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Yu Zhao;
Chong Cui;
Kun Zhang;
Jialin Liu;
Jinfu Xu;
Eric Nisenbaum;
Yixiang Huang;
Guoyou Qin;
Bing Chen;
Michael Hoffer;
Susan H. Blanton;
Fred Telischi;
Joshua M. Hare;
Sylvia Daunert;
Bhavarth Shukla;
Savita G. Pahwa;
Dushyantha T. Jayaweera;
Paul E. Farmer;
Carlos del Rio;
Xuezhong Liu;
Yilai Shu
The COVID-19 outbreak spread rapidly throughout the globe, with worldwide infections and deaths continuing to increase dramatically. To control disease spread and protect healthcare workers, accurate information is necessary. We searched PubMed and Google Scholar for studies published from December 2019 to March 31, 2020 with the terms “COVID-19,” “2019-nCoV,” “SARS-CoV-2,” or “Novel Coronavirus Pneumonia.” The main symptoms of COVID-19 are fever (83–98.6%), cough (59.4–82%), and fatigue (38.1–69.6%). However, only 43.8% of patients have fever early in the disease course, despite still being infectious. These patients may present to clinics lacking proper precautions, leading to nosocomial transmission, and infection of workers. Potential COVID-19 cases must be identified early to initiate proper triage and distinguish them quickly from similar infections. Early identification, accurate triage, and standardized personal protection protocols can reduce the risk of cross infection. Containing disease spread will require protecting healthcare workers.
Traumatic brain injury (TBI) remains a major cause of disability among young adults in both civilian and military settings contributing to a high burden on healthcare systems (Badhiwala et al., 2019). Sequel of TBI, even mild injuries, include motor and sensory dysfunction, neurocognitive decline, neuropsychiatric complications, as well as increased risk of neurodegenerative and neurovascular events such as Alzheimer’s disease and stroke (Breunig et al., 2013; Burke et al., 2013; Li et al., 2017). Despite the acute nature of the insult in TBI, pathological changes in the traumatized brain are better recognized as a chronic rather than an acute neurological disease, a phenomenon that remains under-investigated. Robust clinical data support the role of neuroinflammation in propagating neurodegenerative changes following TBI with a pivotal role of the complement system as an early trigger and chronic propagator of this response (Alawieh et al., 2018, 2021; Mallah et al., 2021). Hereby, we discuss how the role of complement pathways in different phases of injury after TBI was investigated using clinically relevant targeted complement inhibitors (Alawieh and Tomlinson, 2016; Alawieh et al., 2018, 2021; Mallah et al., 2021).
Pseudomonas aeruginosa is a prevalent pathogen in cystic fibrosis (CF) lungs which displays strong resistance to various antibiotic classes, contributing to antimicrobial resistance (AMR). P aeruginosa populations in CF lungs exhibit considerable genetic and phenotypic diversity, raising questions about their susceptibility to non-traditional antimicrobials, such as bacteriocins. R-pyocins, bacteriocins produced by P. aeruginosa, are highly potent, non-replicating phage tail-like protein complexes with a narrow killing spectrum. The diversity of P. aeruginosa variants within CF lung infections may lead to varying susceptibility to R-pyocins due to changes in the lipopolysaccharide (LPS) structure, which acts as the R-pyocin receptor. However, the extent of susceptibility to the five known R-pyocin subtypes (R1-R5) remains unknown, especially considering the diverse P. aeruginosa populations in CF lungs. Additionally, the connection between LPS phenotype and R-pyocin susceptibility is not well understood. We tested 139 P. aeruginosa variants from 17 sputum samples of seven CF patients for R2-pyocin susceptibility and analyzed their LPS phenotypes. Our findings revealed that approximately 83% of sputum samples contained diverse P. aeruginosa populations without R2-pyocin resistant variants, while all samples had some susceptible variants. Moreover, there was no clear correlation between LPS phenotypes and R-pyocin susceptibility. The absence of a clear correlation between LPS phenotypes and R-pyocin susceptibility suggests that LPS packing density may significantly influence R-pyocin susceptibility among CF variants. Our research supports the potential use of R-pyocins as therapeutic agents, as numerous infectious CF variants appear to be susceptible to R2-pyocins, even within diverse P. aeruginosa populations.
