Clinical and molecular findings in a Moroccan family with Jervell and Lange-Nielsen syndrome: a case report

Jervell and Lange-Nielsen syndrome (Online Mendelian Inheritance in Man 220400) is a rare autosomal recessive cardioauditory ion channel disorder that affects 1/200,000 to 1/1,000,000 children. It is character...

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Impact of ingredients on the elemental content of baby foods

Publication date: 15 September 2017
Source:Food Chemistry, Volume 231
Author(s): Judith Adikinyi Khamoni, Toby Hamshaw, Philip H.E. Gardiner
The levels of the minerals: Ca, K, Mg, Na, P, and the trace elements: Cd, Cu, Fe, Mn, Ni, Pb, Se, Zn were determined in foods for 4–6, 7+ and 10+ months old babies in a brand available on the UK market. The mineral contents in the vegetarian meals for all the age groups were similar, in contrast, when compared to the non-vegetarian options, the Ca, Na and P levels were higher in the former. Both the trace elements and minerals levels in the 4–6months vegetarian meal were the lowest of all the products analysed. The Cu, Se and Zn levels in all the meals were comparable to those in mature human breast milk. Calculations of the following molar ratios: Zn:Cu, Fe:Zn, and Fe:Mn, pairs of elements that have been shown to interaction antagonistically, were higher in the vegetarian meals.



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Clinical and cross-sectional imaging features of spontaneous pancreatic pseudocyst-portal vein fistula

Publication date: Available online 1 April 2017
Source:Clinical Imaging
Author(s): Francesco Alessandrino, Corinne Strickland, Amirkasra Mojtahed, Steven C. Eberhardt, Koenraad J. Mortele
PurposeTo evaluate clinical and imaging features of pancreatic pseudocyst-portal vein fistula (PPVF).MethodsPatients with evidence of PPVF on CT/MRI were included. Clinical presentation, outcomes, imaging appearance of the portal vein were recorded.Results75% of patients developed portal hypertension, 62% cavernous transformation of the portal vein and 25% portal biliopathy. PPVF presented on CT as fluid-attenuated portal vein, and on MRI as T2-weighted hyperintense fluid-filled portal vein. PPVF was misdiagnosed as portal vein thrombosis in all patients who underwent CT as initial examination.ConclusionsWhenever PPVF is suspected on CT, MRI can be helpful to achieve accurate diagnosis and avoid unnecessary interventions.



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Benefits of subspecialty adherence after asthma hospitalization and patient perceived barriers to care

Publication date: Available online 1 April 2017
Source:Annals of Allergy, Asthma & Immunology
Author(s): Neema Izadi, Jonathan S. Tam
BackgroundComparative studies have demonstrated that asthma education to pediatric patients decreases average hospital usage and that allergy specialists provide stronger asthma education and more improved outcomes.ObjectiveTo evaluate the real-world benefits of allergy subspecialty involvement outside inpatient consultation and the impediments for patients in establishing allergy subspecialty care.MethodsThe study population was composed mostly of minority children 0 to 18 years old seen at a large university-affiliated stand-alone children's hospital who had a hospital discharge diagnosis of asthma from 2009 to 2013. The retrospective portion of the study compared all variables pertaining to asthma, teaching, and discharge reconciliation for the following subgroups: patients recommended to allergy and immunology (AI) follow-up who adhered to the appointment (adherent), patients recommended to AI follow-up who did not adhere (nonadherent), and patients not recommended to AI follow-up (non-referred). In the phone interview portion of the study, the nonadherent patients were contacted to identify barriers to AI follow-up.ResultsOf the referred sample, the adherent group had significantly fewer visits to the pediatric intensive care unit, days in the pediatric intensive care unit, and days in the hospital. Providing more specific hospital discharge instructions increased AI follow-up and hospital teaching given on the baseline admission decreased hospital visits. Phone interviews showed that nonadherent patients most commonly missed follow-up because the parents believed it unnecessary because their child showed acute improvement or from advice from their primary care physician.ConclusionThese results showed improvement in outcomes for patients who attended AI follow-up and specifically identified key barriers that could be addressed in a standardized form to prevent nonadherence in the future.



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Effect of alfacalcidol on the pulmonary function of adult asthmatic patients: A randomized trial

Publication date: Available online 1 April 2017
Source:Annals of Allergy, Asthma & Immunology
Author(s): Amani M. Ali, Samah Selim, Maggie M. Abbassi, Nirmeen A. Sabry
BackgroundDespite the use of alfacalcidol in the management of corticosteroid-induced osteoporosis, it has never been considered an adjunct treatment for asthma management. It can target vitamin D deficiency, a possible risk factor for asthma, and, hence, improve pulmonary function of patients with asthma.ObjectiveTo explore the effect of alfacalcidol administration on pulmonary function and study the pattern of vitamin D deficiency in adults with asthma in Egypt.MethodsSerum 25-hydroxyvitamin D was measured in 115 adults: 33 healthy subjects and 82 patients with asthma. Then, patients with asthma were randomized to receive standard asthma treatment only (n = 39) or receive it in addition to 1 μg of alfacalcidol daily for 4 months (n = 43). Randomization was stratified by the stage of asthma severity. Spirometry and measurement of 25-hydroxyvitamin were performed at baseline and end of follow-up.ResultsVitamin D deficiency was more common in patients with asthma (57.3%) than in healthy subjects (21.2%; P < .001). In patients with asthma, alfacalcidol significantly improved forced expiratory volume in the first second and forced vital capacity (P < .001 for the 2 tests). Moreover, more patients in the intervention arm showed improvement in asthma severity stage (P = .04). A nonsignificant difference was observed in improvement of forced expiratory volume in the first second between patients with vitamin D deficiency and those without deficiency in the intervention group (P > .05).ConclusionAlfacalcidol supplementation improved the pulmonary function and severity stage of adult patients with asthma regardless of deficiency.Trial RegistrationClinicalTrials.gov Identifier: NCT02747381.



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Mimicker of hereditary angioedema: Idiopathic systemic capillary leak syndrome successfully treated with intravenous immunoglobulin

Publication date: Available online 1 April 2017
Source:Annals of Allergy, Asthma & Immunology
Author(s): Xiao Chloe Wan, Andrew Lai, Tejaswi Kompala, Rosa Ten




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Dual training in allergy/immunology and rheumatology

Publication date: Available online 1 April 2017
Source:Annals of Allergy, Asthma & Immunology
Author(s): Bharat Kumar, Svjetlana Dolovcak, Scott A. Vogelgesang




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Broader concepts of quality of life measurement, encompassing validation

Abstract

Background

Developing and managing measures of Quality of Life (QoL) requires attention to a range of broader concepts, in addition to meeting validation requirements.

Objectives

The aim of this review is to describe development and experience in Cardiff of these concepts and to inform users of Cardiff quality of life tools of aspects of their origin, for the benefit of developers of novel QoL measures or other patient reported outcome measures.

Methods

Publications from the Cardiff team over the last three decades are used to illustrate descriptions of concepts involved in developing and managing QoL measures.

Results

The concepts are grouped into three main themes: A) Design of tools: measurement ability turns ideas into science, QoL measurement based on patient experience, the need for tools to be clinically practical and useful with meaningful scores, different ages need tailored tools. B) Practical management of tools: enabling ease of access, maintenance of single version, translation validity, enabling access to post publication experience and further validation. C) Promoting wider understanding of QoL: examples include educate thinking with disease severity definition; heighten awareness of broader burden, family impact and the time dimension.

Conclusion

The development and management of QoL and other outcome measures involves attention to a wide range of other issues, in addition to meeting validation requirements.

This article is protected by copyright. All rights reserved.

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Diagnostic accuracy of confocal microscopy imaging versus punch biopsy for diagnosing and subtyping basal cell carcinoma

Abstract

Background

In vivo reflectance confocal microscopy (RCM) is a promising non-invasive skin imaging technique that could facilitate early diagnosis of basal cell carcinoma (BCC) instead of routine punch biopsies. However, the clinical value and utility of RCM versus a punch biopsy in diagnosing and subtyping BCC is unknown.

Objective

To assess diagnostic accuracy of RCM versus punch biopsy for diagnosing and subtyping clinically suspected primary BCC.

Methods

A prospective, consecutive cohort of 100 patients with clinically suspected BCC were included at two tertiary hospitals in Amsterdam, the Netherlands, between February 3, 2015 and October 2, 2015. Patients were randomized between two test-treatment pathways: diagnosing and subtyping using RCM imaging followed by direct surgical excision (RCM one-stop-shop) or planned excision based upon the histological diagnosis and subtype of punch biopsy (standard care). The primary outcome was the agreement between the index tests (RCM versus punch biopsy) and reference standard (excision specimen) in correctly diagnosing BCC. The secondary outcome the agreement between the index tests and reference standard in correctly identifying the most aggressive BCC subtypes.

Results

Sensitivity to detect BCC was similar for RCM and punch biopsy (100% versus 93.94%), but a punch biopsy was more specific than RCM (79% versus 38%). RCM expert evaluation for diagnosing BCC had a sensitivity of 100% and a specificity of 75%. The agreement between RCM and excision specimen in identifying the most aggressive BCC subtype ranged from 50% to 85% versus 77% by a punch biopsy.

Conclusion

RCM and punch biopsy have comparable diagnostic accuracy to diagnose and subtype BCC depending on RCM experience. Although experienced RCM users could accurately diagnose BCC at a distance, we found an important difference in subtyping BCC. Future RCM studies need to focus on diagnostic accuracy, reliability and specific criteria to improve BCC subtype differentiation.

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The Effect of Body Weight on the Efficacy and Safety of Ixekizumab: Results from an Integrated Database of 3 Randomized, Controlled Phase 3 Studies of Patients with Moderate-to-Severe Plaque Psoriasis

Abstract

Background

There is concern that increased body weight may impact efficacy of some therapies used to treat psoriasis.

Objective

To evaluate the effect of body weight on response to ixekizumab treatment in moderate-to-severe psoriasis patients.

Methods

Patients were characterized under 3 body weight categories (<80 kg, 80 to 100 kg, ≥100 kg) in this preplanned subgroup analysis from an integrated database of 3 multicenter, randomized, double-blind, controlled Phase 3 clinical studies (UNCOVER -1, UNCOVER-2, and UNCOVER-3). In the first 12 weeks of each study, patients were randomly assigned to receive subcutaneous placebo, 80-mg ixekizumab every 2 weeks (IXE Q2W) or every 4 weeks (IXE Q4W) after a starting dose of 160-mg ixekizumab, or 50-mg etanercept twice weekly (UNCOVER-2 and UNCOVER-3 only).

