How well do parents identify their child's baby teeth? Engagement and accuracy of parent-reported information on a tooth checklist survey.

OBJECTIVES: Naturally exfoliated primary teeth are being increasingly collected in child development studies. Most of these odontological collections and tooth biobanks use parent-reported information from questionnaires or tooth checklists to collect data on offspring teeth. To the best of the authors' knowledge, no studies have assessed parental engagement in tooth checklists, nor parental accuracy in identifying their child's baby tooth. This study aimed to evaluate these dimensions by analysing data from the about this tooth checklist returned with donated primary teeth in a natural experimental study called STRONG (the Stories Teeth Record of Newborn Growth). METHODS: Parental self-reported information were analysed on checklists returned with 825 primary teeth belonging to 199 children. The percentage of blank answers was calculated for each question. The accuracy of parents-reported tooth identification was evaluated by comparing parental ratings to researchers' ratings. Reliability of researchers' tooth identification was first evaluated by calculating intra-observer and inter-observer agreements, as well as Cohen's Kappa values. The percentage of accuracy of parents' tooth identification (relative to researcher's) was then calculated, and logistic regressions were used to evaluate if time elapsed between when exfoliation occurred and the checklist was completed associated with parental accuracy in tooth identification. RESULTS: Parents returned 98.4% of the checklists and completed 74.9% to 97.7% of the questions. Excellent reliability was demonstrated for researchers' intra- and inter-rater tooth identification (agreement percentages >90%; Cohen's Kappa values >.83). Moderate accuracy of parents-reported tooth identifications was found, with parents correctly identifying 49.5% of the donated tooth. Better parental accuracies were highlighted for partial identifications (87.1% of correct jaw, 75.6% of correct tooth type, and 65.8% of correct lateralization). Logistic regressions showed the odds of correct parental identifications decreased on average by 1.8% every 30 days of distance between tooth exfoliation and checklist completion. CONCLUSIONS: While parental engagement is high, parents-reported tooth identifications have moderate accuracy, which decreases over time. High accuracy is however found for partial identifications. Parent-reported information on the accompanying questionnaire of naturally exfoliated primary teeth collection or tooth biobanks, even when filled in a long time after exfoliation took place, should be encouraged. However, expert identifications of teeth should remain best practice.

A qualitative study on the healthcare experiences of adolescents and young adults (AYA) with an uncertain or poor cancer prognosis.

PURPOSE: Treatment advancements have improved life expectancy for adolescents and young adults (AYAs) with an uncertain and/or poor cancer prognosis (UPCP) and change clinical practice. This improved survival requires a different approach and specific expertise to meet the needs of this group. The aim of this study is to explore the health care experiences of AYAs with a UPCP. METHODS: We conducted a multicenter qualitative study using semi-structured interviews and elements of the grounded theory by Corbin and Strauss. RESULTS: Interviews were conducted with 46 AYAs with a UPCP. They were on average 33.4 years old (age range 23-44), and most of them were woman (63%). Additionally, five AYAs with a UPCP participated as AYA research partners in two focus groups. They were on average 31.8 years old and four of them were woman. AYAs with a UPCP reported four pillars for a satisfied healthcare experience: (1) trust, (2) tailored communication, (3) holistic empathic open attitude, and (4) care being offered (pro-)actively. They reported both optimal and suboptimal experiences about distrust based on a delay in diagnostic trajectory, lack of tailored communication and discussion of sensitive topics, preference for a holistic approach, and struggles with finding the way to get additional healthcare support. CONCLUSION: For AYAs with a UPCP, it is important that both age-specific issues and issues related to the UPCP are understood and addressed; however, this seems not yet optimally implemented in clinical practice. This emphasizes the importance of providing this patient group with tailored care incorporating both aspects. Healthcare professionals need to be supported with training and tools to understand the healthcare needs of AYAs with a UPCP. AYAs can be empowered to take more control over their own healthcare needs.

Involving adolescents and young adults (AYA) with an uncertain or poor cancer prognosis as research partners.

