Publications by authors named "Maria Anderson"

44 Publications

Dental trauma in toddlers 1-3 years of age living in multicultural areas of Stockholm, Sweden: A retrospective cohort study.

Dent Traumatol 2021 Apr 10. Epub 2021 Apr 10.

Division of Orthodontics and Pediatric Dentistry, Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden.

Background/aim: Traumatic dental injuries are common and affect many children. The aim of this retrospective study was to investigate the prevalence and characteristics of dental trauma as well as the costs and resource use in a cohort of children aged 1-3 years in low socioeconomic areas (low income and educational level) of Stockholm.

Materials And Methods: Data were extracted from a larger intervention trial and analyzed for the prevalence and other characteristics of dental trauma as well as patient characteristics of children (n = 1346) from six dental clinics in low-income, multicultural areas. Variables describing the trauma, socioeconomic status, direct and indirect costs, and time spent at the emergency visit for the dental trauma were retrieved from the dental records. The study also recorded which healthcare profession handled the first and follow-up visits.

Results: The prevalence of dental trauma in the study cohort was 8.2%, and higher among boys (n = 71) than girls (n = 39). Boys exhibited a significantly higher risk for dental trauma (OR, 1.76; 95% CI = 1.17-2.65). Maxillary incisors were the teeth most often traumatized, and lateral luxation was the most common diagnosis. The mean time spent per child during the first year following the dental trauma was 36 min, and the mean costs per child were EUR 878. The total average per-child cost (direct and indirect costs) for dental trauma was EUR 2107. Dental visits due to traumatic injuries were significantly less common among children with an immigrant background and in families with an income ≤EUR 2000 per month.

Conclusions: Toddlers in families who have a low socioeconomic status, a foreign background, and live in multicultural areas of Stockholm visit dental clinics for traumatic dental injuries less often than non-immigrant children living in families with a high socioeconomic status.
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http://dx.doi.org/10.1111/edt.12677DOI Listing
April 2021

Prevalence and implications of junctional rhythm during transcatheter aortic valve replacement.

Cardiovasc Revasc Med 2020 Nov 12. Epub 2020 Nov 12.

Division of Cardiology, Minneapolis VA Health Care System, Minneapolis, MN, USA; Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA.

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http://dx.doi.org/10.1016/j.carrev.2020.11.014DOI Listing
November 2020

Environmental Enrichment: Disentangling the Influence of Novelty, Social, and Physical Activity on Cerebral Amyloid Angiopathy in a Transgenic Mouse Model.

Int J Mol Sci 2020 Jan 28;21(3). Epub 2020 Jan 28.

Department of Psychology, Stony Brook University, 100 Nicolls Road, Stony Brook, NY 11794, USA.

Cerebral amyloid angiopathy (CAA) is the deposition of amyloid protein in the cerebral vasculature, a common feature in both aging and Alzheimer's disease (AD). However, the effects of environmental factors, particularly cognitive stimulation, social stimulation, and physical activity, on CAA pathology are poorly understood. These factors, delivered in the form of the environmental enrichment (EE) paradigm in rodents, have been shown to have beneficial effects on the brain and behavior in healthy aging and AD models. However, the relative importance of these subcomponents on CAA pathology has not been investigated. Therefore, we assessed the effects of EE, social enrichment (SOC), and cognitive enrichment (COG) compared to a control group that was single housed without enrichment (SIN) from 4 to 8 months of age in wild-type mice (WT) and Tg-SwDI mice, a transgenic mouse model of CAA that exhibits cognitive/behavioral deficits. The results show that individual facets of enrichment can affect an animal model of CAA, though the SOC and combined EE conditions are generally the most effective at producing physiological, cognitive/behavioral, and neuropathological changes, adding to a growing literature supporting the benefits of lifestyle interventions.
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http://dx.doi.org/10.3390/ijms21030843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7038188PMC
January 2020

Voluntary Wheel Running Reduces Amyloid-β42 and Rescues Behavior in Aged Tg2576 Mouse Model of Alzheimer's Disease.

J Alzheimers Dis 2020 ;73(1):359-374

Department of Psychology, Stony Brook University, Stony Brook, NY, USA.

Exercise has been shown to be protective against the risk of dementias, including Alzheimer's disease (AD). Intervention studies have demonstrated its ability to mitigate cognitive and behavioral impairments and reduce disease in both humans and animals. However, information is lacking in regard to the volume and intensity, as well as timing of exercise onset with respect to disease stage, which produces optimal benefits. Here, utilizing the Tg2576 mouse, a model of AD-like parenchymal amyloid pathology and cognitive impairment, we sought to understand the effects of different lengths of daily access to a running wheel on advanced stage disease. This study is the first to determine the benefits of long-term exercise (4 months of voluntary running) and different periods of daily access to a running wheel (0 h, 1 h, 3 h, and 12 h running wheel access) beginning in 14-month-old Tg2576 mice, an age with significant amyloid pathology. We found that exercising Tg2576 animals showed lower levels of some aspects of AD pathology and reduced behavioral dysfunction compared to sedentary Tg2576 animals. High intensity exercise, rather than high volume exercise, was generally most beneficial in reducing amyloid pathology. Our results suggest that engaging in vigorous exercise programs, even after living a sedentary life, may lead to a measurable reduction in AD pathology and preservation of some cognitive abilities.
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http://dx.doi.org/10.3233/JAD-190810DOI Listing
April 2021

Long-term voluntary wheel running does not alter vascular amyloid burden but reduces neuroinflammation in the Tg-SwDI mouse model of cerebral amyloid angiopathy.

