bluuebunny/crossref_metadata_2025 huggingface dataset:
Rondas por la seguridad del paciente: experiencia en el Instituto Nacional Materno Perinatal
Authors: Guevara Ríos Enrique , Pérez Aliaga Carlos
Published: May 2019

Las rondas de seguridad para los pacientes es una práctica recomendada para incrementar la calidad en los servicios clínicos y no clínicos relacionados al cuidado de los pacientes. Consiste en una visita planificada del personal ejecutivo relacionado con el área, para establecer una relación directa con el personal y los pacientes, cuidando en todo momento de guardar una actitud educativa y cuyo objetivo general es fortalecer la cultura por la seguridad del paciente. En el Instituto Nacional Materno Perinatal, establecimiento de categoría III-2 para la atención especializada de la mujer, gestante y recién nacido, se vienen llevando a cabo estas rondas desde el año 2011, y gracias a ellas se han obtenido mejoras en la atención con seguridad de los pacientes. Se presenta la experiencia del Instituto entre los años 2011 y 2017.
Atención del parto centrada en el paciente
Authors: Vera Loyola Edy
Published: May 2019

La atención del parto centrada en el paciente abre una nueva perspectiva para mejorar la calidad de atención de los pacientes. Existen desde hace un par de décadas muchos esfuerzos por lograr este anhelo. Desde la publicación del libro ‘Errar es humano’, ha habido múltiples esfuerzos por evitar el evento adverso en el paciente. En ese sentido, el reto es cómo cumplir este objetivo, sabiendo que el proceso de atención del trabajo de parto es uno en los que más eventos adversos reporta. Basados en recomendaciones de la OMS, se plantea un enfoque que consiste en: a) Sistemas de salud: siendo la cultura de seguridad un hito importante para lograr las metas, que involucra cambios en la organización, es uno de los puntos más álgidos por resolver; b) Profesionales sanitarios: no solo involucra al médico sino a la organización sanitaria, desde un enfoque médico; las personas deberán no solamente tener formación médica, sino especializada y en constante actualización, siendo los retos diferentes si se trata de un personal en formación o de un médico especialista. Existen actualmente formas de cómo lograrlo. Además, se tendrá que romper con los mitos de la atención obstétrica, la cual debe ser basada en evidencias; c) Familia y comunidad: el componente emocional que brinda la familia siempre es una columna fundamental. Sinergizando estos lineamientos, se puede enfocar mejor la atención del parto centrada en la persona.
Metabolismo intermediario basal y posprandial en mujeres posmenopáusicas normales de altura
Authors: Garmendia Fausto , Pando Rosa , Mendoza Yanet , Torres William
Published: May 2019

Objetivos. Estudiar el metabolismo intermediario basal y posprandial en mujeres posmenopáusicas normales de altura, adaptadas a un ambiente de menor presión barométrica, menor presión parcial de oxígeno e hipoxia. Métodos. Estudio experimental con grupo control, que incluyó a 20 mujeres normales de altura-MNA- (Cusco, 3 395 metros sobre el nivel del mar-m.s.n.m.) y a 16 de nivel del mar-MNM- (Lima, 150 m.s.n.m.), de 40 a 70 años de edad, posmenopáusicas. En ayunas se midió glucosa (G), colesterol total (CT), HDL, triglicéridos (Tg), insulina (I), ácidos grasos no esterificados (AGNE) por métodos convencionales, y el VLDL, LDL, no-HDL y HOMA. Después de ingerir un desayuno mixto conteniendo 730 kcal, se midió G, CT, Tg, I y AGNE, durante 6 horas. Resultados. En ayunas, las MNA presentaron glucosa (G) significativamente más baja y los AGNE más altos que las MNM; el CT, HDL, Tg, colesterol VLDL, LDL, no-HDL e insulina fueron similares en ambos grupos. Durante el período posprandial, la G fue más baja, los Tg y AGNE fueron significativamente mayores en las MNA y la insulina fue similar. Conclusiones. El metabolismo intermediario de las MNA es diferente a las MNM y al descrito en varones de altura, tanto en condiciones basales como posprandiales.
Validez diagnóstica del índice de pulsatilidad y velocidad media de la arteria uterina en preeclampsia y restricción del crecimiento intrauterino
Authors: Apaza Valencia John
Published: May 2019

Objetivo. Valorar la validez diagnóstica del índice de pulsatilidad (IP) y velocidad media (VM) de la arteria uterina en la preeclampsia (PE) y la restricción del crecimiento intrauterino (RCIU). Diseño. Estudio transversal analítico realizado en el Hospital III Honorio Delgado de Arequipa, Perú, desde mayo 2014 hasta abril 2015. El grupo de casos lo constituyeron 78 gestantes con PE de inicio precoz (< 34 semanas), PE de inicio tardío (≥ 34 semanas), RCIU y RCIU con PE, y el grupo control estuvo formado por 100 gestantes sin complicaciones, con embarazo único de 20 a 40 semanas. Se realizó ecografía Doppler de las arterias uterinas, calculándose el IP y VM de las arterias uterinas, promedios y pruebas de validez diagnóstica en PE y RCIU. Resultados. La VM en la RCIU tuvo sensibilidad y especificidad de 76,2 y 96,9, respectivamente, y en la PE de inicio tardío, la sensibilidad y especificidad fueron 42,4 y 96,9, respectivamente. El IP en RCIU tuvo sensibilidad y especificidad de 28,6 y 92,2, respectivamente, y en PE de inicio tardío, la sensibilidad y especificidad fueron 30,3 y 92,2, respectivamente. Conclusiones. En el presente estudio de Doppler de la arteria uterina, la medición de la velocidad media tuvo más sensibilidad y especificidad que el índice de pulsatilidad, en la PE de inicio tardío y la RCIU.
El uso de la tecnología Time-Lapse y algoritmo predictivo KIDScore 5 ayudan a mejorar la selección de embriones euploides para la transferencia
Authors: Gazzo Eduardo , Peña Fernando , Valdez Federico , Chung Arturo , Bonomini Claudio , Ascenzo B. Mario , Velit Marcelo , Escudero Ernesto
Published: May 2019

