bluuebunny/crossref_metadata_2025 huggingface dataset:
Parvovirus B19 induces cellular senescence in human dermal fibroblasts: putative role in systemic sclerosis–associated fibrosis
Authors: Arvia Rosaria , Zakrzewska Krystyna , Giovannelli Lisa , Ristori Sara , Frediani Elena , Del Rosso Mario , Mocali Alessandra , Stincarelli Maria A , Laurenzana Anna , Fibbi Gabriella , Margheri Francesca
Published: December 2021

Objective

Emerging evidence demonstrates that excessive accumulation of senescent cells is associated with some chronic diseases and suggests a pathogenic role of cellular senescence in fibrotic processes, such as that occurring in ageing or in SSc. Recently we demonstrated that parvovirus B19 (B19V) activates normal human dermal fibroblasts and induces expression of different profibrotic/pro-inflammatory genes. This observation prompted us to investigate whether it is also able to induce fibroblast senescence as a potential pathogenetic mechanism in B19V-induced fibrosis.

Methods

Primary cultures of fibroblasts were infected with B19V and analysed for the acquisition of senescence markers, such as morphological modifications, senescence-associated β-galactosidase (SA-β-gal) activity, DNA damage response and expression of senescence-associated secretory phenotype (SASP)-related factors.

Results

We demonstrated that B19V-infected fibroblasts develop typical senescence features such as enlarged and flat-shaped morphology and SA-β-gal activity similar to that observed in SSc skin fibroblasts. They also developed an SASP-like phenotype characterized by mRNA expression and release of some pro-inflammatory cytokines, along with activation of the transcription factor nuclear factor κB. Moreover, we observed B19V-induced DNA damage with the comet assay: a subpopulation of fibroblasts from B19V-infected cultures showed a significantly higher level of DNA strand breaks and oxidative damage compared with mock-infected cells. An increased level and nuclear localization of γH2AX, a hallmark of DNA damage response, were also found.

Conclusions

B19V-induced senescence and production of SASP-like factors in normal dermal fibroblasts could represent a new pathogenic mechanism of non-productive B19V infection, which may have a role in the fibrotic process.
You’re Too Old for That! Ageism and Prescriptive Stereotypes in the Workplace
Authors: Hanrahan Elizabeth A , Thomas Courtney L , Finkelstein Lisa M
Published: December 2021

Using a vignette-based design, the current study addresses the question of what happens when a worker violates prescriptive age identity stereotypes (i.e., does not act in ways that align with cultural expectations for people in their age group). The study extends prior research by including a mixed adhering-violating condition, investigating the effects of prescriptive stereotype violation on the application of descriptive age stereotypes, and examining the role of negative affect (a composite of frustration, irritation, and annoyance) as a mediating mechanism in the prescriptive stereotyping process. Results indicate that violators of prescriptive age stereotypes are perceived more negatively in terms of warmth, competence, and desire for workplace interactions. Exhibiting some adhering and some violating behaviors largely did not lessen the effects of violation. The idea that some descriptive age stereotypes would be applied less often to violators did receive some support. Frustration was shown to be a useful mechanism for explaining prescriptive stereotyping effects, but the general absence of age of participant effects raises new questions regarding the role of expectancy violation in this process. Taken together, these findings offer an extension of the research on prescriptive age stereotypes to the workplace context, show that there can be a cost to violating prescriptive age stereotypes, and provide insight into potential mechanisms. We provide several suggestions for expanding this work, including the consideration of the intersection of age with other identity groups and ways to explore the roles of expectancy violations and perceived subjective age in the prescriptive stereotyping process.
Prevalence of SARS-CoV-2 Positivity in Pediatric Surgical Patients Amid the First Wave of the COVID-19 Pandemic in New York City
Authors: Price Jerri C. , Lee Jennifer J. , Ing Caleb , Li Guohua , Narula Jacquelin , Clark Mary K. , Stylianos Steven , Whittington Robert A. , Levy Richard J. , Sun Lena S.
Published: December 2021

Introduction:

New York State implemented an 11-week elective surgery ban in response to the coronavirus disease-2019 (COVID-19) pandemic, during which pediatric patients from the 10 New York Presbyterian network hospitals requiring urgent or emergent surgical procedures were cared for at Morgan Stanley Children’s Hospital (MSCH).

Materials and Methods:

Data was abstracted from the electronic medical record of all patients aged 0 to 20 years who had surgery at MSCH from March 23, 2020 to June 7, 2020. Comparative analysis of demographic and clinical data elements between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive and negative cohorts was conducted using the Fisher exact tests.

Results:

A total of 505 surgical procedures were performed in 451 patients, with 32 procedures (6.3%) performed in 21 SARS-CoV-2-positive children. The prevalence of SARS-CoV-2 positivity in Medicaid beneficiaries was more than twice the prevalence in commercially insured (6.8% vs. 2.6%, P=0.04) children. SARS-CoV-2-positive patients were more likely to undergo multiple surgical procedures (23.8% vs. 7.2%, P=0.02), and to have higher American Society of Anesthesiologists (ASA) class designations (69.8% III to V vs. 47.4% I to II, P=0.03). There was no significant difference in the prevalence of SARS-CoV-2 positivity across sex, age, race, or ethnicity groups, or in emergent case status or surgical procedure type. Thirty-day mortality rate was <0.1% overall, with no deaths in the SARS-CoV-2-positive group.

