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sFRP-mediated Wnt sequestration as a potential therapeutic target for Alzheimer's disease

Warrier S, Marimuthu R, Sekhar S, Bhuvanalakshmi G, Arfuso F, Das AK, et al.

Int J Biochem Cell Biol, 2016 06;75:104-11.
PMID: 27063405 DOI: 10.1016/j.biocel.2016.04.002

The extracellular ligand, Wnt, and its receptors are involved in sign al transduction and play an important role in axis formation and neural development. In neurodegenerative disorders such as Alzheimer's disease (AD), a decrease of the intracellular Wnt effector, β-catenin, has been linked to amyloid-β-peptide-induced neurotoxicity. Despite this knowledge, targeting Wnt inhibitors as potential biomarkers has not been explored, and harnessing Wnt activators as therapeutic candidates remains largely not investigated. A wide acting family of Wnt mediators, secreted frizzled-related proteins (sFRPs), has not been probed so far as molecular indicators of disease occurrence and progression of Alzheimer's. Unlike the effect of the Dickkopf (DKK) family of Wnt antagonists on AD, the sFRP molecules have a more pleiotropic impact on the Wnt signaling cascade and probably have a far-reaching involvement in neurodegeneration. The role of sFRPs has been poorly described in AD, and in this review, we analyze the present status of the role of sFRPs on neurodegeneration, their likely involvement, and potential implications in treatment modalities of AD. This information would provide valuable clues for the development of potential therapeutic targets for aberrant neurodegenerative disorders.
Fulltext An expanded mammal mitogenome dataset from Southeast Asia

Mohd Salleh F, Ramos-Madrigal J, Peñaloza F, Liu S, Mikkel-Holger SS, Riddhi PP, et al.

Gigascience, 2017 08 01;6(8):1-8.
PMID: 28873965 DOI: 10.1093/gigascience/gix053

Southeast (SE) Asia is 1 of the most biodiverse regions in the world, and it holds approximately 20% of all mammal species. Despite this, the majority of SE Asia's genetic diversity is still poorly characterized. The growing interest in using environmental DNA to assess and monitor SE Asian species, in particular threatened mammals-has created the urgent need to expand the available reference database of mitochondrial barcode and complete mitogenome sequences. We have partially addressed this need by generating 72 new mitogenome sequences reconstructed from DNA isolated from a range of historical and modern tissue samples. Approximately 55 gigabases of raw sequence were generated. From this data, we assembled 72 complete mitogenome sequences, with an average depth of coverage of ×102.9 and ×55.2 for modern samples and historical samples, respectively. This dataset represents 52 species, of which 30 species had no previous mitogenome data available. The mitogenomes were geotagged to their sampling location, where known, to display a detailed geographical distribution of the species. Our new database of 52 taxa will strongly enhance the utility of environmental DNA approaches for monitoring mammals in SE Asia as it greatly increases the likelihoods that identification of metabarcoding sequencing reads can be assigned to reference sequences. This magnifies the confidence in species detections and thus allows more robust surveys and monitoring programmes of SE Asia's threatened mammal biodiversity. The extensive collections of historical samples from SE Asia in western and SE Asian museums should serve as additional valuable material to further enrich this reference database.
Fulltext Correction to: Global, regional, and national trends and patterns in physical activity research since 1950: a systematic review

Varela AR, Cruz GIN, Hallal P, Blumenberg C, da Silva SG, Salvo D, et al.

Int J Behav Nutr Phys Act, 2021 Mar 08;18(1):35.
PMID: 33685444 DOI: 10.1186/s12966-021-01100-3
Fulltext Global, regional, and national trends and patterns in physical activity research since 1950: a systematic review

Ramírez Varela A, Cruz GIN, Hallal P, Blumenberg C, da Silva SG, Salvo D, et al.

Int J Behav Nutr Phys Act, 2021 01 07;18(1):5.
PMID: 33413479 DOI: 10.1186/s12966-020-01071-x

BACKGROUND: National, regional and global scientific production and research capacity for physical activity - PA may contribute to improving public health PA policies and programs. There is an uneven distribution of research productivity by region and country income group, where countries with the highest burden of non-communicable diseases attributable to physical inactivity having low research productivity. A first step towards improving global research capacity is to objectively quantify patterns, trends, and gaps in PA research. This study describes national, regional and global trends and patterns of PA research from 1950 to 2019.
METHODS: A systematic review using searches in PubMed, SCOPUS and ISI Web of Knowledge databases was conducted in August 2017 and updated between January and May 2020. The review was registered at the PROSPERO database number CRD42017070153. PA publications per 100,000 inhabitants per country was the main variable of interest. Descriptive and time-trend analyses were conducted in STATA version 16.0.
RESULTS: The search retrieved 555,468 articles of which 75,756 were duplicates, leaving 479,712 eligible articles. After reviewing inclusion and exclusion criteria, 23,860 were eligible for data extraction. Eighty-one percent of countries (n = 176) had at least one PA publication. The overall worldwide publication rate in the PA field was 0.46 articles per 100,000 inhabitants. Europe had the highest rate (1.44 articles per 100,000 inhabitants) and South East Asia had the lowest (0.04 articles per 100,000 inhabitants). A more than a 50-fold difference in publications per 100,000 inhabitants was identified between high and low-income countries. The least productive and poorest regions have rates resembling previous decades of the most productive and the richest.
CONCLUSION: This study showed an increasing number of publications over the last 60 years with a growing number of disciplines and research methods over time. However, striking inequities were revealed and the knowledge gap across geographic regions and by country income groups was substantial over time. The need for regular global surveillance of PA research, particularly in countries with the largest data gaps is clear. A focus on the public health impact and global equity of research will be an important contribution to making the world more active.
Fulltext Global Impact of COVID-19 on Stroke Care and IV Thrombolysis

Nogueira RG, Qureshi MM, Abdalkader M, Martins SO, Yamagami H, Qiu Z, et al.

Neurology, 2021 Jun 08;96(23):e2824-e2838.
PMID: 33766997 DOI: 10.1212/WNL.0000000000011885

OBJECTIVE: To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods.
METHODS: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.
RESULTS: There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95% confidence interval [CI] -11.7 to -11.3, p < 0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95% CI -13.8 to -12.7, p < 0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95% CI -13.7 to -10.3, p = 0.001). Recovery of stroke hospitalization volume (9.5%, 95% CI 9.2-9.8, p < 0.0001) was noted over the 2 later (May, June) vs the 2 earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was noted in 3.3% (1,722/52,026) of all stroke admissions.
CONCLUSIONS: The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID-19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months.
Fulltext Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: A 1-Year Follow-up

Nguyen TN, Qureshi MM, Klein P, Yamagami H, Mikulik R, Czlonkowska A, et al.

Neurology, 2023 Jan 24;100(4):e408-e421.
PMID: 36257718 DOI: 10.1212/WNL.0000000000201426

BACKGROUND AND OBJECTIVES: Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).
METHODS: We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.
RESULTS: There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1-6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1-4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4-5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6-0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31-1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82-2.97], 5,656/195,539) of all stroke hospitalizations.
DISCUSSION: There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year.
TRIAL REGISTRATION INFORMATION: This study is registered under NCT04934020.
Fulltext Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1

Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, et al.

Autophagy, 2021 Jan;17(1):1-382.
PMID: 33634751 DOI: 10.1080/15548627.2020.1797280

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.