• Commentary: Does an expeditious evaluation for high-acuity lung transplant recipients make a difference?

      Shah, Aakash; Pasrija, Chetan; Madathil, Ronson J; Lau, Christine L (Mosby Inc., 2020-03-19)
      A growing body of research has suggested that people with schizophrenia (SZ) exhibit altered patterns of functional and anatomical brain connectivity. For example, many previous resting state functional connectivity (rsFC) studies have shown that, compared to healthy controls (HC), people with SZ demonstrate hyperconnectivity between subregions of the thalamus and sensory cortices, as well as hypoconnectivity between subregions of the thalamus and prefrontal cortex. In addition to thalamic findings, hypoconnectivity between cingulo-opercular brain regions thought to be involved in salience detection has also been commonly reported in people with SZ. However, previous studies have largely relied on seed-based analyses. Seed-based approaches require researchers to define a single a priori brain region, which is then used to create a rsFC map across the entire brain. While useful for testing specific hypotheses, these analyses are limited in that only a subset of connections across the brain are explored. In the current manuscript, we leverage novel network statistical techniques in order to detect latent functional connectivity networks with organized topology that successfully differentiate people with SZ from HCs. Importantly, these techniques do not require a priori seed selection and allow for whole brain investigation, representing a comprehensive, data-driven approach to determining differential connectivity between diagnostic groups. Across two samples, (Sample 1: 35 SZ, 44 HC; Sample 2: 65 SZ, 79 HC), we found evidence for differential rsFC within a network including temporal and thalamic regions. Connectivity in this network was greater for people with SZ compared to HCs. In the second sample, we also found evidence for hypoconnectivity within a cingulo-opercular network of brain regions in people with SZ compared to HCs. In summary, our results replicate and extend previous studies suggesting hyperconnectivity between the thalamus and sensory cortices and hypoconnectivity between cingulo-opercular regions in people with SZ using data-driven statistical and graph theoretical techniques.
    • Walk the Line-The Importance of Well-Informed Interpretation of QT Prolongation.

      Noel, Zachary R; See, Vincent Y; Flannery, Alexander H (SAGE Publications Inc., 2020-06-13)
      Acute care pharmacists play an integral role in identifying drug-drug interactions that may predispose patients to QT prolongation. Although most pharmacists are equipped with a baseline understanding of drug interactions and the risks of QTc prolongation, few understand the limitations of QTc calculation and interpretation. In this commentary, we put forth the notion that at times health care providers, including pharmacists, place an overemphasis on the QTc interval. In the context of using the QTc to guide pharmacotherapy decisions, unintended consequences may include a cascade of effects leading to delays in treatment, suboptimal medication selection, alert fatigue, and overutilization of resources.
    • Listeria Meningitis: An Inconsistent Organism Causing an Inconsistent Disease.

      Hauser, Naomi; Luethy, Paul M; Stamatos, Nicholas (Elsevier Inc., 2020-07-24)
    • Optogenetic activation of muscle contraction .

      Ganji, Elahe; Chan, C Savio; Ward, Christopher W; Killian, Megan L (Taylor and Francis Inc., 2020-08-10)
      Purpose: Optogenetics is an emerging alternative to traditional electrical stimulation to initiate action potentials in activatable cells both ex vivo and in vivo. Optogenetics has been commonly used in mammalian neurons and more recently, it has been adapted for activation of cardiomyocytes and skeletal muscle. Therefore, the aim of this study was to evaluate the stimulation feasibility and sustain isometric muscle contraction and limit decay for an extended period of time (1s), using non-invasive transdermal light activation of skeletal muscle (triceps surae) in vivo. Materials and Methods: We used inducible Cre recombination to target expression of Channelrhodopsin-2 (ChR2(H134R)-EYFP) in skeletal muscle (Acta1-Cre) in mice. Fluorescent imaging confirmed that ChR2 expression is localized in skeletal muscle and does not have specific expression in sciatic nerve branch, therefore, allowing for non-nerve mediated optical stimulation of skeletal muscle. We induced muscle contraction using transdermal exposure to blue light and selected 10 Hz stimulation after controlled optimization experiments to sustain prolonged muscle contraction. Results: Increasing the stimulation frequency from 10 Hz to 40 Hz increased the muscle contraction decay during prolonged 1s stimulation, highlighting frequency dependency and importance of membrane repolarization for effective light activation. Finally, we showed that optimized pulsed optogenetic stimulation of 10 Hz resulted in comparable ankle torque and contractile functionality to that of electrical stimulation. Conclusions: Our results demonstrate the feasibility and repeatability of non-invasive optogenetic stimulation of muscle in vivo and highlight optogenetic stimulation as a powerful tool for non-invasive in vivo direct activation of skeletal muscle.
    • The addition of spices and herbs to vegetables in the National School Lunch Program increased vegetable intake at an urban, economically-underserved, and predominantly African-American high school.