J Neuroinflammation 2019 Jul 11;16(1):144. Epub 2019 Jul 11.

Department of Psychology, Stony Brook University, 100 Nicolls Road, Stony Brook, NY, 11794, USA.

Background: Cardiovascular exercise (CVE) has been shown to be protective against cognitive decline in aging and the risk for dementias, including Alzheimer's Disease (AD). CVE has also been shown to have several beneficial effects on brain pathology and behavioral impairments in mouse models of AD; however, no studies have specifically examined the effects of CVE on cerebral amyloid angiopathy (CAA), which is the accumulation of amyloid-beta (Aβ) in the cerebral vasculature. CAA may be uniquely susceptible to beneficial effects of CVE interventions due to the location and nature of the pathology. Alternatively, CVE may exacerbate CAA pathology, due to added stress on already compromised cerebral vasculature.

Methods: In the current study, we examined the effects of CVE over many months in mice, thereby modeling a lifelong commitment to CVE in humans. We assessed this voluntary CVE in Tg-SwDI mice, a transgenic mouse model of CAA that exhibits behavioral deficits, fibrillar vascular Aβ pathology, and significant perivascular neuroinflammation. Various "doses" of exercise intervention (0 h ("Sedentary"), 1 h, 3 h, 12 h access to running wheel) were assessed from ~ 4 to 12 months of age for effects on physiology, behavior/cognitive performance, and pathology.

Results: The 12 h group performed the greatest volume of exercise, whereas the 1 h and 3 h groups showed high levels of exercise intensity, as defined by more frequent and longer duration running bouts. Tg-SwDI mice exhibited significant cerebral vascular Aβ pathology and increased expression of pro-inflammatory cytokines as compared to WT controls. Tg-SwDI mice did not show motor dysfunction or altered levels of anxiety or sociability compared to WT controls, though Tg-SwDI animals did appear to exhibit a reduced tendency to explore novel environments. At all running levels, CAA pathology in Tg-SwDI mice was not significantly altered, but 12-h high-volume exercise showed increased insoluble Aβ burden. However, CVE attenuated the expression of pro-inflammatory cytokines TNF-α and IL-6 and was generally effective at enhancing motor function and reducing anxiety-like behavior in Tg-SwDI mice, though alterations in learning and memory tasks were varied.

Conclusions: Taken together, these results suggest that CAA can still develop regardless of a lifespan of substantial CVE, although downstream effects on neuroinflammation may be reduced and functional outcomes improved.
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http://dx.doi.org/10.1186/s12974-019-1534-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6621983PMC
July 2019

[Expansion of family medicine in Latin America: challenges and lines of actionExpansão da medicina familiar na América Latina: desafios e linhas de ação].

Rev Panam Salud Publica 2018 4;42:e149. Epub 2018 Oct 4.

Universidad Técnica Particular de Loja, Loja, Ecuador.

This article summarizes the current challenges of family medicine in Latin America and proposes possible lines of action to consolidate its development. In the last 40 years, the health systems of the Region of the Americas have faced reforms whose results were negative in terms of equity, and primary health care, far from being a strategy designed to reduce it, was restricted to a selective and focal policy. In this context, the technical proposals for expansion of training positions in family medicine and their insertion in medical careers have lacked consistency and a clear political direction, and thus their lack of effectiveness can be considered a symptom of these incomplete reforms. In this regard, the Ibero-American Confederation of Family Medicine made recommendations on the political commitment of governments to ensure the necessary structure and funding, consolidate the model of family medicine as a mechanism for the implementation of primary health care, the hierarchy of programs of training, the working conditions of family doctors and professional certification, among others. These technical recommendations, without a consistent and timely political action, will not be more successful than previous attempts.
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http://dx.doi.org/10.26633/RPSP.2018.149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6386095PMC
October 2018

Economic evaluation of an expanded caries-preventive program targeting toddlers in high-risk areas in Sweden.

Acta Odontol Scand 2019 May 14;77(4):303-309. Epub 2019 Jan 14.

a Division of Orthodontics and Pediatric Dentistry, Department of Dental Medicine , Karolinska Institutet , Stockholm , Sweden.

Objective: To economically evaluate a caries-preventive program "Stop Caries Stockholm" (SCS) where a standard program is supplemented with biannual applications of fluoride varnish in toddlers and compared it with the standard preventive program.

Material And Methods: Data from the cluster randomized controlled field trial SCS including 3403 children, conducted in multicultural areas with low socioeconomic status was used. The difference in mean caries increment between the examinations; when the toddlers were 1 and 3 years old, was outcome measure of the intervention. The program was evaluated from a societal as well as a dental health care perspective. The incremental cost-effectiveness ratio (ICER) was calculated as the incremental cost for each defs prevented.

Results: Average dental health care costs per child at age 3 years were EUR 95.77 for the supplemental intervention and EUR 70.52 for the standard intervention. The ICER was EUR 280.56 from a dental health care perspective and EUR 468.67 and considered high.

Conclusions: The supplemental caries intervention program was not found to be cost-effective. The program raised costs without significantly reducing caries development. A better alternative use of the resources is recommended.

Trial Registration: www.controlled-trials.com (ISRCTN35086887).
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http://dx.doi.org/10.1080/00016357.2018.1548709DOI Listing
May 2019

Pifithrin-μ modulates microglial activation and promotes histological recovery following spinal cord injury.

CNS Neurosci Ther 2019 02 2;25(2):200-214. Epub 2018 Jul 2.

Program in Molecular and Cellular Pharmacology, Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY, USA.