BACKGROUND: The interest in patient involvement is increasing in health research, however, is not yet well described in adolescents and young adults (AYA) with palliative cancer, such as AYAs with an uncertain and/or poor cancer prognosis (UPCP). This study aimed to document the process of involving AYAs with a UPCP as partners in research including their experiences, the impact, and our lessons learned. MATERIALS AND METHODS: AYAs with a UPCP were recruited via healthcare professionals and patients to involve as research partners in the qualitative interview study. To define their role and tasks in each research phase we used the participation matrix. RESULTS: In total six AYAs with a UPCP were involved as research partners and five as co-thinkers. They were involved in initiating topics, developing study design, interviewing, analyzing data, and dissemination of information. Together with the researcher, they co-produced the information letters and interview guides and implemented aftercare and extra support. The research partners ensured that the data was relevant, correctly interpreted and that results were translated to peers and clinical practice. AYAs themselves felt useful, found people who understand their challenges, and were able to create a legacy. CONCLUSION: The benefits of involving AYAs with a UPCP as research partners cannot be stressed enough, both for the study as well as for the AYAs themselves, but there are challenges. Researchers should anticipate and address those challenges during the planning phase of the study. This article provides practical tips on how to do so.

"Finding my way in a maze while the clock is ticking": The daily life challenges of adolescents and young adults with an uncertain or poor cancer prognosis.

Introduction: Increasingly more adolescent and young adult (AYA, aged 18-39 years) patients with an uncertain and/or poor cancer prognosis (UPCP) are gaining life-years because of novel treatments or refinement of established therapies, and sometimes even face the prospect of long-term disease control. This study aims to examine the challenges of AYAs with a UPCP in daily life to inform the development of AYA care programs. Methods: Semi-structured in-depth interviews were conducted among AYAs with a UPCP. Since we expected differences in experiences between three AYA subgroups, we interviewed patients of these subgroups (1): traditional survivors (2), low-grade glioma survivors, and (3) new survivors. Interviews were analyzed using elements of grounded theory. AYA patients were actively involved as research partners. Results: In total 46 AYAs with UPCP participated and shared their challenges in daily life. They were on average 33.4 years old (age range 23-44) and most of them were women (63%). The most common tumor types were low-grade gliomas (16), sarcomas (7), breast cancers (6), and lung cancers (6). We identified five primary themes: (1) feeling inferior to previous self and others (e.g. feeling useless, who wants me in a relationship), (2) feeling of being alone (e.g. lonely thoughts, nobody really gets me), (3) ongoing confrontation (e.g. it is always there, own decline), (4) grief about life (e.g. grief about life I did not get, grief about old life), and (5) loss of control over the future (e.g. not able to make future plans, waiting for growth). Although all of the challenges were identified in the three AYA subgroups, the perceived intensity of the challenges differed slightly between the subgroups. Discussion: AYAs living with a UPCP experience challenges associated to their sense of altered identity, their position in the social network, and the future uncertainties. This study highlights the importance to recognize and acknowledge the unique challenges of this group. To provide age-specific care, it is important to embed acceptance and commitment therapy and AYA peer support within the healthcare system and other care programs to support AYAs to live well with their disease.

Germline MBD4 deficiency causes a multi-tumor predisposition syndrome.

We report an autosomal recessive, multi-organ tumor predisposition syndrome, caused by bi-allelic loss-of-function germline variants in the base excision repair (BER) gene MBD4. We identified five individuals with bi-allelic MBD4 variants within four families and these individuals had a personal and/or family history of adenomatous colorectal polyposis, acute myeloid leukemia, and uveal melanoma. MBD4 encodes a glycosylase involved in repair of G:T mismatches resulting from deamination of 5'-methylcytosine. The colorectal adenomas from MBD4-deficient individuals showed a mutator phenotype attributable to mutational signature SBS1, consistent with the function of MBD4. MBD4-deficient polyps harbored somatic mutations in similar driver genes to sporadic colorectal tumors, although AMER1 mutations were more common and KRAS mutations less frequent. Our findings expand the role of BER deficiencies in tumor predisposition. Inclusion of MBD4 in genetic testing for polyposis and multi-tumor phenotypes is warranted to improve disease management.