      D'Adamo, Christopher R; Parker, Elizabeth A; McArdle, Patrick F; Trilling, Ariel; Bowden, Brandin; Bahr-Robertson, Mary K; Keller, Kathleen L; Berman, Brian M (Elsevier Ltd., 2020-09-01)
      Vegetable intake is far below recommendations among African-American adolescents living in economically-underserved urban areas. While the National School Lunch Program (NSLP) helps overcome access barriers, vegetable intake remains challenging and novel interventions are required. A two-year, multi-phase, school-based intervention was conducted at an urban, economically-underserved, and predominantly African-American high school in Baltimore, Maryland to determine whether stakeholder-informed addition of spices and herbs to NSLP vegetables would increase intake. The stakeholder engagement phase included assessment of NSLP vegetable attitudes/preferences among 43 school stakeholders and subsequent student sensory testing. The second phase was conducted in the school cafeteria and consisted of eight weeks comparing student intake of typical vegetable recipes versus otherwise-identical recipes with spices and herbs. 4570 student lunch plates were included in the vegetable intake comparison. Vegetable intake was measured by lunch tray plate waste. Willingness to try vegetables was assessed by the difference between plate waste and estimated mean vegetable served weight. Intake of typical vegetable recipes and vegetable recipes with spices and herbs was compared with student's t-test. Chi-square test was used to compare willingness to try vegetables. Total vegetable intake was 18.2% higher (8.22 g per meal, p < 0.0001) with spices and herbs than with typical recipes. There were no differences in trying vegetables with spices and herbs, although student-led advocacy was associated with increased trying vegetables with spices and herbs (78.8% with advocacy, 67.5% without advocacy, p < 0.0001). The addition of spices and herbs to vegetables in the NSLP was feasible and associated with small increases in vegetable intake at an urban, economically-underserved, and predominantly African-American high school.
    • Angiotensin II and Vasoplegia in Cardiac Surgery: Paradigm Changer or Costly Contender?

      Chow, Jonathan H; Strauss, Erik; Mazzeffi, Michael A (W.B. Saunders, 2020-09-03)
    • US Radiation Oncologists (Re)Defined: An American Society for Radiation Oncology Scope of Practice Study.

