bluuebunny/crossref_metadata_2025 huggingface dataset:
Blood Transfusion Reactions—A Comprehensive Review of the Literature including a Swiss Perspective
Authors: Ackfeld Theresa , Schmutz Thomas , Guechi Youcef , Le Terrier Christophe
Published: May 2022

Blood transfusions have been the cornerstone of life support since the introduction of the ABO classification in the 20th century. The physiologic goal is to restore adequate tissue oxygenation when the demand exceeds the offer. Although it can be a life-saving therapy, blood transfusions can lead to serious adverse effects, and it is essential that physicians remain up to date with the current literature and are aware of the pathophysiology, initial management and risks of each type of transfusion reaction. We aim to provide a structured overview of the pathophysiology, clinical presentation, diagnostic approach and management of acute transfusion reactions based on the literature available in 2022. The numbers of blood transfusions, transfusion reactions and the reporting rate of transfusion reactions differ between countries in Europe. The most frequent transfusion reactions in 2020 were alloimmunizations, febrile non-hemolytic transfusion reactions and allergic transfusion reactions. Transfusion-related acute lung injury, transfusion-associated circulatory overload and septic transfusion reactions were less frequent. Furthermore, the COVID-19 pandemic has challenged the healthcare system with decreasing blood donations and blood supplies, as well as rising concerns within the medical community but also in patients about blood safety and transfusion reactions in COVID-19 patients. The best way to prevent transfusion reactions is to avoid unnecessary blood transfusions and maintain a transfusion-restrictive strategy. Any symptom occurring within 24 h of a blood transfusion should be considered a transfusion reaction and referred to the hemovigilance reporting system. The initial management of blood transfusion reactions requires early identification, immediate interruption of the transfusion, early consultation of the hematologic and ICU departments and fluid resuscitation.
Caries Experience and Increment in Children Attending Kindergartens with an Early Childhood Caries Preventive Program Compared to Basic Prophylaxis Measures—A Retrospective Cohort Study
Authors: Amend Stefanie , Hartmann Thea , Heinzel-Gutenbrunner Monika , Frankenberger Roland , Krämer Norbert , Winter Julia
Published: May 2022

Dental caries constitutes a public health challenge. As preventive strategies are desirable, this retrospective cohort study aimed to assess the caries experience and increment in children attending kindergartens with an early childhood caries (ECC) preventive program (intervention group, IG) compared to basic prophylaxis measures (control group, CG) located in areas of different socioeconomic status (SES) within Marburg (Germany). The long-term caries experience (2009–2019) of these 3–5-year-old kindergarten children was evaluated. For the caries increment, dental records of 2019 were screened for the availability of a minimum of two dental examinations at least 8 months apart. Caries was scored according to the WHO criteria (dmf–t). The data were split by observation period (300–550 and >550 days). Overall, 135 children (Ø 3.7 years) attended IG, and 132 children (Ø 3.6 years) attended CG. After 300–550 days, no significant differences were found between both groups regarding mean caries increment and experience (p > 0.05). After >550 days, IG with low SES exhibited a high caries experience. Fluoride varnish applications could not reduce the caries increment compared to CG in the short-term but slightly decreased the long-term caries experience. Comprehensive ECC prevention measures actively involving parents are needed to overcome the caries burden.
Association between Proton Pump Inhibitor Use and Risk of Hepatocellular Carcinoma: A Korean Nationally Representative Cohort Study
Authors: Kim Soungmun , Jeong Seogsong , Park Sun Jae , Chang Jooyoung , Choi Seulggie , Cho Yoosun , Ahn Joseph C. , Lee Gyeongsil , Son Joung Sik , Park Sang Min
Published: May 2022

(1) Background: The association between proton pump inhibitor (PPI) use and hepatocellular carcinoma (HCC) has been controversial, especially in the general population. We aimed to determine the impact of PPI on HCC risk in participants without liver cirrhosis or chronic hepatitis virus infection. (2) Methods: We assessed 406,057 participants from the Korean National Health Insurance Service database who underwent health screening from 2003 to 2006. We evaluated exposure to PPI before the index date using a standardized daily defined dose (DDD) system. The association of proton pump inhibitor use with the risk of HCC was evaluated using multivariable-adjusted Cox proportional hazards regression. (3) Results: Compared with non-users, PPI use was not associated with the HCC risk in low (<30 DDDs; aHR, 1.07; 95% CI, 0.91–1.27), intermediate (30 ≤ PPI < 60 DDDs; aHR, 0.96; 95% CI, 0.73–1.26), and high (≥60 DDDs; aHR, 0.86; 95% CI, 0.63–1.17) PPI groups in the final adjustment model. In addition, risks of cirrhosis-associated HCC and non-cirrhosis-associated HCC were not significantly associated with PPI use. The results remained consistent after excluding events that occurred within 1, 2, and 3 years to exclude pre-existing conditions that may be associated with the development of HCC. We also found no PPI-associated increase in HCC risk among the selected population, such as those with obesity, older age, and chronic liver diseases. (4) Conclusions: PPI use may not be associated with HCC risk regardless of the amount. We call for future studies conducted in other regions to generalize our findings.
Increased Platelet Reactivity and Proinflammatory Profile Are Associated with Intima–Media Thickness and Arterial Stiffness in Prediabetes
Authors: Di Marco Maurizio , Urbano Francesca , Filippello Agnese , Di Mauro Stefania , Scamporrino Alessandra , Miano Nicoletta , Coppolino Giuseppe , L’Episcopo Giuseppe , Leggio Stefano , Scicali Roberto , Piro Salvatore , Purrello Francesco , Di Pino Antonino
Published: May 2022

