% Percoll gradient. A panel of markers and characteristics of the isolated cells were used to confirm the specificity and efficiency of the method so that their potential as an investigative tool for placental research could be ascertained. RESULTS: Isolated cells were immunoreactive for cytokeratin-7 (CK-7), placental growth factor, placental alkaline phosphatase, human leukocyte antigen G1 (HLA-G1), and α1 and α5 integrins, similarly to the EVT markers from first trimester placental villi. Around 95% of the isolated cells labeled positively for CK-7 and 82% for HLA-G1. No significant change in viability was observed during 48 h of EVT culture as indicated by propidium iodide incorporation and trypan blue test exclusion. Genes for metalloproteinases MMP-2 and MMP9 (positive regulators of trophoblast invasiveness) were expressed up to 48 h of culturing, as also the gelatinolytic activity of the isolated cells. Transforming growth factor (TGF)-beta, which inhibits proliferation, migration, and invasiveness of first-trimester EVT cells, also reduced invasion of isolated term EVT cells in transwell assays, whereas epidermal growth factor was a positive modulator. CONCLUSIONS: Term basal plate may be a viable source of functional EVT cells that is an alternative to villous explant-derived EVT cells and cell lines. Isolated term EVT cells may be particularly useful in investigation of the role of trophoblast cells in pathological gestations, in which the precise regulation and interactive ability of extravillous trophoblast has been impaired.

Experiences of dentists and caregivers of patients with special care needs-A qualitative study.

BACKGROUND: Patients with special care needs (developmental disabilities) have unique and complex needs regarding their oral health and care. This qualitative study aimed to identify the experiences, preferences and challenges of dentists and caregivers regarding behavior guidance techniques for dental care in persons with special care needs. METHODS: Relying on qualitative description as articulated by Sandelowski, we conducted telephone interviews with a purposeful sample of five special care dentists and seven caregivers. We analyzed the data using thematic analysis. RESULTS: Four themes were highlighted: (1) Neither pharmacological or non-pharmacological behavior guidance techniques was universally suitable, (2) A patient-centered approach was critical, (3) The dental environment triggered patients' behaviors and anxiety levels, (4) There was more demand for, than supply of, qualified dentists to treat patients with special care needs. CONCLUSIONS: Persons with special care needs are heterogeneous and respond to various behavioral techniques required to deliver their treatment. Behavior guidance planning should be negotiated carefully with patients and caregivers and then individualized based on patients' capabilities and needs for treatment. The necessity to manage complex behaviors has contributed to the limitation of access to dental care for persons with special care needs. Dentistry as a profession has the obligation to uphold the social contract and meet its responsibility to the dental care needs of this population.

A Retrospective Study on Endodontic Treatment Outcomes in Patients With Special Needs.

INTRODUCTION: Outcomes of endodontic treatment in patients with special needs are not fully understood, leading to reluctance in performing endodontic treatment. METHODS: This retrospective cohort study evaluated the periapical healing and tooth survival in patients with special needs who had permanent teeth endodontically treated in a hospital setting between 1998 and 2019. Data characterization was performed using univariate analyses. Logistic and Cox regression analyses (P < .05) were performed to identify the odds ratio (OR) and hazard ratio (HR) of the potential prognostic factors, respectively. These predictors were chosen from previous outcome studies in the general population and patients with special needs. RESULTS: A total of 61 patients (108 teeth) met the inclusion criteria. The most common treatment modality was initial therapy with 81.5% of cases being managed without a need for general anesthesia. Healing rate for initial endodontic treatment was 89.9% and was affected by no restoration at follow-up (OR = 0.15; 95% confidence interval [CI], 0.12-0.71; P = .02). After a mean follow-up of 79.36 ± 59.6 months, the survival rate was 73% and was correlated with gender (HR for males = 0.3; 95% CI, 0.1-0.6; P < .05) and age (HR for patients >45 years = 3.7; 95% CI, 1.7-8.2; P < .05). The most common reason for tooth extraction was unrestorable tooth fracture. CONCLUSIONS: Endodontic therapy without a need for general anesthesia is a viable treatment option for patients with special needs. If the overall patient condition permits, then treatment can be administered by community dentists rather than waiting for a patient to be seen in a hospital setting.