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Maisam Abu-El-Haija;
Soma Kumar;
J. Antonio Quiros;
Keshawadhana Balakrishnan;
Bradley Barth;
Samuel Bitton;
John F. Eisses;
Elsie Jazmin Foglio;
Victor Fox;
Denease Francis;
Alvin Jay Freeman;
Tanja Gonska;
Amit S. Grover;
Sohail Z. Husain;
Rakesh Kumar;
Sameer Lapsia;
Tom Lin;
Quin Y. Liu;
Asim Maqbool;
Zachary M. Sellers;
Flora Szabo;
Aliye Uc;
Steven L. Werlin;
Veronique D. Morinville
Background: Although the incidence of acute pancreatitis (AP) in children is increasing, management recommendations rely on adult published guidelines. Pediatric-specific recommendations are needed. Methods: The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Pancreas committee performed a MEDLINE review using several preselected key terms relating to management considerations in adult and pediatric AP. The literature was summarized, quality of evidence reviewed, and statements of recommendations developed. The authorship met to discuss the evidence, statements, and voted on recommendations. A consensus of at least 75% was required to approve a recommendation. Results: The diagnosis of pediatric AP should follow the published INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE definitions (by meeting at least 2 out of 3 criteria: (1) abdominal pain compatible with AP, (2) serum amylase and/or lipase values ≥3 times upper limits of normal, (3) imaging findings consistent with AP). Adequate fluid resuscitation with crystalloid appears key especially within the first 24 hours. Analgesia may include opioid medications when opioid-sparing measures are inadequate. Pulmonary, cardiovascular, and renal status should be closely monitored particularly within the first 48 hours. Enteral nutrition should be started as early as tolerated, whether through oral, gastric, or jejunal route. Little evidence supports the use of prophylactic antibiotics, antioxidants, probiotics, and protease inhibitors. Esophago-gastroduodenoscopy, endoscopic retrograde cholangiopancreatography, and endoscopic ultrasonography have limited roles in diagnosis and management. Children should be carefully followed for development of early or late complications and recurrent attacks of AP. Conclusions: This clinical report represents the first English-language recommendations for the management of pediatric AP. Future aims should include prospective multicenter pediatric studies to further validate these recommendations and optimize care for children with AP.
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Khalid Alhasan;
Malik Sallam;
Fadi Aljamaan;
Tariq Ali;
Ahmed Al-jedai;
Ahmed Nazmi;
Aziza Ajlan;
Hassan Aleid;
Enaam Karar;
Moheeb Al-Awwami;
Hamad Almojalli;
Yaser Z Shah;
Amir Eltayeb Ismail Mohammed;
Mazin Barry;
Sarah Alsubaie;
Abdulrahman Altheaby;
Reem S Almaghrabi;
Sumayah Askandarani;
Ziad Memish;
Jaffar A Al-Tawfiq;
Dieter C Broering;
Mohamad H Temsah
Background: In response to the global Mpox outbreaks, this survey aimed to assess the knowledge, perceptions, and advocacy of Mpox vaccines among solid organ transplant healthcare workers (HCWs) in Saudi Arabia. Methods: A cross-sectional survey was conducted among solid organ transplant HCWs in Saudi Arabia from 15 August to 5 September 2022. A total of 199 responses were received from participants primarily working in the kidney (54.8%) and liver (14.6%) transplant units. Results: The survey found that most participants were aware of the 2022 Mpox outbreak, but the majority were more concerned about COVID-19 than Mpox. While the majority of participants thought laboratory personnel and HCWs in direct contact with Mpox patients should receive the vaccine, less than 60% believed that all HCWs should be vaccinated. Additionally, over half of the participants lacked knowledge of animal–human transmission of the virus. Conclusion: The results highlight the need for increased education on Mpox among transplant HCWs in Saudi Arabia, particularly regarding the virus’s transmission dynamics and vaccines. This education is crucial to improve HCWs’ understanding of this emerging disease, especially given their vulnerability during the COVID-19 pandemic.