Conclusions:

During the first wave of the COVID-19 pandemic in New York City, we found a higher prevalence of SARS-CoV-2 positivity in urgent/emergent pediatric surgical patients compared with other institutions in the United States. SARS-CoV-2-positive patients were more likely to be Medicaid beneficiaries, were clinically more complex, and had more surgical procedures.
The Anesthesiologist as Translational Scientist
Authors: Griffiths Keren K. , Gerber Adam , Whittington Robert A.
Published: December 2021

Translational science seeks to accelerate the multi-step process by which scientific discoveries are transformed into therapies that can improve the health of individuals and their communities. To facilitate crossing the traditional boundaries between basic and clinical research for instance, a systematic understanding of the scientific and operational principles that underlie each step of the translational cycle is developed to identify and address barriers to translation. Skills required by translational scientists, such as being systems thinkers and process innovators, overlap with those of anesthesiologists, and therefore, it is no surprise that anesthesiologists have contributed to this field. Indeed, the safety and efficacy of anesthesia care has greatly evolved over many decades because anesthesiologists have recognized the importance of readily incorporating physiological and pharmacological basic research findings into clinical practice. This article highlights the characteristics that make anesthesiologists well suited to be translational scientists. We also discuss one example of anesthesiology contributing to the field of translational science during the COVID-19 pandemic. We show that anesthesiologists, regardless of their specific clinical or research interests, have the skill set to become effective and critical players in the field of translational science and emphasize the importance of continued leadership in this field to academic anesthesiology.
Multisystem Inflammatory Syndrome in Children (MIS-C): Experiences With a New Disease Process
Authors: Ko Riva , Massa Christopher , Saraiya Neeta , Cheung Eva W.
Published: December 2021

On March 20, 2021, the Columbia University Department of Anesthesiology hosted the Papper virtual event dedicated to an academic discussion of various aspects of coronavirus disease-2019. Dr. Eva Cheung, a pediatric intensivist and pediatric cardiologist, spoke about the clinical challenges associated with tackling multisystem inflammatory syndrome in children, a novel clinical entity in pediatric patients related to coronavirus disease-2019, and the experience with confronting multisystem inflammatory syndrome in children in New York.
Qualitative Study of Health Care Providers' Uptake of the Project Extension for Community Health Outcomes for Chronic Pain
Authors: Page M. Gabrielle , Develay Élise , Simard Paul , Parent Jocelyne , Tremblay Nicole , Boulanger Aline
Published: December 2021

Introduction:

There is an enormous need for pain education among all health care professions before and after licensure. The study goal was to explore generic and chronic pain–specific factors that influenced uptake of a continuous education program for chronic pain, the Project Extension for Community Health Outcomes (ECHO) CHUM Douleur chronique.

Methods:

The study team conducted 20 semistructured virtual interviews among participants of the program. Interviews were transcribed verbatim, and two analysts used a reflexive thematic analysis approach to generate study themes.

Results:

Five aspects facilitating engagement, continued participation, and uptake of the Project ECHO were identified: rapid access to reliable information, appraising one's knowledge, cultivating meaningful relationships, breaking the silos of learning and practice, and exponential possibilities of treatment orchestrations for a complex condition with no cure. Although participants' experiences of the program was positive overall, some obstacles to engagement and continued participation were identified: heterogeneity of participants' profiles, feelings of powerlessness and discouragement in the face of complex incurable pain conditions, challenges in applying recommendations, medical hierarchy, and missed opportunity for advocacy.

Discussion:

Many disease-specific and contextual factors contributed to an increased motivation to participate in the ECHO program. Some elements, such as the complexity of diagnosis and treatment, and the multidisciplinary requirements to manage cases were identified as elements motivating one's participation in the program but also acting as a barrier to knowledge uptake. These must be understood in the broader systemic challenges of the current health care system and lack of resources to access allied health care.
Renin–Angiotensin System Blocker in COVID-19. A Single Center Study.
Authors: Job Riya , Abdul Qader Mohamed , Torres Pedro , Al Abbasi Baher , Dewaswala Nakeya , Abdallah Ahmed , Chen Kai , Pino Jesus E. , Chait Robert D.
Published: December 2021

Early during the Coronavirus disease 2019 (Covid-19) pandemic, concerns were raised regarding potential adverse outcomes in patients taking angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs). These concerns were based on animal studies showing increased ACE-2 expression in mice treated with ACEI/ARB. This is a single-center, retrospective, cohort study of 289 patients diagnosed with 2019 Novel Coronavirus (SARS-CoV-2) hospitalized between March of 2020 and June of 2020. The study was intended to investigate the impact of ACEIs and/or ARBs on in-hospital mortality, intensive care unit (ICU) admission, postadmission hemodialysis requirement, and the need for mechanical ventilation in patients with COVID-19. This cohort of 289 patients included 139 of 289 women (48%) with a mean age of 61 ± 19 years. Patients using ACEIs/ARBs were older (69.68 vs. 57.9 years; P < 0.0001), more likely to have a history of hypertension (97% vs. 36%; P < 0.0001), diabetes mellitus (48% vs. 20.9%; P < 0.0001), chronic heart failure (11.39% vs. 4.29%; P < 0.0512), coronary artery disease (20.25% vs. 7.14%; P < 0.0025), stroke/Transient Ischemic Attack (7.59% vs. 2.38%; P < 0.0761), chronic kidney disease (11.39% vs. 3.33%; P < 0.0167), atrial fibrillation/flutter (18.99% vs. 7.14%; P < 0.0080), and dementia (22.7% vs. 11.4%; P < 0.0233) compared with the nonuser group. There was significantly higher in-hospital mortality in patients using ACEIs/ARBs than nonusers, respectively (32.9% vs. 15.2%; P < 0.0015). However, a multivariate logistics regression analysis performed to adjust for common confounders demonstrated no significant difference in all-cause in-patient mortality (P 0.7141). Admission to ICU, postadmission hemodialysis requirement, and mechanical ventilation showed no significant differences between the 2 groups (P = NS). This study suggests that the use of ACEIs and ARBs in patients with COVID-19 was not found to significantly increase all-cause in-hospital mortality, ICU admissions, and hemodialysis and mechanical ventilation requirements.
Pinitol Protects Against Ox-Low-Density Lipoprotein-Induced Endothelial Inflammation and Monocytes Attachment
Authors: Chen Xiao-Hong , Tan Yu , Yu ShuQin , Lu Lijun , Deng Youqing
Published: December 2021