Alterations of glucose homeostasis are associated with subclinical vascular damage; however, the role of platelet reactivity in this process has not been fully investigated. In this cross-sectional study, we evaluated the correlation between markers of platelet reactivity and inflammation and markers of vascular disease in subjects with prediabetes. Markers of platelet reactivity such as 11-dehydro-thromboxane B2 urinary levels (11-dh-TXB2) and mean platelet volume (MPV) and inflammatory indexes such as platelet-to-lymphocyte ratio (PLR) were evaluated in subjects with prediabetes (n = 48), new-onset type 2 diabetes (NODM, n = 60) and controls (n = 62). Furthermore, we assessed the cardiovascular risk profile of the study population with arterial stiffness and quality intima–media thickness (qIMT). Subjects with prediabetes and NODM exhibited higher 11-dh-TXB2 urinary levels and MPV and a proinflammatory profile with an increased PLR, high-sensitivity C-reactive protein, ferritin and fibrinogen. Furthermore, after multiple regression analyses, we found that urinary 11-dh-TXB2 was one of the major determinants of IMT and arterial stiffness parameters. In conclusion, subjects with prediabetes exhibit increased platelet reactivity as well as a proinflammatory profile. Furthermore, this condition is associated with early markers of cardiovascular disease.
Impact of On-Clopidogrel Platelet Reactivity on Incidence of Peri-Interventional Bleeding in Patients Undergoing Transcatheter Aortic Valve Implantation
Authors: Kille Alexander , Franke Kilian , Corpataux Noé , Hromek Julia , Valina Christian M. , Neumann Franz-Josef , Trenk Dietmar , Nührenberg Thomas G. , Hochholzer Willibald
Published: May 2022

Dual anti-platelet therapy (DAPT) with clopidogrel and acetylsalicylic acid (ASA) has previously been recommended after transcatheter aortic valve implantation (TAVI) and is still the standard of care in patients who underwent coronary stent placement within 3 months prior to TAVI. This study sought to evaluate whether on-treatment platelet reactivity is a predictor for the occurrence of bleeding events after TAVI. This study enrolled 484 patients undergoing TAVI from November 2013 until April 2018. Patients were either on long-term DAPT with clopidogrel and ASA or received loading doses of both drugs before TAVI, reflecting the standard of care at the time of the patient’s enrollment. Platelet reactivity was determined by multi-electrode impedance aggregometry before TAVI, at days 1 and 5 thereafter. Peri-interventional bleeding was assessed up to 5 days following TAVI and coded according to BARC-classification. Bleeding events were seen in 199 (41.1%) patients. The most frequent were BARC 2 bleeding cases (24.2%), followed by BARC 1 (6.0%), BARC 3b (5.2%), and BARC 3a (4.5%) cases. Low on-clopidogrel platelet reactivity before TAVI was present in 243 patients, of which 44.4% had a bleeding event. In contrast, the incidence of bleeding was 30.5% in the 95 patients with high on-clopidogrel platelet reactivity. Multivariate logistic regression analysis identified low/normal/high on-clopidogrel platelet reactivity (OR: 0.533; CI: 0.309–0.917; p = 0.023) and use of oral anticoagulation (OR: 1.766; CI: 1.209–2.581; p = 0.003) as strongest predictors for peri-interventional bleeding events. These findings support current recommendations advocating against the routine use of dual antiplatelet therapy following TAVI.
Noninvasive Prenatal Testing in Immunohematology—Clinical, Technical and Ethical Considerations
Authors: Kjeldsen-Kragh Jens , Hellberg Åsa
Published: May 2022

Hemolytic disease of the fetus and newborn (HDFN), as well as fetal and neonatal alloimmune thrombocytopenia (FNAIT), represent two important disease entities that are caused by maternal IgG antibodies directed against nonmaternally inherited antigens on the fetal blood cells. These antibodies are most frequently directed against the RhD antigen on red blood cells (RBCs) or the human platelet antigen 1a (HPA-1a) on platelets. For optimal management of pregnancies where HDFN or FNAIT is suspected, it is essential to determine the RhD or the HPA-1a type of the fetus. Noninvasive fetal RhD typing is also relevant for identifying which RhD-negative pregnant women should receive antenatal RhD prophylaxis. In this review, we will give an overview of the clinical indications and technical challenges related to the noninvasive analysis of fetal RBCs or platelet types. In addition, we will discuss the ethical implications associated with the routine administration of antenatal RhD to all pregnant RhD-negative women and likewise the ethical challenges related to making clinical decisions concerning the mother that have been based on samples collected from the (presumptive) father, which is a common practice when determining the risk of FNAIT.
Association between Statin Use and Risk of Parkinson’s Disease: Evidence from 18 Observational Studies Comprising 3.7 Million Individuals
Authors: Wu Chieh-Chen , Islam Md. Mohaimenul , Lee An-Jen , Su Chun-Hsien , Weng Yung-Ching , Yeh Chih-Yang , Lee Hsun-Hua , Lin Ming-Chin
Published: May 2022

