Miracle-dz/UniFAR-FTUs huggingface dataset:
Topical anesthetic and pain relief using penetration enhancer and transcriptional transactivator peptide multi-decorated nanostructured lipid carriers

Abstract Many strategies have been developed to overcome the stratum corneum (SC) barrier, including functionalized nanostructures. Chemical penetration enhancers (CPEs) and cell-penetrating peptides (CPP) were applied to decorate nanostructured lipid carriers (NLC) for topical anesthetic and pain relief. A novel pyrenebutyrate (PB-PEG-DSPE) compound was synthesized by the amide action of the carboxylic acid group of PB with the amido groups of DSPE-PEG. PB-PEG-DSPE has a hydrophobic group, hydrophilic group, and lipid group. The lipid group can be inserted into NLC to form PB functional NLC. In order to improve the penetrability, TAT and PB multi-decorated NLC were designed for the delivery of lidocaine hydrochloride (LID) (TAT/PB LID NLC). The therapeutic effects of NLC in terms of in vitro skin penetration and in vivo in animal models were further studied. The size of TAT/PB LID NLC tested by DLS was 153.6 ± 4.3 nm. However, the size of undecorated LID NLC was 115.3 ± 3.6 nm. The PDI values of NLC vary from 0.13 ± 0.01 to 0.16 ± 0.03. Zeta potentials of NLC were negative, between −20.7 and −29.3 mV. TAT/PB LID NLC (851.2 ± 25.3 µg/cm2) showed remarkably better percutaneous penetration ability than PB LID NLC (610.7 ± 22.1 µg/cm2), TAT LID NLC (551.9 ± 21.8 µg/cm2) (p < .05) and non-modified LID NLC (428.2 ± 21.4 µg/cm2). TAT/PB LID NLC exhibited the most prominent anesthetic effect than single ligand decorated or undecorated LID NLC in vivo. The resulting TAT/PB LID NLC exhibited good skin penetration and anesthetic efficiency, which could be applied as a promising anesthesia system.
Pathways linking activity, adiposity, and inflammation to bone mineral density in women and men from NHANES 2007 to 2010

Age, sedentary activity, central adiposity, and inflammation have all been independently associated with bone mineral density (BMD). We assessed how the effects of sedentary activity and central adiposity on BMD of the lumbar spine and femoral neck change across early to late adulthood and whether these relationships are mediated by inflammation.
Stress, physical activity, and screen‐related sedentary behaviour within the first month of the COVID‐19 pandemic

Abstract This study investigated how stress, physical activity and sedentary behaviours, of a small sample of Canadians, changed within the first month (i.e. March/April) of the COVID‐19 pandemic and the reasons/barriers associated with such changes. Individuals who regularly wear activity trackers were recruited via social media. Participants (N = 121) completed fillable calendars (March/April 2020) with their step counts and answered an online survey. Separate paired‐sample t‐tests, one‐way ANOVAs and bivariate chi‐squares were conducted, in addition to qualitative analysis. Daily (p <.001) and work (p =.003) stress increased, physical activity (measured by step count) decreased (p =.0014), and screen‐related sedentary behaviour increased (p <.001) as a result of COVID‐19. A decrease in physical activity, as a result of the pandemic, was also associated with a larger increase in work stress, compared with those who self‐reported their physical activity to have been maintained or increased (p =.005). The most common reasons/barriers to changes in physical activity behaviours were access/equipment, time and motivation. Findings provide initial evidence of the impact of the COVID‐19 pandemic on the health of some Canadians and highlight the need for continued monitoring of the health of Canadians throughout the pandemic.
Chemistry of polyfunctional molecules. Part 86. Organoarsenic compounds derived from 1,3-bis(di-iodoarsino)propane with monocyclic, tricyclic, and straight-chain structures; X-ray crystal structure of 2,8,13,14-tetraoxa-1,3,7,9-tetra-arsatricyclo[7.3.1.1]tetradecane