Background: Treatments immediately after spinal cord injury (SCI) are anticipated to decrease neuronal death, disruption of neuronal connections, demyelination, and inflammation, and to improve repair and functional recovery. Currently, little can be done to modify the acute phase, which extends to the first 48 hours post-injury. Efforts to intervene have focused on the subsequent phases - secondary (days to weeks) and chronic (months to years) - to both promote healing, prevent further damage, and support patients suffering from SCI.

Methods: We used a contusion model of SCI in female mice, and delivered a small molecule reagent during the early phase of injury. Histological and behavioral outcomes were assessed and compared.

Results: We find that the reagent Pifithrin-μ (PFT-μ) acts early and directly on microglia in vitro, attenuating their activation. When administered during the acute phase of SCI, PFT-μ resulted in reduced lesion size during the initial inflammatory phase, and reduced the numbers of pro-inflammatory microglia and macrophages. Treatment with PFT-μ during the early stage of injury maintained a stable anti-inflammatory environment.

Conclusions: Our results indicate that a small molecule reagent PFT-μ has sustained immunomodulatory effects following a single dose after injury.
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http://dx.doi.org/10.1111/cns.13000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488873PMC
February 2019

Phase I study of the anti-α5β1 monoclonal antibody MINT1526A with or without bevacizumab in patients with advanced solid tumors.

Cancer Chemother Pharmacol 2018 08 15;82(2):339-351. Epub 2018 Jun 15.

California Cancer Associates for Research & Excellence, Encinitas, CA, USA.

Purpose: MINT1526A is a monoclonal antibody that blocks the interaction of integrin alpha 5 beta 1 (α5β1) with its extracellular matrix ligands. This phase I study evaluated the safety and pharmacokinetics of MINT1526A with or without bevacizumab in patients with advanced solid tumors.

Methods: MINT1526A was administered every 3 weeks (Q3W) as monotherapy (arm 1) or in combination with bevacizumab 15 mg/kg, Q3W (arm 2). Each arm included a 3 + 3 dose-escalation stage and a dose-expansion stage.

Results: Twenty-four patients were enrolled in arm 1 (dose range 2-30 mg/kg) and 30 patients were enrolled in arm 2 (dose range 3-15 mg/kg). Monocyte α5β1 receptor occupancy was saturated at a dose of 15 mg/kg. No dose-limiting toxicities were observed, and the maximum tolerated dose was not reached in either arm. The most common adverse events, regardless of causality, included abdominal pain (25%), diarrhea (25%), nausea (21%), vomiting (21%), and fatigue (21%) in arm 1 and nausea (40%), fatigue (33%), vomiting (30%), dehydration (30%), headache (30%), and hypertension (30%) in arm 2. No grade ≥ 3 bleeding events were observed in either arm. No confirmed partial responses (PR) were observed in arm 1. In arm 2, one patient with thymic carcinoma experienced a confirmed PR and two patients with hepatocellular carcinoma (HCC) experienced durable minor radiographic responses.

Conclusions: MINT1526A, with or without bevacizumab, was well-tolerated. Preliminary evidence of combination efficacy, including in patients with HCC, was observed, but cannot be distinguished from bevacizumab monotherapy in this phase I study.
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http://dx.doi.org/10.1007/s00280-018-3622-8DOI Listing
August 2018

The effects of volume versus intensity of long-term voluntary exercise on physiology and behavior in C57/Bl6 mice.

Physiol Behav 2018 10 4;194:218-232. Epub 2018 Jun 4.

Department of Psychology, Stony Brook University, 100 Nicolls Road, Stony Brook, NY 11794, United States.

Cardiovascular exercise (CVE) is associated with healthy aging and reduced risk of disease in humans, with similar benefits seen in animals. Most rodent studies, however, have used shorter intervention periods of a few weeks to a few months, begging questions as to the effects of longer-term, or even life-long, exercise. Additionally, most animal studies have utilized a single exercise treatment group - usually unlimited running wheel access - resulting in large volumes of exercise that are not clinically relevant. It is therefore incumbent to determine the physiological and cognitive/behavioral effects of a range of exercise intensities and volumes over a long-term period that model a lifelong commitment to CVE. In the current study, C57/Bl6 mice remained sedentary or were allowed either 1, 3, or 12 h of access to a running wheel per day, 5 days/weeks, beginning at 3.5-4 months of age. Following an eight-month intervention period, animals underwent a battery of behavioral testing, then euthanized and blood and tissue were collected. Longer access to a running wheel resulted in greater volume and higher running speed, but more breaks in running. All exercise groups showed similarly reduced body weight, increased muscle mass, improved motor function on the rotarod, and reduced anxiety in the open field. While all exercise groups showed increased food intake, this was greatest in the 12 h group but did not differ between 1 h and 3 h mice. While exercise dose-dependently increased working memory performance in the y-maze, the 1 h and 12 h groups showed the largest changes in the mass of many organs, as well as alterations in several behaviors including social interaction, novel object recognition, and Barnes maze performance. These findings suggest that long-term exercise has widespread effects on physiology, behavior, and cognition, which vary by "dose" and measure, and that even relatively small amounts of daily exercise can provide benefits.
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http://dx.doi.org/10.1016/j.physbeh.2018.06.002DOI Listing
October 2018

Randomized Phase II Trial of Parsatuzumab (Anti-EGFL7) or Placebo in Combination with Carboplatin, Paclitaxel, and Bevacizumab for First-Line Nonsquamous Non-Small Cell Lung Cancer.

Oncologist 2018 06 7;23(6):654-e58. Epub 2018 Feb 7.

