bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Consequences of Depression Treatment: A Potential In Vitro Mechanism for Antidepressants-Induced Reprotoxic Side Effects
Authors: Sołek Przemysław , Mytych Jennifer , Tabęcka-Łonczyńska Anna , Koziorowski Marek
Published: November 2021

The incidence of depression among humans is growing worldwide, and so is the use of antidepressants. However, our fundamental understanding regarding the mechanisms by which these drugs function and their off-target effects against human sexuality remains poorly defined. The present study aimed to determine their differential toxicity on mouse spermatogenic cells and provide mechanistic data of cell-specific response to antidepressant and neuroleptic drug treatment. To directly test reprotoxicity, the spermatogenic cells (GC-1 spg and GC-2 spd cells) were incubated for 48 and 96 h with amitriptyline (hydrochloride) (AMI), escitalopram (ESC), fluoxetine (hydrochloride) (FLU), imipramine (hydrochloride) (IMI), mirtazapine (MIR), olanzapine (OLZ), reboxetine (mesylate) (REB), and venlafaxine (hydrochloride) (VEN), and several cellular and biochemical features were assessed. Obtained results reveal that all investigated substances showed considerable reprotoxic potency leading to micronuclei formation, which, in turn, resulted in upregulation of telomeric binding factor (TRF1/TRF2) protein expression. The TRF-based response was strictly dependent on p53/p21 signaling and was followed by irreversible G2/M cell cycle arrest and finally initiation of apoptotic cell death. In conclusion, our findings suggest that antidepressants promote a telomere-focused DNA damage response in germ cell lines, which broadens the established view of antidepressants’ and neuroleptic drugs’ toxicity and points to the need for further research in this topic with the use of in vivo models and human samples.
Stereoselective Synthesis of 24-Fluoro-25-Hydroxyvitamin D3 Analogues and Their Stability to hCYP24A1-Dependent Catabolism
Authors: Kawagoe Fumihiro , Mototani Sayuri , Yasuda Kaori , Mano Hiroki , Sakaki Toshiyuki , Kittaka Atsushi
Published: November 2021

Two 24-fluoro-25-hydroxyvitamin D3 analogues (3,4) were synthesized in a convergent manner. The introduction of a stereocenter to the vitamin D3 side-chain C24 position was achieved via Sharpless dihydroxylation, and a deoxyfluorination reaction was utilized for the fluorination step. Comparison between (24R)- and (24S)-24-fluoro-25-hydroxyvitamin D3 revealed that the C24-R-configuration isomer 4 was more resistant to CYP24A1-dependent metabolism than its 24S-isomer 3. The new synthetic route of the CYP24A1 main metabolite (24R)-24,25-dihydroxyvitamin D3 (6) and its 24S-isomer (5) was also studied using synthetic intermediates (30,31) in parallel.
Short- and Long-Term Implications of Human Milk Microbiota on Maternal and Child Health
Authors: García-Ricobaraza María , García-Santos José Antonio , Escudero-Marín Mireia , Diéguez Estefanía , Cerdó Tomás , Campoy Cristina
Published: November 2021

Human milk (HM) is considered the most complete food for infants as its nutritional composition is specifically designed to meet infant nutritional requirements during early life. HM also provides numerous biologically active components, such as polyunsaturated fatty acids, milk fat globules, IgA, gangliosides or polyamines, among others; in addition, HM has a “bifidogenic effect”, a prebiotic effect, as a result of the low concentration of proteins and phosphates, as well as the presence of lactoferrin, lactose, nucleotides and oligosaccharides. Recently, has been a growing interest in HM as a potential source of probiotics and commensal bacteria to the infant gut, which might, in turn, influence both the gut colonization and maturation of infant immune system. Our review aims to address practical approaches to the detection of microbial communities in human breast milk samples, delving into their origin, composition and functions. Furthermore, we will summarize the current knowledge of how HM microbiota dysbiosis acts as a short- and long-term predictor of maternal and infant health. Finally, we also provide a critical view of the role of breast milk-related bacteria as a novel probiotic strategy in the prevention and treatment of maternal and offspring diseases.
Tofacitinib Ameliorates Retinal Vascular Leakage in a Murine Model of Diabetic Retinopathy with Type 2 Diabetes
Authors: Byrne Eimear M. , Llorián-Salvador María , Lyons Timothy J. , Chen Mei , Xu Heping
Published: November 2021

We have previously reported that inhibition of the Janus kinase 1 (JAK1) signaling ameliorates IL-17A-mediated blood-retinal barrier (BRB) dysfunction. Higher levels of IL-17A have been observed in the blood and intraocular fluids in patients with diabetic retinopathy (DR), in particular those with diabetic macular oedema. This study aimed to understand whether JAK1 inhibition could prevent BRB dysfunction in db/db mice, a model of type 2 diabetes (T2D). An in vitro study showed that high glucose treatment disrupted the junctional distribution of claudin-5 in bEnd3 cells and ZO-1 in ARPE19 cells and that tofacitinib citrate treatment prevented high glucose-mediated tight junction disruption. Albumin leakage, accompanied by increased levels of the phosphorylated form of JAK1 (pJAK1), was observed in three-month-old db/db mice. Treatment of two-and-a-half-month-old db/db mice with tofacitinib citrate for two weeks significantly reduced retinal albumin leakage and reduced pJAK1 expression. pJAK1 expression was also detected in human DR retina. Our results suggest that JAK1 inhibition can ameliorate BRB dysfunction in T2D, and JAK1 inhibitors such as tofacitinib citrate may be re-purposed for the management of diabetic macular oedema.
Wnt Signaling in Inner Blood–Retinal Barrier Maintenance
Authors: Yemanyi Felix , Bora Kiran , Blomfield Alexandra K. , Wang Zhongxiao , Chen Jing
Published: November 2021