Treatment of (C6H5)3As(CH2)3As(C6H5)2(1) with HI gives under elimination of benzene I2As(CH2)3- AsI2(2). The reduction of (2) with sodium in tetrahydrofuran leads to the heterocyclic compound I[graphic omitted]sI (3). Hydrolysis of (2) yields the new tricyclic compound (CH2)3As4O4(CH2)3(4). The oxidative solvolysis of (2) with H2O2 results in the formation of (HO)2OAs(CH2)3AsO(OH)2(5). All the compounds have been characterized by elemental analysis, i.r. , Raman, 1H n.m. r. , and mass spectra and by conductivity measurements. The crystal structure of compound (4) has been solved by X-ray diffraction. Crystals are monoclinic, space group P21/c, with a= 6.886(2), b= 14.745(5), c= 11.577(4)A, β= 94.15(3)°, and Z= 4. Data collection yielded 4 183 reflections, of which 2 026 with I 3σ(I) gave R= 0.038. The molecule consists of a tricyclic ring system. The main skeleton is an eight-membered As4O4 ring comparable to the endo–endo structure of N4S4. The As atoms are linked together by two (CH2)3 chains forming an open-envelope conformation. The solid state and a solution of (4) in CS2 show appreciable evidence for the existence of intramolecular C–H ⋯ O–As bonding.
Evaluating quality of life in frailty: applicability and clinimetric properties of the SarQoL® questionnaire

The SarQoL® questionnaire was specifically designed to measure quality of life (QoL) in sarcopenia. Frailty and sarcopenia have areas of overlap, notably weak muscle strength and slow gait speed, which may mean that the SarQoL could provide a measure of QoL in frailty. This study aimed to evaluate the clinimetric properties of the SarQoL questionnaire in physical frailty using the Fried criteria.
Structural Determinants of Cholesterol Recognition in Helical Integral Membrane Proteins

Cholesterol (CLR) is an integral component of mammalian membranes. It has been shown to modulate membrane dynamics and alter integral membrane protein (IMP) function. However, understanding the molecular mechanisms of these processes is complicated by limited and conflicting structural data: Specifically, in co-crystal structures of CLR-IMP complexes it is difficult to distinguish specific and biologically relevant CLR-IMP interactions from a nonspecific association captured by the crystallization process. The only widely recognized search algorithm for CLR-IMP interaction sites is sequence-based, i.e. searching for the so-called ‘CRAC’ or ‘CARC’ motifs. While these motifs are present in numerous IMPs, there is inconclusive evidence to support their necessity or sufficiency for CLR binding. Here we leverage the increasing number of experimental CLR-IMP structures to systematically analyze putative interaction sites based on their spatial arrangement and evolutionary conservation. From this analysis we create three-dimensional representations of general CLR interaction sites that form clusters across multiple IMP classes and classify them as being either specific or nonspecific. Information gleaned from our characterization will eventually enable a structure-based approach for prediction and design of CLR-IMP interaction sites. SIGNIFICANCE CLR plays an important role in composition and function of membranes and often surrounds and interacts with IMPs. It is a daunting challenge to disentangle CLRs dual roles as a direct modulator of IMP function through binding or indirect actor as a modulator of membrane plasticity. Only recently studies have delved into characterizing specific CLR-IMP interactions. We build on this previous work by using a combination of structural and evolutionary characteristics to distinguish specific from nonspecific CLR interaction sites. Understanding how CLR interacts with IMPs will underpin future development towards detecting and engineering CLR-IMP interaction sites.
Seasonal Differences in the Cost and Engagement of Facebook Advertisements for a Physical Activity Smartphone App

Purpose: To evaluate the performance of Facebook advertisements for a physical activity smartphone app at different times of the year. Design: A repeated cross-sectional study examined the cost and engagement levels of advertisements during 3 time points: Post-Easter April-May 2019 , Pre-Summer October 2019 , and New Year January 2020 . Setting: Advertisements were delivered on Facebook. Subjects: The target population was Australian females aged 25-60 years. Measures: Cost was evaluated in terms of reach per dollar. Engagement was evaluated in terms of click-through and app downloads per reach. Analysis: ANOVA and Chi-square were used to assess differences in reach per dollar, click-through, and app downloads per reach between time points. Results: Reach per dollar was highest in Post-Easter, but declined in Pre-Summer and New Year (reach/$ 34.8 vs 31.5 vs 27.5; p = .004). Click-through was highest in New Year followed by Post-Easter, then Pre-Summer (click-through 3.2% vs 1.9% vs 1.2%; p < .001). New Year and Post-Easter advertisements achieved higher app downloads per reach than Pre-Summer (downloads 0.9% vs 0.7% vs 0.3%; p < .001). Conclusion: Facebook advertisements were cheaper in the first time-point, and appear to be getting more expensive (i.e. declining reach/$). Advertisements in the New Year achieved the highest click-through and app downloads per reach, suggesting a useful time of year to promote physical activity products.
Impact of detrusor underactivity on the postoperative outcomes after benign prostatic enlargement surgery

