bluuebunny/crossref_metadata_2025 huggingface dataset:
Gender differentials in undernutrition among Tanzanian adolescents: a rural‐urban comparison (LB475)
Authors: Otis Nicholas , Peterman Jerusha , Cordeiro Lorraine
Published: June 2021

Background: Urban population growth has outpaced expectations in developing countries, changing physical, social, and economic landscapes with implications on health across gender. Comparative studies on gender differences in nutritional status by geographic location present mixed findings.

Objective: This study examines gender differentials in undernutrition across rural‐urban residence in a sample of Tanzanian adolescents.

Methods: This cross‐sectional study examines predictors of poor nutritional status across urban and rural adolescents aged 10‐14 (n=892) in Tanzania. Undernutrition was classified as BMI for Age <5th percentile of the NCHS/WHO reference. Logistic regression analysis tested the association between undernutrition, gender, and urban‐rural residence after adjusting for covariates.

Results: The prevalence of undernutrition was 23.7 % among rural and 11.8% among urban adolescents (p<0.05). Among males, prevalence of undernutrition was 28.8% for rural and 17.5% for urban adolescents (p<0.05). The rates for rural females were 18.4% compared to 6% for urban peers (p<0.05). Overall, males more likely to be undernourished than females after adjusting for urban/rural residence and age [OR=2.15 (95%CI: 1.49, 3.09); p<0.05].

Conclusions: Our findings suggest that adolescents in rural settings experience higher rates of undernutrition than urban youth. In particular, programs and policies aiming to improve public health in Tanzania should target rural males. Longitudinal studies are needed to determine whether the gender differential observed in adolescent nutritional status in developing countries has a physiological explanation and whether growth trajectories differ across urban‐rural settings.

Grant Funding Source: Supported by UNICEF/Tanzania, and the Commonwealth Honors College and the Department of Nutrition of the University of Massachusetts Amherst
A spinasterol glycoside repressed expression of the chemokine MDC/CCL22 induced by IFN‐γ and TNF‐α in human keratinocytes and inhibits DNCB‐induced allergic skin inflammation (LB545)
Authors: JUNG MIRA , Lee Tae Hoon , Kim Ji Young
Published: June 2021

The chemokine MDC/CCL22 is considered to be a pivotal mediator in the inflammatory responses during the development of inflammatory skin diseases, such as atopic dermatitis (AD). Expression of MDC/CCL22 gene can be induced by IFN‐γ and TNF‐α in keratinocytes, one of major cell types in the skin. In the present study, we investigated the effects of spinasterol‐Glucose, one of phytosterols from Stewartia koreana leaves, on IFN‐γ/TNF‐α‐induced expression of MDC/CCL22 and on skin inflammation in animal models. Our results showed that spinasterol‐Glc inhibited mRNA and protein expression of MDC/CCL22 in TNF‐α/IFN‐γ‐stimulated HaCaT keratinocytes in dose‐dependent manners. We found that spinasterol‐Glc inhibited IFN‐γ/TNF‐α ‐induced activation of NF‐κB and STAT1. Inhibitors for NF‐κB(Bay11‐7085), JAK/STAT (AG490), p38 (SB203580) reduced production of MDC/CCL22 in HaCaT cells, indicating that spinalsterol‐Glc inhibits expression of MDC/CCL22 via p38 and JAK signaling pathways and the downstream NF‐κB and STAT factors activated by IFN‐γ/TNF‐α. Furthermore, we demonstrated that topical administration of spinasterol‐Glc reduced epidermal thickness and infiltration of inflammatory cells compare to positive control. Levels of serum histamine and IgE were also decreased after the application of spinasterol‐Glc. Our results suggest that spinasterol‐Glc may have significant effects on improving AD‐like conditions via inhibiting expression of inflammatory cytokines and chemokines including MDC/CCL22.
Effects of the Therapeutic Doses of Topiramate on the Placenta of Rats: A Histological and Morphometric Study (LB62)
Authors: Othman Manal , Salem Abdel Halim , Sequeira Reginald , Abu‐Hijleh Marwan , Fadel Raouf
Published: June 2021

The antiepileptic drug topiramate is used in the treatment of epilepsy in many patients including pregnant women. Topiramate was reported to have teratogenic effects. This study is focusing on the effects of topiramate on the placental structure. Pregnant rats were treated with topiramate at doses of 50 and 100 mg/Kg body weight orally. On day 20 the pregnant rats were sacrificed, and the placentae were collected and processed for histological and morphometric evaluation. There were degenerative changes affecting the three layers of the placenta. In the decidual layer, the cells showed deposition of fibrous and hyaline materials. Vacuolization of cells and hemorrhages were also detected. In the basal layer, the trophoblast cell types were affected. This ranged from vacuolization, cytolysis and cyst formation. In the labyrinthine layer, there was increase in the fibrinoid material and fetal mesenchyme. There was also degeneration of cells and congestion of blood vessels. Morphometric data revealed a significant decrease in the thickness of the decidual layer and increase in that of the basal layer of the treated groups compared to control. The results obtained from this study showed harmful effects of topiramate on the placental structure. This may explain one of the possible mechanisms which leads to its teratogenicity.
The Wnt/β‐catenin coupled with HIF‐1α/ VEGF signal pathway involved neurovascular unit protection by galangin against permanent focal cerebral ischemia in rats (LB628)
Authors: Li Shaojing
Published: June 2021

Background In recent years, the concept of the neurovascular unit (NVU) has emerged as a new paradigm for understanding the pathology of central nervous system (CNS) disease, including stroke. Our previous studies reported the neuroprotection of galangin on permanent focal cerebral ischemia in vivo, but its underlying mechanisms are far from clear. In this study, we investigated the effects of galangin on NVU functions and associated signal pathway in rats impaired by middle cerebral artery occlusion (MCAO)‐induced focal cerebral ischemia.

