Selective activation of PFKL suppresses the phagocytic oxidative burst.

In neutrophils, nicotinamide adenine dinucleotide phosphate (NADPH) generated via the pentose phosphate pathway fuels NADPH oxidase NOX2 to produce reactive oxygen species for killing invading pathogens. However, excessive NOX2 activity can exacerbate inflammation, as in acute respiratory distress syndrome (ARDS). Here, we use two unbiased chemical proteomic strategies to show that small-molecule LDC7559, or a more potent designed analog NA-11, inhibits the NOX2-dependent oxidative burst in neutrophils by activating the glycolytic enzyme phosphofructokinase-1 liver type (PFKL) and dampening flux through the pentose phosphate pathway. Accordingly, neutrophils treated with NA-11 had reduced NOX2-dependent outputs, including neutrophil cell death (NETosis) and tissue damage. A high-resolution structure of PFKL confirmed binding of NA-11 to the AMP/ADP allosteric activation site and explained why NA-11 failed to agonize phosphofructokinase-1 platelet type (PFKP) or muscle type (PFKM). Thus, NA-11 represents a tool for selective activation of PFKL, the main phosphofructokinase-1 isoform expressed in immune cells.

Advancing immunomodulatory functions in mesenchymal stem/stromal cells through targeting the GATA6-mediated pathway.

BACKGROUND AIMS: The immunomodulatory capacity of mesenchymal stem/stromal cells (MSCs) is a key feature that makes them particularly valuable for regenerative medicine. However, this potential is affected by the chronological aging of the donors and the cell expansion procedures in culture. We have demonstrated that GATA binding protein 6 (GATA6) plays a pivotal role in the aging of MSCs and inhibiting GATA6 rejuvenates the characteristics of MSCs. METHODS: In this study, we compared the immunomodulatory capabilities of young and old MSC models, using induced pluripotent stem cells-derived rejuvenated MSCs (rMSCs) and their parental MSCs (pMSCs), respectively, to identify a key mechanism involved in the differential regulation of these capabilities. Additionally, we explored the role of GATA6 in mediating the mechanism. RESULTS: Our results demonstrated that rMSCs exhibited downregulated aging-associated regulators, including p53, p21 and GATA6, and showed enhanced suppression of T cell proliferation compared to pMSCs. Through analyzing our previous RNA-seq data and employing target gene knockdown, we determined both suppressors of cytokine signaling 3 (SOCS3) and interleukin 6 were involved in GATA6-induced regulation, collectively affecting the expression of programmed death ligand 1 (PDL1) in both pMSCs and rMSCs. CONCLUSIONS: Our findings underline the significance of the GATA6/SOCS3/PDL1 pathway in regulating aging-associated changes in MSC immunomodulatory activity, providing valuable insights into the potential use of rMSCs in the treatment of immune diseases and regenerative medicine.

Squaric esters as peptide stapling reagents.

We report that squaric esters can serve as bifunctional reagents for selective peptide stapling reactions. Formation of the squaric amide staple occurs under mild conditions with amine-containing side chains. We show that short resin-bound peptides are readily stapled on solid phase and that stapling can occur at various relative positions along the peptide and with various amine tether lengths (e.g. Lysine, ornithine, etc). The squaric amide staples are stable to strong acid conditions used to cleave the stapled peptide from the resin and the stapled peptides show an increase in helicity as analyzed through circular dichroism.

Cancer-associated somatic mutations in human phosphofructokinase-1 reveal a critical electrostatic interaction for allosteric regulation of enzyme activity.