Factors influencing the implementation of pharmaceutical care in outpatient settings: A systematic review applying the Consolidated Framework for Implementation Research.

BACKGROUND: Pharmaceutical care in outpatient settings is a type of health service that has been shown to contribute to decreasing drug-related morbidity and mortality rates. However, every process of implementing a new service brings about changes and transformations in the work routine, thus posing challenges. OBJECTIVES: This systematic review aims to identify barriers to and facilitators for the implementation of pharmaceutical care in outpatient settings by applying the CFIR method, a framework based on the theory of health services, used to analyze and synthesize research data, which can direct strategies for the service to work as planned. METHODS: A systematic review was conducted exploring the barriers to and facilitators for the implementation of pharmaceutical care in outpatient settings. The MEDLINE, EMBASE, CINAHL, COCHRANE, and LILACS databases were consulted. RESULTS: Eight studies were included: five qualitative ones, two mixed-method ones, and a quantitative one. The most frequent CFIR constructs identified were Patient Needs and Resources (n = 30, 10.75%), Knowledge and Beliefs about the Intervention (n = 31, 11.11%), Networks and Communications (n = 34, 12.19%), and Available Resources (n = 56, 20.07%). The most cited barriers were: insufficient human resources, patients' unawareness of the existence of the pharmaceutical care service, and pharmacists' resistance to changes. Facilitators included: the opportune presentation of the service to the healthcare team; the use of electronic devices for specific guidance; and the assessment of patient satisfaction. CONCLUSIONS: This systematic review allowed detecting key guidelines to improve the implementation process, including (1) defining an implementation method and exploring it extensively during the pre-implementation phase, (2) ensuring human and financial resources, (3) determining how the new service will interact with other existing services. More research is needed to understand how these factors can affect the implementation of clinical services.

Dental microstructure records life history events: A histological study of mandrills (Mandrillus sphinx) from Gabon.

Accentuated lines in dental microstructure are hypothesized to correlate with potentially stressful life history events, but our understanding of when, how and why such accentuated lines form in relation to stressful events is limited. We examined accentuated line formation and life history events in the teeth of three naturally deceased mandrills (Mandrillus sphinx, Cercopithecidae), for whom we had detailed life history information. We determined the ages at formation of accentuated lines in histological tooth sections and used dates of birth and death to calibrate dental histology to calendar time and individual age. We found accentuated lines that matched their mother's resumption of sexual cycles in two individuals, and possibly in the third individual. The subjects also formed lines when their mothers were mate-guarded by males or wounded. Accentuated lines matched the birth of the next sibling in one of two cases. Both females formed accentuated lines when they experienced their own sexual swelling cycles, but lines did not match all sexual swelling cycles. Mate-guarding matched an accentuated line in one case, but not in another. Lines matched all three parturitions in the two females. Changes in alpha male and captures did not consistently coincide with accentuated line formation, but repeated captures were associated with lines. Using simulated data, we show that the observed number of matches between lines and events would be very unlikely under a null hypothesis of random line formation. Our results support the hypothesis that some life history events are physiologically stressful enough to cause accentuated line formation in teeth. They contribute to our understanding of how primate life histories are recorded during dental development and enhance our ability to use teeth to reconstruct life history in the absence of direct observation.

Majewski/Microcephalic Osteodysplastic Primordial Dwarfism Type II (MOPDII) with generalised microdontia in the 4th millennium BCE Eastern Mediterranean.