The potential impact of statins on the risk of Parkinson’s disease (PD) is still controversial; therefore, we conducted a comprehensive meta-analysis of observational studies to examine the effect of statin use on the risk of PD. We searched electronic databases, such as PubMed, EMBASE, Scopus, and Web of Science, for articles published between 1 January 2000 and 15 March 2022. Cohort studies which examined the association between statins and PD risk in the general population were also included. Two authors assessed the data and extracted all potential information for analysis. Random effects meta-analyses were performed to measure the risk ratio (RR) and 95% confidence intervals (CIs). Eighteen cohort studies including 3.7 million individuals with 31,153 PD participants were identified. In statin users, compared with non-users, the RR for PD was 0.79 (95% CI: 0.68–0.91). In a subgroup analysis of PD, this association was observed with medium and high quality, and the studies were adjusted for age, gender, and smoking status. When the data were stratified according to the duration of exposure, long-duration statin use was associated with a decreased risk of PD (RR = 0.49; 95% CI: 0.26–0.92). There was no significant decrease in the risk of PD in short-term statin users (RR = 0.94; 95% CI: 0.67–1.31). Moreover, no significant difference in the reduction in the risk of PD was observed between men (RR = 0.80; 95% CI: 0.75–0.86) and women (RR = 0.80; 95% CI: 0.75–0.86). Although our findings confirm a reduction in the PD risk associated with statin treatment and suggest that statins play a clinically favorable role, these findings should be interpreted with caution. Future randomized control trials with an ad hoc design are needed to confirm the potential utility of statins in reducing the risk of PD.
A New Compartmentalized Scale (PN) for Measuring Polarity Applied to Novel Ether-Functionalized Amino Acid Ionic Liquids
Authors: Zheng Xu , Guo Chun , Wu Wenqing , Tong Jing
Published: May 2022

Functionalized and environmentally friendly ionic liquids are required in many fields, but convenient methods for measuring their polarity are lacking. Two novel ether-functionalized amino acid ionic liquids, 1-(2-methoxyethyl)-3-methylimidazolium alanine ([C1OC2mim][Ala]) and 1-(2-ethoxyethyl)-3-methylimidazolium alanine ([C2OC2mim][Ala]), were synthesized by a neutralization method and their structures confirmed by NMR spectroscopy. Density, surface tension, and refractive index were determined using the standard addition method. The strength of intermolecular interactions within these ionic liquids was examined in terms of standard entropy, lattice energy, and association enthalpy. A new polarity scale, PN, is now proposed, which divides polarity into two compartments: the surface and the body of the liquid. Surface tension is predicted via an improved Lorentz-Lorenz equation, and molar surface entropy is used to determine the polarity of the surface. This new PN scale is based on easily measured physicochemical parameters, is validated against alternative polarity scales, and is applicable to both ionic and molecular liquids.
Parental Influence in Disengagement during Robot-Assisted Activities: A Case Study of a Parent and Child with Autism Spectrum Disorder
Authors: Kim SunKyoung , Hirokawa Masakazu , Funahashi Atsushi , Suzuki Kenji
Published: May 2022

We examined the influence of a parent on robot-assisted activities for a child with Autism Spectrum Disorder. We observed the interactions between a robot and the child wearing a wearable device during free play sessions. The child participated in four sessions with the parent and interacted willingly with the robot, therapist, and parent. The parent intervened when the child did not interact with the robot, considered “disengagement with the robot”. The number and method of intervention were decided solely by the parent. This study adopted video recording for behavioral observations and specifically observed the situations before the disengagement with the robot, the child’s behaviors during disengagement, and the parent’s intervention. The results showed that mostly the child abruptly discontinued the interactions with the robot without being stimulated by the surrounding environment. The second most common reason was being distracted by various devices in the play sessions, such as the wearable device, a video camera, and a laptop. Once he was disengaged with the robot, he primarily exhibited inappropriate and repetitive behaviors accentuating the symptoms of autism spectrum disorder. The child could re-initiate the interaction with the robot with an 80% chance through the parent’s intervention. This suggests that engagement with a robot may differ depending on the parent’s participation. Moreover, we must consider types of parental feedback to re-initiate engagement with a robot to benefit from the therapy adequately. In addition, environmental distractions must be considered, especially when using multiple devices for therapy.
Medievals and Moderns in Conversation: Co-Designing Creative Futures for Underused Historic Churches in Rural Communities
Authors: Senior Timothy J. , Metcalfe Tom , McClean Stuart , Wilson Alexander , Bowen Simon , Ailes Marianne , McGregor Ed
Published: May 2022

For many living in rural areas, the loss of traditional community assets and increased social fragmentation are a common feature of everyday life. The empty village church is a poignant symbol of these challenges; yet, these are sites that hold considerable potential for new placemaking solutions that respond to the needs of communities today. This means looking beyond “the traditional village church” to recognise a longer history of church adaptation and resilience within the lives of communities. In this paper we ask: how can co-design, projected through a Wicked problems and Clumsy solutions lens, help imagine new futures for communities and their historic churches today? Clumsy solutions consider a plurality of different perspectives on the nature of problems and their resolution to deliver more effective solutions with broad appeal. In the search for clumsiness, we turn to ‘long history’ and ‘slow technology’ for inspiration, uncovering deeper resonance with historical communities of place and anchoring that continuity within church sites themselves. Our paper demonstrates how Wicked/Clumsy thinking can account for the challenges faced by rural communities today, bootstrap co-design activities in the development of clumsy solutions, and uncover clumsiness in long history and slow technology dimensions—together laying the foundation for new placemaking strategies.
Novel Modeling Approach to Analyze Threshold Voltage Variability in Short Gate-Length (15–22 nm) Nanowire FETs with Various Channel Diameters
Authors: Lee Seunghwan , Yoon Jun-Sik , Lee Junjong , Jeong Jinsu , Yun Hyeok , Lim Jaewan , Lee Sanguk , Baek Rock-Hyun
Published: May 2022

