Recent Research Articles from UNTHSC
Testing daily-level drinking and negative consequences as predictors of next-day drinking cognitions
Addict Behav. 2021 Jul 8;122:107042. doi: 10.1016/j.addbeh.2021.107042. Online ahead of print.
OBJECTIVE: Limited research has examined how alcohol use and related consequences affect drinking-related cognitions, which is important as these cognitions may contribute to future drinking. The current study examines daily associations between alcohol use and alcohol-related negative consequences with next-day Prototype Willingness Model (PWM) social reaction pathway cognitions.
METHOD: Participants ages 15-25 years (N = 124, Mean age 18.7, SD = 2.87) completed daily surveys for up to three weeks (i.e., up to 11 surveys/week) using an ecological momentary assessment design. Linear mixed models and Poisson generalized mixed models were conducted to examine whether number of alcoholic drinks or number of negative alcohol-related consequences were associated with next-day PWM social reaction cognitions, including perceived vulnerability, descriptive normative perceptions of number of drinks consumed and the percentage of friends who drink, prototype favorability, prototype similarity, and willingness (i.e., openness) to drink.
RESULTS: Within-person results indicated more alcohol use on a given day was associated with lower next-day normative perceptions of the percentage of friends who drink on that day of the week and higher prototype similarity. Furthermore, within-person results indicated that experiencing more negative alcohol-related consequences on a given day was associated with higher perceived vulnerability and lower willingness to drink the next day.
CONCLUSIONS: Findings showed that next-day social reaction PWM cognitions were associated with prior day alcohol use and negative alcohol-related consequences, suggesting that an intervention might be timed to target drinking cognitions the morning following a drinking event, particularly after experiencing negative alcohol-related consequences.
Am J Pharm Educ. 2021 Jul 22:8562. doi: 10.5688/ajpe8562. Online ahead of print.
Objective. Within pharmacy experiential education, practicing literature evaluation skills usually occurs via journal clubs. Clinical debates have gained traction as an engaging alternative during advanced pharmacy practice experiences (APPEs). The purpose of this study was to compare clinical knowledge and literature evaluation application between journal clubs and clinical debates during APPEs.Methods. This mixed-methods prospective study was conducted in fourth year pharmacy students completing inpatient general medicine APPEs at four institutions. Students participated in a journal club and clinical debate during their experience. After each, students completed a 10-item knowledge assessment. Differences in journal club and clinical debate assessment scores were analyzed. Following completion of both activities, a perception survey was administered to gauge preferences and opinions. Differences in perception survey scores for journal clubs compared to clinical debates were evaluated quantitatively and a thematic analysis was completed for qualitative responses.Results. Fifty students participated in both activities. There were no differences between journal club and clinical debate assessment scores (57.4 ± 21.0% and 62.9 ± 20.7%, respectively). Forty students completed the post-perceptions survey and globally agreed or strongly agreed that both journal clubs and clinical debates improved confidence in literature evaluation and clinical skills. Common themes identified included applicability to pharmacists' roles and need for clear instructions and examples.Conclusion. There was no difference in knowledge assessments of journal clubs versus clinical debates and students found both activities to be beneficial. Clinical debates are a reasonable alternative to journal clubs to improve knowledge and literature evaluation skills.
Effect of Dimer Structure and Inhomogeneous Broadening of Energy Levels on the Action of Flavomononucleotide in Rigid Polyvinyl Alcohol Films
Int J Mol Sci. 2021 Jul 20;22(14):7759. doi: 10.3390/ijms22147759.
The results of time-resolved fluorescence measurements of flavin mononucleotide (FMN) in rigid polyvinyl alcohol films (PVA) demonstrate that fluorescence intensity decays are strongly accelerated in the presence of fluorescent dimers and nonradiative energy transfer processes. The fluorescence decay originating both from H and J dimer states of FMN was experimentally observed for the first time. The mean fluorescence lifetimes for FMN dimers were obtained: τfl = 2.66 ns (at λexc = 445 nm) and τfl = 2.02 (at λexc = 487 nm) at λobs = 600 nm and T = 253 K from H and J state of dimers, respectively. We show that inhomogeneous orientational broadening of energy levels (IOBEL) affects the shape of the fluorescence decay and leads to the dependence of the average monomer fluorescence lifetime on excitation wavelength. IOBEL affected the nonradiative energy transfer and indicated that different flavin positioning in the protein pocket could (1) change the spectroscopic properties of flavins due to the existence of "blue" and "red" fluorescence centers, and (2) diminish the effectiveness of energy transfer between FMN molecules.