Metabolic reprogramming, including increased glucose uptake and lactic acid excretion, is a hallmark of cancer. The glycolytic 'gatekeeper' enzyme phosphofructokinase-1 (PFK1), which catalyzes the step committing glucose to breakdown, is dysregulated in cancers. While altered PFK1 activity and expression in tumors have been demonstrated, little is known about the effects of cancer-associated somatic mutations. Somatic mutations in PFK1 inform our understanding of allosteric regulation by identifying key amino acid residues involved in the regulation of enzyme activity. Here, we characterized mutations disrupting an evolutionarily conserved salt bridge between aspartic acid and arginine in human platelet (PFKP) and liver (PFKL) isoforms. Using purified recombinant proteins, we showed that disruption of the Asp-Arg pair in two PFK1 isoforms decreased enzyme activity and altered allosteric regulation. We determined the crystal structure of PFK1 to 3.6 Šresolution and used molecular dynamic simulations to understand molecular mechanisms of altered allosteric regulation. We showed that PFKP-D564N had a decreased total system energy and changes in the electrostatic surface potential of the effector site. Cells expressing PFKP-D564N demonstrated a decreased rate of glycolysis, while their ability to induce glycolytic flux under conditions of low cellular energy was enhanced compared with cells expressing wild-type PFKP. Taken together, these results suggest that mutations in Arg-Asp pair at the interface of the catalytic-regulatory domains stabilizes the t-state and presents novel mechanistic insight for therapeutic development in cancer.

Impact of restricted family presence during the COVID-19 pandemic on critically ill patients, families, and critical care clinicians: a qualitative systematic review.

BACKGROUND: We aimed to synthesize the qualitative evidence on the impacts of COVID-19-related restricted family presence policies from the perspective of patients, families, and healthcare professionals from neonatal (NICU), pediatric (PICU), or adult ICUs. METHODS: We searched MEDLINE, EMBASE, Cochrane Databases of Reviews and Clinical Trials, CINAHL, Scopus, PsycINFO, and Web of Science. Two researchers independently reviewed titles/abstracts and full-text articles for inclusion. Thematic analysis was completed following appraising article quality and assessing confidence in the individual review findings using standardized tools. RESULTS: We synthesized 54 findings from 184 studies, revealing the impacts of these policies in children and adults on: (1) Family integrated care and patient and family-centered care (e.g., disruption to breastfeeding/kangaroo care, dehumanizing of patients); (2) Patients, families, and healthcare professionals (e.g., negative mental health consequences, moral distress); (3) Support systems (e.g., loss of support from friends/families); and (4) Relationships (e.g., loss of essential bonding with infant, struggle to develop trust). Strategies to mitigate these impacts are reported. CONCLUSION: This review highlights the multifaceted impacts of restricted visitation policies across distinct care settings and strategies to mitigate the harmful effects of these policies and guide the creation of compassionate family presence policies in future health crises. REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=290263 .

An Integrative Literature Review of Heart Rate Variability Measures to Determine Autonomic Nervous System Responsiveness Using Pharmacological Manipulation.

BACKGROUND: Heart rate variability (HRV) is defined as the difference in the timing of intervals between successive heartbeats and is used as a surrogate measure to the responsiveness of the autonomic nervous system. A review and synthesis of HRV as an indicator of autonomic nervous system responsiveness to pharmacologic stimulation/blockade of sympathetic and/or parasympathetic nervous system branches have not been completed. PURPOSE: The aim of this integrative review is to synthesize research examining pharmacological modulation of the autonomic nervous system and the response of time domain, frequency domain, and nonlinear measures of HRV. CONCLUSIONS: Sympathetic nervous system blockade resulted in a consistent decrease in the standard deviation of normal-normal interval metric across studies. Stimulation of the parasympathetic nervous system was associated with an increase in several time, frequency, and nonlinear HRV indices, whereas blockade of the parasympathetic nervous system led to a decrease in similar indices. CLINICAL IMPLICATIONS: Recommendations to improve the reproducibility of future HRV research are provided for standardization of recording, analysis, and metric decisions and more thorough reporting of HRV indices in published studies. Alterations in autonomic nervous system input to the cardiovascular system are associated with an increased risk for adverse patient outcomes and increased mortality; therefore, understanding the influence of pharmacologic autonomic nervous system modulation on HRV indices and important considerations for reproducible HRV research design will inform future translational research on cardiovascular risk reduction.

