bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality of Informed Consent in Mammography Screening—The Polish Experience
Authors: Zagaja Anna , Bogusz Renata , Sak Jarosław , Wiechetek Michał , Pawlikowski Jakub
Published: May 2022

Breast cancer is one of the leading forms of cancers in women worldwide. In Poland, it accounts for approx. 20% of all cancers diagnosed, with approximately 11,000 new cases and 5000 deaths from this disease annually. To prevent unfavourable statistics, Poland introduced free breast cancer screening programmes, available to women aged 50–69. Over a million women take advantage of this programme each year. The aim of the research was to assess the quality of consent women give prior to mammography screening and address the question of whether this quality is sufficient to make an informed choice. The study was conducted on a representative group of 600 Polish women over 50 years old (475 of them had undergone mammography screening), who agreed to take part in the study. Using the computer-assisted interview technology (CATI) method, all women were asked about their perception of breast cancer and screening and those who had undergone mammography were quizzed about the consent process. They will form the focus of this research. The validated tool contained items on both the benefits and risks of screening. The results indicate that the quality of informed consent was insufficient. A discrepancy was observed in the awareness between the benefits and risks of mammography screening. The main motivations to undergo screening were: prophylactic purposes and the free-of-charge nature of this health service. Population-based screening programmes for breast cancer should be reconsidered in terms of information policy, and the quality of informed consent should be increased.
Impact of Backpacks on Ergonomics: Biomechanical and Physiological Effects: A Narrative Review
Authors: Genitrini Matteo , Dotti Francesca , Bianca Eleonora , Ferri Ada
Published: May 2022

(1) Background: the effects of load carriage packs on human gait biomechanics, physiology and metabolism depend on the weight carried, the design of the pack and its interaction with the user. (2) Methods: An extensive search in the PubMed database was performed to find all the relevant articles using the following keywords: backpack, rucksack, backpack ergonomy and sports backpack; 60 articles were included. (3) Results and significance: Double pack (DP) and T-pack (TP) designs are recommended solutions for school children, compared with backpacks (BP). For soldiers and hikers, a backpack remains the best compromise. A hip belt is recommended for BPs as well as for the back of DPs. Shorter and stiffer shoulder straps combined with a higher and tighter load placement on the back provide the best combination in terms of balance, muscle activation and energy expenditure. It is, therefore, possible to determine guidelines for designing the optimal load carriage system, depending on the application. (4) Conclusions: based on the available evidence, DP and TP are advantageous in terms of posture. DP is better than conventional BPs in terms of balance and muscle activation, but has the disadvantage of limited visibility, thermal sensation and obstructed ventilation. In general, it is desirable not to exceed 40% of body mass (BM).
Maternal Prenatal Inflammation Increases Brain Damage Susceptibility of Lipopolysaccharide in Adult Rat Offspring via COX-2/PGD-2/DPs Pathway Activation
Authors: Zhang Jiahua , Yao Peishuang , Han Wenli , Luo Ying , Li Yuke , Yang Yang , Xia Hui , Chen Zhihao , Chen Qi , Wang Hong , Yang Lu , Li Huan , Hu Congli , Huang Haifeng , Peng Zhe , Tan Xiaodan , Li Miaomiao , Yang Junqing
Published: May 2022

A growing body of research suggests that inflammatory insult contributes to the etiology of central nervous system diseases, such as depression, Alzheimer’s disease, and so forth. However, the effect of prenatal systemic inflammation exposure on offspring brain development and cerebral susceptibility to inflammatory insult remains unknown. In this study, we utilized the prenatal inflammatory insult model in vivo and the neuronal damage model in vitro. The results obtained show that prenatal maternal inflammation exacerbates LPS-induced memory impairment, neuronal necrosis, brain inflammatory response, and significantly increases protein expressions of COX-2, DP2, APP, and Aβ, while obviously decreasing that of DP1 and the exploratory behaviors of offspring rats. Meloxicam significantly inhibited memory impairment, neuronal necrosis, oxidative stress, and inflammatory response, and down-regulated the expressions of APP, Aβ, COX-2, and DP2, whereas significantly increased exploring behaviors and the expression of DP1 in vivo. Collectively, these findings suggested that maternal inflammation could cause offspring suffering from inflammatory and behavioral disorders and increase the susceptibility of offspring to cerebral pathological factors, accompanied by COX-2/PGD-2/DPs pathway activation, which could be ameliorated significantly by COX-2 inhibitor meloxicam treatment.
Diagnostic, Prognostic, and Mechanistic Biomarkers of Diabetes Mellitus-Associated Cognitive Decline
Authors: Ehtewish Hanan , Arredouani Abdelilah , El-Agnaf Omar
Published: May 2022

Cognitive dysfunctions such as mild cognitive impairment (MCI), Alzheimer’s disease (AD), and other forms of dementia are recognized as common comorbidities of type 2 diabetes mellitus (T2DM). Currently, there are no disease-modifying therapies or definitive clinical diagnostic and prognostic tools for dementia, and the mechanisms underpinning the link between T2DM and cognitive dysfunction remain equivocal. Some of the suggested pathophysiological mechanisms underlying cognitive decline in diabetes patients include hyperglycemia, insulin resistance and altered insulin signaling, neuroinflammation, cerebral microvascular injury, and buildup of cerebral amyloid and tau proteins. Given the skyrocketing global rates of diabetes and neurodegenerative disorders, there is an urgent need to discover novel biomarkers relevant to the co-morbidity of both conditions to guide future diagnostic approaches. This review aims to provide a comprehensive background of the potential risk factors, the identified biomarkers of diabetes-related cognitive decrements, and the underlying processes of diabetes-associated cognitive dysfunction. Aging, poor glycemic control, hypoglycemia and hyperglycemic episodes, depression, and vascular complications are associated with increased risk of dementia. Conclusive research studies that have attempted to find specific biomarkers are limited. However, the most frequent considerations in such investigations are related to C reactive protein, tau protein, brain-derived neurotrophic factor, advanced glycation end products, glycosylated hemoglobin, and adipokines.
Renal Injuries after Cardiac Arrest: A Morphological Ultrastructural Study
Authors: Tsivilika Maria , Kavvadas Dimitrios , Karachrysafi Sofia , Kotzampassi Katerina , Grosomanidis Vasilis , Doumaki Eleni , Meditskou Soultana , Sioga Antonia , Papamitsou Theodora
Published: May 2022

