Recent Research Articles from UNTHSC

A Comprehensive Summary of the Knowledge on COVID-19 Treatment.

Thu, 02/04/2021 - 07:44
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A Comprehensive Summary of the Knowledge on COVID-19 Treatment.

Aging Dis. 2021 Feb;12(1):155-191

Authors: Peng Y, Tao H, Satyanarayanan SK, Jin K, Su H

Abstract
Currently, the world is challenged by the coronavirus disease 2019 (COVID-19) pandemic. Epidemiologists and researchers worldwide are invariably trying to understand and combat this precarious new disease. Scrutinizing available drug options and developing potential new drugs are urgent needs to subdue this pandemic. Several intervention strategies are being considered and handled worldwide with limited success, and many drug candidates are yet in the trial phase. Despite these limitations, the development of COVID-19 treatment strategies has been accelerated to improve the clinical outcome of patients with COVID-19, and some countries have efficiently kept it under control. Recently, the use of natural and traditional medicine has also set the trend in coronavirus treatment. This review aimed to discuss the prevailing COVID-19 treatment strategies available globally by examining their efficacy, potential mechanisms, limitations, and challenges in predicting a future potential treatment candidate and bridging them with the effective traditional Chinese medicine (TCM). The findings might enrich the knowledge on traditional alternative medication and its complementary role with Western medicine in managing the COVID-19 epidemic.

PMID: 33532135 [PubMed]

Interdisciplinary Research in Alzheimer's Disease and the Roles International Societies Can Play.

Thu, 02/04/2021 - 07:44
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Interdisciplinary Research in Alzheimer's Disease and the Roles International Societies Can Play.

Aging Dis. 2021 Feb;12(1):36-41

Authors: Tan SZK, Zhao RC, Chakrabarti S, Stambler I, Jin K, Lim LW

Abstract
An ever-increasing ageing population has elevated Alzheimer's disease to be one of the biggest challenges in modern medicine. Alzheimer's disease is highly complex, and we are still no closer to understanding the causes, let alone an effective treatment. The lack of good experimental models and lack of critical understanding has led to high failure rates of clinical trials with high associated costs, as well as difficulties in implementing treatments. The multifaceted nature of this disease highlights the need for an interdisciplinary approach to address these concerns. In this essay, we suggest how collaborative work can be useful in addressing some of the above issues. We then propose that international organisations and publishers need to support interdisciplinary research by creating platforms, lobbying funders, and pushing for interdisciplinary publications. We further highlight some of the issues involved in implementing these suggestions and argue that willpower of the research community, together with a re-evaluation of evaluation metrics and incentive systems, are needed in order to foster interdisciplinary research. Overall, we emphasise the need for interdisciplinary research in Alzheimer's disease and suggest that international societies should play a huge role in this endeavour.

PMID: 33532125 [PubMed]

Pexidartinib (TURALIO™): The First FDA-Indicated Systemic Treatment for Tenosynovial Giant Cell Tumor.

Thu, 02/04/2021 - 07:44
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Pexidartinib (TURALIO™): The First FDA-Indicated Systemic Treatment for Tenosynovial Giant Cell Tumor.

Drugs R D. 2020 Sep;20(3):189-195

Authors: Monestime S, Lazaridis D

Abstract
Tenosynovial giant cell tumor is a rare proliferative tumor that arises from the synovium, bursae, or tendon sheaths due to an overproduction of colony-stimulating factor 1. Historically, treatment options for patients with local or diffuse tenosynovial giant cell tumor have been limited to surgical interventions. However, for some patients, surgical resection could worsen functional limitations and/or morbidity. In August 2019, the FDA approved pexidartinib (TURALIO™, Daiichi Sankyo), the first systemic treatment option for adult patients with symptomatic tenosynovial giant cell tumor associated with severe morbidity or functional limitations that were not amenable to improvement with surgery. Pexidartinib is an oral tyrosine kinase inhibitor with selective inhibition of colony-stimulating factor 1 receptor and is the first systemic therapy to show significant improvement in overall response rates when compared with placebo. Clinicians using pexidartinib should monitor for liver-related adverse events, which may require treatment interruption, dose reduction, or treatment discontinuation. Pexidartinib provides a novel non-surgical treatment option for patients with tenosynovial giant cell tumor that may significantly improve patients' overall response, range of motion, physical function, tumor volume, and stiffness.