Atherosclerosis is a cardiovascular disease that affects a majority of people around the world at old age. Atherosclerosis is slow to develop and challenging to treat. Endothelial dysfunction caused by oxidative stress, inflammation, and other pathological factors drives the process of atherogenesis. LOX-1 is one of the main scavenging receptors for oxidized low-density lipoprotein (ox-LDL) and contributes to atherogenesis by inducing overproduction of reactive oxygen species, increased expression of proinflammatory cytokines, and secretion of cellular adhesion molecules. In addition, activation of LOX-1 inhibits the expression of KLF2, a key protective factor against atherosclerosis. In this study, we investigated the effects of pinitol, and naturally occurring cyclic polyol, on endothelial dysfunction induced by ox-LDL. Our findings show that pinitol revealed a good safety profile, as evidenced by reducing lactate dehydrogenase release in human aortic endothelial cells. In our experiments, pinitol reduced the production of reactive oxygen species and expression of IL-6 and monocyte chemoattractant protein-1 induced by ox-LDL. Pinitol also significantly reduced the attachment of THP-1 monocytes to endothelial cells via downregulation of vascular cellular adhesion molecule-1 and E-selectin. Importantly, we found that pinitol reduced the expression of LOX-1 induced by ox-LDL and rescued the expression of KLF2, which is dependent on ERK5 expression. Together, our findings provide notable evidence that pinitol may have potential implication in the prevention and treatment of atherosclerosis.
Successful Treatment of a Balamuthia mandrillaris Cerebral Abscess in a Pediatric Patient With Complete Surgical Resection and Antimicrobial Therapy
Authors: Cuoco Joshua A. , Klein Brendan J. , LeBel David P. , Faulhaber Jason , Apfel Lisa S. , Witcher Mark R.
Published: December 2021

Cerebral amebic encephalitis due to Balamuthia mandrillaris is a rare yet typically fatal disease. As such, identification of the clinical characteristics, appropriate diagnostic workup and commencement of treatment is frequently delayed. Here, we present a case of a 4-year-old male with a B. mandrillaris cerebral abscess successfully treated with expedited neurosurgical resection and broad-spectrum antimicrobial therapy.
Long-term neuropathic pain behaviors correlate with synaptic plasticity and limbic circuit alteration: a comparative observational study in mice
Authors: Guida Francesca , Iannotta Monica , Misso Gabriella , Ricciardi Flavia , Boccella Serena , Tirino Virginia , Falco Michela , Desiderio Vincenzo , Infantino Rosmara , Pieretti Gorizio , de Novellis Vito , Papaccio Gianpaolo , Luongo Livio , Caraglia Michele , Maione Sabatino
Published: December 2021

Neuropathic pain has long-term consequences in affective and cognitive disturbances, suggesting the involvement of supraspinal mechanisms. In this study, we used the spared nerve injury (SNI) model to characterize the development of sensory and aversive components of neuropathic pain and to determine their electrophysiological impact across prefrontal cortex and limbic regions. Moreover, we evaluated the regulation of several genes involved in immune response and inflammation triggered by SNI. We showed that SNI led to sensorial hypersensitivity (cold and mechanical stimuli) and depressive-like behavior lasting 12 months after nerve injury. Of interest, changes in nonemotional cognitive tasks (novel object recognition and Y maze) showed in 1-month SNI mice were not evident normal in the 12-month SNI animals. In vivo electrophysiology revealed an impaired long-term potentiation at prefrontal cortex-nucleus accumbens core pathway in both the 1-month and 12-month SNI mice. On the other hand, a reduced neural activity was recorded in the lateral entorhinal cortex-dentate gyrus pathway in the 1-month SNI mice, but not in the 12-month SNI mice. Finally, we observed the upregulation of specific genes involved in immune response in the hippocampus of 1-month SNI mice, but not in the 12-month SNI mice, suggesting a neuroinflammatory response that may contribute to the SNI phenotype. These data suggest that distinct brain circuits may drive the psychiatric components of neuropathic pain and pave the way for better investigation of the long-term consequences of peripheral nerve injury for which most of the available drugs are to date unsatisfactory.
Stevens-Johnson syndrome linked to tramadol use and ultraviolet radiation
Authors: McKinley Blake J. , Parkinson J. Scott
Published: December 2021

Rationale:

Stevens-Johnson syndrome (SJS) is a cutaneous reaction characterized by necrosis and epidermal detachment, commonly triggered by medications. Tramadol rarely causes SJS, and ultraviolet radiation (UVR) has limited recognition as being linked to SJS presentations.