Background: This study aims to investigate the probable lesions and injuries induced in the renal tissue after a cardiac arrest. The renal ischemia–reperfusion model in cardiac arrest describes the effects of ischemia in the kidneys, alongside a whole-body ischemia–reperfusion injury. This protocol excludes ischemic conditions caused by surgical vascular manipulation, venous injury or venous congestion. Methods: For the experimental study, 24 swine were subjected to cardiac arrest. Seven minutes later, the cardiopulmonary resuscitation technique was performed for 5 min. Afterwards, advanced life support was provided. The resuscitated swine consisted one group and the non-resuscitated the other. Tissue samples were obtained from both groups for light and electron microscopy evaluation. Results: Tissue lesions were observed in the tubules, parallel to destruction of the microvilli, reduction in the basal membrane invaginations, enlarged mitochondria, cellular vacuolization, cellular apoptosis and disorganization. In addition, fusion of the podocytes, destruction of the Bowman’s capsule parietal epithelium and abnormal peripheral urinary space was observed. The damage appeared more extensive in the non-resuscitated swine group. Conclusions: Acute kidney injury is not the leading cause of death after cardiac arrest. However, evidence suggests that the kidney damage after a cardiac arrest should be highly considered in the prognosis of the patients’ health outcome.
The Disordered EZH2 Loop: Atomic Level Characterization by 1HN- and 1Hα-Detected NMR Approaches, Interaction with the Long Noncoding HOTAIR RNA
Authors: Szabó Csenge Lilla , Szabó Beáta , Sebák Fanni , Bermel Wolfgang , Tantos Agnes , Bodor Andrea
Published: May 2022

The 96-residue-long loop of EZH2 is proposed to play a role in the interaction with long non-coding RNAs (lncRNAs) and to contribute to EZH2 recruitment to the chromatin. However, molecular details of RNA recognition have not been described so far. Cellular studies have suggested that phosphorylation of the Thr345 residue localized in this loop influences RNA binding; however, no mechanistic explanation has been offered. To address these issues, a systematic NMR study was performed. As the 1HN-detected NMR approach presents many challenges under physiological conditions, our earlier developed, as well as improved, 1Hα-detected experiments were used. As a result of the successful resonance assignment, the obtained chemical shift values indicate the highly disordered nature of the EZH2 loop, with some nascent helical tendency in the Ser407–Ser412 region. Further investigations conducted on the phosphomimetic mutant EZH2T345D showed that the mutation has only a local effect, and that the loop remains disordered. On the other hand, the mutation influences the cis/trans Pro346 equilibrium. Interactions of both the wild-type and the phosphomimetic mutant with the lncRNA HOTAIR140 (1–140 nt) highlight that the Thr367–Ser375 region is affected. This segment does not resemble any of the previously reported RNA-binding motifs, therefore the identified binding region is unique. As no structural changes occur in the EZH2 loop upon RNA binding, we can consider the protein–RNA interaction as a “fuzzy” complex.
Nanosecond Pulsed Electric Field (nsPEF): Opening the Biotechnological Pandora’s Box
Authors: Ruiz-Fernández Alvaro R. , Campos Leonardo , Gutierrez-Maldonado Sebastian E. , Núñez Gonzalo , Villanelo Felipe , Perez-Acle Tomas
Published: May 2022

Nanosecond Pulsed Electric Field (nsPEF) is an electrostimulation technique first developed in 1995; nsPEF requires the delivery of a series of pulses of high electric fields in the order of nanoseconds into biological tissues or cells. They primary effects in cells is the formation of membrane nanopores and the activation of ionic channels, leading to an incremental increase in cytoplasmic Ca2+ concentration, which triggers a signaling cascade producing a variety of effects: from apoptosis up to cell differentiation and proliferation. Further, nsPEF may affect organelles, making nsPEF a unique tool to manipulate and study cells. This technique is exploited in a broad spectrum of applications, such as: sterilization in the food industry, seed germination, anti-parasitic effects, wound healing, increased immune response, activation of neurons and myocites, cell proliferation, cellular phenotype manipulation, modulation of gene expression, and as a novel cancer treatment. This review thoroughly explores both nsPEF’s history and applications, with emphasis on the cellular effects from a biophysics perspective, highlighting the role of ionic channels as a mechanistic driver of the increase in cytoplasmic Ca2+ concentration.
Prime Editing Permits the Introduction of Specific Mutations in the Gene Responsible for Duchenne Muscular Dystrophy
Authors: Happi Mbakam Cédric , Rousseau Joël , Tremblay Guillaume , Yameogo Pouiré , Tremblay Jacques P.
Published: May 2022

