bluuebunny/crossref_metadata_2025 huggingface dataset:
Cherry Polyphenol Extract Ameliorated Dextran Sodium Sulfate-Induced Ulcerative Colitis in Mice by Suppressing Wnt/β-Catenin Signaling Pathway
Authors: Li Fuhua , Yan Huiming , Jiang Ling , Zhao Jichun , Lei Xiaojuan , Ming Jian
Published: December 2021

Ulcerative colitis (UC) is a chronic and nonspecific inflammatory disease of the colon and rectum, and its etiology remains obscure. Cherry polyphenols showed potential health-promoting effects. However, both the protective effect and mechanism of cherry polyphenols on UC are still unclear. This study aimed to investigate the potential role of the free polyphenol extract of cherry in alleviating UC and its possible mechanism of action. Our study revealed that the free polyphenol extract of cherry management significantly alleviated UC symptoms, such as weight loss, colon shortening, the thickening of colonic mucous layer, etc. The free polyphenol extract of cherry treatment also introduced a significant reduction in levels of malondialdehyde (MDA), myeloperoxidase (MPO) and nitric oxide (NO), while causing a significant elevation in levels of catalase (CAT), glutathione (GSH-Px), superoxide dismutase (SOD), as well as the downregulation of pro-inflammatory cytokines. This indicated that such positive effects were performed through reducing oxidative damage or in a cytokine-specific manner. The immunofluorescence analysis of ZO-1 and occludin proteins declared that the free polyphenol extract of cherry had the potential to prompt intestinal barrier function. The reduced expression levels of β-catenin, c-myc, cyclin D1 and GSK-3β suggested that the cherry extract performed its positive effect on UC by suppressing the Wnt/β-ctenin pathway. This finding may pave the way into further understanding the mechanism of cherry polyphenols ameliorating ulcerative colitis.
Optimization of Commercial Microwave Assisted-Extraction Conditions for Recovery of Phenolics from Lemon-Scented Tee Tree (Leptospermum petersonii) and Comparison with Other Extraction Techniques
Authors: Saifullah Md , Akanbi Taiwo Olusesan , McCullum Rebecca , Vuong Quan Van
Published: December 2021

The lemon-scented tea tree (LSTT) is an Australian native herb and is a rich source of essential oil and phenolics. The ETHOS X extraction system is known as a commercial microwave-assisted extraction (MAE) system for extracting bioactive compounds from plant materials. This study investigated the influence of soaking time, radiation time, microwave power, and sample to solvent ratio on the extraction efficiency of polyphenols and antioxidant properties from lemon-scented tea tree leaves and optimized the extraction conditions using response surface methodology (RSM). The effectiveness of ETHOS X was further compared with ultrasound-assisted extraction (UAE) and shaking water bath (SWB) techniques. The results revealed that soaking time did not significantly affect the recovery of phenolics from the leaves (p > 0.05). Thus, soaking is not required for the ETHOS X extraction of polyphenols from LSTT leaves. RSM was successfully applied to explore the impact of ETHOS X extraction conditions and optimize the extraction conditions. Radiation time significantly affects the recovery yield of phenolics (p < 0.05) positively, whereas irradiation power and sample to solvent ratio adversely influenced the extraction yields of phenolics. The optimal ETHOS X extraction conditions were: radiation time of 60 min, irradiation power of 600 W, and sample to solvent ratio of 2 g/100 mL. Under these conditions, 119.21 ± 7.09 mg of phenolic, 85.31 ± 4.55 mg of flavonoids, and 137.51 ± 12.52 mg of proanthocyanidins can be extracted from a gram of dried LSTT leaves. In comparison with UAE and SWB, ETHOS X is not more effective for the extraction of phenolics than UAE and SWB. However, this technique can save half of the solvent volume compared to UAE and SWB techniques.
Dynamic Programming for Computing Power Indices for Weighted Voting Games with Precoalitions
Authors: Staudacher Jochen , Wagner Felix , Filipp Jan
Published: December 2021

We study the efficient computation of power indices for weighted voting games with precoalitions amongst subsets of players (reflecting, e.g., ideological proximity) using the paradigm of dynamic programming. Starting from the state-of-the-art algorithms for computing the Banzhaf and Shapley–Shubik indices for weighted voting games, we present a framework for fast algorithms for the three most common power indices with precoalitions, i.e., the Owen index, the Banzhaf–Owen index and the symmetric coalitional Banzhaf index, and point out why our new algorithms are applicable for large numbers of players. We discuss implementations of our algorithms for the three power indices with precoalitions in C++ and review computing times, as well as storage requirements.
Enhancement of Anti-Inflammatory Activity of Optimized Niosomal Colchicine Loaded into Jojoba Oil-Based Emulgel Using Response Surface Methodology
Authors: Elsewedy Heba S. , Younis Nancy S. , Shehata Tamer M. , Mohamed Maged E. , Soliman Wafaa E.
Published: December 2021