Process-related Factors Are as Important as Outcomes for Patients Undergoing Nonsurgical Root Canal Treatment, Nonsurgical Root Canal Retreatment, and Endodontic Microsurgery.

INTRODUCTION: There is considerable variation in the reporting of treatment outcomes in endodontics. Patient-centered outcomes are often inadequately reported in endodontic outcome studies. This paper explores patients' expectations and reported outcomes in nonsurgical root canal treatment (NS-RCT), nonsurgical root canal retreatment (NS-ReTx), and endodontic microsurgery (EMS). METHODS: We used a qualitative description approach and conducted telephone and virtual semi-structured interviews with participants who had the following treatments within the preceding 3-12 months: NS-RCT (n = 10), NS-ReTx (n = 10), or EMS (n = 10). Half of these treatments were performed by senior endodontic residents in an academic setting and the other half by a community-based endodontist at a private practice. RESULTS: Participants identified several outcomes that were important to them and integral to treatment success, such as tooth survival, resolution of symptoms, aesthetics, and radiographic healing. Process-related factors were as important as treatment outcomes for participants. Communicating with and educating patients during treatment increased participants' satisfaction and lowered their stress. Dissatisfaction was linked to the lack of a comprehensive treatment and follow-up plan. Thorough planning ensured that patients were fully informed and had a structured approach to achieving their desired outcomes. CONCLUSIONS: This study provides a list of outcomes that are important for patients undergoing NS-RCT, NS-ReTx, and EMS. These outcomes should be considered when developing a core outcome set related to endodontic treatments. Additionally, this study reports patients' expectations regarding process-related factors that are essential for providing patient-centered care and improving patient experience.

Oral health-related quality of life among women early postpartum: A cross-sectional study.

BACKGROUND: Periodontal diseases can negatively impact the oral health-related quality of life (OHRQoL) of pregnant women. This study investigates the association between maternal oral inflammatory load (OIL), sociodemographic characteristics, and the OHRQoL in postpartum women. METHODS: In this cross-sectional study, breastfeeding mothers were recruited from St. Michael's Hospital, Toronto within 2-4 weeks postpartum. Mothers were categorized into "Normal/low" and "High" OIL groups based on the absolute counts of oral polymorphonuclear neutrophils (oPMNs). The Oral Health Impact Profile-14 questionnaire was used to assess the impact of the maternal OIL on the OHRQoL. Multiple linear regression analyses were performed to examine the association between maternal sociodemographic factors including age, marital status, education level, employment status, parity, and their OHRQoL. RESULTS: Forty-seven mothers were included in this study. Mothers with high OIL reported higher impact on their OHRQoL (30%) than mothers with normal/low OIL (21%), but these differences were not statistically different. There was a negative relationship between the mother's education level and the extent of impact of OHRQoL on the "physical pain" dimension (p < 0.05), and between the mothers' age and employment status and the "physical disability" dimension (p < 0.05). A positive correlation was noted between multi-parity and the extent of impact of OHRQoL on the "physical disability" dimension (p = 0.009), and between the marital status and the "psychological disability" dimension (p < 0.05). CONCLUSION: This study highlighted the significant impact of sociodemographic characteristics on the OHRQoL of mothers, showcasing the importance of considering these factors when implementing targeted preventive dental care programs for mothers.

A Scoping Review of Four Decades of Outcomes in Nonsurgical Root Canal Treatment, Nonsurgical Retreatment, and Apexification Studies: Part 3-A Proposed Framework for Standardized Data Collection and Reporting of Endodontic Outcome Studies.