Results

This analysis included 3855 patients with baseline body weight in the IXE Q4W (N=1159), IXE Q2W (N=1168), placebo (N=789), and etanercept (N=739) groups. Distribution of patients across body weight categories was similar between treatment groups. Baseline demographics and patients characteristics were generally consistent across treatment groups within each body weight category. Across all body weight categories, a significantly higher percent of patients treated with IXE Q2W or IXE Q4W than with placebo or etanercept achieved PASI75, PASI90, or PASI100 at Week 12. No meaningful differences in PASI75 response rates were observed across body weight categories. Some numerical differences in PASI 90 and PASI100 response rates were observed between body weight categories with IXE Q2W providing numerically higher response rates than IXE Q4W. The incidence of treatment-emergent adverse events was similar in the treatment groups and across body weight categories.

Conclusion

Ixekizumab was efficacious in the treatment of moderate-to-severe psoriasis regardless of body weight. The safety profile of ixekizumab was also similar across body weight categories and no safety signals were identified specific to any of the body weight categories.

This article is protected by copyright. All rights reserved.

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The Icatibant Outcome Survey: experience of hereditary angioedema management from six European countries

Abstract

Background

Hereditary angioedema (HAE) due to C1 INH deficiency (C1-INH-HAE) is a rare, potentially fatal, bradykinin-mediated disease. Icatibant is a bradykinin B2 receptor antagonist originally approved in 2008 in the European Union and 2011 in the United States, as an acute therapy option for HAE attacks in adults.

Objective

To compare demographics, disease characteristics and treatment outcomes of icatibant-treated HAE attacks in patients with C1-INH-HAE enrolled in the Icatibant Outcome Survey across six European countries: Austria, France, Germany, Italy, Spain and the United Kingdom.

Methods

The Icatibant Outcome Survey (IOS; Shire, Zug, Switzerland [NCT01034969]) is an international observational study monitoring the safety and effectiveness of icatibant. Descriptive, retrospective analyses compared IOS country data derived during July 2009 – April 2015.

Results

Overall, 481 patients with C1-INH-HAE provided demographic data. A significant difference across countries in age at onset (P = 0.003) and baseline attack frequency (P < 0.001) was found though no significant differences were found with respect to gender (majority female; P = 0.109), age at diagnosis (P = 0.182) or delay in diagnosis (P=0.059). Icatibant was used to treat 1893 attacks in 325 patients with majority self-administration in all countries. Overall, significant differences (all P< 0.001) were found across countries in time to treatment (median 1.8 hours; median range: 0.0 [Germany-Austria] to 4.4 [France] hours), time to resolution (median 6.5 hours; median range: 3 [Germany-Austria] to 12 [France] hours) and attack duration (median 10.5 hours; median range: 3.1 [Germany-Austria] to 18.5 [France] hours.

Conclusion

These data form the first European cross-country comparison of disease characteristics and icatibant use in patients with C1-INH-HAE who are enrolled in IOS. International variation in icatibant practice and treatment outcomes across the six European countries assessed highlight the need to further investigate the range of country-specific parameters driving regional variations in icatibant use.

This article is protected by copyright. All rights reserved.

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Topical treatment of psoriasis: questionnaire results on topical therapy accessibility and influence of body surface area on usage

Abstract

Background

Topical treatment of mild to moderate psoriasis is first line treatment and exhibits varying degrees of success across patient groups. Key factors influencing treatment success are physician topical treatment choice (high efficacy, low adverse events) and strict patient adherence. Currently, no formalized, international consensus guidelines exist to direct optimal topical treatment, although many countries have national guidelines.

Objective

To describe and analyze cross-regional variations in the use and access of psoriasis topical therapies.

Methods

The study was conducted as an observational cross-sectional study. A survey was distributed to dermatologists from the International Psoriasis Council (IPC) to assess topical therapy accessibility in 26 countries and to understand how body surface area (BSA) categories guide clinical decisions on topical use.

Results

Variation in the availability of tars, topical retinoids, dithranol and balneotherapy was reported. The vast majority of respondents (100% and 88,4%) used topical therapy as first line monotherapy in situations with BSA<3% and BSA between 3% and 10%, respectively. However, with disease severity increasing to BSA>10%, the number of respondents who prescribe topical therapy decreased considerably. In addition, combination therapy of a topical drug and a systemic drug was frequently reported when BSA measured >10%.

Conclusion

This physician survey provides new evidence on topical access and the influence of disease severity on topical usage in an effort to improve treatment strategies on a global level.

This article is protected by copyright. All rights reserved.

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Clinical and molecular findings in a Moroccan family with Jervell and Lange-Nielsen syndrome: a case report

Jervell and Lange-Nielsen syndrome (Online Mendelian Inheritance in Man 220400) is a rare autosomal recessive cardioauditory ion channel disorder that affects 1/200,000 to 1/1,000,000 children. It is character...

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Fixed-Level Frequency Threshold Testing for Ototoxicity Monitoring.

Related Articles

Fixed-Level Frequency Threshold Testing for Ototoxicity Monitoring.

Ear Hear. 2017 Mar 30;:

Authors: Rieke CC, Clavier OH, Allen LV, Anderson AP, Brooks CA, Fellows AM, Brungart DS, Buckey JC

Abstract
OBJECTIVES: Hearing loss from ototoxicity is often most pronounced at high frequencies. To improve patient monitoring and compliance, high-frequency testing methods should be short and easy to administer. We evaluated the repeatability and accuracy of a Békésy-like, fixed-level frequency threshold (FLFT) technique. This test takes less than a minute and could provide a rapid and effective way to determine the highest audible frequency. We hypothesized the FLFT test would be repeatable in normal-hearing subjects, and accurate when compared with Békésy fixed-frequency audiometry in the sensitive region for ototoxicity (SRO).
DESIGN: Twenty-nine normal-hearing subjects (20 females, 9 males) performed 2 different automated audiometry tests at least 4 times over a period of no less than 3 weeks. Ages ranged from 23 to 35 years (average = 28 years). Subjects completed testing under Sennheiser HDA-200 headsets. Initial fixed-frequency audiometry thresholds were obtained at frequencies ranging from 0.5 to 20 kHz to identify each subject's highest audible frequency, which was used to determine the SRO. The SRO was defined as the seven frequencies at and below the highest audible frequency in 1/6-octave steps. These frequencies were monitored with fixed-frequency audiometry. At each session, the FLFT test was administered at 80 dB SPL. Subjects used a Békésy-style tracking method to determine the frequency threshold. All testing was completed in a sound booth (single wall, Industrial Acoustics Company) using a computerized, laptop-based, system. FLFT repeatability was calculated as the root mean square difference from the first test session. FLFT accuracy was calculated as the difference from the highest audible frequency determined from fixed-frequency audiometry interpolated to 80 dB SPL level.
RESULTS: The FLFT average RMSD for intersession variability was 0.05 ± 0.05 octaves. The test showed no learning effect [F(3,78) = 0.7; p = 0.6]. The overall intersession variability for SRO fixed-frequency audiometry thresholds at all frequencies was within clinically acceptable test-retest variability (10 dB) at 5.8 dB (range 2.7 to 9.9 dB). The SRO fixed-frequency audiometry therefore served as a repeatable basis of comparison for accuracy of the FLFT test. The mean absolute difference between the fixed-frequency audiometry and FLFT-determined highest audible frequency was 0.03 octaves. The FLFT and the highest audible frequency via fixed-frequency audiometry at 80 dB SPL were not different statistically (p = 0.12). The FLFT took approximately 30 seconds to complete, compared with approximately 4.5 min for fixed-frequency audiometry SRO and 20 to 25 min for a traditional ototoxic audiometric assessment.
CONCLUSIONS: The Békésy-style FLFT was repeatable within 1/12 octave (1 step size in the testing procedure). The FLFT agreed well with the highest audible frequency determined via fixed-frequency audiometry at 80 dB SPL. The FLFT test is amenable to automatic and self-administration and may enable quick, accurate, noise-tolerant ototoxicity, and high-frequency hearing monitoring.

PMID: 28362673 [PubMed - as supplied by publisher]

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Realisation of voicing by French-speaking CI children after long-term implant use: An acoustic study.

Related Articles

Realisation of voicing by French-speaking CI children after long-term implant use: An acoustic study.

Clin Linguist Phon. 2017 Mar 31;:1-14

Authors: Grandon B, Vilain A, Lœvenbruck H, Schmerber S, Truy E

Abstract
Studies of speech production in French-speaking cochlear-implanted (CI) children are very scarce. Yet, difficulties in speech production have been shown to impact the intelligibility of these children. The goal of this study is to understand the effect of long-term use of cochlear implant on speech production, and more precisely on the coordination of laryngeal-oral gestures in stop production. The participants were all monolingual French children: 13 6;6- to 10;7-year-old CI children and 20 age-matched normally hearing (NH) children. We compared /p/, /t/, /k/, /b/, /d/ and /g/ in word-initial consonant-vowel sequences, produced in isolation in two different tasks, and we studied the effects of CI use, vowel context, task and age factors (i.e. chronological age, age at implantation and duration of implant use). Statistical analyses show a difference in voicing production between groups for voiceless consonants (shorter Voice Onset Times for CI children), with significance reached only for /k/, but no difference for voiced consonants. Our study indicates that in the long run, use of CI seems to have limited effects on the acquisition of oro-laryngeal coordination needed to produce voicing, except for specific difficulties located on velars. In a follow-up study, further acoustic analyses on vowel and fricative production by the same children reveal more difficulties, which suggest that cochlear implantation impacts frequency-based features (second formant of vowels and spectral moments of fricatives) more than durational cues (voicing).

PMID: 28362227 [PubMed - as supplied by publisher]

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Validity of auditory perceptual assessment of velopharyngeal function and dysfunction - the VPC-Sum and the VPC-Rate.

Related Articles

Validity of auditory perceptual assessment of velopharyngeal function and dysfunction - the VPC-Sum and the VPC-Rate.