The Prime editing technique derived from the CRISPR/Cas9 discovery permits the modification of selected nucleotides in a specific gene. We used it to insert specific point mutations in exons 9, 20, 35, 43, 55 and 61 of the Duchenne Muscular Dystrophy (DMD) gene coding for the dystrophin protein, which is absent in DMD patients. Up to 11% and 21% desired mutations of the DMD gene in HEK293T cells were obtained with the PRIME Editor 2 (PE2) and PE3, respectively. Three repeated treatments increased the percentage of specific mutations with PE2 to 16%. An additional mutation in the protospacer adjacent motif (PAM) sequence improved the PE3 result to 38% after a single treatment. We also carried out the correction of c.428 G>A point mutation in exon 6 of the DMD gene in a patient myoblast. Myoblast electroporation showed up to 8% and 28% modifications, respectively, for one and three repeated treatments using the PE3 system. The myoblast correction led to dystrophin expression in myotubes detected by Western blot. Thus, prime editing can be used for the correction of point mutations in the DMD gene.
Changes in the Transcriptome Caused by Mutations in the Ribosomal Protein uS10 Associated with a Predisposition to Colorectal Cancer
Authors: Tian Yueming , Babaylova Elena S. , Gopanenko Alexander V. , Tupikin Alexey E. , Kabilov Marsel R. , Malygin Alexey A. , Karpova Galina G.
Published: May 2022

A number of mutations in the RPS20 gene encoding the ribosomal protein uS10 have been found to be associated with a predisposition to hereditary non-polyposis colorectal carcinoma (CRC). We transfected HEK293T cells with constructs carrying the uS10 minigene with mutations identical to those mentioned above and examined the effects of the produced proteins on the cellular transcriptome. We showed that uS10 with mutations p.V50SfsX23 or p.L61EfsX11 cannot be incorporated into 40S ribosomal subunits, while the protein with the missense mutation p.V54L functionally replaces the respective endogenous protein in the 40S subunit assembly and the translation process. The comparison of RNA-seq data obtained from cells producing aberrant forms of uS10 with data for those producing the wild-type protein revealed overlapping sets of upregulated and downregulated differently expressed genes (DEGs) related to several pathways. Among the limited number of upregulated DEGs, there were genes directly associated with the progression of CRC, e.g., PPM1D and PIGN. Our findings indicate that the accumulation of the mutant forms of uS10 triggers a cascade of cellular events, similar to that which is triggered when the cell responds to a large number of erroneous proteins, suggesting that this may increase the risk of cancer.
Indoleamine 2,3 Dioxygenase 1—The Potential Link between the Innate Immunity and the Ischemia-Reperfusion-Induced Acute Kidney Injury?
Authors: Krupa Anna , Krupa Mikolaj M. , Pawlak Krystyna
Published: May 2022

Ischemia-reperfusion injury (IRI) is of the most common causes of acute kidney injury (AKI); nevertheless, the mechanisms responsible for both early kidney injury and the reparative phase are not fully recognised. The inflammatory response following ischemia is characterised by the crosstalk between cells belonging to the innate immune system—dendritic cells (DCs), macrophages, neutrophils, natural killer (NK) cells, and renal tubular epithelial cells (RTECs). A tough inflammatory response can damage the renal tissue; it may also have a protective effect leading to the repair after IRI. Indoleamine 2,3 dioxygenase 1 (IDO1), the principal enzyme of the kynurenine pathway (KP), has a broad spectrum of immunological activity from stimulation to immunosuppressive activity in inflamed areas. IDO1 expression occurs in cells of the innate immunity and RTECs during IRI, resulting in local tryptophan (TRP) depletion and generation of kynurenines, and both of these mechanisms contribute to the immunosuppressive effect. Nonetheless, it is unknown if the above mechanism can play a harmful or preventive role in IRI-induced AKI. Despite the scarcity of literature in this field, the current review attempts to present a possible role of IDO1 activation in the regulation of the innate immune system in IRI-induced AKI.
Photo-Crosslinked Hyaluronic Acid/Carboxymethyl Cellulose Composite Hydrogel as a Dural Substitute to Prevent Post-Surgical Adhesion
Authors: Huang Yin-Cheng , Liu Zhuo-Hao , Kuo Chang-Yi , Chen Jyh-Ping
Published: May 2022

A dural substitute is frequently used to repair dura mater during neurosurgical procedures. Although autologous or commercially available dural substitutes matched most of the requirements; difficulties during dural repair, including insufficient space for suturing, insufficient mechanical strength, easy tear and cerebrospinal fluid leakage, represent major challenges. To meet this need, a photo-crosslinked hydrogel was developed as a dural substitute/anti-adhesion barrier in this study, which can show sol-to-gel phase transition in situ upon short-time exposure to visible light. For this purpose, hyaluronic acid (HA) and carboxymethyl cellulose (CMC), materials used in abdominal surgery for anti-adhesion purposes, were reacted separately with glycidyl methacrylate to form hyaluronic acid methacrylate (HAMA) and carboxymethyl cellulose methacrylate (CMCMA). The HA/CMC (HC) hydrogels with different HA compositions could be prepared by photo-crosslinking HAMA and CMCMA with a 400 nm light source using lithium phenyl-2,4,6-trimethylbenzoylphosphinate as a photo-initiator. From studies of physico-chemical and biological properties of HC composite hydrogels, they are bio-compatible, bio-degradable and mechanically robust, to be suitable as a dural substitute. By drastically reducing attachment and penetration of adhesion-forming fibroblasts in vitro, the HC hydrogel can also act as an anti-adhesion barrier to prevent adhesion formation after dural repair. From in vivo study in rabbits, the HC hydrogel can repair dural defects as well as protect the dura from post-operative adhesion, endorsing the possible application of this hydrogel as a novel dural substitute.
Evaluation of Physiological and Biochemical Parameters and Some Bioindicators of Barium Tolerance in Limbarda crithmoides and Helianthus annuus
Authors: Dridi Nesrine , Bouslimi Houda , Duarte Bernardo , Caçador Isabel , Sleimi Noomene
Published: May 2022