INTRODUCTION: Despite initiatives to standardize and improve reporting of rapidly growing endodontic outcome research studies, issues related to missing and ambiguous information are still of great concern. In this article, we propose a framework for standardized data collection and a compiled checklist for reporting of various study designs on endodontic outcome. METHODS: A comprehensive search was carried out to locate randomized controlled trials, cohorts, case-control studies, or case series of >100 patients that reported on endodontic outcomes. We reviewed these articles to develop a Data Collection Template and compiled a checklist for reporting of future endodontic outcome research. RESULTS: Out of 354 eligible articles previously reported in our scoping review on endodontic outcome studies, 109 articles were selected and screened for study variables or levels of categorization. Our complied Data Collection Template was developed in 19 domains to highlight important demographic, preoperative, intraoperative, and postoperative variables. Because of the specific needs for endodontic outcome literature, we also proposed a compiled checklist (consisting of 4 main domains) to facilitate the reporting of various study designs on endodontic outcome studies. This checklist included simple descriptions of the required items and examples on reporting from published endodontic studies. CONCLUSIONS: By facilitating the collection and reporting of relevant research data by investigators in private practice and academia, we hope that the proposed Data Collection Template and reporting guideline can highlight the importance of standardization among clinicians and researchers while producing valid scientific information that will support evidence-based treatment decisions.

Perspectives for Combining Viral Oncolysis With Additional Immunotherapies for the Treatment of Melanoma.

Melanoma is the deadliest type of skin cancer with steadily increasing incidence worldwide during the last few decades. In addition to its tumor associated antigens (TAAs), melanoma has a high mutation rate compared to other tumors, which promotes the appearance of tumor specific antigens (TSAs) as well as increased lymphocytic infiltration, inviting the use of therapeutic tools that evoke new or restore pre-existing immune responses. Innovative therapeutic proposals, such as immune checkpoint inhibitors (ICIs), have emerged as effective options for melanoma. However, a significant portion of these patients relapse and become refractory to treatment. Likewise, strategies using viral vectors, replicative or not, have garnered confidence and approval by different regulatory agencies around the world. It is possible that further success of immune therapies against melanoma will come from synergistic combinations of different approaches. In this review we outline molecular features inherent to melanoma and how this supports the use of viral oncolysis and immunotherapies when used as monotherapies or in combination.

A Scoping Review of 4 Decades of Outcomes in Nonsurgical Root Canal Treatment, Nonsurgical Retreatment, and Apexification Studies-Part 2: Outcome Measures.

INTRODUCTION: Inconsistencies in the definitions of endodontic outcome terminology jeopardize evaluations of proposed interventions and patient care quality. This scoping review aimed to provide groundwork to develop a set of basic outcomes in endodontics. METHODS: We performed a comprehensive literature search for randomized controlled trials, cohort studies, case-control studies, and case series (≥10 patients) published after 1980 with patients ≥10 years of age with any preoperative pulpal and periapical diagnosis in permanent teeth requiring nonsurgical root canal treatment, retreatment, or apexification. Abstracted data on outcome assessment methods, assessors, and domains were reported after univariate and bivariate analyses. RESULTS: Treatment outcomes were evaluated radiographically (88%) or clinically (73%). Although 2-dimensional radiography exceeded 3-dimensional radiography, the use of the latter has increased since 2010, mostly for nonsurgical retreatments. Of 19 identified outcomes, 5 were most frequent: success (168 studies, 40%), radiographic healing (128 studies, 30%), survival (of an asymptomatic tooth [48 studies, 12%] or of a procedure code in administrative databases [31 studies, 7%]), pain assessment (14 studies, 3%), and quality of life (11 studies, 3%). Clinician-centered outcomes have been most frequently studied since the 1980s (71%), in academic settings (76%), and using a prospective design (45%). Patient-centered outcomes were reported in 19% of studies before 2010 and 30% since 2010. They were more common among retrospective studies (49%). CONCLUSIONS: Patient-centered outcome measures are lacking in endodontic studies. The state of available research can provide a baseline for the development of a core outcome set in endodontics, which should represent the important patient-centered outcomes in conjunction with well-validated clinician-centered outcomes.