Cancers (Basel). 2021 Jul 9;13(14):3445. doi: 10.3390/cancers13143445.
Akt, also known as protein kinase B (PKB), belongs to the AGC family of protein kinases. It acts downstream of the phosphatidylinositol 3-kinase (PI3K) and regulates diverse cellular processes, including cell proliferation, cell survival, metabolism, tumor growth and metastasis. The PI3K/Akt signaling pathway is frequently deregulated in breast cancer and plays an important role in the development and progression of breast cancer. There are three closely related members in the Akt family, namely Akt1(PKBα), Akt2(PKBβ) and Akt3(PKBγ). Although Akt isoforms share similar structures, they exhibit redundant, distinct as well as opposite functions. While the Akt signaling pathway is an important target for cancer therapy, an understanding of the isoform-specific function of Akt is critical to effectively target this pathway. However, our perception regarding how Akt isoforms contribute to the genesis and progression of breast cancer changes as we gain new knowledge. The purpose of this review article is to analyze current literatures on distinct functions of Akt isoforms in breast cancer.
NRMNet: Building a National Resource for Mentorship, Networking and Professional Development to Enhance Diversity
Ethn Dis. 2021 Jul 15;31(3):469-480. doi: 10.18865/ed.31.3.469. eCollection 2021 Summer.
BACKGROUND: To address the need for diversifying the biomedical research workforce, the National Institutes of Health (NIH) established the Diversity Program Consortium (DPC) with the goal of developing, implementing, assessing, and disseminating interventions and programs to enhance the participation and persistence of individuals from underrepresented backgrounds in biomedical research careers.
INTERVENTION: As part of the DPC initiative, the NIH funded the National Research Mentoring Network (NRMN), which aimed to increase diversity of the biomedical research workforce through culturally responsive mentorship, networking, and professional development. In 2015, the NRMNet portal was developed to provide a broad-based network of mentors who are accessible to diverse mentees across the country. The portal also provides networking and professional development resources that support mentee transitions from one career stage to the next.
RESULTS: NRMNet is the gateway for career stage-specific mentorship, networking, resources, and professional development programs for trainees across the biomedical, behavioral, clinical, and social sciences. In the first five years, the NRMN strategic recruitment efforts resulted in an expanded network of nearly 13,000 diverse mentors and mentees with NRMN representation in all 50 states and Puerto Rico. Consistently, over the first five years, racial and ethnic diversity was reflected in composition of mentee and mentor groups: 66% of 6,526 mentees and 33% of 3,866 mentors were from underrepresented groups.
CONCLUSIONS: The NRMNet portal is a promising effort for enhancing participation and continued engagement of undrerepresented individuals in biomedical research careers by providing culturally responsive mentorship, networking, and professional development for individuals at all career stages.
Intermittent Hypoxia Training Prevents Deficient Learning-Memory Behavior in Mice Modeling Alzheimer's Disease: A Pilot Study
Front Aging Neurosci. 2021 Jul 1;13:674688. doi: 10.3389/fnagi.2021.674688. eCollection 2021.