The retina is a light-sensing ocular tissue that sends information to the brain to enable vision. The blood–retinal barrier (BRB) contributes to maintaining homeostasis in the retinal microenvironment by selectively regulating flux of molecules between systemic circulation and the retina. Maintaining such physiological balance is fundamental to visual function by facilitating the delivery of nutrients and oxygen and for protection from blood-borne toxins. The inner BRB (iBRB), composed mostly of inner retinal vasculature, controls substance exchange mainly via transportation processes between (paracellular) and through (transcellular) the retinal microvascular endothelium. Disruption of iBRB, characterized by retinal edema, is observed in many eye diseases and disturbs the physiological quiescence in the retina’s extracellular space, resulting in vision loss. Consequently, understanding the mechanisms of iBRB formation, maintenance, and breakdown is pivotal to discovering potential targets to restore function to compromised physiological barriers. These unraveled targets can also inform potential drug delivery strategies across the BRB and the blood–brain barrier into retinas and brain tissues, respectively. This review summarizes mechanistic insights into the development and maintenance of iBRB in health and disease, with a specific focus on the Wnt signaling pathway and its regulatory role in both paracellular and transcellular transport across the retinal vascular endothelium.
R2R3-MYB Transcription Factor PlMYB108 Confers Drought Tolerance in Herbaceous Peony (Paeonia lactiflora Pall.)
Authors: Wu Yanqing , Li Tingting , Cheng Zhuoya , Zhao Daqiu , Tao Jun
Published: November 2021

The MYB transcription factor (TF) is crucial for plant growth, development, and response to abiotic stress, but it is rarely reported in the herbaceous peony (Paeonia lactiflora Pall.). Here, an MYB TF gene was isolated, and based on our prior mRNA data from P. lactiflora samples, it was treated with drought stress (DS). Its complete cDNA structure was 1314 bp, which encoded 291 amino acids (aa). Furthermore, using sequence alignment analysis, we demonstrated that PlMYB108 was an R2R3-MYB TF. We also revealed that PlMYB108 was primarily localized in the nucleus. Its levels rose during DS, and it was positively correlated with drought tolerance (DT) in P. lactiflora. In addition, when PlMYB108 was overexpressed in tobacco plants, the flavonoid content, antioxidant enzyme activities, and photosynthesis were markedly elevated. Hence, the transgenic plants had stronger DT with a higher leaf water content and lower H2O2 accumulation compared to the wild-type (WT) plants. Based on these results, PlMYB108 is a vital gene that serves to increase flavonoid accumulation, reactive oxygen species (ROS), scavenging capacity, and photosynthesis to confer DT. The results would provide a genetic resource for molecular breeding to enhance plant DT.
Recombinase Polymerase Amplification Assay with and without Nuclease-Dependent-Labeled Oligonucleotide Probe
Authors: Ivanov Aleksandr V. , Safenkova Irina V. , Zherdev Anatoly V. , Dzantiev Boris B.
Published: November 2021

The combination of recombinase polymerase amplification (RPA) and lateral flow test (LFT) is a strong diagnostic tool for rapid pathogen detection in resource-limited conditions. Here, we compared two methods generating labeled RPA amplicons following their detection by LFT: (1) the basic one with primers modified with different tags at the terminals and (2) the nuclease-dependent one with the primers and labeled oligonucleotide probe for nuclease digestion that was recommended for the high specificity of the assay. Using both methods, we developed an RPA-LFT assay for the detection of worldwide distributed phytopathogen—alfalfa mosaic virus (AMV). A forward primer modified with fluorescein and a reverse primer with biotin and fluorescein-labeled oligonucleotide probe were designed and verified by RPA. Both labeling approaches and their related assays were characterized using the in vitro-transcribed mRNA of AMV and reverse transcription reaction. The results demonstrated that the RPA-LFT assay based on primers-labeling detected 103 copies of RNA in reaction during 30 min and had a half-maximal binding concentration 22 times lower than probe-dependent RPA-LFT. The developed RPA-LFT was successfully applied for the detection of AMV-infected plants. The results can be the main reason for choosing simple labeling with primers for RPA-LFT for the detection of other pathogens.
Circulating miRNAs as Potential Biomarkers Distinguishing Relapsing–Remitting from Secondary Progressive Multiple Sclerosis. A Review
Authors: Pietrasik Sylwia , Dziedzic Angela , Miller Elzbieta , Starosta Michal , Saluk-Bijak Joanna
Published: November 2021

Multiple sclerosis (MS) is a debilitating neurodegenerative, highly heterogeneous disease with a variable course. The most common MS subtype is relapsing–remitting (RR), having interchanging periods of worsening and relative stabilization. After a decade, in most RR patients, it alters into the secondary progressive (SP) phase, the most debilitating one with no clear remissions, leading to progressive disability deterioration. Among the greatest challenges for clinicians is understanding disease progression molecular mechanisms, since RR is mainly characterized by inflammatory processes, while in SP, the neurodegeneration prevails. This is especially important because distinguishing RR from the SP subtype early will enable faster implementation of appropriate treatment. Currently, the MS course is not well-correlated with the biomarkers routinely used in clinical practice. Despite many studies, there are still no reliable indicators correlating with the disease stage and its activity degree. Circulating microRNAs (miRNAs) may be considered valuable molecules for the MS diagnosis and, presumably, helpful in predicting disease subtype. MiRNA expression dysregulation is commonly observed in the MS course. Moreover, knowledge of diverse miRNA panel expression between RRMS and SPMS may allow for deterring disability progression through successful treatment. Therefore, in this review, we address the current state of research on differences in miRNA panel expression between the phases.
Overexpression of ZNT1 and NRAMP4 from the Ni Hyperaccumulator Noccaea caerulescens Population Monte Prinzera in Arabidopsis thaliana Perturbs Fe, Mn, and Ni Accumulation
Authors: Fasani Elisa , DalCorso Giovanni , Zorzi Gianluca , Agrimonti Caterina , Fragni Rosaria , Visioli Giovanna , Furini Antonella
Published: November 2021