LungenClinic Grosshansdorf, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Grosshansdorf, Germany

Lessons Learned: The lack of efficacy associated with anti-EGFL7 combined with standard bevacizumab and chemotherapy in this phase II trial in non-small cell lung carcinoma is consistent with the lack of benefit observed in colorectal carcinoma, highlighting the challenge of enhancing the efficacy of VEGF inhibition in unselected populations.Future efforts with agents like anti-EGFL7 should be guided by advances in pharmacodynamic and predictive biomarker development for antiangiogenic agents.

Background: Epidermal growth factor-like domain 7 (EGFL7) is an extracellular matrix-associated protein that is upregulated during angiogenesis and supports endothelial cell survival. This phase II trial evaluated the efficacy of the anti-EGFL7 antibody, parsatuzumab, in combination with bevacizumab plus platinum-based therapy for advanced or recurrent nonsquamous non-small cell lung cancer (NS-NSCLC).

Methods: Patients ( = 104) were randomized to either placebo or parsatuzumab (600 mg) in combination with bevacizumab (15 mg/kg) and carboplatin/paclitaxel, administered on day 1 of each 21-day cycle. Carboplatin and paclitaxel were administered for up to six cycles. Bevacizumab and parsatuzumab/placebo were administered for a maximum of 24 months.

Results: The progression-free survival (PFS) hazard ratio (HR) was 1.7 (95% confidence interval [CI], 1.0-2.8;  = .047). The median PFS was 6.7 months for the parsatuzumab arm versus 8.1 months for the placebo arm. The hazard ratio for overall survival (OS) was 1.1 (95% CI, 0.5-2.2;  = .847). The objective response rate (ORR) was 29% in the parsatuzumab arm and 56% in the placebo arm. Overall safety and tolerability were consistent with the established toxicity profile of bevacizumab.

Conclusion: There was no evidence of efficacy for the addition of parsatuzumab to the combination of bevacizumab and chemotherapy for first-line NS-NSCLC.
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http://dx.doi.org/10.1634/theoncologist.2017-0690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067939PMC
June 2018

Approaching Spirituality Using the Patient-Centered Clinical Method.

J Relig Health 2019 Feb;58(1):109-118

Universidade Federal do Mato Grosso do Sul, Campo Grande, Brazil.

Although the scientific literature already suggests the importance of spiritual care in clinical practice, this topic has been apart from the routine of many practitioners, and many physicians still have difficulties in how to carry out such approaches in the clinical setting. This article reflects on the importance of spirituality in the health-disease process and provides an approach to the biopsychosocial-spiritual care in the practice of primary care. In addition, the aim of the authors is to propose a spiritual approach based on the patient-centered clinical method. This method has been used for clinical communication and can be powerful for exploring spiritual history. Thus, using a fictional case scenario as a practical example, the authors guide readers to understand the patient-centered approach they propose.
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http://dx.doi.org/10.1007/s10943-017-0534-6DOI Listing
February 2019

Mapping the Nephron Exercise Incorporates Multiple Learning Strategies.

MedEdPORTAL 2017 09 28;13:10635. Epub 2017 Sep 28.

First-year Medical Student, Indiana University School of Medicine.

Introduction: Understanding the location and action of nephron transporters and channels is important to the understanding of renal function. As each region of the nephron is unique in its inclusion of specific transporters and channels, mapping of the nephron is an effective first step in understanding overall nephron processing. We describe a small-group, active-learning exercise that facilitates students' ability to understand renal processing within each region of the nephron.

Methods: Following an overview lecture on renal transporters and channels, small groups of students worked cooperatively to map the nephron. This 2-hour, collaborative exercise was developed to reinforce key concepts in renal processing of ions and nutrients and, at the same time, utilize effective learning strategies. Learning strategies incorporated in this exercise include small-group collaboration, peer teaching, retrieval practice using an audience response system, and elaboration through discussion.

Results: Written examination was used to assess student understanding. Students demonstrated higher performance on a subset of questions related to this learning activity compared to the overall exam. Highly positive feedback was provided by a convenience sample of students completing an anonymous survey.

Discussion: This nephron-mapping exercise was an effective means to promote synthesis and analysis of lecture content and engage students in methods that enhance learning.
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http://dx.doi.org/10.15766/mep_2374-8265.10635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338137PMC
September 2017

Impact of biannual treatment with fluoride varnish on tooth-surface-level caries progression in children aged 1-3 years.

J Dent 2017 Oct 22;65:83-88. Epub 2017 Jul 22.

Department of Dental Medicine (DENTMED), OF, Division 6, Pedodontics, Box 4064, 141 04, Huddinge, Sweden; Pediatric Dentistry, Public Dental Service, Eastman Institute, Dalagatan 11, SE-11324, Stockholm, Sweden; Center for Pediatric Oral Health Research, Pediatric Dentistry, Public Dental Service, Eastman Institute, Dalagatan 11, SE-11324, Stockholm, Sweden. Electronic address:

Objective: This study describes caries progression at tooth-surface level in children from 1 to 3 years of age and the impact of biannual treatment with fluoride varnish.

Methods: Children who participated in a cluster-randomized controlled trial and had shown signs of dental caries were included in this study (n=801). International Caries Detection and Assessment System (ICDAS) was used to classify dental caries. The present study compared children receiving a standard yearly intervention to children receiving the same standard preventive intervention supplemented with an application of fluoride varnish every half year.