Soils and water resources of our ecosystems may contain Barium (Ba), a toxic metal naturally existent in the Earth’s crust and also can be derived from recycled wastes produced of several anthropogenic activities. As a result of this fact, the accumulation of Ba in agriculture soils would increase to reach the crops and eventually end up in the human food chain. The purpose of this work was to study tolerance and accumulation abilities in Limbarda crithmoides and Helianthus annuus treated with increasing concentrations of barium (from 0 to 500 µM) for 45 days. In order to evaluate the response of these species to Ba stress, the biomass production, the water status, and the accumulation of the secondary metabolites, macronutrients, total inorganic nitrogen (TIN), and Ba in shoots and roots, as well as chlorophyll levels, and metal tolerance index of the entire plant were assessed. Results showed an increase in plant biomass production and tolerance index in the two species with increasing Ba concentration. A significant increase in polyphenols and flavonoids levels was also shown with no negative effect on the macronutrients and TIN; however, the latter were found reduced in roots of L. crithmoides. Chlorophylls also were not affected. An average of 3000 µg·g−1 DW of Ba was accumulated in each organ of L. crithmoides while H. annuus accumulated up to 1350 µg·g−1 DW in the shoots. Our findings proved that L. crithmoides and H. annuus were susceptible to tolerate Ba-induced stress with high levels of Ba accumulation in the aboveground parts as well as in the roots during the 45 days of the experiments.
Elemental Relationships in the Wood of Four Siberian Conifers: Whether Elements Are an Occasional Mixture
Authors: Gavrikov Vladimir , Fertikov Alexey , Sharafutdinov Ruslan , Vaganov Eugeniy
Published: May 2022

In the abundant literature on plant chemistry, little attention is paid to correlations among chemical elements in tissues. The goal of the research is to establish consistent correlations among elements in the xylem of four widespread Siberian conifers. X-ray fluorescent analysis has been applied to find out the elements contained in the xylem. The method allowed finding the mean count rates of Al, P, S, K, Ca, Ti, Mn, Fe, Cu, Zn, and Sr in trunks of trees. Moreover, the xylem samples were chemically treated twice, first in alcohol and then in HCl. It was found that species factor exerts a significant influence on the elemental content of a few elements, but not on all of them. The chemical treatment decreases the impact of the species factor. The treatment increases the number of significant correlations and strength of them. In some cases (especially with Al), the correlations may change the sign of the relationship. The consistent correlations may help arrange more profound chemical research revealing the forms in which the elements exist in xylem.
Vitamin D for Clinical Diseases in Women: An Indispensable Factor in Medicine and Dentistry
Authors: Calafiore Dario , Fortunato Leonzio , Migliario Mario
Published: May 2022

Vitamin D deficiency is a global health problem occurring in all age groups and in countries with both high and low levels of sunlight, and improving its role in nutrition could be considered as a public health priority [...]
Special Issue: “Exercise Intervention during Pregnancy and Maternal Health”
Authors: Barakat Rubén , Refoyo Ignacio
Published: May 2022

For nine months, the process of pregnancy modifies all the organs and systems of the woman’s body in order to achieve adequate fetal growth and development [...]
Exploring Retinal Blood Vessel Diameters as Biomarkers in Multiple Sclerosis
Authors: Drobnjak Nes Dragana , Berg-Hansen Pål , de Rodez Benavent Sigrid A. , Høgestøl Einar A. , Beyer Mona K. , Rinker Daniel A. , Veiby Nina , Karabeg Mia , Petrovski Beáta Éva , Celius Elisabeth G. , Harbo Hanne F. , Petrovski Goran
Published: May 2022

We aimed to determine whether retinal vessel diameters and retinal oxygen saturation in newly diagnosed patients with multiple sclerosis (pwMS) are different from those of a healthy population. Retinal blood vessel diameters were measured using imaging with a spectrophotometric non-invasive retinal oximeter. Twenty-three newly diagnosed untreated relapsing-remitting MS (RRMS) patients (mean age: 32.2 ± 7.5 years, age range = 18–50 years, 56.5% female) were measured and compared to 23 age- and sex-matched healthy controls (HCs) (mean age: 34.8 ± 8.1 years). Patients with Optic Neuritis were excluded. Retinal venular diameter (143.8 µm versus 157.8 µm: mean; p = 0.0013) and retinal arteriolar diameter (112.6 µm versus 120.6 µm: mean; p = 0.0089) were smaller in pwMS when compared with HCs, respectively. There was no significant difference in the oxygen saturation in retinal venules and arterioles in pwMS (mean: 60.0% and 93.7%; p = 0.5980) compared to HCs (mean: 59.3% and 91.5%; p = 0.8934), respectively. There was a significant difference in the median low contrast visual acuity (2.5% contrast) between the pwMS and the HC groups (p = 0.0143) Retinal arteriolar and venular diameter may have potential as objective biomarkers for MS.
Sex-Related Differences in Left Atrial Low-Voltage Areas According to CHA2DS2-VA Scores among Patients with Atrial Fibrillation
Authors: Kim Do Young , Kim Yun Gi , Choi Ha Young , Choi Yun Young , Boo Ki Yung , Lee Kwang-No , Roh Seung-Young , Shim Jaemin , Choi Jong-Il , Kim Young-Hoon
Published: May 2022