      Fung, Claire Y; Vapiwala, Neha; Mattes, Malcolm D; Mohindra, Pranshu; Shah, Chirag; Yechieli, Raphael; Truong, Minh-Tam; Sanders, Tim; Arnone, Anna; Royce, Trevor J; et al. (Elsevier Ltd., 2020-09-18)
      Purpose: To assess US radiation oncologists’ views on practice scope and the ideal role of the radiation oncologist (RO), the American Society for Radiation Oncology (ASTRO) conducted a scope of practice survey. Methods and Materials: In spring 2019, ASTRO distributed an online survey to 3822 US RO members. The survey generated 984 complete responses (26% response rate) for analysis. Face validity testing confirmed respondents were representative of ASTRO's RO membership. Results: Nearly all respondents agreed that “ROs should be leaders in oncologic care.” Respondents indicated the ideal approach to patient care was to provide “an independent opinion on radiation therapy and other treatment options” (82.5%) or “an independent opinion on radiation therapy but not outside of it” (16.1%), with only 1.4% favoring provision of “radiation therapy at the request of the referring physician” as the ideal approach. Actual practice fully matched the ideal approach in 18.2% of respondents. For the remaining majority, actual practice did not always match the ideal and comprised a mix of approaches that included providing radiation at the referring physician's request 24.0% of the time on average. Reasons for the mismatch included fear of alienating referring physicians and concern for offering an unwelcome opinion. One-fifth of respondents expressed a desire to expand the scope of service though interspecialty politics and insufficient training were potential barriers. Respondents interested in expanding scope of practice were on average earlier in their career (average years in practice 13.3) than those who were not interested (average years in practice 17.2, P < .001). Radiopharmaceuticals administration, medical marijuana and anticancer medications prescribing, and RO inpatient service represented areas of interest for expansion but also knowledge gaps. Conclusions: These results provide insight regarding US ROs’ scope of practice and attitudes on the ideal role of the RO. For most ROs, to provide an independent opinion on treatment options represented the ideal approach to care, but barriers such as concern of alienating referring physicians prevented many from fully adhering to their ideal in practice. Actual practice commonly comprised a mixed approach, including the least favored scenario of delivering radiation at the referring physician's request one-quarter of the time, highlighting the influence of interspecialty politics on practice behavior. Advocacy for open communication and meaningful interdisciplinary collaboration presents an actionable solution toward a more balanced relationship with other specialties as ROs strive to better fulfill the vision of being leaders in oncologic care and being our best for our patients. The study also identified interest in expanding into nontraditional domains that offer opportunities to address unmet needs in the cancer patient's journey and elevate radiation oncology within the increasingly value-based US health care system.
    • A Cross-sectional Survey on the Impact of Coronavirus Disease 2019 on the Clinical Practice of Endodontists across the United States.

      Martinho, Frederico C; Griffin, Ina L (Elsevier Ltd., 2020-10-12)
      This survey investigated the effect of the coronavirus disease 2019 (COVID-19) pandemic on the clinical practice of endodontics among the American Association of Endodontists (AAE) members by evaluating the impact on clinical activities, patient screening, infection control measurements, potential transmission, clinical protocols, as well as psychological concerns. A descriptive, cross-sectional survey was developed to query AAE members from all 7 districts. The survey consisted of 24 questions, 8 demographic questions and 16 questions related to the COVID-19 pandemic impact on the clinical practice. A total of 454 AAE members participated in the survey. As of July 2020, most endodontists were active in front-line treatment of dental patients (82%). N95 respirator face mask was described by 83.1% of the participants as special measures beyond the regular personal protective equipment. Rubber dam isolation was recognized by the majority of the participants at some level to reduce the chance of COVID-19 cross infection. Most of the endodontist participants acknowledged trauma followed by swelling, pain, and postoperative complication to be emergencies. The majority of respondents reported being concerned about the effect of COVID-19 on their practice. No differences in worries about COVID-19 infection were related to demographics (P > .05). The majority of the endodontists are aware of the COVID-19 pandemic, are taking special precautions, and are concerned about contracting and spreading the virus. Despite the conflict between their roles as health care providers and family members with the potential risk of exposing their families, most of them remain on duty providing front-line care for dental treatment.
    • Reduction in Revascularization With Icosapent Ethyl: Insights From REDUCE-IT Revascularization Analyses.