OBJECTIVE: This research evaluates the occurrence of generalised microdontia and proportionate osteodysplasia in human remains from a Chalcolithic cemetery with early evidence of metalworking in Cyprus (Souskiou-Laona; 3500-2800 BCE). MATERIALS: Skeletal and dental remains from Tomb 236 Individual A, in comparison with other human remains from Souskiou-Laona (MNI: 203). METHODS: Macroscopic, microscopic, and metric observation of osteodysplasia and microdontia. RESULTS: Smaller than usual permanent teeth and adult long bones were discovered, with epiphyseal fusion complete. The cranium, and the zygomatic bones were smaller than other adult remains. CONCLUSIONS: Differential diagnosis includes pituitary dwarfism and Majewski/Microcephalic Osteodysplastic Primordial Dwarfism Type II (MOPDII), which are two types of proportionate dwarfism with presentation of microdontia. This individual appears to display skeletal changes consistent with Majewski/Microcephalic Osteodysplastic Primordial Dwarfism Type II. SIGNIFICANCE: This is the first case of MOPDII in the archaeological record worldwide, and it is the oldest case of proportionate dwarfism known to date. The presence of an adult probable female with primordial dwarfism at Chalcolithic cemetery of Souskiou-Laona indicates that mutations of the pericentrin (PCNT) gene were present in this early period. LIMITATIONS: The remains of the individual were incomplete and poorly preserved. SUGGESTIONS FOR FURTHER RESEARCH: Histology may lead to more detailed information on the individual's age and life story (osteobiography).

First permanent molars with accentuated line patterns: Assessment of childhood health in an urban complex of the fifth millennium before the present.

OBJECTIVES: The objectives are 1) to calculate the position of highly accentuated lines in dental enamel of a group of individuals from Shahr-i-Sokhta, a thriving urban centre in Bronze Age South West Asia; 2) to identify peak frequencies of physiologically stressful periods during early childhood of these individuals; and 3) to relate these peak frequencies to developmental milestones at population level. DESIGN: We analysed highly accentuated lines in the enamel of nine (n = 9) permanent mandibular first molars of nine individuals from the 5th millennium before the present urban and long-distance-trading complex, Shahr-i Sokhta (Iran). Age at death ranged between 4.5 years and 18-20 years. Permanent mandibular first molar enamel begins to mineralise before birth, and is normally completed sometime between 2.1-3.3 years, giving us insight to early childhood physiological stress, the ages at which it occurs, and any peaks in the frequencies in highly accentuated line formation, through histological sections investigated using transmitted light microscopy. RESULTS: Highly accentuated line peak frequencies occur in the sample at c. four, nine, eleven, and twelve months. After 1 year of age, no more peaks occur. CONCLUSION: The peak frequencies coincide with the timing timing of the type of developmental milestones which may have exposed the individuals to an increased pathogen load, injury, or sub-optimal diet. We note similarity in peak timings in the few published, disparate populations, suggest a potential link with attainment of developmental milestones connected with morbidity, and propose reporting standardised statistics to enable exploration of differences between populations in terms of postnatal health-related stress.

Dimethyl fumarate-induced lymphocyte count drop is related to clinical effectiveness in relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: Dimethyl fumarate (DMF) causes a mean lymphocyte count drop of approximately 30% in relapsing-remitting multiple sclerosis (RRMS) patients. The relationship between this reduction and DMF effectiveness is controversial. The objective was to investigate if the decrease in absolute lymphocyte count (ALC) from baseline during DMF treatment is associated with clinical and magnetic resonance imaging (MRI) disease activity. A secondary aim was to evaluate ALC variations over time in a real-life cohort of DMF-treated patients. METHODS: Demographic, laboratory, clinical and MRI data were collected in this observational multicentre study, conducted on RRMS patients treated with DMF for at least 6 months. Multivariate Cox models were performed to evaluate the impact of 6-month ALC drop on time to no evidence of disease activity (NEDA-3) status loss. NEDA-3 is defined as absence of clinical relapses, MRI disease activity and confirmed disability progression. RESULTS: In all, 476 patients (312 females, age at DMF start 38.4 ± 9.97 years) were analysed up to 5-year follow-up. A greater lymphocyte decrease was associated with a lower risk of NEDA-3 status loss (hazard ratio 0.87, P = 0.01). A worse outcome in patients with lower ALC drop (<11.5%), compared with higher tertiles (11.5%-40.5% and >40.5%), was observed (P = 0.008). The nadir of ALC drop (-33.6%) and 35% of grade III lymphopaenia cases occurred after 12 months of treatment. CONCLUSION: A higher lymphocyte count drop at 6 months is related to better outcomes in DMF-treated patients. A careful ALC monitoring should be pursued up to 24 months of treatment.