(1) Background: We hypothesized that female sex would have a differential impact on left atrial (LA) low-voltage areas (LVAs) according to CHA2DS2-VA scores. (2) Methods: This study included 553 patients who underwent radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF). LVAs were defined as regions with bipolar peak-to-peak voltages of <0.5 mV. The proportion of LVAs was calculated by dividing the total LVA by the LA surface area. (3) Results: There was no sex-related difference in LA LVAs among patients with a CHA2DS2-VA scores ≤ 2. The proportion of LVAs was significantly higher in females among patients with CHA2DS2-VA scores of 3 or 4 (10.1 (4.7–15.1)% vs. 15.8 (9.2–32.1)%; p = 0.027). Female sex was significantly associated with extensive LVAs (LVA proportion ≥ 30%). Females had odd ratios of 27.82 (95% confidence interval (CI) 3.33–756.8, p = 0.01), and 1.53 (95% CI 0.81–2.83, p = 0.184) for extensive LAVs in patients with CHA2DS2-VA scores ≥ 3 and CHA2DS2-VA scores < 3, respectively. In the multiple regression model, female patients with a CHA2DS2-VA ≥3 were significantly associated with a higher proportion of LVAs (β = 8.52, p = 0.039). (4) Conclusions: Female sex was significantly associated with extensive LVAs, particularly when their CHA2DS2-VA scores were ≥3. This result suggests that female sex has a differential effect on the extent of LVAs based on the presence of additional risk factors.
Polysomnographic Evaluation of Sleep Bruxism Intensity and Sleep Architecture in Nonapneic Hypertensives: A Prospective, Observational Study
Authors: Kanclerska Justyna , Wieckiewicz Mieszko , Poreba Rafal , Szymanska-Chabowska Anna , Gac Pawel , Wojakowska Anna , Frosztega Weronika , Michalek-Zrabkowska Monika , Mazur Grzegorz , Martynowicz Helena
Published: May 2022

Sleep bruxism (SB) is a repetitive jaw muscle activity characterized by clenching or grinding of the teeth, which is classified under sleep-related movement disorders in the International Classification of Sleep Disorders—Third Edition. Because the potential common pathomechanism of SB and arterial hypertension is the activation of the sympathetic system as well as an increase in inflammatory factors, we aimed to examine the intensity of SB and the sleep architecture among patients with arterial hypertension. The study included a total of 91 Caucasian adult patients, among whom 31 had arterial hypertension diagnosed according to the current European Society of Cardiology/European Society of Hypertension (ESC/EHS) hypertension guidelines. The control group consisted of 61 normotensive patients. Patients with obstructive sleep apnea were excluded. A single full-night polysomnographic examination was conducted in the Sleep Laboratory, and then the results were analyzed based on the guidelines of the American Academy of Sleep Medicine. Bruxism episode index (BEI) was higher in the hypertensive group compared to normotensives. The groups also showed statistically significant differences in polysomnographic sleep indexes. Similar to BEI, arousal index, apnea–hypopnea index, and snoring were higher in hypertensives compared to normotensives. On the other hand, the mean and minimal oxygen saturation were lower in hypertensives compared to normotensives. A statistically significant positive correlation was observed between oxygen desaturation index and BEI in the hypertensive group, whereas this correlation was not statistically significant in the case of normotensives. In summary, nonapneic hypertensives had higher SB intensity, altered sleep architecture, decreased mean oxygen saturation, and increased snoring compared to normotensives. The results suggest that dental screening is necessary for patients with arterial hypertension, especially those presenting with the symptoms of SB.
Endometrial Cancer and BRCA Mutations: A Systematic Review
Authors: Gasparri Maria , Bellaminutti Serena , Farooqi Ammad , Cuccu Ilaria , Di Donato Violante , Papadia Andrea
Published: May 2022

This systematic review identifies, evaluates, and summarises the findings of all relevant individual studies on the prevalence of BRCA mutation (BRCAm) in endometrial cancer patients and the incidence of endometrial cancer in BRCAm women patients. Consequently, the benefits and limits of a prophylactic hysterectomy at the time of the risk-reducing salpingo-oophorectomy are analysed and discussed. A systematic literature search was performed in the databases of PubMed, Cochrane, and Web of Science until May 2022; 13 studies met the eligibility criteria. Overall, 1613 endometrial cancer patients from 11 cohorts were tested for BRCA1/2 mutation. BRCA1/2m were identified in 4.3% of women with endometrial cancer (70/1613). BRCA1m was the most represented (71.4%) pathogenic variant. Alongside, a total of 209 BRCAm carriers from 14 studies were diagnosed with endometrial cancer. Only 5 out of 14 studies found a correlation between BRCAm and an increased risk of endometrial cancer. Nevertheless, two studies found a statistical difference only for BRCA1m women. The present systematic review does not provide strong evidence in favour of performing routine hysterectomy at the time of risk-reducing salpingo-oophorectomy; however, it provides epidemiological data that can be useful for counselling patients in order to offer a tailored approach.
When to Achieve Complete Revascularization in Infarct-Related Cardiogenic Shock
Authors: Masiero Giulia , Cardaioli Francesco , Rodinò Giulio , Tarantini Giuseppe
Published: May 2022

Acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) is a life-threatening condition frequently encountered in patients with multivessel coronary artery disease (CAD). Despite prompt revascularization, in particular, percutaneous coronary intervention (PCI), and therapeutic and technological advances, the mortality rate for patients with CS related to AMI remains unacceptably high. Differently form a hemodynamically stable setting, a culprit lesion-only (CLO) revascularization strategy is currently suggested for AMI–CS patients, based on the results of recent randomized evidence burdened by several limitations and conflicting results from non-randomized studies. Furthermore, mechanical circulatory support (MCS) devices have emerged as a key therapeutic option in CS, especially in the case of their early implantation without delaying revascularization and before irreversible organ damage has occurred. We provide an in-depth review of the current evidence on optimal revascularization strategies of multivessel CAD in infarct-related CS, assessing the role of different types of MCS devices and highlighting the importance of shock teams and medical care system networks to effectively impact on clinical outcomes.
Special Issue: Sudden Cardiac Death: Clinical Updates and Perspectives
Authors: Schupp Tobias , Akin Ibrahim , Behnes Michael
Published: May 2022

Sudden cardiac death (SCD) is defined as unexpected sudden death due to cardiac causes, occurring within one hour after the onset of symptoms [...]
Vascular Occlusion in Kidney Biopsy Is Characteristic of Clinically Manifesting Thrombotic Microangiopathy
Authors: Kovala Marja , Seppälä Minna , Kaartinen Kati , Meri Seppo , Honkanen Eero , Räisänen-Sokolowski Anne
Published: May 2022

Thrombotic microangiopathy (TMA) can sometimes manifest only histologically. Our aim was to retrospectively compare biopsy-proven adult TMA patients showing only histological (h-TMA) or both histological and clinical (c-TMA) TMA in 2006–2017. All native kidney biopsies with TMA were included. Biopsies were re-evaluated by light and electron microscopy, and immunofluorescence. Clinical characteristics, laboratory variables, and treatments were recorded from the electronic medical database. Patients were categorized into h-TMA and c-TMA and these groups were compared. In total, 30 biopsy-proven cases among 7943 kidney biopsies were identified and, of these, 15 had h-TMA and 15 c-TMA. Mean follow-up was 6.3 y, and 73.3% had secondary hemolytic uremic syndrome (HUS) and the rest were atypical HUS. Patient characteristics, treatments, and kidney, and patient survival in the groups were similar. Statistically significant differences were found in histological variables. Vascular myxoid swelling and vascular onion-skinning were almost exclusively detected in c-TMA and, thus, vascular occlusive changes indicate clinically apparent rather than merely histological TMA. In addition, regardless of clinical presentation, kidney and patient survival times were similar in the patient groups highlighting the importance of a kidney biopsy in the case of any kidney-related symptoms.
The Supraclavicular Artery Island Flap for Pharynx Reconstruction
Authors: Nikolaidou Eirini , Pantazi Glykeria , Sovatzidis Apostolos , Vakouli Stella , Vardaxi Chrysoula , Evangelopoulos Iraklis , Gougousis Spyridon
Published: May 2022

The supraclavicular artery island flap (SCAIF) is a reliable, easy-to-harvest and versatile fasciocutaneous flap that can be used for pharynx reconstruction. Instead of free flaps, it requires no microsurgical technique, reduced operating time and postoperative care, making it an ideal option, especially during the COVID-19 pandemic. The primary aim of our study was to present two cases of a total laryngectomy and reconstruction with the SCAIF during the pandemic. The secondary aim was to review the literature concerning surgical techniques, complications and contradictions of the SCAIF for pharynx reconstruction. A literature search was performed using the PubMed, ScienceDirect, Wiley Online Library, Google Scholar, Scopus and Cochrane Library databases, using MeSH terms: larynx AND reconstruction AND flap. Ten full-text articles comprising 92 patients with 93 supraclavicular flaps were included. The patch graft, pharyngeal interposition graft, tubularization or “U”-shaped SCAIF were the main surgical techniques. Pharyngocutaneous fistula was the most frequent postoperative complication, especially in patients with previous radiotherapy, but just 19% of patients required secondary intervention. The lack of donor-site morbidity, low flap loss rates and stenosis rates favored this reconstructive option. This review underlined that the SCAIF has comparable results with other reconstructive options, consolidating this flap in the workhorse of pharynx reconstruction.
Remdesivir in the Treatment of COVID-19: A Propensity Score-Matched Analysis from a Public Hospital in New York City Assessing Renal and Hepatic Safety
Authors: Lim Hyomin , Palaiodimos Leonidas , Berto Cesar G. , Tedunjaiye Oluwatitomi , Malik Paras , Nagraj Sanjana , Choi Hansol , Hti Lar Seng Nang San , Kladas Michail , Kharawala Amrin , Karamanis Dimitrios , Varma Nidhi , Anjali Acharya
Published: May 2022

While the relative efficacy of remdesivir as a therapeutic agent in selected patients with COVID-19 has been established, safety concerns have been raised regarding potential nephrotoxicity and hepatotoxicity. Our main objective was to investigate the kidney- and liver-related safety outcomes in patients with COVID-19 treated with remdesivir in a public hospital in New York. A propensity score-matched retrospective study was conducted in hospitalized patients with COVID-19 from 1 June 2020 to 10 March 2021. A total of 927 patients were included in this study (remdesivir: 427, non-remdesivir: 500; women: 51.8%; median age 61 years; median BMI: 28.5 kg/m2). Matching without replacement yielded a cohort of 248 patients (124 in each group). In the matched cohort, the remdesivir group had a significantly lower rate of acute kidney injury (AKI) (12.1% vs. 21.8%, p = 0.042), a lower rate of acute liver injury (ALI) on the verge of statistical significance (7.3% vs. 14.5%, p = 0.067), and non-significantly lower death rate (13.7% vs. 16.1%, p = 0.593) compared to the non-remdesivir group. Multivariable analyses revealed that patients treated with remdesivir were found to be associated with a significantly lower likelihood for AKI (OR: 0.40; 95% CI: 0.24–0.67, p < 0.001), no association was found for ALI (OR: 0.68; 95% CI: 0.35–1.30, p = 0.241), while a trend towards an association of patients treated with remdesivir with a lower likelihood for in-hospital death was observed (OR: 0.57; 95% CI: 0.32–1.01, p = 0.053). In conclusion, no safety concerns with regards to renal and liver outcomes were raised in patients with COVID-19 treated with remdesivir. Instead, there were signals of possible nephroprotection and improved in-hospital mortality.
Aromatase Inhibitors and Risk of Metabolic and Cardiovascular Adverse Effects in Breast Cancer Patients—A Systematic Review and Meta-Analysis
Authors: Boszkiewicz Kamila , Piwowar Agnieszka , Petryszyn Paweł
Published: May 2022