Methods Neurological scores were used to reflect the therapeutic effect of galangin. Cerebral edema and the detection of Evan’s blue (EB) concentration in brain tissue were utilized to evaluate the permeability of BBB. The pathological changes of NVU ultrastructure and BBB permeability were observed by transmission electron microscopy (TEM) after MCAO visually. The protective mechanism of galangin was operated through Real‐time quantitative polymerase chain reaction (RT‐PCR) and Western blot.

Results Results showed that galangin could ameliorate neurological scores and brain edema, reduce the concentration of EB in brain tissue after MCAO.

Meanwhile, ultrastructural changes of NVU were improved by galangin. Moreover, the results of RT‐PCR and Western blot revealed that galangin protect NVU through Wnt/β‐catenin pathway coupled with HIF‐1α/vascular endothelial growth factor (VEGF). VEGF was activated in an HIF‐1α dependent way. VEGF and β‐catenin could be the key joints of these two coupled pathways.

Conclusions All these data in this study firstly demonstrated that anti‐cerebral ischemia mechanism of galangin might through its regulation effect that enhance angiogenesis and neurogenesis in NVU. Galangin might function as a potential multi‐target drug in the treatment of ischemic stroke.

Grant Funding Source: the National Natural Science Foundation of China (No. 81274133 and 81303261) and the Major Scientific and Technological Special Project for “Significant New Drugs Creation” (No. 2012ZX09103‐201‐055)
Assessment of physiological parameters in the rat following intravenous injection of superparamagnetic iron oxide nanoparticles (SPION’s) (LB730)
Authors: Edge Deirdre , Shortt Christine , Markos Farouk , Barry Elaine
Published: June 2021

With a growing number of applications associated with nanostructures, characterization in‐vivo is imperative. Previous MRI studies have described the accumulation of SPION’s in the rat and pig kidneys following intravenous (i.v) injection. Since intra‐renal accumulation of SPION’s may lead to acute kidney injury, we sought to assess an array of physiological parameters including renal function following injection of SPION’s.

Adult male Wistar rats (n=16) were anaesthetised with an i.p. injection of sodium pentobarbital (60mg/kg bw). Mean arterial pressure (MAP) was continually monitored. Plasma and urine samples were collected over 20 minute clearance periods, two prior to and two following injection of 2mg/kg SPION’s (MF66 or OD15). Plasma and urine were analysed for electrolyte measurements and determination of the glomerular filtration rate (GFR).

I.v. injection of both SPION’s led to a significant transient drop in MAP. Glomerular filtration rate (GFR) was not significantly affected following SPION injection, however fractional sodium excretion (FENa) and absolute sodium excretion (UVNa) significantly increased in SPION‐treated animals compared to baseline values, (p=0.0313, one‐tailed Wilcoxin signed rank test).

The mechanisms of this MAP drop and natriuresis is unclear but may involve vasodilator release, e.g. prostaglandins, which oppose the actions of the Renin Angiotensin System.

Grant Funding Source: Framework Project 7
The effects of early maternal separation on gastric mucosa maturation and stress response (LB739)
Authors: Ogias Daniela , Gama Patricia
Published: June 2021

Repeated maternal separation (MS) is a potent and chronic stressor that activates the HPA axis response. We demonstrated that few hours of fasting elevate plasma corticosterone (CORT) in pups, but it also increases CBG binding and reduces glucocorticoid receptor (GR) intracellular traffic in the gastric epithelium. In the stomach, complete cell differentiation occurs by the third postnatal week, in parallel with plasma CORT augment. However, it is not clear how CORT and maternal separation affect gastric epithelium growth and maturation. Currently, our aims were to evaluate: the impacts of MS on body weight; total CORT plasma levels by RIA; gr expression, and the consequences on rat gastric mucosa cell differentiation through the evaluation of developmental target genes by qPCR. For this purpose we used 10, 14, 18, 21 and 30‐ day‐ old rats divided into two groups: 1) Maternal separated group (MS) in which pups were removed from their dams and placed in a clean cage (32° C) for 3 h/day (from postnatal day 2‐ 21),; 2) Control group (C), in which pups were equally manipulated, but were maintained with the dams until weaning (21 days). MS resulted in loss of body weight in the developing rats (p <0.05), but such difference did not persist until 30‐ d‐old rats. Total CORT levels increased only in 18‐ and 30‐d‐old MS rats (p< 0.05).gr expression was down‐ regulated by MS only in 18‐ d‐ old pups (p <0.05). Mucin 6 expression increased after MS in 18‐ and 30‐ d‐ old rats, but decreased at 21 days (p <0.05). Mist1 increased only in 18‐ and 30‐d‐old rats (p <0.05), while Pepsinogen C expression was amplified only in 18‐ d‐old MS pups (p <0.05). In conclusion, repeated MS during early postnatal life reduced body mass, altered total CORT plasma levels and modified the profile of gastric genes expression throughout postnatal development.

Grant Funding Source: Supported by Grant 2011/17415‐3 and 2012/10948‐9, São Paulo Research Foundation (FAPESP)
Modeling Life and Consciousness as Qualities (LB853)
Authors: Ghosh Santibrata
Published: June 2021

We are familiar with the so called seven characteristics of life, featured in text books. These by themselves only describe a typical living being, but not what represents “life”. While mathematical modeling in dynamical systems have been done, by many investigators including this author, to simulate biochemical and biophysical processes in vivo, in health and in disease, a description of what life is has been elusive.

One may ,however, say that at the moment of death, everything in the body ( viz molecules and their motions ) remain identical to what it was at the last moment of life. The difference being that Life has something more than the underlying physical and chemical aspects, more than the reductive elements. 'Life' is a totality, which is more like a flow, i.e. a time derivative or differential, as in Zeno’s paradox on “arrow in flight”. This is what may be called , in a dialectical sense, a new quality that is 'life'.

