bluuebunny/crossref_metadata_2025 huggingface dataset:
Orientation and Frequency Analysis of Topographic Lineaments in the Miringa Volcanic Zone of the Biu Plateau Region, Borno State, Nigeria
Authors: Mohammed Yakubu , Gazali Ashe Kalli , Odihi John Onu , Daura Mohammed Mala
Published: December 2020

The aim of present study is to spatially analyze the topographic lineaments of tectonic origin in the Miringa Volcanic Zone located in the northwestern part of the Biu Plateau. To achieve such aim, SRTM of spatial resolution 12.5 m was utilized. The lineaments were automatically extracted by using PCI GEOMARTICA software version 10. This was followed by field work for ground thruting and to establish field relationships. ArcGis 10.5 software version was used for spatial analysis of lineaments while Rockworks version 16 was used in creating the Rossace used in lineament trend analysis and other related statistical variables associated with the lineaments of the study area. 2036 linear structures were identified in the area with a total length of 30,193.85 m. The maximum length of lineament recorded in the study area is 150 m while the minimum is 3.68 m. Field work revealed that most of the lineaments in the area developed from the weathering of contacts between successive volcanic beds in areas overlaid by the highly dissected plateaus, escarpment slopes and denudation hills. Trend analysis of lineaments of the study area indicates that the direction of lineaments tend to lie in the North-east to southwest direction (Azimuth 45°-225°) which has same direction with major drainage system and most of the volcanoes of the area. This signifies the presence of a major fissure trending in the north-east to south-west direction as the primary tectonic structure of the area. Subsequent exogenic processes exploited this structure leading to the formation of other micro-lineaments that trend along the same direction.
Contribution of Sentinel Radar Images 1Ato the Extraction of Lineaments from the Lobo Watershed (Center-West of the Ivory Coast)
Authors: Kouadio J. O. K. , Dibi B. , Mangoua M. J. , Waidhet A. B. Konan- , Kamagaté B.
Published: December 2020

The improvement of the conditions of access to drinking water for the populations of the Lobo watershed requires the exploitation of groundwater because of the surface water which remains exposed to climatic hazards and the impacts of anthropic activities. And yet, these underground waters finds himself bedrock aquifer which are complex aquifers. Thus, the objective of this study is to characterize those fissure aquifers that who govern underground run-off in the aquifer system of the Lobo catchment area. The methodology adopted consisted in using 1A sentinel radar images to map fractures and their spatial distribution. The validation of the lineaments first consisted in comparing and highlighting the lineaments from the radar images and the fractures revealed from photo-geological images. Next, we superimposed the map of lineaments on the map of boreholes with a flow rate greater than or equal to 5 m3/h, which were considered as productive boreholes. To determine the traffic corridors, this fracturing map was superimposed on the piezometric map. This work made it possible to extract 9,753 lineaments over a surface area of 7,000 km². The various validation techniques enabled us to confirm 121 major fractures with an average length of 9 km. In addition, the most productive boreholes are located on average less than 300 m from the fractures. The analysis of the distribution of the orientations of these fractures revealed a heterogeneity of direction and a predominance of the N-S; NW-SE and NE-SW families. The Fracturing density maps and density of the number of fracture crossing points highlight the spatial heterogeneity of the fracture network which is controlled by geomorphology, geological formations and lithological contacts. The river Lobo and its main tributary the Dé, flow preferentially in fractures. This river and its tributary drains the aquifer system. The results obtained from different thematic maps are useful for the realisation of future high-yield hydraulic wells (Q ≥ 5 m3/h).
Antiviral Treatment for COVID-19: A Systematic Review
Authors: Arias Francisco A. , Chavez Pier Teran- , Panato Alessandra Maggi- , Ortega Diego Flores- , Ortega Alex Rojas-
Published: December 2020

Aim: In December 2019, there were reports of a new type of coronavirus that affects the different health systems of the world. We have carried out a systematic review of the possible antivirals studied that could be useful in this public health catastrophe.

Data Sources: A search strategy with MESH terms was performed in PubMed, Web of Science, and Scopus. Also, RCTs published in clinicaltrials.gov were reviewed. The databases were searched between April and June 2020.

Study Selection: We selected all Randomized Controlled Trials evaluating the effects of antivirals and 5 studies were included from a research database of 280 articles collected between. After removing duplicated articles, 43 were selected for review. Finally, 5 articles were eligible for full-text review and included in the article.

Results: Current randomized controlled trial data showed no clinical improvement in terms of mortality, need for oxygen support or need for intubation in patients who used antivirals versus those who did not. No clinical improvement was demonstrated. It was observed that there is difficulty in calculating clinical improvement, this large difference makes the eligible studies difficult to compare.