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Aloke Finn;
Michael John;
Gaku Nakazawa;
Rohini Polavarapu;
Vinit Karmali;
Xin Xu;
Qi Cheng;
Talina Davis;
Chitra Raghunathan;
Eduardo Acampado;
Tucker Ezell;
Scott Lajoie;
Michael Eppihimer;
Frank D Kolodgie;
Renu Virmani;
Herman Kalman Gold
Rationale: Sirolimus-eluting coronary stents (SESs) and paclitaxel-eluting coronary stents (PESs) are used to reduce restenosis but have different sites of action. The molecular targets of sirolimus overlap with those of the peroxisome proliferator-activated receptor (PPAR)γ agonist rosiglitazone (RSG) but the consequence of this interaction on endothelialization is unknown. Objective: Using the New Zealand white rabbit iliac model of stenting, we examined the effects of RSG on SESs, PESs, and bare metal stents endothelialization. Methods and Results: Animals receiving SESs, PESs, or bare metal stents and either RSG (3 mg/kg per day) or placebo were euthanized at 28 days, and arteries were evaluated by scanning electron microscopy. Fourteen-day organ culture and Western blotting of iliac arteries and tissue culture experiments were conducted. Endothelialization was significantly reduced by RSG in SESs but not in PESs or bare metal stents. Organ culture revealed reduced vascular endothelial growth factor in SESs receiving RSG compared to RSG animals receiving bare metal stent or PESs. Quantitative polymerase chain reaction in human aortic endothelial cells (HAECs) revealed that sirolimus (but not paclitaxel) inhibited RSG-induced vascular endothelial growth factor transcription. Western blotting demonstrated that inhibition of molecular signaling in SES+RSG-treated arteries was similar to findings in HAECs treated with RSG and small interfering RNA to PPARγ, suggesting that sirolimus inhibits PPARγ. Transfection of HAECs with mTOR (mammalian target of rapamycin) short hairpin RNA and with Akt2 small interfering RNA significantly inhibited RSG-mediated transcriptional upregulation of heme oxygenase-1, a PPARγ target gene. Chromatin immunoprecipitation assay demonstrated sirolimus interferes with binding of PPARγ to its response elements in heme oxygenase-1 promoter. Conclusions: mTOR/Akt2 is required for optimal PPARγ activation. Patients who receive SESs during concomitant RSG treatment may be at risk for delayed stent healing.
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Jayeeta Ghose;
Ada Dona;
Mariam Murtadha;
Emine Gulsen Gunes;
Enrico Caserta;
Ji Young Yoo;
Luke Russell;
Alena Cristina Jaime-Ramirez;
Benjamin Barwick;
Vikas Gupta;
James F Sanchez;
Douglas W Sborov;
Steven T Rosen;
Amrita Krishnan;
Lawrence Boise;
Balveen Kaur;
Craig Hofmeister;
Flavia Pichiorri
Because most patients with multiple myeloma (MM) develop resistance to current regimens, novel approaches are needed. Genetically modified, replication-competent oncolytic viruses exhibit high tropism for tumor cells regardless of cancer stage and prior treatment. Receptors of oncolytic herpes simplex virus 1 (oHSV-1), NECTIN-1, and HVEM are expressed on MM cells, prompting us to investigate the use of oHSV-1 against MM. Using oHSV-1-expressing GFP, we found a dose-dependent increase in the GFP+ signal in MM cell lines and primary MM cells. Whereas NECTIN-1 expression is variable among MM cells, we discovered that HVEM is ubiquitously and highly expressed on all samples tested. Expression of HVEM was consistently higher on CD138+/CD38+ plasma cells than in non-plasma cells. HVEM blocking demonstrated the requirement of this receptor for infection. However, we observed that, although oHSV-1 could efficiently infect and kill all MM cell lines tested, no viral replication occurred. Instead, we identified that oHSV-1 induced MM cell apoptosis via caspase-3 cleavage. We further noted that oHSV-1 yielded a significant decrease in tumor volume in two mouse xenograft models. Therefore, oHSV-1 warrants exploration as a novel potentially effective treatment option in MM, and HVEM should be investigated as a possible therapeutic target.