Something else accompanies life in animals having a full‐fledged nervous system . Through the sense organs, the system, a living being or an animal, perceives all that happens ; it also stores, compiles and integrates all incoming information as on a hard disk for later use. This has to do with what we call consciousness, a much discussed aspect of life. Now if one becomes unconscious but still alive, we may use the same metaphor as above; i.e. that all the molecular information are the same at the moment one conscious animal becomes unconscious, making the flow of consciousness a 'totality'. Call it manifestation, emergence or qualia, it really represents a quality in the dialectical sense.

This ability, however, needs the input of vital energy from life, implying that consciousness needs life but not vice versa, though ‘life’ may need the autonomic nervous system (involuntary nervous system) acting largely below the level of consciousness.
Kappa Opioid Receptor‐Based Treatments for Pain (LB88)
Authors: Assana C. , Feller C. , Fogel M. , Frelka A. , Gottfried S. , Jaber R. , Keyes M. , Koehler M. , Kujawa K. , Lautz N. , Olson S. , Pena J. , Ries L. , Schauer L. , Scherrer C. , Strandberg C. , Strandberg S. , Cunningham Christopher
Published: June 2021

Dangerous painkillers may cause serious problems for those who fall into drugs’ addictive trap, such as former NFL quarterback Brett Favre. The addictiveness of painkillers such as OxyContin and Vicodin is largely attributed to the response they trigger in proteins such as mu opioid receptors (MOPs). This receptor activates cellular signaling pathways responsible for dulling pain; however, the protein also has the ability to stimulate cellular signaling pathways that makes MOP‐based painkillers rewarding. An alternate target that alleviates pain but does not produce reward is the kappa opioid receptor (KOP). Unfortunately, many KOP agonists also activate signaling pathways that produce hallucinogenic effects. To investigate the changes that occur when KOP binds to different ligands, the Divine Savior Holy Angels SMART (Students Modeling A Research Topic) Team has used 3D printing technology to model the active site of the KOP with salvinorin A, to see how the induced fit changes the signal transduction pathways in a neuron. Manipulating receptor proteins like the KOP to inhibit pain pathways without the addictive effect of MOP‐targeting painkillers would be a breakthrough in chronic pain management. Computer‐aided drug design helps streamline the development of KOP ligands that activate this receptor in ways that result in less hallucinogenic effects.

Grant Funding Source: Supported by a grant from NIH‐CTSA.
Physical Model of p300 Acetyltransferase and Bromodomain (LB89)
Authors: Assad Fatima , Briglall Annie , Eusebio Diana , Flores Edwin , Ramirez Hillary , Simon Margarita , Valentin Tashina , Zaman Mohammed , Granberry Allison , Houck‐Loomis Brian
Published: June 2021

In the nucleus of a cell, chromatin is structured into nucleosomes in which the DNA is wrapped around a histone core, condensing the DNA. In this form, DNA is not readily accessible for gene expression. Post‐translational modification to the histone proteins, such as acetylation, regulates gene expression. Histone acetyltranferase (HAT) catlyzes the transfer of an acetyl group to a target lysine by aligning an acetyl‐CoA group with a lysine on the unstructured histone tail region. The acetylated lysine tail then becomes a binding site for other factors. Bromodomain‐containing proteins (BRD) recognize and bind to the acetylated lysine and recruit transcription factors and RNA polymerase II complex to the DNA. The transcriptional coactivator p300 contains both a HAT and BRD region and is known to play an important role in cell cycle and tumor suppression. The activity of the p300 HAT is in part dependent upon the activity of its BRD, and disruption of the BRD can significantly affect transcription of p300‐regulated gene targets. The Hostos‐Lincoln Academy SMART (Students Modeling A Research Topic)Team has generated models of both the HAT (3biy.pdb) and BRD (3i3j.pdb) of p300 using 3D printing technology to illustrate the interplay between HAT and BRD in the transcription of p300 genes.

Grant Funding Source: Supported by grants from the NIH‐SEPA and NIH‐CTSA.
Impact of edaravone on serum CXC chemokine ligand-13 levels and perioperative neurocognitive disorders in elderly patients with hip replacement
Authors: Xie Hai-Hui , Ma Hong-Yan , Zhang Shu , Li Jian-Wen , Han Qi , Chen Hui-Qun , Su Bo-Qin , Zhou Jian-Ping
Published: June 2021

Background:

Perioperative neurocognitive disorders (PND) are a series of severe complications in the perioperative and anesthetic periods with a decline in memory, execution ability, and information processing speed as the primary clinical manifestation. This study aimed to evaluate the impact of edaravone (EDA) on PND and peripheral blood C-X-C motif chemokine ligand 13 (CXCL13) levels in elderly patients with hip replacement.

Methods:

A total of 160 elderly patients undergoing hip arthroplasty in Affiliated Dongguan People's Hospital of Southern Medical University (from March 2016 to March 2018) were randomly and double-blindly categorized into an EDA group and a control group (CON). Group EDA was administered intravenously EDA 30 min before surgery, and group CON was administered intravenously saline. The cognitive function of the two groups was evaluated 1-day before the operation and at 1 and 12 months after surgery, and the incidence of post-operative delirium was tested on days 1, 3, and 7 after surgery using the Chinese version of the confusion assessment method. Serum CXCL13 and interleukin (IL)-6 concentrations were measured before anesthesia, during surgery (30 min after skin incision), and on days 1, 3, and 7 after surgery. The continuous variables in accordance with normal distribution were tested using the Student's t test, the continuous variables without normal distribution using the Mann-Whitney U test, and categorical variables by the χ
2 test or Fisher exact test.