Metalliferous soils are characterized by a high content of metal compounds that can hamper plant growth. The pseudometallophyte Noccaea caerulescens is able to grow on metalliferous substrates by implementing both tolerance and accumulation of usually toxic metal ions. Expression of particular transmembrane transporter proteins (e.g., members of the ZIP and NRAMP families) leads to metal tolerance and accumulation, and its comparison between hyperaccumulator N. caerulescens with non-accumulator relatives Arabidopsis thaliana and Thlaspi arvense has deepened our knowledge on mechanisms adopted by plants to survive in metalliferous soils. In this work, two transporters, ZNT1 and NRAMP4, expressed in a serpentinic population of N. caerulescens identified on the Monte Prinzera (Italy) are considered, and their expression has been induced in yeast and in A. thaliana. In the latter, single transgenic lines were crossed to test the effect of the combined over-expression of the two transporters. An enhanced iron and manganese translocation towards the shoot was induced by overexpression of NcZNT1. The combined overexpression of NcZNT1 and NcNRAMP4 did perturb the metal accumulation in plants.
A Novel Spo11 Homologue Functions as a Positive Regulator in Cyst Differentiation in Giardia lamblia
Authors: Chen Yu-Chien , Tung Szu-Yu , Huang Chia-Wei , Gan Soo-Wah , Lin Bo-Chi , Chen Chia-Wei , Lin Zi-Qi , Sun Chin-Hung
Published: November 2021

Giardia lamblia persists in a dormant state with a protective cyst wall for transmission. It is incompletely known how three cyst wall proteins (CWPs) are coordinately synthesized during encystation. Meiotic recombination is required for sexual reproduction in animals, fungi, and plants. It is initiated by formation of double-stranded breaks by a topoisomerase-like Spo11. It has been shown that exchange of genetic material in the fused nuclei occurs during Giardia encystation, suggesting parasexual recombination processes of this protozoan. Giardia possesses an evolutionarily conserved Spo11 with typical domains for cleavage reaction and an upregulated expression pattern during encystation. In this study, we asked whether Spo11 can activate encystation process, like other topoisomerases we previously characterized. We found that Spo11 was capable of binding to both single-stranded and double-stranded DNA in vitro and that it could also bind to the cwp promoters in vivo as accessed in chromatin immunoprecipitation assays. Spo11 interacted with WRKY and MYB2 (named from myeloblastosis), transcription factors that can activate cwp gene expression during encystation. Interestingly, overexpression of Spo11 resulted in increased expression of cwp1-3 and myb2 genes and cyst formation. Mutation of the Tyr residue for the active site or two conserved residues corresponding to key DNA-binding residues for Arabidopsis Spo11 reduced the levels of cwp1-3 and myb2 gene expression and cyst formation. Targeted disruption of spo11 gene with CRISPR/Cas9 system led to a significant decrease in cwp1-3 and myb2 gene expression and cyst number. Our results suggest that Spo11 acts as a positive regulator for Giardia differentiation into cyst.
Increased Collagen Crosslinking in Stiff Clubfoot Tissue: Implications for the Improvement of Therapeutic Strategies
Authors: Knitlova Jarmila , Doubkova Martina , Eckhardt Adam , Ostadal Martin , Musilkova Jana , Bacakova Lucie , Novotny Tomas
Published: November 2021

Congenital clubfoot is a complex musculoskeletal deformity, in which a stiff, contracted tissue forms in the medial part of the foot. Fibrotic changes are associated with increased collagen deposition and lysyl oxidase (LOX)-mediated crosslinking, which impair collagen degradation and increase the tissue stiffness. First, we studied collagen deposition, as well as the expression of collagen and the amount of pyridinoline and deoxypyridinoline crosslinks in the tissue of relapsed clubfoot by immunohistochemistry, real-time PCR, and enzyme-linked immunosorbent assay (ELISA). We then isolated fibroblast-like cells from the contracted tissue to study the potential inhibition of these processes in vitro. We assessed the effects of a LOX inhibitor, β-aminopropionitrile (BAPN), on the cells by a hydroxyproline assay, ELISA, and Second Harmonic Generation imaging. We also evaluated the cell-mediated contraction of extracellular matrix in 3D cell-populated collagen gels. For the first time, we have confirmed significantly increased crosslinking and excessive collagen type I deposition in the clubfoot-contracted tissue. We successfully reduced these processes in vitro in a dose-dependent manner with 10–40 µg/mL of BAPN, and we observed an increasing trend in the inhibition of the cell-mediated contraction of collagen gels. The in vitro inhibitory effects indicate that BAPN has good potential for the treatment of relapsed and resistant clubfeet.
Pollen Feeding Reduces Predation of Northern Corn Rootworm Eggs (Coleoptera: Chrysomelidae, Diabrotica barberi) by a Soil-Dwelling Mite (Acari: Laelapidae: Stratiolaelaps scimitus)
Authors: Prischmann-Voldseth Deirdre A. , Swenson Stephanie J. , Brenner Robert
Published: November 2021