Conclusion: These predictors, however, need further work to validate reliability. More clinical trials involving antivirals are needed to observe a relationship between clinical improvement or mortality from SARS-CoV-19.
Evaluation of Physicochemical Parameters of Piroxicam 20 mg Tablets Commercially Available in District Larkana, Sindh
Authors: Ahmed Waqar , Ghoto Muhammad Ali , Mughal Ubed-ur-Rehman , Dayo Abdullah , Arain Mudassar Iqbal , Ahmer Arslan , Irfan Rao , Shaikh Bilawal , Qazi Maryam , Khan Komal Zaman
Published: December 2020

The objective of this study is to evaluate the physicochemical parameters of Piroxicam 20 mg Tablet brands. A comparative qualitative research study was conducted for a period of six months. A total of five different brands of active Piroxicam tablets were selected. All samples were purchased from various local markets of Larkana Sindh. These collected samples were coded as PIX01, PIX02, PIX03, PIX04 and PIX05 for minimalism. Specific physicochemical quality control lab tests included Aesthetic test, Diameter and Thickness test, Weight variation, Mechanical strength and Friability test were performed on each sample according to standards and results were compared. Packing of all samples was observed according to GMP guidelines. Data was analyzed by using statistical software SPSS 24.00. Most of the brands were within official limits of United State Pharmacopeia (USP) except brand PIX05 showing variation in hardness test, whereas two brands PIX03 and PIX05 fail in friability test as well as powder material seen inside of blisters in aesthetic test. Dissolution test for each brand of Piroxicam was performed in which PIX02, 04 and 05 failed. It was concluded that from this study after in vitro physical evaluation of various brands of Piroxicam tablets, most of the brands are being manufactured under compliance of GMP guidelines as well as specifications described under USP. Traces of powder material inside of blister in aesthetic test and unsatisfactory result in friability and hardness test in same brand indicating the deviation of GMP guidelines and USP specification which may cause the out of specification result in chemical test.
Puzzle Out the Reason behind Habitual Miscarriage
Authors: Ahmad Waqas , Bilal Shahid , Azhar Sarah , Khan Muhammad Aitmaud Uddolah , Iqbal Nasima , Farooq Lubna
Published: December 2020

Aims: As no data is available in Pakistan so the aim of current study is to find out the link of multiple risk factors with recurrent pregnancy loss (RPL) in Pakistan.

Study Design: Case control study.

Place and Duration of Study: Study conducted in Obstetrics and Gynecology Clinic of Benazir Bhutto Hospital, Holy Family Hospital Rawalpindi and Polyclinic Hospital Islamabad from November 2018 to April 2019.

Methodology: Subjects were investigated on the basis of an in depth Performa. For data analysis Statistical package for social sciences version-20 was used. Beside this, height in cm, weight in kg and blood pressure in mmHg were recorded. All the statistical calculations were performed by using SPSS 20. For association analysis of qualitative variables Spearman bivariate correlation was calculated while for numerical variables ANOVA was applied. Multinomial logistic regression model was used and the odd ratio and relative risk were calculated.

Results: Among cases 91.34% were having spontaneous miscarriage and majority (64.86%) were during first trimester. Spearman bivariate correlation reported a strong association of recurrent pregnancy loss with the risk factors including family history, smoking, obesity, history of hypertension and history of diabetes, having highly significant p-values, on the hand, significant association of maternal age with the frequency of recurrent pregnancy loss was found but not with the paternal age and parity. The multinomial logistic regression model showed that smokers were19.012 times more prone to develop recurrent pregnancy loss.

Conclusion: The multiple risk factors including maternal age, obesity, smoking, family history, body mass index, hypertension and diabetes have a strong association with the recurrent pregnancy loss. So keeping these risk factors in mind a careful evaluation of each pregnancy is necessary to reduce the risk of recurrent pregnancy loss.
Novel PLEKHG5 mutations in a patient with childhood‐onset lower motor neuron disease
Authors: Gonzalez‐Quereda Lidia , Pagola Inmaculada , Fuentes Prior Pablo , Bernal Sara , Rodriguez Maria Jose , Torné Laura , Salgado Garrido Josefa , Gallano Pia , Jericó Ivonne
Published: December 2020

The PLEKHG5 gene encodes a protein that activates the nuclear factor kappa B (NFκB) signaling pathway. Mutations in this gene have been associated with distal spinal muscular atrophy IV and intermediate axonal neuropathy C, both with an autosomal recessive mode of inheritance. Two families with low motor neuron disease (LMND) caused by mutations in PLEKHG5 have been reported to date. We present a third LMND family, the first nonconsanguineous, due to two not previously reported PLEKHG5 mutations. Our results confirm and extend previous findings linking PLEKHG5 mutations to lower motor neuron diseases.
Focused Ion Beam Parameters for the Preparation of Oxidic Ceramic Materials
Authors: Brachhold Nora , Berek Harry , Fruhstorfer Jens , Aneziris Christos G.
Published: December 2020

The interaction of a Ga+ focused ion beam (FIB) with oxidic materials (mullite, alumina, titania, MgO‐partially stabilized ZrO2 (Mg‐PSZ), Y2O3‐partially stabilized ZrO2 (Y‐PSZ), MgO) is investigated to identify suitable parameters for sample preparation for surface‐sensitive analytical methods, e.g., electron backscatter diffraction (EBSD) by varying the parameters glancing angle and applied power. The statistical analysis shows that the influence of the FIB parameters on the surface quality corresponds well to the literature. The data yield that mild parameter levels reduce the surface damage and should be used for final preparation steps of oxides. Furthermore, correlations between the theoretical damage depth and observed EBSD data are only partly confirmed and other properties are relevant to understanding the materials' behavior. For Al2O3 and MgO, the theoretical damaging behavior corresponds well to the observed data. Mullite shows similar properties to alumina and magnesia and deviations are related to a possibly strong Ga+ implantation. Zirconia and titania interact strongly with the ion beam. ZrO2 shows a phase transformation due to heating and the stabilization of high‐temperature phases because of gallium oxide implantation. For TiO2, a strong surface amorphization is registered, which is related to preferential sputtering of oxygen and the existence of various oxidation states.
Conductive Materials for Healing Wounds: Their Incorporation in Electroactive Wound Dressings, Characterization, and Perspectives
Authors: Korupalli Chiranjeevi , Li Hui , Nguyen Nhien , Mi Fwu‐Long , Chang Yen , Lin Yu‐Jung , Sung Hsing‐Wen
Published: December 2020