In mouse models of Alzheimer's disease (AD), normobaric intermittent hypoxia training (IHT) can preserve neurobehavioral function when applied before deficits develop, but IHT's effectiveness after onset of amyloid-β (Aβ) accumulation is unclear. This study tested the hypothesis that IHT improves learning-memory behavior, diminishes Aβ accumulation in cerebral cortex and hippocampus, and enhances cerebrocortical contents of the neuroprotective trophic factors erythropoietin and brain-derived neurotrophic factor (BDNF) in mice manifesting AD traits. Twelve-month-old female 3xTg-AD mice were assigned to untreated 3xTg-AD (n = 6), AD+IHT (n = 6), and AD+sham-IHT (n = 6) groups; 8 untreated wild-type (WT) mice also were studied. AD+IHT mice alternately breathed 10% O2 for 6 min and room air for 4 min, 10 cycles/day for 21 days; AD+sham-IHT mice breathed room air. Spatial learning-memory was assessed by Morris water maze. Cerebrocortical and hippocampal Aβ40 and Aβ42 contents were determined by ELISA, and cerebrocortical erythropoietin and BDNF were analyzed by immunoblotting and ELISA. The significance of time (12 vs. 12 months + 21 days) and treatment (IHT vs. sham-IHT) was evaluated by two-factor ANOVA. The change in swimming distance to find the water maze platform after 21 d IHT (-1.6 ± 1.8 m) differed from that after sham-IHT (+5.8 ± 2.6 m). Cerebrocortical and hippocampal Aβ42 contents were greater in 3xTg-AD than WT mice, but neither time nor treatment significantly affected Aβ40 or Aβ42 contents in the 3xTg-AD mice. Cerebrocortical erythropoietin and BDNF contents increased appreciably after IHT as compared to untreated 3xTg-AD and AD+sham-IHT mice. In conclusion, moderate, normobaric IHT prevented spatial learning-memory decline and restored cerebrocortical erythropoietin and BDNF contents despite ongoing Aβ accumulation in 3xTg-AD mice.
Influence of Ischemia-reperfusion Injury on Endothelial Function in Men and Women with Similar Serum Estradiol Concentrations
Am J Physiol Regul Integr Comp Physiol. 2021 Jul 14. doi: 10.1152/ajpregu.00147.2021. Online ahead of print.
Prior data suggest that relative to the early follicular phase, women in the late follicular phase are protected against endothelial ischemia-reperfusion (I/R) injury when estradiol concentrations are highest. In addition, endothelial I/R injury is consistently observed in men with naturally low endogenous estradiol concentrations that are similar to women in the early follicular phase. Therefore, the purpose of this study was to determine if the vasodeleterious effect of I/R injury differs between women in the early follicular phase of the menstrual cycle and age-matched men. We tested the hypothesis that I/R injury would attenuate endothelium-dependent vasodilation to the same extent in women and age-matched men with similar circulating estradiol concentrations. Endothelium-dependent vasodilation was assessed via brachial artery flow-mediated dilation (duplex ultrasound) in young healthy men (N = 22) and women (N = 12) before (pre-I/R) and immediately after I/R injury (post-I/R), which was induced via 20 min of arm circulatory arrest followed by 20 min reperfusion. Serum estradiol concentrations did not differ between sexes (men, 115.0 ± 33.9 pg ml-1 vs. women, 90.5 ± 40.8 pg ml-1; P = 0.2). The magnitude by which I/R injury attenuated endothelium-dependent vasodilation did not differ between men (pre-I/R, 5.4 ± 2.4 % vs. post-I/R 3.0 ± 2.7 %;) and women (pre-I/R, 6.1 ± 2.8 % vs. post-I/R 3.7 ± 2.7 %; P = 0.9). Our data demonstrate that I/R injury similarly reduces endothelial function in women in the early follicular phase of the menstrual cycle and age-matched men with similar estradiol concentrations.
J Opioid Manag. 2021 May-Jun;17(3):215-225. doi: 10.5055/jom.2021.0632.
OBJECTIVE: Examine the relationship between prescription opioid analgesic use during pregnancy and preterm birth or term low birthweight.
DESIGN, SETTING, AND PARTICIPANTS: We analyzed data from the National Birth Defects Prevention Study, a US multisite, population-based study, for births from 1997 to 2011. We defined exposure as self-reported prescription opioid use between one month before conception and the end of pregnancy, and we dichotomized opioid use duration by ≤7 days and >7 days.
MAIN OUTCOME MEASURES: We examined the association between opioid use and preterm birth (defined as gestational age <37 weeks) and term low birthweight (defined as <2500 g at gestational age ≥37 weeks).