Recent progression in investigational studies aiming to integrate natural products and plant oils in developing new dosage forms that would provide optimal therapeutic effect. Therefore, the aim of the present exploration was to inspect the influence of jojoba oil in boosting the anti-inflammatory effect of colchicine natural product. To our knowledge, there is no formulation comprising colchicine and jojoba oil together to form a niosomal emulgel preparation anticipated for topical application. Colchicine is a natural product extracted from Colchicum autumnale that has been evidenced to show respectable anti-inflammatory activity. Owing to its drawbacks and low therapeutic index, it was preferable to be formulated into topical dosage form. The current study inspected colchicine transdermal delivery by developing niosomal preparation as a potential nanocarrier included into emulgel prepared with jojoba oil. Box Behnken design was constructed to develop 17 niosomal emulgel formulations. The optimized colchicine niosomal emulgel was evaluated for its physical characteristics and in vitro release studies. The in vivo anti-inflammatory activity was estimated via carrageenan-induced rat hind paw edema method. The developed colchicine niosomal preparation revealed particle size of 220.7 nm with PDI value 0.22, entrapment efficiency 65.3%. The formulation was found to be stable showing no significant difference in particle size and entrapment efficiency up on storage at 4 °C and 25 °C for 3 months. The optimized colchicine niosomal emulgel exhibited a pH value 6.73, viscosity 4598 cP, and spreadability 38.3 mm. In vitro release study of colchicine from niosomal emulgel formulation was around 52.4% over 6 h. Apparently, the proficient anti-inflammatory activity of colchicine niosomal emulgel was confirmed via carrageenan-induced rat hind paw edema test. Overall, the results recommend the combination of niosomal preparation with jojoba oil-based emulgel that might signify a favorable delivery of anti-inflammatory drug such as colchicine.
Effects of the Expression of Random Sequence Clones on Growth and Transcriptome Regulation in Escherichia coli
Authors: Bhave Devika , Tautz Diethard
Published: December 2021

Comparative genomic analyses have provided evidence that new genetic functions can emerge out of random nucleotide sequences. Here, we apply a direct experimental approach to study the effects of plasmids harboring random sequence inserts under the control of an inducible promoter. Based on data from previously described experiments dealing with the growth of clones within whole libraries, we extracted specific clones that had shown either negative, neutral or positive effects on relative cell growth. We analyzed these individually with respect to growth characteristics and the impact on the transcriptome. We find that candidate clones for negative peptides lead to growth arrest by eliciting a general stress response. Overexpression of positive clones, on the other hand, does not change the exponential growth rates of hosts, and they show a growth advantage over a neutral clone when tested in direct competition experiments. Transcriptomic changes in positive clones are relatively moderate and specific to each clone. We conclude from our experiments that random sequence peptides are indeed a suitable source for the de novo evolution of genetic functions.
Transcriptomic Analysis of MSTN Knockout in the Early Differentiation of Chicken Fetal Myoblasts
Authors: Xu Ke , Zhou Hao , Han Chengxiao , Xu Zhong , Ding Jinmei , Zhu Jianshen , Qin Chao , Luo Huaixi , Chen Kangchun , Jiang Shengyao , Liu Jiajia , Zhu Wenqi , Meng He
Published: December 2021

In mammals, Myostatin (MSTN) is a known negative regulator of muscle growth and development, but its role in birds is poorly understood. To investigate the molecular mechanism of MSTN on muscle growth and development in chickens, we knocked out MSTN in chicken fetal myoblasts (CFMs) and sequenced the mRNA transcriptomes. The amplicon sequencing results show that the editing efficiency of the cells was 76%. The transcriptomic results showed that 296 differentially expressed genes were generated after down-regulation of MSTN, including angiotensin I converting enzyme (ACE), extracellular fatty acid-binding protein (EXFABP) and troponin T1, slow skeletal type (TNNT1). These genes are closely associated with myoblast differentiation, muscle growth and energy metabolism. Subsequent enrichment analysis showed that DEGs of CFMs were related to MAPK, Pl3K/Akt, and STAT3 signaling pathways. The MAPK and Pl3K/Akt signaling pathways are two of the three known signaling pathways involved in the biological effects of MSTN in mammals, and the STAT3 pathway is also significantly enriched in MSTN knock out chicken leg muscles. The results of this study will help to understand the possible molecular mechanism of MSTN regulating the early differentiation of CFMs and lay a foundation for further research on the molecular mechanism of MSTN involvement in muscle growth and development.
Heterotopic Potential of Darkness: Exploration and Experimentation of Queer Space in Sarah Waters’s Neo-Victorian Trilogy
Authors: Suwa Akira
Published: December 2021

This article argues that darkness contributes to the creation of, and expands the concept of, heterotopias. In Sarah Waters’s neo-Victorian trilogy, consisting of Tipping the Velvet (1998), Affinity (1999), and Fingersmith (2002), her characters utilize darkness as their queer heterotopic space in order to call into question dominant heteronormative ideologies. Darkness plays an important role at the inception of the characters’ romantic relationships by facilitating space that allows their non-normative feelings to be expressed, thereby bringing queer desire to the forefront of each narrative. Darkness is a critical factor that renders a space heterotopic, as it blurs the boundary between heteronormative and queer, hence allowing transgression of the characters within Waters’s novels. Within queer heterotopic space created out of the darkness, there is a confluence of opposing values that enables the characters to examine the possibility of transcending heteronormativity and envisioning queer futures.
Posttraumatic Growth after the Fukushima Nuclear Disaster: Examination of Free Descriptions among Fukushima Residents Who Lived in the Evacuation Area
Authors: Iwasa Hajime , Nakayama Chihiro , Moriyama Nobuaki , Orui Masatsugu , Yasumura Seiji
Published: December 2021