      Peterson, Benjamin E; Bhatt, Deepak L; Steg, Ph Gabriel; Miller, Michael; Brinton, Eliot A; Jacobson, Terry A; Ketchum, Steven B; Juliano, Rebecca A; Jiao, Lixia; Doyle, Ralph T; et al. (Wolters Kluwer Health, 2020-11-05)
      A total of 8179 randomly assigned patients were followed for 4.9 years (median). First revascularizations were reduced to 9.2% (22.5/1000 patient-years) with icosapent ethyl versus 13.3% (33.7/1000 patient-years) with placebo (hazard ratio, 0.66 [95% CI, 0.58-0.76]; P<0.0001; number needed to treat for 4.9 years=24); similar reductions were observed in total (first and subsequent) revascularizations (negative binomial rate ratio, 0.64 [95% CI, 0.56-0.74]; P<0.0001), and across elective, urgent, and emergent revascularizations. Icosapent ethyl significantly reduced percutaneous coronary intervention (hazard ratio, 0.68 [95% CI, 0.59-0.79]; P<0.0001) and coronary artery bypass grafting (hazard ratio, 0.61 [95% CI, 0.45-0.81]; P=0.0005).
    • SARS-CoV-2 and nervous system: From pathogenesis to clinical manifestation.

      Keyhanian, Kiandokht; Umeton, Raffaella Pizzolato; Mohit, Babak; Davoudi, Vahid; Hajighasemi, Fatemeh; Ghasemi, Mehdi (Elsevier B.V., 2020-11-07)
      Since the coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a growing body of evidence indicates that besides common COVID-19 symptoms, patients may develop various neurological manifestations affecting both the central and peripheral nervous systems as well as skeletal muscles. These manifestations can occur prior, during and even after the onset of COVID-19 general symptoms. In this Review, we discuss the possible neuroimmunological mechanisms underlying the nervous system and skeletal muscle involvement, and viral triggered neuroimmunological conditions associated with SARS-CoV-2, as well as therapeutic approaches that have been considered for these specific complications worldwide.
    • Chronic verrucous plaques on bilateral lower extremities.

      Bulte, Camille A; Clements, Stephanie; Driscoll, Marcia S (Elsevier Ltd., 2020-11-09)
    • Optimizing preventive medicine to bridge the gap between clinical medicine and public health for disease control in China: A lesson from COVID-19.

      Zeng, Wu; Li, Guohong; Turbat, Vincent; Hu, Guoqing; Ahn, Haksoon; Shen, Jie (Elsevier Ltd., 2020-11-10)
      The pandemic of Coronavirus Disease 2019 (COVID-19) highlights the importance of early detection of disease outbreaks, taking swift and decisive public health actions, and strengthening public health systems. Preventive medicine, as a specialty of medicine, trains students on both clinical medicine and public health and is of a particular need in battling against this pandemic. In China, preventive medicine plays a unique role in the disease control system where preventive medicine graduates represent a large share of the workforce. However, there is a shortage of qualified staff in the Chinese disease control system. The reasons for such a shortage are multifaceted. From the human resource perspective, the undergraduate preventive medicine curricula and exclusive public health training for preventive medicine postgraduates limit their clinical capacities. A series of disease control and public health education reforms may further incapacitate preventive medicine graduates' clinical skills, unintentionally widening the gap between public health and clinical medicine and thus posing threats to effective disease detection and control. The authors call for reforming and optimizing preventive medicine to bridge the gap between clinical medicine and public health by strengthening curricula on clinical medicine, diversifying curricula on public health, enhancing preventive medicine residency programs, and rectifying regulations that restrict preventive medicine graduates from practicing curative medicine.
    • Medications in Post-Acute and Long-Term Care: Challenges and Controversies

      Sloane, Philip D; Brandt, Nicole J; Cherubini, Antonio; Dharmarajan, T S; Dosa, David; Hanlon, Joseph T; Katz, Paul; Koopmans, Raymond T C M; Laird, Rosemary D; Petrovic, Mirko; et al. (American Medical Association, 2020-11-27)
    • Durability of Responses after SARS-CoV-2 mRNA-1273 Vaccination.

      Widge, Alicia T; Rouphael, Nadine G; Jackson, Lisa A; Anderson, Evan J; Roberts, Paul C; Makhene, Mamodikoe; Chappell, James D; Denison, Mark R; Stevens, Laura J; Pruijssers, Andrea J; et al. (Massachusetts Medical Society, 2020-12-03)
    • A rare case of extensive sternoclavicular septic arthritis treated without surgical intervention.