Patient concerns:

A previously healthy 18-year-old female presented to the emergency department with what she believed to be a severe sunburn. Five days prior, she was exposed to extensive sun exposure while swimming all day at a lake. The following day, she developed a rash on her shoulders, which became widespread, extending to the palms of her hands and soles of her feet, and eventually involved her oral and ocular mucosa. At the time of hospital admission, the rash had progressed to form vesicles/bullae with skin sloughing and a positive Nikolsky sign, bleeding ulcers throughout the oral mucosa, and bilateral conjunctival hyperemia with purulent discharge.

Diagnosis:

The patient reported no medication use apart from a single dose of tramadol 7 to 10 days prior to rash onset. Given the clinical presentation and histopathological findings that were consistent with SJS, a diagnosis of SJS was made. The nature of this patient's rash onset, character, and progression suggests that UVR precipitated the event in conjunction with tramadol as the causative agent.

Interventions:

The patient received fluid resuscitation and was transferred via air ambulance to a trauma and burn center to receive treatment.

Outcomes:

Complete resolution of the patient's cutaneous and oral mucosal lesions occurred 4 weeks after discharge; however, hypopigmentation was evident in areas where cutaneous re-epithelialization had occurred. The patient was advised to strictly avoid the use of tramadol and limit her exposure to UVR.

Lesson:

Physicians should be aware that tramadol may cause SJS and that UVR may precipitate SJS in patients taking tramadol. Rapid diagnosis of SJS and transfer to a trauma or burn center improves patient outcomes.
A Retrospective analysis of four cases of pacemaker exit block
Authors: Guo QiFeng , Kuang DeJun , Xu XiangLin , Guo Ling
Published: December 2021

Introduction:

Exit block has been defined as a delay or failure of a pacemaker impulse to discharge the surrounding myocardium, including atrial and ventricular pacemaker exit blocks. The present report analyzed the etiology and electrocardiogram characteristics of pacemaker exit blocks, providing ideas for its diagnosis and treatment.

Patient concerns:

The patients in cases 1 and 2 sought medical advice for symptoms such as palpitations, chest tightness and shortness of breath. Both the patients had a dual-chamber pacemaker implant due to sick sinus syndrome Patients in cases 3 and 4 sought medical advice for symptoms such as chest tightness, chest pain, and dizziness. Both patients had a single-chamber ventricular pacemaker implant due to third-degree atrioventricular block.

Diagnosis:

Considering the symptoms and prolonged latency of atrial pacing, Cases 1 and 2 were diagnosed as first-degree atrial pacemaker exit blocks. Case 3 presented prolonged ventricular pacing latency, diagnosed as first-degree ventricular pacemaker exit block. Case 4 presented prolonged ventricular pacing latency and partial loss of capture diagnosed as second-degree ventricular pacemaker exit block.

Interventions:

In case 1, the patient required no treatment. In case 2, the AV interval was adjusted to ensure sequential pacing of the atrioventricular. In case 3, the serum potassium level was lowered. In case 4, the patient refused further treatment.

Outcomes:

In case 1, the patient had no discomfort, and the follow-up electrocardiogram was unchanged. The symptoms improved after treatment in case 2. After 1 year, the patient had no discomfort, and the follow-up electrocardiogram was similar to that before. In case 3, the exit block disappeared after lowering the serum potassium level. The pacemaker worked normally after 1 year of follow-up. In case 4, the exit block disappeared half an hour after the chest pain was relieved. The patient was lost to follow-up.

Conclusion:

A first-degree atrial pacemaker exit block may be misdiagnosed as atrial pacing dysfunction. This can be identified using the programming control of a pacemaker. For exit block of ventricular pacing, eliminating the cause of the disease is usually the most effective measure, and if necessary, a temporary pacemaker should be implanted.
Hemophagocytic Lymphohistiocytosis Secondary to Juvenile Myelomonocytic Leukemia: A Case Report and Review of the Literature
Authors: Zheng Fangyuan , Jia Yueping , Zhang Leping , Qin Jiong
Published: December 2021

Rationale:

Juvenile myelomonocytic leukemia (JMML) is a rare hematopoietic disorder, which is more rarely accompanied by monosomy 5 or deletion of the long arm of chromosome 5q (−5/5q−) or monosomy 5 (5q−/−5), and hemophagocytic lymphohistiocytosis (HLH) is a rare, uncontrolled hyperinflammation condition, which is more rarely secondary to JMML. Up to now, only a few cases of JMML with −5/5q− and HLH secondary to JMML were described. Here we described an extremely rare case of HLH second to JMML with 5q−.

Patient Concerns:

The patient had multiple cafe-au-lait-spots at birth and was found that NF1 gene mutation was positive. At his 6 years old, he developed hepatosplenomegaly, anemia, thrombocytopenia, monocyte count 4.12×109/L in peripheral blood, 13% blasts in peripheral blood, and 11% blasts in bone marrow, without BCR/ABL rearrangement, combining with positive NF1 gene mutation, he was diagnosed as JMML. In the bone marrow, there was chromosomal abnormalities with −5/5q−. In the treatment, HLH occurred.

Diagnoses:

The patient was diagnosed as secondary HLH to JMML.