Results:

The incidence of post-operative delirium within 7 days after surgery was significantly higher in group CON than that in group EDA (31.3% vs. 15.0%, t = −5.6, P < 0.001). The modified telephone interview for cognitive status and activities of daily life scores were significantly higher in the group EDA than those in the group CON at 1 month (39.63 ± 4.35 vs. 33.63 ± 5.81, t = −2.13, P < 0.05 and 74.3 ± 12.6 vs. 61.2 ± 13.1, t = −1.69, P < 0.05) and 12 months (40.13 ± 5.93 vs. 34.13 ± 5.36, t = −3.37, P < 0.05 and 79.6 ± 11.7 vs. 65.6 ± 16.6, t = −2.08, P < 0.05) after surgery; and the incidence of neurocognitive dysfunction was significantly lower in the group EDA than that in the group CON (P < 0.05). Serum CXCL13 and IL-6 concentrations were significantly lower in the group EDA than those in the group CON during and after surgery (P < 0.05).

Conclusion:

EDA can significantly reduce the serum concentrations of CXCL13 and IL-6 and improve the PND of patients.
Risk assessment of malignancy in solitary pulmonary nodules in lung computed tomography: a multivariable predictive model study
Authors: Liu Hai-Yang , Zhao Xing-Ru , Chi Meng , Cheng Xiang-Song , Wang Zi-Qi , Xu Zhi-Wei , Li Yong-Li , Yang Rui , Wu Yong-Jun , Zhang Xiao-Ju
Published: June 2021

Background:

Computed tomography images are easy to misjudge because of their complexity, especially images of solitary pulmonary nodules, of which diagnosis as benign or malignant is extremely important in lung cancer treatment. Therefore, there is an urgent need for a more effective strategy in lung cancer diagnosis. In our study, we aimed to externally validate and revise the Mayo model, and a new model was established.

Methods:

A total of 1450 patients from three centers with solitary pulmonary nodules who underwent surgery were included in the study and were divided into training, internal validation, and external validation sets (n = 849, 365, and 236, respectively). External verification and recalibration of the Mayo model and establishment of new logistic regression model were performed on the training set. Overall performance of each model was evaluated using area under receiver operating characteristic curve (AUC). Finally, the model validation was completed on the validation data set.

Results:

The AUC of the Mayo model on the training set was 0.653 (95% confidence interval [CI]: 0.613–0.694). After re-estimation of the coefficients of all covariates included in the original Mayo model, the revised Mayo model achieved an AUC of 0.671 (95% CI: 0.635–0.706). We then developed a new model that achieved a higher AUC of 0.891 (95% CI: 0.865–0.917). It had an AUC of 0.888 (95% CI: 0.842–0.934) on the internal validation set, which was significantly higher than that of the revised Mayo model (AUC: 0.577, 95% CI: 0.509–0.646) and the Mayo model (AUC: 0.609, 95% CI, 0.544–0.675) (P < 0.001). The AUC of the new model was 0.876 (95% CI: 0.831–0.920) on the external verification set, which was higher than the corresponding value of the Mayo model (AUC: 0.705, 95% CI: 0.639–0.772) and revised Mayo model (AUC: 0.706, 95% CI: 0.640–0.772) (P < 0.001). Then the prediction model was presented as a nomogram, which is easier to generalize.

Conclusions:

After external verification and recalibration of the Mayo model, the results show that they are not suitable for the prediction of malignant pulmonary nodules in the Chinese population. Therefore, a new model was established by a backward stepwise process. The new model was constructed to rapidly discriminate benign from malignant pulmonary nodules, which could achieve accurate diagnosis of potential patients with lung cancer.
A multicenter retrospective study on the real-world outcomes of autologous vs. allogeneic hematopoietic stem cell transplantation for peripheral T-cell lymphoma in China
Authors: Gu Zhen-Yang , Dong Yu-Jun , Fu Xiao-Rui , Li Nai-Nong , Liu Yao , Wu Xiao-Xiong , Wang Yi-Ni , Li Yu-Hang , Ren Han-Yun , Zhang Ming-Zhi , Li Xiao-Fan , Wang Mai-Hong , Wu Ya-Mei , Liu Dai-Hong , Wang Zhao , Hu Liang-Ding , Huang Wen-Rong
Published: June 2021

Background:

There were few studies on real-world data about autologous hematopoietic stem cell transplantation (auto-HSCT) or allogeneic HSCT (allo-HSCT) in peripheral T-cell lymphoma (PTCL). This study aimed to investigate the clinical outcomes of patients who received auto-HSCT or allo-HSCT in China.

Methods:

From July 2007 to June 2017, a total of 128 patients who received auto-HSCT (n 
= 72) or allo-HSCT (n 
= 56) at eight medical centers across China were included in this study. We retrospectively collected their demographic and clinical data and compared the clinical outcomes between groups.

Results:

Patients receiving allo-HSCT were more likely to be diagnosed with stage III or IV disease (95% vs. 82%, P = 0.027), bone marrow involvement (42% vs. 15%, P = 0.001), chemotherapy-resistant disease (41% vs. 8%, P = 0.001), and progression disease (32% vs. 4%, P < 0.001) at transplantation than those receiving auto-HSCT. With a median follow-up of 30 (2–143) months, 3-year overall survival (OS) and progression-free survival (PFS) in the auto-HSCT group were 70%(48/63) and 59%(42/63), respectively. Three-year OS and PFS for allo-HSCT recipients were 46%(27/54) and 44%(29/54), respectively. There was no difference in relapse rate (34%[17/63] in auto-HSCT vs. 29%[15/54] in allo-HSCT, P = 0.840). Three-year non-relapse mortality rate in auto-HSCT recipients was 6%(4/63) compared with 27%(14/54) for allo-HSCT recipients (P = 0.004). Subanalyses showed that patients with lower prognostic index scores for PTCL (PIT) who received auto-HSCT in an upfront setting had a better outcome than patients with higher PIT scores (3-year OS: 85% vs. 40%, P = 0.003). Patients with complete remission (CR) undergoing auto-HSCT had better survival (3-year OS: 88% vs. 48% in allo-HSCT, P = 0.008). For patients beyond CR, the outcome of patients who received allo-HSCT was similar to that in the atuo-HSCT group (3-year OS: 51% vs. 46%, P = 0.300).