Objetivos. Evaluar si el uso del algoritmo KIDScore 5 (known implantation data) puede ayudar a seleccionar entre los embriones euploides, para mejorar las tasas de embarazo e implantación en pacientes sometidas a procedimientos de reproducción asistida. Métodos. Estudio de cohorte retrospectivo en una clínica de fertilidad, desde octubre 2016 a diciembre 2018. Se estudió 1 049 embriones provenientes de 328 pacientes. Todos los embriones fueron cultivados en la incubadora Time-Lapse, Embryoscope® (Vitrolife®, Canadá) durante 5 a 6 días. De estos, 896 embriones (85,4%) fueron biopsiados y analizados mediante NGS y recibieron una valoración otorgada por el algoritmo predictivo KIDScore 5 (Vitrolife®, Canadá). Los 153 embriones restantes (14,6%) únicamente recibieron la valoración mediante el algoritmo predictivo KIDScore 5. Se realizó 256 transferencias únicas de embriones euploides en parejas sometidas a tratamientos de FIV en el laboratorio de reproducción asistida de la Clínica Inmater, Lima – Perú. Resultados. La tasa de implantación de los embriones euploides transferidos con valores de KIDScore = 6 versus los transferidos con valores de KIDScore = 1 tuvo diferencia estadísticamente signficativa (73,5% vs. 50,8%; p=0,030). Al evaluar la relación entre la tasa de euploidia embrionaria versus el resultado del valor de KIDScore 5, se obtuvo diferencias altamente significativas en las tasas de euploidia en los embriones con resultados de KIDScore 6 y 5 versus los de KIDScore 0 y 1 (60,5% vs. 45,7%; p=0,0004). Conclusiones. La selección embrionaria con ayuda del algoritmo KIDScore 5 ofrece ventaja en las tasas de implantación y embarazo únicamente cuando se transfieren embriones euploides. Su uso como criterio adicional a la selección embrionaria debiera ser considerado siempre que se acompañe estudio genético a los embriones a transferir. Los embriones euploides con valor más alto en la escala del algoritmo KIDScore 5, tienen mejores tasas de implantación y euploidía que los embriones con el valor mínimo de dicho algoritmo.
Con referencia al artículo ‘Microsomía hemifacial fetal: entendiendo el espectro fenotípico en el reporte de un caso’
Authors: Díaz Kuan Alicia
Published: May 2019

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Kısırlık Sorunu Yaşayan Erkek Hastaların TAT ve Rorschach Tepkilerinin Olgu Düzeyinde İncelenmesi
Authors: Okray Zihniye
Published: May 2019

Kısırlıkla ilgili anlatılar
neredeyse insanlık tarihi kadar eskidir. Fakat kısırlık söz konusu olunca kadın
kısırlığı ilk akla gelen olarak erkek kısırlığı hep ikinci planda tutulmuştur.
Bu çalışmanın amacı kısırlık tanısı almış erkek olguların projektif
değerlendirme teknikleri olan Rorschach ve TAT (Tematik Algı Testi) ile
birlikte değerlendirilmesi ve psişik dünyalarında nasıl bir kişilik
örgütlenmesine sahip olduklarının tespitine çalışılmasıdır. Araştırmanın temel
bulguları olarak erkek faktörlü kısırlık tanısı almış olan bu iki olguda;
özdeşleşme, cinsler arası fark, kuşaklararası ileti ve kuşaklararası
farklılıkların net bir biçimde ortaya konamadığı yetişkin olguların aksine daha
çocuksu özdeşleşlemelerin yapıldığı, baba ile ilişki kurulamadığı
görülmektedir. Her iki olguda da anne/kadın bir taraftan tümgüçlü olarak
değerlendirilirken diğer taraftan değersizleştirilmiştir. Kullanılan dil yapısı
sürekli tereddütler, yinelenen kelimeler içermektedir. Olgular bu dil yapısı
ile karar vermede güçlük, kontrol duygusunun yoğunluğu ve kararsızlıklarını
göstermektedirler. Olguların klinisyenden dayanak almamaları; ne dış dünyaya ne
de kendi içsel süreçlerine yatırım yapmadıklarını gösteren bir bulgu olarak
değerlendirilebilinir. Bu iki olgunun protokollerinde neredeyse tüm yanıtların
bütün yanıtlardan oluşması da dış gerçekliğe aşırı bağlı, tekil ve bütüncül
kalma çabası olarak değerlendirilmiştir. Diğer taraftan dış gerçekliğe aşırı
bağlı kalmış olmalarının yanı sıra içsel süreçlerine yatırım yapmadıklarının
bir göstergesi de afektif ve dürtüsel dünyayı gösteren renk ve hareket
yanıtlarının protokoldeki eksikliğidir. Protokollerdeki hareket ve renk
yanıtlarının azlığı test materyali ile ortaya çıkan bilinçdışı afektif dünyayı
kontrol altına alma çabası olarak değerlendirilmiştir. Bu çalışma erkek
faktörlü kısırlık tanısı almış olan olgularla yapılan -yazarın bilgisi dâhilinde-
ilk çalışma olduğu için alanyazına önemli katkı sağlayacağı düşünülmektedir.
BAL ARILARINDA (Apis mellifera L.) İKİ ANALI KOLONİ YÖNETİMİNİN KOLONİ PERFORMANSI VE VARROA (Varroa destructor Anderson &Trueman) BULAŞIKLIK DÜZEYİNE ETKİSİ
Authors: Cengiz Mahir Murat
Published: May 2019