In this study, threshold voltage (Vth) variability was investigated in silicon nanowire field-effect transistors (SNWFETs) with short gate-lengths of 15–22 nm and various channel diameters (DNW) of 7, 9, and 12 nm. Linear slope and nonzero y-intercept were observed in a Pelgrom plot of the standard deviation of Vth (σVth), which originated from random and process variations. Interestingly, the slope and y-intercept differed for each DNW, and σVth was the smallest at a median DNW of 9 nm. To analyze the observed DNW tendency of σVth, a novel modeling approach based on the error propagation law was proposed. The contribution of gate-metal work function, channel dopant concentration (Nch), and DNW variations (WFV, ∆Nch, and ∆DNW) to σVth were evaluated by directly fitting the developed model to measured σVth. As a result, WFV induced by metal gate granularity increased as channel area increases, and the slope of WFV in Pelgrom plot is similar to that of σVth. As DNW decreased, SNWFETs became robust to ∆Nch but vulnerable to ∆DNW. Consequently, the contribution of ∆DNW, WFV, and ∆Nch is dominant at DNW of 7 nm, 9 nm, and 12, respectively. The proposed model enables the quantifying of the contribution of various variation sources of Vth variation, and it is applicable to all SNWFETs with various LG and DNW.
Performance of SS304 Modified by Silver Micro/Nano-Dendrite Coating with Hot-Water Super-Repellency in Simulated PEMFC Cathode Environment
Authors: Xuan Junji , Li Bingzhi , Xu Likun , Zhang Zhaoqi , Xin Yonglei , Xue Lili , Li Li
Published: May 2022

In this study, an silver (Ag) plating with micro/nano-dendrite structures is prepared on the 304 stainless steel (SS304) surface by potentiostatic deposition (Ag/SS304). After being modified by n-dodecyl mercaptan (NDM) with the low surface energy, the obtained sample (NDM@Ag/SS304) exhibits stable superhydrophobicity and excellent hot-water repellency. The surface morphology and composition of NDM@Ag/SS304 are analyzed by scanning electron microscope (SEM), X-ray spectrometer (EDS), X-ray diffractometer (XRD), and X-ray photoelectron spectrometer (XPS) characterization. The electrochemical measurements, tests of water contact angle (WCA), and interfacial contact resistance (ICR) are employed to systematically study the performance of the NDM@Ag/SS304 in the simulated cathode environment of proton exchange membrane fuel cell (PEMFC). The results show that the NDM@Ag/SS304 has high corrosion potential (~0.25 V) and low corrosion current density (~4.04 μA/cm2); after potentiostatic polarization (0.6 V, 5 h), the NDM@Ag/SS304 also shows high superhydrophobic stability.
Low Concentrations of Silver Nanoparticles Inhibit Spore Germination and Disturb Gender Differentiation of Ceratopteris thalictroides (L.) Brongn
Authors: Lu Zhenwei , Yin Liyan , Li Wei , Jiang Hong-Sheng
Published: May 2022

Because of their excellent antibacterial properties, silver nanoparticles (AgNPs) are widely used in all walks of life, which has caused them to be discharged into aquatic environments with possible negative effects on aquatic plants. In the present study, we used an aquatic fern, Ceratopteris thalictroides, as a model to investigate the effects of AgNPs on its spore germination, gametophytes, sex differentiation, and growth. The results demonstrated that AgNPs significantly inhibited spore germination of C. thalictroides at a AgNP concentration higher than 0.02 mg/L. Additionally, we found sex-dependent effects of AgNPs on the development and growth of the gametophyte of C. thalictroides. The proportion of hermaphrodites in the gametophytes and the area of gametophytes significantly decreased under AgNP treatment, while no significant effect was observed in the male gametophytes. Using the AgNP filtrate (without nanoparticles) and AgNPs plus cysteine (Ag+ chelator), we found that the release of Ag+ from nanoparticles was not the cause of the toxicity of AgNPs on C. thalictroides. The EC50 of AgNPs on spore germination was 0.0492 mg/L, thus indicating an ecological risk of AgNPs on this species even at concentrations lower than the Ag element concentration of the WHO guidelines for drinking-water quality.
Alternative Options for Complex, Recurrent Pain States Using Cannabinoids, Psilocybin, and Ketamine: A Narrative Review of Clinical Evidence
Authors: Edinoff Amber N. , Fort Juliana M. , Singh Christina , Wagner Sarah E. , Rodriguez Jessica R. , Johnson Catherine A. , Cornett Elyse M. , Murnane Kevin S. , Kaye Adam M. , Kaye Alan D.
Published: May 2022

With emerging information about the potential for morbidity and reduced life expectancy with long-term use of opioids, it is logical to evaluate nonopioid analgesic treatments to manage pain states. Combinations of drugs can provide additive and/or synergistic effects that can benefit the management of pain states. In this regard, tetrahydrocannabinol (THC) and cannabidiol (CBD) modulate nociceptive signals and have been studied for chronic pain treatment. Psilocybin, commonly known as “magic mushrooms”, works at the serotonin receptor, 5-HT2A. Psilocybin has been found in current studies to help with migraines since it has a tryptamine structure and works similarly to triptans. Psilocybin also has the potential for use in chronic pain treatment. However, the studies that have looked at alternative plant-based medications such as THC, CBD, and psilocybin have been small in terms of their sample size and may not consider the demographic or genetic differences in the population because of their small sample sizes. At present, it is unclear whether the effects reported in these studies translate to the general population or even are significant. In summary, additional studies are warranted to evaluate chronic pain management with alternative and combinations of medications in the treatment of chronic pain.
Trigeminal Herpes Zoster Transited to Ipsilateral Occipital Neuralgia
Authors: Takizawa Keita , Yan Zhimin , Nakata Jumi , Young Andrew , Khan Junad , Kalladka Mythili , Noma Noboru
Published: May 2022

