Miracle-dz/UniFAR-FTUs huggingface dataset:
In vitro digested milk proteins: Evaluation of angiotensin-1-converting enzyme inhibitory and antioxidant activities, peptidomic profile, and mucin gene expression in HT29-MTX cells.

Over the past decades, several studies investigated the health-promoting functions of milk peptides. However, to date many hurdles still exist regarding the widespread use of milk-derived bioactive peptides, as they may be degraded during gastrointestinal digestion. Thus, the aim of our study was to in vitro digest intact whey protein isolate (WPI) and casein proteins (CNP), mimicking in vivo digestion, to investigate their bioactive effects and to identify the potential peptides involved. Whey protein isolate and CNP were digested using a pepsin-pancreatin protocol and ultra-filtered (3-kDa cutoff membrane). A permeate (<3 kDa) and a retentate (>3 kDa) were obtained. Soy protein was included as a control (CTR). Angiotensin-1-converting enzyme inhibitory (ACE1-I) and antioxidant activity (AOX) were assessed and compared with those observed in undigested proteins and CTR. Furthermore, the permeate was characterized by nano-liquid chromatography electrospray ionization tandem mass spectrometry (LC-nano ESI MS/MS) using a shotgun peptidomic approach, and retentate was further digested with trypsin and analyzed by MS using a shotgun proteomic approach to identify potentially bioactive peptides. Further, the effects of WPI, CNP, and CTR retentate on cell metabolic activity and on mucus production (MUC5AC and MUC2 gene expression) were assessed in intestinal goblet HT29-MTX-E12 cells. Results showed that WPI permeate induced a significant ACE1-I inhibitory effect [49.2 ± 0.64% (SEM)] compared with undigested WPI, CNP permeate, and retentate or CTR permeate (10.40 ± 1.07%). A significant increase in AOX (1.58 ± 0.04 and 1.61 ± 0.02 µmol of trolox AOX equivalents per mg of protein, respectively) upon digestion was found in WPI. Potentially bioactive peptides associated with ACE1-I and antihypertensive effects were identified in WPI permeate and CNP retentate. At specific concentrations, WPI, CNP, and CTR retentate were able to stimulate metabolic activity in HT29-MTX-E12 cells. Expression of MUC5AC was increased by CNP retentate and unaltered by WPI retentate; MUC2 expression was significantly increased by 0.33 mg/g of CNP and reduced by 1.33 mg/g of CNP. Our results confirm that milk proteins may be rich sources of bioactive compounds, with the greatest beneficial potential of CNP at the intestinal goblet cell level.
Role of Sleep Duration in the Association Between Socioecological Protective Factors and Health Risk Behaviors in Adolescents.

OBJECTIVE The purpose of this study was to examine the associations of sleep duration and socioecological protective factors with patterns of adolescent risk behaviors in Fairfax County, VA-one of the largest public school districts in the United States. METHODS A total of 21,360 and 20,330 students in 10th and 12th grades who completed the Youth Risk Behavior Survey were included in this cross-sectional analysis. Sleep duration was measured by self-report of the average number of hours of sleep on a school night. Ten socioecological protective factors included peer-individual, family, school, and community domains. Latent class analysis was used to classify 7 risk behaviors (alcohol use, cigarette use, illicit drug use, inappropriate prescription drug use, risky sexual behavior, deviant behavior, and academic failure) into 4 class memberships (low, some, moderate, and high). Multinomial regression models were adjusted for age, sex, and race. RESULTS Adolescents who reported sleeping the recommended 8 to 9 hours were significantly less likely to belong to the class memberships of greater risk behaviors compared with those who reported short and long sleep duration after controlling for age, sex, race, and survey year. There was a significant inverse relationship between the number of socioecological protective factors and risk behaviors for both 10th and 12th graders. Potential risks of age, sex, and race on risk behaviors were observed. No significant interaction between sleep duration and protective factors was found in either grade. CONCLUSION This study highlights the significant associations between sleep duration and risk behaviors in adolescents with diverse socioecological protective factors. Prioritization of prevention-focused resources should consider sleep duration in addition to the socioecological protective factors commonly cited in the literature when addressing adolescent risk behaviors.
Dual drug nanocrystals loaded microparticles for fixed dose combination of simvastatin and ezetimibe