Clin Linguist Phon. 2017 Mar 31;:1-9

Authors: Lohmander A, Hagberg E, Persson C, Willadsen E, Lundeborg I, Davies J, Havstam C, Boers M, Kisling-Møller M, Alaluusua S, Aukner R, Pedersen NH, Turunen L, Nyberg J

Abstract
Overall weighted or composite variables for perceptual auditory estimation of velopharyngeal closure or competence have been used in several studies for evaluation of velopharyngeal function during speech. The aim of the present study was to investigate the validity of a composite score (VPC-Sum) and of auditory perceptual ratings of velopharyngeal competence (VPC-Rate). Available VPC-Sum scores and judgments of associated variables (hypernasality, audible nasal air leakage, weak pressure consonants, and non-oral articulation) from 391 5-year olds with repaired cleft palate (the Scandcleft project) were used to investigate content validity, and 339 of these were compared with an overall judgment of velopharyngeal competence (VPC-Rate) on the same patients by the same listeners. Significant positive correlations were found between the VPC-Sum and each of the associated variables (Cronbachs alpha 0.55-0.87, P < 0.001), and a moderately significant positive correlation between VPC-Sum and VPC-Rate (Rho 0.698, P < 0.01). The latter classified cases well when VPC-Sum was dichotomized with 67% predicted velopharyngeal competence and 90% velopharyngeal incompetence. The validity of the VPC-Sum was good and the VPC-Rate a good predictor, suggesting possible use of both measures depending on the objective.

PMID: 28362219 [PubMed - as supplied by publisher]

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Relations between awareness of morphosyntactic structures in Chinese compound words and reading abilities: A short report.

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Relations between awareness of morphosyntactic structures in Chinese compound words and reading abilities: A short report.

Clin Linguist Phon. 2017 Mar 31;:1-11

Authors: Lau DK, Liang Y, Leung MT

Abstract
This is a short report of the investigation of the relationship between awareness of morphosyntactic structures in Chinese compound words and reading abilities on 268 fourth graders studying in three mainstream schools in Shenzhen. All children were assessed using reading and cognitive tasks including rapid automatized naming, phonological, orthographic and morphological awareness. A compound production task using pseudo compound words with different morphosyntactic structures in the first and second levels as stimuli was also conducted. Results of ANOVA indicated that main effect of first level morphosyntactic structures, main effect of second level morphosyntactic structures and interaction effects between the two were significant. Children's awareness of different morphosyntactic structures were affected by frequency of usage of individual morphosyntactic structures in the language. Results of hierarchical regression analyses revealed that the awareness of morphosyntactic structures in Chinese compound words is strongly associated with Chinese reading abilities. Theoretical and clinical implications were discussed.

PMID: 28362193 [PubMed - as supplied by publisher]

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Analogical reasoning in children with specific language impairment: Evidence from a scene analogy task.

Related Articles

Analogical reasoning in children with specific language impairment: Evidence from a scene analogy task.

Clin Linguist Phon. 2017 Mar 31;:1-16

Authors: Krzemien M, Jemel B, Maillart C

Abstract
Analogical reasoning is a human ability that maps systems of relations. It develops along with relational knowledge, working memory and executive functions such as inhibition. It also maintains a mutual influence on language development. Some authors have taken a greater interest in the analogical reasoning ability of children with language disorders, specifically those with specific language impairment (SLI). These children apparently have weaker analogical reasoning abilities than their aged-matched peers without language disorders. Following cognitive theories of language acquisition, this deficit could be one of the causes of language disorders in SLI, especially those concerning productivity. To confirm this deficit and its link to language disorders, we use a scene analogy task to evaluate the analogical performance of SLI children and compare them to controls of the same age and linguistic abilities. Results show that children with SLI perform worse than age-matched peers, but similar to language-matched peers. They are more influenced by increased task difficulty. The association between language disorders and analogical reasoning in SLI can be confirmed. The hypothesis of limited processing capacity in SLI is also being considered.

PMID: 28362136 [PubMed - as supplied by publisher]

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Antipsychotic activity of embelin isolated from Embelia ribes: A preliminary study

Publication date: June 2017
Source:Biomedicine & Pharmacotherapy, Volume 90
Author(s): Sharanbasappa Durg, Naveen Kumar B., Ravichandra Vandal, Shivsharan B. Dhadde, B.S. Thippeswamy, Veeresh P. Veerapur, Shrishailappa Badami
BackgroundEmbelia ribes is claimed in Indian traditional medical practice to be useful in the treatment of nervous diseases. Embelin, an alkyl substituted hydroxy benzoquinone, is a major active constituent of E. ribes. The present preliminary study was intended to evaluate antipsychotic activity of embelin against apomorphine-induced climbing behaviour in mice and stereotyped behaviour in rats.MethodsTwo doses of embelin (5 and 10mg/kg) were administered once daily for 15days before exposure to apomorphine. On the concluding day of pre-treatment, after apomorphine-injection, the rodents were assessed for climbing and stereotyped behaviours according to the published scoring system. Thereafter, neurotransmitters (dopamine, noradrenaline and serotonin) levels were estimated in rodent brains.ResultsEmbelin pre-treatment significantly inhibited apomorphine-induced climbing and stereotyped behaviours in mice and rats, respectively. Further, embelin also statistically reversed elevated levels of dopamine, noradrenaline and serotonin neurotransmitters in the brain of mice and rats. Embelin showed more significant results at high dose (10mg/kg) than low dose (5mg/kg) in both the tested models.ConclusionConsidering the present pharmacological profile of embelin, it is suggested that embelin possesses antipsychotic activity in the treatment of psychotic disorders. However, further research is warranted for evaluating its exact mechanism of action.



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Wip1 inhibition leads to severe pro-inflammatory phenotype in skin in response to chemical irritation

Publication date: Available online 1 April 2017
Source:Journal of Dermatological Science
Author(s): Grigorash B. Bogdan, Uyanik Burhan, Kochetkova Y. Elena, Goloudina R. Anastasia, Demidov N. Oleg




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Real-time detection of organic contamination events in water distribution systems by principal components analysis of ultraviolet spectral data

Abstract

The detection of organic contaminants in water distribution systems is essential to protect public health from potential harmful compounds resulting from accidental spills or intentional releases. Existing methods for detecting organic contaminants are based on quantitative analyses such as chemical testing and gas/liquid chromatography, which are time- and reagent-consuming and involve costly maintenance. This study proposes a novel procedure based on discrete wavelet transform and principal component analysis for detecting organic contamination events from ultraviolet spectral data. Firstly, the spectrum of each observation is transformed using discrete wavelet with a coiflet mother wavelet to capture the abrupt change along the wavelength. Principal component analysis is then employed to approximate the spectra based on capture and fusion features. The significant value of Hotelling's T² statistics is calculated and used to detect outliers. An alarm of contamination event is triggered by sequential Bayesian analysis when the outliers appear continuously in several observations. The effectiveness of the proposed procedure is tested on-line using a pilot-scale setup and experimental data.

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Characteristics and impacts of trace elements in atmospheric deposition at a high-elevation site, southern China

Abstract

To investigate the regional background trace element (TE) level in atmospheric deposition (dry and wet), TEs (Fe, Al, V, Cr, Mn, Ni, Cu, Zn, As, Se, Mo, Cd, Ba, and Pb) in 52 rainwater samples and 73 total suspended particles (TSP) samples collected in Mt. Lushan, Southern China, were analyzed using inductively coupled plasma-mass spectrometry (ICP-MS). The results showed that TEs in wet and dry deposition of the target area were significantly elevated compared within and outside China and the volume weight mean pH of rainwater was 4.43. The relative contributions of wet and dry depositions of TEs vary significantly among elements. The wet deposition fluxes of V, As, Cr, Se, Zn, and Cd exceeded considerably their dry deposition fluxes while dry deposition dominated the removal of pollution elements such as Mo, Cu, Ni, Mn, and Al. The summed dry deposition flux was four times higher than the summed wet deposition flux. Prediction results based on a simple accumulation model found that the content of seven toxic elements (Cr, Ni, Cu, Zn, As, Cd, and Pb) in soils could increase rapidly due to the impact of annual atmospheric deposition, and the increasing amounts of them reached 0.063, 0.012, 0.026, 0.459, 0.076, 0.004, and 0.145 mg kg⁻¹, respectively. In addition, the annual increasing rates ranged from 0.05% (Cr and Ni) to 2.08% (Cd). It was also predicted that atmospheric deposition induced the accumulation of Cr and Cd in surface soils. Cd was the critical element with the greatest potential ecological risk among all the elements in atmospheric deposition.

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Sleep disturbances in obsessive-compulsive disorder: Association with non-response to repetitive transcranial magnetic stimulation (rTMS)

Publication date: Available online 31 March 2017
Source:Journal of Anxiety Disorders
Author(s): Lana Donse, Alexander T. Sack, Paul B. Fitzgerald, Martijn Arns
Background Repetitive transcranial magnetic stimulation (rTMS) is a promising augmentation strategy for treatment-refractory OCD. However, a substantial group still fails to respond. Sleep disorders, e.g. circadian rhythm sleep disorders (CRSD), are highly prevalent in OCD and might mediate treatment response. The aims of the current study were to compare sleep disturbances between OCD patients and healthy subjects as well as between rTMS responders and non-responders, and most importantly to determine sleep-related predictors of rTMS non-response.Methods 22 OCD patients received at least 10 sessions rTMS combined with psychotherapy. Sleep disturbances were measured using questionnaires and actigraphy. Sleep in patients was compared to healthy subjects. Treatment response was defined as >35% reduction on YBOCS. Treatment response prediction models were based on measures of CRSD and insomnia.Results Sleep disturbances were more prevalent in OCD patients than healthy subjects. The OCD group consisted of 12 responders and 10 non-responders. The CRSD model could accurately predict non-response with 83% sensitivity and 63% specificity, whereas the insomnia model could not.Conclusions CRSD is more prevalent in OCD patients than healthy subjects, specifically in rTMS non-responders. Therefore, CRSD may serve as a biomarker for different subtypes of OCD corresponding with response to specific treatment approaches.