ÖZ

2017 yılında
yürütülen bu çalışmada, Erzurum şartlarında iki ana arılı koloni yönetiminin
koloni performansına etkileri incelenmiştir. Koloni başına ortalama arılı
çerçeve sayısı tek analı kolonilerde 15.20±0.84 adet, iki analı kolonilerde
21.75±1.63 adet olarak bulunmuştur. Ortalama arılı çerçeve miktarı bakımından
gruplar arasında gözlenen farklılık Mayıs ayında istatistiki açıdan önemsizken,
Haziran, Temmuz ve Ağustos aylarında çok önemli (p<0.01) bulunmuştur. Koloni
başına ortalama yavru alanı miktarı tek ve iki analı kolonilerde sırasıyla
4016.85±508.65 cm2 ve 5300.31±380.73 cm2 olarak
gerçekleşirken; kuluçka alanı gelişimi bakımından grupların birbirlerinden
farkı çok önemli (p<0.01) bulunmuştur. İki analı kolonilerde koloni başına
ortalama 22.74±1.94 kg bal elde edilirken tek analı kolonilerde bu değer
15.76±1.64 kg olarak tespit edilmiştir. Koloni başına ortalama varroa
bulaşıklık oranı tek analı ve iki analı kolonilerde sırasıyla %4.30±0.55 ve
%7.62±1.12 olarak belirlendi. Varroa bulaşıklık oranı açısından ortalama
değerler Mayıs, Haziran, Temmuz ve Ağustos aylarında sırasıyla % 0.89 ± 0.76,%
3.17 ± 0.27, 6.36 ± 0.63 ve% 13.05 ± 1.23 olarak bulundu.
LD50 VALUES MAY BE MISLEADING PREDICTORS OF NEONICOTINOID TOXICITY ACROSS DIFFERENT BEE SPECIES
Authors: Mayack Christopher
Published: May 2019

The importance of not only honey bees (Apis mellifera) but also other
non-managed bee species and their pollination services has come to light with
their recently reported declines. One contributing factor in these declines is
thought to be sub-lethal exposure to neonicotinoid insecticides such as
thiacloprid. However, current government regulatory agencies do not require the
assessment of insecticide toxicity on bee species other than the honey bee,
even though previous studies have demonstrated that sensitivity to insecticides
is not likely to be generalizable from honey bees to non-managed bee species.
Replicating standardized protocols and testing five different doses of
thiacloprid on individual caged bees, we assessed the acute contact toxicity by
calculating mortality and the lethal dose (LD50) value for three bee
species with different life history traits: Apis
mellifera, Bombus terrestris, and Osmia bicornis. We found that Apis
mellifera and Osmia bicornis had
significantly higher mortality in comparison to Bombus terrestris, but there was no dose-dependent response for any
of the three bee species. Bee size and sex were also not useful predictors of
thiacloprid toxicity. These results suggest that solely relying on LD50
values, especially when they do not produce a dose-dependent response, may be
misleading when assessing insecticide toxicity risk for honey bees and other
non-managed bee species.
Sistem Pedukung Keputusan Seleksi Proposal Program Penerapan Iptek Bagi Masyarakat
Authors: Yanto Robi , Guntur Mohammad
Published: May 2019

Pengabdian masyarakat merupakan salah satu bagian terpenting bagi perguruan tinggi untuk mewujudkan peran serta pembangunan bangsa dan negara. Banyaknya kriteria penilaian yang digunakan dalam proses seleksi proposal pengabdian masyarakat menuntut unit kegiatan pengabdian masyarakat untuk lebih teliti dalam melakukan proses seleksi sesuai dengan hasil penilaian reviewer. Untuk dapat membantu proses seleksi proposal pengabdian masyarakat dibutuhkan sistem pendukung keputusan yang dapat membantu proses penilaian yang lebih tepat dan objektif. Adapun tujuan penelitian ini adalah membangun Sistem pendukung keputusan menggunakan metode Simple Multi Attribute Rating Technique, dimana metode ini digunakan sebagai media bantu penentuan kriteria pemilihan berdasarkan bobot dari kriteria dan subkriteria untuk proses perangkingan terhadap alternatif. Dari analisa metode dan sistem dihasilkan penilaian terhadap proposal pengabdian masyarakat Tahun 2017 dengan rekomendasi sangat layak yaitu A1 dengan hasil perangkingan 83,75, A4=88, rekomendasi Layak yaitu A2 dengan hasil perangkingan 60,75 dan A5=63,25 dan rekomendasi tidak layak adalah A3 dengan hasil perangkingan 33.

 

Kata kunci: Pengabdian Masyarakat, PPIM, Sistem Pendukung Keputusan, Smart

 

Abstract

 Community service is one of the most important parts for universities to realize the role of the nation and state development. A large number of assessment criteria used in the community service proposal selection process requires the community service unit to be more thorough in carrying out the selection process in accordance with the results of the reviewer assessment. To be able to help the community service proposal selection process, a decision support system is needed that can help a more precise and objective assessment process. The purpose of this study is to build a decision support system using the Simple Multi-Attribute Rating Technique method, where this method is used as an auxiliary media to determine selection criteria based on the weight of the criteria and sub-criteria for the ranking process against alternatives. From the analysis of methods and systems results in an assessment of 2017 community service proposals with recommendations that are very feasible namely A1 with a ranking of 83.75, A4 = 88, Worthy recommendation is A2 with ranking results of 60.75 and A5 = 63.25 and recommendations are not feasible is A3 with a ranking of 33.