Abstract Dual drug nanocrystals loaded nano embedded microparticles (DNEMs) were prepared for fixed dose combination of simvastatin (SIM) and ezetimibe (EZE) using NanoCrySP technology. The purpose was to generate nanonized SIM and EZE dispersed in matrix of single crystallization inducing excipient and investigate their in vitro performance. DNEM were prepared using mannitol (MAN) as crystallization inducer (active pharmaceutical ingredients (APIs)/MAN = 3:7 w/w) using spray drying. TPGS (0.1% w/v) was used as surfactant for stabilization of nanocrystals. Crystallinity of DNEM was confirmed by solid-state characterization using DSC and PXRD. Particle size analysis was carried out using Zetasizer® and the Scherrer equation as primary techniques and SEM and TEM as orthogonal techniques. Size of both SIM and EZE in DNEM was close to 600 nm. In vitro performance was assessed using USP apparatus II in 0.025% SLS containing sodium phosphate buffer. Powder dissolution of DNEM increased 1.45 times for SIM and 1.65 times for EZE as compared to their physical mixture in discriminatory medium. MAN did not plasticize SIM or EZE by virtue of its immiscibility with the two drugs. However, MAN helped in inducing crystallization via heterogeneous nucleation. The generated DNEM were stable in terms of assay, polymorphic form and dissolution for 90 days of accelerated storage at 40 °C/75% RH. Graphical Abstract
Mitochondrial Glutathione Transferase Zeta 1 is Inactivated More Rapidly by Dichloroacetate than the Cytosolic Enzyme in Adult and Juvenile Rat Liver.

Dichloroacetate (DCA) has potential for treating mitochondrial disorders and cancer by activating the mitochondrial pyruvate dehydrogenase complex. Repeated dosing of DCA results in reduced drug clearance due to inactivation of glutathione transferase ζ1 (GSTZ1), its metabolizing enzyme. We investigated the time course of inactivation of GSTZ1 in hepatic cytosol and mitochondria after one oral dose of 100 mg/kg DCA to female Sprague-Dawley rats aged 4 wk (young) and 52 wk (adult) as models for children and adults, respectively. GSTZ1 activity with both DCA and an endogenous substrate, maleylacetone (MA), as well as GSTZ1 protein expression were rapidly reduced in cytosol from both ages following DCA treatment. In mitochondria, loss of GSTZ1 protein and activity with DCA were even more rapid. The cytosolic in vivo half-lives of loss of GSTZ1 activity with DCA were 1.05 ± 0.03 and 0.82 ± 0.02 h (mean ± S.D., n=6) for young and adult rats, respectively, with inactivation significantly more rapid in adult rats, p<0.001. The mitochondrial inactivation half-lives were similar in young (0.57 ± 0.02 h) and adult rats (0.54 ± 0.02 h), and were significantly (p< 0.0001) shorter than cytosolic inactivation half-lives. By 24 h after DCA administration, activity and expression remained at 10% or less than control values. The in vitro GSTZ1 inactivation half-lives following incubation with 2 mM DCA in the presence of physiological chloride (Cl-) concentrations (cytosol 44 mM, mitochondria 1-2 mM) exhibited marked differences between subcellular fractions, being 3 times longer in the cytosol than mitochondria, regardless of age, suggesting that the lower Cl- concentration in mitochondria explained the faster degradation of GSTZ1. These results demonstrate for the first time that rat mitochondrial GSTZ1 is more readily inactivated by DCA than cytosolic GSTZ1, and cytosolic GSTZ1 is inactivated more rapidly in adult than young rats.
ShenQi FuZheng injection as an adjunctive treatment to chemotherapy in breast cancer patients: a meta-analysis