OBJECTIVES: Emotional stress may disproportionally affect young women with ischemic heart disease. We sought to examine whether mental stress-induced myocardial ischemia (MSIMI), but not exercise-induced ischemia, is more common in young women with previous myocardial infarction (MI) than in men.
METHODS: We studied 98 post-MI patients (49 women and 49 men) aged 38 to 60 years. Women and men were matched for age, MI type, and months since MI. Patients underwent technetium-99m sestamibi perfusion imaging at rest, after mental stress, and after exercise/pharmacological stress. Perfusion defect scores were obtained with observer-independent software. A summed difference score (SDS), the difference between stress and rest scores, was used to quantify ischemia under both stress conditions.
RESULTS: Women 50 years or younger, but not older women, showed a more adverse psychosocial profile than did age-matched men but did not differ for conventional risk factors and tended to have less angiographic coronary artery disease. Compared with age-matched men, women 50 years or younger exhibited a higher SDS with mental stress (3.1 versus 1.5, p = .029) and had twice the rate of MSIMI (SDS ≥3 52% versus 25%), whereas ischemia with physical stress did not differ (36% versus 25%). In older patients, there were no sex differences in MSIMI. The higher prevalence of MSIMI in young women persisted when adjusting for sociodemographic and life-style factors, coronary artery disease severity, and depression.
CONCLUSIONS: MSIMI post-MI is more common in women 50 years or younger compared with age-matched men. These sex differences are not observed in post-MI patients who are older than 50 years.
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Jessica A Turner;
Vince Calhoun;
Paul M Thompson;
Neda Jahanshad;
Christopher RK Ching;
Sophia Thomopoulos;
Eric Verner;
Gregory P Strauss;
Anthony O Ahmed;
Matthew D Turner;
Sunitha Basodi;
Judith M Ford;
Daniel H Mathalon;
Adrian Preda;
Ayesnil Belger;
Bryon A Mueller;
Kelvin O Lim;
Theo GM van Erp
The FAIR principles, as applied to clinical and neuroimaging data, reflect the goal of making research products Findable, Accessible, Interoperable, and Reusable. The use of the Collaborative Informatics and Neuroimaging Suite Toolkit for Anonymized Computation (COINSTAC) platform in the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium combines the technological approach of decentralized analyses with the sociological approach of sharing data. In addition, ENIGMA + COINSTAC provides a platform to facilitate the use of machine-actionable data objects. We first present how ENIGMA and COINSTAC support the FAIR principles, and then showcase their integration with a decentralized meta-analysis of sex differences in negative symptom severity in schizophrenia, and finally present ongoing activities and plans to advance FAIR principles in ENIGMA + COINSTAC. ENIGMA and COINSTAC currently represent efforts toward improved Access, Interoperability, and Reusability. We highlight additional improvements needed in these areas, as well as future connections to other resources for expanded Findability.
Extreme acidosis is a life-threatening physiological state that causes disturbances in the cardiovascular, pulmonary, immune, and hematological systems. Trauma patients commonly present to the operating room (OR) in hypovolemic shock, leading to tissue hypoperfusion and the development of acute metabolic acidosis with or without a respiratory component. It is often believed that trauma patients presenting to the OR in severe metabolic acidosis (pH <7.0) will have a nearly universal mortality rate despite aggressive resuscitation and damage control. The current literature does not include reports of successful resuscitations from a lower pH, which may lead providers to assume that a good outcome is not possible. However, here we describe a case of successful resuscitation from an initial pH of 6.5 with survival to discharge home 95 days after admission with almost full recovery. We describe the effects of acute acidosis on the respiratory and cardiovascular systems and hemostasis. Finally, we discuss the pillars of management in patients with extreme acute acidosis due to hemorrhage: transfusion, treatment of hyperkalemia, and consideration of buffering acidosis with bicarbonate and hyperventilation.