  Keywords: Community Service, PPIM, Decision Support System, Smart.
MASYARAKAT HUKUM ADAT DATUK SINARO PUTIH PASANG SURUT KEKUASAAN ADAT DI TENGAH HEGEMONI NEGARA
Authors: Ridwan  , Isman
Published: May 2019

The Bungo District Government issued Bungo District Regulation No. 9 of 2007 concerning the mention of the Village Chief  to Rio, the Village Becomes Dusun and Dusun Being the Kampung has raised several fundamental problems faced by the Indigenous Government of Datuk Sinaro Putih. The problem is the existence of dualism at the level of village institutions, which is caused by the Role of Rio (Village Chief) who is so free to regulate all adat issues in the indigenous law community Datuk Sinaro Putih which has been regulated by Customary Institutions led by Customary Leader. The method used is descriptive qualitative method. Existence of Customary Law Society Datuk Sinaro Putih still exists. Because they were officially recognized by the Bungo District Regulation No. 6 of 2006 concerning Customary Law Society Datuk Sinaro Putih. They still have customary forests as the ancestral heritage of Datuk Sinar Putih. The Hamlet Government has replaced the power of Datuk Sinaro Putih in the field of general government. However, customary power is still held by Datuk Sinaro Putih, including control of customary forest areas. The descendants of Datuk Sinaro Putih make an effort to maintain their existence, including designing Village Regulations on the Customary Law Community Datuk Sinaro Putih and holding annual and five-year events in the form of traditional vows and traditional art performances in the traditional unit of Datuk Sinaro Putih.

 Keywords: customary law community, Datuk Sinaro Putih, customary power, state hegemony
ACCOUNTING SYSTEM DESIGN FOR THE OPERATION OF RENTAL FLATS AND SPORTS VENUE OF RIAU PROVINCE
Authors: Salmiah Neneng , Oemar Fahmi , Farwitawati Reni
Published: May 2019

The study aimed at conducting an analysis towards the operation of Athlete Homestead for the National Sports Week in 2012 belonging to Riau Province. Regarding the Finance Operation System in the form of Sub-district Development Program-Regional Public Service Agency (PPK BLUD), the researcher designed the Accounting System for the Regional Public Service Agency of the Rental Flats and Sports Venue. The data analysis in this study used the descriptive qualitative method by describing the accounting system design for the operation of Rental Flats and Sports Venue through the Sub-district Development Program-Regional Public Service Agency (PPK BLUD) with the procedure comprising: designing the rent system and procedure of the Rental Flats and Sports Venue, designing the system of cash management from the rent income, implementing focused-group discussion with the related parties and the government, working on the policy improvement draft for the operation of the Rental Flats and Sports Venue belonging to Riau Province.Based on the result of the study and discussion, it can be concluded that in order to improve the effectiveness of the service and operation of Rental Flats and Sports Venue with sound business practice, it is necessary to implement the Finance Operation System in the form of Sub-district Development Program-Regional Public Service Agency (PPK BLUD). The design system of the Sub-district Development Program-Regional Public Service Agency (PPK BLUD) comprising the organization chart, the transaction proof document, and the financial management procedure
Enfrentamiento Práctico del Paciente con Síndrome de Boca Urente, una Propuesta para el Estudio y Tratamiento
Authors: Gonzalez-Cuevas Ruben , Rojas- Alcayaga Gonzalo
Published: May 2019

El Síndrome de Boca Urente (SBU) clásicamente se define como un dolor oral quemante sin hallazgos en el examen físico o de laboratorio. Muchas veces puede ser asociado a procedimientos dentales o alteraciones psiquiátricas pero en En la gran mayoría de los casos, no existe un fenómeno relacionado. Sin embargo, no existe consenso en su evaluación clínica, lo que se refleja en lo heterogéneo de los estudios de prevalencia, patogenia y tratamiento. Es por esto que muchas veces, representa un desafío el diagnóstico y tratamiento, especialmente cuando especialmente cuando existe un serio deterioro de la calidad de vida, sin una causa identificable. Este artículo tiene como objetivo contribuir en la identificación de causas y en la definición de pautas para el diagnostico y manejo clínico del SBU, proponiendo un esquema de estudio y manejo en base a la revisión de la literatura y la experiencia clínica.
Women Outperform Men in Verbal Episodic Memory Even in Oldest-Old Age: 13-Year Longitudinal Results of the AgeCoDe/AgeQualiDe Study
Authors: Golchert Johannes , Roehr Susanne , Luck Tobias , Wagner Michael , Fuchs Angela , Wiese Birgitt , van den Bussche Hendrik , Brettschneider Christian , Werle Jochen , Bickel Horst , Pentzek Michael , Oey Anke , Eisele Marion , König Hans-Helmut , Weyerer Siegfried , Mösch Edelgard , Maier Wolfgang , Scherer Martin , Heser Kathrin , Riedel-Heller Steffi G.
Published: May 2019

Background:

Sex differences in verbal episodic memory function have been widely reported. However, sex-specific effects on rates of episodic memory decline remain controversial, and evidence is particularly scarce in the oldest-old population.

Objective:

We aimed to investigate sex differences in trajectories of episodic memory performance in oldest-old individuals.

Methods:

Based on 13-year longitudinal data with 9 follow-up assessments of a large sample of cognitively unimpaired old (75+) primary care patients ( n = 3,254) participating in the German AgeCoDe/AgeQualiDe study, we used linear mixed effects analyses to model sex-specific trajectories of change in verbal episodic memory while accounting for covarying factors.

Results:

We found that even in the highest age group women outperformed men in immediate ( b = –1.71, p < 0.001) and delayed ( b = –0.85, p < 0.001) free recall conditions. Associated late-life trajectories, however, did not differ significantly between the sexes. We further demonstrated that younger age, higher education, and an absence of depressive symptoms predicted better performance in both sexes. In contrast, past occurrences of stroke and APOE ɛ4 carrier status showed a negative relation to test scores.

Conclusion:

Our findings confirm previous research suggesting that women perform better in verbal episodic memory tests. We add that this advantage is still present in the oldest-old age groups. Our results indicate that sociodemographic and health related factors are as important as genetically based APOE ɛ4 carrier status in the prediction of normal cognitive development in advanced old age.
Moral Emotions in Frontotemporal Dementia
Authors: Teichmann Marc , Daigmorte Chloé , Funkiewiez Aurélie , Sanches Clara , Camus Maeva , Mauras Thomas , Le Ber Isabelle , Dubois Bruno , Levy Richard , Azuar Carole
Published: May 2019

Background:

Emotions, with or without moral valence, appear to be altered in the behavioral variant of frontotemporal dementia (bvFTD) but the relative degree of moral emotion breakdown, which could be a marker of bvFTD diagnosis, remains unexplored.