The use of conductive materials to promote the activity of electrically responsive cells is an effective means of accelerating wound healing. This article focuses on recent advancements in conductive materials, with emphasis on overviewing their incorporation with non‐conducting polymers to fabricate electroactive wound dressings. The characteristics of these electroactive dressings are deliberated, and the mechanisms on how they accelerate the wound healing process are discussed. Potential directions for the future development of electroactive wound dressings and their potential in monitoring the course of wound healing in vivo concomitantly are also proposed.
Deep Drug Penetration of Nanodrug Aggregates at Tumor Tissues by Fast Extracellular Drug Release
Authors: Yao Yongchao , Dai Xin , Tan Yifeng , Chen Ying , Liao Chunyan , Yang Tian , Chen Yun , Yu Yunlong , Zhang Shiyong
Published: December 2020

Herein, a new nanodrug of azobenzene‐functionalized interfacial cross‐linked reverse micelles (AICRM) with 5‐fluorouracil loading (5‐FU@AICRM) is reported. Upon irradiation with 530 nm light in water, the surface azobenzenes of the nanoparticles change from polar cis‐conformation to nonpolar trans‐conformation, resulting in the aggregation of 5‐FU@AICRM within minutes. Simultaneously, the conformation change unlocks hydrophilic 5‐FU with a strong water immigration propensity, allowing them to spray out from the AICRM quickly. This fast release ensures a thorough release of the drug, before the aggregates are internalized by adjacent cells, making it possible to achieve deep tissue penetration. A study of in vivo anticancer activity in A549 tumor‐bearing nude mice shows that the tumor inhibition rate (TIR) of 5‐FU@AICRM is up to ≈86.2%, 31.6% higher than that of group without green light irradiation and 20.7% higher than that of carmofur (CF, a hydrophobic analog of 5‐FU)‐loaded AICRM (CF@AICRM), in which CF is released slowly under light irradiation because of its hydrophobicity. Fast drug release upon nanodrug aggregation provides a good solution for balancing the contradiction of “aggregation and penetration” in tumor treatment with nanodrugs.
Combination Therapy of Killing Diseases by Injectable Hydrogels: From Concept to Medical Applications
Authors: Poustchi Fatemeh , Amani Hamed , Ahmadian Zainab , Niknezhad Seyyed Vahid , Mehrabi Soraya , Santos Hélder A. , Shahbazi Mohammad‐Ali
Published: December 2020

The complexity of hard‐to‐treat diseases strongly undermines the therapeutic potential of available treatment options. Therefore, a paradigm shift from monotherapy toward combination therapy has been observed in clinical research to improve the efficiency of available treatment options. The advantages of combination therapy include the possibility of synchronous alteration of different biological pathways, reducing the required effective therapeutic dose, reducing drug resistance, and lowering the overall costs of treatment. The tunable physical properties, excellent biocompatibility, facile preparation, and ease of administration with minimal invasiveness of injectable hydrogels (IHs) have made them excellent candidates to solve the clinical and pharmacological limitations of present systems for multitherapy by direct delivery of therapeutic payloads and improving therapeutic responses through the formation of depots containing drugs, genes, cells, or a combination of them in the body after a single injection. In this review, currently available methods for the design and fabrication of IHs are systematically discussed in the first section. Next, as a step toward establishing IHs for future multimodal synergistic therapies, recent advances in cancer combination therapy, wound healing, and tissue engineering are addressed in detail in the following sections. Finally, opportunities and challenges associated with IHs for multitherapy are listed and further discussed.
Extremely Stable Luminescent Crosslinked Perovskite Nanoparticles under Harsh Environments over 1.5 Years
Authors: Jang Junho , Kim Young‐Hoon , Park Sunjoong , Yoo Dongsuk , Cho Hyunjin , Jang Jinhyeong , Jeong Han Beom , Lee Hyunhwan , Yuk Jong Min , Park Chan Beum , Jeon Duk Young , Kim Yong‐Hyun , Bae Byeong‐Soo , Lee Tae‐Woo
Published: December 2020

Organic–inorganic hybrid perovskite nanoparticles (NPs) are a very strong candidate emitter that can meet the high luminescence efficiency and high color standard of Rec.2020. However, the instability of perovskite NPs is the most critical unsolved problem that limits their practical application. Here, an extremely stable crosslinked perovskite NP (CPN) is reported that maintains high photoluminescence quantum yield for 1.5 years (>600 d) in air and in harsher liquid environments (e.g., in water, acid, or base solutions, and in various polar solvents), and for more than 100 d under 85 °C and 85% relative humidity without additional encapsulation. Unsaturated hydrocarbons in both the acid and base ligands of NPs are chemically crosslinked with a methacrylate‐functionalized matrix, which prevents decomposition of the perovskite crystals. Counterintuitively, water vapor permeating through the crosslinked matrix chemically passivates surface defects in the NPs and reduces nonradiative recombination. Green‐emitting and white‐emitting flexible large‐area displays are demonstrated, which are stable for >400 d in air and in water. The high stability of the CPN in water enables biocompatible cell proliferation which is usually impossible when toxic Pb elements are present. The stable materials design strategies provide a breakthrough toward commercialization of perovskite NPs in displays and bio‐related applications.
Recent Progress in Short‐ to Long‐Wave Infrared Photodetection Using 2D Materials and Heterostructures
Authors: Guan Xinwei , Yu Xuechao , Periyanagounder Dharmaraj , Benzigar Mercy Rose , Huang Jing‐Kai , Lin Chun‐Ho , Kim Jiyun , Singh Simrjit , Hu Long , Liu Guozhen , Li Dehui , He Jr‐Hau , Yan Feng , Wang Qi Jie , Wu Tom
Published: December 2020