Correlation of Presynaptic and Postsynaptic Proteins with Pathology in Alzheimer's Disease.

Synaptic transmission is essential for nervous system function and the loss of synapses is a known major contributor to dementia. Alzheimer's disease dementia (ADD) is characterized by synaptic loss in the mesial temporal lobe and cerebral neocortex, both of which are brain areas associated with memory and cognition. The association of synaptic loss and ADD was established in the late 1980s, and it has been estimated that 30-50% of neocortical synaptic protein is lost in ADD, but there has not yet been a quantitative profiling of different synaptic proteins in different brain regions in ADD from the same individuals. Very recently, positron emission tomography (PET) imaging of synapses is being developed, accelerating the focus on the role of synaptic loss in ADD and other conditions. In this study, we quantified the densities of two synaptic proteins, the presynaptic protein Synaptosome Associated Protein 25 (SNAP25) and the postsynaptic protein postsynaptic density protein 95 (PSD95) in the human brain, using enzyme-linked immunosorbent assays (ELISA). Protein was extracted from the cingulate gyrus, hippocampus, frontal, primary visual, and entorhinal cortex from cognitively unimpaired controls, subjects with mild cognitive impairment (MCI), and subjects with dementia that have different levels of Alzheimer's pathology. SNAP25 is significantly reduced in ADD when compared to controls in the frontal cortex, visual cortex, and cingulate, while the hippocampus showed a smaller, non-significant reduction, and entorhinal cortex concentrations were not different. In contrast, all brain areas showed lower PSD95 concentrations in ADD when compared to controls without dementia, although in the hippocampus, this failed to reach significance. Interestingly, cognitively unimpaired cases with high levels of AD pathology had higher levels of both synaptic proteins in all brain regions. SNAP25 and PSD95 concentrations significantly correlated with densities of neurofibrillary tangles, amyloid plaques, and Mini Mental State Examination (MMSE) scores. Our results suggest that synaptic transmission is affected by ADD in multiple brain regions. The differences were less marked in the entorhinal cortex and the hippocampus, most likely due to a ceiling effect imposed by the very early development of neurofibrillary tangles in older people in these brain regions.

Structural Analysis of Non-native Peptide-Based Catalysts Using 2D NMR-Guided MD Simulations.

Proteins and enzymes generally achieve their functions by creating well-defined 3D architectures that pre-organize reactive functionalities. Mimicking this approach to supramolecular pre-organization is leading to the development of highly versatile artificial chemical environments, including new biomaterials, medicines, artificial enzymes, and enzyme-like catalysts. The use of ß-turn and α-helical motifs is one approach that enables the precise placement of reactive functional groups to enable selective substrate activation and reactivity/selectivity that approaches natural enzymes. Our recent work has demonstrated that helical peptides can serve as scaffolds for pre-organizing two reactive groups to achieve enzyme-like catalysis. In this study, we used CYANA and AmberTools to develop a computational approach for determining how the structure of our peptide catalysts can lead to enhancements in reactivity. These results support our hypothesis that the bifunctional nature of the peptide enables catalysis by pre-organizing the two catalysts in reactive conformations that accelerate catalysis by proximity. We also present evidence that the low reactivity of monofunctional peptides can be attributed to interactions between the peptide-bound catalyst and the helical backbone, which are not observed in the bifunctional peptide.

Reliability and Validity of the State-Trait Hopelessness Scale in a Primarily Rural Population of Adults With Ischemic Heart Disease in the US Great Plains.