We examined the differences in the posttraumatic growth (PTG) free descriptions from clusters of Fukushima residents (evacuation and non-evacuation zones) who experienced the Great East Japan Earthquake, and the relationship between “recovery from radiation anxiety” and the PTG-free description classification in these regions. A mail survey was conducted in August 2016 among Fukushima residents aged 20–79 years for free descriptions of their PTG. Participants were then divided into the “no anxiety,” “recovered from anxiety,” and “unrecovered from anxiety” groups based on their “recovery from radiation anxiety.” Data from 786 responses were analyzed. The PTG-free descriptions were classified into eight categories. Among those who lived in the evacuation zone versus those in the non-evacuation zone, “relating to others” (non-evacuation zone: 11.9% vs. evacuation zone: 18.4%) and “appreciation of life” (non-evacuation zone: 2.7% vs. evacuation zone: 9.8%) were significantly higher, and “increased awareness of disaster prevention” (non-evacuation zone: 20.4% vs. evacuation zone: 8.0%) was significantly lower. In the evacuation zone, “renewed recognition of nuclear issues” was significantly lower than the expected value in the no anxiety group (3.1%) and significantly higher than the expected value in the recovered group (22.9%). Further studies are needed to build support measures and potentially aid in preparing for future disasters.
How Prepared Are the Health Care Professionals for Disaster Medicine Management? An Insight from Pakistan
Authors: Gillani Ali Hassan , Li Shi , Akbar Jamshaid , Omer Sumaira , Fatima Bakhtawar , Ibrahim Mohamed Izham Mohamed , Fang Yu
Published: December 2021

Countries need healthcare professionals who are competent first responders with a positive attitude and prepared to deal with catastrophes. The study evaluated the knowledge, attitude, and readiness of the practice of healthcare professionals towards disaster management. A survey was carried out among hospital healthcare professionals using a self-administered validated questionnaire. The questionnaire comprised knowledge, attitude, and readiness to practice items. Descriptive and inferential statistics (Mann–Whitney, Kruskal–Wallis, correlation and regression tests) at alpha = 0.05 were used in the analysis. The mean (SD) score of knowledge was 12.25 (4.27) (range: 3.00 to 20.00), attitude (39.32 ± 9.55; range: 18.00 to 61.00), readiness to practice (32.41 ± 6.69; range: 21.00 to 61.00), and KArP (83.99 ± 12.21; range: 60.00 to 124.00). The average knowledge score was moderate, low attitude score, moderate readiness to practice score, and an average score of overall KArP. Attitude is a significant predictor of readiness to practice (p = 0.000). The levels of knowledge, attitude, and readiness of the practice of healthcare professionals were not satisfactory. The educators and health policymakers should build a robust curriculum in disaster medicine management and preparedness to prepare for the future of competent healthcare professionals for the nation.
Comparative Study of Salivary pH, Buffer Capacity, and Flow in Patients with and without Gastroesophageal Reflux Disease
Authors: Bechir Farah , Pacurar Mariana , Tohati Adrian , Bataga Simona Maria
Published: December 2021

The oral cavity has specific and individualized characteristics, with pH, saliva flow, buffer capacity, temperature, and microorganisms content influencing oral health. Currently, the prevalence of gastroesophageal reflux disease (GERD) is constantly increasing. The objective of this study was to evaluate and compare the saliva quantity at 5 min, salivary pH, and salivary buffer capacity in patients with and without GERD, necessary for establishing the correct dental treatment plan. A Saliva-Check Buffer (GC) kit was used for the determination of salivary variables. The total number of 80 patients included in the study were divided into a study group and a control group, each containing 40 patients. Saliva quantity at 5 min was lower in patients suffering from GERD. The salivary pH of these patients turned to acid values compared to the salivary pH of controls, where the values were within the normal range. In patients with GERD, the determined salivary buffer capacity was low or very low. The use of the Saliva-Check Buffer (GC) kit is a simple, easy, non-invasive and patient-accepted method, which can also be used in the dentist’s office to assess the saliva buffer capacity and pH, variables that are important for establishing a correct dental treatment plan.
Cardiovascular Risk Factors and Physical Activity for the Prevention of Cardiovascular Diseases in the Elderly
Authors: Ciumărnean Lorena , Milaciu Mircea Vasile , Negrean Vasile , Orășan Olga Hilda , Vesa Stefan Cristian , Sălăgean Octavia , Iluţ Silvina , Vlaicu Sonia Irina
Published: December 2021

Cardiovascular diseases create an important burden on the public health systems, especially in the elderly, mostly because this group of patients frequently suffer from multiple comorbidities. Accumulating cardiovascular risk factors during their lifetime has a detrimental effect on an older adult‘s health status. The modifiable and non-modifiable cardiovascular risk factors are very diverse, and are frequently in a close relationship with the metabolic comorbidities of the elderly, mainly obesity and Diabetes Mellitus. In this review, we aim to present the most important cardiovascular risk factors which link aging and cardiovascular diseases, starting from the pathophysiological links between these factors and the aging process. Next, we will further review the main interconnections between obesity and Diabetes Mellitus and cardiovascular diseases of the elderly. Lastly, we consider the most important aspects related to prevention through lifestyle changes and physical activity on the occurrence of cardiovascular diseases in the elderly.
Mercy Procedure or a Nightmare? Attitude towards Pregnancy Termination among Polish University Students
Authors: Stokłosa Maciej , Stokłosa Iga , Porwolik Mateusz , Bugajski Maciej , Więckiewicz Gniewko , Męcik-Kronenberg Tomasz , Piegza Magdalena , Pudlo Robert , Gorczyca Piotr
Published: December 2021