The pain of occipital neuralgia (ON) is thought to be secondary to trauma or injury to the occipital nerve at any point along the course of the nerve. ON may also be caused by an infectious process (herpes zoster) or compression of the nerve. The patient, in this case, presented to our clinic with complaints of occipital pain and rash and swelling of the right lower jaw. One week before presenting to our clinic, the patient developed severe pain in the first division of the trigeminal region with erythema and vesicles. A blood test showed a remarkably high antibody titer for varicella–zoster virus (VZV). The patient was prescribed oral valacyclovir (Valtrex®) (3000 mg/day), which resulted in the complete remission of the rash and blisters in the occipital region. This highlights the importance of considering neuroanatomy of the trigeminal region and cervical nerve.
From Gut Microbiota through Low-Grade Inflammation to Obesity: Key Players and Potential Targets
Authors: Vetrani Claudia , Di Nisio Andrea , Paschou Stavroula A. , Barrea Luigi , Muscogiuri Giovanna , Graziadio Chiara , Savastano Silvia , Colao Annamaria ,   on behalf of the Obesity Programs of Nutrition, Education, Research and Assessment (OPERA) Group
Published: May 2022

During the last decades, the gut microbiota has gained much interest in relation to human health. Mounting evidence has shown a strict association between gut microbiota and obesity and its related diseases. Inflammation has been appointed as the driving force behind this association. Therefore, a better understanding of the mechanisms by which gut microbiota might influence inflammation in the host could pave for the identification of effective strategies to reduce inflammation-related diseases, such as obesity and obesity-related diseases. For this purpose, we carried out an extensive literature search for studies published in the English language during the last 10 years. Most relevant studies were used to provide a comprehensive view of all aspects related to the association of gut microbiota and low-grade inflammation with obesity. Accordingly, this narrative review reports the evidence on the key players supporting the role of gut microbiota in the modulation of inflammation in relation to obesity and its complications. Moreover, therapeutic approaches to reduce microbiota-related inflammation are discussed to provide potential targets for future research.
A Focused Insight into Thyme: Biological, Chemical, and Therapeutic Properties of an Indigenous Mediterranean Herb
Authors: Hammoudi Halat Dalal , Krayem Maha , Khaled Sanaa , Younes Samar
Published: May 2022

A perennial wild shrub from the Lamiaceae family and native to the Mediterranean region, thyme is considered an important wild edible plant studied for centuries for its unique importance in the food, pharmaceutical, and cosmetic industry. Thyme is loaded with phytonutrients, minerals and vitamins. It is pungent in taste, yet rich in moisture, proteins, crude fiber, minerals and vitamins. Its chemical composition may vary with geographical location but is mainly composed of flavonoids and antioxidants. Previous studies have illustrated the therapeutic effects of thyme and its essential oils, especially thymol and carvacrol, against various diseases. This is attributed to its multi-pharmacological properties that include, but are not limited to, antioxidant, anti-inflammatory, and antineoplastic actions. Moreover, thyme has long been known for its antiviral, antibacterial, antifungal, and antiseptic activities, in addition to remarkable disruption of microbial biofilms. In the COVID-19 era, some thyme constituents were investigated for their potential in viral binding. As such, thyme presents a wide range of functional possibilities in food, drugs, and other fields and prominent interest as a nutraceutical. The aims of the current review are to present botanical and nutritive values of this herb, elaborate its major constituents, and review available literature on its dietetic and biological activities.
Sesamin Promotes Osteoporotic Fracture Healing by Activating Chondrogenesis and Angiogenesis Pathways
Authors: Yang Zhengmeng , Feng Lu , Wang Ming , Li Yucong , Bai Shanshan , Lu Xuan , Wang Haixing , Zhang Xiaoting , Wang Yaofeng , Lin Sien , Tortorella Micky D. , Li Gang
Published: May 2022

Osteoporotic fracture has been regarded as one of the most common bone disorders in the aging society. The natural herb-derived small molecules were revealed as potential treatment approaches for osteoporotic fracture healing. Sesamin is a member of lignan family, which possesses estrogenic activity and plays a significant role in modulating bone homeostasis. Our previous study reported the promoting effect of sesamin on postmenopausal osteoporosis treatment. However, the role of sesamin in osteoporotic fracture healing has not been well studied yet. In this study, we further investigated the putative treatment effect of sesamin on osteoporotic fracture healing. Our study indicated that sesamin could activate bone morphogenetic protein 2 (BMP2) signaling pathway and further promotes in vitro chondrogenesis and angiogenesis activities. This promoting effect was abolished by the treatment of ERα inhibitor. In the osteoporotic bone fracture model, we demonstrated that sesamin markedly improves the callus formation and increases the cartilaginous area at the early-stage, as well as narrowing the fracture gap, and expands callus volume at the late-stage fracture healing site of the OVX mice femur. Furthermore, the angiogenesis at the osteoporotic fracture site was also significantly improved by sesamin treatment. In conclusion, our research illustrated the therapeutic potential and underlying regulation mechanisms of sesamin on osteoporotic fracture healing. Our studies shed light on developing herb-derived bioactive compounds as novel drugs for the treatment of osteoporotic fracture healing, especially for postmenopausal women with low estrogen level.
Metabolic and Nutritional Aspects in Paediatric Patients with Klinefelter Syndrome: A Narrative Review
Authors: Mameli Chiara , Fiore Giulia , Sangiorgio Arianna , Agostinelli Marta , Zichichi Giulia , Zuccotti Gianvincenzo , Verduci Elvira
Published: May 2022