RESULTS: Among 10,491 singleton mother/infant pairs, 470 (4.5 percent) reported opioid use. Among women reporting opioid use, 236 (50 percent) used opioids for > 7 days; codeine (170, 36 percent) and hydrocodone (163, 35 percent) were the most commonly reported opioids. Opioid use was associated with slightly increased risk for preterm birth [adjusted odds ratio, 1.4; 95 percent confidence interval, 1.0, 1.9], particularly with hydrocodone [1.6; 1.0, 2.6], meperidine [2.5; 1.2, 5.2], or morphine [3.0; 1.5, 6.1] use for any duration; however, opioid use was not significantly associated with term low birthweight.
CONCLUSIONS: Preterm birth occurred more frequently among infants of women reporting prescription opioid use during pregnancy. However, we could not determine if these risks relate to the drug or to indications for use. Patients who use opioids during pregnancy should be counseled by their practitioners about this and other potential risks associated with opioid use in pregnancy.
J Cereb Blood Flow Metab. 2021 Jul 14:271678X211032029. doi: 10.1177/0271678X211032029. Online ahead of print.
Optimizing cerebral perfusion is key to rescuing salvageable ischemic brain tissue. Despite being an important determinant of cerebral perfusion, there are no effective guidelines for blood pressure (BP) management in acute stroke. The control of cerebral blood flow (CBF) involves a myriad of complex pathways which are largely unaccounted for in stroke management. Due to its unique anatomy and physiology, the cerebrovascular circulation is often treated as a stand-alone system rather than an integral component of the cardiovascular system. In order to optimize the strategies for BP management in acute ischemic stroke, a critical reappraisal of the mechanisms involved in CBF control is needed. In this review, we highlight the important role of collateral circulation and re-examine the pathophysiology of CBF control, namely the determinants of cerebral perfusion pressure gradient and resistance, in the context of stroke. Finally, we summarize the state of our knowledge regarding cardiovascular and cerebrovascular interaction and explore some potential avenues for future research in ischemic stroke.
MyNRMN: A national mentoring and networking platform to enhance connectivity and diversity in the biomedical sciences
FASEB Bioadv. 2021 Mar 31;3(7):497-509. doi: 10.1096/fba.2020-00102. eCollection 2021 Jul.
AIMS: Increasing the diversity of the biomedical sciences workforce is a national priority. Having a mentor, and more crucially, a personal network of mentors, improves the likelihood that an individual will pursue an advanced degree and career in the biomedical sciences. The chief mission of the National Research Mentoring Network (NRMN) is to reduce racial and ethnic disparities in the biosciences workforce through the mentoring of historically underrepresented individuals.
METHODS: To address this need, we created MyNRMN, an online mentoring platform that connects mentors and mentees nationwide. The platform enables multiple forms of mentoring and recommends connections to mentees that will help them build their personal networks.
RESULTS: The MyNRMN online platform has registered more than 13,500 active mentors and mentees across all 50 states and from more than 2100 institutions. Black and Hispanic mentees are highly represented.
DISCUSSION: MyNRMN has expanded opportunities for mentorship in the biomedical sciences, particularly among those not from a culture or institution that historically supports mentorship. The platform's robust search and recommendation capabilities and graph database technology enable members to grow their personal network of mentors.
CONCLUSION: The MyNRMN online platform has proven successful in connecting mentees and mentors nationwide, expanding the pipeline in biomedical science careers to attract a more diverse workforce.
Community Dent Oral Epidemiol. 2021 Jul 12. doi: 10.1111/cdoe.12678. Online ahead of print.
OBJECTIVES: Healthcare (including dental care) service use is influenced by predisposing, enabling and need factors. One area with limited research is the association of acculturation (defined as behavioural changes in the adaptation to another culture) as a predisposing factor for dental care preventive service use. Preventive service use is a primary objective of Healthy People, 2030. The purpose of this study was to determine the association of acculturation with the preventive dental service use of dental pit-and-fissure sealant placement, among children in the United States, ages 6-18 years.