Abstract Context: Shenqi FuZheng injection (SFI) has been suggested as a complementary treatment of chemotherapy in China. However, little is known about it in western countries. Objective: This study assesses the clinical effect of SFI combined with chemotherapy for breast cancer patients. Materials and methods: Both English and Chinese databases were searched covering the time period of 1999– 2018 for relevant studies comparing the effect of SFI plus chemotherapy treatment with chemotherapy alone in patients with breast cancer. Target outcomes concerning treatment effect, performance status, immune system and toxic effects were extracted and combined using Stata version 15.0 software. Quality assessment was performed using the Jadad scale. Results: Forty-nine trials were included based on certain selection criteria. Only seven studies were rated as high-quality publications. Results of meta-analysis showed that SFI intervention can significantly improve objective tumour response, performance status, NK, CD3+, CD4+ and CD4+/CD8+ ratio and reduce occurrence of leucopenia, thrombocytopenia, haemoglobin reduction, liver dysfunction, gastrointestinal reaction, nausea and vomiting, bone marrow suppression and ECG changes. However, no significant difference was found between SFI and the control group regarding CD8+ levels, and renal disorders. Discussion and conclusions: SFI intervention appeared to be effective in improving clinical efficacy, immune function and reducing toxicity when combined with chemotherapy for breast cancer. However, our findings still need verification by high-quality trials.
Garlic antagonizes skeletal muscle ischemia reperfusion injury through regulating inflammation, apoptosis and desmin expression in adult male rats.

BACKGROUND Skeletal muscle injuries with subsequent bleeding is common cause of death on both sports and battle grounds. Application and removal of tourniquet is fast intervention to control hemorrhage resulting ischemia reperfusion (IR) injury. The effect of IR in skeletal muscle is far more severe compared to other body tissues because of the devastating systemic complication. Garlic has beneficial effects in IR of various organs. However, using garlic in IR of skeletal muscle is deficient Goals: To investigate the possible protective effect of garlic in rat model of hind limb IR and its possible mechanisms of action. METHODS Fifty adult male rats divided into five groups; C: control, IR: ischemia/reperfusion group subjected to 2 hours ischemia followed by 2 hours reperfusion (2/2 hr IR) and three garlic treated groups; G1+IR: 24 hr before I/R, G2+IR: 30 min before IR and G3+IR: immediately before reperfusion. We measured wet to dry weight ratio (W/D) of gastrocnemius muscle, serum creatine kinase (CK), Interleukin 1β (IL-1β), Interleukin-10 (IL-10), gastrocnemius caspase-3 and desmin expression and histopathological damage score. RESULTS Garlic treatment caused significant decrease in W/D, serum CK, IL-1β, caspase-3 expression and significant increase in IL-10 as well as desmin expression when compared to IR group. Garlic ameliorated IR-induced histopathological damage and significantly reduced the apoptosis score. Better results obtained with earlier administration before IR. CONCLUSION Garlic protected against IR-induced skeletal muscle damage through reducing inflammation, apoptosis score and elevating desmin expression. We recommend the earlier use of garlic as prophylactic natural medicine in skeletal muscle IR.
The Big Five Personality Traits as Predictors of Loneliness among Older Men in Israel

Abstract Loneliness may have complex implications for the mental and physical health of older people. It could have unique expressions among older men due to the social construction of gender, which raises an expectation that men should be strong, assertive, and capable of independently coping with their difficulties. As a result, older men suffering from loneliness may avoid talking about it and seeking help for this matter. The Big Five personality traits were found to be associated with many life domains, including loneliness, yet this issue has received limited research attention with regard to older adults in general and older men in particular. Therefore, the current study explores the contribution of the Big Five personality traits to understanding loneliness among older men in Israel, while controlling for several demographic factors. The data were collected through structured questionnaires administered to a sample of 392 older men. The results indicate that agreeableness, emotional stability, and openness to experiences were negatively associated with older men’s loneliness. In addition, no association was found between extraversion and conscientiousness and respondents’ loneliness, and no significant association was found between age and loneliness, and being employed and being in a relationship were associated with lower levels of loneliness. The conclusion is that it is important that professionals working with older men utilize the Big Five personality traits to understand loneliness and offer them interventions for reducing their loneliness. Furthermore, it is essential to promote social awareness of the importance of intimate relationships, as well as of employment, in the old age.
The utility of mini-Clinical Evaluation Exercise in undergraduate and postgraduate medical education: A BEME review: BEME Guide No. 59