The extraordinary electronic, optical, and mechanical characteristics of 2D materials make them promising candidates for optoelectronics, specifically in infrared (IR) detectors owing to their flexible composition and tunable optoelectronic properties. This review presents the recent progress in IR detectors composed of 2D materials and their hybrid structures, including graphene, black phosphorous, transition metal dichalcogenides, halide perovskite as well as other new layered materials and their heterostructures. The focus is on the short‐wave, mid‐wave, and long‐wave infrared regimes, which pose a grand challenge for rational materials and device designs. The dependence of the device performance on the optical and electronic properties of 2D materials is extensively discussed, aiming to present the general strategies for designing optoelectronic devices with optimal performance. Furthermore, the recent results on 2D material‐based heterostructures are presented with an emphasis on the relationship between band alignment, charge transfer, and IR photodetection. Finally, a summary is given as well as the discussion of existing challenges and future directions.
Spatial Engineering Direct Cooperativity between Binding Sites for Uranium Sequestration
Authors: Sun Qi , Song Yanpei , Aguila Briana , Ivanov Aleksandr S. , Bryantsev Vyacheslav S. , Ma Shengqian
Published: December 2020

Preorganization is a basic design principle used by nature that allows for synergistic pathways to be expressed. Herein, a full account of the conceptual and experimental development from randomly distributed functionalities to a convergent arrangement that facilitates cooperative binding is given, thus conferring exceptional affinity toward the analyte of interest. The resulting material with chelating groups populated adjacently in a spatially locked manner displays up to two orders of magnitude improvement compared to a random and isolated manner using uranium sequestration as a model application. This adsorbent shows exceptional extraction efficiencies, capable of reducing the uranium concentration from 5 ppm to less than 1 ppb within 10 min, even though the system is permeated with high concentrations of competing ions. The efficiency is further supported by its ability to extract uranium from seawater with an uptake capability of 5.01 mg g−1, placing it among the highest‐capacity seawater uranium extraction materials described to date. The concept presented here uncovers a new paradigm in the design of efficient sorbent materials by manipulating the spatial distribution to amplify the cooperation of functions.
Autonomous Chemotactic Light‐Emitting Swimmers with Trajectories of Increasing Complexity
Authors: Pavel Ileana-Alexandra , Salinas Gerardo , Perro Adeline , Kuhn Alexander
Published: December 2020

Miniaturized autonomous swimmers have become more and more important in many areas of research due to various fields of use, ranging from biomedical to environmental tasks. Precise and predictable control of their trajectories is a key ingredient for increasing their application potential. This can be typically achieved by using external forces such as magnetic or electric fields. An interesting alternative is to use intrinsic features of the swimmers, which allow them to exhibit chemotaxis. Such a built‐in “intelligence” enables more complex trajectories, relying on mechanisms that can be considered very basic analogs of decision‐making processes. Herein, autonomous light‐emitting chemoelectronic swimmers are presented that are able to navigate along trajectories with increasing complexity. Their decision‐making capacities are characterized by recording the light emitted along their path by a fully integrated light‐emitting diode. Chemotaxis is found to be the main driving force behind their behavior, allowing envisioning such systems for solving complex maze patterns.
Periodontal pathogens and their association with incident all‐cause and Alzheimer’s disease dementia in a large national survey
Authors: Beydoun May A , Beydoun Hind A , Hossain Sharmin A , El‐Hajj Ziad W , Weiss Jordan , Zonderman Alan
Published: December 2020

Background

Infectious agents including periodontal pathogens have recently appeared as important actors in Alzheimer’s Disease (AD) pathology. We examined associations of serum immunoglobulin G (IgG) against periodontal pathogens and Pd markers with incident all‐cause and AD dementia as well as AD mortality among U.S. middle‐aged and older adults.

Method

Periodontal disease (Pd) markers [Clinical Attachment Loss (CAL); probing depth and periodontal pathogen immunoglobulin G (IgG)] were investigated in relation to AD and all‐cause dementia incidence and to AD mortality, using data from the third National Health and Nutrition Examination Surveys (NHANES III, 1988‐1994) linked longitudinally with National Death Index and Medicare data through January 1st, 2014, with up to 26y of follow‐up. Sex‐ and age group‐specific multivariable‐adjusted Cox proportional hazards models were conducted.