      Doub, James B (Elsevier Ltd., 2020-12-09)
      This is a rare case of a 55 year-old immunocompetent female who developed Methicillin sensitive Staphylococcus aureus sternoclavicular septic arthritis. The infection was not limited to the joint space but extended into adjacent bones and superior mediastinum. However the patient was successfully treated without surgical intervention and preservation of joint function was obtained with only intravenous antibiotic therapy.
    • Control of synaptic transmission and neuronal excitability in the parabrachial nucleus.

      Cramer, Nathan; Silva-Cardoso, Gleice; Masri, Radi; Keller, Asaf (Elsevier B.V., 2020-12-14)
      The parabrachial nucleus (PB) is a hub for aversive behaviors, including those related to pain. We have shown that the expression of chronic pain is causally related to amplified activity of PB neurons, and to changes in synaptic inhibition of these neurons. These findings indicate that regulation of synaptic activity in PB may modulate pain perception and be involved in the pathophysiology of chronic pain. Here, we identify the roles in PB of signaling pathways that modulate synaptic functions. In pharmacologically isolated lateral PB neurons in acute mouse slices we find that baclofen, a GABAB receptor agonist, suppresses the frequency of miniature inhibitory and excitatory postsynaptic currents (mIPSCs and mEPSC). Activation of µ-opioid peptide receptors with DAMGO had similar suppressive effects on excitatory and inhibitory synapses, while the κ-opioid peptide receptor agonist U-69593 suppressed mIPSC release but had no consistent effects on mEPSCs. Activation of cannabinoid type 1 receptors with WIN 55,212-2 reduced the frequency of both inhibitory and excitatory synaptic events, while the CB1 receptor inverse agonist AM251 had opposite effects on mIPSC and mEPSC frequencies. AM251 increased the frequency of inhibitory events but led to a reduction in excitatory events through a GABAB mediated mechanism. Although none of the treatments produced a consistent effect on mIPSC or mEPSC amplitudes, baclofen and DAMGO both reliably activated a postsynaptic conductance. These results demonstrate that multiple signaling pathways can alter synaptic transmission and neuronal excitability in PB and provide a basis for investigating the contributions of these systems to the development and maintenance of chronic pain.
    • Mobile device location data reveal human mobility response to state-level stay-at-home orders during the COVID-19 pandemic in the USA

      Xiong, Chenfeng; Hu, Songhua; Yang, Mofeng; Younes, Hannah; Luo, Weiyu; Ghader, Sepehr; Zhang, Lei (The Royal Society, 2020-12-16)
      One approach to delaying the spread of the novel coronavirus (COVID-19) is to reduce human travel by imposing travel restriction policies. Understanding the actual human mobility response to such policies remains a challenge owing to the lack of an observed and large-scale dataset describing human mobility during the pandemic. This study uses an integrated dataset, consisting of anonymized and privacy-protected location data from over 150 million monthly active samples in the USA, COVID-19 case data and census population information, to uncover mobility changes during COVID-19 and under the stay-at-home state orders in the USA. The study successfully quantifies human mobility responses with three important metrics: daily average number of trips per person; daily average person-miles travelled; and daily percentage of residents staying at home. The data analytics reveal a spontaneous mobility reduction that occurred regardless of government actions and a 'floor' phenomenon, where human mobility reached a lower bound and stopped decreasing soon after each state announced the stay-at-home order. A set of longitudinal models is then developed and confirms that the states' stay-at-home policies have only led to about a 5% reduction in average daily human mobility. Lessons learned from the data analytics and longitudinal models offer valuable insights for government actions in preparation for another COVID-19 surge or another virus outbreak in the future.
    • Comparison of clinical outcomes with two Transcranial Magnetic Stimulation treatment protocols for major depressive disorder