METHODS: A cross-sectional, secondary data analysis study was completed using National Health and Nutrition Examination Survey (NHANES), 2013-2016 data. NHANES is a nationally representative survey of noninstitutionalized individuals across the United States. In the data set, children, ages 6-18 years, had been evaluated for pit-and-fissure dental sealant use. Information that served as proxies for acculturation was length of stay in the United States (a citizen at the time of the survey; not a citizen and in the country <5 years; or not a citizen and in the country ≥5 years) and whether English was spoken at home (yes; no). Data were analysed for descriptive statistics. Multivariable logistic regressions were used to examine strength of the associations. Odds ratios for pit-and-fissure sealants among groups were determined.
RESULTS: There were 2220 children participants whose data were used for this study. Less than half (45.5%) had received dental pit-and-fissure sealants. A majority (53.3%) were white and were ages 12-18 years (51.6%). The mean number of dental pit-and-fissure sealants among all children was 5.5. There was a lower percentage of children living in the United States <5 years who had received pit-and-fissure sealants than children who were citizens of the United States (22.2% vs 48.9%, respectively). The adjusted odds ratio was lower for dental pit-and-fissure sealants among children who were in the United States <5 years than children who were citizens of the United States (adjusted odds ratio, 0.38; 95% Confidence Interval: 0.24, 0.58).
CONCLUSIONS: In this study, children who had lived in the United States <5 years were less likely to have pit-and-fissure sealants than children who were citizens of the United States. There is a need to reach all children with preventive services to improve dental quality of life, reduce the need for dental restorations and decrease overall financial burden regardless of time in the United States.
J Physiol. 2021 Jul 10. doi: 10.1113/JP281730. Online ahead of print.
KEY POINTS: Humans suffering from polycythaemia undergo multiple circulatory adaptations including changes in blood rheology and structural and functional vascular adaptations to maintain normal blood pressure and vascular shear stresses, despite high blood viscosity. During exercise, several circulatory adaptations are observed, especially involving adrenergic and non-adrenergic mechanisms within non-active and active skeletal muscle to maintain exercise capacity, which is not observed in animal models. Despite profound circulatory stress, i.e., polycythaemia, several adaptations can occur to maintain exercise capacity, therefore making early identification of the disease difficult without overt symptomology. Pharmacological treatment of the background heightened sympathetic activity may impair the adaptive sympathetic response needed to match local oxygen delivery to active skeletal muscle oxygen demand and therefore inadvertently impair exercise capacity.
ABSTRACT: Excessive haematocrit and blood viscosity can increase blood pressure, cardiac work and reduce aerobic capacity. However, past clinical investigations have demonstrated that certain human high-altitude populations suffering from excessive erythrocytosis, Andeans with chronic mountain sickness, appear to have phenotypically adapted to life with polycythaemia, as their exercise capacity is comparable to healthy Andeans and even with sea level inhabitants residing at high altitude. By studying this unique population, which has adapted thru natural selection, this study aimed to describe how humans can adapt to life with polycythaemia. Experimental studies included Andeans with (n = 19) and without (n = 17) chronic mountain sickness, documenting exercise capacity, and characterizing the transport of oxygen thru blood rheology, including haemoglobin mass, blood and plasma volume & blood viscosity, cardiac output, blood pressure and changes in total and local vascular resistances thru pharmacological dissected of α-adrenergic signalling pathways within non-active and active skeletal muscle. At rest, Andeans with chronic mountain sickness had a substantial plasma volume contraction, which alongside a higher red blood cell volume, caused an increase in blood viscosity yet similar total blood volume. Moreover, both morphological and functional alterations in the periphery normalized vascular shear stress and blood pressure despite high sympathetic nerve activity. During exercise, blood pressure, cardiac work and global oxygen delivery increased similar to healthy Andeans but were sustained by modifications in both non-active and active skeletal muscle vascular function. These findings highlight widespread physiological adaptations that can occur in response to polycythaemia, which allow the maintenance of exercise capacity. This article is protected by copyright. All rights reserved.
Impact of Fall Risk and Direct Oral Anticoagulant Treatment on Quality-Adjusted Life-Years in Older Adults with Atrial Fibrillation: A Markov Decision Analysis
Drugs Aging. 2021 Jul 8. doi: 10.1007/s40266-021-00870-6. Online ahead of print.