Landscape diversification with flowering plants can benefit pollinators and natural enemies, although insect pests can also use floral resources for nutrition and chemoprotection. Corn rootworms (Coleoptera: Chrysomelidae, Diabrotica spp.) are major pests of corn (Zea mays L.), and while subterranean larvae primarily feed on corn roots, adult rootworms commonly consume floral resources from other plant species. We quantified the species, density, and sex of adult corn Diabroticite rootworm beetles on wild and cultivated sunflower, corn, and squash, quantified pollen within the bodies of adult northern corn rootworms [NCR, D. barberi (Smith & Lawrence)], and investigated how consumption of sunflower and corn pollen by NCR adults impacted predation of their eggs by two soil-dwelling mites with different feeding specialization. NCR were the most common Diabroticite species on sunflower inflorescences and western corn rootworm (WCR, D. v. virgifera LeConte) were more abundant in corn and squash blossoms. Pollen feeding by NCR adults did not impact egg predation by omnivorous Tyrophagus putrescentiae (Schrank) (Acari: Sarcoptiformes, Acaridae), but predatory Stratiolaelaps scimitus (Womersley) (Acari: Mesostigmata, Laelapidae) ate eggs less frequently and took longer to feed on eggs from NCR females that had fed on sunflower pollen. This research suggests pollen feeding by adult NCR can impact predation of their eggs. While increasing plant diversity can benefit natural enemies and pest control within agroecosystems, it is important to consider how floral resources alter dietary preferences of biocontrol agents.
Echoentomography for Assessing Braconid Parasitization on Soft-Bodied Tephritid Hosts
Authors: Ricciardi Renato , Izzetti Rossana , Romanelli Marco , Caramella Davide , Lucchi Andrea , Benelli Giovanni
Published: November 2021

Entomological approaches currently available for assessing host parasitization require dissection, polymerase chain reaction (PCR), or waiting for adult emergence. The first two methods are relatively fast but destructive, whereas the third one allows the emergence of the parasitoid but it is time consuming. In this framework, new diagnostic imaging tools may contribute to solve the lack of an accurate, rapid, and non-invasive approach to evaluate the parasitization of soft-bodied insects by their endoparasitoids. In this study, ultra-high frequency ultrasound (UHFUS) technology, which is currently used in medical and preclinical fields, was adopted to assess the parasitization of the invasive polyphagous Mediterranean fruit fly, Ceratitis capitata (Diptera: Tephritidae), testing 2nd and 3rd instar larvae. Parasitization assays were carried out with the solitary koinobiont endophagous parasitoid Psyttalia concolor (Hymenoptera: Braconidae: Opiinae). The efficacy of UHFUS-based echoentomography was compared with the classical method of dissecting the larval host under a stereomicroscope. Our results showed that the UHFUS diagnostic capability was statistically comparable with that of dissection, both on C. capitata 2nd and 3rd larvae. Overall, UHFUS-based echoentomography may be further considered as a fast, non-invasive, and effective approach to evaluate the parasitoid’s ability to successfully oviposit in soft-bodied hosts.
Relationships between the Pathogen Erysiphe alphitoides, the Phytophagous Mite Schizotetranychus garmani (Acari: Tetranychidae) and the Predatory Mite Euseius finlandicus (Acari: Phytoseiidae) in Oak
Authors: Milanović Slobodan , Mladenović Katarina , Stojnić Bojan , Solla Alejandro , Milenković Ivan , Uremović Vanja , Tack Ayco J. M.
Published: November 2021

Food webs on forest trees include plant pathogens, arthropods, and their natural enemies. To increase the understanding of the impact of a plant pathogen on herbivore-natural enemy interactions, we studied the powdery mildew fungus Erysiphe alphitoides, the phytophagous mite Schizotetranychus garmani, and the predatory and mycophagous mite Euseius finlandicus in pedunculate oak (Quercus robur) leaves. In June, July and August of 2016, we assessed the severity of powdery mildew, mite population density and adult female mite size in 30 trees in three forests near Belgrade, Serbia. In August, the infection severity of E. alphitoides related positively to the population density of S. garmani and negatively to the body size of S. garmani females. Throughout the vegetative season, the infection severity of E. alphitoides related positively to the population density of E. finlandicus but not to its body size. The effect of E. alphitoides on the population density and adult size of S. garmani was not mediated by the population density of E. finlandicus, and vice versa. Interactions were consistent in all forests and varied with the summer month. Our findings indicate that E. alphitoides can influence the average body size and population densities of prey and predatory mites studied, irrespective of predator-prey relationships.
Comparison of Auxin and Cytokinins Concentrations, and the Structure of Bacterial Community between Host Twigs and Lithosaphonecrus arcoverticus Galls
Authors: Yang Xue-Mei , Hui Yu , Zhao Lv-Quan , Zhu Dao-Hong , Zeng Yang , Yang Xiao-Hui
Published: November 2021