PMID: 32617868 [PubMed - indexed for MEDLINE]

Genomic Analysis of Salivary Gland Cancer and Treatment of Salivary Gland Cancers.

Wed, 02/03/2021 - 06:33
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Genomic Analysis of Salivary Gland Cancer and Treatment of Salivary Gland Cancers.

Surg Pathol Clin. 2021 Mar;14(1):151-163

Authors: Palsgrove D, Allahabadi S, Khan SA

Abstract
Salivary gland cancer is a heterogenous group of tumors that presents challenges with both diagnosis and therapy. Recent advances in the classification of salivary gland cancers have led to distinct histologic and genomic criteria that successfully differentiate between cancers with similar clinical behavior and appearance. Genomic abnormalities have led to the emergence of targeted therapies being used in their therapy with drastic improvements in outcomes as well as reductions in treatment-related toxicity. Dramatic results seen with molecular targets, such as HER2, TRK, and others, indicate that this approach has the potential to yield even better treatments for the future.

PMID: 33526219 [PubMed - in process]

Dysfunction of the SNARE complex in neurological and psychiatric disorders.

Tue, 02/02/2021 - 08:34
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Dysfunction of the SNARE complex in neurological and psychiatric disorders.

Pharmacol Res. 2021 Jan 29;:105469

Authors: Chen F, Chen H, Chen Y, Wei W, Sun Y, Zhang L, Cui L, Wang Y

Abstract
The communication between neurons constitutes the basis of all neural activities, and synaptic vesicle exocytosis is the fundamental biological event that mediates most communication between neurons in the central nervous system. The SNARE complex is the core component of the protein machinery that facilitates the fusion of synaptic vesicles with presynaptic terminals and thereby the release of neurotransmitters. In synapses, each release event is dependent on the assembly of the SNARE complex. In recent years, basic research on the SNARE complex has provided a clearer understanding of the mechanism underlying the formation of the SNARE complex and its role in vesicle formation. Emerging evidence indicates that abnormal expression or dysfunction of the SNARE complex in synapse physiology might contribute to abnormal neurotransmission and ultimately to synaptic dysfunction. Clinical research using postmortem tissues suggests that SNARE complex dysfunction is correlated with various neurological diseases, and some basic research has also confirmed the important role of the SNARE complex in the pathology of these diseases. Genetic and pharmacogenetic studies suggest that the SNARE complex and individual proteins might represent important molecular targets in neurological disease. In this review, we summarize the recent progress toward understanding the SNARE complex in regulating membrane fusion events and provide an update of the recent discoveries from clinical and basic research on the SNARE complex in neurodegenerative, neuropsychiatric, and neurodevelopmental diseases.

PMID: 33524541 [PubMed - as supplied by publisher]

Graph Algorithms for Mixture Interpretation.

Sun, 01/31/2021 - 12:57
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Graph Algorithms for Mixture Interpretation.

Genes (Basel). 2021 Jan 27;12(2):

Authors: Crysup B, Woerner AE, King JL, Budowle B

Abstract
The scale of genetic methods are presently being expanded: forensic genetic assays previously were limited to tens of loci, but now technologies allow for a transition to forensic genomic approaches that assess thousands to millions of loci. However, there are subtle distinctions between genetic assays and their genomic counterparts (especially in the context of forensics). For instance, forensic genetic approaches tend to describe a locus as a haplotype, be it a microhaplotype or a short tandem repeat with its accompanying flanking information. In contrast, genomic assays tend to provide not haplotypes but sequence variants or differences, variants which in turn describe how the alleles apparently differ from the reference sequence. By the given construction, mitochondrial genetic assays can be thought of as genomic as they often describe genetic differences in a similar way. The mitochondrial genetics literature makes clear that sequence differences, unlike the haplotypes they encode, are not comparable to each other. Different alignment algorithms and different variant calling conventions may cause the same haplotype to be encoded in multiple ways. This ambiguity can affect evidence and reference profile comparisons as well as how "match" statistics are computed. In this study, a graph algorithm is described (and implemented in the MMDIT (Mitochondrial Mixture Database and Interpretation Tool) R package) that permits the assessment of forensic match statistics on mitochondrial DNA mixtures in a way that is invariant to both the variant calling conventions followed and the alignment parameters considered. The algorithm described, given a few modest constraints, can be used to compute the "random man not excluded" statistic or the likelihood ratio. The performance of the approach is assessed in in silico mitochondrial DNA mixtures.