Aromatase inhibitors (AIs) have been considered first-line therapy for patients with hormone-dependent breast cancer due to their high efficacy and good tolerability. However, AIs are not free of adverse events, and studies show that therapy with AIs is associated with an increased risk of cardiovascular events and the development of insulin resistance and diabetes. We searched the Cochrane Central Register of Controlled Trials, PubMed and EMBASE up to 27 October 2020 for the prevalence of cardiovascular and/or metabolic adverse effects during treatment with AIs in postmenopausal women with breast cancer. A meta-analysis was performed using a random effects model. Odds ratios and 95% confidence intervals were calculated and illustrated using forest plot charts. We performed separate analyses depending on trial design. Twenty two studies met the inclusion criteria. AIs were associated with a higher risk of cardiovascular events, especially when we compared study arms in which AIs were used (alone or in sequence with TAM) with the arms in which TAM was used alone (OR = 1.16; 95%CI 1.04–1.30) or when comparing patients taking AIs alone to patients taking TAM alone or in sequence with AIs (OR = 1.24; 95%CI 1.11–1.38). A pooled analysis of five trials comparing adjuvant AIs to TAM showed the odds for arterial hypertension being 1.31 times higher for patients taking AIs; however, this did not reach statistical significance (OR = 1.31; 95%CI 0.47–3.65). We have not shown an increased risk of dyslipidemia or weight gain with the use of AIs. Our results suggest that postmenopausal women with breast cancer treated with AIs have an increased risk of cardiovascular events in comparison with TAM, potentially due more to a cardioprotective effect of the latter than the cardiotoxicity of AIs. We were unable to prove a similar association for hypertension, dyslipidemia, hyperglycemia or weight gain. Further high-quality RCTs and post-marketing safety observational studies are needed to definitively evaluate the impact of AIs on metabolic disorders in breast cancer patients.
Vitamin B12 Deficiency and Clinical Neuropathy with Metformin Use in Type 2 Diabetes
Authors: Farooq Malik Dilaver , Tak Farooq Ahmad , Ara Fauzia , Rashid Samia , Mir Irfan Ahmad
Published: May 2022

Introduction: Type 2 diabetes (T2DM), which is more prevalent (more than 90% of all diabetes cases) and the main driver of the diabetes epidemic, now affects 5.9% of the world’s adult population, with almost 80% of the total in developing countries. At present, 537 million adults (20–79 years) are living with diabetes—1 in 10. This number is predicted to rise to 643 million by 2030 and 783 million by 2045. In India, reports show that 69.2 million people are living with diabetes (8.7%) as per 2015 data. Long-term metformin treatment is a known pharmacological cause of vitamin B12 (Vit B12) deficiency, as was evident within the first 10–12 years after it started to be used. Methods: This was a cross-sectional study conducted in the Postgraduate Department of Medicine in one of the tertiary hospitals in Kashmir. A total of 1600 consecutive patients with T2DM were taken for the study. Out of which 700 patients met the inclusion criteria. These 700 patients were divided into two groups: those taking metformin, and those who were not on metformin. Cumulative metformin doses were recorded in patients taking metformin, using history of dose and duration of treatment. Serum Vit B12 levels were taken for all patients. Based on the results of Vit B12 levels, patients were classified into normal levels (20 pmol/L), possible B12 deficiency (150–220 pmol/l), and definite deficiency (<150 pmol/L). Results: Our results depicted that patients on prolonged metformin therapy showed an increase in Vit B12 deficiency by 11.16%. The prevalence of clinical neuropathy in the metformin-exposed group was 45%, whereas, a prevalence of 31.8% was found in the non-metformin group. The mean age of patients with neuropathy was higher than those without neuropathy (59.01 ± 7.14 vs. 49.95 ± 7.47) (p-value < 0.514, statistically insignificant). Conclusions: In our study, we found that metformin use is associated with Vit B12 deficiency, which is dependent upon the cumulative dose of metformin. Importantly, prolonged metformin use is also associated with an increase in the prevalence of clinical neuropathy.
Digital Anthropometry for Body Circumference Measurements: European Phenotypic Variations throughout the Decades
Authors: Minetto Marco Alessandro , Pietrobelli Angelo , Busso Chiara , Bennett Jonathan P. , Ferraris Andrea , Shepherd John A. , Heymsfield Steven B.
Published: May 2022