BACKGROUND AND OBJECTIVE: The decision to initiate anticoagulation in older adults with atrial fibrillation is complicated by the benefit of ischemic stroke prevention vs the risk of falls resulting in major bleeds. The objective of this study was to assess the impact of different treatments including direct oral anticoagulants on quality-adjusted life-years (QALYs) in patients aged 75 years and older with atrial fibrillation in the context of falls.
METHODS: A Markov decision process was constructed for older patients with atrial fibrillation taking no anti-thrombotic, aspirin, warfarin, rivaroxaban, and apixaban. Input probabilities for clinical events were estimated from the available literature. One-way and two-way sensitivity analyses were performed by measuring the impact of varying input probabilities of clinical events on QALY outcomes.
RESULTS: The base-case scenario estimated that older adults treated with no anti-thrombotic, aspirin, warfarin, rivaroxaban, and apixaban had QALYs of 8.03, 8.69, 10.38, 11.02, and 11.56, respectively. The sensitivity analysis estimated that an older adult would need to fall over 45 (rivaroxaban) and 458 (apixaban) times per year for the QALY of a direct oral anticoagulant to be lower than that of aspirin.
CONCLUSIONS: Older adults with atrial fibrillation benefit from stroke protection of anticoagulants, especially direct oral anticoagulants, even if they are at high risk of falls. Clinicians should not consider fall risk as a deciding factor for withholding anticoagulation in this population of patients.
Functional Ability Classification Based on Moderate and Severe Kinesophobia and Demoralization Scores in Degenerative Spine Patients
Spine (Phila Pa 1976). 2021 Aug 1;46(15):E826-E831. doi: 10.1097/BRS.0000000000003943.
STUDY DESIGN: A prospective cohort study.
OBJECTIVE: To assess the relationship of fear avoidance and demoralization on gait and balance and determine a threshold score for the Tampa Scale for Kinesophobia (TSK) and the Demoralization Scale (DS) that identifies spine patients with gait and balance dysfunction amplified by underlying psychological factors.
SUMMARY OF BACKGROUND DATA: Fear avoidance and demoralization are crucial components of mental health that impact the outcomes in spine surgery. However, interpreting their effect on patient function remains challenging. Further establishing this correlation and identifying a threshold of severity can aid in identifying patients in whom a portion of their altered gait and balance may be amplified by underlying psychologic distress.
METHODS: Four hundred five symptomatic spine patients were given the TSK and DS questionnaires. Patient's gait and balance were tested with a human motion capture system. A TSK score of 41 and a DS score of 30 were chosen as thresholds to classify moderate versus severe dysfunction based on literature and statistical analysis.
RESULTS: Higher TSK and DS scores were correlated with worse walking speed (P < 0.001), longer stride time (P = 0.001), decreased stride length (P < 0.048), and wider step width (<0.001) during gait as well as increased sway across planes (P = 0.001) during standing balance. When classified by TSK scores >41, patients with more severe fear avoidance had slower walking speed (P < 0.001), longer stride time (P = 0.001), shorter stride length (P = 0.004), increased step width (P < 0.001), and increased sway (P = 0.001) compared with their lower scoring counterparts. Similarly, patients with DS > 30 had slower walking speed (P = 0.012), longer stride time (P = 0.022), and increased sway (P = 0.003) compared with their lower scoring counterparts.
CONCLUSION: This study demonstrates that fear avoidance and demoralization directly correlate with worsening gait and balance. Furthermore, patients with TSK > 41 and DS > 30 have more underlying psychological factors that contribute to significantly worse function compared with lower scoring peers. Understanding this relationship and using these guidelines can help identify and treat patients whose gait dysfunction may be amplified by psychologic distress.Level of Evidence: 3.
Transl Stroke Res. 2021 Jul 5. doi: 10.1007/s12975-021-00916-2. Online ahead of print.