PMID: 33514030 [PubMed - as supplied by publisher]

Methylenedioxymethamphetamine-like discriminative stimulus effects of seven cathinones in rats.

Sat, 01/30/2021 - 16:14
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Methylenedioxymethamphetamine-like discriminative stimulus effects of seven cathinones in rats.

Behav Pharmacol. 2020 06;31(4):378-384

Authors: Gatch MB, Dolan SB, Forster MJ

Abstract
Synthetic cathinone derivatives are commonly considered quasi-legal alternatives for stimulant drugs, such as cocaine and methamphetamine, but some derivatives are increasingly being detected in club drug formulations of Ecstasy or 'Molly' as substitutes for methylenedioxymethamphetamine (±-MDMA). Although several studies have evaluated the psychostimulant-like effects of synthetic cathinones, few cathinone compounds have been assessed for MDMA-like activity. In order to determine their likelihood of interchangeability with entactogenic club drugs, the discriminative stimulus effects of methcathinone, 4-fluoromethcathinone, 4-methylmethcathinone, 4-methylethcathinone, 3-fluoromethcathinone, pentedrone, and ethylone were assessed in Sprague-Dawley rats trained to discriminate 1.5 mg/kg racemic methylenedioxymethamphetamine (±-MDMA) from vehicle. Methamphetamine and the cathinones 4-fluoromethcathinone, 4-methylmethcathinone, 4-methylethcathinone, 3-fluoromethcathinone, pentedrone, and ethylone fully substituted for the discriminative stimulus effects of ±-MDMA. In contrast, methcathinone produced a maximum of only 43% ±-MDMA-appropriate responding and higher doses suppressed responding. Most, but not all of the cathinone compounds tested have discriminative stimulus effects similar to those of MDMA as well as psychostimulant-like effects; however, the potency of MDMA versus psychostimulant substitution varies substantially among the compounds, suggesting that a subset of synthetic cathinones are more MDMA-like than psychostimulant-like. These findings further highlight the highly-variable pharmacology of this class of compounds and suggest that those cathinones with MDMA-like effects may also have increased use as club drugs.

PMID: 31895060 [PubMed - indexed for MEDLINE]

The Implementation of an Interpersonal Violence Screening Program in Primary Care Settings: Lessons Learned.

Fri, 01/29/2021 - 05:45
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The Implementation of an Interpersonal Violence Screening Program in Primary Care Settings: Lessons Learned.

Health Promot Pract. 2021 Jan 27;:1524839921989273

Authors: Thompson EL, Fulda KG, Grace J, Galvin AM, Spence EE

Abstract
BACKGROUND: Interpersonal violence (IPV) is a public health issue that disproportionately affects women. IPV screening improves likelihood of survivor disclosure and access to additional support. To enhance primary care IPV screening, Technology Enhanced Screening and Supportive Assistance (TESSA) uses integrated technological systems to deliver bidirectional, evidence-informed health navigation, health management, and safety interventions. This study evaluates TESSA implementation in primary care clinics using the Consolidated Framework for Implementation Research (CFIR).
METHOD: CFIR is a metatheoretical framework used for evaluating clinical intervention implementation. Salient constructs within CFIR's five domains (intervention characteristics, outer setting, inner setting, characteristics of individuals, and process) were identified (23 constructs), and pertinent implementation details were examined.
RESULTS: Key lessons learned included intervention characteristic constructs like intervention source (e.g., selecting tablets that can screen for items integral to the program's aims) and adaptability (e.g., ensuring tablets worked with electronic medical records for each clinic), process constructs like engaging champions (e.g., garnering buy-in from key clinic stakeholders and staff), outer setting constructs like patient needs and resources (e.g., addressing pertinent patient resource needs) and external policies and incentives (e.g., incentivizing clinics by addressing clinic needs), and inner setting constructs like leadership engagement (e.g., ensuring buy-in from organizational leaders as leadership changed frequently).
CONCLUSIONS: CFIR identifies important implementation factors for programs like TESSA that screen for high-risk populations and implement in primary care settings. The TESSA program implementation permits increased IPV screening among primary health care populations, thus promoting access to resources for otherwise hard-to-reach populations.

PMID: 33504222 [PubMed - as supplied by publisher]

Electronic cigarette explosion/burn and poisoning related emergency department visits, 2018-2019.