Insect galls are the abnormal growth of plant tissues induced by a wide variety of galling insects and characterized by high concentrations of auxins and cytokinins. It remains unclear whether the auxins and cytokinins affect the bacterial community structure of insect galls. We determined the concentrations of indoleacetic acid (IAA) as an example of auxin, trans-zeatin riboside (tZR) and isopentenyladenine (iP) as cytokinins in Lithosaphonecrus arcoverticus (Hymenoptera: Cynipidae) galls and the galled twigs of Lithocarpus glaber (Fagaceae) using liquid chromatography–tandem mass spectrometry. Moreover, for the first time, we compared the bacterial community structure of L. arcoverticus galls and galled twigs by high-throughput sequencing, and calculated the Spearman correlation and associated degree of significance between the IAA, tZR and iP concentrations and the bacterial community structure. Our results indicated the concentrations of IAA, tZR and iP were higher in L. arcoverticus galls than in galled twigs, and positively correlated with the bacterial community structure of L. arcoverticus galls. We suggest the high concentrations of IAA, tZR and iP may affect the bacterial community structure of L. arcoverticus galls.
CSI Pollen: Diversity of Honey Bee Collected Pollen Studied by Citizen Scientists
Authors: Brodschneider Robert , Kalcher-Sommersguter Elfriede , Kuchling Sabrina , Dietemann Vincent , Gray Alison , Božič Janko , Briedis Andrejs , Carreck Norman L. , Chlebo Robert , Crailsheim Karl , Coffey Mary Frances , Dahle Bjørn , González-Porto Amelia Virginia , Filipi Janja , de Graaf Dirk C. , Hatjina Fani , Ioannidis Pavlos , Ion Nicoleta , Jørgensen Asger Søgaard , Kristiansen Preben , Lecocq Antoine , Odoux Jean-François , Özkirim Asli , Peterson Magnus , Podrižnik Blaž , Rašić Slađan , Retschnig Gina , Schiesser Aygün , Tosi Simone , Vejsnæs Flemming , Williams Geoffrey , van der Steen Jozef J.M.
Published: November 2021

A diverse supply of pollen is an important factor for honey bee health, but information about the pollen diversity available to colonies at the landscape scale is largely missing. In this COLOSS study, beekeeper citizen scientists sampled and analyzed the diversity of pollen collected by honey bee colonies. As a simple measure of diversity, beekeepers determined the number of colors found in pollen samples that were collected in a coordinated and standardized way. Altogether, 750 beekeepers from 28 different regions from 24 countries participated in the two-year study and collected and analyzed almost 18,000 pollen samples. Pollen samples contained approximately six different colors in total throughout the sampling period, of which four colors were abundant. We ran generalized linear mixed models to test for possible effects of diverse factors such as collection, i.e., whether a minimum amount of pollen was collected or not, and habitat type on the number of colors found in pollen samples. To identify habitat effects on pollen diversity, beekeepers’ descriptions of the surrounding landscape and CORINE land cover classes were investigated in two different models, which both showed that both the total number and the rare number of colors in pollen samples were positively affected by ‘urban’ habitats or ‘artificial surfaces’, respectively. This citizen science study underlines the importance of the habitat for pollen diversity for bees and suggests higher diversity in urban areas.
Professional Status of Persistent Spinal Pain Syndrome Patients after Spinal Surgery (PSPS-T2): What Really Matters? A Prospective Study Introducing the Concept of “Adapted Professional Activity” Inferred from Clinical, Psychological and Social Influence
Authors: Naiditch Nicolas , Billot Maxime , Goudman Lisa , Cornet Philippe , Roulaud Manuel , Ounajim Amine , Page Philippe , Lorgeoux Bertille , Baron Sandrine , Nivole Kevin , Pries Pierre , Moufid Yassine Abdollah , Swennen Cécile , Teyssedou Simon , Vendeuvre Tanguy , Charrier Elodie , Poupin Laure , Rannou Delphine , de Montgazon Géraldine Brumauld , Descoins Pierre François , Roy-Moreau Brigitte , Grimaud Nelly , David Romain , Moens Maarten , Rigoard Philippe
Published: November 2021

Persistent Spinal Pain Syndrome Type 2 (PSPS-T2) represents a main cause of work disruption. Beyond its societal consequences, occupational inactivity is responsible for a major decrease in physical/mental health in individuals but remains poorly analyzed. We designed a study to prospectively examine Professional Status (PS) evolution and its association with key bio-psychological markers. Data from 151 consecutively included working-age PSPS-T2 patients were analyzed to determine the proportion of professional inactivity and the relationships between PS and Social Gradient of Health (SGH), Numeric Pain Rating Scale (NPRS), EuroQol 5-Dimensional 5-Level (EQ-5D-5L), Oswestry Disability Index (ODI), Hospital Anxiety and Depression Scale (HADS), and Fear-Avoidance Belief Questionnaire work subscale (FABQ-W). Despite optimized medical management, 73.5% of PSPS-T2 patients remained inactive after 1 year of follow-up/p = 0.18. Inactive patients presented a low SGH/p = 0.002, higher NPRS/p = 0.048, lower EQ-5D-5L/p < 0.001, higher ODI/p = 0.018, higher HADS-D/p = 0.019 and higher FABQ-W/p < 0.001. No significant mediation effect of FABQ-W on SGH consequences regarding PS was observed in our structural model/p = 0.057. The link between unemployment and bio-psycho-social pain dimensions appears bidirectional and justifies intense collaboration with social workers. Optimizing therapeutical sequencing towards personalized professional plans implies restoring “Adapted Physical Function” as an initial goal, and tailoring an “Adapted Professional Activity”, matching with patient expectations and capabilities, as a final objective.
Similarities in Quantitative Computed Tomography Imaging of the Lung in Severe Asthma with Persistent Airflow Limitation and Chronic Obstructive Pulmonary Disease
Authors: Obojski Andrzej , Patyk Mateusz , Zaleska-Dorobisz Urszula
Published: November 2021