Objective:

To assess moral emotions in bvFTD, to differentiate bvFTD from typical Alzheimer’s disease (AD) based on moral emotion processing, and to provide a sensitive and specific assessment tool contributing to bvFTD diagnosis.

Methods:

We investigated moral emotions in 22 bvFTD patients, 15 patients with typical AD having positive CSF AD biomarkers, and 45 healthy controls. The ‘Moral Emotions Assessment’ task consisted in 42 scenarios exploring positive and negative moral emotions. To control for moral-specificity, we contrasted the 42 moral scenarios with 18 extra-moral scenarios eliciting the emotions without involving any inter-human moral context.

Results:

bvFTD patients were more impaired in emotion processing than AD patients and healthy controls and had significantly poorer performance in the processing of moral emotions than of emotions without moral valence. ROC analyses of data on moral scenarios showed a high area under the curve (83%), and indicated a cut-off score (< 37/42) for differentiating bvFTD from AD with a sensitivity of 82% and specificity of 73%.

Conclusion:

Our findings demonstrate that bvFTD patients have disorders in emotion processing which is mainly related to failure regarding moral emotions. They also show that this deficit is reliably detected by the ‘Moral Emotions Assessment’ which represents a sensitive and specific diagnostic tool detecting bvFTD and differentiating it from AD.
Detecting Apathy in Older Adults with Cognitive Disorders Using Automatic Speech Analysis
Authors: König Alexandra , Linz Nicklas , Zeghari Radia , Klinge Xenia , Tröger Johannes , Alexandersson Jan , Robert Philippe
Published: May 2019

Background:

Apathy is present in several psychiatric and neurological conditions and has been found to have a severe negative effect on disease progression. In older people, it can be a predictor of increased dementia risk. Current assessment methods lack objectivity and sensitivity, thus new diagnostic tools and broad-scale screening technologies are needed.

Objective:

This study is the first of its kind aiming to investigate whether automatic speech analysis could be used for characterization and detection of apathy.

Methods:

A group of apathetic and non-apathetic patients ( n = 60) with mild to moderate neurocognitive disorder were recorded while performing two short narrative speech tasks. Paralinguistic markers relating to prosodic, formant, source, and temporal qualities of speech were automatically extracted, examined between the groups and compared to baseline assessments. Machine learning experiments were carried out to validate the diagnostic power of extracted markers.

Results:

Correlations between apathy sub-scales and features revealed a relation between temporal aspects of speech and the subdomains of reduction in interest and initiative, as well as between prosody features and the affective domain. Group differences were found to vary for males and females, depending on the task. Differences in temporal aspects of speech were found to be the most consistent difference between apathetic and non-apathetic patients. Machine learning models trained on speech features achieved top performances of AUC = 0.88 for males and AUC = 0.77 for females.

Conclusions:

These findings reinforce the usability of speech as a reliable biomarker in the detection and assessment of apathy.
Rate of Cognitive Decline in Alzheimer’s Disease Stratified by Age
Authors: Stanley Karen , Whitfield Tim , Kuchenbaecker Karoline , Sanders Oliver , Stevens Tim , Walker Zuzana
Published: May 2019

Background:

There is only limited information available about the effect of age on course of cognitive decline in patients with onset of Alzheimer’s disease (AD) over the age of 64 years.

Objective:

We compared the rate of, and factors affecting, cognitive decline in patients with AD aged < 65 years (young-onset AD), 65–74 years (middle-onset AD), and ≥75 years (late-onset AD).

Method:

The study used longitudinal data from the Essex Memory Clinic which included a total of 305 participants; 56 had YOAD, 73 had MOAD, and 176 had LOAD. The rate of cognitive decline was measured using scores from the Mini-Mental State Examination (MMSE), and the data were examined using multilevel models analysis.

Results:

There was evidence of a difference in cognitive decline across the age groups with the YOAD group declining 2.8 MMSE points per year, those with MOAD declined 2.0 MMSE points per year, and the LOAD group declined 1.4 MMSE points per year.

Conclusions:

Patients with LOAD have a better prognosis than YOAD and MOAD. However, even between the MOAD and LOAD groups, age is a significant predictor of cognitive decline, with older patients having a more benign course.
Serum Metabolite Markers of Dementia Through Quantitative NMR Analysis: The Importance of Threonine-Linked Metabolic Pathways
Authors: Figueira João , Adolfsson Rolf , Nordin Adolfsson Annelie , Nyberg Lars , Öhman Anders
Published: May 2019

There is a great need for diagnostic biomarkers of impending dementia. Metabolite markers in blood have been investigated in several studies, but inconclusive findings encourage further investigation, particularly in the pre-diagnostic phase. In the present study, the serum metabolomes of 110 dementia or pre-diagnostic dementia individuals and 201 healthy individuals matched for age, gender, and education were analyzed by nuclear magnetic resonance spectroscopy in combination with multivariate data analysis. 58 metabolites were quantified in each of the 311 samples. Individuals with dementia were discriminated from controls using a panel of seven metabolites, while the pre-diagnostic dementia subjects were distinguished from controls using a separate set of seven metabolites, where threonine was a common significant metabolite in both panels. Metabolite and pathway alterations specific for dementia and pre-diagnostic dementia were identified, in particular a disturbed threonine catabolism at the pre-diagnostic stage that extends to several threonine-linked pathways at the dementia stage.
Willingness to Adhere to Current UK Low-Risk Alcohol Guidelines to Potentially Reduce Dementia Risk: A National Survey of People Aged 50 and Over
Authors: Oliveira Deborah , Jones Katy A. , Ogollah Reuben , Ozupek Semanur , Hogervorst Eef , Orrell Martin
Published: May 2019

Background:

People over 50 are increasing their alcohol intake, potentially increasing their risk of dementia.