Fri, 01/29/2021 - 05:45
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Electronic cigarette explosion/burn and poisoning related emergency department visits, 2018-2019.

Am J Emerg Med. 2020 12;38(12):2637-2640

Authors: Rossheim ME, McDonald KK, Soule EK, Gimm GW, Livingston MD, Barnett TE, Jernigan DH, Thombs DL

Abstract
BACKGROUND: Electronic cigarette (ECIG) use has increased dramatically in recent years. Negative ECIG-related acute health effects have included explosion/burn injuries from battery failure and child ingestion/poisoning of liquid nicotine. However, there is an urgent need for continued surveillance of ECIG health effects to determine whether these outcomes change as ECIG devices and liquids rapidly evolve. This study updates national estimates of ECIG-related emergency department (ED) visits and describes the context of these injuries.
METHODS: A keyword search of case narrative text was used to identify ECIG-related ED visits in the National Electronic Injury Surveillance System (NEISS) data. These cross-sectional data are designed to be weighted to provide national estimates of consumer product-related injuries treated in EDs. ECIG-related injuries were described and categorized, and sampling weights applied to model national estimates.
RESULTS: From 2015 to 2019 there were an estimated 3369 ED visits from ECIG explosion/burn injuries (95% CI = 2020, 4718), and an estimated 676 visits from 2019 alone (95% CI = 315, 1036). In 2018-2019, there were an estimated 1550 cases of children <5 years old ingesting ECIG liquids (95% CI = 778, 2322).
CONCLUSIONS: Despite a notable shift in the US market towards ECIG devices that use lower electrical power and disposable "pods" (e.g., JUUL), liquid chemical ingestion among young children and ECIG explosion/burn injuries persist. Improved product regulations are urgently needed to prevent negative health effects caused by ECIGs, as well as prevent their ingestion and use by children.

PMID: 33041151 [PubMed - indexed for MEDLINE]

Abnormal Nutritive Sucking as an Indicator of Neonatal Brain Injury

Fri, 01/29/2021 - 05:00

Front Pediatr. 2021 Jan 12;8:599633. doi: 10.3389/fped.2020.599633. eCollection 2020.

ABSTRACT

A term neonate is born with the ability to suck; this neuronal network is already formed and functional by 28 weeks gestational age and continues to evolve into adulthood. Because of the necessity of acquiring nutrition, the complexity of the neuronal network needed to suck, and neuroplasticity in infancy, the skill of sucking has the unique ability to give insight into areas of the brain that may be damaged either during or before birth. Interpretation of the behaviors during sucking shows promise in guiding therapies and how to potentially repair the damage early in life, when neuroplasticity is high. Sucking requires coordinated suck-swallow-breathe actions and is classified into two basic types, nutritive and non-nutritive. Each type of suck has particular characteristics that can be measured and used to learn about the infant's neuronal circuitry. Basic sucking and swallowing are present in embryos and further develop to incorporate breathing ex utero. Due to the rhythmic nature of the suck-swallow-breathe process, these motor functions are controlled by central pattern generators. The coordination of swallowing, breathing, and sucking is an enormously complex sensorimotor process. Because of this complexity, brain injury before birth can have an effect on these sucking patterns. Clinical assessments allow evaluators to score the oral-motor pattern, however, they remain ultimately subjective. Thus, clinicians are in need of objective measures to identify the specific area of deficit in the sucking pattern of each infant to tailor therapies to their specific needs. Therapeutic approaches involve pacifiers, cheek/chin support, tactile, oral kinesthetic, auditory, vestibular, and/or visual sensorimotor inputs. These therapies are performed to train the infant to suck appropriately using these subjective assessments along with the experience of the therapist (usually a speech therapist), but newer, more objective measures are coming along. Recent studies have correlated pathological sucking patterns with neuroimaging data to get a map of the affected brain regions to better inform therapies. The purpose of this review is to provide a broad scope synopsis of the research field of infant nutritive and non-nutritive feeding, their underlying neurophysiology, and relationship of abnormal activity with brain injury in preterm and term infants.

PMID:33511093 | PMC:PMC7835320 | DOI:10.3389/fped.2020.599633

Will COVID-19 Lead to a Resurgence of Vaccine-Preventable Diseases?

Thu, 01/28/2021 - 06:48
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Will COVID-19 Lead to a Resurgence of Vaccine-Preventable Diseases?