Worldwide, there are about 121 million unintended pregnancies per year. The aim of the study was to assess the attitudes in different groups of students from 40 Polish universities towards pregnancy termination. In total, 9686 university students (20.1% male and 79.9% female) took part in our research. Questions about attitudes towards abortion in all possible circumstances were involved in the survey, which also included a socio-demographic questionnaire. Overall, 94.5% of women and 90.7% of men consider that abortion should be legal in the situation of a threat to the mother’s life, while only 52% of women and 38.7% of men accept it in the case of a hard financial situation for the mother. Most students stand for abortion in the situation of a threat to the mother’s life, in the case of rape, or in the case of a mortal fetus defect. Less than half of the students interviewed consider that abortion should be legal in the case of a hard financial situation for the mother or on the mother’s demand. People who declare a religious affiliation more often disagree with abortion, even in the hardest cases such as a danger to the mother’s life or a mortal fetus defect. The factor that influences the strongest on attitudes towards abortion is being an active Roman Catholic. The majority of students have a pro-choice attitude in respect of pregnancy termination.
Gait Improvement in Chronic Stroke Survivors by Using an Innovative Gait Training Machine: A Randomized Controlled Trial
Authors: Kooncumchoo Patcharee , Namdaeng Phuwarin , Hanmanop Somrudee , Rungroungdouyboon Bunyong , Klarod Kultida , Kiatkulanusorn Sirirat , Luangpon Nongnuch
Published: December 2021

Chronic stroke leads to the impairment of lower limb function and gait performance. After in-hospital rehabilitation, most individuals lack continuous gait training because of the limited number of physical therapists. This study aimed to evaluate the effects of a newly invented gait training machine (I-Walk) on lower limb function and gait performance in chronic stroke individuals. Thirty community-dwelling chronic stroke individuals were allocated to the I-Walk machine group (n = 15) or the overground gait training (control) group (n = 15). Both groups received 30 min of upper limb and hand movement and sit-to-stand training. After that, the I-Walk group received 30 min of I-Walk training, while the control followed a 30-minute overground training program. All the individuals were trained 3 days/week for 8 weeks. The primary outcome of the motor recovery of lower limb impairment was measured using the Fugl–Meyer Assessment (FMA). The secondary outcomes for gait performance were the 6-minute walk test (6 MWT), the 10-meter walk test (10 MWT), and the Timed Up and Go (TUG). The two-way mixed-model ANOVA with the Bonferroni test was used to compare means within and between groups. The post-intervention motor and sensory subscales of the FMA significantly increased compared to the baseline in both groups. Moreover, the 6 MWT and 10 MWT values also improved in both groups. In addition, the mean difference of TUG in the I-Walk was higher than the control. The efficiency of I-Walk training was comparable to overground training and might be applied for chronic stroke gait training in the community.
Validating Insomnia Severity Index (ISI) in a Bangladeshi Population: Using Classical Test Theory and Rasch Analysis
Authors: Mamun Mohammed A. , Alimoradi Zainab , Gozal David , Manzar Md Dilshad , Broström Anders , Lin Chung-Ying , Huang Ru-Yi , Pakpour Amir H.
Published: December 2021

The COVID-19 outbreak is associated with sleep problems and mental health issues among individuals. Therefore, there is a need to assess sleep efficiency during this tough period. Unfortunately, the commonly used instrument on insomnia severity—the Insomnia Severity Index (ISI)—has never been translated and validated among Bangladeshis. Additionally, the ISI has never been validated during a major protracted disaster (such as the COVID-19 outbreak) when individuals encounter mental health problems. The present study aimed to translate the ISI into Bangla language (ISI-Bangla) and validate its psychometric properties. First, the linguistic validity of the ISI-Bangla was established. Then, 9790 Bangladeshis (mean age = 26.7 years; SD = 8.5; 5489 [56.1%] males) completed the Bangla versions of the following questionnaires: ISI, Fear of COVID-19 Scale (FCV-19S), and Patient Health Questionnaire-9 (PHQ-9). All the participants also answered an item on suicidal ideation. Classical test theory and Rasch analyses were conducted to evaluate the psychometric properties of the ISI-Bangla. Both classical test theory and Rasch analyses support a one-factor structure for the ISI-Bangla. Moreover, no substantial differential item functioning was observed across different subgroups (gender, depression status (determined using PHQ-9), and suicidal ideation). Additionally, concurrent validity of the ISI-Bangla was supported by significant and moderate correlations with FCV-19S and PHQ-9; known-group validity was established by the significant difference of the ISI-Bangla scores between participants who experienced suicidal ideation and those without. The present psychometric validation conducted during the COVID-19 outbreak suggests that the ISI-Bangla is a promising and operationally adequate instrument to assess insomnia in Bangladeshis.
Farmer Mental Health Interventions: A Systematic Review
Authors: Younker Terasa , Radunovich Heidi Liss
Published: December 2021

The prevalence of mental health disorders and suicide amongst agricultural producers is a global problem. Community leaders, researchers, policymakers, and clinicians have mobilized to develop programs to address this issue. This study reviewed a wide range of mental health interventions targeting farmer mental health spanning over 50 years and examined their reported effectiveness and constraints. A total of ninety-two articles on farmer mental health were included in a final systematic review. Most articles were written concerning mental health literacy and peer and paraprofessional support interventions in the United States and Australia. Among the 56 studies reporting empirical evaluative data, 21 were mixed-method, 20 quantitative, 11 qualitative, and 5 literature synthesis. Non-experimental, self-reported, and qualitative data suggest efficacy of mental health literacy programs, peer and paraprofessional support, and community-based and agroecological interventions. However, most interventions were not subject to rigorous evaluation and only one intervention was evaluated using a control condition. The heterogeneity of existing studies and paucity of rigorous evaluation proscribes firm conclusions related to program-type efficacy. This review demonstrates that there is still a need for a stronger and broader evidence base in the field of farmer mental health interventions, which should focus on both holistic, multi-component programs and targeted approaches.
Anatomy of the Nervous System in Chelifer cancroides (Arachnida: Pseudoscorpiones) with a Distinct Sensory Pathway Associated with the Pedipalps
Authors: Stemme Torben , Pfeffer Sarah E.
Published: December 2021