A Scoping Review of 4 Decades of Outcomes in Nonsurgical Root Canal Treatment, Nonsurgical Retreatment, and Apexification Studies-Part 1: Process and General Results.

INTRODUCTION: Despite initiatives to standardize reports, variances in study design, outcomes assessed, and tools used are persistent in the literature. This review scoped the existing literature on endodontic outcome studies for future development of core outcome sets. METHODS: A comprehensive literature search of randomized controlled trials, cohort studies, case-control studies, and case series (≥10 patients) published after 1980 including patients ≥10 years of age with any preoperative pulpal and periapical diagnosis in permanent teeth requiring nonsurgical root canal treatment (NS-RCT), retreatment (NS-ReTx), or apexification was performed. Abstracted data were reported through descriptive statistics. RESULTS: Of the 9957 studies screened, 354 were included. An increase in the quantity of endodontic outcome publications and levels of evidence in their study design was noted over the past 4 decades. Although 41% of the studies included participants 26-50 years of age, literature including participants >50 years old has increased since 2000. Apexification and NS-ReTx were mostly provided by specialists and postgraduate students. The most common follow-up period was 2-5 years (35%), and most randomized controlled trials (58%) reported follow-up times <1 year. Multiple-visit treatment was most common in apexification studies (85%). Deficiency, inconsistency, and ambiguity were observed across many reports. CONCLUSIONS: NS-ReTx and NS-RCT/NS-ReTx studies have increased over the past 2 decades, particularly those focusing on molars and patients >50 years old. Despite the progress in endodontic research, heterogeneity in reporting styles yields considerable limitations, particularly data standardization challenges and inconsistencies in methods and results reporting. This scoping review highlighted the state of available research and supported the development of standardized guidelines for future investigations.

Prognostic value of integrin αV expression and localization pattern in invasive breast carcinomas.

Invasion of surrounding stroma is an early event in breast cancer metastatic progression, and involves loss of cell polarity, loss of myoepithelial layer, epithelial-mesenchymal transition (EMT) and remodeling of the extracellular matrix (ECM). Integrins are transmembrane receptors responsible for cell-ECM binding, which triggers signals that regulate many aspects of cell behavior and fate. Changes in the expression, localization and pairing of integrins contribute for abnormal responses found in transformed epithelia. We analyzed 345 human breast cancer samples in tissue microarrays (TMA) from cases diagnosed with invasive breast carcinoma to assess the expression and localization pattern of integrin αV and correlation with clinical parameters. Patients with lower levels of integrin αV staining showed reduced cancer specific survival. A subset of cases presented a peripheral staining of integrin αV surrounding tumor cell clusters, possibly matching the remaining myoepithelial layer. Indeed, the majority of ductal carcinoma in situ (DCIS) components found in the TMA presented integrin αV at their periphery, whereas this pattern was mostly lost in invasive components, even in the same sample. The lack of peripheral integrin αV correlated with decreased cancer specific survival. In addition, we observed that the presence of integrin αV in the stroma was an indicative of poor survival and metastatic disease. Consistently, by interrogating publicly available datasets we found that, although patients with higher mRNA levels of integrin αV had increased risk of developing metastasis, high co-expression of integrin αV and a myoepithelial cell marker (MYH11) mRNA levels correlated with better clinical outcomes. Finally, a 3D cell culture model of non-malignant and malignant cells reproduced the integrin αV pattern seen in patient samples. Taken together, our data indicate that both the expression levels of integrin αV and its tissue localization in primary tumors have prognostic value, and thus, could be used to help predict patients at higher risk of developing metastasis.

Profile of autoantibodies against phosphorylcholine and cross-reactivity to oxidation-specific neoantigens in selective IgA deficiency with or without autoimmune diseases.