Klinefelter syndrome is the most common sex chromosomal aneuploidy in males. It is well known that patients with this syndrome have greater mortality and morbidity compared to the general population due to cardiovascular diseases and endocrine metabolism disorders. This augmented risk is due both to hypogonadism and to the syndrome itself. Therefore, correct hormonal replacement therapy and early primary prevention are crucial to these patients. Even though different studies are available on this topic in adult patients, only a few authors have focused on the paediatric population. Thus, in this narrative review, we report the current knowledge of metabolic and nutritional aspects in children with Klinefelter syndrome.
Relationships between Maternal Gene Polymorphisms in One Carbon Metabolism and Adverse Pregnancy Outcomes: A Prospective Mother and Child Cohort Study in China
Authors: Wang Shuxia , Duan Yifan , Jiang Shan , Bi Ye , Pang Xuehong , Liu Changqing , Yang Zhenyu , Lai Jianqiang
Published: May 2022

Background: To investigate relationships between five single nucleotide polymorphisms (SNP) in four maternal genes involved in one carbon metabolism and adverse pregnancy outcomes, including preterm birth (PTB), low birth weight (LBW), and small-for-gestational-age (SGA). Methods: This was a prospective mother and child cohort study in Wuqiang, China. Pregnant women (n = 939) were recruited from Jun 2016 to Oct 2018. Pregnancy outcomes (PTB, LBW, and SGA) were extracted from medical records and other information including age at childbearing, maternal education level, gravidity, parity, pre-pregnancy weight and height was collected by using a structured questionnaire. The maternal serum folate concentration was measured by using Abbott Architect i2000SR chemiluminescence analyzer in the first prenatal care visit. DNA genotyping of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, methionine synthase reductase (MTRR) A66G, methionine synthase (MTR) A2756G, and thymidylate synthetase (TYMS) rs3819102 was processed by Sequenom MassARRAY iPLEX Platform. Univariate and multivariate logistics regression analysis were used to test the relationships between 5 SNPs and PTB, LBW, SGA. Results: Totally, 849 dyads of women and infants were included in the analysis. The prevalence of PTD, LBW, and SGA were 3.76%, 1.58%, and 5.31% respectively. The homozygote frequencies of MTHFR C677T, MTHFR A1298C, MTRR A66G, MTR A2756G, and TYMS rs3819102 were 44.2%, 1.4%, 6.7%, 1.3%, and 3.2%, and the alt allele frequencies were 66.1%, 10.8%, 24.9%, 10.5%, and 20.5% respectively. The average serum folate concentration was 11.95 ng/mL and the folate deficiency rate was 0.47%. There were no significant associations between MTHFR C677T, MTHFR A1298C, MTRR A66G, MTR A2756G, TYMS rs3819102 alleles and PTD, LBW, SGA (p > 0.05). Conclusions: In the population with adequate folate status and low prevalence of adverse pregnancy outcomes, MTHFR C677T, MTHFR A1298C, MTRR A66G, MTR A2756G, TYMS rs3819102 alleles may not be related to PTD, LBW, and SGA.
Bioenergetic Balance of Continuous Venovenous Hemofiltration, a Retrospective Analysis
Authors: Jonckheer Joop , Van Hoorn Alex , Oshima Taku , De Waele Elisabeth
Published: May 2022

(1) Background: Nutrition therapy guided by indirect calorimetry (IC) is the gold standard and is associated with lower morbidity and mortality in critically ill patients. When performing IC during continuous venovenous hemofiltration (CVVH), the measured VCO2 should be corrected for the exchanged CO2 to calculate the ‘true’ Resting Energy Expenditure (REE). After the determination of the true REE, the caloric prescription should be adapted to the removal and addition of non-intentional calories due to citrate, glucose, and lactate in dialysis fluids to avoid over- and underfeeding. We aimed to evaluate this bioenergetic balance during CVVH and how nutrition therapy should be adapted. (2) Methods: This post hoc analysis evaluated citrate, glucose, and lactate exchange. Bioenergetic balances were calculated based on these values during three different CVVH settings: low dose with citrate, high dose with citrate, and low dose without citrate. The caloric load of these non-intentional calories during a CVVH-run was compared to the true REE. (3) Results: We included 19 CVVH-runs. The bioenergetic balance during the low dose with citrate was 498 ± 110 kcal/day (range 339 to 681 kcal/day) or 26 ± 9% (range 14 to 42%) of the true REE. During the high dose with citrate, it was 262 ± 222 kcal/day (range 56 to 262 kcal/day) or 17 ± 11% (range 7 to 32%) of the true REE. During the low dose without citrate, the bioenergetic balance was −189 ± 77 kcal/day (range −298 to −92 kcal/day) or −13 ± 8% (range −28 to −5%) of the true REE. (4) Conclusions: Different CVVH settings resulted in different bioenergetic balances ranging from −28% up to +42% of the true REE depending on the CVVH fluids chosen. When formulating a caloric prescription during CVVH, an individual approach considering the impact of these non-intentional calories is warranted.
Biocontrol of Wheat Crown Rot Using Bacillus halotolerans QTH8
Authors: Li Shen , Xu Jianqiang , Fu Liming , Xu Guohui , Lin Xiaomin , Qiao Junqing , Xia Yanfei
Published: May 2022