Previous studies suggest that men with detrusor underactivity (DUA) have less symptomatic improvement after prostate surgery than those with normal contractility, but the available data is controversial. We aim to determine the differences in functional outcomes of patients with or without DUA who underwent photovaporization of the prostate (PVP) with GreenLight™180 W XPS.
Conversion of a racemate into a single enantiomer in one step by chiral liquid chromatography: Studies with rac-2,2′-diiodobiphenyl

The enantiomers of rac-2,2′-diiodobiphenyl were separated by liquid chromatography on microcrystalline triacetylcellulose. The conformational lability, a large separation factor α, and a suitable capacity factor k′(+) of this biphenyl allowed us to convert the racemate into 90% of enantiomerically pure (-)-2,2′-diiodobiphenyl and 10% of pure (+)-2,2′-diiodobiphenyl, respectively, by a series of in situ racemization-elution cycles. The much better retained (+)-enantiomer was racemized on the chromatographic column at 50°C after the less retained (-)-enantiomer has already been eluted at 8°C. © 1995 Wiley-Liss, Inc.
Distinct Profile Differences in Subjective Cognitive Decline in the General Public Are Associated with Metacognition, Negative Affective Symptoms, Neuroticism, Stress, and Poor Quality of Life

Background: Subjective cognitive decline (SCD) is increasingly recognized in both the clinical and research arenas as a risk factor for mild cognitive impairment (MCI) and dementia. Although SCD is etiologically heterogeneous and potentially treatable, in comparison to MCI and Alzheimer’s disease, SCD remains poorly characterized with its clinical relevance often questioned. Objective: This study’s aim was to improve the characterization of SCD within the general public. Methods: Individuals with SCD were compared to those without via a battery of measures. Results: Both the SCD and the non-SCD group correlational analysis identified significant relationships between worse SCD, worse metacognitive dysfunction, negative affective symptoms, and greater levels of stress. The SCD group displayed additional correlational relationships between Cognitive Change Index (Self report) (CCI-S) scores, higher neuroticism scores, and poorer quality of life (QoL). Partial correlation analysis in the SCD group suggests CCI-S scores, anxiety, depression, and metacognition are intercorrelated. Ad hoc analyses using metacognition as the grouping variable found that those experiencing worse metacognitive dysfunction were significantly more likely to experience poorer SCD, psychological and social QoL, greater levels of anxiety, depression, stress, and neuroticism. Conclusion: The emerging pattern from the analysis indicates that SCD appears associated with sub-clinical negative affective difficulties, metacognitive, and other psycho-social issues, and poorer QoL. Dysfunctional cognitive control at a meta-level may impact someone’s ability to rationally identify cognitive changes, increase worry about cognitive changes, and allow such changes to impact their lives more than those with superior metacognitive control. Findings could impact SCD assessment, monitoring, early intervention, and ultimately reducing risk of further decline.
Loneliness During the COVID-19 Pandemic Among Older Adults With Chronic Conditions

The COVID-19 pandemic may intensify loneliness among older adults with chronic conditions who are at high risk of severe illness, but little is known about factors associated with loneliness during the pandemic. We considered factors linked to loneliness among 701 adults aged 50 years and older with chronic conditions from Michigan (82.5%) and 33 other U.S. states. Participants completed an anonymous online survey between May 14 and July 9, 2020. About two thirds (66.4%) reported moderate to severe loneliness. The fully adjusted regression model revealed that being a person of color, having a spouse or cohabiting partner, and more emotional support were associated with lower levels of loneliness. Higher anxiety symptoms, more worry about COVID-19 infection, and more financial strain because of the pandemic were linked to greater loneliness. These findings inform strategies to support a vulnerable subgroup of older adults during this pandemic and in future public health crises.
How would preclinical Alzheimer’s disease (AD pathology) occur? An insight from a genomic instability mouse model