Abstract Background: This BEME review aims at exploring, analyzing, and synthesizing the evidence considering the utility of the mini-CEX for assessing undergraduate and postgraduate medical trainees, specifically as it relates to reliability, validity, educational impact, acceptability, and cost. Methods: This registered BEME review applied a systematic search strategy in seven databases to identify studies on validity, reliability, educational impact, acceptability, or cost of the mini-CEX. Data extraction and quality assessment were carried out by two authors. Discrepancies were resolved by a third reviewer. Descriptive synthesis was mainly used to address the review questions. A meta-analysis was performed for Cronbach’s alpha. Results: Fifty-eight papers were included. Only two studies evaluated all five utility criteria. Forty-seven (81%) of the included studies met seven or more of the quality criteria. Cronbach’s alpha ranged from 0.58 to 0.97 (weighted mean = 0.90). Reported G coefficients, Standard error of measurement, and confidence interval were diverse and varied based on the number of encounters and the nested or crossed design of the study. The calculated number of encounters needed for a desirable G coefficient also varied greatly. Content coverage was reported satisfactory in several studies. Mini-CEX discriminated between various levels of competency. Factor analyses revealed a single dimension. The six competencies showed high levels of correlation with statistical significance with the overall competence. Moderate to high correlations between mini-CEX scores and other clinical exams were reported. The mini-CEX improved students’ performance in other examinations. By providing a framework for structured observation and feedback, the mini-CEX exerts a favorable educational impact. Included studies revealed that feedback was provided in most encounters but its quality was questionable. The completion rates were generally above 50%. Feasibility and high satisfaction were reported. Conclusion: The mini-CEX has reasonable validity, reliability, and educational impact. Acceptability and feasibility should be interpreted given the required number of encounters.
Synthesis and Photochemical Studies on Gallium and Indium Complexes of DTPA-PEG3-ArN3 for Radiolabeling Antibodies.

Photochemistry is a rich source of inspiration for developing alternative methods to functionalize proteins with drug molecules, fluorophores, and radioactive probes. Here, we report the synthesis and photochemical reactivity of a modified diethylenediamine pentaacetic acid chelate that was derivatized with a light-responsive aryl azide group (DTPA-PEG3-ArN3, compound 1). The corresponding nonradioactive and radioactive nat/68Ga3+ and nat/111In3+ complexes of DTPA-PEG3-ArN3 were synthesized and their physical and photochemical properties were studied to evaluate the potential of employing this ligand system in the photochemical synthesis of radiolabeled antibodies. Photodegradation kinetics revealed that irradiation with ultraviolet light (365 nm) induced rapid photoactivation of compound 1 and the metal complexes nat/68Ga-1- and nat/111In-1-. Light-induced reactions were complete in <100 s, with measured first-order rate constants of 0.078 ± 0.045 s-1, 0.093 ± 0.009 s-1, and 0.117 ± 0.054 s-1 (n = 2, per species) for compound 1, natGa-1-, and natIn-1-, respectively. Photochemically induced bioconjugation reactions between DTPA-PEG3-ArN3 and the monoclonal antibody trastuzumab, as well as pre- and postconjugation 68Ga- and 111In-radiolabeling experiments, were performed using either a one-pot or two-step strategy. Both approaches yielded radiolabeled trastuzumab ([68Ga]GaDTPA-azepin-trastuzumab) with average radiochemical conversions of 3.9 ± 1.0% (n = 4, one-pot), and 10.0 ± 1.0% (n = 3, two-step). One-pot radiolabeling reactions with [111In]InCl3 produced the corresponding [111In]InDTPA-azepin-trastuzumab radiotracer in a similar radiochemical conversion of 5.4 ± 0.8% (n = 3). Radiochemical conversions for the desired bimolecular coupling between the chelate and the protein were comparatively low. This observation is likely caused by the high photoinduced reactivity of the compounds and subsequent competition with background reactions. Nevertheless, access to DTPA-PEG3-ArN3 increases the scope of photoradiochemical methods to include metal ions like In3+ that form complexes with higher coordination numbers.
Patient Satisfaction Surveys in the Outpatient Clinic Setting: The Variability of Response With Positively or Negatively Toned Questions