Infect Drug Resist. 2021;14:119-124

Authors: Khatiwada AP, Shrestha N, Shrestha S

Abstract
The outbreak of coronavirus disease (COVID-19) has been affecting various sectors, including regular health services negatively. Vaccination, which saves the lives of 2-3 million populations of different age groups every year, is one of the most affected services by COVID-19. The routine vaccination services and outreach programs have been halted owing to lockdowns imposed on account of escalated cases of COVID-19 all over the world, affecting millions of lives at the stake of vaccine-preventable disease (VPD) henceforth. However, as it is becoming evident that we will have to live with COVID-19 for some time and many countries have lifted the lockdown, vaccination programs and campaigns have resumed with stringent preventive measures to be followed for COVID-19. These programs and campaigns have been trying to overlook and provide the missed vaccination during the imposed lockdown period and continue the other vaccination services to the public in the best possible ways. The collaborative approaches of various health-related organisations, governments and the healthcare workers are necessary to deliver the routine and mass vaccination services in an improvised manner.

PMID: 33500634 [PubMed]

A Continuous Statistical Phasing Framework for the Analysis of Forensic Mitochondrial DNA Mixtures.

Thu, 01/28/2021 - 06:48
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A Continuous Statistical Phasing Framework for the Analysis of Forensic Mitochondrial DNA Mixtures.

Genes (Basel). 2021 Jan 20;12(2):

Authors: Smart U, Cihlar JC, Mandape SN, Muenzler M, King JL, Budowle B, Woerner AE

Abstract
Despite the benefits of quantitative data generated by massively parallel sequencing, resolving mitotypes from mixtures occurring in certain ratios remains challenging. In this study, a bioinformatic mixture deconvolution method centered on population-based phasing was developed and validated. The method was first tested on 270 in silico two-person mixtures varying in mixture proportions. An assortment of external reference panels containing information on haplotypic variation (from similar and different haplogroups) was leveraged to assess the effect of panel composition on phasing accuracy. Building on these simulations, mitochondrial genomes from the Human Mitochondrial DataBase were sourced to populate the panels and key parameter values were identified by deconvolving an additional 7290 in silico two-person mixtures. Finally, employing an optimized reference panel and phasing parameters, the approach was validated with in vitro two-person mixtures with differing proportions. Deconvolution was most accurate when the haplotypes in the mixture were similar to haplotypes present in the reference panel and when the mixture ratios were neither highly imbalanced nor subequal (e.g., 4:1). Overall, errors in haplotype estimation were largely bounded by the accuracy of the mixture's genotype results. The proposed framework is the first available approach that automates the reconstruction of complete individual mitotypes from mixtures, even in ratios that have traditionally been considered problematic.

PMID: 33498312 [PubMed - in process]

Reductive Stress-Induced Mitochondrial Dysfunction and Cardiomyopathy.

Thu, 01/28/2021 - 06:48
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Reductive Stress-Induced Mitochondrial Dysfunction and Cardiomyopathy.

Oxid Med Cell Longev. 2020;2020:5136957

Authors: Ma WX, Li CY, Tao R, Wang XP, Yan LJ

Abstract
The goal of this review was to summarize reported studies focusing on cellular reductive stress-induced mitochondrial dysfunction, cardiomyopathy, dithiothreitol- (DTT-) induced reductive stress, and reductive stress-related free radical reactions published in the past five years. Reductive stress is considered to be a double-edged sword in terms of antioxidation and disease induction. As many underlying mechanisms are still unclear, further investigations are obviously warranted. Nonetheless, reductive stress is thought to be caused by elevated levels of cellular reducing power such as NADH, glutathione, and NADPH; and this area of research has attracted increasing attention lately. Albeit, we think there is a need to conduct further studies in identifying more indicators of the risk assessment and prevention of developing heart damage as well as exploring more targets for cardiomyopathy treatment. Hence, it is expected that further investigation of underlying mechanisms of reductive stress-induced mitochondrial dysfunction will provide novel insights into therapeutic approaches for ameliorating reductive stress-induced cardiomyopathy.

PMID: 32566086 [PubMed - indexed for MEDLINE]

Vertical Clinging and Leaping Ahead: How Bamboo Has Shaped the Anatomy and Physiology of Hapalemur.