Odontochronologies in male and female mandrills (Mandrillus sphinx) and the development of dental sexual dimorphism.

OBJECTIVES: We examine how dental sexual dimorphism develops in mandrills, an extremely sexually dimorphic primate. We aimed to (a) establish the chronology of dental development (odontochronology) in male and female mandrills, (b) understand interindividual and intersex variation in odontochronologies, and (c) determine how dental sexual dimorphism is achieved. MATERIALS AND METHODS: We prepared histological ground sections from the permanent teeth of four female and four male mandrills from the semi-free ranging colony at the Centre International de Recherches Médicales, Franceville, Gabon. We used the microscopic growth increments in the sections to create odontochronologies. We compared ages at crown initiation, crown formation times (CFT) and crown extension rates (CER) between individuals and sexes to assess interindividual and intersex variation. RESULTS: All mandrill teeth are sexually dimorphic in size. Dental sexual dimorphism in mandrills is achieved via sex differences in the duration of growth (bimaturism) and in growth rates. We also found interindividual and intersex variation in the ages at initiation and completion of crown formation. DISCUSSION: Our results show that the rate of ameloblast differentiation varies between individuals and that selection for both the age at tooth initiation and CER has occurred independently in males and females to ensure that the teeth develop at appropriate times relative to the growth of the sexually dimorphic jaws. They also show that canine dimorphism is achieved through differences in both CER and CFT, unlike extant great apes or Cantius. Given at least three mechanisms for achieving canine dimorphism, we need more information to trace the evolution of this trait in primates.

Climate Change and Schools: Environmental Hazards and Resiliency.

The changing climate is creating additional challenges in maintaining a healthy school environment in the United States (U.S.) where over 50 million people, mostly children, spend approximately a third of their waking hours. Chronic low prioritization of funds and resources to support environmental health in schools and lack of clear regulatory oversight in the U.S. undergird the new risks from climate change. We illustrate the extent of risk and the variation in vulnerability by geographic region, in the context of sparse systematically collected and comparable data particularly about school infrastructure. Additionally, we frame different resilience building initiatives, focusing on interventions that target root causes, or social determinants of health. Disaster response and recovery are also framed as resilience building efforts. Examples from U.S. Federal Region 2 (New Jersey, New York, Puerto Rico, and the U.S. Virgin Islands) and nationally are used to illustrate these concepts. We conclude that better surveillance, more research, and increased federal and state oversight of environmental factors in schools (specific to climate risks) is necessary, as exposures result in short- and long term negative health effects and climate change risks will increase over time.

Glaucarubulone glucoside from Castela macrophylla suppresses MCF-7 breast cancer cell growth and attenuates benzo[a]pyrene-mediated CYP1A gene induction.

Quassinoids often exhibit antioxidant and antiproliferative activity. Emerging evidence suggests that these natural metabolites also display chemopreventive actions. In this study, we investigated the potential for the quassinoid glaucarubulone glucoside (Gg), isolated from the endemic Jamaican plant Castela macrophylla (Simaroubaceae), to display potent cytotoxicity and inhibit human cytochrome P450s (CYPs), particularly CYP1A enzymes, known to convert polyaromatic hydrocarbons into carcinogenic metabolites. Gg reduced the viability of MCF-7 breast adenocarcinoma cells (IC50 = 121 nm) to a greater extent than standard of care anticancer agents 5-fluorouracil, tamoxifen (IC50 >10 µm) and the tamoxifen metabolite 4-hydroxytamoxifen (IC50 = 2.6 µm), yet was not cytotoxic to non-tumorigenic MCF-10A breast epithelial cells. Additionally, Gg induced MCF-7 breast cancer cell death. Gg blocked increases in reactive oxygen species in MCF-10A cells mediated by the polyaromatic hydrocarbon benzo[a]pyrene (B[a]P) metabolite B[a]P 1,6-quinone, yet downregulated the expression of genes that promote antioxidant activity in MCF-7 cells. This implies that Gg exhibits antioxidant and cytoprotective actions in non-tumorigenic breast epithelial cells and pro-oxidant, cytotoxic actions in breast cancer cells. Furthermore, Gg inhibited the activities of human CYP1A according to non-competitive kinetics and attenuated the ability of B[a]P to induce CYP1A gene expression in MCF-7 cells. These data indicate that Gg selectively suppresses MCF-7 breast cancer cell growth without impacting non-tumorigenic breast epithelial cells and blocks B[a]P-mediated CYP1A induction. Taken together, our data provide a rationale for further investigations of Gg and similar plant isolates as potential agents to treat and prevent breast cancer. Copyright © 2017 John Wiley & Sons, Ltd.