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The Affective Tie That Binds: Examining the Contribution of Positive Emotions and Anxiety to Relationship Formation in Social Anxiety Disorder

Publication date: Available online 31 March 2017
Source:Journal of Anxiety Disorders
Author(s): Charles T. Taylor, Sarah Pearlstein, Murray B. Stein
Individuals with social anxiety disorder (SAD) have difficulty forming social relationships. The prevailing clinical perspective is that negative emotions such as anxiety inhibit one's capacity to develop satisfying social connections. However, empirical findings from social psychology and affective neuroscience suggest that positive emotional experiences are fundamental to establishing new social bonds. To reconcile these perspectives, we collected repeated measurements of anxiety, positive emotions (pleasantness), and connectedness over the course of a controlled relationship formation encounter in 56 participants diagnosed with SAD (64% female; Mage=23.3, SD=4.7). Participants experienced both increases in positive emotions and decreases in anxiety throughout the interaction. Change in positive emotions was the most robust predictor of subsequent increases in connectedness, as well as a greater desire to engage one's partner in future social activities, above and beyond reductions in anxiety (medium to large sized effects). Those findings suggest that anxiety-based models alone may not fully explain difficulties in relationship formation in SAD, and underscore the potential value of considering positive emotional experiences in conceptual and treatment models of SAD.



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Harm expectancy violation during exposure therapy for posttraumatic stress disorder

Publication date: Available online 31 March 2017
Source:Journal of Anxiety Disorders
Author(s): Rianne A. de Kleine, Lotte Hendriks, Eni S. Becker, Theo G. Broekman, Agnes van Minnen
Exposure therapy has proven efficacy in the treatment of posttraumatic stress disorder (PTSD). Emotional processing theory proposes that fear habituation is a central mechanism in symptom reduction, but the empirical evidence supporting this is mixed. Recently it has been proposed that violation of harm expectancies is a crucial mechanism of action in exposure therapy. But to date, changes in harm expectancies have not been examined during exposure therapy in PTSD. The goal of the current study was to examine harm expectancy violation as mechanism of change in exposure therapy for posttraumatic stress disorder (PTSD). Patients (N=50, 44 female) with a primary diagnosis of chronic PTSD received intensive exposure therapy. Harm expectancies, harm experiences and subjective units of distress (SUDs) were assessed at each imaginal exposure session, and PTSD symptoms were assessed pre- and posttreatment with the Clinician Administered PTSD Scale (CAPS). Results showed that harm expectancies were violated within and strongly declined in-between exposure therapy sessions. However, expectancy violation was not related to PTSD symptom change. Fear habituation measures were moderately related to PTSD symptom reductions. In line with theory, exposure therapy promotes expectancy violation in PTSD patients, but this is not related to exposure therapy outcome. More work is warranted to investigate mechanisms of change during exposure therapy in PTSD.



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ACKNOWLEDGEMENT

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Reduced Inhibition within Layer IV of Sert Knockout Rat Barrel Cortex is Associated with Faster Sensory Integration

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Neural activity is essential for the maturation of sensory systems. In the rodent primary somatosensory cortex (S1), high extracellular serotonin (5-HT) levels during development impair neural transmission between the thalamus and cortical input layer IV (LIV). Rodent models of impaired 5-HT transporter (SERT) function show disruption in their topological organization of S1 and in the expression of activity-regulated genes essential for inhibitory cortical network formation. It remains unclear how such alterations affect the sensory information processing within cortical LIV. Using serotonin transporter knockout (<span style="font-style:italic;">Sert</span>^−/−) rats, we demonstrate that high extracellular serotonin levels are associated with impaired feedforward inhibition (FFI), fewer perisomatic inhibitory synapses, a depolarized GABA reversal potential and reduced expression of KCC2 transporters in juvenile animals. At the neural population level, reduced FFI increases the excitatory drive originating from LIV, facilitating evoked representations in the supragranular layers II/III. The behavioral consequence of these changes in network excitability is faster integration of the sensory information during whisker-based tactile navigation, as <span style="font-style:italic;">Sert</span>^−/− rats require fewer whisker contacts with tactile targets and perform object localization with faster reaction times. These results highlight the association of serotonergic homeostasis with formation and excitability of sensory cortical networks, and consequently with sensory perception.</span>

http://ift.tt/2oLNfKb

Different Effects of Sleep Deprivation and Torpor on EEG Slow-Wave Characteristics in Djungarian Hamsters

<span class="paragraphSection"><div class="boxTitle">Abstract</div>It has been shown previously in Djungarian hamsters that the initial electroencephalography (EEG) slow-wave activity (power in the 0.5–4.0 Hz band; SWA) in non-rapid eye movement (NREM) sleep following an episode of daily torpor is consistently enhanced, similar to the SWA increase after sleep deprivation (SD). However, it is unknown whether the network mechanisms underlying the SWA increase after torpor and SD are similar. EEG slow waves recorded in the neocortex during sleep reflect synchronized transitions between periods of activity and silence among large neuronal populations. We therefore set out to investigate characteristics of individual cortical EEG slow waves recorded during NREM sleep after 4 h SD and during sleep after emergence from an episode of daily torpor in adult male Djungarian hamsters. We found that during the first hour after both SD and torpor, the SWA increase was associated with an increase in slow-wave incidence and amplitude. However, the slopes of single slow waves during NREM sleep were steeper in the first hour after SD but not after torpor, and, in contrast to sleep after SD, the magnitude of change in slopes after torpor was unrelated to the changes in SWA. Furthermore, slow-wave slopes decreased progressively within the first 2 h after SD, while a progressive increase in slow-wave slopes was apparent during the first 2 h after torpor. The data suggest that prolonged waking and torpor have different effects on cortical network activity underlying slow-wave characteristics, while resulting in a similar homeostatic sleep response of SWA. We suggest that sleep plays an important role in network homeostasis after both waking and torpor, consistent with a recovery function for both states.</span>

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Positive and Negative Somatotopic BOLD Responses in Contralateral Versus Ipsilateral Penfield Homunculus

<span class="paragraphSection"><div class="boxTitle">Abstract</div>One of the basic properties of sensory cortices is their topographical organization. Most imaging studies explored this organization using the positive blood oxygenation level-dependent (BOLD) signal. Here, we studied the topographical organization of both positive and negative BOLD in contralateral and ipsilateral primary somatosensory cortex (S1). Using phase-locking mapping methods, we verified the topographical organization of contralateral S1, and further showed that different body segments elicit pronounced negative BOLD responses in both hemispheres. In the contralateral hemisphere, we found a sharpening mechanism in which stimulation of a given body segment triggered a gradient of activation with a significant deactivation in more remote areas. In the ipsilateral cortex, deactivation was not only located in the homolog area of the stimulated parts but rather was widespread across many parts of S1. Additionally, analysis of resting-state functional magnetic resonance imaging signal showed a gradient of connectivity to the neighboring contralateral body parts as well as to the ipsilateral homologous area for each body part. Taken together, our results indicate a complex pattern of baseline and activity-dependent responses in the contralateral and ipsilateral sides. Both primary sensory areas were characterized by unique negative BOLD responses, suggesting that they are an important component in topographic organization of sensory cortices.</span>

http://ift.tt/2oLUSAt

Cc2d1a Loss of Function Disrupts Functional and Morphological Development in Forebrain Neurons Leading to Cognitive and Social Deficits

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Loss-of-function (LOF) mutations in <span style="font-style:italic;">CC2D1A</span> cause a spectrum of neurodevelopmental disorders, including intellectual disability, autism spectrum disorder, and seizures, identifying a critical role for this gene in cognitive and social development. CC2D1A regulates intracellular signaling processes that are critical for neuronal function, but previous attempts to model the human LOF phenotypes have been prevented by perinatal lethality in <span style="font-style:italic;">Cc2d1a</span>-deficient mice. To overcome this challenge, we generated a floxed <span style="font-style:italic;">Cc2d1a</span> allele for conditional removal of Cc2d1a in the brain using Cre recombinase. While removal of Cc2d1a in neuronal progenitors using Cre expressed from the <span style="font-style:italic;">Nestin</span> promoter still causes death at birth, conditional postnatal removal of Cc2d1a in the forebrain via calcium/calmodulin-dependent protein kinase II-alpha (<span style="font-style:italic;">CamKIIa</span>) promoter-driven Cre generates animals that are viable and fertile with grossly normal anatomy. Analysis of neuronal morphology identified abnormal cortical dendrite organization and a reduction in dendritic spine density. These animals display deficits in neuronal plasticity and in spatial learning and memory that are accompanied by reduced sociability, hyperactivity, anxiety, and excessive grooming. Cc2d1a conditional knockout mice therefore recapitulate features of both cognitive and social impairment caused by human <span style="font-style:italic;">CC2D1A</span> mutation, and represent a model that could provide much needed insights into the developmental mechanisms underlying nonsyndromic neurodevelopmental disorders.</span>

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Cerebral Activation During Initial Motor Learning Forecasts Subsequent Sleep-Facilitated Memory Consolidation in Older Adults

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Older adults exhibit deficits in motor memory consolidation; however, little is known about the cerebral correlates of this impairment. We thus employed fMRI to investigate the neural substrates underlying motor sequence memory consolidation, and the modulatory influence of post-learning sleep, in healthy older adults. Participants were trained on a motor sequence and retested following an 8-h interval including wake or diurnal sleep as well as a 22-h interval including a night of sleep. Results demonstrated that a post-learning nap improved offline consolidation across same- and next-day retests. This enhanced consolidation was reflected by increased activity in the putamen and the medial temporal lobe, including the hippocampus, regions that have previously been implicated in sleep-dependent neural plasticity in young adults. Moreover, for the first time in older adults, the neural substrates subserving initial motor learning, including the putamen, cerebellum, and parietal cortex, were shown to forecast subsequent consolidation depending on whether a post-learning nap was afforded. Specifically, sufficient activation in a motor-related network appears to be necessary to trigger sleep-facilitated consolidation in older adults. Our findings not only demonstrate that post-learning sleep can enhance motor memory consolidation in older adults, but also provide the system-level neural correlates of this beneficial effect.</span>

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ADAM10-Initiated Release of Notch Intracellular Domain Regulates Microtubule Stability and Radial Migration of Cortical Neurons