PURPOSE: Hopelessness and rurality are each independently associated with increased mortality in adults with ischemic heart disease (IHD), yet there is no known research examining hopelessness in rural patients with IHD. The authors of this study evaluated the reliability and validity of the State-Trait Hopelessness Scale (STHS) in a primarily rural population of adults with IHD living in West North Central United States (US Great Plains). METHODS: Reliability, concurrent validity, and convergent validity were evaluated for 115 adults hospitalized for IHD. Rural-Urban Commuting Area codes were used to stratify participants by rurality level, with 66% categorized as rural. Principal component analysis was used to examine potential factor structure of the STHS. FINDINGS: Cronbach α for the State and Trait Hopelessness subscales were 0.884 and 0.903, respectively. Concurrent validity was supported for the State and Trait subscales using the Patient Health Questionnaire-8 (State: r = 0.50, P < .001; Trait: r = 0.35, P < .001). Convergent validity was supported for the State subscale using the Duke Activity Status Index ( r = -0.23, P = .013). Principal component analysis showed 2 factors (hopelessness present and hopelessness absent) for the State and Trait subscales, accounting for 63% and 58% of variance, respectively. CONCLUSIONS: Findings support the reliability and validity of the STHS for evaluation of hopelessness in rural adults with IHD in clinical and research settings. Results replicated the same factor structure found in testing of the STHS in a primarily urban sample. Because of the prevalence of hopelessness in rural adults with IHD and association with increased mortality, hopelessness should be assessed during hospitalization and in the recovery period.

Measuring Up: A Comparison of TapeStation 4200 and Bioanalyzer 2100 as Measurement Tools for RNA Quality in Postmortem Human Brain Samples.

The determination of RNA integrity is a critical quality assessment tool for gene expression studies where the experiment's success is highly dependent on the sample quality. Since its introduction in 1999, the gold standard in the scientific community has been the Agilent 2100 Bioanalyzer's RNA integrity number (RIN), which uses a 1-10 value system, from 1 being the most degraded, to 10 being the most intact. In 2015, Agilent launched 4200 TapeStation's RIN equivalent, and reported a strong correlation of r2 of 0.936 and a median error < ±0.4 RIN units. To evaluate this claim, we compared the Agilent 4200 TapeStation's RIN equivalent (RINe) and DV200 to the Agilent 2100 Bioanalyzer's RIN for 183 parallel RNA samples. In our study, using RNA from a total of 183 human postmortem brain samples, we found that the RIN and RINe values only weakly correlate, with an r2 of 0.393 and an average difference of 3.2 RIN units. DV200 also only weakly correlated with RIN (r2 of 0.182) and RINe (r2 of 0.347). Finally, when applying a cut-off value of 6.5 for both metrics, we found that 95.6% of samples passed with RIN, while only 23.5% passed with RINe. Our results suggest that even though RIN (Bioanalyzer) and RINe (TapeStation) use the same 1-10 value system, they should not be used interchangeably, and cut-off values should be calculated independently.

Detection of Vegetable Oil Adulteration in Pre-Grated Bovine Hard Cheeses via 1H NMR Spectroscopy.

Adulteration of food products is a widespread problem of great concern to society and dairy products are no exception to this. Due to new methods of adulteration being devised in order to circumvent existing detection methods, new detection methods must be developed to counter fraud. Bovine hard cheeses such as Asiago, Parmesan, and Romano are widely sold and consumed in pre-grated form for convenience. Due to being processed products, there is ample opportunity for the introduction of inexpensive adulterants and as such, there is concern regarding the authenticity of these products. An analytical method was developed using a simple organic extraction to verify the authenticity of bovine hard cheese products by examining the lipid profile of these cheeses via proton Nuclear Magnetic Resonance (NMR) spectroscopy. In this study, 52 samples of pre-grated hard cheese were analyzed as a market survey and a significant number of these samples were found to be adulterated with vegetable oils. This method is well suited to high throughput analysis of these products and relies on ratiometrics of the lipids in the samples themselves. Genuine cheeses were found to have a very consistent lipid profile from sample to sample, improving the power of this approach to detect vegetable oil adulteration. The method is purely ratiometric with no need for internal or external references, reducing sample preparation time and reducing the potential for the introduction of error.

Patient, Public, and Healthcare Professionals' Sepsis Awareness, Knowledge, and Information Seeking Behaviors: A Scoping Review.