Interventions:

The patient received the chemotherapy treatment of the improved diffuse alveolar hemorrhage protocol, and meanwhile, he prepared for hematopoietic stem cell transplantation. Then on the basis of anti-infection, symptomatic and supportive therapy, he was commenced the treatment according to the HLH-2004 protocol.

Outcomes:

He had a partial response, manifesting that his fever resolved, but the blood coagulation function did not improve, and the severe thrombocytopenia remained. Then, the parents refused the continual treatment, and the child died of intracranial hemorrhage 3 months after the diagnosis of JMML.

Lessons:

JMML and HLH were relatively easy to diagnose based on clinical and laboratory results. Due to the low incidence of JMML with −5/5q− and HLH secondary to JMML, no clinical practice guidelines for the treatment of the disease have been established yet. The clinical data of a case of HLH secondary to JMML with 5q− were analyzed, and relevant studies were studied.
Coagulation Abnormalities and Clinical Complications in Children With SARS-CoV-2: A Systematic Review of 48,322 Patients
Authors: McDaniel Charles Griffin , Commander Sarah J. , DeLaura Isabel , Cantrell Sarah , Leraas Harold J. , Moore Carrie B. , Reed Christopher R. , Pahl Kristy S. , Tracy Elisabeth T.
Published: December 2021

Given the limited information on the coagulation abnormalities of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in pediatric patients, we designed a systematic review to evaluate this topic. A comprehensive literature search was conducted for “SARS-CoV-2,” “coagulopathy,” and “pediatrics.” Two authors independently screened the articles that the search returned for bleeding, thrombosis, anticoagulant and/or antiplatelet usage, and abnormal laboratory markers in pediatric patients with SARS-CoV-2, and the authors then extracted the relevant data. One hundred twenty-six publications were included. Thirty-four (27%) studies reported thrombotic complications in 504 patients. Thirty-one (25%) studies reported bleeding complications in 410 patients. Ninety-eight (78%) studies reported abnormal laboratory values in 6580 patients. Finally, 56 (44%) studies reported anticoagulant and/or antiplatelet usage in 3124 patients. The variety of laboratory abnormalities and coagulation complications associated with SARS-CoV-2 presented in this review highlights the complexity and variability of the disease presentation in infants and children.
Advice From a Millennial Nurse About Becoming a New Aesthetic Injector in 2021
Authors: Brennan Savannah
Published: December 2021

Some may believe that being an injector is a dream job and that the job is easy. These individuals may believe there is a lot of money to be made and that injectors can choose their own hours making people beautiful and enjoying their passion. In this article, I will talk about my experience breaking into aesthetics, describe what it is like to be a new nurse injector in 2021, explain what you should expect as a new nurse breaking into this field, delineate some tips I have learned along the way, and provide some advice from my experience thus far.
Improving Interprofessional Teamwork in Plastic Surgery: A Novel Approach to Microsurgical Skills Training
Authors: Gowda Siri , Elsabra Rhona , Lindero Ella , Mohan Arvind
Published: December 2021

Shared mental models between surgeons and nurses allow them to effectively communicate and react to intraoperative complications. Microsurgery poses unique challenges that include the use of an operating microscope, fine instruments, and a restricted view of the operative field. We designed and delivered a microsurgical skills session for surgical nurses consisting of an introduction to the operating microscope and 3 practical stations involving increasingly complex motor tasks designed to highlight the importance of instrument handling and improve awareness of microsurgical challenges. Consultant plastic surgeons acted as scrub persons to add an element of role-reversal. All participants enjoyed the training session and felt that it improved their understanding of microsurgery and was relevant and helpful to their day-to-day role. All attendees reported that they would partake in similar sessions in the future. Our work suggests that role-reversal and skills-based education and training are valuable tools in improving multidisciplinary collaboration during microsurgery. Increasing shared knowledge of complex procedures encourages effective teamwork and communication, which leads to improved efficiency and better patient care. Our study is a first step toward development of a standardized microsurgical skills course for plastic surgical nurses and has broader implications for interprofessional education across all surgical specialties.
Providing Optimal Rejuvenation to the Jawline and Perioral Area Using Neuromodulators and Hyaluronic Acid Dermal Fillers
Authors: Varga Rachel
Published: December 2021

Including the jawline in aesthetic assessment has become increasingly popular when using both surgical and nonsurgical techniques. Facial aging processes include bone resorption, fat pad atrophy, and a breakdown of the quality of collagen and elastin in the skin. To provide optimal treatment of the jawline using nonsurgical techniques, it is important to consider all of these aspects before planning treatment. Men and women have different facial aging processes and ideal facial ratios that must be respected. The objective of this article is to discuss the use of botulinum toxin A and hyaluronic acid filler injectable treatments, deoxycholic acid injectable treatments, and cryolipolysis treatments and explain how these treatments can be utilized for optimal rejuvenation of the jawline and perioral area.
Anaerostipes hominis sp. nov., a novel butyrate-producing bacteria isolated from faeces of a patient with Crohn's disease
Authors: Lee Jae-Yun , Kang Woorim , Shin Na-Ri , Hyun Dong-Wook , Kim Pil Soo , Kim Hyun Sik , Lee June-Young , Tak Euon Jung , Sung Hojun , Bae Jin-Woo
Published: December 2021