Many arachnid taxa have evolved unique, highly specialized sensory structures such as antenniform legs in Amblypygi (whip spiders), for instance, or mesosomal pectines in scorpions. Knowledge of the neuroanatomy as well as functional aspects of these sensory organs is rather scarce, especially in comparison to other arthropod clades. In pseudoscorpions, no special sensory structures have been discovered so far. Nevertheless, these animals possess dominant, multifunctional pedipalps, which are good candidates for being the primary sensory appendages. However, only little is known about the anatomy of the nervous system and the projection pattern of pedipalpal afferents in this taxon. By using immunofluorescent labeling of neuronal structures as well as lipophilic dye labeling of pedipalpal pathways, we identified the arcuate body, as well as a comparatively small mushroom body, the latter showing some similarities to that of Solifugae (sun spiders and camel spiders). Furthermore, afferents from the pedipalps terminate in a glomerular and a layered neuropil. Due to the innervation pattern and structural appearance, we conclude that these neuropils are the first integration centers of the chemosensory and mechanosensory afferents. Within Arthropoda, but also other invertebrates or even vertebrates, sensory structures show rather similar neuronal arrangement. Thus, these similarities in the sensory systems of different evolutionary origin have to be interpreted as functional prerequisites of the respective modality.
Concomitant Assessment of Monocyte HLA-DR Expression and Ex Vivo TNF-α Release as Markers of Adverse Outcome after Various Injuries—Insights from the REALISM Study
Authors: Bidar Frank , Bodinier Maxime , Venet Fabienne , Lukaszewicz Anne-Claire , Brengel-Pesce Karen , Conti Filippo , Quemeneur Laurence , Leissner Philippe , Tan Lionel K. , Textoris Julien , Rimmelé Thomas , Monneret Guillaume ,   on behalf of the Realism Study Group
Published: December 2021

Intensive care unit (ICU) patients develop an altered host immune response after severe injuries. This response may evolve towards a state of persistent immunosuppression that is associated with adverse clinical outcomes. The expression of human leukocyte antigen DR on circulating monocytes (mHLA-DR) and ex vivo release of tumor necrosis factor α (TNF-α) by lipopolysaccharide-stimulated whole blood are two related biomarkers offered to characterize this phenomenon. The purpose of this study was to concomitantly evaluate the association between mHLA-DR and TNF-α release and adverse clinical outcome (i.e., death or secondary infection) after severe trauma, sepsis or surgery in a cohort of 353 ICU patients. mHLA-DR and TNF-α release was similarly and significantly reduced in patients whatever the type of injury. Persistent decreases in both markers at days 5–7 (post-admission) were significantly associated with adverse outcomes. Overall, mHLA-DR (measured by flow cytometry) appears to be a more robust and standardized parameter. Each marker can be used individually as a surrogate of immunosuppression, depending on center facilities. Combining these two parameters could be of interest to identify the most immunosuppressed patients presenting with a high risk of worsening. This last aspect deserves further exploration.
Effects of Resistance Training Intervention along with Leucine-Enriched Whey Protein Supplementation on Sarcopenia and Frailty in Post-Hospitalized Older Adults: Preliminary Findings of a Randomized Controlled Trial
Authors: Amasene Maria , Cadenas-Sanchez Cristina , Echeverria Iñaki , Sanz Begoña , Alonso Cristina , Tobalina Ignacio , Irazusta Jon , Labayen Idoia , Besga Ariadna
Published: December 2021

Resistance training and protein supplementation are expected to exert the greatest effect in counteracting muscle-wasting conditions. Myokines might play a key role, but this remains to be elucidated. The aim of this study (NCT03815201) was to examine the effects of a resistance training program with post-exercise leucine-enriched protein supplementation on sarcopenia and frailty status and on the plasma myokine concentrations of post-hospitalized older adults. A total of 41 participants were included in this 12-week resistance training intervention and randomized either to the placebo group or the protein group. Sarcopenia, frailty, body composition and blood-based myokines were measured at baseline and after 12 weeks. Both groups improved in terms of physical performance (p < 0.005) and frailty (p < 0.07) following the resistance training intervention, but without any difference between groups. Myokine concentrations did not change after the intervention in either group. Changes in myostatin concentrations were associated with greater improvements in appendicular skeletal muscle mass at the end of the intervention (p < 0.05). In conclusion, the implementation of resistance training programs after hospitalization in older adults should be prioritized to combat sarcopenia and frailty immediately. The results regarding myostatin should be taken as preliminary findings.
Cognitive Impairement in Non-Cirrhotic Portal Hypertension: Highlights on Physiopathology, Diagnosis and Management
Authors: Gioia Stefania , Nardelli Silvia , Riggio Oliviero , Faccioli Jessica , Ridola Lorenzo
Published: December 2021