OBJECTIVES: Sepsis awareness and understanding are important aspects of prevention, recognition, and clinical management of sepsis. We conducted a scoping review to identify and map the literature related to sepsis awareness, general knowledge, and information-seeking behaviors with a goal to inform future sepsis research and knowledge translation campaigns. DESIGN: Scoping review. SETTING: Using Arksey and O'Malley's methodological framework, we conducted a systematic search on May 3, 2021, across four databases (MEDLINE, EMBASE, CINAHL, and Education Research Complete). Title/abstract and full-text screening was done in duplicate. One researcher extracted the data for each included article, and a second researcher checked data accuracy. The protocol was registered on Open Science Framework ( https://doi.org/10.17605/OSF.IO/YX7AU ). SUBJECTS: Articles related to sepsis awareness, knowledge, and information seeking behaviors among patients, public, and healthcare professionals. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 5,927 unique studies, 80 reported on patient ( n = 13/80;16.3%), public ( n = 15/80;18.8%), or healthcare professional (nurses, physicians, emergency medical technicians) ( n = 48/80; 60%) awareness and knowledge of sepsis. Healthcare professional awareness and knowledge of sepsis is high compared with patients/public. The proportion of patients/public who had heard of the term sepsis ranged from 2% (Japan) to 88.6% (Germany). The proportions of patients/public who correctly identified the definition of sepsis ranged from 4.2% (Singapore) to 92% (Sweden). The results from the included studies appear to suggest that patient/public awareness of sepsis gradually improved over time. We found that the definition of sepsis was inconsistent in the literature and that few studies reported on patient, public, or healthcare professional knowledge of sepsis risk factors. Most patient/public get their sepsis information from the internet, whereas healthcare professionals get it from their role in healthcare through job training or educational training. CONCLUSIONS: Patient, public, and healthcare professional awareness and knowledge of sepsis vary globally. Future research may benefit from a consistent definition as well as country-specific data to support targeted public awareness campaigns.

Metaplasticity: a key to visual recovery from amblyopia in adulthood?

PURPOSE OF REVIEW: We examine the development of amblyopia and the effectiveness of conventional and emerging therapies through the lens of the Bienenstock, Cooper, and Munro (BCM) theory of synaptic modification. RECENT FINDINGS: The BCM theory posits metaplastic adjustment in the threshold for synaptic potentiation, governed by prior neuronal activity. Viewing established clinical principles of amblyopia treatment from the perspective of the BCM theory, occlusion, blur, or release of interocular suppression reduce visual cortical activity in the amblyopic state to lower the modification threshold and enable amblyopic eye strengthening. Although efficacy of these treatment approaches declines with age, significant loss of vision in the fellow eye by damage or disease can trigger visual acuity improvements in the amblyopic eye of adults. Likewise, reversible retinal inactivation stimulates recovery of amblyopic eye visual function in adult mice and cats. SUMMARY: Conventional and emerging amblyopia treatment responses abide by the framework of BCM theory. Preclinical studies support that the dramatic reduction in cortical activity accompanying temporary retinal silencing can promote recovery from amblyopia even in adulthood, highlighting a promising therapeutic avenue.

Psychometric validity and reliability of the 10- and 2-item Connor-Davidson resilience scales among a national sample of Americans responding to the Covid-19 pandemic: an item response theory analysis.