More than 95% of Alzheimer ’s disease (AD) is late-onset, in which patients show cl inical cognit ion/behavior symptoms after age 65. Unlike early-onset AD that comes with mutations in genes directly involved in amyloid metabolism (APP, PSEN), genetic predispositions associated with late-onset AD are harder to pinpoint, and their mechanistic links to AD development need further investigation. Although the development mechanism of late-onset AD remains controversial, amyloid-beta accumulation, initiated in middle age, is widely accepted as the triggering event for early AD pathology (Du Bois et al., 2010; Sterling et al., 2011). In 2018, we reported a genomic instability mouse model (Sgo1) in which amyloid-beta accumulates in the brain in old age without early-onset AD mutation (Rao et al., 2018). The identification led us to anticipate that the model may reveal the development mechanism of late-onset AD. In a new study that appeared in Aging Cell (Rao et al., 2020a), we identified GSK3 inactivation in middle age as a cause for triggering the amyloid-beta accumulation. Inactivation of GSK3 appeared to affect amyloid-beta generation in two ways: (i) via increasing ARC/Arg3.1, which can generate amyloidbeta in an activity-dependent manner, and (ii) via activating canonical Wnt signaling and driving the cell cycle in the brain, thus activating the “amyloid-beta accumulation cycle” (Rao et al., 2020b). Since the Sgo1 condition prolongs mitosis, during which amyloid-beta generation and accumulation is facilitated, Sgo1 may be mimicking the aneuploid condition prevalent in patients with mild cognitive impairment (MCI) and AD (Potter et al., 2019). Our studies (a) support the notion of the critical roles of genomic instability and aneuploidy in AD development, (b) suggest a role of GSK3 in the onset of amyloid-beta accumulation and onset of AD pathology in middle age, and (c) suggest the usefulness of the mouse model for testing drug candidates for late-onset AD.
Time to Colonoscopy After Abnormal Stool-Based Screening and Risk for Colorectal Cancer Incidence and Mortality.

BACKGROUND AND AIMS The optimal time interval for diagnostic colonoscopy completion after an abnormal stool-based colorectal cancer (CRC) screening test is uncertain. We examined the association between time to colonoscopy and CRC outcomes among individuals who underwent diagnostic colonoscopy after abnormal stool-based screening. METHODS We performed a retrospective cohort study of veterans age 50 to 75 years with an abnormal fecal occult blood test (FOBT) or fecal immunochemical test (FIT) between 1999 and 2010. We used multivariable Cox proportional hazards to generate CRC-specific incidence and mortality hazard ratios (HRs) and 95% confidence intervals (CI) for 3-month colonoscopy intervals, with 1 to 3 months as the reference group. Association of time to colonoscopy with late-stage CRC diagnosis was also examined. RESULTS Our cohort included 204,733 patients. Mean age was 61 years (SD 6.9). Compared with patients who received a colonoscopy at 1 to 3 months, there was an increased CRC risk for patients who received a colonoscopy at 13 to 15 months (HR 1.13; 95% CI 1.00-1.27), 16 to 18 months (HR 1.25; 95% CI 1.10-1.43), 19 to 21 months (HR 1.28; 95% CI: 1.11-1.48), and 22 to 24 months (HR 1.26; 95% CI 1.07-1.47). Compared with patients who received a colonoscopy at 1 to 3 months, mortality risk was higher in groups who received a colonoscopy at 19 to 21 months (HR 1.52; 95% CI 1.51-1.99) and 22 to 44 months (HR 1.39; 95% CI 1.03-1.88). Odds for late-stage CRC increased at 16 months. CONCLUSIONS Increased time to colonoscopy is associated with higher risk of CRC incidence, death, and late-stage CRC after abnormal FIT/FOBT. Interventions to improve CRC outcomes should emphasize diagnostic follow-up within 1 year of an abnormal FIT/FOBT result.
Influence of a combined hot air and UV-C treatment on quality parameters of fresh-cut broccoli florets at 0 °C