Fusarium pseudograminearum causes crown rot in wheat. This study aimed to assess the effects of the bacterial strain QTH8 isolated from Cotinus coggygria rhizosphere soil against F. pseudograminearum. Bacterial strain QTH8 was identified as Bacillus halotolerans in accordance with the phenotypic traits and the phylogenetic analysis of 16S rDNA and gyrB gene sequence. Culture filtrates of bacterial strain QTH8 inhibited the mycelial growth of F. pseudograminearum and resulted in mycelial malformation such as tumor formation, protoplast condensation, and mycelial fracture. In addition, bacterial strain QTH8 also inhibited the mycelial growth of Hainesia lythri, Pestalotiopsis sp., Botrytis cinerea, Curvularia lunata, Phyllosticta theaefolia, Fusarium graminearum, Phytophthora nicotianae, and Sclerotinia sclerotiorum. The active compounds produced by bacterial strain QTH8 were resistant to pH, ultraviolet irradiation, and low temperature, and were relatively sensitive to high temperature. After 4 h exposure, culture filtrates of bacterial strain QTH8—when applied at 5%, 10%, 15%, 20%, 25%, and 30%—significantly reduced conidial germination of F. pseudograminearum. The coleoptile infection assay proved that bacterial strain QTH8 reduced the disease index of wheat crown rot. In vivo application of QTH8 to wheat seedlings decreased the disease index of wheat crown rot and increased root length, plant height, and fresh weight. Iturin, surfactin, and fengycin were detected in the culture extract of bacterial strain QTH8 by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Bacterial strain QTH8 was identified for the presence of the ituC, bacA, bmyB, spaS, srfAB, fend, and srfAA genes using the specific polymerase chain reaction primers. B. halotolerans QTH8 has a vital potential for the sustainable biocontrol of wheat crown rot.
Tofacitinib May Inhibit Myofibroblast Differentiation from Rheumatoid-Fibroblast-like Synoviocytes Induced by TGF-β and IL-6
Authors: Ruscitti Piero , Liakouli Vasiliki , Panzera Noemi , Angelucci Adriano , Berardicurti Onorina , Di Nino Elena , Navarini Luca , Vomero Marta , Ursini Francesco , Mauro Daniele , Dolo Vincenza , Ciccia Francesco , Giacomelli Roberto , Cipriani Paola
Published: May 2022

During rheumatoid arthritis (RA), the pathogenic role of resident cells within the synovial membrane is suggested, especially for a population frequently referred to as fibroblast-like synoviocytes (FLSs). In this study, we assess the markers of myofibroblast differentiation of RA-FLSs by ex vivo observations and in vitro evaluations following the stimulation with both TGF-β and IL-6. Furthermore, we investigated the possible inhibiting role of tofacitinib, a JAK inhibitor, in this context. Myofibroblast differentiation markers were evaluated on RA synovial tissues by immune-fluorescence or immune-histochemistry. RA-FLSs, stimulated with transforming growth factor (TGF-β) and interleukin-6 (IL-6) with/without tofacitinib, were assessed for myofibroblast differentiation markers expression by qRT-PCR and Western blot. The same markers were evaluated following JAK-1 silencing by siRNA assay. The presence of myofibroblast differentiation markers in RA synovial tissue was significantly higher than healthy controls. Ex vivo, α-SMA was increased, whereas E-Cadherin decreased. In vitro, TGF-β and IL-6 stimulation of RA-FLSs promoted a significant increased mRNA expression of collagen I and α-SMA, whereas E-Cadherin mRNA expression was decreased. In the same conditions, the stimulation with tofacitinib significantly reduced the mRNA expression of collagen I and α-SMA, even if the Western blot did not confirm this finding. JAK-1 gene silencing did not fully prevent the effects of stimulation with TGF-β and IL-6 on these features. TGF-β and IL-6 stimulation may play a role in mediating myofibroblast differentiation from RA-FLSs, promoting collagen I and α-SMA while decreasing E-Cadherin. Following the same stimulation, tofacitinib reduced the increases of both collagen I and α-SMA on RA-FLSs, although further studies are needed to fully evaluate this issue and confirm our results.
Targeting Nuclear Receptors in Lung Cancer—Novel Therapeutic Prospects
Authors: Gangwar Shailendra Kumar , Kumar Aviral , Yap Kenneth Chun-Hong , Jose Sandra , Parama Dey , Sethi Gautam , Kumar Alan Prem , Kunnumakkara Ajaikumar B.
Published: May 2022

Lung cancer, the second most commonly diagnosed cancer, is the major cause of fatalities worldwide for both men and women, with an estimated 2.2 million new incidences and 1.8 million deaths, according to GLOBOCAN 2020. Although various risk factors for lung cancer pathogenesis have been reported, controlling smoking alone has a significant value as a preventive measure. In spite of decades of extensive research, mechanistic cues and targets need to be profoundly explored to develop potential diagnostics, treatments, and reliable therapies for this disease. Nuclear receptors (NRs) function as transcription factors that control diverse biological processes such as cell growth, differentiation, development, and metabolism. The aberrant expression of NRs has been involved in a variety of disorders, including cancer. Deregulation of distinct NRs in lung cancer has been associated with numerous events, including mutations, epigenetic modifications, and different signaling cascades. Substantial efforts have been made to develop several small molecules as agonists or antagonists directed to target specific NRs for inhibiting tumor cell growth, migration, and invasion and inducing apoptosis in lung cancer, which makes NRs promising candidates for reliable lung cancer therapeutics. The current work focuses on the importance of various NRs in the development and progression of lung cancer and highlights the different small molecules (e.g., agonist or antagonist) that influence NR expression, with the goal of establishing them as viable therapeutics to combat lung cancer.
Behavior of Regular Insulin in a Parenteral Nutrition Admixture: Validation of an LC/MS-MS Assay and the In Vitro Evaluation of Insulin Glycation
Authors: Henry Heloise , Goossens Jean-François , Kouach Mostafa , Lannoy Damien , Seguy David , Dine Thierry , Odou Pascal , Foulon Catherine
Published: May 2022