Background: Severe asthma with persistent airflow limitation (SA-PAL) and chronic obstructive pulmonary disease (COPD) are characterised by irreversible airflow limitation and the remodelling of the airways. The phenotypes of the diseases overlap and may cause diagnostic and therapeutic concerns. Methods: There were 10 patients with SA-PAL, 11 patients with COPD, and 10 healthy volunteers (HV) enrolled in this study. The patients were examined with a 128-multislice scanner at full inspiration. Measurements were taken from the third to ninth bronchial generations. Results: The thickness of the bronchial wall was greater in the SA-PAL than in the COPD group for most bronchial generations (p < 0.05). The mean lung density was the lowest in the SA-PAL group (−846 HU), followed by the COPD group (−836 HU), with no statistical difference between these two groups. The low-attenuation volume percentage (LAV% < −950 HU) was significantly higher in the SA-PAL group (15.8%) and COPD group (10.4%) compared with the HV group (7%) (p = 0.03). Conclusion: Severe asthma with persistent airflow limitation and COPD become similar with time within the functional and morphological dimensions. Emphysema qualities are present in COPD and in SA-PAL patients.
Role of 18F-FDG PET/CT Radiomics Features in the Differential Diagnosis of Solitary Pulmonary Nodules: Diagnostic Accuracy and Comparison between Two Different PET/CT Scanners
Authors: Albano Domenico , Gatta Roberto , Marini Matteo , Rodella Carlo , Camoni Luca , Dondi Francesco , Giubbini Raffaele , Bertagna Francesco
Published: November 2021

The aim of this retrospective study was to investigate the ability of 18 fluorine-fluorodeoxyglucose positron emission tomography/CT (18F-FDG-PET/CT) metrics and radiomics features (RFs) in predicting the final diagnosis of solitary pulmonary nodules (SPN). We retrospectively recruited 202 patients who underwent a 18F-FDG-PET/CT before any treatment in two PET scanners. After volumetric segmentation of each lung nodule, 8 PET metrics and 42 RFs were extracted. All the features were tested for significant differences between the two PET scanners. The performances of all features in predicting the nature of SPN were analyzed by testing three classes of final logistic regression predictive models: two were built/trained through exploiting the separate data from the two scanners, and the other joined the data together. One hundred and twenty-seven patients had a final diagnosis of malignancy, while 64 were of a benign nature. Comparing the two PET scanners, we found that all metabolic features and most of RFs were significantly different, despite the cross correlation being quite similar. For scanner 1, a combination between grey level co-occurrence matrix (GLCM), histogram, and grey-level zone length matrix (GLZLM) related features presented the best performances to predict the diagnosis; for scanner 2, it was GLCM and histogram-related features and metabolic tumour volume (MTV); and for scanner 1 + 2, it was histogram features, standardized uptake value (SUV) metrics, and MTV. RFs had a significant role in predicting the diagnosis of SPN, but their accuracies were directly related to the scanner.
Improvements in the Effectiveness of Early Detection in Colorectal Cancer with Open-Label Randomised Study
Authors: Álvarez-Delgado A. , García M. L. Pérez , García-González J. M. , de Sena H. Iglesias , Chamorro A. J. , Gómez M. F. Lorenzo , Marcos M. , Mirón-Canelo J. A.
Published: November 2021

Introduction: The general objective of this research is to improve the quality of colorectal cancer screening (CRC) by assessing, as an indicator of effectiveness, the ability of colonoscopy to detect more advanced adenomas in the exposed group than in the control group. Material and Methods: The present work is designed as an open-label randomized study on cancer screening, using two groups based on their exposure to the protocol: an exposed to intervention group (EIG, 167), and a control group (CG, 167), without the intervention of the protocol and by 1:1 matching. Results: In 167 patients in the GEI, 449 polyps are visualized and 274 are adenomas (80.58%), of which 100 (36.49%) are advanced adenomas. In the CG (n = 174), there are 321 polyps and 152 adenomas (82.60%). The variables significantly associated by logistic regression to the detection of adenomas are the male sex with an OR of 2.52. The variable time to withdrawal, ≥9 min, is significant at 99% confidence (p = 0.002/OR 34.67) and the fractional dose is significant at 99% (p = 0.009, OR 7.81). Conclusion: Based on the observations made, our study suggests that the intervention in collaboration between primary care and hospital care is effective from a preventive point of view and achieves the objective of effectiveness and quality of the PCCR.
Cardiopulmonary Exercise Test Parameters in Athletic Population: A Review
Authors: Mazaheri Reza , Schmied Christian , Niederseer David , Guazzi Marco
Published: November 2021

Although still underutilized, cardiopulmonary exercise testing (CPET) allows the most accurate and reproducible measurement of cardiorespiratory fitness and performance in athletes. It provides functional physiologic indices which are key variables in the assessment of athletes in different disciplines. CPET is valuable in clinical and physiological investigation of individuals with loss of performance or minor symptoms that might indicate subclinical cardiovascular, pulmonary or musculoskeletal disorders. Highly trained athletes have improved CPET values, so having just normal values may hide a medical disorder. In the present review, applications of CPET in athletes with special attention on physiological parameters such as VO2max, ventilatory thresholds, oxygen pulse, and ventilatory equivalent for oxygen and exercise economy in the assessment of athletic performance are discussed. The role of CPET in the evaluation of possible latent diseases and overtraining syndrome, as well as CPET-based exercise prescription, are outlined.
Gut Microbiome in Chronic Coronary Syndrome Patients
Authors: Sawicka-Smiarowska Emilia , Bondarczuk Kinga , Bauer Witold , Niemira Magdalena , Szalkowska Anna , Raczkowska Justyna , Kwasniewski Miroslaw , Tarasiuk Ewa , Dubatowka Marlena , Lapinska Magda , Szpakowicz Malgorzata , Stachurska Zofia , Szpakowicz Anna , Sowa Pawel , Raczkowski Andrzej , Kondraciuk Marcin , Gierej Magdalena , Motyka Joanna , Jamiolkowski Jacek , Bondarczuk Mateusz , Chlabicz Malgorzata , Bucko Jolanta , Kozuch Marcin , Dobrzycki Slawomir , Bychowski Jerzy , Musial Wlodzimierz Jerzy , Godlewski Adrian , Ciborowski Michal , Gyenesei Attila , Kretowski Adam , Kaminski Karol Adam
Published: November 2021