Objective:

This study investigates whether people would be willing to adhere to current United Kingdom (UK, “low-risk”) alcohol guidelines to reduce dementia risk.

Methods:

A national cross-sectional online survey recruited a non-probabilistic sample of 3,948 individuals aged 50 and over without dementia in the UK. Self-reported willingness to comply with low-risk guidelines was predicted using logistic regression. Other relevant self-reported variables included physical health, lifestyle, and current alcohol intake.

Results:

Majority of the sample (90%, n = 3,527) reported drinking alcohol at least once a month with 23% ( n = 795) exceeding the low-risk guidelines (> 14 units per week). A larger proportion of men, those who were overweight, and people without a partner reported drinking above the recommended level. Most people who consumed alcohol ( n = 2,934; 74.3%) appeared willing to adhere to low-risk guidelines if they were told that their risk of having dementia could be reduced. Increased willingness was found in women (OR 1.81; CI 1.47–2.23), in people who had at least one child (OR 1.36; CI 1.09–1.70), and those who slept well (OR 1.45; CI 1.06–2.00). People who were obese (OR 0.72; CI 0.54–0.95), those who drank alcohol above limits (OR 0.13; CI 0.11–0.16), and those who were smokers (OR 0.56; CI 0.36–0.88) were less willing to adhere to current guidelines.

Conclusion:

Men and people with more lifestyle risk factors for common chronic diseases (e.g., smoking, obesity, and excess alcohol consumption) are less willing to adhere to current alcohol low-risk guidelines to reduce dementia risk.
A Bird’s-Eye View of the Multiple Biochemical Mechanisms that Propel Pathology of Alzheimer’s Disease: Recent Advances and Mechanistic Perspectives on How to Halt the Disease Progression Targeting Multiple Pathways
Authors: Vegh Caleb , Stokes Kyle , Ma Dennis , Wear Darcy , Cohen Jerome , Ray Sidhartha D. , Pandey Siyaram
Published: May 2019

Neurons consume the highest amount of oxygen, depend on oxidative metabolism for energy, and survive for the lifetime of an individual. Therefore, neurons are vulnerable to death caused by oxidative-stress, accumulation of damaged and dysfunctional proteins and organelles. There is an exponential increase in the number of patients diagnosed with neurodegenerative diseases such as Alzheimer’s (AD) as the number of elderly increases exponentially. Development of AD pathology is a complex phenomenon characterized by neuronal death, accumulation of extracellular amyloid-β plaques and neurofibrillary tangles, and most importantly loss of memory and cognition. These pathologies are most likely caused by mechanisms including oxidative stress, mitochondrial dysfunction/stress, accumulation of misfolded proteins, and defective organelles due to impaired proteasome and autophagy mechanisms. Currently, there are no effective treatments to halt the progression of this disease. In order to treat this complex disease with multiple biochemical pathways involved, a complex treatment regimen targeting different mechanisms should be investigated. Furthermore, as AD is a progressive disease-causing morbidity over many years, any chemo-modulator for treatment must be used over long period of time. Therefore, treatments must be safe and non-interfering with other processes. Ideally, a treatment like medicinal food or a supplement that can be taken regularly without any side effect capable of reducing oxidative stress, stabilizing mitochondria, activating autophagy or proteasome, and increasing energy levels of neurons would be the best solution. This review summarizes progress in research on different mechanisms of AD development and some of the potential therapeutic development strategies targeting the aforementioned pathologies.
Sex Difference in the Association of APOE4 with Memory Decline in Mild Cognitive Impairment
Authors: Wang Xiwu , Zhou Wenjun , Ye Teng , Lin Xiaodong , Zhang Jie ,   for Alzheimer’s Disease Neuroimaging Initiative
Published: May 2019

Our aim was to examine whether the influence of apolipoprotein E4 (APOE4) genotype on cognitive decline differs in male and female across the Alzheimer’s disease (AD) continuum. Among individuals with normal cognition (NC; n = 415), mild cognitive impairment (MCI; n = 870), and AD ( n = 334), we investigated the longitudinal associations of APOE4 genotype and sex with cognitive decline over 13 years. Our cognitive outcomes were Rey Auditory Verbal Learning Test (RAVLT) total learning score and delayed recall and Mini-Mental State Examination (MMSE) score. There were significant effects of the APOE4×sex interaction on change in verbal memory in the MCI group, but not the NC or AD group. Specifically, among individuals with MCI, female APOE4 carriers had a steeper decline in RAVLT total learning score, but not delayed recall or MMSE score compared to all other groups (APOE4 + /Male, APOE4-/Female, APOE4-/Male). In conclusion, female APOE4 carriers have faster rates of memory decline than their male counterparts among MCI individuals.
Mutation Analysis of the Genes Linked to Early Onset Alzheimer’s Disease and Frontotemporal Lobar Degeneration
Authors: Luukkainen Laura , Helisalmi Seppo , Kytövuori Laura , Ahmasalo Riitta , Solje Eino , Haapasalo Annakaisa , Hiltunen Mikko , Remes Anne M. , Krüger Johanna
Published: May 2019

A lot of effort has been done to unravel the genetics underlying early-onset Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD). However, many familial early-onset dementia (EOD) cases still show an unclear genetic background. The aim of this study was to evaluate the role of the known causative mutations and possible pathogenic variants associated with AD and FTLD in a Finnish EOD cohort. The cohort consisted of 39 patients (mean age at onset 54.8 years, range 39–65) with a positive family history of dementia or an atypical or rapidly progressive course of the disease. None of the patients carried the C9orf72 hexanucleotide repeat expansion. Mutations and variants in APP, PSEN1, PSEN2, MAPT, GRN, VCP, CHMP2B, FUS, TARDBP, TREM2, TMEM106B, UBQLN2, SOD1, PRNP, UBQLN1, and BIN1 were screened by using a targeted next generation sequencing panel. Two previously reported pathogenic mutations ( PSEN1 p.His163Arg and MAPT p.Arg406Trp) were identified in the cohort. Both patients had familial dementia with an atypical early onset phenotype. In addition, a heterozygous p.Arg71Trp mutation in PSEN2 with an uncertain pathogenic nature was identified in a patient with neuropathologically confirmed AD. In conclusion, targeted investigation of the known dementia-linked genes is worthwhile in patients with onset age under 55 and a positive family history, as well as in patients with atypical features.
Circulating and Extracellular Vesicles Levels of N-(1-Carboxymethyl)-L-Lysine (CML) Differentiate Early to Moderate Alzheimer’s Disease
Authors: Haddad Mohamed , Perrotte Morgane , Landri Sarra , Lepage Aurelie , Fülöp Tamàs , Ramassamy Charles
Published: May 2019