Results: The maxillary incisors were the first teeth to develop cavitation (ICDAS 3-6) and also mostly affected. Further analyses focusing on maxillary incisors buccal surfaces showed that sound surfaces had least progression and that progression to extensive decay was more common in teeth that had exhibited moderate decay. A summarizing progression index (PI) was calculated for the buccal surfaces of the maxillary incisors. Between 1 and 2 years of age PI was 26% and between 2 and 3 years of age PI was 21%. The progression on buccal incisors and on occlusal first primary molars did not differ between intervention groups (p≤0,05).

Conclusion: No impact on caries progression for biannual treatment with fluoride varnish was found.

Clinical Significance: Using fluoride varnish as a complement to standard intervention in toddlers did not add in the prevention of dental caries or its progression. The education of parents in the use fluoride toothpaste as they start brushing the teeth of their children is essential.
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http://dx.doi.org/10.1016/j.jdent.2017.07.009DOI Listing
October 2017

Randomized Phase II Trial of Parsatuzumab (Anti-EGFL7) or Placebo in Combination with FOLFOX and Bevacizumab for First-Line Metastatic Colorectal Cancer.

Oncologist 2017 04 8;22(4):375-e30. Epub 2017 Mar 8.

Duke Clinical Research Institute, Durham, North Carolina, USA

Lessons Learned: These negative phase II results for parsatuzumab highlight the challenges of developing an agent intended to enhance the efficacy of vascular endothelial growth factor inhibition without the benefit of validated pharmacodynamic biomarkers or strong predictive biomarker hypotheses.Any further clinical development of anti-EGFL7 is likely to require new mechanistic insights and biomarker development for antiangiogenic agents.

Background: EGFL7 (epidermal growth factor-like domain 7) is a tumor-enriched vascular extracellular matrix protein that supports endothelial cell survival. This phase II trial evaluated the efficacy of parsatuzumab (also known as MEGF0444A), a humanized anti-EGFL7 IgG monoclonal antibody, in combination with modified FOLFOX6 (mFOLFOX6) (folinic acid, 5-fluorouracil, and oxaliplatin) bevacizumab in patients with previously untreated metastatic colorectal cancer (mCRC).

Methods: One-hundred twenty-seven patients were randomly assigned to parsatuzumab, 400 mg, or placebo, in combination with mFOLFOX6 plus bevacizumab, 5 mg/kg. Treatment cycles were repeated every 2 weeks until disease progression or unacceptable toxicity for a maximum of 24 months, with the exception of oxaliplatin, which was administered for up to 8 cycles.

Results: The progression-free survival (PFS) hazard ratio was 1.17 (95% confidence interval [CI], 0.71-1.93;  = .548). The median PFS was 12 months for the experimental arm versus 11.9 months for the control arm. The hazard ratio for overall survival was 0.97 (95% CI, 0.46-2.1;  = .943). The overall response rate was 59% in the parsatuzumab arm and 64% in the placebo arm. The adverse event profile was similar in both arms.

Conclusions: There was no evidence of efficacy for the addition of parsatuzumab to the combination of bevacizumab and chemotherapy for first-line mCRC. 2017;22:375-e30.
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http://dx.doi.org/10.1634/theoncologist.2016-0133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5388369PMC
April 2017

Oral microflora in preschool children attending a fluoride varnish program: a cross-sectional study.

BMC Oral Health 2016 Dec 8;16(1):130. Epub 2016 Dec 8.

Department of Odontology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Background: To compare the oral microflora in preschool children attending a fluoride varnish program with a reference group receiving a standard oral health program without fluoride varnish applications. A second aim was to relate the microbial composition to the caries prevalence.

Methods: Five hundred seven 3-year-old children were enrolled from a cohort of 3403 preschool children taking part in a community based oral health project. Two hundred sixty-three of them had attended caries-preventive program with semi-annual applications of a fluoride varnish since the age of 1 year (test group) while 237 had received standard preventive care (reference group). Oral samples were collected with a sterile swab and analysed with checkerboard DNA-DNA hybridization using 12 pre-determined bacterial probes. Caries and background data were collected from clinical examinations and questionnaires.

Results: Gram-positive streptococci (S. intermedius, S. salivarius, S. oralis) were most frequently detected and displayed the highest counts in both groups. There were no significant differences between the groups concerning prevalence of any of the selected bacterial strains except for S. oralis that occurred less frequently in the reference group. In children with caries, V. parvula were significantly more common (p < 0.05) while strains of Lactobacillus, Bifidobacterium and Neisseria were more prevalent among the caries-free children (p < 0.05).

Conclusions: A 2-year community program with semi-annual fluoride varnish applications did not seem to significantly influence the oral microflora in preschool children.

Trial Registration: www.controlled-trials.com (ISRCTN35086887) 20131216 'retrospectively registered'.
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http://dx.doi.org/10.1186/s12903-016-0325-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5146842PMC
December 2016

Randomized Phase II Study of Duligotuzumab (MEHD7945A) vs. Cetuximab in Squamous Cell Carcinoma of the Head and Neck (MEHGAN Study).

Front Oncol 2016 31;6:232. Epub 2016 Oct 31.

Antwerp University Hospital , Edegem , Belgium.

Background: Duligotuzumab, a novel dual-action humanized IgG1 antibody that blocks ligand binding to epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 3 (HER3), inhibits signaling from all ligand-dependent HER dimers, and can elicit antibody-dependent cell-mediated cytotoxicity. High tumor-expression of neuregulin 1 (NRG1), a ligand to HER3, may enhance sensitivity to duligotuzumab.