Molecular Targets and Angiogenesis in Renal Cell Carcinoma, A Multitarget Approach: Mini Review.

BACKGROUND: Renal cell carcinoma (RCC) accounts for 2% of all adult malignancies and is associated with a case fatality rate as high as 40%. RCC has been on the rise for the last 6 decades at a steady increase of 2% per annum. Much work has been done to uncover the pathogenesis of the disease and the role of angiogenesis has been a recurrent denominator connected to vascular endothelial growth factor (VEGF) and its downstream effectors along with the mammalian target of rapamycin (mTOR) mediated signal transduction pathway. OBJECTIVE: This review will discuss relevant inhibitors of key biomarkers to the disease in hopes of paving the way for novel treatments geared towards improving RCC morbidity and mortality rates. RESULTS AND CONCLUSION: Currently, treatment of advanced RCC includes one or more of the following: partial or radical nephrectomy, systemic therapy, immunotherapy and targeted therapy. Still drug resistance continues to be a challenge to many of the approved drugs and those undergoing clinical trials. However, the inclusion of targeted therapies has improved advanced RCC treatment success rates over that of surgery alone, and over that of the use of traditional chemotherapy for this relatively chemo-resistant disease. In an era of personalized medicine, research utilizing a polypharmacology approach could enhance efficacy of drug leads to treating RCC.

Effectiveness of an oral health program for mothers and their infants.

BACKGROUND: The baby oral health program (bOHP) provides pregnant women and their future babies with oral care. AIM: To assess the bOHP effectiveness by comparing caries prevalence in infants enrolled and not enrolled in the oral health program (OHP). DESIGN: Mothers who had been invited to participate in the bOHP from 2006 to 2009 were contacted. Two groups were formed: 87 pairs of mothers and infants who effectively participated in the OHP (G1) and 107 pairs who did not (G2). Mothers and infants were given a dental examination. Socio-economic status (SES) and education level (EL) questionnaires were completed. t-tests and multivariate logistic regression were used in analyzing data. RESULTS: Statistically significant differences were observed in the mean age of mothers (G1 = 33.8 years; G2 = 35.6 years; P = 0.015) and mean decayed, missed and filled surface (DMFS) score (G1 = 24.71; G2 = 32.58; P < 0.001), not in SES (P = 0.758) and EL (P = 0.109). Mean age and mean dmfs scores of G1 and G2 children were 4.2 and 4.4 years (P = 0.068), and 0.25 and 4.12 (P < 0.001), respectively. The odds ratio (OR) for children in G2 to develop dentine lesions, as opposed to those in G1, was 48.56. CONCLUSION: The bOHP was effective in preventing caries in infants enrolled in the program.

Draft Genome Sequence of Salmonella enterica subsp. enterica Serovar Gallinarum Biovar Pullorum Strain FCAV198, a Brazilian Chicken Pathogen.

Salmonella enterica subsp. enterica serovar Gallinarum biovar Pullorum is a bird-restricted pathogen which causes pullorum disease. The strain FCAV198 was isolated from a pool of chicken ovaries in Brazil, and its genome may be helpful for studies involving molecular mechanisms related to pathogenesis and other related applications.