Thu, 01/28/2021 - 06:48
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Vertical Clinging and Leaping Ahead: How Bamboo Has Shaped the Anatomy and Physiology of Hapalemur.

Anat Rec (Hoboken). 2020 02;303(2):295-307

Authors: Hemingway HW, Burrows AM, Omstead KM, Zohdy S, Pastor JF, Muchlinski MN

Abstract
Hapalemur sps. and Prolemur simus (bamboo lemurs, collectively) stand out from the relatively homogeneous lemurids because they are bamboo feeders and vertical clingers and leapers. This unique diet presents equally unique challenges, like its verticality, toughness, and toxicity. The bamboo lemurs share the generalized anatomy of the other lemurids, but also display some well-documented skeletal adaptations, perhaps to overcome the problems presented by their specialization. Soft-tissue adaptations, however, remain largely unexplored. Explored here are possible soft-tissue adaptations in Hapalemur griseus. We compare H. griseus with other lemurids, Propithecus, Galago, Tarsier, and a tree shrew. Based on the available anatomical and physiological data, we hypothesize that Hapalemur and Prolemur species will have differences in hindlimb morphology when compared with other lemurids. We predict that H. griseus will have more hindlimb muscle mass and will amplify muscle mass differences with increased type II muscle fibers. Relative hindlimb muscle mass in H. griseus is less than other prosimians sampled, yet relative sural muscle mass is significantly heavier (P < 0.01) in H. griseus. Results show that the soleus muscle of H. griseus has a higher amount of type II (fast) fibers in plantarflexors. These findings indicate although H. griseus shares some generalized lemurid morphology, its diet of bamboo may have pushed this generalized lemurid to an anatomical extreme. We suspect additional bamboo-specific adaptations in their anatomy and physiology will be uncovered with further examination into the anatomy of the bamboo lemurs. Anat Rec, 2019. © 2019 Wiley Periodicals, Inc. Anat Rec, 303:295-307, 2020. © 2019 American Association for Anatomy.

PMID: 31148418 [PubMed - indexed for MEDLINE]

Therapeutic efficacy of α7 ligands after acute ischemic stroke is linked to conductive states of α7 nAChRs.

Wed, 01/27/2021 - 10:05
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Therapeutic efficacy of α7 ligands after acute ischemic stroke is linked to conductive states of α7 nAChRs.

Br J Pharmacol. 2021 Jan 26;:

Authors: Gaidhani N, Tucci FC, Kem WR, Beaton G, Uteshev VV

Abstract
BACKGROUND AND PURPOSE: Targeting α7 nicotinic acetylcholine receptors (nAChRs) in neuroinflammatory disorders including acute ischemic stroke (AIS) holds significant therapeutic promise. However, therapeutically-relevant signaling mechanisms remain unidentified. Activation of neuronal α7 nAChRs triggers ionotropic signaling, but there is limited evidence for it in immunoglial tissues. The α7 ligands which are effective in reducing AIS damage promote α7 ionotropic activity, suggesting a link between their therapeutic effects for treating AIS and activation of α7 conductive states.
EXPERIMENTAL APPROACH: This hypothesis was tested using a transient middle cerebral artery occlusion (MCAO) model of AIS, NS6740, a known selective non-ionotropic agonist of α7 nAChRs and 4OH-GTS-21, a partial α7 agonist. NS6740-like ligands exhibiting low efficacy/potency for ionotropic activity will be referred to as non-ionotropic agonists or metagonists.
KEY RESULTS: 4OH-GTS-21, used as a positive control, significantly reduced neurological deficits and brain injury after MCAO as compared to vehicle and NS6740. By contrast, NS6740 was ineffective in identical assays and reversed the effects of 4OH-GTS-21 when these compounds were co-applied. Electrophysiological recordings from acute hippocampal slices obtained from NS6740-injected animals demonstrated its remarkable brain availability and protracted effects on α7 nAChRs as evidenced by sustained (>8 h) alterations in α7 ionotropic responsiveness.
CONCLUSION AND IMPLICATIONS: These results suggest that α7 ionotropic activity may be obligatory for therapeutic efficacy of α7 ligands after AIS yet, highlight the potential for selective application of α7 ligands to disease states based on their mode of receptor activation.

PMID: 33496352 [PubMed - as supplied by publisher]

Appropriateness of Term Limits for Administrative Appointments in Pharmacy Programs.