Despite knowledge of classical coronary artery disease (CAD) risk factors, the morbidity and mortality associated with this disease remain high. Therefore, new factors that may affect the development of CAD, such as the gut microbiome, are extensively investigated. This study aimed to evaluate gut microbiome composition in CAD patients in relation to the control group. We examined 169 CAD patients and 166 people in the control group, without CAD, matched in terms of age and sex to the study group. Both populations underwent a detailed health assessment. The microbiome analysis was based on the V3–V4 region of the 16S rRNA gene (NGS method). Among 4074 identified taxonomic units in the whole population, 1070 differed between study groups. The most common bacterial types were Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. Furthermore, a higher Firmicutes/Bacteroidetes ratio in the CAD group compared with the control was demonstrated. Firmicutes/Bacteroidetes ratio, independent of age, sex, CAD status, LDL cholesterol concentration, and statins treatment, was related to altered phosphatidylcholine concentrations obtained in targeted metabolomics. Altered alpha-biodiversity (Kruskal–Wallis test, p = 0.001) and beta-biodiversity (Bray–Curtis metric, p < 0.001) in the CAD group were observed. Moreover, a predicted functional analysis revealed some taxonomic units, metabolic pathways, and proteins that might be characteristic of the CAD patients’ microbiome, such as increased expressions of 6-phospho-β-glucosidase and protein-N(pi)-phosphohistidine-sugar phosphotransferase and decreased expressions of DNA topoisomerase, oxaloacetate decarboxylase, and 6-beta-glucosidase. In summary, CAD is associated with altered gut microbiome composition and function.
Karyotype Abnormalities in the X Chromosome Predict Response to the Growth Hormone Therapy in Turner Syndrome
Authors: Kasprzyk Jakub , Włodarczyk Marcin , Sobolewska-Włodarczyk Aleksandra , Wieczorek-Szukała Katarzyna , Stawerska Renata , Hilczer Maciej , Lewiński Andrzej
Published: November 2021

Short stature is characteristic for Turner syndrome (TS) patients, and particular karyotype abnormalities of the X chromosome may be associated with different responsiveness to recombinant human GH (rhGH) therapy. The aim of the study was to analyze the effect of different types of TS karyotype abnormalities on the response to rhGH therapy. A total of 57 prepubertal patients with TS treated with rhGH with a 3 year follow-up were enrolled in the study and categorized according to their karyotype as X monosomy (n = 35), isochromosome (n = 11), marker chromosome (n = 5), or X-mosaicism (n = 6). Height and height velocity (HV) were evaluated annually. In the first year, all groups responded well to the therapy. In the second year, HV deteriorated significantly in X-monosomy and isochromosome in comparison to the remaining two groups (p = 0.0007). After 3 years of therapy, all patients improved the score in comparison to their target height, but better outcomes were achieved in patients with marker chromosome and X-mosaicism (p = 0.0072). X-monosomy or isochromosome determined a poorer response during the second and third year of rhGH therapy. The results of the study indicate that the effects of rhGH therapy in patients with TS may depend on the type of TS karyotype causing the syndrome.
The Emerging Role of Gut Microbiota in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Current Evidence and Potential Therapeutic Applications
Authors: Varesi Angelica , Deumer Undine-Sophie , Ananth Sanjana , Ricevuti Giovanni
Published: November 2021

The well-known symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) are chronic pain, cognitive dysfunction, post-exertional malaise and severe fatigue. Another class of symptoms commonly reported in the context of ME/CFS are gastrointestinal (GI) problems. These may occur due to comorbidities such as Crohn’s disease or irritable bowel syndrome (IBS), or as a symptom of ME/CFS itself due to an interruption of the complex interplay between the gut microbiota (GM) and the host GI tract. An altered composition and overall decrease in diversity of GM has been observed in ME/CFS cases compared to controls. In this review, we reflect on genetics, infections, and other influences that may factor into the alterations seen in the GM of ME/CFS individuals, we discuss consequences arising from these changes, and we contemplate the therapeutic potential of treating the gut to alleviate ME/CFS symptoms holistically.
Hindbrain Administration of Oxytocin Reduces Food Intake, Weight Gain and Activates Catecholamine Neurons in the Hindbrain Nucleus of the Solitary Tract in Rats
Authors: Anekonda Vishwanath T. , Thompson Benjamin W. , Ho Jacqueline M. , Roberts Zachary S. , Edwards Melise M. , Nguyen Ha K. , Dodson Andrew D. , Wolden-Hanson Tami , Chukri Daniel W. , Herbertson Adam J. , Graham James L. , Havel Peter J. , Wietecha Tomasz A. , O’Brien Kevin D. , Blevins James E.
Published: November 2021