Cultivation and isolation of gut bacteria are necessary for understanding their role in the intestinal ecosystem. We isolated a novel bacterium, designated strain BG01T, from the faeces of a patient with Crohn's disease. Strain BG01T was a strictly anaerobic, rod-shaped, Gram-variable and endospore-forming bacterium. Strain BG01T possessed C12 : 0, C18 : 0 dimethyl aldehyde (DMA) and C18 : 1
 ω9c DMA as predominant cellular fatty acids and meso-diaminopimelic acid as a diagnostic diamino acid. Strain BG01T grew at 15–45 °C (optimum, 37 °C), with 0–4 % (w/v) NaCl (optimum, 0–1 %), at pH 6–10 (optimum, pH 7) and was resistant to bile salt, but not to ampicillin, metronidazole, vancomycin and cefoperazone. Butyrate, propionate, oxalacetate and fumarate were produced as fermentation end products from Gifu anaerobic medium broth. Strain BG01T showed 97.7 % 16S rRNA gene sequence similarity, and 92.0 and 48.5 % of average nucleotide identity and digital DNA–DNA hybridization values, respectively, with

Anaerostipes caccae

KCTC 15019T. Genomic analysis indicated that strain BG01T had a butyrate-producing pathway. The genomic G+C content of the strain was 43.5 mol%. Results of the phenotypic, phylogenetic and genotypic analyses indicated that strain BG01T represents a novel butyrate-producing species of the genus

Anaerostipes

, for which the name Anaerostipes hominis sp. nov. is proposed. The type strain is BG01T (=KCTC 15617T=JCM 32275T).
Plasma oxylipin profile discriminates ethnicities in subjects with Non-alcoholic steatohepatitis: An exploratory analysis
Authors: Mazi Tagreed A. , Borkowski Kamil , Fiehn Oliver , Bowlus Christopher L. , Sarkar Souvik , Matsukuma Karen , Ali Mohamed R. , Kieffer Dorothy A. , Wan Yu-Jui Y. , Stanhope Kimber L. , Havel Peter J. , Newman John W. , Medici Valentina
Published: December 2021

Non-alcoholic fatty liver disease (NAFLD) includes a range of liver pathologies from steatosis (NAFL) to non-alcoholic steatohepatitis (NASH). With no clear mechanism, it affects Hispanics in the U.S. disproportionately compared to other ethnicities. Polyunsaturated fatty acids (PUFAs) metabolism and downstream inflammatory lipid mediators including oxylipin (OXL) and endocannabinoid (eCB) are altered in NAFLD and thought to contribute to its pathogenesis. It is not clear if variations in PUFA metabolism and downstream lipid mediators characterize ethnicity in NAFLD. This pilot study employed targeted lipidomic profiling for plasma PUFAs, non-esterified OXLs and eCBs in White Hispanics (HIS, n =10) and Caucasians (CAU, n =8) with obesity and biopsy-confirmed NAFL, compared with healthy control subjects (HC; n =14 HIS; n =8 CAU). Results indicate diminished long chain PUFA profile in HIS with NAFL and NASH, independent of obesity and histological severity. The profiling data also detected differences in plasma OXLs and eCBs profiles by ethnicity group in NASH, including lower levels of arachidonic acid derived OXLs observed in HIS. We conducted a secondary analysis to compare ethnicities within NASH (n =12 HIS; n =17 CAU). Results showed that plasma OXL profiles distinguished ethnicities with NASH and confirmed ethnicity-related differences in arachidonic acid metabolism. Our data also suggest lower lipoxygenase(s) and higher soluble epoxide hydrolase(s) activities in HIS compared to CAU with NASH. The underlying causes and implications of these differences on NAFLD severity are not clear and worth further investigation. Our findings provide preliminary data suggesting ethnicity-specific plasma lipidomic signature characterizing NASH that requires validation.
Online Phylogenetics using Parsimony Produces Slightly Better Trees and is Dramatically More Efficient for Large SARS-CoV-2 Phylogenies than de novo and Maximum-Likelihood Approaches
Authors: Thornlow Bryan , Kramer Alexander , Ye Cheng , De Maio Nicola , McBroome Jakob , Hinrichs Angie S. , Lanfear Robert , Turakhia Yatish , Corbett-Detig Russell
Published: December 2021

Phylogenetics has been foundational to SARS-CoV-2 research and public health policy, assisting in genomic surveillance, contact tracing, and assessing emergence and spread of new variants. However, phylogenetic analyses of SARS-CoV-2 have often relied on tools designed for de novo phylogenetic inference, in which all data are collected before any analysis is performed and the phylogeny is inferred once from scratch. SARS-CoV-2 datasets do not fit this mould. There are currently over 10 million sequenced SARS-CoV-2 genomes in online databases, with tens of thousands of new genomes added every day. Continuous data collection, combined with the public health relevance of SARS-CoV-2, invites an “online” approach to phylogenetics, in which new samples are added to existing phylogenetic trees every day. The extremely dense sampling of SARS-CoV-2 genomes also invites a comparison between likelihood and parsimony approaches to phylogenetic inference. Maximum likelihood (ML) methods are more accurate when there are multiple changes at a single site on a single branch, but this accuracy comes at a large computational cost, and the dense sampling of SARS-CoV-2 genomes means that these instances will be extremely rare because each internal branch is expected to be extremely short. Therefore, it may be that approaches based on maximum parsimony (MP) are sufficiently accurate for reconstructing phylogenies of SARS-CoV-2, and their simplicity means that they can be applied to much larger datasets. Here, we evaluate the performance of de novo and online phylogenetic approaches, and ML and MP frameworks, for inferring large and dense SARS-CoV-2 phylogenies. Overall, we find that online phylogenetics produces similar phylogenetic trees to de novo analyses for SARS-CoV-2, and that MP optimizations produce more accurate SARS-CoV-2 phylogenies than do ML optimizations. Since MP is thousands of times faster than presently available implementations of ML and online phylogenetics is faster than de novo, we therefore propose that, in the context of comprehensive genomic epidemiology of SARS-CoV-2, MP online phylogenetics approaches should be favored.
Drug repurposing screening identified tropifexor as a SARS-CoV-2 papain-like protease inhibitor
Authors: Ma Chunlong , Wang Yuyin , Choza Juliana , Wang Jun
Published: December 2021