Conclusions:

Our study provided real-world data about auto-HSCT and allo-HSCT in China. Auto-HSCT seemed to be associated with better survival for patients in good condition (lower PIT score and/or better disease control). For patients possessing unfavorable characteristics, the survival of patients receiving allo-HSCT group was similar to that in the auto-HSCT group.
Alterations in thymocyte populations under conditions of endotoxin tolerance
Authors: Tao Yi-Jing , Zhao Juan-Juan , Rao Li-Hua , Yang Song , Zhang Guo-Liang , Guo Meng-Meng , Chen Chao , Xu Lin
Published: June 2021

Background:

Endotoxin tolerance (ET) is a protective phenomenon in which pre-treatment with a tolerance dose of lipopolysaccharide (LPS) leads to dramatically elevated survival. Accumulating evidence has shown that peripheral T cells contribute to the induction of ET. However, what happens to T cell development in the thymus under ET conditions remains unclear. The purpose of this study was to analyze the alterations in thymocyte populations (double-positive [DP] and single-positive [SP] cells) under ET conditions.

Methods:

Mice were intraperitoneally injected with LPS at a concentration of 5 mg/kg to establish an LPS tolerance model and were divided into two groups: a group examined 72 h after LPS injection (72-h group) and a group examined 8 days after LPS injection (8-day group). Injection of phosphate-buffered saline was used as a control (control group). Changes in thymus weight, cell counts, and morphology were detected in the three groups. Moreover, surface molecules such as CD4, CD8, CD44, CD69, and CD62L were analyzed using flow cytometry. Furthermore, proliferation, apoptosis, cytokine production, and extracellular signal-regulated kinase (ERK) pathway signaling were analyzed in thymocyte populations. The polymorphism and length of the T-cell receptor (TCR) β chain complementarity-determining region 3 (CDR3) were analyzed using capillary electrophoresis DNA laser scanning analysis (ABI 3730).

Results:

Thymus weight and cell counts were decreased in the early stage but recovered by the late stage in a murine model of LPS-induced ET. Moreover, the proportions of DP cells (control: 72.130 ± 4.074, 72-h: 10.600 ± 3.517, 8-day: 84.770 ± 2.228), CD4+ SP cells (control: 15.770 ± 4.419, 72-h: 44.670 ± 3.089, 8-day: 6.367 ± 0.513), and CD8+ SP cells (control: 7.000 ± 1.916, 72-h: 34.030 ± 3.850, 8-day: 5.133 ± 0.647) were obviously different at different stages of ET. The polymorphism and length of TCR β chain CDR3 also changed obviously, indicating the occurrence of TCR rearrangement and thymocyte diversification. Further analysis showed that the expression of surface molecules, including CD44, CD69, and CD62L, on thymocyte populations (DP and SP cells) were changed to different degrees. Finally, the proliferation, apoptosis, cytokine production, and ERK pathway signaling of thymocyte populations were changed significantly.

Conclusion:

These data reveal that alterations in thymocyte populations might contribute to the establishment of ET.
Chondrodermatitis Nodularis Nasi: A Case Report of a Rare Variant of Chondrodermatitis Nodularis Helicis
Authors: Bal Arjun , Rashid Zaina , Shamma H. Nicholas
Published: June 2021

Chondrodermatitis nodularis helicis is an inflammatory condition affecting the helix or antihelix of the ear. It is commonly described as a solitary, painful, ulcerated nodule affecting the cartilage or skin because of continuous pressure, trauma, sun exposure, or ischemic changes. In this case report, we present a rare variant of chondrodermatitis, named chondrodermatitis nodularis nasi, which affects the skin and cartilage of the nose. Clinical resemblance to neoplasms of the skin such as squamous cell carcinoma and basal cell carcinoma requires that a biopsy be performed for definitive diagnosis. On histopathological examination, chondrodermatitis presents as a central ulcer bordered by epidermal hyperplasia, hypergranulosis, hyperkeratosis, and parakeratosis with fibrin deposits in the papillary dermis admixed with sparse inflammatory cells. Included in this case report is a discussion of the clinical and histopathology of chondrodermatitis nodularis nasi. With increased frequency of diagnosing this rare variant, better management and treatments can be explored.
Comparative Immunohistochemical Study of Hidroacanthoma Simplex and Clonal Seborrheic Keratosis With GATA3 and p63
Authors: Lin Chien-Yio , Kuo Tseng-tong , Chang Ya-Ching
Published: June 2021

Histopathologically both hidroacanthoma simplex (HS) and clonal seborrheic keratosis (CSK) are characterized by intraepidermal nests of tumor cells. Although they show subtle microscopic differences, they can be difficult to accurately differentiate. Previous immunohistochemical studies have been inconclusive. We conducted an immunohistochemical study with GATA3 and p63 on cases of HS and CSK tentatively identified by their microscopic appearances and cases of eccrine poroma and seborrheic keratosis as their respective controls. The clinical, histopathological, and dermoscopic findings of these cases were also reviewed. All cases of HS and poroma were negative for GATA3, whereas all cases of CSK and seborrheic keratosis were positive for GATA3. HS, CSK, and their controls were all positive for p63. Microscopic, clinical, and dermoscopic differences were also found between HS and CSK. Our study demonstrated that GATA3 is useful for differentiating HS from CSK. Our initial microscopic observations also proved to be reliable, but immunostaining with GATA3 is helpful for confirming the diagnosis or establishing the diagnosis of uncertain cases. Awareness of the clinical and dermoscopic features of these 2 entities could also avoid misdiagnosis based solely on pathological observation.
Adding Perplexity to Rarity: Diffuse S100-Protein and SOX10 Expression in a Molecularly Confirmed PAX7-Positive Primary Cutaneous Ewing Sarcoma
Authors: Parra Ourania , Thuraisingam Ravina , Baker Michael L. , Kerr Darcy A. , Linos Konstantinos
Published: June 2021