Methods: This multicenter, open-label, randomized phase II study (MEHGAN) evaluated drug efficacy in patients with recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) progressive on/after chemotherapy and among patients with NRG1-high tumors. Patients received duligotuzumab (1100 mg IV, q2w) or cetuximab (400 mg/m load, 250 mg/m IV, q1w) until progression or intolerable toxicity. Tumor samples were assayed for biomarkers [, and human papillomavirus (HPV) status].

Results: Patients ( = 121) were randomized (duligotuzumab:cetuximab; 59:62), median age 62 years; ECOG 0-2. Both arms (duligotuzumab vs. cetuximab, respectively) showed comparable progression-free survival [4.2 vs. 4.0 months; HR: 1.23 (90% confidence interval (CI): 0.89-1.70)], overall survival [7.2 vs. 8.7 months; HR 1.15 (90% CI: 0.81-1.63)], and objective response rate (12 vs. 14.5%), with no difference between patients with -high tumors or -low tumors. Responses in both arms were confined to HPV-negative patients. Grade ≥3 adverse events (AEs) (duligotuzumab vs. cetuximab, respectively) included infections (22 vs. 11.5%) and GI disorders (17 vs. 7%), contributing to higher rates of serious AEs (41 vs. 29.5%). Metabolic disorders were less frequent with duligotuzumab (10 vs. 16%); any grade rash-related events were less with duligotuzumab (49 vs. 67%).

Conclusion: While several lines of preclinical evidence had supported the premise that the blockade of HER3 in addition to that of EGFR may improve outcomes for patients with R/M SCCHN overall or specifically in those patients whose tumors express high levels of , this study provided definitive clinical evidence refuting this hypothesis. Duligotuzumab did not improve patient outcomes in comparison to cetuximab despite frequent expression of . These data indicate that inhibition of EGFR alone is sufficient to block EGFR-HER3 signaling, suggesting that HER2 plays a minimal role in this disease. Extensive biomarker analyses further show that HPV-negative SCCHN but not HPV-positive SCCHN are most likely to respond to EGFR blockage by cetuximab or duligotuzumab.
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http://dx.doi.org/10.3389/fonc.2016.00232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5086582PMC
October 2016

Intensive 'Brain Training' Intervention Fails to Reduce Amyloid Pathologies or Cognitive Deficits in Transgenic Mouse Models of Alzheimer's Disease.

J Alzheimers Dis 2017 ;55(3):1109-1121

Department of Psychology, Stony Brook University Stony Brook, NY, USA.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is the leading cause of dementia in the elderly. Amyloid-β protein (Aβ) depositions in both the brain parenchyma and the cerebral vasculature are recognized as important pathological components that contribute to the cognitive impairments found in individuals with AD. Because pharmacological options have been minimally effective in treating cognitive impairment to date, interest in the development of preventative lifestyle intervention strategies has increased in the field. One controversial strategy, cognitive-specific stimulation, has been studied previously in human participants and has been widely commercialized in the form of 'brain-training games.' In the present study, we developed a highly controlled, isolated cognitive training intervention program for mice. Two transgenic mouse lines, one that develops Aβ deposition largely in brain parenchyma, and another in the cerebral microvasculature, progressed through a series of domain-specific tasks for an average of 4 months. Despite the high intensity and duration of the intervention, we found little evidence of positive benefits for AD amyloid pathologies and post-training cognitive testing in these two models. Taken together, these results support the current evidence in human studies that cognitive-specific stimulation does not lead to a measurable reduction in AD pathology or an improvement in general brain health.
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http://dx.doi.org/10.3233/JAD-160674DOI Listing
February 2018

450th anniversary of the city of Rio de Janeiro: Primary Health Care Reform.

Cien Saude Colet 2016 May;21(5):1324-6

Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Brasil.

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http://dx.doi.org/10.1590/1413-81232015215.06482016DOI Listing
May 2016

Dicarboxylic Acid Excretion in Normal Formula-Fed and Breastfed Infants.

Nutr Clin Pract 2016 Dec 9;31(6):819-823. Epub 2016 Jul 9.

2 Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University, St Louis, Missouri, USA.

Purpose: Infant formulas are often supplemented with medium-chain triglycerides (MCTs) to optimize calories for small for gestational age or preterm infants. High amounts of MCTs have been associated with an increase in dicarboxylic acid (DCA) in the urine. Elevated DCA in the urine is also a clinical indicator for fatty acid metabolism disorders. The purpose of this study was to identify if there is an amount of MCTs that can be provided without elevating urinary DCA excretion.

Methods: A metabolic screening laboratory provided urinary DCA excretion data for 175 infants. It was verified that no infants were diagnosed with metabolic disorders and therefore were considered "metabolically normal." All infants were either formula fed or breastfed at the time of screening. The type and volume of formula provided at the time of urine screening was documented. The exact amount of MCTs provided to each infant was calculated.

Results: The mean age of the infants was 3.09 months. The mean total DCA was determined for both the breastfeeding and formula groups. Within the formula group, the means were 32.07, 13.36, and 5.77 mmol/mol creatinine for adipic, suberic, and sebacic acids, respectively. Spearman correlation coefficient indicated correlations of r = 0.0693, r = 0.0166, and r = -0.0128 between percent MCT and adipic, suberic, and sebacic acids, respectively. No value was statistically significant. DCA excretion amounts did not vary between breastfed and formula-fed infants. Our data suggest that clinicians should not expect elevated dicarboxylic aciduria in infants who are fed a standard formula without added MCT oil.
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http://dx.doi.org/10.1177/0884533616648330DOI Listing
December 2016

Effectiveness of Early Preventive Intervention with Semiannual Fluoride Varnish Application in Toddlers Living in High-Risk Areas: A Stratified Cluster-Randomized Controlled Trial.