Result

Among those ≥65y, AD incidence and mortality were consistently associated with probing depth, two factors and one cluster comprised of IgG titers against Porphyromonas gingivalis (Pg), Prevotella melaninogenica (Pm) and Campylobacter rectus (Cr) among others. Specifically, AD incidence was linked to a composite of Cr and Pg titers (per SD, aHR=1.22; 95% CI, 1.04‐1.43, P=0.012), while AD mortality risk was increased with another composite (per SD, aHR=1.46; 95% CI, 1.09‐1.96, P=0.017) loading highly on Pg, Prevotella intermedia, Prevotella nigrescens, Fusobacterium nucleatum, Cr, Streptococcus intermedius, Capnocylophaga Ochracea and Pm.

Conclusion

This study provides evidence for an association between periodontal pathogens and AD, which was stronger for older adults. Effectiveness of periodontal pathogen treatment on reducing sequelae of neurodegeneration should be tested in randomized controlled trials.
Lower CSF amyloid level is associated with sooner anti‐psychotic use in Alzheimer disease: A survival analysis
Authors: Cahan Joshua Gabriel , Bonakdarpour Borna
Published: December 2020

Background

Behavioral and psychological symptoms of dementia (BPSD) are a common feature of Alzheimer disease (AD). Antipsychotics (AP) remain a mainstay of BPSD treatment but have serious adverse effects and may serve as a proxy for BPSD in retrospective studies. Alzheimer biomarkers have been associated with neuropsychiatric symptoms and risk of post‐operative delirium. Potential associations between CSF markers of Alzheimer disease and antipsychotic use have not been explored. Here we used a survival analysis approach to probe the relationship between CSF AD biomarkers and BPSD by looking at AP use.

Method

A retrospective cohort of 86 patients(average 72 y/o +/‐5, 46.5 %M) over the age of 65 with AD confirmed on CSF testing between December 2010 and March 2018 and no premorbid primary psychiatric diagnosis was identified using Northwestern Memorial Hospital’s Enterprise Data Warehouse. Patients were stratified by levels of amyloid‐Beta 42(AB42), phosphorylated tau, total tau, and amyloid to tau index(ATI) with a median split. We looked at time‐to‐AP use for each group using a Kaplan‐Meier analysis. A log rank test was used to calculate statistical significance. Chi‐square was used to compare nominal and Mann‐Whitney U for quantitative features of each group.

Result

Altogether 11 patients received APs following CSF testing. There was no difference in AP use if groups were stratified by total tau, phosphorylated tau, or ATI. Nine (20.0%) of patients in the lower AB42 group compared with only 2 (4.5%) in the higher AB42 group received an AP. Patients in the lower AB42 group had sooner time‐to‐AP use on Kaplan‐Meier analysis, confirmed with a log‐rank test (p=0.04) (Figure 1). Comparing the two groups of 43 patients stratified by AB42 level, we did not detect a significant difference in demographics, MMSE scores, AD specific medication use, and comorbidities by the Charlson Comorbidity Index (Table 1).

Conclusion

These results suggest a relationship between lower CSF amyloid levels and sooner AP use. This study supports prior work showing a relationship between amyloid deposition on PET imaging and neuropsychiatric symptoms. CSF AB42 appears important towards developing a biological framework of neuropsychiatric symptoms in Alzheimer dementia and may help with BPSD prognostication.
The 23‐pneumococcal polysaccharide vaccine (PPV23) importance in an Alzheimer’s community from the south of Brazil
Authors: Nakakogue Lindsey Mitie , Baena Cristina Pellegrino , Sacchi Beatriz Chiquito , Cotrim Ivana de Oliveira , dos Santos Vitória Karoline Justino
Published: December 2020

Background

Pneumonia is the leading cause of death in Alzheimer's patients. The importance of PPV23 on this population is unknown.

Method

510 patients diagnosed with Alzheimer's Disease or Mixed Dementia treated at a public outpatient clinic in Londrina ‐ Paraná‐ Brazil, from January 1, 2015 to December 31, 2018 were selected. The following data were collected: gender, age, education, type of dementia, dementia classification by Clinical Dementia Rating, degree of functionality for basic activities (Katz), evolution of the Mini Mental State Examination in the period, Body Mass Index, incidence of delirium symptoms (agitation and aggression), date of vaccination with PPV23, Pneumococcal Conjugate Vaccine 13 (PCV13) and Influenza, if living in nursing home, presence of comorbidities such as stroke, myocardial infarction, hypertension, diabetes, chronic lung disease, chronic renal failure or immunosuppressive disease, if they were alcoholics or smokers and if they had diagnosis, hospitalization or death from pneumonia or other causes. Means were compared between groups by Student's t test and the proportions by Fisher's exact test. Logistic regression models were created to test the association between vaccination and outcomes, with adjustment for confounding factors.

Result

The sample consisted of 510 elderly, 65% women, 53.5% with 1‐4 years of schooling. The predominant age group was 80‐89 years (47.3%), 88% had a diagnosis of AD and most was CDR I (47%), ie mild dementia. Less than half (46.5%) were vaccinated with PPV23. There was no significant association between vaccination with PPV23 and the risk of pneumonia or death. Vaccination was associated with a higher risk of hospitalization for pneumonia (p 0.045), however, this association disappears with adjustment for age and CDR.