Hepatic encephalopathy (HE) is one of the most frequent complications of cirrhosis. Several studies and case reports have shown that cognitive impairment may also be a tangible complication of portal hypertension secondary to chronic portal vein thrombosis and to porto-sinusoidal vascular disease (PSVD). In these conditions, representing the main causes of non-cirrhotic portal hypertension (NCPH) in the Western world, both overt and minimal/covert HE occurs in a non-neglectable proportion of patients, even lower than in cirrhosis, and it is mainly sustained by the presence of large porto-systemic shunt. In these patients, the liver function is usually preserved or only mildly altered, and the development of porto-systemic shunt is either spontaneous or iatrogenically frequent; HE is an example of type-B HE. To date, in the absence of strong evidence and large cooperative studies, for the diagnosis and the management of HE in NCPH, the same approach used for HE occurring in cirrhosis is applied. The aim of this paper is to provide an overview of type B hepatic encephalopathy, focusing on its pathophysiology, diagnostic tools and management in patients affected by porto-sinusoidal vascular disease and chronic portal vein thrombosis.
Prone Positioning as a Potential Risk Factor for Deep Vein Thrombosis in COVID-19 Patients: A Hypothesis Generating Observation
Authors: Gebhard Caroline E. , Zellweger Núria , Gebhard Catherine , Hollinger Alexa , Chrobok Leon , Stähli David , Schönenberger Christof M. , Todorov Atanas , Aschwanden Markus , Siegemund Martin
Published: December 2021

Aims of the study: Virchow’s triad with stasis, activated coagulation, and endothelial damage is common in SARS-CoV2. Therefore, we sought to retrospectively assess whether the duration of prone position may serve as a risk factor for deep vein thrombosis in critically ill patients. Methods: In this single center retrospective study of a tertiary referral hospital, patients with acute respiratory distress syndrome (ARDS) due to COVID-19 pneumonia admitted to critical care underwent venous ultrasound screening for deep vein thrombosis (DVT). Data on DVT diagnosis, duration of prone positioning, demographic, respiratory, and laboratory parameters were retrospectively collected and compared between DVT and non-DVT patients. Results: 21 patients with ARDS from COVID-19 pneumonia were analyzed. DVT was detected in 11 (52%) patients (76.2% male, median age 64 (58; 68.5) years, median body mass index 31 (27; 33.8) kg/m2). In patients diagnosed with DVT, median prone ventilation had been maintained twice as long as compared to patients without DVT (57 (19; 72) versus 28 (0; 56.3) h, p = 0.227) on ICU day 5 with a trend towards longer prone position time (71 (19; 104) versus 28 (0; 73) h, p = 0.06) on ICU day 7. Conclusions: Prone ventilation and constitutional factors may constitute an additional risk factor for DVT in COVID-19 patients. Since recent studies have shown that therapeutic anticoagulation does not impact the occurrence of thromboembolic events, it may be worthwhile to consider mechanical factors potentially affecting blood flow stasis in this high-risk population. However, due to the limited number of patients, our observations should only be considered as hypothesis-generating. Future studies, sufficiently powered and preferably prospective, will be needed to confirm our hypothesis.
Role of Clinical Characteristics and Biomarkers at Admission to Predict One-Year Mortality in Elderly Patients with Pneumonia
Authors: Malézieux-Picard Astrid , Azurmendi Leire , Pagano Sabrina , Vuilleumier Nicolas , Sanchez Jean-Charles , Zekry Dina , Reny Jean-Luc , Stirnemann Jérôme , Garin Nicolas , Prendki Virginie ,   on behalf of the PneumOldCT Study Group
Published: December 2021

Background: A hospitalization for community-acquired pneumonia results in a decrease in long-term survival in elderly patients. We assessed biomarkers at admission to predict one-year mortality in a cohort of elderly patients with pneumonia. Methods: A prospective observational study included patients >65 years hospitalized with pneumonia. Assessment of PSI, CURB-65, and biomarkers (C-reactive protein (CRP), procalcitonin (PCT), NT-pro-B-type natriuretic peptide (NT-proBNP), interleukin (IL)-6 and -8, tumor necrosis factor alpha (TNF-α), serum amyloid A (SAA), neopterin (NP), myeloperoxidase (MPO), anti-apolipoprotein A-1 IgG (anti-apoA-1), and anti-phosphorylcholine IgM (anti-PC IgM)) was used to calculate prognostic values for one-year mortality using ROC curve analyses. Post hoc optimal cutoffs with corresponding sensitivity (SE) and specificity (SP) were determined using the Youden index. Results: A total of 133 patients were included (median age 83 years [IQR: 78–89]). Age, dementia, BMI, NT-proBNP (AUROC 0.65 (95% CI: 0.55–0.77)), and IL-8 (AUROC 0.66 (95% CI: 0.56–0.75)) were significantly associated with mortality, with NT-proBNP (HR 1.01 (95% CI 1.00–1.02) and BMI (HR 0.92 (95% CI 0.85–1.000) being independent of age, gender, comorbidities, and PSI with Cox regression. At the cutoff value of 2200 ng/L, NT-proBNP had 67% sensitivity and 70% specificity. PSI and CURB-65 were not associated with mortality. Conclusions: NT-proBNP levels upon admission and BMI displayed the highest prognostic accuracy for one-year mortality and may help clinicians to identify patients with poor long-term prognosis.
New Perspectives in the Pathophysiology and Treatment of Pain in Patients with Dry Eye Disease
Authors: Giannaccare Giuseppe , Ghelardini Carla , Mancini Alessandra , Scorcia Vincenzo , Di Cesare Mannelli Lorenzo
Published: December 2021