Immunoglobulin A deficiency (IgAD) is considered the most common form of primary immunodeficiency. The majority of IgA-deficient individuals are considered asymptomatic, even though IgAD has been associated with an increased frequency of recurrent infections, allergy, and autoimmune diseases. In this study we evaluate the Natural autoantibodies (NatAbs) reactivity to phosphorylcholine (PC) and to some pro-inflammatory molecules in IgAD with or without autoimmune disorders. We observed that in the absence of IgA there is an enhancement of IgG subclasses functioning as NatAbs against PC. Immunoglobulin G (IgG) against lipopolysaccharide, C-reactive protein, and IgA was found in IgAD, regardless of the autoimmune manifestations. Nonetheless, IgAD patients with autoimmune disease showed significantly higher IgG reactivity against pro-inflammatory molecules, such as cardiolipin, oxidized low-density lipoproteins, and phosphatidylserine, with positive correlation between them. In conclusion, the IgG NatAbs against PC may represent a compensatory defense mechanism against infections and control excess of inflammation, explaining the asymptomatic status in the IgA deficiency.

Older adults and the disparity in oral health status; the problem and innovative ways to address it.

The impact of oral health inequalities on one's ability to maintain good oral health is cumulative throughout life and accentuated in older age groups. While studies on factors influencing the decisions made by elders to seek dental care have been conducted in Israel and worldwide, the issue of access to and provision of dental care is complex. However, the need to address oral health issues is being voiced in high-level international meetings and there was never a better momentum to rethink the current oral health care delivery model beyond issues related solely to accessibility. Here we outline unique opportunities to ensure sustainable models of preventive services and oral health the effects of which would be amplified in concert with increases in the availability universal dental healthcare.

Reexamining dental outreach programs: A model for local empowerment and sustainable development.

BACKGROUND: To address the inadequacy of oral health care in developing nations, outreach programs have facilitated the provision of dental services by foreign volunteers to areas of need. However, the effectiveness of the current aid model on the long-term well-being of the recipient population and sustainability of efforts remains uncertain. The authors examine the strengths and areas of improvement of outreach initiatives to inform a reorientation of the aid model. METHODS: The authors conducted a PubMed search and reviewed included articles to assess the current limitations and recommended strategies for outreach programs. The identified limitations and strategies were sorted into 4 key areas of change and organized using the Theory of Change framework to inform an improved aid model. RESULTS: The current aid models were found to have limitations in scope and coverage, interventions that were not applicable or integrated into local systems, and an inadequate evidence base. To address these limitations, efforts should be directed at the capacity building of local workers through individual training and evidence-based interventions, improved understanding of local contexts, and integration and alignment with local systems. CONCLUSIONS: The empowerment of local communities is critical in ensuring an effective and sustainable aid model in developing nations. PRACTICAL IMPLICATIONS: By adopting an improved aid model, outreach programs can enhance the long-term access and availability of quality oral health care that is delivered by local providers and communities.

Combined p14ARF and Interferon-ß Gene Transfer to the Human Melanoma Cell Line SK-MEL-147 Promotes Oncolysis and Immune Activation.

Immune evasion is an important cancer hallmark and the understanding of its mechanisms has generated successful therapeutic approaches. Induction of immunogenic cell death (ICD) is expected to attract immune cell populations that promote innate and adaptive immune responses. Here, we present a critical advance for our adenovirus-mediated gene therapy approach, where the combined p14ARF and human interferon-ß (IFNß) gene transfer to human melanoma cells led to oncolysis, ICD and subsequent activation of immune cells. Our results indicate that IFNß alone or in combination with p14ARF was able to induce massive cell death in the human melanoma cell line SK-MEL-147, though caspase 3/7 activation was not essential. In situ gene therapy of s.c. SK-MEL-147 tumors in Nod-Scid mice revealed inhibition of tumor growth and increased survival in response to IFNß alone or in combination with p14ARF. Emission of critical markers of ICD (exposition of calreticulin, secretion of ATP and IFNß) was stronger when cells were treated with combined p14ARF and IFNß gene transfer. Co-culture of previously transduced SK-MEL-147 cells with monocyte-derived dendritic cells (Mo-DCs) derived from healthy donors resulted in increased levels of activation markers HLA-DR, CD80, and CD86. Activated Mo-DCs were able to prime autologous and allogeneic T cells, resulting in increased secretion of IFNγ, TNF-α, and IL-10. Preliminary data showed that T cells primed by Mo-DCs activated with p14ARF+IFNß-transduced SK-MEL-147 cells were able to induce the loss of viability of fresh non-transduced SK-MEL-147 cells, suggesting the induction of a specific cytotoxic population that recognized and killed SK-MEL-147 cells. Collectively, our results indicate that p14ARF and IFNß delivered by our adenoviral system induced oncolysis in human melanoma cells accompanied by adaptive immune response activation and regulation.