The ischemic penumbra defined four decades ago has been the main battleground of ischemic stroke. The evolving ischemic penumbra concept has been providing insight for the development of vascular and cellular approaches as well as diagnostic tools for the treatment of ischemic stroke. rt-PA thrombolytic therapy to prevent the transition of ischemic penumbra to core has been approved for acute ischemic stroke within 3 h and was later recommended to extend to 4.5 h after symptom onset. Mechanical thrombectomy was introduced for the treatment of acute ischemic stroke with a therapeutic window of up to 24 h after stroke onset. Multiple modalities brain imaging techniques have been developed that provide guidance to define ischemic penumbra for reperfusion therapy in clinical practice. Cellular and molecular dissection of ischemic penumbra has been providing targets for the development of neuroprotective therapy for ischemic stroke. However, the dynamic nature of ischemic penumbra implicates that infarct core eventually expands into penumbra over time without reperfusion, dictating relative short therapeutic windows and limiting the impact of current reperfusion intervention. Entering the 5th decade since the introduction, ischemic penumbra remains the main focus of ischemic stroke research and clinical practice. In this review, we summarized the evolving ischemic penumbra concept and its implication in the development of vascular and cellular interventions as well as diagnostic tools for acute ischemic stroke. In addition, we discussed future perspectives on expansion of the campaign beyond ischemic penumbra to develop treatment for ischemic stroke.
Proc (Bayl Univ Med Cent). 2021 Mar 23;34(4):469-472. doi: 10.1080/08998280.2021.1899730.
Cutaneous injury and irritation among health care workers has substantially risen during the COVID-19 pandemic. In a field already laden with skin-induced injury and irritation due to high levels of handwashing and glove wearing, increases have been reported in handwashing-induced xerosis, irritant dermatitis, and contact dermatitis from N95 respirators and other surgical masks. Masks, goggles, face shields, and gloves all potentially create abrasions from long hours of use, leading to itching, pain, and aggravation of underlying skin conditions. Personal protective equipment (PPE)-related skin injury can be serious, and the American Academy of Dermatology has released recommendations on preventing and treating occupationally induced dermatologic conditions during the COVID-19 pandemic. These are reviewed and discussed in conjunction with overarching guidelines for mitigating the spread of the virus.
Exercise as a multi-modal disease-modifying medicine in systemic sclerosis: An introduction by The Global Fellowship on Rehabilitation and Exercise in Systemic Sclerosis (G-FoRSS)
Best Pract Res Clin Rheumatol. 2021 Jun 30:101695. doi: 10.1016/j.berh.2021.101695. Online ahead of print.
Systemic sclerosis (SSc) is a heterogeneous multisystem autoimmune disease whereby its main pathological drivers of disability and damage are vascular injury, inflammatory cell infiltration, and fibrosis. These mechanisms result in diffuse and diverse impairments arising from ischemic circulatory dysfunction leading to painful skin ulceration and calcinosis, neurovascular aberrations hindering gastrointestinal (GI) motility, progressive painful, incapacitating or immobilizing effects of inflammatory and fibrotic effects on the lungs, skin, articular and periarticular structures, and muscle. SSc-related impairments impede routine activities of daily living (ADLs) and disrupt three critical life areas: work, family, social/leisure, and also impact on psychological well-being. Physical activity and exercise are globally recommended; however, for connective tissue diseases, this guidance carries greater impact on inflammatory disease manifestations, recovery, and cardiovascular health. Exercise, through myogenic and vascular phenomena, naturally targets key pathogenic drivers by downregulating multiple inflammatory and fibrotic pathways in serum and tissue, while increasing circulation and vascular repair. G-FoRSS, The Global Fellowship on Rehabilitation and Exercise in Systemic Sclerosis recognizes the scientific basis of and advocates for education and research of exercise as a systemic and targeted SSc disease-modifying treatment. An overview of biophysiological mechanisms of physical activity and exercise are herein imparted for patients, clinicians, and researchers, and applied to SSc disease mechanisms, manifestations, and impairment. A preliminary guidance on exercise in SSc, a research agenda, and the current state of research and outcome measures are set forth.
Sci Rep. 2021 Jul 1;11(1):13627. doi: 10.1038/s41598-021-93164-1.