Primary cutaneous Ewing sarcoma (EWS) is a very rare neoplasm that shares similar morphologic, immunohistochemical, and molecular features with its osseous counterpart. Herein, we present an extraordinarily rare case of PAX7-positive cutaneous EWS in a 9-year-old girl that was also diffusely positive for SOX10 and S100-protein. Next generation sequencing detected the EWSR1-FLI1 fusion supporting the diagnosis, which was further validated by break-apart EWSR1 fluorescence in situ hybridization. Diffuse S100-protein and SOX10 expression has been reported only in a handful of cases of EWS and may pose significant diagnostic challenges for dermatopathologists. PAX7 is a recently introduced marker, which is highly sensitive for EWS and can potentially have discriminatory power in the differential diagnosis of cutaneous undifferentiated round blue cell tumors.
Intraoperative Diagnosis of Histologic Change in Irradiated Skeletal Muscle
Authors: Guffey Darren J. , Guerra Ricardo , Malhi Jasmine K. , Russell Mark
Published: June 2021

Adjuvant radiation may be used to reduce the recurrence of high-risk cutaneous squamous cell carcinoma after resection. Adjuvant radiation can produce histologic changes in the skeletal muscle that mimic keratinocyte atypia, presenting a diagnostic challenge during subsequent resections. We present a case of cutaneous squamous cell carcinoma and histologic changes observed in a fresh frozen section that were consistent with degenerative changes of irradiated skeletal muscle that had a muscle-specific actin+, Melan-A−, and cytokeratin− immunophenotype on paraffin-embedded permanent sections. We also reviewed the literature of other similar reported findings on irradiated skeletal muscle.
Acylated Ghrelin Attenuates l-Thyroxin–induced Cardiac Damage in Rats by Antioxidant and Anti-inflammatory Effects and Downregulating Components of the Cardiac Renin–angiotensin System
Authors: Badi Rehab
Published: June 2021

This study investigated the protective effect of acylated ghrelin (AG) against l-thyroxin (l-Thy)-induced cardiac damage in rats and examined possible mechanisms. Male rats were divided into five intervention groups of 12 rats/group: control, control + AG, l-Thy, l-Thy + AG, and l-Thy + AG + [D-Lys3]-GHRP-6 (AG antagonist). l-Thy significantly reduced the levels of AG and des-acyl ghrelin and the AG to des-acyl ghrelin ratio. Administration of AG to l-Thy–treated rats reduced cardiac weights and levels of reactive oxygen species and preserved the function and structure of the left ventricle. In addition, AG also reduced the protein levels of cleaved caspase-3 and cytochrome c and prevented mitochondrial permeability transition pore opening. In the left ventricle of both control + AG-treated and l-Thy + AG-treated rats, AG significantly increased left ventricular levels of manganese superoxide dismutase (SOD2), total glutathione (GSH), and Bcl2. It also reduced the levels of malondialdehyde, tumor necrosis factor-α (TNF-α), interleukin-6, and Bax and the nuclear activity of nuclear factor-kappa B. Concomitantly, in both treated groups, AG reduced the mRNA and protein levels of NADPH oxidase 1, angiotensin (Ang) II type 1 receptor, and Ang-converting enzyme 2. All the beneficial effects of AG in l-Thy–treated rats were prevented by the coadministration of [D-Lys3]-GHRP-6, a selective growth hormone secretagogue receptor subtype 1a antagonist. In conclusion, AG protects against hyperthyroidism-induced cardiac hypertrophy and damage, which is mainly due to its antioxidant and anti-inflammatory potentials and requires the activation of GHS-R1a.
Wogonin Alleviates Cisplatin-induced Cardiotoxicity in Mice Via Inhibiting Gasdermin D-mediated Pyroptosis
Authors: Xu Jiajun , Zhang Bin , Chu Zhenliang , Jiang Fenfen , Han Jibo
Published: June 2021

Cardiotoxicity has been well documented as a side effect of cisplatin (CDDP) treatment. The inflammatory response plays a crucial role in the pathological process of CDDP-induced cardiotoxicity. Wogonin is a natural flavonoid compound that possesses cardioprotective and anti-inflammatory qualities. Knowledge of the pharmacological effect and mechanism of wogonin could reveal an efficient way to identify therapeutic strategies. In this study, the potential of wogonin to antagonize CDDP-induced cardiotoxicity was evaluated in C57BL/6 mice in vivo and in H9c2 cells in vitro. The results showed that wogonin protected against CDDP-induced cardiac dysfunction, myocardial injury, and pyroptosis in vivo. Using a Gasdermin D expression plasmid, we revealed that wogonin dramatically reduced CDDP-induced pyroptosis by modulating the Gasdermin D protein in H9c2 cells. In conclusion, wogonin has great potential in attenuating CDDP-induced cardiotoxicity. In addition, greater emphasis should be placed on the antipyroptotic effects of wogonin for the treatment of other diseases.
Impact of Breast Reconstruction Patients on Cosmetic Practice
Authors: Cooper Danielle C. , Qureshi Ali A. , Sharma Ketan , Tenenbaum Marissa M. , Myckatyn Terence M.
Published: June 2021

Background:

Postmastectomy breast reconstruction can often restore a patient’s self-image. A notable percentage of women will go on to seek elective aesthetic procedures to further improve their perceived appearance. The purpose of this study was to determine the percentage of primary breast reconstruction patients who go on to receive a cosmetic procedure. We identify factors that may increase the likelihood that a patient subsequently chooses to pursue a cosmetic procedure.