Caries Res 2016 22;50(1):17-23. Epub 2016 Jan 22.

Division of Pediatric Dentistry, Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden.

This study evaluated whether toddlers in an extended preventive program of semiannual fluoride varnish applications from 1 year of age had a lower incidence of caries than those undergoing a standard program. A cohort of 1-year-old children (n = 3,403) living in multicultural areas of low socioeconomic standing in Stockholm participated in a cluster-randomized controlled field trial with two parallel arms. The children attended 23 dental clinics. Using the ICDAS II criteria, the examiners recorded caries at baseline and after 1 and 2 years. The children in the reference group received a standardized oral health program once yearly between 1 and 3 years of age. The children in the test group received the same standard program supplemented with topical applications of fluoride varnish every 6 months. We compared the test group and the reference group for the prevalence and increment of caries. At baseline, 5% of the children had already developed caries (ICDAS II 1-6). We reexamined the children after 1 year (n = 2,675) and after 2 years (n = 2,536). Neither prevalence nor caries increment differed between the groups. At 3 years of age, 12% of the children had developed moderate and severe carious lesions (ICDAS II 3-6), with a mean increment of 0.5 (SD 2.4) in the test group and 0.6 (SD 2.2) in the reference group. In conclusion, semiannual professional applications of fluoride varnish, as a supplement to a standard oral health program, failed to reduce caries development in toddlers from high-risk communities.
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http://dx.doi.org/10.1159/000442675DOI Listing
September 2017

Particle- and Gaseous Emissions from an LNG Powered Ship.

Environ Sci Technol 2015 Oct 8;49(20):12568-75. Epub 2015 Oct 8.

Department of Shipping and Marine Technology, Chalmers University of Technology , 412 96 Gothenburg, Sweden.

Measurements of particle number and mass concentrations and number size distribution of particles from a ship running on liquefied natural gas (LNG) were made on-board a ship with dual-fuel engines installed. Today there is a large interest in LNG as a marine fuel, as a means to comply with sulfur and NOX regulations. Particles were studied in a wide size range together with measurements of other exhaust gases under different engine loads and different mixtures of LNG and marine gas oil. Results from these measurements show that emissions of particles, NOX, and CO2 are considerably lower for LNG compared to present marine fuel oils. Emitted particles were mainly of volatile character and mainly had diameters below 50 nm. Number size distribution for LNG showed a distinct peak at 9-10 nm and a part of a peak at diameter 6 nm and below. Emissions of total hydrocarbons and carbon monoxide are higher for LNG compared to present marine fuel oils, which points to the importance of considering the methane slip from combustion of LNG.
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http://dx.doi.org/10.1021/acs.est.5b02678DOI Listing
October 2015

Dynamic microglial modulation of spatial learning and social behavior.

Brain Behav Immun 2016 07 5;55:6-16. Epub 2015 Sep 5.

Program in Molecular and Cellular Pharmacology, Stony Brook University, New York 11794-8651, United States; Department of Pharmacological Sciences, Stony Brook University, New York 11794-8651, United States. Electronic address:

Microglia are active players in inflammation, but also have important supporting roles in CNS maintenance and function, including modulation of neuronal activity. We previously observed an increase in the frequency of excitatory postsynaptic current in organotypic brain slices after depletion of microglia using clodronate. Here, we describe that local hippocampal depletion of microglia by clodronate alters performance in tests of spatial memory and sociability. Global depletion of microglia by high-dose oral administration of a Csf1R inhibitor transiently altered spatial memory but produced no change in sociability behavior. Microglia depletion and behavior effects were both reversible, consistent with a dynamic role for microglia in the regulation of such behaviors.
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http://dx.doi.org/10.1016/j.bbi.2015.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4779430PMC
July 2016

The need for global primary care development indicators.

Lancet 2015 Aug;386(9995):737

Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UK; World Organization of Family Doctors, Silom, Bangrak, Bangkok 10500, Thailand. Electronic address:

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http://dx.doi.org/10.1016/S0140-6736(15)61532-XDOI Listing
August 2015

A workshop on asthma management programs and centers in Brazil: reviewing and explaining concepts.

J Bras Pneumol 2015 Jan-Feb;41(1):3-15

Uruguaiana Municipal Department of Health, Uruguaiana, Brazil. Programa Infantil de Prevenção de Asma - PIPA, Children's Asthma Prevention Program - Uruguaiana Municipal Department of Health, Uruguaiana, Brazil.

Objective: To report the results of a workshop regarding asthma management programs and centers (AMPCs) in Brazil, so that they can be used as a tool for the improvement and advancement of current and future AMPCs.

Methods: The workshop consisted of five presentations and the corresponding group discussions. The working groups discussed the following themes: implementation of asthma management strategies; human resources needed for AMPCs; financial resources needed for AMPCs; and operational maintenance of AMPCs.

Results: The workshop involved 39 participants, from all regions of the country, representing associations of asthma patients (n = 3), universities (n = 7), and AMPCs (n = 29). We found a direct relationship between a lack of planning and the failure of AMPCs. Based on the experiences reported during the workshop, the common assumptions about AMPCs in Brazil were the importance of raising awareness of managers; greater community participation; interdependence between primary care and specialized care; awareness of regionalization; and use of medications available in the public health system.