The global COVID-19 pandemic underscores the dire need of effective antivirals. Encouraging progress has been made in developing small molecule inhibitors targeting the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and main protease (Mpro). However, the development of papain-like protease (PLpro) inhibitors faces several obstacles. Nevertheless, PLpro represents a high-profile drug target given its multifaceted roles in viral replication. PLpro is involved in not only the cleavage of viral polyprotein but also modulation of host immune response. In this study, we conducted a drug-repurposing screening of PLpro against the MedChemExpress bioactive compound library and identified three hits, EACC, KY-226, and tropifexor, as potent PLpro inhibitors with IC50 values ranging from 3.39 to 8.28 µM. The three hits showed dose-dependent binding to PLpro in the thermal shift assay. In addition, tropifexor inhibited the cellular PLpro activity in the FlipGFP assay with an IC50 of 10.6 µM. Gratifyingly, tropifexor showed antiviral activity against SARS-CoV-2 in Calu-3 cells with an EC50 of 4.03 µM, a 7.8-fold increase compared to GRL0617 (EC50 = 31.4 µM). Overall, tropifexor represents a novel PLpro inhibitor that can be further developed as SARS-CoV-2 antivirals.
Genetic insights into the management and conservation of Arctic charr in North Wales
Authors: Beck Samantha V. , Carvalho Gary R. , McCarthy Ian , Hanks Walter , Evans Robert , Edwards Robert , Taylor Martin , de Bruyn Mark
Published: December 2021

Aquatic species throughout the world are threatened by extinction in many parts of their range, particularly in their most southerly distributions. Arctic charr (Salvelinus alpinus) is a Holarctic species with a distribution that includes the glacial lakes of North Wales, towards it southern limit. To date, no genetic studies have been conducted to determine the genetic health of the three remaining native Arctic charr populations in North Wales, despite exposure to stocking and adverse environmental and ecological conditions. We used seven microsatellite loci to determine whether: 1) genetic differentiation existed between native populations; 2) translocated populations from Llyn Peris were genetically similar to the historically connected Llyn Padarn population; and 3) hatchery supplementation negatively impacted genetic diversity in Llyn Padarn. All three native populations retained their genetic integrity, with Llyn Bodlyn showing high levels of divergence (FST= 0.26 ± 0.02SD) as well as low genetic diversity (HO0.30) compared to remaining populations (HO0.64 ± 0.14SD). Although evidence suggests that stocking increased the effective population size of Llyn Padarn in the short term without impacting genetic diversity, the long term effects of such practices are yet to be seen. Results provide baseline data for conservation management, and highlight the need for protection of small isolated populations that are being negatively impacted by the processes of genetic drift due to escalating anthropogenic pressures. Continual monitoring of both Arctic charr and their habitats using a combination of methods will increase the likelihood that these threatened and iconic populations will persist in the future.
Multimodal Analyses of Stable Vitiligo Skin Identify Tissue Interactions That Control Disease Persistence
Authors: Shiu Jessica , Zhang Lihua , Lentsch Griffin , Flesher Jessica L , Jin Suoqin , Polleys Christopher , Jo Seong Jin , Mizzoni Craig , Mobasher Pezhman , Kwan Jasmine , Ruis-Diaz Francisca , Tromberg Bruce J , Georgakoudi Irene , Nie Qing , Balu Mihaela , Ganesan Anand K
Published: December 2021

Vitiligo is an autoimmune skin disease that is characterized by the progressive destruction of melanocytes by autoreactive CD8+ T cells. Melanocyte destruction in active vitiligo is mediated by CD8+ T cells but why white patches in stable disease persist is poorly understood. The interaction between immune cells, melanocytes, and keratinocytes in situ in human skin has been difficult to study due to the lack of proper tools. Here, we combine non-invasive multiphoton microscopy (MPM) imaging and single-cell RNA sequencing (scRNA-seq) to identify distinct subpopulations of keratinocytes in lesional skin of stable vitiligo patients. We show that these keratinocytes are enriched in lesional vitiligo skin and differ in metabolism, an observation corroborated by both MPM and scRNA-seq. Systematic investigation of cell-cell communication show that CXCL is the prominent signaling change in this small population of keratinocytes, which secrete CXCL9 and CXCL10 to create local inflammatory cytokine loops with T cells to drive stable vitiligo persistence. Pseudotemporal dynamics analyses predict an alternative keratinocyte differentiation trajectory that generates this new population of keratinocytes in vitiligo skin. In summary, we couple advanced imaging with transcriptomics and bioinformatics to discover cellcell communication networks and keratinocyte cell states that perpetuate inflammation and prevent repigmentation.