Conclusion

This study didn’t found difference for diagnosis or hospitalization for pneumonia between vaccinated and non‐vaccinated patients. Future studies should explore the causes, contributing factors and impact of pneumonia prevention in this elderly population with dementia.
Effect of cumulative exposure to psychosocial stressors at work on global cognitive function: A 25‐year longitudinal study
Authors: Duchaine Caroline S , Brisson Chantal , Talbot Denis , Gilbert‐Ouimet Mahée , Trudel Xavier , Vézina Michel , Diorio Caroline , Giguère Yves , Milot Alain , Laurin Danielle
Published: December 2020

Background

By 2050, an estimated 152 million people will be living with dementia. Prospective studies suggest that exposure to psychosocial stressors at work could be associated with a higher risk of mild cognitive impairment or dementia, but the evidence is still not clear.

Method

This study aimed to evaluate the effect of cumulative exposure to psychosocial stressors at work on global cognitive function in a cohort followed for over 25 years. At baseline in 1991‐1993 (T1), 9,188 white‐collar workers were recruited. Two follow‐ups were carried out in 1999‐2001 (T2) and 2015‐2019 (T3). This analysis was done among 5,728 participants working in T2, which participated in T3. Global cognitive function was evaluated with the validated Montreal Cognitive Assessment test (Nasreddine, 2005) and categorized in three groups according to standardized cut‐offs. Psychosocial stressors at work were evaluated with the validated Job Content Questionnaire (Karasek, 1979) at each time. The effect of cumulative exposure to psychosocial stressors at work at T1 and T2 on cognitive function categories at T3 was estimated with marginal structural models using inverse probability of treatment and censoring weights. Each observation was weighted for the inverse of the probability of death and lost to follow‐up and adjusted for potential confounders measured at T1 (age, sex, education, number of years in the same job, comorbidities, and lifestyle habits). Multiple imputation of missing data was performed.

Result

Workers exposed to low job demand and those exposed to a passive job (low job demand combined with low job control) at both T1 and T2 were at higher risk of moderate to severe cognitive impairment than non‐exposed workers (prevalence ratios (PR) and 95% confidence intervals (CI) of 1.34 (1.10;1.63), p=0.003, and 1.27 (1.05;1.54), p=0.012 respectively). Men, but not women, exposed to low job control at both T1 and T2 were at higher risk of moderate to severe cognitive impairment than non‐exposed workers (PR and 95% CI: 1.38 (1.07;1.79), p=0.015). No statistically significant associations were observed with the risk of mild cognitive impairment.

Conclusion

Primary prevention of cognitive impairment could be possible with the reduction of these frequent and modifiable psychosocial stressors at work.
Oral immunization with soybean storage protein containing amyloid β4‐10 prevents spatial learning decline
Authors: Kawarabayashi Takeshi , Nakamura Takumi , Takatama Masamitsu , Shoji Mikio
Published: December 2020

Background

Amyloid‐β protein (Aβ) plays a central role in the pathogenesis of Alzheimer’s disease (AD). Because AD pathologies begin two decades before the onset of dementia, prevention of Aβ amyloidosis has been proposed as a mean to block the pathological cascade. We generated a transgenic plant‐based vaccine, a soybean storage protein containing Aβ4‐10, named Aβ+, for oral Aβ immunization.

Method

One mg of Aβ+ or control protein (Aβ‐) with 10 mg cholera toxin subunit B was orally administered via a catheter to TgCRND8 mice once a week from 9 weeks. Extended Morris water maze tests for 10 consecutive days were examined every 4 weeks. Mice were analyzed at 23 weeks (Aβ+ n = 9, Aβ– n = 11), 43 weeks (Aβ+ n = 7, Aβ– n = 6), and 59 weeks (Aβ+ n = 6, Aβ– n = 7).

Result

Aβ+ immunization raised both anti‐Aβ antibodies and cellular immune responses. Plasma from Aβ+ treated mice showed staining of Aβ oligomers. Spatial learning decline was prevented in the Aβ+ immunized group from 21 weeks. In Tris‐buffered saline (TBS), sodium dodecyl sulfate (SDS), and formic acid (FA) serial extractions, all sets of Aβ species from Aβ monomer, low to high molecular weight Aβ oligomers, and Aβ smears had different solubility in TgCRND8 brains. Aβ oligomers decreased in TBS fractions, corresponding to an increase in high molecular weight Aβ oligomers in SDS extracts and Aβ smears in FA fraction of the Aβ+ treated group. There was significant inhibition of histological Aβ burden, especially in diffuse plaques, and suppression of microglial inflammation. Processing of amyloid‐β protein precursor was not different between Aβ+ and Aβ‐ groups. No evidence of amyloid‐related inflammatory angiopathy was observed.

Conclusion

Aβ+ oral immunization could be a promising, cheap, and long‐term safe disease‐modifying therapy to prevent the pathological process in AD.
A phase II, single center, randomized, double‐blind, placebo‐controlled study of the safety and therapeutic effectiveness of intranasal glulisine in amnestic mild cognitive impairment and probable mild Alzheimer’s disease
Authors: Rosenbloom Michael H. , Barclay Terry R , Erickson Lauren O , Pyle Maria , Green Emily A. , Svitak Aleta , Hage Lyndsay M. , Frey William H. , Hanson Leah R.
Published: December 2020

Background

IN insulin is a potential treatment for neurodegenerative disease shown to increase cerebral glucose update, reduce amyloid plaques and improve verbal memory in cognitively‐impaired as well as normal adults. Investigations have suggested that rapid‐acting (RA) insulins such as glulisine may result in superior cognitive benefits compared to regular insulin.