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Proper neuronal migration is orchestrated by combined membrane signal paradigms, whereas the role and mechanism of regulated intramembrane proteolysis (RIP) remain to be illustrated. We show here that the disintegrin and metalloprotease-domain containing protein 10 (ADAM10) regulates cortical neurons migration by initiating the RIP of Notch. We found that Notch intracellular domain (NICD) significantly rescued the migration defect of ADAM10-deficient neurons. Moreover, ADAM10 deficiency led to reduced neuronal motility and disrupted microtubule (MT) structure, which were associated with downregulated expression of acetylated tubulin and MT-associated proteins. Specifically, the NICD/RBPJ complex bound directly to the promoter, and regulated the neuronal expression level of doublecortin (DCX), a modulator of the MT cytoskeleton. Functionally, DCX overexpression largely restored neuron motility and reversed migration defect caused by ADAM10 knockout. Taken together, these findings demonstrate the direct requirement of ADAM10 in cortical radial migration and reveal the underlying mechanism by linking ADAM10-initiated RIP of Notch to the regulation of MT cytoskeleton through transcriptional control of <span style="font-style:italic;">Dcx</span> expression.</span>

http://ift.tt/2ooiRte

Heparan Sulfates Support Pyramidal Cell Excitability, Synaptic Plasticity, and Context Discrimination

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Heparan sulfate (HS) proteoglycans represent a major component of the extracellular matrix and are critical for brain development. However, their function in the mature brain remains to be characterized. Here, acute enzymatic digestion of HS side chains was used to uncover how HSs support hippocampal function in vitro and in vivo. We found that long-term potentiation (LTP) of synaptic transmission at CA3–CA1 Schaffer collateral synapses was impaired after removal of highly sulfated HSs with heparinase 1. This reduction was associated with decreased Ca²⁺ influx during LTP induction, which was the consequence of a reduced excitability of CA1 pyramidal neurons. At the subcellular level, heparinase treatment resulted in reorganization of the distal axon initial segment, as detected by a reduction in ankyrin G expression. In vivo, digestion of HSs impaired context discrimination in a fear conditioning paradigm and oscillatory network activity in the low theta band after fear conditioning. Thus, HSs maintain neuronal excitability and, as a consequence, support synaptic plasticity and learning.</span>

http://ift.tt/2oLXFcM

In Vivo Evidence of Reduced Integrity of the Gray–White Matter Boundary in Autism Spectrum Disorder

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Atypical cortical organization and reduced integrity of the gray–white matter boundary have been reported by postmortem studies in individuals with autism spectrum disorder (ASD). However, there are no in vivo studies that examine these particular features of cortical organization in ASD. Hence, we used structural magnetic resonance imaging to examine differences in tissue contrast between gray and white matter in 98 adults with ASD and 98 typically developing controls, to test the hypothesis that individuals with ASD have significantly reduced tissue contrast. More specifically, we examined contrast as a percentage between gray and white matter tissue signal intensities (GWPC) sampled at the gray–white matter boundary, and across different cortical layers. We found that individuals with ASD had significantly reduced GWPC in several clusters throughout the cortex (cluster, <span style="font-style:italic;">P</span> < 0.05). As expected, these reductions were greatest when tissue intensities were sampled close to gray–white matter interface, which indicates a less distinct gray–white matter boundary in ASD. Our in vivo findings of reduced GWPC in ASD are therefore consistent with prior postmortem findings of a less well-defined gray–white matter boundary in ASD. Taken together, these results indicate that GWPC might be utilized as an in vivo proxy measure of atypical cortical microstructural organization in future studies.</span>

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Reduced Hippocampal Functional Connectivity During Episodic Memory Retrieval in Autism

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Increasing recent research has sought to understand the recollection impairments experienced by individuals with autism spectrum disorder (ASD). Here, we tested whether these memory deficits reflect a reduction in the probability of retrieval success or in the precision of memory representations. We also used functional magnetic resonance imaging (fMRI) to study the neural mechanisms underlying memory encoding and retrieval in ASD, focusing particularly on the functional connectivity of core episodic memory networks. Adults with ASD and typical control participants completed a memory task that involved studying visual displays and subsequently using a continuous dial to recreate their appearance. The ASD group exhibited reduced retrieval success, but there was no evidence of a difference in retrieval precision. fMRI data revealed similar patterns of brain activity and functional connectivity during memory encoding in the 2 groups, though encoding-related lateral frontal activity predicted subsequent retrieval success only in the control group. During memory retrieval, the ASD group exhibited attenuated lateral frontal activity and substantially reduced hippocampal connectivity, particularly between hippocampus and regions of the fronto-parietal control network. These findings demonstrate notable differences in brain function during episodic memory retrieval in ASD and highlight the importance of functional connectivity to understanding recollection-related retrieval deficits in this population.</span>

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Compensatory Actions of Ldb Adaptor Proteins During Corticospinal Motor Neuron Differentiation

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Although many genes that specify neocortical projection neuron subtypes have been identified, the downstream effectors that control differentiation of those subtypes remain largely unknown. Here, we demonstrate that the LIM domain-binding proteins Ldb1 and Ldb2 exhibit dynamic and inversely correlated expression patterns during cerebral cortical development. <span style="font-style:italic;">Ldb1</span>-deficient brains display severe defects in proliferation and changes in regionalization, phenotypes resembling those of <span style="font-style:italic;">Lhx</span> mutants. <span style="font-style:italic;">Ldb2</span>-deficient brains, on the other hand, exhibit striking phenotypes affecting layer 5 pyramidal neurons: Immature neurons have an impaired capacity to segregate into mature callosal and subcerebral projection neurons. The analysis of <span style="font-style:italic;">Ldb2</span> single-mutant mice reveals a compensatory role of <span style="font-style:italic;">Ldb1</span> for <span style="font-style:italic;">Ldb2</span> during corticospinal motor neuron (CSMN) differentiation. Animals lacking both <span style="font-style:italic;">Ldb1</span> and <span style="font-style:italic;">Ldb2</span> uncover the requirement for <span style="font-style:italic;">Ldb2</span> during CSMN differentiation, manifested as incomplete CSMN differentiation, and ultimately leading to a failure of the corticospinal tract.</span>

http://ift.tt/2oolNWC

Hippocampus and Prefrontal Cortex Predict Distinct Timescales of Activation in the Human Ventral Tegmental Area

<span class="paragraphSection"><div class="boxTitle">Abstract</div>The mesolimbic dopamine system contributes to a remarkable variety of behaviors at multiple timescales. Midbrain neurons have fast and slow signaling components, and specific afferent systems, such as the hippocampus (HPC) and prefrontal cortex (PFC), have been demonstrated to drive these components in anesthetized animals. Whether these interactions exist during behavior, however, is unknown. To address this question, we developed a novel analysis of human functional magnetic resonance imaging data that fits models of network excitation and inhibition on ventral tegmental area (VTA) activation. We show that specific afferent systems predict distinct temporal components of midbrain VTA signal. We found that PFC, but not HPC, positively predicted transient, event-evoked VTA activation. In contrast, HPC, but not PFC, positively predicted slow shifts in VTA baseline variability. Thus, unique functional contributions of afferent systems to VTA physiology are detectable at the network level in behaving humans. The findings support models of dopamine function in which dissociable neural circuits support different aspects of motivated behavior via active regulation of tonic and phasic signals.</span>

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NKCC1-Mediated GABAergic Signaling Promotes Postnatal Cell Death in Neocortical Cajal–Retzius Cells

<span class="paragraphSection"><div class="boxTitle">Abstract</div>During early development, a substantial proportion of central neurons undergoes programmed cell death. This activity-dependent process is essential for the proper structural and functional development of the brain. To uncover cell type-specific differences in the regulation of neuronal survival versus apoptosis, we studied activity-regulated cell death in Cajal–Retzius neurons (CRNs) and the overall neuronal population in the developing mouse cerebral cortex. CRNs in the upper neocortical layer represent an early-born neuronal population, which is important for cortical development and largely disappears by apoptosis during neonatal stages. In contrast to the overall neuronal population, activity blockade with tetrodotoxin improved survival of CRNs in culture. Activation of GABA_A receptors also blocked spontaneous activity and caused overall cell death including apoptosis of CRNs. Blockade of the Na–K–Cl transporter NKCC1 in vitro or its genetic deletion in vivo rescued CRNs from apoptosis. This effect was mediated by blockade of the p75^NTR receptor signaling pathway. In summary, we discovered a novel developmental death pathway mediated by NKCC1, via GABA_A receptor-mediated membrane depolarization and p75^NTR signaling in CRNs. This pathway controls apoptosis of CRNs and may be critically involved in neurodevelopmental disorders such as autism and schizophrenia.</span>

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Gradient COUP-TFI Expression Is Required for Functional Organization of the Hippocampal Septo-Temporal Longitudinal Axis

<span class="paragraphSection"><div class="boxTitle">Abstract</div>The hippocampus (HP), a medial cortical structure, is subdivided into a distinct dorsal (septal) and ventral (temporal) portion, which is separated by an intermediate region lying on a longitudinal curvature. While the dorsal portion is more dedicated to spatial navigation and memory, the most ventral part processes emotional information. Genetic factors expressed in gradient during development seem to control the size and correct positioning of the HP along its longitudinal axis; however, their roles in regulating differential growth and in supporting its anatomical and functional dissociation remain unexplored. Here, we challenge the in vivo function of the nuclear receptor COUP-TFI (chicken ovalbumin upstream promoter transcription factor 1) in controlling the hippocampal, anatomical, and functional properties along its longitudinal axis. Loss of cortical COUP-TFI function results in a dysmorphic HP with altered shape, volume, and connectivity, particularly in its dorsal and intermediate regions. Notably, topographic inputs from the entorhinal cortex are strongly impaired in the dorsal portion of <span style="font-style:italic;">COUP-TFI</span> mutants. These severe morphological changes are associated with selective spatial learning and memory impairment. These findings identify a novel transcriptional regulator required in the functional organization along the hippocampal septo-temporal axis supporting a genetic basis of the hippocampal volumetric growth with its final shape, circuit, and type of memory function.</span>

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cAMP-Dependent Calcium Oscillations of Astrocytes: An Implication for Pathology