Background:

Both advanced glycation end products (AGEs) N-(1-carboxymethyl)-L-lysine (CML) and pentosidine were found in the brain from Alzheimer’s disease (AD) patients and were associated with the neuropathological hallmarks of AD. In AD patients, the circulating level of both AGEs remains unknown. Moreover, their levels in peripheral extracellular vesicles (EVs) and their association with AD remain to be determined. Finally, it is not known if neuronal cells can release AGEs via EVs and propagate AGEs.

Objective:

To determine the levels of circulating CML and pentosidine during the progression of AD. Moreover, their levels in circulating EVs were determined and their association with the clinical cognitive scores were analyzed. Finally, we have studied the possibility that neuronal cells eliminate and transfer these AGEs through EVs.

Methods:

CML and pentosidine levels were measured in serum and in circulating EVs. Released-EVs from SK-N-SH neuronal cells were isolated and CML levels were also determined.

Results:

The levels of CML in albumin-free serum proteins were higher in the early stage of AD while the levels of pentosidine remained unchanged. In contrast, the levels of CML in the EVs were lower in the moderate stage of AD. Interestingly, the levels of CML in serum were negatively correlated with the clinical cognitive scores MMSE and MoCA. For the first time, we were able to demonstrate that CML was present in EVs released from neuronal cells in culture.

Conclusion:

Peripheral and circulating EVs levels of CML can differentiate early to moderate AD. In the brain, neuronal CML can propagate from cells-to-cells via EVs.
The Reliability and Validity of the Chinese Version of Confusion Assessment Method Based Scoring System for Delirium Severity (CAM-S)
Authors: Mei Xinchun , Chen Yupeng , Zheng Hailin , Shi Zhongyong , Marcantonio Edward R. , Xie Zhongcong , Shen Yuan
Published: May 2019

Previous studies showed that the Confusion Assessment Method based delirium severity evaluation tool (CAM-S) had good reliability and validity. However, there is no Chinese version of the CAM-S. Therefore, we set out to perform a prospective investigation in older Chinese patients who had total joint replacement surgery under general anesthesia in Tenth People’s Hospital in Shanghai, P.R. China. A total of 576 participants, aged 60 years or older, were screened, 179 participants were enrolled, and 125 of them were included for the final analysis. Pre-operative evaluations were conducted one day before the surgery. Postoperative evaluations were conducted twice daily from postoperative day 1 to day 3. The incidence of postoperative delirium was 24.8%. The Chinese version of CAM-S [including a Short Form (CAM-S Short Form) and a Long Form (CAM-S Long Form)] had an optimal reliability reflected by internal consistency (Cronbach’s α= 0.748 and 0.839 for CAM-S Short Form and CAM-S Long Form respectively), split-halves reliability (Pearson correlation coefficient = 0.372 and 0.384 for CAM-S Short Form and CAM-S Long Form respectively), and inter-rater reliability (intra-class correlation coefficients = 0.629 and 0.945 for CAM-S Short Form and CAM-S Long Form respectively). Additionally, the Chinese version of CAM-S also showed a good discriminate validity. The domain scores of CAM-S were inversely correlated with corresponding domain scores of the MMSE. Finally, a receiver operating characteristic (ROC) analysis obtained an optimal cutoff point of 2.5 for CAM-S Short Form and 3.5 for CAM-S Long Form in recognizing delirium diagnosed by CAM. The areas under the ROC were 0.989 (95% CI 0.972 – 1.000, p < 0.001) and 0.964 (95% CI 0.946 – 0.982, p < 0.001), respectively. These data suggest that the Chinese version of CAM-S has good reliability and validity in evaluating postoperative delirium in geriatric Chinese patients and may be a useful tool to assess the severity of delirium.
Hospital-Treated Pneumonia Associated with Opioid Use Among Community Dwellers with Alzheimer’s Disease
Authors: Hamina Aleksi , Taipale Heidi , Karttunen Niina , Tanskanen Antti , Tiihonen Jari , Tolppanen Anna-Maija , Hartikainen Sirpa
Published: May 2019

Background:

Pneumonia is a common cause for hospitalization and excess mortality among persons with Alzheimer’s disease (AD), but little research exists evaluating drug use as its risk factor.

Objective:

We investigated the association between opioid use and hospital-treated pneumonia among community dwellers with AD.

Methods:

This study was part of the Medication use and Alzheimer’s Disease (MEDALZ) cohort. We included all community dwellers newly diagnosed with AD during 2010–2011 in Finland with incident prescription opioid use ( n = 5,623) and age-, sex-, and time since AD diagnosis-matched nonusers ( n = 5,623). Opioid use data, modelled from pharmacy dispensing data, and hospital-treated pneumonia were retrieved from nationwide registers. Patients with active cancer treatment were excluded. Hazard models compared opioid users to nonusers, adjusting for comorbidities, socioeconomic position. and other drug use.

Results:

Incident opioid use was associated with an increased risk of hospital-treated pneumonia compared to nonuse (adjusted HR, aHR 1.34, 95% CI 1.14–1.57). Highest risk was observed during the first two months of use (aHR 2.58, 95% CI 1.87–3.55). Compared to weak opioids, buprenorphine was not associated with a higher risk of pneumonia (aHR 1.20, 95% CI 0.83–1.76), but strong opioids were (aHR 1.84, 95% CI 1.15–2.97). The risk was higher for those using ≥50 morphine milligram equivalents (MME)/day (aHR 2.03, 95% CI 1.24–3.31), compared to using <50 MME/day.