Method

We performed a single center, randomized, double‐blind, placebo‐controlled study to evaluate the efficacy of IN glulisine versus placebo in N=35 memory impaired (MCI/AD) subjects. Subjects with non‐insulin dependent diabetes mellitus (NIDDM) were included in the study. IN administration utilized the Impel NeuroPharma I109 Precision Olfactory Delivery (POD®) device. The ADAS‐Cog13, CDR global score, and FAQ were measured at baseline, 3, and 6 months. Secondary outcome measures included digit span forward/backwards, Trailmaking part A/B, COWAT, and WMS logical memory. Depression and suicidality were assessed using the GDS and C‐SSRS

Results

Subjects in the saline group were significantly older than those in the saline group (p=0.022). No significant differences in gender, education, ApoE4 status, and MOCA score existed between treatment groups. Overall, the number of adverse events per person was similar between groups (2.32 vs. 2.24, p=0.824); although subjects receiving IN glulisine had higher rates of nasal irritation (25.0% vs 13.9%) and respiratory symptoms (15.9% vs 8.3%) compared to placebo. Glucose<70 was observed in one subject receiving RA insulin, but otherwise, there were no other cases of hypoglycemia, including three NIDDM patients. Insulin levels and blood pressure was unaffected by treatment. No significant difference for ADAS‐Cog 13, CDR‐SOB or FAQ scores were found between treatment groups at 3 and 6 months. There was no impact of IN glulisine on depression or suicidality.

Conclusion

IN glulisine was safe and well‐tolerated and did not consistently impact peripheral glucose or insulin levels. There were no enhancing effects of IN glulisine on cognition, function, or mood, but the ability to detect significance was limited by number of subjects successfully enrolled and study duration. Additional investigations following a larger MCI/AD cohort inclusive of NIDDM subjects over a longer duration are necessary to better evaluate RA insulin efficacy in this population.
White matter microstructural damage as an early sign of subjective cognitive decline
Authors: Zhao Hui , Luo Cai Mei , Li Chun Meng
Published: December 2020

Background

Subjective cognitive decline (SCD) is considered a preclinical state of Alzheimer's disease (AD) and may represent a more advanced preclinical status than amnestic mild cognitive impairment (aMCI). Our aim was to explore changes in the white matter (WM) microstructure and their correlation with cognitive function in these AD‐spectrum patients.

Method

Diffusion tensor images from 43 individuals with normal cognition (NC), 38 SCD patients and 36 aMCI patients were compared using an atlas‐based segmentation strategy. The correlation between diffusion parameters and cognitive function was further analysed.

Result

The anatomical pattern of WM impairment was generally similar between SCD and aMCI patients. However, aMCI patients showed significantly lower fractional anisotropy (FA) values in corpus callosum (forceps major (Fma) and forceps minor (Fmi)), as well as significantly increased mean diffusivity (MD) in the bilateral anterior thalamic radiation (ATR), left corticospinal tract (CST. L), Fmi, left Cingulum (cingulate gyrus) (CgC. L), left cingulum (hippocampus) (CgH. L), and left inferior fronto‐occipital fasciculus (IFO. L), than those of SCD subjects, indicating a disruption in WM microstructural integrity in the aMCI. Individuals with microstructural disruption in Fmi, CgC. L and CgH. L tracts performed worse in general cognition and memory function tests, as indicated by line regression analysis.

Conclusion

SCD individuals had extensive WM microstructural damage in a pattern similar to that seen in aMCI, although presenting a cognitive performance comparable to cognitively healthy individuals. Our results suggest that WM integrity might precede objectively measurable memory decline and may be a potential early biomarker for AD.
Age and cognitive diagnosis influence cerebrospinal fluid ketone levels after a triglyceride infusion in older adults
Authors: Hanson Angela J. , Banks William A. , Bettcher Lisa F. , Pepin Robert , Raftery Daniel , Craft Suzanne
Published: December 2020

Background

Ketone bodies and diets which increase plasma ketones are being investigated for treatments for Alzheimer’s disease (AD), but little is known about what influences ketone body levels in the brain.

Method

Older adults (n=21, age 67.7 ± 8.6) underwent a 5‐hour TG and saline infusion on different days in random crossover design; CSF was collected at the end of the infusion. Targeted aqueous metabolites were measured using Shimadzu Nexera 20/AB‐Sciex 6500 Triple Quadrupole Liquid Chromatography‐Mass Spectroscopy which targets 216 metabolites representing over 35 different metabolic pathways. Data were analyzed using MetaboAnalyst 4.0 and SAS.

Result

Of 216 possible metabolites, 99 were detectable in the CSF, with an average of 88 metabolites per sample which did not differ by treatment (saline 87.6 ± 1.4, TG 87.7 ± 1.7). Three metabolites significantly differed by treatment: 3‐hydroxybutyrate (HBA), glutamic acid and methylguanosine (Table). The top hit HBA further differed by cognitive diagnosis. Fasting HBA was similar for both groups but TG‐induced increases in HBA were over 3 times higher for those with cognitive impairment (change score normal control 9.8 uM ± 8.3, cog impair 32.4 uM ±7.4, p value log transformed levels 0.0198). None of the metabolites in Table differed by APOE status or by sex. Age positively correlated with fasting HBA whereas systolic blood pressure and fasting glucose positively correlated with TG HBA and HBA change score. Fasting lipid levels did not predict fasting or TG‐induced HBA.