One Sentence Summary

Communication between keratinocytes, immune cells, and melanocytes maintain depigmented patches in stable vitiligo.
ABCC1/MRP1 exports cGAMP and modulates cGAS-dependent immunity
Authors: Maltbaek Joanna H. , Snyder Jessica M. , Stetson Daniel B.
Published: December 2021

The DNA sensor cyclic GMP-AMP synthase (cGAS) is important for antiviral and anti-tumor immunity. cGAS generates cyclic GMP-AMP (cGAMP), a diffusible cyclic dinucleotide that activates the antiviral response through the adapter protein Stimulator of Interferon Genes (STING). cGAMP is negatively charged and cannot passively cross cell membranes, but recent advances have established a role for extracellular cGAMP as an “immunotransmitter” that can be imported into cells. However, the mechanism by which cGAMP exits cells remains unknown. Here, we identify ABCC1/MRP1 as an ATP-dependent cGAMP exporter that influences STING signaling and type I interferon production. We demonstrate that ABCC1 deficiency exacerbates cGAS-dependent autoimmunity in theTrex1-/-mouse model of Aicardi-Goutières syndrome. These studies identify ABCC1-mediated cGAMP export as a key regulatory mechanism of the cGAS-STING pathway.
Regulation with cell size ensures mitochondrial DNA homeostasis during cell growth
Authors: Seel Anika , Padovani Francesco , Finster Alissa , Mayer Moritz , Bureik Daniela , Osman Christof , Klecker Till , Schmoller Kurt M.
Published: December 2021

To maintain stable DNA concentrations, proliferating cells need to coordinate DNA replication with cell growth. For nuclear DNA, eukaryotic cells achieve this by coupling DNA replication to cell cycle progression, ensuring that DNA is doubled exactly once per cell cycle. By contrast, mitochondrial DNA replication is typically not strictly coupled to the cell cycle, leaving the open question of how cells maintain the correct amount of mitochondrial DNA during cell growth. Here, we show that in budding yeast, mitochondrial DNA copy number increases with cell volume, both in asynchronously cycling populations and during G1 arrest. Our findings suggest that cell-volume-dependent mitochondrial DNA maintenance is achieved through nuclear encoded limiting factors, including the mitochondrial DNA polymerase Mip1 and the packaging factor Abf2, whose amount increases in proportion to cell volume. By directly linking mitochondrial DNA maintenance to nuclear protein synthesis, and thus cell growth, constant mitochondrial DNA concentrations can be robustly maintained without a need for cell-cycle-dependent regulation.
The high-resolution structure of cell membranes revealed by in situ cryo-electron tomography
Authors: Zhao Guanfang , Cheng Sihang , Yu Yang , Zou Tianyi , Wang Huili , Tao Changlu , Bi Guoqiang , Zhou Z. Hong , Wang Hongda
Published: December 2021

As the structural unit of life, cell is defined by the membrane system. The cell membrane separates the internal and external environment of the cell, and the endomembrane system defines the organelles to perform different functions1-3. However, lack of tools to in situ observe membrane proteins at a molecular resolution has limited our understanding of membrane organization and membrane protein interactions. Here we characterize the high-resolution 3D structure of human red blood cell (hRBC) membranes and the membrane proteins for the first time in situ by cryo-electron tomography (CryoET)4-7. By analyzing tomograms, we have obtained the first fine three-dimensional (3D) structure of hRBC membranes and found the asymmetrical distribution of membrane proteins on both sides of the membranes. We found that the membrane proteins are mainly located on the cytoplasmic side of hRBC membranes, with protein sizes ranging from 6nm to 8nm, in contrast to the ectoplasmic side with basically no proteins. Quantitative analysis of the density of hRBC membrane proteins shows that the membranes with higher protein occupancy have less phospholipid, making the membranes more rigid. Meanwhile, we obtained the channel protein-like structures by preliminary analysis of the membrane protein. Our results represent the first in situ structure characterization of the cell membranes and membrane proteins through cryoET and opens the door for understanding the biological functions of cell membranes in their physiological environments.
Unconventional secretion of unglycosylated ORF8 is critical for the cytokine storm during SARS-CoV-2 infection
Authors: Lin Xiaoyuan , Fu Beibei , Xiong Yan , Xing Na , Xue Weiwei , Guo Dong , Zaky Mohamed Y. , Pavani Krishna Chaitanya , Kunec Dusan , Trimpert Jakob , Wu Haibo
Published: December 2021

Coronavirus disease 2019 is a respiratory infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidence on the pathogenesis of SARS-CoV-2 is accumulating rapidly. In addition to structural proteins such as Spike and Envelope, the functional roles of non-structural and accessory proteins in regulating viral life cycle and host immune responses remain to be understood. Here, we show that open reading frame 8 (ORF8) acts as messenger for inter-cellular communication between alveolar epithelial cells and macrophages during SARS-CoV-2 infection. Mechanistically, ORF8 is a secretory protein that can be secreted by infected epithelial cells via both conventional and unconventional secretory pathways. The unconventionally secreted ORF8 recognizes the IL17RA receptor of macrophages and induces cytokine release. However, conventionally secreted ORF8 cannot bind to IL17RA due to N-linked glycosylation. Furthermore, we found that Yip1 interacting factor homolog B (YIF1B) is a channel protein that translocates unglycosylated ORF8 into vesicles for unconventional secretion. Blocking the unconventional secretion of ORF8 via a YIF1B knockout in hACE2 mice attenuates inflammation and yields delayed mortality following SARS-CoV-2 challenge.