Parenteral-nutrition (PN)-induced hyperglycemia increases morbidity and mortality and must be treated with insulin. Unfortunately, the addition of insulin to a ternary PN admixture leads to a rapid decrease in insulin content. Our study’s objective was to determine the mechanistic basis of insulin’s disappearance. The literature data suggested the presence of a glycation reaction; we therefore validated an LC-MS/MS assay for insulin and glycated insulin. In a 24-h stability study, 20 IU/L of insulin was added to a binary PN admixture at pH 3.6 or 6.3. When the samples were diluted before analysis with a near-neutral diluent, insulin was fully stable at pH 3.6, while a loss of around 50% was observed at pH 6.3. Its disappearance was shown to be inversely correlated with the appearance of monoglycated insulin (probably a Schiff base adduct). Monoglycated insulin might also undergo a back-reaction to form insulin after acidic dilution. Furthermore, a second monoglycated insulin species appeared in the PN admixture after more than 24 h at high temperature (40 °C) and a high insulin concentration (1000 IU/L). It was stable at acidic pH and might be an Amadori product. The impact of insulin glycation under non-forced conditions on insulin’s bioactivity requires further investigation.
Targeting Peptide, Fluorescent Reagent Modified Magnetic Liposomes Coated with Rapamycin Target Early Atherosclerotic Plaque and Therapy
Authors: Huang Chen , Huang Wentao , Zhang Lifen , Zhang Chunyu , Zhou Chengqian , Wei Wei , Li Yongsheng , Zhou Quan , Chen Wenli , Tang Yukuan
Published: May 2022

Atherosclerosis is the leading cause of global morbidity and mortality. Its therapy requires research in several areas, such as diagnosis of early arteriosclerosis, improvement of the pharmacokinetics and bioavailability of rapamycin as its therapeutic agents. Here, we used the targeting peptide VHPKQHR (VHP) (or fluorescent reagent) to modify the phospholipid molecules to target vascular cell adhesion molecule-1 (VCAM-1) and loaded ultrasmall paramagnetic iron oxide (USPIO/Fe3O4) plus rapamycin (Rap) to Rap/Fe3O4@VHP-Lipo (VHPKQHR-modified magnetic liposomes coated with Rap). This nanoparticle can be used for both the diagnosis and therapy of early atherosclerosis. We designed both an ex vivo system with mouse aortic endothelial cells (MAECs) and an in vivo system with ApoE knockout mice to test the labeling and delivering potential of Rap/Fe3O4@VHP-Lipo with fluorescent microscopy, flow cytometry and MRI. Our results of MRI imaging and fluorescence imaging showed that the T2 relaxation time of the Rap/Fe3O4@VHP-Lipo group was reduced by 2.7 times and 1.5 times, and the fluorescence intensity increased by 3.4 times and 2.5 times, respectively, compared with the normal saline group and the control liposome treatment group. It showed that Rap/Fe3O4@VHP-Lipo realized the diagnosis of early AS. Additionally, our results showed that, compared with the normal saline and control liposomes treatment group, the aortic fluorescence intensity of the Rap/Fe3O4@VHP-Lipo treatment group was significantly weaker, and the T2 relaxation time was prolonged by 8.9 times and 2.0 times, indicating that the targeted diagnostic agent detected the least plaques in the Rap/Fe3O4@VHP-Lipo treatment group. Based on our results, the synthesized theragnostic Rap/Fe3O4@VHP-Lipo serves as a great label for both MRI and fluorescence bimodal imaging of atherosclerosis. It also has therapeutic effects for the early treatment of atherosclerosis, and it has great potential for early diagnosis and can achieve the same level of therapy with a lower dose of Rap.
Electronic Absorption, Emission, and Two-Photon Absorption Properties of Some Extended 2,4,6-Triphenyl-1,3,5-Triazines
Authors: Barnes Alison G. , Richy Nicolas , Amar Anissa , Blanchard-Desce Mireille , Boucekkine Abdou , Mongin Olivier , Paul Frédéric
Published: May 2022

We report herein the linear optical properties of some extended 2,4,6-triphenyl-s-triazines of formula 2,4,6-[(1,4-C6H4)C≡C(4-C6H4X)]3-1,3,5-(C3H3N3) (3-X; X = NO2, CN, OMe, NMe2, NPh2) and related analogues 4 and 7-X (X = H, NPh2), before briefly discussing their two-photon absorption (2PA) cross-sections. Their 2PA performance is discussed in relation to 2PA values previously measured for closely related octupoles such as N,N′,N″-triphenylisocyanurates (1-X, 5, and 6-X) or 1,3,5-triphenylbenzenes (2-X). While s-triazines are usually much better two-photon absorbers in the near-IR range than these molecules, especially when functionalised by electron-releasing substituents at their periphery, they present a decreased transparency window in the visible range due to their red-shifted first 1PA peak, in particular when compared with corresponding isocyanurates analogues. In contrast, due to their significantly larger two-photon brilliancy, 2,4,6-triphenyl-s-triazines appear more promising than the latter for two-photon fluorescence bio-imaging purposes. Rationalisation of these unexpected outcomes is proposed based on DFT calculations.