PURPOSE: Psychometric validity/reliability of 10-item and 2-item abbreviations of the Connor-Davidson Resilience Scale (CD-RISC-10; CD-RISC-2) was investigated via item response theory and classic approaches. METHODS: We sampled 5023 adult American participants in a June/July 2020 survey on the COVID-19 pandemic's psychological effects. Our questionnaire incorporated the CD-RISC-10 with other validated measures. CD-RISC-10 items were ranked on item-to-scale correlations, loadings on a one-factor confirmatory factor analysis model, and item slope/threshold parameters plus information curves from a unidimensional graded response model. Concurrent validity of the highest ranked item pair was evaluated vis-à-vis the CD-RISC-10 and CD-RISC-2. Internal consistency, based on average variance extracted (AVE) and multiple reliability coefficients, was also compared. Convergent/divergent validity was tested by correlating anxiety, depression, fear of COVID-19, anxiety sensitivity, coping, and personality measures with both scales and the highest ranked item pair. Binary agreement/classification indexes assessed inter-rater reliability. RESULTS: Items 2 and 9 from CD-RISC-10 ranked the highest. Reliability coefficients were > 0.93, > 0.72, and > 0.82 for the CD-RISC-10, CD-RISC-2, vs summation of items 2 and 9. AVEs were 0.66, 0.67, and 0.77. CD-RISC abbreviations and the summation of items 2 and 9 correlated negatively with anxiety (> - 0.43), depression (> - 0.42), and fear of COVID-19 (> - 0.34); positively with emotional stability (> 0.53) and conscientiousness (> 0.40). Compared to the CD-RISC-2, summative scores of items 2 and 9 more efficiently classified/discriminated high resilience on the CD-RISC-10. CONCLUSION: We confirmed construct validity/reliability of copyrighted CD-RISC abbreviations. The CD-RISC-10's items 2 and 9 were psychometrically more salient than the CD-RISC-2.

How do prenatal people describe their experiences with anxiety? a qualitative analysis of blog content.

BACKGROUND: Despite elevated prevalence rates of prenatal (antenatal) anxiety across studies (13-21%), and prenatal people's use of the Internet to search for pregnancy-related information and support, research investigating prenatal people's experiences with online mental health communication, such as blogs, is lacking. This study examined blog entries focused on anxiety in pregnancy to better understand prenatal people's Internet discourse concerning their experiences with anxiety. METHODS: A Google search using the keywords "anxiety," "pregnant," and "blog" resulted in N = 18 blogs that met inclusion criteria (public blog written in English describing a personal experience with prenatal anxiety in 250 words or more). Blog content was analyzed using a thematic analytic approach based on grounded theory principles. RESULTS: Three main themes capturing prenatal people's experiences with anxiety as written in public blog content were developed from qualitative analyses: 1) etiology (subthemes: before pregnancy, during the current pregnancy, related to a previous pregnancy), 2) triggers (subthemes: uncertainty, perceived lack of control, and guilt and shame for not having a normal pregnancy), and 3) symptoms (subthemes: intertwined emotional, cognitive and physical symptoms, in addition to behavioural symptoms). CONCLUSIONS: Our findings demonstrate a need for perinatal professionals to address anxiety symptoms and triggers in pregnancy. One way to address this may be by providing credible information regarding prenatal mental and physical health to pregnant people through online mediums, such as blogs. Bloggers often discussed experiencing a combination of emotional, cognitive, physical, and behavioural symptoms, which suggests that medical and mental health professionals should work collaboratively to provide care for prenatal people experiencing anxiety. Furthermore, Cognitive Behavioural Therapy (CBT) addresses these types of symptoms, which suggests that interventions developed or adapted to meet this populations' needs could employ this therapeutic approach. Future research should explore the reasons why prenatal people experiencing anxiety engage with blogs, the characteristics of bloggers and readers, the impact of the blogging experience on both the blogger and their audience, and the information quality of blog content.

An evaluation of the quality of online perinatal depression information.