      Carpenter, LindaL; Aaronson, ScottT; Hutton, Todd M; Mina, Miriam; Pages, Kenneth; Verdoliva, Sarah; West, W Scott; Sackeim, HaroldA (Elsevier Inc., 2020-12-17)
      Background: Transcranial magnetic stimulation (TMS) is an effective treatment for major depressive disorder (MDD). The rest time between pulse trains is the inter-train interval (ITI). Since 2016, some TMS clinicians have adopted a stimulation protocol with shorter ITIs than were used in regulatory clinical trials. Objective: To contrast treatment outcomes with the Standard TMS protocol (38.5 min per session) and the “Dash” protocol, which, at the shortest ITI, has a session duration of 18.75 min. Methods: Registry data were collected at 103 practice sites. Of 7759 participants, 5010 were included in an intent-to-treat (ITT) sample, defined as a primary MDD diagnosis, age ≥ 18, and completion of the PHQ-9 before TMS and with at least one PHQ-9 assessment after baseline. Completers (N = 3814) were responders or had received ≥ 20 sessions and had an end of acute treatment PHQ-9 assessment. Within the ITT sample, 613 patients were treated with the Standard NeuroStar 38-min protocol and 1493 patients with the new Dash protocol. CGI-S ratings were obtained in smaller samples. Treatment outcomes were also examined in subgroups considered Completers, as well as the subgroups who met criteria for Full Adherence to the Standard or Dash protocol parameters. Results: In the ITT, Completer, and Fully Adherent samples, response (58–72%) and remission (28–53%) rates were notably high across PHQ-9 and CGI-S ratings. The Standard and Dash protocols did not differ in number of treatment sessions, and both manifested strong antidepressant effects. Conclusions: The Standard and Dash protocols did not meaningfully differ in efficacy.
    • DNA Methylation in Prostate Tumor Tissue Is Associated with Gleason Score

      Barry, Kathryn Hughes; Mohanty, Kareshma; Erickson, Patricia A; Wang, Difei; Shi, Jianxin; Rose, Gary; Cellini, Ashley; Clark, Kimberly; Ambulos, Nicholas; Yin, Jing; et al. (MDPI AG, 2020-12-24)
      Increasing evidence suggests a role of epigenetic mechanisms at chromosome 8q24, an important cancer genetic susceptibility region, in prostate cancer. We investigated whether MYC DNA methylation at 8q24 (six CpG sites from exon 3 to the 3' UTR) in prostate tumor was associated with tumor aggressiveness (based on Gleason score, GS), and we incorporated RNA expression data to investigate the function. We accessed radical prostatectomy tissue for 50 Caucasian and 50 African American prostate cancer patients at the University of Maryland Medical Center, selecting an equal number of GS 6 and GS 7 cases per group. MYC DNA methylation was lower in tumor than paired normal prostate tissue for all six CpG sites (median difference: -14.74 to -0.20 percentage points), and we observed similar results for two nearby sites in The Cancer Genome Atlas (p < 0.0001). We observed significantly lower methylation for more aggressive (GS 7) than less aggressive (GS 6) tumors for three exon 3 sites (for CpG 212 (chr8:128753145), GS 6 median = 89.7%; GS 7 median = 85.8%; p-value = 9.4 × 10-4). MYC DNA methylation was not associated with MYC expression, but was inversely associated with PRNCR1 expression after multiple comparison adjustment (q-value = 0.04). Findings suggest that prostate tumor MYC exon 3 hypomethylation is associated with increased aggressiveness.
    • Postpartum depression and its association with intimate partner violence and inadequate social support in Ethiopia: a systematic review and meta-analysis.

      Desta, Melaku; Memiah, Peter; Kassie, Bekalu; Ketema, Daniel Bekele; Amha, Haile; Getaneh, Temesgen; Sintayehu, Mezinew (Elsevier B.V., 2021-01)
      We systematically searched international databases like PubMed, Web of Science, SCOPUS, CINAHL, PsycINFO, Google Scholar, Science Direct, and the Cochrane Library. All identified observational studies reporting the postpartum depression and or its predictors in Ethiopia were included. Two authors independently extracted all necessary data using a standardized data extraction format. The I2 statistics were used to assess the heterogeneity of the studies. A random-effects model was computed to estimate the pooled prevalence of postpartum depression and its associations with the selected predictors.