Methods:

A retrospective review of primary breast reconstruction patients of the two senior authors was conducted from January 2014 through December 2015. Demographics, types of cosmetic procedures received, and time to first cosmetic procedure were obtained. Time to first cosmetic procedure was assessed from date of mastectomy through December 2017. Logistic regression was performed to identify factors associated with obtaining cosmetic procedures.

Results:

There were 289 patients in our cohort with ~10% who subsequently sought a cosmetic procedure at our practice. The average time to conversion was ~9 months after mastectomy. The majority (67%) underwent noninvasive procedures only. Patients with lower-staged breast cancers were more likely to undergo a cosmetic procedure (P < 0.042).

Conclusions:

At least 10% of patients undergoing primary breast reconstruction over a year period went on to have a cosmetic procedure during the study period. The majority of patients pursued noninvasive cosmetic procedures. Reconstruction of women with higher cancer stages was associated with a lower likelihood of pursuing a cosmetic procedure during the time period studied.
Plastic Surgery and Music: Examining Plastic Surgery References in Hit Songs
Authors: Castro Ruben , Tsutsumi Kotaro , Sayadi Jamasb J. , Hu James , Vyas Raj M. , Sayadi Lohrasb R.
Published: June 2021

The purpose of this study was to assess the frequency by which plastic surgery-related terms have been included in the lyrics of Western music hits from the 1970s to the present day as a proxy for estimating the cultural impact of plastic surgery. A list of the Billboard Year-End Hot 100 songs from 1968 to 2019 and the Billboard Year-End Hot R&B/Hip-Hop songs from 1970 to 2019 was obtained for a combined total of 8550 songs. Lyrics for each song were extracted via a web-scraping system, and a database of plastic surgery-related terms was developed by our team. Each term was then queried amongst the compiled lyrics data sets, and the total frequency of plastic surgery-related terms per year and per decade was determined. Each term was also examined in its context of usage to validate its relevance to plastic surgery and determine its connotation through sentiment analysis. The frequency of plastic surgery-related terms referenced in the Billboard Year-End Hot 100 and Billboard Year-End Hot R&B/Hip-Hop charts has increased 15-fold from the 1970s (n = 1 song) to 2010s (n = 15 songs). The terms most often mentioned included “doctor,” “silicone,” “plastic,” “surgery,” “nip-tuck,” and “lipo.” Artists who most frequently used plastic surgery-related terms were Kanye West, 2 Chainz, and Nicki Minaj. The current study is the first to evaluate trends in plastic surgery references in music formally. In turn, this study helps further our understanding of the interplay between plastic surgery and popular culture.
New Therapies for Corneal Endothelial Diseases: 2020 and Beyond
Authors: Soh Yu Qiang , Poh Stanley S. J. , Peh Gary S. L. , Mehta Jodhbir S.
Published: June 2021

Penetrating keratoplasty used to be the only surgical technique for the treatment of end-stage corneal endothelial diseases. Improvements in surgical techniques over the past decade have now firmly established endothelial keratoplasty as a safe and effective modality for the treatment of corneal endothelial diseases. However, there is a worldwide shortage of corneal tissue, with more than 50% of the world having no access to cadaveric tissue. Cell injection therapy and tissue-engineered endothelial keratoplasty may potentially offer comparable results as endothelial keratoplasty while maximizing the use of cadaveric donor corneal tissue. Descemet stripping only, Descemet membrane transplantation, and selective endothelial removal are novel therapeutic modalities that take this a step further by relying on endogenous corneal endothelial cell regeneration, instead of allogenic corneal endothelial cell transfer. Gene therapy modalities, including antisense oligonucleotides and clustered regularly interspaced short palindromic repeats–based gene editing, offer the holy grail of potentially suppressing the phenotypic expression of genetically determined corneal endothelial diseases at the asymptomatic stage. We now stand at the crossroads of exciting developments in medical technologies that will likely revolutionize the way we treat corneal endothelial diseases over the next 2 decades.
Impact of Sample Collection Order on the Diagnostic Performance of Metagenomic Deep Sequencing for Infectious Keratitis
Authors: Redd Travis K. , Lalitha Prajna , Prajna N. Venkatesh , Sikha Misra , Gunasekaran Rameshkumar , Hinterwirth Armin , Chen Cindi , Zhong Lina , Liu Zijun , Lietman Thomas M. , Keenan Jeremy D. , Doan Thuy , Seitzman Gerami D.
Published: June 2021

Purpose:

The purpose of this article was to evaluate the impact of sample collection order on the diagnostic yield of metagenomic deep sequencing (MDS) for determining the causative pathogen in infectious keratitis.

Methods:

We performed a cross-sectional diagnostic test evaluation among subjects with infectious keratitis at Aravind Eye Hospital in Madurai, India. All subjects underwent corneal scrapings of the affected eye to obtain potassium hydroxide smear, Gram stain, bacterial culture, and fungal culture, in this order. The order of MDS specimen collection relative to smear and culture samples was randomized and served as the primary predictor. Outcomes included the normalized copy number of pathogenic RNA detected by MDS, the proportion of MDS samples that were diagnostic, and the agreement of MDS results with cultures.

Results:

MDS samples from 46 subjects with corneal ulcers were evaluated. MDS was positive in 33 subjects (76%) and had 74% overall agreement with culture results. There was no association between order of MDS sample collection and normalized copy number of genetic material detected (P = 0.62) or the likelihood of MDS positivity (P = 0.46). However, the likelihood of agreement between MDS and cultures decreased when MDS corneal swabs were collected after other diagnostic corneal scrapings (P = 0.05).