Summary Broccoli is a horticultural product with a high nutritional value that can be consumed fresh but also minimally processed. However, broccoli is highly perishable since it develops a senescence quickly that deteriorates commercial and nutritional quality of the product. In this work we analysed the effect of a combination of UV-C and heat treatment on quality and senescence of fresh-cut broccoli florets stored at 0 °C. Combined treatment delayed yellowing as evidenced by higher Hue values and lower chlorophyll degradation. The treatment diminished respiratory activity indicating higher tissue integrity. Treated samples showed higher phenolic content and antioxidant capacity. On day 21 of storage, treated samples had higher levels of total sugars, and total proteins. The results suggest that a combined treatment with heat and UV-C may reduce senescence, tissue damage and helps to maintain a better quality of the product during storage at 0 °C.
Combinatorial glucose, nicotinic acid and N-acetylcysteine therapy has synergistic effect in preclinical C. elegans and zebrafish models of mitochondrial complex I disease

Abstract Mitochondrial respiratory chain disorders are empirically managed with variable antioxidant, cofactor and vitamin ‘cocktails’. However, clinical trial validated and approved compounds, or doses, do not exist for any single or combinatorial mitochondrial disease therapy. Here, we sought to pre-clinically evaluate whether rationally designed mitochondrial medicine combinatorial regimens might synergistically improve survival, health and physiology in translational animal models of respiratory chain complex I disease. Having previously demonstrated that gas-1(fc21) complex I subunit ndufs2−/− C. elegans have short lifespan that can be significantly rescued with 17 different metabolic modifiers, signaling modifiers or antioxidants, here we evaluated 11 random combinations of these three treatment classes on gas-1(fc21) lifespan. Synergistic rescue occurred only with glucose, nicotinic acid and N-acetylcysteine (Glu + NA + NAC), yielding improved mitochondrial membrane potential that reflects integrated respiratory chain function, without exacerbating oxidative stress, and while reducing mitochondrial stress (UPRmt) and improving intermediary metabolic disruptions at the levels of the transcriptome, steady-state metabolites and intermediary metabolic flux. Equimolar Glu + NA + NAC dosing in a zebrafish vertebrate model of rotenone-based complex I inhibition synergistically rescued larval activity, brain death, lactate, ATP and glutathione levels. Overall, these data provide objective preclinical evidence in two evolutionary-divergent animal models of mitochondrial complex I disease to demonstrate that combinatorial Glu + NA + NAC therapy significantly improved animal resiliency, even in the face of stressors that cause severe metabolic deficiency, thereby preventing acute neurologic and biochemical decompensation. Clinical trials are warranted to evaluate the efficacy of this lead combinatorial therapy regimen to improve resiliency and health outcomes in human subjects with mitochondrial disease.
Ochratoxin A in Wine: Its Determination and Photostability

Abstract Due to the growing public concern regarding food safety, reliable, nondemanding and robust analytical methods are needed for quantitative determination of toxic compounds in complex matrices. Sample preparation is frequently a crucial step in determination of ochratoxin A (OTA) in wine, and a simplified and automated procedure is described, using solid‐phase extraction coupled on‐line to high pressure liquid chromatography (HPLC) with fluorimetric detection (λex=333 nm, λem=460 nm). While the limit of quantitation is frequently better compared to off‐line procedures (30 ng/L), the decisive advantages of the new procedure are the absence of all sample manipulation during preconcentration and subsequent analysis, and consequentially no risk of analyte loss or sample contamination. Furthermore, using the standard addition method, matrix interferences can be avoided and the determination of extraction efficiency is unnecessary. These improvements have important consequences for the overall uncertainty of the analytical procedure. The developed method was applied for determination of OTA in 12 selected Slovenian wines. The typical relative standard deviation (RSD) was 10%. In none of the samples, did the OTA amount exceeded 2 µg/kg, the limit regulated by the EC. The photo‐stability of the mycotoxin in solutions was examined. During irradiation of OTA solutions, its content was quickly reduced, while three fluorescent degradation products were detected. The degradation proceeds faster in water and 12% ethanolic solutions than in organic solvents or wine. Identification of the fluorescent degradation products was attempted using LC‐MS/MS with electrospray ionization.