Corneal innervation plays a major role in the pathobiology of diabetic corneal disease. However, innervation impact has mainly been investigated in the context of diabetic epitheliopathy and wound healing. Further studies are warranted in the corneal stroma-nerve interactions. This study unravels the nerve influence on corneal stroma metabolism. Corneal stromal cells were isolated from healthy (HCFs) and diabetes mellitus (Type1DM and Type2 DM) donors. Cells were cultured on polycarbonate membranes, stimulated by stable Vitamin C, and stroma-only and stroma-nerve co-cultures were investigated for metabolic alterations. Innervated compared to stroma-only constructs exhibited significant alterations in pyrimidine, glycerol phosphate shuttle, electron transport chain and glycolysis. The most highly altered metabolites between healthy and T1DMs innervated were phosphatidylethanolamine biosynthesis, and pyrimidine, methionine, aspartate metabolism. Healthy and T2DMs main pathways included aspartate, glycerol phosphate shuttle, electron transport chain, and gluconeogenesis. The metabolic impact on T1DMs and T2DMs was pyrimidine, purine, aspartate, and methionine. Interestingly, the glucose-6-phosphate and oxaloacetate was higher in T2DMs compared to T1DMs. Our in vitro co-culture model allows the examination of key metabolic pathways corresponding to corneal innervation in the diabetic stroma. These novel findings can pave the way for future studies to fully understand the metabolic distinctions in the diabetic cornea.
[β-Glu<sup>2</sup>]TRH Is a Functional Antagonist of Thyrotropin-Releasing Hormone (TRH) in the Rodent Brain
Int J Mol Sci. 2021 Jun 9;22(12):6230. doi: 10.3390/ijms22126230.
Selective antagonists of thyrotropin-releasing hormone (TRH; pGlu-His-Pro-NH2), in order to enable a better understanding of this peptide's central functions, have not been identified. Using pGlu-Glu-Pro-NH2 ([Glu2]TRH) as a lead peptide and with modification at its central residue, our studies focused on some of its analogues synthesized as potential functional antagonists of TRH in the rodent brain. Among the peptides studied, the novel isomeric analogue [β-Glu2]TRH was found to suppress the analeptic and antidepressant-like pharmacological activities of TRH without eliciting intrinsic effects in these paradigms. [β-Glu2]TRH also completely reversed TRH's stimulation of acetylcholine turnover in the rat hippocampus without a cholinergic activity of its own, which was demonstrated through in vivo microdialysis experiments. Altogether, [β-Glu2]TRH emerged as the first selective functional antagonist of TRH's prominent cholinergic actions, by which this endogenous peptide elicits a vast array of central effects.
Development of In Situ Self-Assembly Nanoparticles to Encapsulate Lopinavir and Ritonavir for Long-Acting Subcutaneous Injection
Pharmaceutics. 2021 Jun 18;13(6):904. doi: 10.3390/pharmaceutics13060904.
Most antiretroviral medications for human immunodeficiency virus treatment and prevention require high levels of patient adherence, such that medications need to be administered daily without missing doses. Here, a long-acting subcutaneous injection of lopinavir (LPV) in combination with ritonavir (RTV) using in situ self-assembly nanoparticles (ISNPs) was developed to potentially overcome adherence barriers. The ISNP approach can improve the pharmacokinetic profiles of the drugs. The ISNPs were characterized in terms of particle size, drug entrapment efficiency, drug loading, in vitro release study, and in vivo pharmacokinetic study. LPV/RTV ISNPs were 167.8 nm in size, with a polydispersity index of less than 0.35. The entrapment efficiency was over 98% for both LPV and RTV, with drug loadings of 25% LPV and 6.3% RTV. A slow release rate of LPV was observed at about 20% on day 5, followed by a sustained release beyond 14 days. RTV released faster than LPV in the first 5 days and slower than LPV thereafter. LPV trough concentration remained above 160 ng/mL and RTV trough concentration was above 50 ng/mL after 6 days with one subcutaneous injection. Overall, the ISNP-based LPV/RTV injection showed sustained release profiles in both in vitro and in vivo studies.