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Astrocytes in various brain regions exhibit spontaneous intracellular calcium elevations both in vitro and in vivo; however, neither the temporal pattern underlying this activity nor its function has been fully evaluated. Here, we utilized a long-term optical imaging technique to analyze the calcium activity of more than 4000 astrocytes in acute hippocampal slices as well as in the neocortex and hippocampus of head-restrained mice. Although astrocytic calcium activity was largely sparse and irregular, we observed a subset of cells in which the fluctuating calcium oscillations repeated at a regular interval of ∼30 s. These intermittent oscillations i) depended on type 2 inositol 1,4,5-trisphosphate receptors; ii) consisted of a complex reverberatory interaction between the soma and processes of individual astrocytes; iii) did not synchronize with those of other astrocytes; iv) did not require neuronal firing; v) were modulated through cAMP-protein kinase A signaling; vi) were facilitated under pathological conditions, such as energy deprivation and epileptiform hyperexcitation; and vii) were associated with enhanced hypertrophy in astrocytic processes, an early hallmark of reactive gliosis, which is observed in ischemia and epilepsy. Therefore, calcium oscillations appear to be associated with a pathological state in astrocytes.</span>

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Regulation of Cognitive Processing by Hippocampal Cholinergic Tone

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Cholinergic dysfunction has been associated with cognitive abnormalities in a variety of neurodegenerative and neuropsychiatric diseases. Here we tested how information processing is regulated by cholinergic tone in genetically modified mice targeting the vesicular acetylcholine transporter (VAChT), a protein required for acetylcholine release. We measured long-term potentiation of Schaffer collateral-CA1 synapses in vivo and assessed information processing by using a mouse touchscreen version of paired associates learning task (PAL). Acquisition of information in the mouse PAL task correlated to levels of hippocampal VAChT, suggesting a critical role for cholinergic tone. Accordingly, synaptic plasticity in the hippocampus in vivo was disturbed, but not completely abolished, by decreased hippocampal cholinergic signaling. Disrupted forebrain cholinergic signaling also affected working memory, a result reproduced by selectively decreasing VAChT in the hippocampus. In contrast, spatial memory was relatively preserved, whereas reversal spatial memory was sensitive to decreased hippocampal cholinergic signaling. This work provides a refined roadmap of how synaptically secreted acetylcholine influences distinct behaviors and suggests that distinct forms of cognitive processing may be regulated in different ways by cholinergic activity.</span>

http://ift.tt/2oLOJUE

Direct Recordings from Human Anterior Insula Reveal its Leading Role within the Error-Monitoring Network

<span class="paragraphSection"><div class="boxTitle">Abstract</div>The ability to monitor our own errors is mediated by a network that includes dorsomedial prefrontal cortex (dmPFC) and anterior insula (AI). However, the dynamics of the underlying neurophysiological processes remain unclear. In particular, whether AI is on the receiving or driving end of the error-monitoring network is unresolved. Here, we recorded intracerebral electroencephalography signals simultaneously from AI and dmPFC in epileptic patients while they performed a stop-signal task. We found that errors selectively modulated broadband neural activity in human AI. Granger causality estimates revealed that errors were immediately followed by a feedforward influence from AI onto anterior cingulate cortex and, subsequently, onto presupplementary motor area. The reverse pattern of information flow was observed on correct responses. Our findings provide the first direct electrophysiological evidence indicating that the anterior insula rapidly detects and conveys error signals to dmPFC, while the latter might use this input to adapt behavior following inappropriate actions.</span>

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Whole Transcriptome Screening Reveals Myelination Deficits in Dysplastic Human Temporal Neocortex

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Focal cortical dysplasias (FCDs) are local malformations of the human neocortex with strong epileptogenic potential. To investigate the underlying pathomechanisms, we performed a whole human transcriptome screening to compare the gene expression pattern of dysplastic versus nondysplastic temporal neocortex. Tissue obtained from FCD IIIa cases (mean age 20.5 years) who had undergone surgical treatment, due to intractable epilepsy, was compared with nondysplastic specimens (mean age 19.9 years) by means of Affymetrix arrays covering 28 869 genes. We found 211 differentially expressed genes (DEX) among which mainly genes important for oligodendrocyte differentiation and myelination were downregulated in FCD IIIa. These findings were confirmed as functionally important by Database for Annotation, Visualization, and Integrated Discovery (DAVID) analysis. The reduced expression of myelin-associated transcripts was confirmed for FCD Ia, IIa, and IIIa by real-time RT–qPCR. In addition, we found that the density of myelin basic protein mRNA-expressing oligodendrocytes and of 2′,3′-cyclic nucleotide 3′-phosphodiesterase-positive myelin fibers was significantly reduced in dysplastic cortex. Moreover, high-resolution confocal imaging and 3D reconstruction revealed that the myelin fiber network was severely disorganized in dysplastic neocortex, indicating a disturbance of myelin sheath formation and maintenance in FCD.</span>

http://ift.tt/2oMbok0

Asc-1 Transporter Regulation of Synaptic Activity via the Tonic Release of d -Serine in the Forebrain

<span class="paragraphSection"><div class="boxTitle">Abstract</div><span style="text-transform:lowercase;font-variant:small-caps;">d</span>-Serine is a co-agonist of NMDA receptors (NMDARs) whose activity is potentially regulated by Asc-1 (SLC7A10), a transporter that displays high affinity for <span style="text-transform:lowercase;font-variant:small-caps;">d</span>-serine and glycine. Asc-1 operates as a facilitative transporter and as an antiporter, though the preferred direction of <span style="text-transform:lowercase;font-variant:small-caps;">d</span>-serine transport is uncertain. We developed a selective Asc-1 blocker, Lu AE00527, that blocks <span style="text-transform:lowercase;font-variant:small-caps;">d</span>-serine release mediated by all the transport modes of Asc-1 in primary cultures and neocortical slices. Furthermore, <span style="text-transform:lowercase;font-variant:small-caps;">d</span>-serine release is reduced in slices from Asc-1 knockout (KO) mice, indicating that <span style="text-transform:lowercase;font-variant:small-caps;">d</span>-serine efflux is the preferred direction of Asc-1. The selectivity of Lu AE00527 is assured by the lack of effect on slices from Asc-1-KO mice, and the lack of interaction with the co-agonist site of NMDARs. Moreover, in vivo injection of Lu AE00527 in P-glycoprotein-deficient mice recapitulates a hyperekplexia-like phenotype similar to that in Asc-1-KO mice. In slices, Lu AE00527 decreases the long-term potentiation at the Schaffer collateral-CA1 synapses, but does not affect the long-term depression. Lu AE00527 blocks NMDAR synaptic potentials when typical Asc-1 extracellular substrates are present, but it does not affect AMPAR transmission. Our data demonstrate that Asc-1 mediates tonic co-agonist release, which is required for optimal NMDAR activation and synaptic plasticity.</span>

http://ift.tt/2ookCXt

Common Neural Representations for Visually Guided Reorientation and Spatial Imagery

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Spatial knowledge about an environment can be cued from memory by perception of a visual scene during active navigation or by imagination of the relationships between nonvisible landmarks, such as when providing directions. It is not known whether these different ways of accessing spatial knowledge elicit the same representations in the brain. To address this issue, we scanned participants with fMRI, while they performed a judgment of relative direction (JRD) task that required them to retrieve real-world spatial relationships in response to either pictorial or verbal cues. Multivoxel pattern analyses revealed several brain regions that exhibited representations that were independent of the cues to access spatial memory. Specifically, entorhinal cortex in the medial temporal lobe and the retrosplenial complex (RSC) in the medial parietal lobe coded for the heading assumed on a particular trial, whereas the parahippocampal place area (PPA) contained information about the starting location of the JRD. These results demonstrate the existence of spatial representations in RSC, ERC, and PPA that are common to visually guided navigation and spatial imagery.</span>

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Morphological characteristics of external auditory canal in congenital aural stenosis patients

ObjectiveTo investigate characteristics of congenital aural stenosis (CAS) patients' external auditory canal (EAC) (position, length, orientation, etc.) and compare them with normal EAC.

http://ift.tt/2ooiOgT

Clinical and audiological characteristics of 1000Hz audiometric notch patients

Among the hearing loss patients, we can confirm that the hearing loss of the specific frequency decreases, such as the 2000Hz notch in otosclerosis and the 4000Hz notch (c5-dip) in noise-induced hearing loss. The 1000Hz notch (c3-dip), however, is rarely studied. We fortuitously encountered a group of patients with a 1kHz hearing loss and report it with a review of the literature.

http://ift.tt/2ns2pmQ

Social attention and autism symptoms in high functioning women with autism spectrum disorders

Publication date: May 2017
Source:Research in Developmental Disabilities, Volume 64
Author(s): Mieke P. Ketelaars, Anne In't Velt, Audrey Mol, Hanna Swaab, Fenne Bodrij, Sophie van Rijn
BackgroundResearch has suggested a different, less visible, clinical manifestation of Autism Spectrum Disorders (ASD) in females. There is, however, limited research into possible underlying mechanisms explaining the female phenotype.AimsThis study investigates social attention in females with ASD.Methods and procedures26 women diagnosed with ASD and 26 typical female controls were shown three video clips containing intense emotions. Social attention was assessed by measuring eye fixation patterns during the video clips. Autism symptoms were assessed using the informant reported Social Responsiveness Scale (SRS).Outcome and resultsResults show normal time to first fixation to the face, but lower fixation duration to the face in women with ASD. Analyzing the visual patterns further, there were similar impairments in fixation to mouth, eyes and other facial areas. Relating social attention to autism symptoms revealed several significant correlations within the ASD group.Conclusions and implicationsWomen with ASD show abnormalities in social attention and these abnormalities are related to level of autism symptoms. In contrast to other studies which investigate male dominated ASD samples, a hyperfocus to the mouth area could not be found.



http://ift.tt/2onOp20

Morphological characteristics of external auditory canal in congenital aural stenosis patients

ObjectiveTo investigate characteristics of congenital aural stenosis (CAS) patients' external auditory canal (EAC) (position, length, orientation, etc.) and compare them with normal EAC.

http://ift.tt/2ooiOgT

Clinical and audiological characteristics of 1000Hz audiometric notch patients

Among the hearing loss patients, we can confirm that the hearing loss of the specific frequency decreases, such as the 2000Hz notch in otosclerosis and the 4000Hz notch (c5-dip) in noise-induced hearing loss. The 1000Hz notch (c3-dip), however, is rarely studied. We fortuitously encountered a group of patients with a 1kHz hearing loss and report it with a review of the literature.

http://ift.tt/2ns2pmQ

Zuckerkandl’s tubercle and its relationship to the recurrent laryngeal nerve: A cadaveric dissection and meta-analysis