Conclusions:

The overall yield of MDS for detecting the cause of infectious keratitis was not affected by sample collection order. However, diagnostic agreement between MDS and cultures decreased when MDS samples were collected after other specimens. Additional investigation is warranted to determine whether this represents increased sensitivity of MDS compared with cultures or higher susceptibility to contaminants.
Use of Cenegermin in the Presence of Bandage Contact Lenses
Authors: Cheung Albert Y. , Shah Amar P. , Pierson Kasey L. , Denny Matthew R. , Nordlund Michael L. , Holland Edward J.
Published: June 2021

Purpose:

The aim of this study was to characterize the outcomes of eyes with neurotrophic keratitis (NK) treated with a course of cenegermin-bkbj in the presence of a bandage contact lens (BCL).

Methods:

A retrospective chart review of all eyes with a clinical diagnosis of NK treated with cenegermin-bkbj was performed between 2018 and 2020. Inclusion criteria included cenegermin-bkbj treatment with a BCL in place. Demographics, etiology, visual acuity, pretreatment and posttreatment corneal sensation, and treatment outcomes were assessed.

Results:

There were 18 eyes of 16 patients (69% female) with NK treated with cenegermin-bkbj while having a BCL in place. After cenegermin-bkbj treatment, presence of corneal sensation significantly increased from 7% of eyes to 79% of eyes (P < 0.0001). There was also a significant increase in the number of quadrants with corneal sensation (mean of 0.1 quadrants increased to 1.6 quadrants, P =0.0005). Six of 10 eyes (67%; P = 0.004) with a persistent epithelial defect (PED) experienced complete resolution at the conclusion of treatment, while 3 additional eyes experienced a decrease in the defect size. Despite all 18 eyes necessitating a chronic BCL before cenegermin-bkbj treatment, 4 were able to maintain their epithelium without a BCL after treatment for at least some period.

Conclusions:

Cenegermin-bkbj treatment for NK with a BCL in place demonstrated improvement in corneal sensation, epithelial defect size, and fluorescein staining. In eyes demonstrating previous ocular surface decompensation with discontinuation of a BCL, maintenance of BCL use during treatment with cenegermin-bkbj may be considered.
Genome-wide DNA methylation profiling and gut flora analysis in intestinal polyps patients
Authors: Liu Lili , Chen Yanjie , Liu Taotao , Yu Jie , Ma Lili , Wu Hao
Published: June 2021

Background

The intestinal polyp is the precancerous lesion of colorectal cancer. DNA methylation and intestinal microbiota may play an important role in the development of intestinal polyp.

Materials and methods

In this study, we included 10 patients with intestinal polyps who received the colonoscopy examination. We applied the Illumina Human Methylation 850K array to investigate the epigenome-wide DNA methylation patterns. Then, we filtered out the hub genes in the protein–protein interaction networks using functional epigenetic modules analysis. We also analyzed the colonizing bacteria on the surface of polyps compared with those in normal colonic mucosal epithelium with 16S ribosomal DNA sequencing.

Results

We identified 323 hypermethylated sites and 7992 hypomethylated sites between intestinal polyps and normal samples. Five hub genes, including CREB1, LPA, SVIL and KRT18, were identified in five modules. Hypomethylation of CREB1 is a candidate marker of colorectal adenoma. Gut microbiota analysis showed that Butyricicoccus was significantly decreased in the intestinal polyp groups.

Conclusion

In conclusion, we identified DNA methylation disparities in intestinal polyps compared with normal tissue, of which methylation of CREB1 may hold clinical significance in colorectal cancer progress. Colonizing bacteria in the colonic epithelium might be related to the formation of intestinal polyps.
The value of intravenous contrast medium in PSMA PET/CT imaging in patients with biochemical recurrence of prostate cancer
Authors: Winiger Alain , Pérez Lago Maria del Sol , Lehnick Dirk , Roos Justus E. , Strobel Klaus
Published: June 2021

Purpose

To investigate the added value of diagnostic abdominal contrast-enhanced computed tomography (ceCT) in Ga-68 PSMA PET/CT in prostate cancer patients with biochemical recurrence (BCR).

Methods

Eighty-two consecutive patients (median age, 69 years; range, 45–86 years) with BCR underwent Ga-68 PSMA PET/CT with low-dose nonenhanced (ne) whole-body CT and diagnostic ceCT. Imaging results were retrospectively reviewed by two readers (R1, R2) for diagnostic certainty, local recurrence, lymph node metastasis (LNM) and bone metastasis. Interobserver agreement was assessed. Histopathology served as reference standard in 7, imaging and clinical follow-up in 65 and clinical follow-up alone in 10 patients.

Results

Certain local recurrence, LNM and bone metastasis diagnoses increased substantially from ceCT (R1: 5%/18%/32%; R2: 37%/50%/82%) to nePET/CT (R1: 78%/87%/93%; R2: 81%/87%/95%) for both readers, but the difference between nePET/CT and cePET/CT (R1: 77%/96%/92%; R2: 89%/94%/96%) was marginal. Interobserver agreement was minimal with ceCT (Krippendorff’s alpha: 0.04–0.26), substantial with nePET/CT (0.60–0.86) and best with cePET/CT (0.76–0.86). The areas under the receiver operating characteristic curve (AUCs) for local recurrence for R1/R2 were 0.60/0.65 for ceCT, 0.81/0.79 for nePET/CT and 0.81/0.82 for cePET/CT. AUCs for LNMs for R1/R2 were 0.67/0.77 for ceCT, 0.91/0.82 for nePET/CT and 0.92/0.87 for cePET/CT. AUCs for BMs for R1/R2 were 0.60/0.53 for ceCT, 0.93/0.84 for nePET/CT and 0.93/0.86 for cePET/CT.

Conclusion

Diagnostic abdominal ceCT increases the diagnostic certainty and interobserver agreement in Ga-68 PSMA PET/CT in BCR of prostate cancer. The diagnostic performance of cePET/CT is significantly better than ceCT alone but not nePET/CT.