BACKGROUND: During the perinatal period (including pregnancy and up to 12 months after childbirth), expectant and new mothers are at an elevated risk of developing depression. Inadequate knowledge about perinatal depression and treatment options may contribute to the low help-seeking rates exhibited by perinatal people. The Internet can be an accessible source of information about perinatal depression; however, the quality of this information remains to be evaluated. The purpose of this study was to assess the quality of perinatal depression information websites. METHODS: After review, 37 websites were included in our sample. To assess overall website quality, we rated websites based on their reading level (Simple Measure of Gobbledegook; SMOG), information quality (DISCERN), usability (Patient Education Materials Assessment Tool; PEMAT), and visual design (Visual Aesthetics of Website Inventory; VisAWI). RESULTS: Websites often exceeded the National Institute of Health's recommended reading level of grades 6-8, with scores ranging from 6.8 to 13.5. Website information quality ratings ranged from 1.8 to 4.3 out of 5, with websites often containing insufficient information about treatment choices. Website usability ratings were negatively impacted by the lack of information summaries, visual aids, and tangible tools. Visual design ratings ranged from 3.2 to 6.6 out of 7, with a need for more creative design elements to enhance user engagement. CONCLUSIONS: This study outlines the characteristics of high-quality perinatal depression information websites. Our findings illustrate that perinatal depression websites are not meeting the needs of users in terms of reading level, information quality, usability, and visual design. Our results may be helpful in guiding healthcare providers to reliable, evidence-based online resources for their perinatal patients.

The Socioeconomic Indicators Linked to Parent Health-Related Technology Use: Cross-sectional Survey.

BACKGROUND: Despite the prevalence of parent health information seeking on the internet and its impact on parenting behavior, there is a paucity of research on parents of young children (ages 3 to 8 years). Given the importance of this developmental period, exploring how family socioeconomic indicators linked to the digital divide and health inequities affect parent proxy- and self-seeking is critical to further understanding variability in health information seeking and associated outcomes. OBJECTIVE: This study aimed to explore parental health-related technology use (HTU), the process by which parents engage in support, advice, and information-seeking behavior related to their (self-seeking) and their children's (proxy seeking) health across a range of hardware devices (eg, tablet, wearable, smartphone, laptop, and desktop computer) and sources (eg, search engines, mobile applications, social media, and other digital media). METHODS: A cross-sectional study including 313 parents and guardians of children ages 3 to 8 years recruited through Amazon Mechanical Turk (MTurk) was conducted. Parents were asked to complete a self-administered questionnaire on a broad range of parenting and parent-related constructs, including sociodemographic information, technology device ownership, and engagement in and use, features, and perceptions of HTU. Descriptive and bivariate analyses (chi-square tests) were performed to identify patterns and investigate associations between family socioeconomic indicators and parent HTU. RESULTS: The overwhelming majority (301/313, 96%) of parents of young children reported engaging in HTU, of which 99% (300/301) reported using search engines (eg, Google), followed by social media (62%, 188/301), other forms of digital media (eg, podcasts; 145/301, 48%), and mobile applications (114/301, 38%). Parents who engaged in HTU reported seeking information about their child's behavior and discipline practices (260/313, 83%), mental or physical health (181/313, 58%), and academic performance (142/313, 45%). Additionally, nearly half (134/313, 43%) of parents reported searching for advice on managing their stress. Among parents who reported using each source, an overwhelming majority (280/300, 93%) indicated that search engines were a helpful online source for proxy- and self-seeking, followed by social media (89%, 167/188), other digital media (120/145, 83%), and mobile apps (87/114, 76%). Among parents who reported using any technology source, approximately one-fifth reported that technology sources were most comfortable (61/311, 20%), most understanding (69/311, 22%), and most influential toward behavior change (73/312, 23%) compared to traditional sources of health information-seeking, including mental health professionals, other health care professionals, school professionals, community leaders, friends, and family members. Indicators of family socioeconomic status were differentially associated with frequency and perceptions of and search content associated with parent HTU across technology sources. CONCLUSIONS: The findings of this study underscore critical considerations in the design and dissemination of digital resources, programs, and interventions targeting parent and child health, especially for families in traditionally underserved communities.

Effect of Carbohydrate Mouth Rinse on Resistance Exercise Performance.