Zuckerkandl's tubercle (ZT), when present, is an anatomical landmark by which surrounding structures such as the recurrent laryngeal nerve (RLN) can be identified intraoperatively. This study aimed to investigate the prevalence and anatomical characteristics of Zuckerkandl's tubercle by combining cadaveric dissection with a meta-analysis.

http://ift.tt/2nuNitT

Rejuvenation of mucosal immunosenescence by adipose tissue-derived mesenchymal stem cells

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Age-associated alterations in the mucosal immune system are generally termed mucosal immunosenescence. The major change seen in the aged mucosa is a failure to elicit an antigen-specific secretory IgA (SIgA) antibody response, which is a central player for host defense from various pathogens at mucosal surfaces. In this regard, it would be a first priority to compensate for mucosal dysregulation in the elderly in order to maintain their health in aging. We have successfully established antigen-specific SIgA antibody responses in aged (2 years old) mice, which provide protective immunity from <span style="font-style:italic;">Streptococcus pneumoniae</span> and influenza virus infections, by using a new adjuvant system consisting of a plasmid encoding Flt3 ligand (pFL) and CpG ODN. In order to explore possible use of current mucosal vaccine strategies for the elderly, we have adoptively transferred adipose tissue-derived mesenchymal stem cells (AMSCs) to aged mice prior to mucosal vaccination. This immune therapy successfully resulted in protective antigen-specific antibody responses in the intestinal mucosa of aged mice that were comparable to those seen in young adult mice. In this regard, we postulate that adoptively transferred AMSCs could augment dendritic cell functions in aged mice. The potential cellular and molecular mechanisms whereby AMSCs restore mucosal immunity in immunosenescence are discussed in this short review. A stem cell transfer system could be an attractive and effective immunologic intervention strategy to reverse mucosal immunosenescence.</span>

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Cover

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Important Announcement

<span class="paragraphSection"><span style="font-style:italic;">International Immunology</span> is the official journal of the Japanese Society for Immunology (JSI) and was launched in partnership with Oxford University Press in 1989 with Professor Tomio Tada as its inaugural Editor-in-Chief. Through Professor Tada's efforts <span style="font-style:italic;">International Immunology</span> firmly established itself as an internationally renowned, first rate immunology journal.</span>

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In This Issue

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Subscriptions

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Table of Contents

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Mesenchymal stem cell-derived extracellular vesicles: a glimmer of hope in treating Alzheimer’s disease

<span class="paragraphSection"><div class="boxTitle">Abstract</div>One of the pathological hallmarks of Alzheimer's disease (AD) is the presence of extracellular plaques resulting from the accumulation of beta-amyloid peptide (Aβ). To date, a definitive cure for this disease is still lacking as the currently approved drugs used are mainly symptomatic treatments. The revolutionary discovery of extracellular vesicles (EVs) has shed new light on the development of disease-modifying treatments for AD, owing to their potential in delivering the therapeutic agents to the brain. The feasibility of harnessing EVs for clinical applications is highly dependent on the donor cell, which determines the intrinsic properties of EVs. The merit of mesenchymal stem cells (MSCs) as therapeutic delivery vehicles, and the proven therapeutic effects of the EVs derived from these cells, make researchers esteem MSCs as ideal producers of EVs. Therefore, MSC-derived EVs (MSC-EVs) emerge to be an appealing therapeutic delivery approach for the treatment of AD. Here, we discuss perspectives on the therapeutic strategies using MSC-EVs to treat AD and the associated challenges in clinical application.</span>

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Inflammatory and anti-inflammatory states of adipose tissue in transgenic mice bearing a single TCR

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Obesity is accompanied by chronic, low-grade inflammation in adipose tissue, which is associated with insulin resistance and consequent multiple metabolic diseases. In addition to M1 macrophage infiltration, multiple involvements of adipose tissue T lymphocytes in the progression of inflammation have been highlighted recently. Here, we isolated a specific Vα5/Vβ8.2 TCR-bearing T cell that accumulated in obese adipose tissue of mice, and generated transgenic mice expressing this TCR. Under lean conditions with a normal chow diet, CD4⁺FoxP3⁺ T_reg cells and M2 macrophages increased in adipose tissue with ageing in wild-type mice, but not in transgenic mice. However, both mice exhibited no obvious adipose tissue inflammation such as the formation of crown-like structures (CLSs) of infiltrating macrophages. When fed a high-fat diet, the proportion of adipose tissue T_reg cells was markedly small at a similar level in transgenic and wild-type mice. Both types of mice exhibited comparable inflammatory states in adipose tissue, including vast formation of macrophage CLSs, accompanied by insulin resistance. Together, our findings suggest that the absence of an increase in T_reg cells and M2 macrophages is not sufficient to initiate inflammatory macrophage infiltration in lean adipose tissue and also provide a new view about the involvement of T cells in promoting obesity-associated inflammation.</span>

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The spleen is the site where mast cells are induced in the development of food allergy

<span class="paragraphSection"><div class="boxTitle">Abstract</div>It has been reported that splenic immune responses play pivotal roles in the development of allergic diseases; however, the precise role of the spleen remains unclear. Herein, we demonstrated a novel role of the spleen in the pathogenesis of food allergy (FA). We found that mast cells (MCs) developed from progenitor cells present in spleen during an antigen-specific T-cell response <span style="font-style:italic;">in vitro</span>. In a T_h2 response-mediated FA model, significant expansion of MCs was also observed in spleen. The incidence of allergic diarrhea was profoundly reduced in splenectomized mice, whereas adoptive transfer of <span style="font-style:italic;">in vitro</span>-induced splenic MCs into these mice restored allergic symptoms, suggesting that the splenic MCs functioned as the pathogenic cells in the development of FA. The <span style="font-style:italic;">in vitro</span>-generated MCs required not only IL-3 but also IFN-γ, and treatment of FA-induced mice with anti-IFN-γ antibody suppressed expansion of MCs in spleen as well as diarrhea development, highlighting that IFN-γ in the spleen orchestrated the development of FA, which was followed by a T_h2 response in the local lesion. Overall, we propose that the role of the spleen in the development of FA is to provide a unique site where antigen-specific T cells induce development of pathogenic MCs.</span>

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Zuckerkandl’s tubercle and its relationship to the recurrent laryngeal nerve: A cadaveric dissection and meta-analysis

Zuckerkandl's tubercle (ZT), when present, is an anatomical landmark by which surrounding structures such as the recurrent laryngeal nerve (RLN) can be identified intraoperatively. This study aimed to investigate the prevalence and anatomical characteristics of Zuckerkandl's tubercle by combining cadaveric dissection with a meta-analysis.

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RE: “AGE AND SEX DIFFERENCES IN BODY MASS INDEX AS A PREDICTOR OF HIP FRACTURE: A NOREPOS STUDY”

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Correction of Selection Bias in Survey Data: Is the Statistical Cure Worse Than the Bias?

<span class="paragraphSection"><div class="boxTitle">Abstract</div>In previous articles in the <span style="font-style:italic;">American Journal of Epidemiology</span> (<span style="font-style:italic;">Am J Epidemiol</span>. 2013;177(5):431–442) and <span style="font-style:italic;">American Journal of Public Health</span> (<span style="font-style:italic;">Am J Public Health</span>. 2013;103(10):1895–1901), Masters et al. reported age-specific hazard ratios for the contrasts in mortality rates between obesity categories. They corrected the observed hazard ratios for selection bias caused by what they postulated was the nonrepresentativeness of the participants in the National Health Interview Study that increased with age, obesity, and ill health. However, it is possible that their regression approach to remove the alleged bias has not produced, and in general cannot produce, sensible hazard ratio estimates. First, one must consider how many nonparticipants there might have been in each category of obesity and of age at entry and how much higher the mortality rates would have to be in nonparticipants than in participants in these same categories. What plausible set of numerical values would convert the ("biased") decreasing-with-age hazard ratios seen in the data into the ("unbiased") increasing-with-age ratios that they computed? Can these values be encapsulated in (and can sensible values be recovered from) 1 additional internal variable in a regression model? Second, one must examine the age pattern of the hazard ratios that have been adjusted for selection. Without the correction, the hazard ratios are attenuated with increasing age. With it, the hazard ratios at older ages are considerably higher, but those at younger ages are well below 1. Third, one must test whether the regression approach suggested by Masters et al. would correct the nonrepresentativeness that increased with age and ill health that I introduced into real and hypothetical data sets. I found that the approach did not recover the hazard ratio patterns present in the unselected data sets: The corrections overshot the target at older ages and undershot it at lower ages.</span>

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Masters et al. Respond

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Editorial: Note About Inaccurate Results Published in the American Journal of Epidemiology and the American Journal of Public Health

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Testing for Gene-Environment Interactions Using a Prospective Family Cohort Design: Body Mass Index in Early and Later Adulthood and Risk of Breast Cancer

<span class="paragraphSection"><div class="boxTitle">Abstract</div>The ability to classify people according to their underlying genetic susceptibility to a disease is increasing with new knowledge, better family data, and more sophisticated risk prediction models, allowing for more effective prevention and screening. To do so, however, we need to know whether risk associations are the same for people with different genetic susceptibilities. To illustrate one way to estimate such gene-environment interactions, we used prospective data from 3 Australian family cancer cohort studies, 2 enriched for familial risk of breast cancer. There were 288 incident breast cancers in 9,126 participants from 3,222 families. We used Cox proportional hazards models to investigate whether associations of breast cancer with body mass index (BMI; weight (kg)/height (m)²) at age 18–21 years, BMI at baseline, and change in BMI differed according to genetic risk based on lifetime breast cancer risk from birth, as estimated by BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) software, adjusted for age at baseline data collection. Although no interactions were statistically significant, we have demonstrated the power with which gene-environment interactions can be investigated using a cohort enriched for persons with increased genetic risk and a continuous measure of genetic risk based on family history.</span>

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Assessment of Confounders in Comparative Effectiveness Studies From Secondary Databases

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Secondary clinical databases are an important and growing source of data for comparative effectiveness research (CER) studies. However, measurement of confounders, such as biomarker values or patient-reported health status, in secondary clinical databases may not align with the initiation of a new treatment. In many published CER analyses of registry data, investigators assessed confounders based on the first questionnaire in which the new exposure was recorded. However, it is known that adjustment for confounders measured after the start of exposure can lead to biased treatment effect estimates. In the present study, we conducted simulations to compare assessment strategies for a dynamic clinical confounder in a registry-based comparative effectiveness study of 2 therapies. As expected, we found that adjustment for the confounder value at the time of the first questionnaire after the start of exposure creates a biased estimate the total effect of exposure choice on outcome when the confounder mediates part of the effect. However, adjustment for the prior value can also be badly biased when measured long before exposure initiation. Thus, investigators should carefully consider the timing of confounder measurements relative to exposure initiation and the rate of change in the confounder in order to choose the most relevant measure for each patient.</span>