Ocular discomfort and eye pain are frequently reported by patients with dry eye disease (DED), and their management remains a real therapeutic challenge for the Ophthalmologist. In DED patients, injury at the level of each structure of the ocular surface can determine variable symptoms, ranging from mild ocular discomfort up to an intolerable pain evoked by innocuous stimuli. In refractory cases, the persistence of this harmful signal is able to evoke a mechanism of maladaptive plasticity of the nervous system that leads to increased pain responsiveness. Peripheral and, subsequently, central sensitization cause nociceptor hyperexcitability and persistent pain perception that can culminate in the paradoxical situation of perceiving eye pain even in the absence of ocular surface abnormalities. Effective therapeutic strategies of these cases are challenging, and new options are desirable. Recently, a theoretical novel therapeutic approach concerns enkephalins thanks to the evidence that eye pain sensations are modulated by endogenous opioid peptides (enkephalins, endorphins and dynorphins). In this regard, new topical agents open up a new theoretical scenario in the treatment of ocular discomfort and eye pain in the setting of DED, such as, for example, a multimolecular complex based on proteins and glycosaminoglycans also containing opiorphin that may assist the physiological pain-relieving mechanism of the eye.
Beyond Bronchiolitis Obliterans: In-Depth Histopathologic Characterization of Bronchiolitis Obliterans Syndrome after Lung Transplantation
Authors: Vanstapel Arno , Verleden Stijn , Verbeken Eric , Braubach Peter , Goos Tinne , De Sadeleer Laurens , Kaes Janne , Vanaudenaerde Bart , Jonigk Danny , Ackermann Maximilian , Ceulemans Laurens , Van Raemdonck Dirk , Neyrinck Arne , Vos Robin , Verleden Geert , Weynand Birgit ,   on behalf of the Leuven Lung Transplant Group
Published: December 2021

Bronchiolitis obliterans syndrome (BOS) is considered an airway-centered disease, with bronchiolitis obliterans (BO) as pathologic hallmark. However, the histologic spectrum of pure clinical BOS remains poorly characterized. We provide the first in-depth histopathologic description of well-characterized BOS patients and patients without chronic lung allograft dysfunction (CLAD), defined according to the recent consensus guidelines. Explant lung tissue from 52 clinically-defined BOS and 26 non-CLAD patients (collected 1993–2018) was analyzed for histologic parameters, including but not limited to airway lesions, vasculopathy and fibrosis. In BOS, BO lesions were evident in 38 (73%) patients and varied from concentric sub-epithelial fibrotic BO to inflammatory BO, while 10/14 patients without BO displayed ‘vanishing airways’, defined by a discordance between arteries and airways. Chronic vascular abnormalities were detected in 22 (42%) patients. Ashcroft fibrosis scores revealed a median of 43% (IQR: 23–69) of normal lung parenchyma per patient; 26% (IQR: 18–37) of minimal alveolar fibrous thickening; and 11% (IQR: 4–18) of moderate alveolar thickening without architectural damage. Patchy areas of definite fibrotic damage to the lung structure (i.e., Ashcroft score ≥5) were present in 28 (54%) patients. Fibrosis was classified as bronchocentric (n = 21/28, 75%), paraseptal (n = 17/28, 61%) and subpleural (n = 15/28, 54%). In non-CLAD patients, BO lesions were absent, chronic vascular abnormalities present in 1 (4%) patient and mean Ashcroft scores were significantly lower compared to BOS (p = 0.0038) with 78% (IQR: 64–88) normally preserved lung parenchyma. BOS explant lungs revealed evidence of various histopathologic findings, including vasculopathy and fibrotic changes, which may contribute to the pathophysiology of BOS.
Multiple Primary Malignancies in Patients with Gynecologic Cancer
Authors: Yang Eun-Jung , Lee Ji-Hyeon , Lee A-Jin , Kim Nae-Ry , Ouh Yong-Taek , Kim Mi-Kyung , Shim Seung-Hyuk , Lee Sun-Joo , Kim Tae-Jin , So Kyeong-A
Published: December 2021

Objective: To investigate the prevalence and oncologic outcomes of patients with multiple primary malignant tumors (MPMT) with gynecologic cancer. Methods: This retrospective study included 1929 patients diagnosed with gynecologic cancer at a tertiary medical center between August 2005 and April 2021. The clinical data included cancer location, age at primary malignancy diagnosis, interval between primary and secondary cancer, stage of cancer, family history of cancer, genetic testing, dates of last follow-up, recurrence, and death. Results: The prevalence of MPMT with gynecologic cancer in patients was 8.6% and the mean diagnostic period between primary and secondary cancer was 60 months. Furthermore, 20 of the 165 patients with MPMT had multiple primary gynecologic cancers (MPGC), whereas 145 had gynecologic cancer coexisting with non-gynecologic cancer (GNC). Endometrial-ovarian cancer (60%) was the most common coexisting cancer in the MPGC group, whereas the most common non-gynecologic cancer in the GNC group was breast cancer (34.5%). There were 48 patients with synchronous cancer and 117 patients with metachronous cancer. The incidence of synchronous cancer was higher in the MPGC group than in the GNC group (p = 0.037). Significantly more patients had early-stage ovarian cancer in the MPGC group than in the GNC group (p = 0.031). The overall recurrence and mortality rates were 15.8% and 8.5%, respectively, in patients with MPMT. Conclusion: Synchronous cancer incidence was significantly higher in the MPGC than in the GNC group. Early-stage ovarian cancer was more highly diagnosed in patients with MPGC than in those with GNC. A systematic examination after primary cancer diagnosis could facilitate the early diagnosis of secondary primary malignancy, thereby improving patient prognosis.
Platelet Defects in Acute Myeloid Leukemia—Potential for Hemorrhagic Events
Authors: Bumbea Horia , Vladareanu Ana Maria , Dumitru Ion , Popov Viola Maria , Ciufu Cristina , Nicolescu Anca , Onisai Minodora , Marinescu Cristina , Cisleanu Diana , Voican Irina , Sarghi Sinziana
Published: December 2021