The purpose of this study was to determine whether a patient satisfaction survey in the outpatient clinic setting using questions with either a positive or negative tone would produce consistent responses. This was a prospective study using a 20-question paper survey delivered to medical students who were asked to rate on a scale of 1 to 10 to what degree they either agree or disagree with statements regarding their most recent personal outpatient clinic health care visit (any medical specialty). The same survey was administered again through an e-mail link 1 week later. One hundred fifty (77%) students completed the 20-item survey and 53 (35%) of the participating students completed the follow-up e-mail survey. Seven of the 10 question pairs on the paper survey revealed statistically significant differences in responses based on tone, with greater values for disagreement with negatively toned questions than values representing agreement with positive-toned questions. The match rates for similar questions posed on the paper survey and then the e-mail survey 1 week later ranged between 27.8% and 56.6%. This study demonstrated that, with an outpatient health care patient satisfaction survey, disagreement with a negative-toned question was stronger than agreement with a positive-toned question. There was poor correlation between survey responses when first posed on a paper survey and then repeated on a digital survey 1 week later. These findings suggest that the wording of survey questions may affect responses and that survey answers change with time and across delivery platforms.
Invasive Neuromodulation as a Treatment for Tinnitus: A Systematic Review

Although the prevalence and burden of tinnitus is high, none of the available tinnitus treatments has been proven to be effective for the majority of tinnitus patients so far. Neuromodulation is currently gaining more interest to explore as tinnitus treatment. Because noninvasive neuromodulation has been shown to be effective in some tinnitus patients in the short term, more invasive techniques have been applied with variable success and without clear clinical applicability. As new insights into the neuropathophysiology of tinnitus arise, it seems essential to recapitulate the current evidence of invasive neuromodulation for tinnitus, to assess the quality of the available studies and identify gaps in this research domain.
Metformin suppresses aortic ultrastrucural damage and hypertension induced by diabetes: a potential role of advanced glycation end products

ABSTRACT Cardiovascular disease secondary to diabetes represents a significant challenge to the health community. The advanced glycation end products (AGEs) play an important role in diabetes-mediated vascular injury. We tested whether metformin can suppress aortic AGEs production and protect against aortic injuries (aortopathy) and hypertension in streptozotocin-induced type 2 diabetes mellitus (T2DM) animal model. T2DM was induced in rats two weeks after being fed on a high carbohydrate and fat diet (HCFD), and continued on a HCFD until being sacrificed at week 12 (model group). The protective group was put on metformin two weeks before diabetic induction and continued on metformin and HCFD until the end of the experiment, at week 12. Using electron microscopy examinations, we observed in the model group substantial damage to the ultrastructure of aortic endothelial and vascular smooth muscle layers as demonstrated by markedly distorted vacuolated endothelial and vascular smooth muscle cells with pyknotic nuclei detached from the underlying basement membrane, which were protected by metformin. Also, metformin significantly (p < .05) decreased both systolic and diastolic blood pressure, aortic levels of AGEs, and blood levels of oxidative stress and inflammatory biomarkers. We conclude that metformin protects against T2DM-induced aortopathy and hypertension, possibly via the inhibition of AGEs, inflammation, and oxidative stress.
Association between posttraumatic stress disorder and nonfatal drug overdose.

OBJECTIVE North America is in the midst of a growing drug overdose crisis. While prescription opioid misuse and synthetic opioids such as fentanyl have been implicated in the overdose crisis, less attention has been given to the role that posttraumatic stress disorder (PTSD) may play in this crisis. As such, this study sought to examine the relationship between PTSD and risk of nonfatal overdose among people who use drugs (PWUD). METHOD Data were derived from three prospective cohorts of PWUD in Vancouver, Canada. For each participant, PTSD was assessed using the PTSD Checklist for the DSM-5. Multivariate logistic regression analysis was used to estimate the relationship between PTSD and nonfatal overdose, adjusting for potential confounders. RESULTS Between 2016 and 2018 among 1,059 PWUD, including 363 (34%) nonmale participants, 171 (16%) experienced a nonfatal drug overdose in the past 6 months, and 414 (39%) met criteria for a provisional PTSD diagnosis. In multivariate analysis, PTSD (adjusted odds ratio = 1.98, 95% confidence interval [1.4, 2.79]) remained independently associated with nonfatal overdose after adjustment for a range of confounders. CONCLUSIONS Among participants in these community-recruited cohorts of PWUD, having a provisional PTSD diagnosis nearly doubled the risk of nonfatal overdose. The findings from this study support the need to incorporate a trauma-informed approach within the current overdose prevention framework. Education and training relating to trauma and PTSD should be prioritized for health care professionals who work with and treat PWUD. (PsycINFO Database Record (c) 2019 APA, all rights reserved).