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THE AUTHORS REPLY

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Mode of Delivery and Asthma at School Age in 9 European Birth Cohorts

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Evidence on the association between mode of delivery and asthma at school age is inconclusive. We assessed the associations between specific modes of delivery and asthma in children from 9 European birth cohorts that enrolled participants between 1996 and 2006. Cohort-specific crude and adjusted risk ratios for asthma at ages 5–9 years were calculated using Poisson regression models and pooled. A sensitivity analysis was carried out in children born at term to reduce confounding due to perinatal factors. The study included 67,613 participants. Cohort-specific rates of cesarean delivery varied from 9.4% to 37.5%. Cesarean delivery, as opposed to vaginal delivery, was associated with an increased risk of asthma (adjusted risk ratio (aRR) = 1.22, 95% confidence interval (CI): 1.02, 1.46). Compared with spontaneous vaginal delivery, the adjusted risk ratio was 1.33 (95% CI: 1.02, 1.75) for elective cesarean delivery, 1.07 (95% CI: 0.94, 1.22) for emergency cesarean delivery, and 0.97 (95% CI: 0.84, 1.12) for operative vaginal delivery. In children born at term, the associations were strengthened only for elective cesarean delivery (aRR = 1.49, 95% CI: 1.13, 1.97). The large sample size allowed analysis of the associations between specific modes of delivery and asthma at school age. The increased risk of asthma associated with elective cesarean delivery, especially among children born at term, is relevant in counteracting the increasing use of this procedure, which is often performed without a clear medical indication.</span>

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Conducting Privacy-Preserving Multivariable Propensity Score Analysis When Patient Covariate Information Is Stored in Separate Locations

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Distributed networks of health-care data sources are increasingly being utilized to conduct pharmacoepidemiologic database studies. Such networks may contain data that are not physically pooled but instead are distributed horizontally (separate patients within each data source) or vertically (separate measures within each data source) in order to preserve patient privacy. While multivariable methods for the analysis of horizontally distributed data are frequently employed, few practical approaches have been put forth to deal with vertically distributed health-care databases. In this paper, we propose 2 propensity score–based approaches to vertically distributed data analysis and test their performance using 5 example studies. We found that these approaches produced point estimates close to what could be achieved without partitioning. We further found a performance benefit (i.e., lower mean squared error) for sequentially passing a propensity score through each data domain (called the "sequential approach") as compared with fitting separate domain-specific propensity scores (called the "parallel approach"). These results were validated in a small simulation study. This proof-of-concept study suggests a new multivariable analysis approach to vertically distributed health-care databases that is practical, preserves patient privacy, and warrants further investigation for use in clinical research applications that rely on health-care databases.</span>

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Chronic Noncommunicable Diseases in 6 Low- and Middle-Income Countries: Findings From Wave 1 of the World Health Organization's Study on Global Ageing and Adult Health (SAGE)

<span class="paragraphSection"><div class="boxTitle">Abstract</div>In this paper, we examine patterns of self-reported diagnosis of noncommunicable diseases (NCDs) and prevalences of algorithm/measured test-based, undiagnosed, and untreated NCDs in China, Ghana, India, Mexico, Russia, and South Africa. Nationally representative samples of older adults aged ≥50 years were analyzed from wave 1 of the World Health Organization's Study on Global Ageing and Adult Health (2007–2010; <span style="font-style:italic;">n</span> = 34,149). Analyses focused on 6 conditions: angina, arthritis, asthma, chronic lung disease, depression, and hypertension. Outcomes for these NCDs were: 1) self-reported disease, 2) algorithm/measured test-based disease, 3) undiagnosed disease, and 4) untreated disease. Algorithm/measured test-based prevalence of NCDs was much higher than self-reported prevalence in all 6 countries, indicating underestimation of NCD prevalence in low- and middle-income countries. Undiagnosed prevalence of NCDs was highest for hypertension, ranging from 19.7% (95% confidence interval (CI): 18.1, 21.3) in India to 49.6% (95% CI: 46.2, 53.0) in South Africa. The proportion untreated among all diseases was highest for depression, ranging from 69.5% (95% CI: 57.1, 81.9) in South Africa to 93.2% (95% CI: 90.1, 95.7) in India. Higher levels of education and wealth significantly reduced the odds of an undiagnosed condition and untreated morbidity. A high prevalence of undiagnosed NCDs and an even higher proportion of untreated NCDs highlights the inadequacies in diagnosis and management of NCDs in local health-care systems.</span>

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Interactions Between Genome-Wide Significant Genetic Variants and Circulating Concentrations of 25-Hydroxyvitamin D in Relation to Prostate Cancer Risk in the National Cancer Institute BPC3

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Genome-wide association studies (GWAS) have identified over 100 single nucleotide polymorphisms (SNPs) associated with prostate cancer. However, information on the mechanistic basis for some associations is limited. Recent research has been directed towards the potential association of vitamin D concentrations and prostate cancer, but little is known about whether the aforementioned genetic associations are modified by vitamin D. We investigated the associations of 46 GWAS-identified SNPs, circulating concentrations of 25-hydroxyvitamin D (25(OH)D), and prostate cancer (3,811 cases, 511 of whom died from the disease, compared with 2,980 controls—from 5 cohort studies that recruited participants over several periods beginning in the 1980s). We used logistic regression models with data from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3) to evaluate interactions on the multiplicative and additive scales. After allowing for multiple testing, none of the SNPs examined was significantly associated with 25(OH)D concentration, and the SNP–prostate cancer associations did not differ by these concentrations. A statistically significant interaction was observed for each of 2 SNPs in the 8q24 region (rs620861 and rs16902094), 25(OH)D concentration, and fatal prostate cancer on both multiplicative and additive scales (<span style="font-style:italic;">P</span> ≤ 0.001). We did not find strong evidence that associations between GWAS-identified SNPs and prostate cancer are modified by circulating concentrations of 25(OH)D. The intriguing interactions between rs620861 and rs16902094, 25(OH)D concentration, and fatal prostate cancer warrant replication.</span>

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Invited Commentary: Foreclosures and Health in a Neighborhood Context

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Recent systematic reviews link foreclosure to worse health at both the individual and population levels. In this issue of the <span style="font-style:italic;">Journal</span>, Downing et al. (<span style="font-style:italic;">Am J Epidemiol</span>. 2017;185(6):429–435) add to what is known about foreclosure and health by examining annual measures of glycemic control in relation to local foreclosure activity. They provided evidence that between 2007 and 2010, glycemic control was not associated with rates of completed foreclosure among a continuously insured managed-care population of persons with type 2 diabetes living in 9 California counties. In this commentary, I consider 5 possible interpretations of the null results: 1) foreclosures do not affect health in general, 2) glycated hemoglobin is insensitive to local foreclosure activity, 3) the presence of real estate owned foreclosures (rather than the competed foreclosure rate) affects health, 4) an integrated health-care delivery system buffers patients from the effects of the foreclosure crisis, and 5) community conditions and responses to the foreclosure crisis buffer patients from the effects of the foreclosure crisis. I close by arguing that research on the contextual effects of foreclosure on health should continue despite the ongoing recovery of the housing market.</span>

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Beyond the Great Recession: Was the Foreclosure Crisis Harmful to the Health of Individuals With Diabetes?

<span class="paragraphSection"><div class="boxTitle">Abstract</div>The housing foreclosure crisis was harmful to the financial well-being of many households. In the present study, we investigated the health effects of the housing foreclosure crisis on glycemic control within a population of patients with diabetes. We hypothesized that an increase in the neighborhood foreclosure rate could worsen glycemic control by activating stressors such as higher neighborhood crime, lower housing prices, and erosion of neighborhood social cohesion. To test this, we linked public foreclosure records at the census-block level with clinical records from 2006 to 2009 of patients with diabetes. We specified individual fixed-effects models and controlled for individual time-invariant confounders and area-level time-varying confounders, including housing prices and unemployment rate, to estimate the effect of the foreclosure rate per census-block group on glycated hemoglobin. We found no statistically significant relationship between changes in the neighborhood foreclosure rate per block group in the prior year and changes in glycated hemoglobin. There is no evidence that increased foreclosure rates worsened glycemic control in this continuously insured population with diabetes. More research is needed to inform our knowledge of the role of insurance and health-care delivery systems in protecting the health of diabetic patients during times of economic stress.</span>

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Downing et al. Respond to “Foreclosures and Health in a Neighborhood Context”

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Diet-Induced Overweight and Obesity and Periodontitis Risk: An Application of the Parametric G-Formula in the 1982 Pelotas Birth Cohort

<span class="paragraphSection"><div class="boxTitle">Abstract</div>We aimed to estimate hypothetical effects of habits (smoking, alcohol consumption, and fat and carbohydrates consumption) combined with diet-induced overweight/obesity on the risk of periodontitis. The risk of any periodontitis, moderate/severe periodontitis, and the combination of bleeding on probing (BOP) and clinical attachment loss (CAL) was estimated using the parametric g-formula in adults aged 31 years from the 1982 Pelotas Birth Cohort in Brazil. Individuals in this cohort have been followed since birth. Hypothetical conditions were set independently for each risk factor and in combination for the entire population. A total of 539 participants had oral examinations in 2013. The cumulative 31-year risk under no intervention was 33.3% for any periodontitis, 14.3%, for moderate/severe periodontitis, and 14.7%, for BOP and CAL. According to our statistical approach, diet-induced overweight/obesity increased the risk of all outcomes: 11% (overweight) and 22% (obesity) higher risk of periodontitis; 12% (overweight) and 27% (obesity) higher risk of moderate/severe periodontitis; 21% (overweight) and 57% (obesity) higher risk of CAL and BOP. When overweight/obesity was combined with other unhealthy habits, the risk was even greater. Our findings suggest that the combination of diet-induced obesity with other risk factors may increase the risk of periodontitis. Further research in the field is required to corroborate our study.</span>

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