Environmental control of mammary carcinoma cell expansion by acidification and spheroid formation in vitro.

Breast cancer is the leading cause of cancer death among women worldwide. Like other cancers, mammary carcinoma progression involves acidification of the tumor microenvironment, which is an important factor for cancer detection and treatment strategies. However, the effects of acidity on mammary carcinoma cell morphology and phenotype have not been thoroughly characterized. Here, we evaluated fundamental effects of environmental acidification on mammary carcinoma cells in standard two-dimensional cultures and three-dimensional spheroids. Acidification decreased overall mammary carcinoma cell viability, while increasing their resistance to the anthracycline doxorubicin. Environmental acidification also increased extracellular vesicle production by mammary carcinoma cells. Conditioned media containing these vesicles appeared to increase fibroblast motility. Acidification also increased mammary carcinoma cell motility when cultured with fibroblasts in spheroids. Taken together, results from this study suggest that environmental acidification induces drug resistance and extracellular vesicle production by mammary carcinoma cells that promote tumor expansion.

Chemokine (C-C motif) ligand 25 expressed by trophoblast cells and leukocytes bearing its receptor Ccr9: An alliance during embryo implantation?

PROBLEM: We hypothesized that trophoblast expression of Ccl25 attracts a specific leukocyte cell population to the implantation site for local regulation. METHOD OF STUDY: Mice blastocysts, ectoplacental cones, and decidua at gestational days 3.5-7.5 were evaluated for Ccl25 and Ccr9 expressions. Peripheral availability and characterization of Ccr9+ leukocytes were determined by flow cytometry. Leukocyte chemotaxis was assessed in the presence of Ccl25 recombinant protein and embryos using antisense oligomers (ODNs) to Ccl25 and Ccr9 neutralizing antibody. RESULTS: Ccl25 was expressed by embryonic cells, whereas Ccr9 expression was strong at the maternal compartment and in PBMC. Immunolocalization confirmed this expression. In vitro, chemotaxis assays showed that the embryonic Ccl25 signals to Ccr9+ PBMCs. Maternal Ccr9+α4ß7+ monocytes switch from an anti-inflammatory phenotype (F4/80+11b+Ly6C-TGF-ß+ cells, pre-implantation) to an inflammatory profile (F4/80+11b+Ly6C+TNF-α+ cells, post-implantation). CONCLUSION: Our data support the establishment of a CCL25/CCR9-axis at the maternal-fetal interface in mice, which may be involved in immune regulatory mechanisms during embryo implantation.

Trichomes related to an unusual method of water retention and protection of the stem apex in an arid zone perennial species.