Conclusions: Brazil already has a core of experience in the area of asthma management programs. The implementation of strategies for the management of chronic respiratory disease and their incorporation into health care system protocols would seem to be a natural progression. However, there is minimal experience in this area. Joint efforts by individuals with expertise in AMPCs could promote the implementation of asthma management strategies, thus speeding the creation of treatment networks, which might have a multiplier effect, precluding the need for isolated centers to start from zero.
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http://dx.doi.org/10.1590/S1806-37132015000100002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4350820PMC
July 2015

Cerebral microvascular rather than parenchymal amyloid-β protein pathology promotes early cognitive impairment in transgenic mice.

J Alzheimers Dis 2014 ;38(3):621-32

Department of Psychology, Stony Brook University, Stony Brook, NY, USA.

Alzheimer's disease (AD) is an age-dependent neurodegenerative condition that causes a progressive decline in cognitive function. Accumulation of amyloid β-protein (Aβ) in the brain is a prominent feature of AD and related disorders. However, the levels of Aβ accumulation alone are not a reliable predictor of cognitive deficits. Aβ accumulates in AD brain in the form of parenchymal amyloid plaques and cerebral vascular deposits. Although both types of lesions can contribute to cognitive decline, their temporal impact remains unclear. Moreover, cerebral microvascular pathology is identified as an early driver of cognitive impairment. Here for the first time, we compared two transgenic mouse strains, Tg-5xFAD and Tg-SwDI, which exhibit similar onset and anatomical accumulation of Aβ, but with distinct parenchymal and microvascular compartmental deposition, respectively, to assess their impact on cognitive impairment. Cohorts of each line were tested at 3 and 6 months of age to assess the relationship between spatial working memory performance and quantitative pathology. At 3 months of age, Tg-SwDI mice with onset of cerebral microvascular amyloid were behaviorally impaired, while the Tg-5xFAD, which had disproportionately higher levels of total Aβ, soluble oligomeric Aβ, and parenchymal amyloid were not. However, at 6 months of age, behavioral deficits for both groups of transgenic mice were evident, as the levels of Aβ pathologies in the Tg-5xFAD accumulated to extremely high amounts. The present findings suggest early-onset cerebral microvascular amyloid deposition, that precedes high parenchymal levels of Aβ, may be an important early factor in the development of cognitive deficits.
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http://dx.doi.org/10.3233/JAD-130758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4566953PMC
July 2014

Galanin, through GalR1 but not GalR2 receptors, decreases motivation at times of high appetitive behavior.

Behav Brain Res 2013 Feb 8;239:90-3. Epub 2012 Nov 8.

Department of Psychology, Stony Brook University, Stony Brook, NY 11794, USA.

Galanin is a 29/30-amino acid long neuropeptide that has been implicated in many physiological and behavioral functions. Previous research has shown that i.c.v. administration of galanin strongly stimulates food intake in sated rats when food is freely available, but fails to stimulate this consumption when an operant response requirement is present. Using fixed ratio (FR) schedules, we sought to further clarify galanin's role in motivated behavior by administering galanin i.c.v. to rats working on fixed ratio schedules requiring either a low work condition (FR1) or higher work conditions (FR>1) to obtain a 0.2% saccharin reward. Rats in the FR>1 group were assigned to either an FR3, FR5 or FR7 schedule of reinforcement. The rate of reinforcement decreased for only the FR>1 group as compared to saline controls. Furthermore, injections of GalR1 receptor agonist M617 led to a similar, marginally significant decrease in the number of reinforcers received in the FR>1 condition, but a decrease was not seen after injections of GalR2 receptor agonist M1153. Taken together, these results show that galanin may be playing a role in decreasing motivation at times of high appetitive behavior, and that this effect is likely mediated by the GalR1 receptor.
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http://dx.doi.org/10.1016/j.bbr.2012.10.045DOI Listing
February 2013

Depression and diabetes: the role and impact of models of health care systems.

J Affect Disord 2012 Oct;142 Suppl:S80-8

University of Wisconsin School of Medicine & Public Health, Madison, WI 53715, USA.

Objectives: Depression and diabetes often occur together and their comorbidity has a significant and detrimental impact on health outcomes. The aims of this paper are to review the existing international literature on approaches to health care for comorbid depression and diabetes and draw out the key conclusions for both research and future development in health care delivery.

Methods: Narrative review of the literature with synthesis by an international team of authors.

Results: The synthesized findings are discussed under four main headings: specialty and generalist care; models for co-ordinating and integrating care; community approaches to service delivery; and the role of health policy.

Limitations: The review only included literature published in English.

Conclusions: Translating basic and clinical research findings into improved treatment and outcomes of those with depression and diabetes remains a substantial challenge. There is little research on the difficulties of identifying and implementing best practice into routine health care. Systems need to be designed so that evidence-based interventions are provided in a timely way, with appropriate professional expertise where required.
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http://dx.doi.org/10.1016/S0165-0327(12)70012-5DOI Listing
October 2012

Treatment of language, motor speech impairments, and Dysphagia.

Continuum (Minneap Minn) 2011 Jun;17(3 Neurorehabilitation):471-93

Language, speech, cognitive-associated communication deficits, and dysphagia are common following acquired brain injury (stroke, traumatic brain injury, and others). Treatment of these disorders can be divided into restorative, compensatory, and supportive approaches. Although therapy must be individualized for each person, components of all three approaches are necessary to maximize an individual's recovery. This article provides a general overview of traditional as well as state-of-the-art treatment for aphasia, cognitive-linguistic impairments, dysarthria, apraxia, and dysphagia.
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http://dx.doi.org/10.1212/01.CON.0000399068.77191.12DOI Listing
June 2011