Existing studies show that CNS oxytocin (OT) signaling is important in the control of energy balance, but it is unclear which neurons may contribute to these effects. Our goals were to examine (1) the dose-response effects of acute OT administration into the third (3V; forebrain) and fourth (4V; hindbrain) ventricles to assess sensitivity to OT in forebrain and hindbrain sites, (2) the extent to which chronic 4V administration of OT reduces weight gain associated with the progression of diet-induced obesity, and (3) whether nucleus tractus solitarius (NTS) catecholamine neurons are downstream targets of 4V OT. Initially, we examined the dose-response effects of 3V and 4V OT (0.04, 0.2, 1, or 5 μg). 3V and 4V OT (5 μg) suppressed 0.5-h food intake by 71.7 ± 6.0% and 60 ± 12.9%, respectively. 4V OT (0.04, 0.2, 1 μg) reduced food intake by 30.9 ± 12.9, 42.1 ± 9.4, and 56.4 ± 9.0%, respectively, whereas 3V administration of OT (1 μg) was only effective at reducing 0.5-h food intake by 38.3 ± 10.9%. We subsequently found that chronic 4V OT infusion, as with chronic 3V infusion, reduced body weight gain (specific to fat mass) and tended to reduce plasma leptin in high-fat diet (HFD)-fed rats, in part, through a reduction in energy intake. Lastly, we determined that 4V OT increased the number of hindbrain caudal NTS Fos (+) neurons (156 ± 25) relative to vehicle (12 ± 3). The 4V OT also induced Fos in tyrosine hydroxylase (TH; marker of catecholamine neurons) (+) neurons (25 ± 7%) relative to vehicle (0.8 ± 0.3%). Collectively, these findings support the hypothesis that OT within the hindbrain is effective at reducing food intake, weight gain, and adiposity and that NTS catecholamine neurons in addition to non-catecholaminergic neurons are downstream targets of CNS OT.
Results after Repair of Functional Tricuspid Regurgitation with a Three-Dimensional Annuloplasty Ring
Authors: Dzilic Elda , Guenther Thomas , Bouziani Amel , Voss Bernhard , Voss Stephanie , Vitanova Keti , Krane Markus , Lange Ruediger
Published: November 2021

Background: Tricuspid valve (TV) repair is the recommended treatment for severe functional tricuspid regurgitation (fTR) in patients undergoing left-sided surgery. For this purpose, a wide range of annuloplasty devices differing in form and flexibility are available. This study reports the results using a three-dimensional annuloplasty ring (Medtronic, Contour 3D Ring) for TV repair and analysis of risk factors. Methods: A cohort of 468 patients who underwent TV repair (TVr) with a concomitant cardiac procedure from December 2010 to January 2017 was retrospectively analyzed. Results: At follow-up, 96.1% of patients had no/trivial or mild TR. The 30-day mortality was 4.7%; it significantly differed between electively performed operations (2.7%) and urgent/emergent operations (11.7%). Risk factors for recurrent moderate and severe TR were LVEF < 50%, TAPSE < 16 mm, and moderate mitral valve (MV) regurgitation at follow-up. Preoperatively reduced renal function lead to a higher 30-day and overall mortality. Reoperation of the TV was required in six patients (1.6%). Risk factors for TV related reoperations were preoperative TV annulus over 50 mm and an implanted permanent pacemaker. Conclusions: TVr with the Contour 3D annuloplasty ring shows low TR recurrence and reoperation rates. Risk-factor analysis for the recurrence of TR revealed the importance of left- and right-ventricular function.
The Effects of Preterm Birth on Musculoskeletal Health-Related Disorders
Authors: Schachinger Florian , Farr Sebastian
Published: November 2021

Preterm birth is associated with various diseases and conditions which demand multidisciplinary medical care. Approximately 10% of all neonates are born prematurely with an increasing survival rate in almost all Western countries. This ongoing, yet desirable trend is creating new challenges for sufficient medical treatment regimens, which should be upheld throughout the patients’ lives. Orthopedic surgeons are focused on musculoskeletal disorders and the improvement of patients’ ability to cope with the challenges of everyday life. The most common conditions associated with preterm birth are cerebral palsy and a dysregulation of the calcium/phosphorus metabolism, which may lead to fractures. These diseases may vary greatly in their organic manifestation and clinical presentation. This demands multidisciplinary cooperation and parental support. Clinical management is aimed on the early enhancement of a patient’s physical, as well as neurological condition, and to prevent the development of secondary musculoskeletal disorders. In this article, we give an overview of the current literature on the most common musculoskeletal disorders associated with preterm birth and critically discuss state of the art diagnostic standards and treatment algorithms.
An Observational Study on Patients with Acute Limb Ischemia and SARS-CoV-2 Infection: Early and Late Results in Limb Salvage Rate
Authors: Barac Sorin , Onofrei Roxana Ramona , Neagoe Petru Vlad , Popescu Alexandra Ioana , Pantea Stelian , Rață Andreea Luciana
Published: November 2021

An observational study on 22 patients presenting with acute limb ischemia and SARS-CoV-2 infection, and without any other embolic risk factors, was performed. All patients were classified according to Rutherford classification for acute limb ischemia. The primary goal of this study was to assess the risk of amputation in these patients after revascularization procedures. The secondary goal was to find the correlation between acute limb ischemia (ALI) severity, patient comorbidities, risk of death, and the association of SARS-CoV-2 infection. The patients were treated by open surgery (18 patients—81.81%) or by the means of endovascular techniques (four patients—18.18%). The amputation-free survival rate was 81.81% in hospital and 86.36% at 1-month follow-up. In this study, the presence of SARS-CoV-2 infection did not influence the amputation-free survival rate: it was only the risk factor for the arterial thrombosis and the trigger for the acute ischemic event. The application of the standard treatment—open surgery or endovascular revascularization—in patients with acute limb ischemia and SARS-CoV-2 infection represents the key to success for lower limb salvage.