It is well known that trichomes protect plant organs, and several studies have investigated their role in the adaptation of plants to harsh environments. Recent studies have shown that the production of hydrophilic substances by glandular trichomes and the deposition of this secretion on young organs may facilitate water retention, thus preventing desiccation and favouring organ growth until the plant develops other protective mechanisms. Lychnophora diamantinana is a species endemic to the Brazilian 'campos rupestres' (rocky fields), a region characterized by intense solar radiation and water deficits. This study sought to investigate trichomes and the origin of the substances observed on the stem apices of L. diamantinana. Samples of stem apices, young and expanded leaves were studied using standard techniques, including light microscopy and scanning and transmission electron microscopy. Histochemical tests were used to identify the major groups of metabolites present in the trichomes and the hyaline material deposited on the apices. Non-glandular trichomes and glandular trichomes were observed. The material deposited on the stem apices was hyaline, highly hydrophilic and viscous. This hyaline material primarily consists of carbohydrates that result from the partial degradation of the cell wall of uniseriate trichomes. This degradation occurs at the same time that glandular trichomes secrete terpenoids, phenolic compounds and proteins. These results suggest that the non-glandular trichomes on the leaves of L. diamantinana help protect the young organ, particularly against desiccation, by deposition of highly hydrated substances on the apices. Furthermore, the secretion of glandular trichomes probably repels herbivore and pathogen attacks.

Niemann-Pick disease type C: a case series of Brazilian patients.

UNLABELLED: The aim of the study was to analyze a series of Brazilian patients with Niemann-Pick disease type C (NP-C). METHOD: Correlations between clinical findings, laboratory data, molecular findings and treatment response are presented. RESULT: The sample consisted of 5 patients aged 8 to 26 years. Vertical supranuclear gaze palsy, cerebellar ataxia, dementia, dystonia and dysarthria were present in all cases. Filipin staining showed the "classical" pattern in two patients and a "variant" pattern in three patients. Molecular analysis found mutations in the NPC1 gene in all alleles. Miglustat treatment was administered to 4 patients. CONCLUSION: Although filipin staining should be used to confirm the diagnosis, bone marrow sea-blue histiocytes often help to diagnosis of NP-C. The p.P1007A mutation seems to be correlated with the "variant" pattern in filipin staining. Miglustat treatment response seems to be correlated with the age at disease onset and disability scale score at diagnosis.

TLR7/TLR8 Activation Restores Defective Cytokine Secretion by Myeloid Dendritic Cells but Not by Plasmacytoid Dendritic Cells in HIV-Infected Pregnant Women and Newborns.

Mother-to-child transmission (MTCT) of HIV-1 has been significantly reduced with the use of antiretroviral therapies, resulting in an increased number of HIV-exposed uninfected infants. The consequences of HIV infection on the innate immune system of both mother-newborn are not well understood. In this study, we analyzed peripheral blood and umbilical cord blood (CB) collected from HIV-1-infected and uninfected pregnant women. We measured TNF-α, IL-10 and IFN-α secretion after the stimulation of the cells with agonists of both extracellular Toll-like receptors (TLRs) (TLR2, TLR4 and TLR5) and intracellular TLRs (TLR7, TLR7/8 and TLR9). Moreover, as an indicator of the innate immune response, we evaluated the responsiveness of myeloid dendritic cells (mDCs) and plasmacytoid DCs (pDCs) to TLRs that are associated with the antiviral response. Our results showed that peripheral blood mononuclear cells (PBMCs) from HIV-1-infected mothers and CB were defective in TNF-α production after activation by TLR2, TLR5, TLR3 and TLR7. However, the TNF-α response was preserved after TLR7/8 (CL097) stimulation, mainly in the neonatal cells. Furthermore, only CL097 activation was able to induce IL-10 and IFN-α secretion in both maternal and CB cells in the infected group. An increase in IFN-α secretion was observed in CL097-treated CB from HIV-infected mothers compared with control mothers. The effectiveness of CL097 stimulation was confirmed by observation of similar mRNA levels of interferon regulatory factor-7 (IRF-7), IFN-α and TNF-α in PBMCs of both groups. The function of both mDCs and pDCs was markedly compromised in the HIV-infected group, and although TLR7/TLR8 activation overcame the impairment in TNF-α secretion by mDCs, such stimulation was unable to reverse the dysfunctional type I IFN response by pDCs in the HIV-infected samples. Our findings highlight the dysfunction of innate immunity in HIV-infected mother-newborn pairs. The activation of the TLR7/8 pathway could function as an adjuvant to improve maternal-neonatal innate immunity.