Wed, 01/27/2021 - 10:05
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Appropriateness of Term Limits for Administrative Appointments in Pharmacy Programs.

Am J Pharm Educ. 2020 01;84(1):7462

Authors: Malcom DR, Farris K, Feola DJ, Gannett PM, Law AV, O'Neal KS, Salinitri FD, Tromp K, White A

Abstract
The appropriateness of term limits for administrative appointments is a subject of much discussion, not just within pharmacy programs, but in organizations of all types. The prospect of term limits for involves a wide variety of important organizational issues, including succession planning, institutional memory, strategic decision-making, and concepts regarding leadership styles overall. This paper examines both sides of the debate regarding the appropriateness of term limits for administrative appointments. Arguments supporting term limits include the ability for strategic changes in the diversity of leaders as well as a more focused effort on continuous quality improvement. The arguments against term limits focus around the need for stability and the time involved in the development of effective leaders.

PMID: 32292194 [PubMed - indexed for MEDLINE]

STRait Razor Online: An enhanced user interface to facilitate interpretation of MPS data.

Tue, 01/26/2021 - 05:49
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STRait Razor Online: An enhanced user interface to facilitate interpretation of MPS data.

Forensic Sci Int Genet. 2021 Jan 13;52:102463

Authors: King JL, Woerner AE, Mandape SN, Kapema KB, Moura-Neto RS, Silva R, Budowle B

Abstract
Since 2013, STRait Razor has enabled analysis of massively parallel sequencing (MPS) data from various marker systems such as short tandem repeats, single nucleotide polymorphisms, insertion/deletions, and mitochondrial DNA. In this paper, STRait Razor Online (SRO), available at https://www.unthsc.edu/straitrazor, is introduced as an interactive, Shiny-based user interface for primary analysis of MPS data and secondary analysis of STRait Razor haplotype pileups. This software can be accessed from any common browser via desktop, tablet, or smartphone device. SRO is available also as a standalone application and open-source R script available at https://github.com/ExpectationsManaged/STRaitRazorOnline. The local application is capable of batch processing of both fastq files and primary analysis output. Processed batches generate individual report folders and summary reports at the locus- and haplotype-level in a matter of minutes. For example, the processing of data from ∼700 samples generated with the ForenSeq Signature Preparation Kit from allsequences.txt to a final table can be performed in ∼40 min whereas the Excel-based workbooks can take 35-60 h to compile a subset of the tables generated by SRO. To facilitate analysis of single-source, reference samples, a preliminary triaging system was implemented that calls potential alleles and flags loci suspected of severe heterozygote imbalance. When compared to published, manually curated data sets, 98.72 % of software-assigned allele calls without manual interpretation were consistent with curated data sets, 0.99 % loci were presented to the user for interpretation due to heterozygote imbalance, and the remaining 0.29 % of loci were inconsistent due to the analytical thresholds used across the studies.

PMID: 33493821 [PubMed - as supplied by publisher]

Recursive Support Vector Machine Biomarker Selection for Alzheimer's Disease.

Tue, 01/26/2021 - 05:49
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Recursive Support Vector Machine Biomarker Selection for Alzheimer's Disease.

J Alzheimers Dis. 2021 Jan 18;:

Authors: Zhang F, Petersen M, Johnson L, Hall J, O'Bryant SE

Abstract
BACKGROUND: There is a need for more reliable diagnostic tools for the early detection of Alzheimer's disease (AD). This can be a challenge due to a number of factors and logistics making machine learning a viable option.
OBJECTIVE: In this paper, we present on a Support Vector Machine Leave-One-Out Recursive Feature Elimination and Cross Validation (SVM-RFE-LOO) algorithm for use in the early detection of AD and show how the SVM-RFE-LOO method can be used for both classification and prediction of AD.
METHODS: Data were analyzed on n = 300 participants (n = 150 AD; n = 150 cognitively normal controls). Serum samples were assayed via a multi-plex biomarker assay platform using electrochemiluminescence (ECL).
RESULTS: The SVM-RFE-LOO method reduced the number of features in the model from 21 to 16 biomarkers and achieved an area under the curve (AUC) of 0.980 with a sensitivity of 94.0% and a specificity of 93.3%. When the classification and prediction performance of SVM-RFE-LOO was compared to that of SVM and SVM-RFE, we found similar performance across the models; however, the SVM-RFE-LOO method utilized fewer markers.
CONCLUSION: We found that 1) the SVM-RFE-LOO is suitable for analyzing noisy high-throughput proteomic data, 2) it outperforms SVM-RFE in the robustness to noise and in the ability to recover informative features, and 3) it can improve the prediction performance. Our recursive feature elimination model can serve as a general model for biomarker discovery in other diseases.