Conclusions:

Opioid use was associated with a risk of hospital-treated pneumonia in a dose-dependent manner among persons with AD. Risk-minimization strategies should be considered if opioid therapy is needed.
Repetitive Transcranial Magnetic Stimulation Induced Hypoconnectivity Within the Default Mode Network Yields Cognitive Improvements in Amnestic Mild Cognitive Impairment: A Randomized Controlled Study
Authors: Cui Hailun , Ren Rujing , Lin Guozhen , Zou Yang , Jiang Lijuan , Wei Zhengde , Li Chunbo , Wang Gang
Published: May 2019

Background:

Repetitive transcranial magnetic stimulation (rTMS) is thought to be effective in alleviating cognitive symptoms in patients with amnestic mild cognitive impairment (aMCI), but the mechanisms related to network modification are poorly understood.

Objective:

Here we tested rTMS efficacy and explored the effect of rTMS-induced changes in the default mode network (DMN) and their predictive value for treatment response.

Methods:

Twenty-one subjects clinically diagnosed with aMCI were recruited to complete a 10-session randomized and sham-controlled rTMS treatment targeting the right dorsolateral prefrontal cortex. Resting-state functional magnetic resonance imaging in tandem with neuropsychological assessments were administered before and after the intervention. Changes in functional connectivity of the DMN and relevant brain regions, as well as the correlations between baseline functional connectivity and clinical rating scales were calculated in order to elucidate the mechanism of treatment response to rTMS therapy.

Results:

Compared to the sham group, the rTMS group achieved improvement of neuropsychological performance and significant functional connectivity changes within the DMN. Group×Time interactions were found between posterior cingulate gyrus and right fusiform gyrus (F (1,19)  = 17.154, p = 0.001), and also left anterior cingulate gyrus (F (1,19)  = 3.908, p = 0.063), showing an rTMS-induced deactivation of functional connectivity within the DMN. Baseline functional connectivity analysis of seeds within the DMN in the rTMS group revealed negative correlation with AVLT-Recognition score changes.

Conclusion:

rTMS-induced hypoconnectivity within DMN is associated with clinical cognitive improvements in patients with aMCI. Further, pre-rTMS baseline activity of the DMN at rest may be a predictor for favorable rTMS treatment response.
Air Pollution, Stress, and Allostatic Load: Linking Systemic and Central Nervous System Impacts
Authors: Thomson Errol M.
Published: May 2019

Air pollution is a risk factor for cardiovascular and respiratory morbidity and mortality. A growing literature also links exposure to diverse air pollutants (e.g., nanoparticles, particulate matter, ozone, traffic-related air pollution) with brain health, including increased incidence of neurological and psychiatric disorders such as cognitive decline, dementia (including Alzheimer’s disease), anxiety, depression, and suicide. A critical gap in our understanding of adverse impacts of pollutants on the central nervous system (CNS) is the early initiating events triggered by pollutant inhalation that contribute to disease progression. Recent experimental evidence has shown that particulate matter and ozone, two common pollutants with differing characteristics and reactivity, can activate the hypothalamic-pituitary-adrenal (HPA) axis and release glucocorticoid stress hormones (cortisol in humans, corticosterone in rodents) as part of a neuroendocrine stress response. The brain is highly sensitive to stress: stress hormones affect cognition and mental health, and chronic stress can produce profound biochemical and structural changes in the brain. Chronic activation and/or dysfunction of the HPA axis also increases the burden on physiological stress response systems, conceptualized as allostatic load, and is a common pathway implicated in many diseases. The present paper provides an overview of how systemic stress-dependent biological responses common to particulate matter and ozone may provide insight into early CNS effects of pollutants, including links with oxidative, inflammatory, and metabolic processes. Evidence of pollutant effect modification by non-chemical stressors (e.g., socioeconomic position, psychosocial, noise), age (prenatal to elderly), and sex will also be reviewed in the context of susceptibility across the lifespan.
Dysregulation of BDNF in Prefrontal Cortex in Alzheimer’s Disease
Authors: Aarons Toby , Bradburn Steven , Robinson Andrew , Payton Antony , Pendleton Neil , Murgatroyd Chris
Published: May 2019

Background:

Brain-derived neurotrophic factor (BDNF) is essential for neurogenesis and has been implicated in Alzheimer’s disease (AD). However, few studies have investigated together the epigenetic, transcriptional, and translational regulation of this peptide in the brain in relation to AD.

Objective:

To investigate mechanisms underlying how BDNF is possibly dysregulated in the brain in relation to aging and AD neuropathology.

Methods:

Prefrontal cortex tissues were acquired from the Manchester Brain Bank (N = 67). BDNF exon I, and exon IV-containing transcripts and total long 3’ transcript gene expression were determined by quantitative PCR and bisulfite pyrosequencing was used to quantify DNA methylation within promoters I and IV. Protein concentrations were quantified via ELISA.

Results:

BDNF exon IV and total long 3’ isoform gene expression levels negatively associated with donor’s age at death ( IV: r = –0.291, p = 0.020; total: r = –0.354, p = 0.004). Expression of BDNF exon I- containing isoform was significantly higher in Met-carriers of the rs6265 variant, compared to Val-homozygotes, when accounting for donor ages (F = 6.455, p = 0.014). BDNF total long 3’ transcript expression was significantly lower in those with early AD neuropathology, compared to those without any neuropathology ( p = 0.021). There were no associations between BDNF promoter I and IV methylation or protein levels with ages, rs6265 genotype or AD neuropathology status.

Conclusion:

Prefrontal cortex BDNF gene expression is associated with aging, rs6265 carrier status, and AD neuropathology in a variant-specific manner that seems to be independent of DNA methylation influences.