Background and objectives: In acute myeloid leukemia (AML), extensive bleeding is one of the most frequent causes of death. Impaired activation and aggregation processes were identified in previous studies on platelet behaviour associated with this disease. This study’s aim was to examine platelet function in correlation with other haemorrhage risk factors (fever, sepsis, recent bleeding, uraemia, leucocytosis, haematocrit value, treatment). Design and methods: The analysis of platelet surface proteins (Glycoprotein Ib-IX (CD42b, CD42a), Glycoprotein IIb-IIIa (CD41, CD61), p-selectin (CD62P), granulophysin (CD63)) was conducted by flowcytometry from samples of whole blood in patients with acute myeloid leukaemia in different stages of diagnosis and therapy (n = 22) in comparison with healthy human controls (n = 10). Results and interpretations: Our results show a significant decrease in fluorescence level associated with platelet activation markers (CD63 (14.11% vs. 40.78 % p < 0.05); CD62P (15.26% vs. 28.23% p < 0.05)); adhesion markers (CD42b (69.08% vs. 84.41% p < 0.05)) and aggregation markers (CD61 (83.79% vs. 98.62% p < 0.001)) in patients compared to controls. The levels of CD41 (80.62% vs. 86.31%, p = 0.290) and CD42a (77.98% vs. 94.15%, p = 0.99) demonstrate no significant differences in the two groups. Conclusion: The AML patients present changes in adhesion receptors and activation markers, suggesting a functional defect or denatured intracellular signalling in platelets. The exposed data indicate that flow cytometry can effectively identify multiple functional platelet impairments in AML pathogenesis.
TXI (Texture and Color Enhancement Imaging) for Serrated Colorectal Lesions
Authors: Nishizawa Toshihiro , Toyoshima Osamu , Yoshida Shuntaro , Uekura Chie , Kurokawa Ken , Munkhjargal Munkhbayar , Obata Miho , Yamada Tomoharu , Fujishiro Mitsuhiro , Ebinuma Hirotoshi , Suzuki Hidekazu
Published: December 2021

Background and aim: Olympus Corporation released the texture and color enhancement imaging (TXI) technology as a novel image-enhancing endoscopic technique. We investigated the effectiveness of TXI in the imaging of serrated colorectal polyps, including sessile serrated lesions (SSLs). Methods: Serrated colorectal polyps were observed using white light imaging (WLI), TXI, narrow-band imaging (NBI), and chromoendoscopy with and without magnification. Serrated polyps were histologically confirmed. TXI was compared with WLI, NBI, and chromoendoscopy for the visibility of the lesions without magnification and for that of the vessel and surface patterns with magnification. Three expert endoscopists evaluated the visibility scores, which were classified from 1 to 4. Results: Twenty-nine consecutive serrated polyps were evaluated. In the visibility score without magnification, TXI was significantly superior to WLI but inferior to chromoendoscopy in the imaging of serrated polyps and the sub-analysis of SSLs. In the visibility score for vessel patterns with magnification, TXI was significantly superior to WLI and chromoendoscopy in the imaging of serrated polyps and the sub-analysis of SSLs. In the visibility score for surface patterns with magnification, TXI was significantly superior to WLI but inferior to NBI in serrated polyps and in the sub-analysis of SSLs and hyperplastic polyps. Conclusions: TXI provided higher visibility than did WLI for serrated, colorectal polyps, including SSLs.
Canonical (CD74/CD44) and Non-Canonical (CXCR2, 4 and 7) MIF Receptors Are Differentially Expressed in Rheumatoid Arthritis Patients Evaluated by DAS28-ESR
Authors: Sánchez-Zuno Gabriela Athziri , Bucala Richard , Hernández-Bello Jorge , Román-Fernández Ilce Valeria , García-Chagollán Mariel , Nicoletti Ferdinando , Matuz-Flores Mónica Guadalupe , García-Arellano Samuel , Esparza-Michel Judith Alejandra , Cerpa-Cruz Sergio , Pérez-Guerrero Edsaúl Emilio , Muñoz-Valle José Francisco
Published: December 2021

Macrophage migration inhibitory factor (MIF) significantly contributes to rheumatoid arthritis (RA) pathogenesis. We aimed to evaluate the canonical (CD74/CD44) and non-canonical MIF receptors (CXCR2,4 and 7) expression and sCD74 to establish their association with RA clinical activity according to DAS28-ESR. Methodology: 101 RA patients with different clinical activities (remission (n = 27), low (n = 16), moderate (n = 35) and high (n = 23)) and 9 control subjects (CS) were included. Expression was evaluated by flow cytometry and levels of soluble CD74 (sCD74) by ELISA. Data analysis was performed with FlowJov10.0, STATAv12.0, and GraphPad Prism v7.0. Results: According to disease activity, CXCR7 expression (percentage of expression and mean fluorescence intensity (MFI)) was higher in granulocytes from patients in remission, while the expression of CXCR4 was higher in patients with high disease activity (p < 0.05). The expression of CD74 was higher in B cells (p < 0.05) and monocytes (p < 0.01) from patients in remission. Regarding sCD74 levels these were higher in patients with high disease activity when compared to those in remission (p <0.05). Conclusions: The results support the need for further study of the role of sCD74 as a soluble MIF decoy receptor, sequestering it to negatively regulate MIF signaling though its membrane receptors. The expression patterns of CXCR4 and CXCR7 show that the latter is a scavenger-type receptor that prevents endocytosis and even degradation of CXCR4 under inflammatory conditions.