Conclusion

We detected metabolites in human CSF, and most metabolites did not change after a TG infusion. The top metabolite was the ketone body HBA, and levels were influenced by age, cognitive diagnosis, and markers of the metabolic syndrome. These results suggest that interventions that increase plasma ketones may lead to higher brain ketones in groups at risk for AD.
In vivo measurement of widespread synaptic loss and associated tau accumulation in early Alzheimer’s disease
Authors: Mecca Adam P. , O'Dell Ryan S. , Chen Ming‐Kai , Naganawa Mika , Toyonaga Takuya , Godek Tyler A. , Harris Joanna E. , Bartlett Hugh H. , Zhao Wenzhen , Gallezot Jean‐Dominique , Nabulsi Nabeel B. , Ropchan Jim R. , Ye Yunpeng , Wyk Brent C. Vander , Arnsten Amy F.T. , Huang Yiyun , Carson Richard E. , van Dyck Christopher H.
Published: December 2020

Background

Using [11C]UCB‐J–PET we have shown significant reductions in hippocampal SV2A specific binding as a marker of synaptic density in participants with early Alzheimer’s disease (AD). However, postmortem studies have suggested more widespread neocortical reductions in synaptic density that are associated with fibrillary tau accumulation.

Methods

We measured SV2A binding with [11C]UCB‐J‐PET in 34 participants with early AD (MMSE=23.1±4.1, CDR=0.5‐1.0) and 19 cognitively normal (CN) participants (MMSE=29.3±1.1, CDR=0). Amyloid status was confirmed by [11C]PiB‐PET. For [11C]UCB‐J‐PET, we calculated the distribution volume ratio (DVR) using a cerebellum reference. In a subset of 10 CN and 10 AD participants, we measured tau accumulation using [18F]flortaucipir‐PET. [18F]Flortaucipir standardized uptake value ratios (SUVRs) were calculated using an inferior cerebellum reference.

Results

Our primary analysis of group differences in SV2A binding demonstrated a significant effect of group (F(1,51)=33.4, P<0.00001) and group*region (F(10,510)=2.4, P=0.01) as predictors of SV2A binding (DVR). Post‐hoc comparisons revealed significant group differences in all medial temporal regions and more broadly in neocortical regions (Figure 1). SV2A reductions in AD were most pronounced in the hippocampus (DVR–17.3%, P<0.00001; BP
ND–19.8%) and entorhinal cortex (DVR–15.7%, P<0.00001; BP
ND–17.6%), but also present in parahippocampal, amygdala, lateral temporal, prefrontal, posterior cingulate/precuneus, lateral parietal, and pericentral regions. These reductions were largely maintained after correction for volume loss and were more extensive than decreases in gray matter volume. In a smaller sample of participants with tau PET, AD participants demonstrated significantly higher entorhinal cortical (ERC) [18F]flortaucipir binding compared to CN participants (CN SUVR=1.11±0.12, AD SUVR=1.68±0.16, p<0.00001). ERC‐tau was inversely associated with hippocampal synaptic density (r=‐0.63, P=0.005). Synaptic density and tau were inversely associated in regions of early and later Braak stages (r=‐0.45 to ‐0.59, P<0.05).

Conclusion

We observed widespread reductions of synaptic density with [11C]UCB‐J‐PET in medial temporal and neocortical regions in early AD. ERC tau accumulation was associated with lower hippocampal synaptic density. This inverse association may reflect synaptic failure due to tau pathology in ERC neurons projecting to the hippocampus. Further longitudinal studies are needed to elucidate the chronology and topography of tau accumulation and synaptic loss in AD and their relationship.
The impact of an innovative intergenerational respite program on workforce development through attitude change in college student volunteers
Authors: Gans Daphna , Guerrero Lourdes , Garcia Maribel , Tan Zaldy S
Published: December 2020

Introduction

TimeOut@UCLA is an intergenerational program that trains and mobilizes undergraduate college students to provide companionship to older adults with early stage Alzheimer’s or other forms of dementia. The program goals are: (1) strengthen student interest and experience in geriatrics and gerontology; (2) reduce the isolation of frail older adults; and, (3) support family caregivers. The aim of this study was to determine program’s effect on students' knowledge and attitudes toward people with Alzheimer's disease.

Methods

Following focused training (in‐person and via online module) on aging and dementia, college students volunteered twice a week for 10 weeks (60 hours) in the TimeOut@UCLA program. Each student was matched with a cognitively‐impaired older adult based on shared interests and fostered intergenerational relationship through conversation and structured activities. The Dementia Attitude Scale (DAS)1, a validated 20‐question, 170‐point scale validated tool and a self‐rated confidence survey in working with seniors were administered before and at the conclusion of the program.

Results

Fifty‐three students participated in this study with 41 responded to the survey. The students experienced a significant (P < 0.001) increase (26 points) on the Dementia Attitude Scale following participation in the program. Moreover, 95% (39/41) of the students reported that the intergenerational program improved their ability to work with seniors.

Conclusion

Meaningful interactions with older adults within the TimeOut@UCLA intergenerational respite program increases college students’ positive attitudes towards, and reported ability to work with, persons with Alzheimer’s or other forms of dementia. With the increasing numbers of persons with dementia, it is imperative to develop programs that reduce the stigma among young people of working with cognitively‐impairment older adults and to promote careers in geriatrics and gerontology.