PMID: 33492292 [PubMed - as supplied by publisher]

Optimizing Patient Outcomes with PD-1/PD-L1 Immune Checkpoint Inhibitors for the First-Line Treatment of Advanced Non-Small Cell Lung Cancer.

Tue, 01/26/2021 - 05:49
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Optimizing Patient Outcomes with PD-1/PD-L1 Immune Checkpoint Inhibitors for the First-Line Treatment of Advanced Non-Small Cell Lung Cancer.

Pharmacotherapy. 2020 03;40(3):239-255

Authors: La-Beck NM, Nguyen DT, Le AD, Alzghari SK, Trinh ST

Abstract
The rapidly expanding repertoire of immune checkpoint inhibitors (ICIs) now includes two agents, pembrolizumab and atezolizumab, approved for first-line treatment of advanced non-small cell lung cancer (aNSCLC) as monotherapy or as part of chemoimmunotherapy. This review summarizes the clinical evidence supporting these indications, with a focus on strategies to optimize patient outcomes. These strategies include patient and tumor factors, adverse-effect profiles, pharmacokinetic and pharmacodynamic drug interactions, and quality of life and cost-effectiveness considerations. We performed a systematic literature search of the PubMed, Scopus, and Google Scholar databases, as well as a search of the conference proceedings of the American Society of Clinical Oncology, European Society for Medical Oncology, and American Association for Cancer Research (through August 31, 2019). The addition of ICIs to conventional chemotherapy as first-line treatment against aNSCLC is now part of the standard of care options. However, even though ICIs may be cost-effective in patients with aNSCLC, high drug and other associated costs can still be a barrier to treatment for patients. Moreover, the adverse-effect profiles of ICIs differ significantly from conventional chemotherapy, and some immune-related adverse effects may have a lasting impact on quality of life. Therefore, in adhering to a patient-centered model of care, clinicians should be mindful of patient- and treatment-specific factors when considering therapeutic options for patients with aNSCLC. Although the role of the immune system in cancer progression and regression has not been fully elucidated, the full clinical potential of immunotherapeutics in the treatment of cancer likely remains to be unleashed.

PMID: 31930528 [PubMed - indexed for MEDLINE]

Effects of elastic band exercise on the frailty states in pre-frail elderly people.

Fri, 01/22/2021 - 09:39
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Effects of elastic band exercise on the frailty states in pre-frail elderly people.

Physiother Theory Pract. 2020 Sep;36(9):1000-1008

Authors: Chen R, Wu Q, Wang D, Li Z, Liu H, Liu G, Cui Y, Song L

Abstract
OBJECTIVE: To discuss the effects of elastic band exercise on the frailty states in pre-frail elderly people.
METHODS: This study was a randomized controlled trial. Trial registration number is ChiCTR-IOC-17012579. Seventy pre-frail elderly people were randomly divided into elastic band group (n = 35) and control group (n = 35). Elastic band exercise was applied to elastic band group, 45-60 min per time for 8 weeks by 3 days a week; no exercise was applied to the control group. The frailty states, grip strength (female/male), walking speed, and physical activity were measured by the Fried frailty phenotype at pre-intervention, 4, and 8 weeks after intervention to assess the effects of exercise.
RESULTS: The elastic band group showed significant improvements in the frailty states, grip strength (female) and walking speed both after 4-week and 8-week intervention (P< 0.001), and significant improvements in grip strength (male) and physical activity after 8-week intervention (P< 0.05). Within-group analysis (pre-intervention vs. after 4-week, after 4-week vs after 8-week, pre-intervention vs after 8-week) showed significant improvements (P< 0.001) in grip strength (female/male) and walking speed in the elastic band group over time, while no significant differences in the control group (P > 0.05).
CONCLUSION: Elastic band exercise can improve frailty states in pre-frail elderly people, make them broke away from pre-frailty and restore them to non-frailty through improving the grip strength, walking speed and physical activity, and the effects after 8 weeks are better than those after 4 weeks.

PMID: 30741081 [PubMed - indexed for MEDLINE]

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