ABSTRACT: Green, MS, Kimmel, CS, Martin, TD, Mouser, JG, and Brune, MP. Effect of carbohydrate mouth rinse on resistance exercise performance. J Strength Cond Res 36(7): 1916-1921, 2022-A carbohydrate mouth rinse (CMR) has been shown to enhance short duration endurance performance and raises the possibility that a similar strategy could improve performance during resistance exercise. Eighteen male and female (N = 36) resistance trained subjects (mean values ± SD; age: 21.5 ± 1.6 years, height: 1.72 ± 0.09 m, body mass: 72.8 ± 13.4 kg, and body fat: 16.7 ± 5.8%) performed 3 experimental visits during which bench press resistance exercise (4 × 10 repetitions at 65% of 1 repetition maximum [1RM] with 120 seconds recovery) and repetitions to failure at 60% 1RM were performed. Subjects rinsed 25 ml of water (WAT), noncaloric placebo (PLA), or 6.4% maltodextrin (CHO) solution for 10 seconds during exercise in a crossover, counter-balanced manner. Rating of perceived exertion (RPE), pleasure-displeasure (FS), number of repetitions to fatigue (REPS), and postexercise blood glucose (GLU) and lactate (LA) were measured. Compared to WAT (17.7 ± 0.8), PLA (19.0 ± 0.7; p = 0.025), and CHO (18.7 ± 0.8; p = 0.039) treatments resulted in higher REPS, with no difference between PLA and CHO treatments (p = 0.310). Rating of perceived exertion progressively increased each set (p < 0.0001), but was not affected by treatment (p = 0.897). Pleasure-displeasure declined during recovery from sets 3 and 4 (p < 0.05) but was also not affected by treatment (p = 0.692). Postexercise GLU (p = 0.103) and LA (p = 0.620) were not different between treatments. Although a placebo effect was present for REPS, this study failed to detect an effect of CMR on REPS, RPE, FS, GLU, or LA on upper-body resistance exercise.

Delta-8 Tetrahydrocannabinol Product Impurities.

Due to increased concerns regarding unidentified impurities in delta-8 tetrahydrocannabinol (Δ-8 THC) consumer products, a study using Nuclear Magnetic Resonance (NMR), high performance liquid chromatography (HPLC), and mass spectrometry (MS) was conducted to further investigate these products. Ten Δ-8 THC products, including distillates and ready to use vaporizer cartridges, were analyzed. The results yield findings that the tested products contain several impurities in concentrations far beyond what is declared on certificates of analysis for these products. As Δ-8 THC is a synthetic product synthesized from cannabidiol (CBD), there are valid concerns regarding the presence of impurities in these products with unknown effects on the human body. Compounding this problem is apparent inadequate testing of these products by producers and independent laboratories.

Tau PET imaging with 18F-PI-2620 in aging and neurodegenerative diseases.

PURPOSE: In vivo measurement of the spatial distribution of neurofibrillary tangle pathology is critical for early diagnosis and disease monitoring of Alzheimer's disease (AD). METHODS: Forty-nine participants were scanned with 18F-PI-2620 PET to examine the distribution of this novel PET ligand throughout the course of AD: 36 older healthy controls (HC) (age range 61 to 86), 11 beta-amyloid+ (Aß+) participants with cognitive impairment (CI; clinical diagnosis of either mild cognitive impairment or AD dementia, age range 57 to 86), and 2 participants with semantic variant primary progressive aphasia (svPPA, age 66 and 78). Group differences in brain regions relevant in AD (medial temporal lobe, posterior cingulate cortex, and lateral parietal cortex) were examined using standardized uptake value ratios (SUVRs) normalized to the inferior gray matter of the cerebellum. RESULTS: SUVRs in target regions were relatively stable 60 to 90 min post-injection, with the exception of very high binders who continued to show increases over time. Robust elevations in 18F-PI-2620 were observed between HC and Aß+ CI across all AD regions. Within the HC group, older age was associated with subtle elevations in target regions. Mildly elevated focal uptake was observed in the anterior temporal pole in one svPPA patient. CONCLUSION: Preliminary results suggest strong differences in the medial temporal lobe and cortical regions known to be impacted in AD using 18F-PI-2620 in patients along the AD trajectory. This work confirms that 18F-PI-2620 holds promise as a tool to visualize tau aggregations in AD.