This review summarizes body circumference-based anthropometrics that are in common use for research and in some cases clinical application. These include waist and hip circumference-based central body indices to predict cardiometabolic risk: waist circumference, waist-to-hip ratio, waist-to-height ratio, waist-to-thigh ratio, body adiposity index, a body shape index (ABSI), hip index (HI), and body roundness index (BRI). Limb circumference measurements are most often used to assess sarcopenia and include: thigh circumference, calf circumference, and mid-arm circumference. Additionally, this review presents fascinating recent developments in optic-based imaging technologies that have elucidated changes over the last decades in average body size and shape in European populations. The classical apple and pear shape concepts of body shape difference remain useful, but novel and exciting 3-D optical “e-taper” measurements provide a potentially powerful new future vista in anthropometrics.
Quality of Life for Patients Receiving Elective Interventions for Abdominal Aortic Aneurysms
Authors: Barrena-Blázquez Silvestra , Díez-Alonso Manuel , Riera del Moral Luis Felipe , Coll Salvador Sanchez , García-Honduvilla Natalio , Alvarez-Mon Melchor , Ortega Miguel A. , Ruiz-Grande Fernando
Published: May 2022

Objectives: Information on the quality of life of patients operated on for abdominal aortic aneurysm (AAA) is scarce. The objective of this study was to analyse these patients’ health-related quality of life (HRQoL). Materials and Methods: This was a cross-sectional observational study. Patients undergoing elective AAA surgery from January 2013 to December 2020 were included. The Spanish version of the SF-36 questionnaire was administered to participants one to sixty months after surgery. Results: During the study period, 178 patients underwent surgery for AAA, 109 (61.23%) had open abdominal aortic repair (AAR) and 69 (38.54%) had endovascular aneurysm repair (EVAR). Mortality before the month of surgery was higher among those treated by AAR than EVAR (2.7% and 1.45%, respectively), while late mortality was higher in the EVAR group than in the AAR group (11.5% and 2.7%, respectively). In the late postoperative period, 12.5% of patients who underwent AAR presented complications compared to 25% of those treated with EVAR. The questionnaire was administered to 151 patients (91 AAR and 60 EVAR patients). The AAR patients compared to the EVAR patients had significantly higher mean scores on the health scales of the SF-36 questionnaire in Physical Function (p = 0.001), Vitality (p = 0.003), General Health (p = 0.37), Social Function (p = 0.023) and Mental Health (p = 0.006). Scores on the Mental Summary Component were significantly higher in the AAR group (p = 0.026). Conclusions: The group of patients treated with AAR showed the highest average scores on the scales of the SF-36 questionnaire in Physical Function, Vitality, General Health and Mental Health. The worst result was found in the Social Function scale for EVAR patients and was related to a higher rate of late complications.
In Vivo Verification of Treatment Source Dwell Times in Brachytherapy of Postoperative Endometrial Carcinoma: A Feasibility Study
Authors: Herreros Antonio , Pérez-Calatayud José , Ballester Facundo , Barrera-Gómez Jose , Abellana Rosa , Melo Joana , Moutinho Luis , Tagliaferri Luca , Rovirosa Ángeles
Published: May 2022

(1) Background: In brachytherapy, there are still many manual procedures that can cause adverse events which can be detected with in vivo dosimetry systems. Plastic scintillator dosimeters (PSD) have interesting properties to achieve this objective such as real-time reading, linearity, repeatability, and small size to fit inside brachytherapy catheters. The purpose of this study was to evaluate the performance of a PSD in postoperative endometrial brachytherapy in terms of source dwell time accuracy. (2) Methods: Measurements were carried out in a PMMA phantom to characterise the PSD. Patient measurements in 121 dwell positions were analysed to obtain the differences between planned and measured dwell times. (3) Results: The repeatability test showed a relative standard deviation below 1% for the measured dwell times. The relative standard deviation of the PSD sensitivity with accumulated absorbed dose was lower than 1.2%. The equipment operated linearly in total counts with respect to absorbed dose and also in count rate versus absorbed dose rate. The mean (standard deviation) of the absolute differences between planned and measured dwell times in patient treatments was 0.0 (0.2) seconds. (4) Conclusions: The PSD system is useful as a quality assurance tool for brachytherapy treatments.
Cardiac Allograft Rejection Induces Changes in Nucleocytoplasmic Transport: RANGAP1 as a Potential Non-Invasive Biomarker
Authors: Lozano-Edo Silvia , Roselló-Lletí Esther , Sánchez-Lázaro Ignacio , Tarazón Estefanía , Portolés Manuel , Ezzitouny Maryem , Lopez-Vilella Raquel , Arnau Miguel Angel , Almenar Luis , Martínez-Dolz Luis
Published: May 2022

The non-invasive diagnosis of acute cellular rejection (ACR) is a major challenge. We performed a molecular study analyzing the predictive capacity of serum RanGTPase AP1 (RANGAP1) for diagnosing ACR during the first year after heart transplantation (HT). We included the serum samples of 75 consecutive HT patients, extracted after clinical stability, to determine the RANGAP1 levels through ELISA. In addition, various clinical, analytical, and echocardiographic variables, as well as endomyocardial biopsy results, were collected. RANGAP1 levels were higher in patients who developed ACR (median 63.15 ng/mL; (inter-quartile range (IQR), 36.61–105.69) vs. 35.33 ng/mL (IQR, 19.18–64.59); p = 0.02). Receiver operating characteristic (ROC) curve analysis confirmed that RANGAP1 differentiated between patients with and without ACR (area under curve (AUC), 0.70; p = 0.02), and a RANGAP1 level exceeding the cut-off point (≥90 ng/mL) was identified as a risk factor for the development of ACR (OR, 6.8; p = 0.006). Two independent predictors of ACR identified in this study were higher RANGAP1 and N-terminal pro-brain natriuretic peptide levels. The analysis of the ROC curve of the model showed a significant AUC of 0.77, p = 0.001. Our findings suggest that RANGAP1 quantification facilitates risk prediction for the occurrence of ACR and could be considered as a novel non-invasive biomarker of ACR.