Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers.

There is an unmet clinical need for improved tissue and liquid biopsy tools for cancer detection. We investigated the proteomic profile of extracellular vesicles and particles (EVPs) in 426 human samples from tissue explants (TEs), plasma, and other bodily fluids. Among traditional exosome markers, CD9, HSPA8, ALIX, and HSP90AB1 represent pan-EVP markers, while ACTB, MSN, and RAP1B are novel pan-EVP markers. To confirm that EVPs are ideal diagnostic tools, we analyzed proteomes of TE- (n = 151) and plasma-derived (n = 120) EVPs. Comparison of TE EVPs identified proteins (e.g., VCAN, TNC, and THBS2) that distinguish tumors from normal tissues with 90% sensitivity/94% specificity. Machine-learning classification of plasma-derived EVP cargo, including immunoglobulins, revealed 95% sensitivity/90% specificity in detecting cancer. Finally, we defined a panel of tumor-type-specific EVP proteins in TEs and plasma, which can classify tumors of unknown primary origin. Thus, EVP proteins can serve as reliable biomarkers for cancer detection and determining cancer type.

Current Knowledge About the Impact of Maternal and Infant Nutrition on the Development of the Microbiota-Gut-Brain Axis.

The prenatal and early postnatal periods are stages during which dynamic changes and the development of the brain and gut microbiota occur, and nutrition is one of the most important modifiable factors that influences this process. Given the bidirectional cross talk between the gut microbiota and the brain through the microbiota-gut-brain axis (MGBA), there is growing interest in evaluating the potential effects of nutritional interventions administered during these critical developmental windows on gut microbiota composition and function and their association with neurodevelopmental outcomes. We review recent preclinical and clinical evidence from animal studies and infant/child populations. Although further research is needed, growing evidence suggests that different functional nutrients affect the establishment and development of the microbiota-gut-brain axis and could have preventive and therapeutic use in the treatment of neuropsychiatric disorders. Therefore, more in-depth knowledge regarding the effect of nutrition on the MGBA during critical developmental windows may enable the prevention of later neurocognitive and behavioral disorders and allow the establishment of individualized nutrition-based programs that can be used from the prenatal to the early and middle stages of life.

Silver(I) Octanuclear Complexes Containing N'-(4-Oxotiazolidin-2-Iliden)picolinohydrazonamide and Nitrate as Bridge Ligands. An Example of Solvatomorphism?

The versatile coordination chemistry of (2Z,N'E)-N'-(4-oxothiazolidin-2-ylidene)picolinohydrazonamide (HAmDHotaz) facilitated the synthesis of new complexes with different silver(I) salts. This paper describes the synthesis and characterization, through elemental analysis and spectroscopic techniques (when solubility permits), of a series of compounds that illustrate the coordinative and structural diversity achievable with the HAmDHotaz ligand. Five silver clusters containing the [Ag8(AmDHotaz)4]4+ nucleus were structurally analyzed by single-crystal X-ray diffraction and were found to exhibit solvomorphism. The compositions of these are [Ag8(AmDHotaz)4(NO3)3(MeOH)(H2O)](NO3)·MeOH·7.5H2O (1), {[Ag8(AmDHotaz)4(NO3)3(H2O)2](NO3)·9.5(H2O)}n (2), {[Ag8(AmDHotaz)4(NO3)3(H2O)2](NO3)·11.5(H2O)}n (2a), {[Ag8(AmDHotaz)4(NO3)2(H2O)2](NO3)(OH)·6H2O}n (3), and {[Ag8(AmDHotaz)4(NO3)2(H2O)](NO3)(OH)·4.5H2O}n (3a). Argentophilic interactions are present in each of the octanuclear structures, where Ag···Ag distances range from 2.828(2) to 2.986(1) Å. These distances are influenced by crystal packing, determined by the counterion and solvent molecules in the structure. In the solvatomorphs, solvent molecules were observed to be disordered. Various hydrogen-bonding interactions, such as N-H···O-N, O-H···O, N-H···O═C, C-H···O-N, and π-π stacking interactions, contribute to the crystal packing. The influence of these weak interactions on the crystal packing was further analyzed using DFT calculations and Bader's theory of atoms-in-molecules, with a focus on argentophilic interactions and Ag···S interactions.

SARS-CoV-2's brain impact: revealing cortical and cerebellar differences via cluster analysis in COVID-19 recovered patients.

BACKGROUND: COVID-19 is a disease known for its neurological involvement. SARS-CoV-2 infection triggers neuroinflammation, which could significantly contribute to the development of long-term neurological symptoms and structural alterations in the gray matter. However, the existence of a consistent pattern of cerebral atrophy remains uncertain. OBJECTIVE: Our study aimed to identify patterns of brain involvement in recovered COVID-19 patients and explore potential relationships with clinical variables during hospitalization. METHODOLOGY: In this study, we included 39 recovered patients and 39 controls from a pre-pandemic database to ensure their non-exposure to the virus. We obtained clinical data of the patients during hospitalization, and 3 months later; in addition we obtained T1-weighted magnetic resonance images and performed standard screening cognitive tests. RESULTS: We identified two groups of recovered patients based on a cluster analysis of the significant cortical thickness differences between patients and controls. Group 1 displayed significant cortical thickness differences in specific cerebral regions, while Group 2 exhibited significant differences in the cerebellum, though neither group showed cognitive deterioration at the group level. Notably, Group 1 showed a tendency of higher D-dimer values during hospitalization compared to Group 2, prior to p-value correction. CONCLUSION: This data-driven division into two groups based on the brain structural differences, and the possible link to D-dimer values may provide insights into the underlying mechanisms of SARS-COV-2 neurological disruption and its impact on the brain during and after recovery from the disease.

Clinical prediction scale approach derived from a retrospective study to reduce the number of urgent, low-value cranial CT scans.

PURPOSE: Fifty percent of cranial CT scans performed achieve no benefit and entail risks. Our aim is to determine the yield of non-traumatic urgent cranial-CT and develop a pretest clinical probability scale approach. METHODS: Adult patients seen in our emergency department between 2017-2021 and referred for urgent cranial-CT for non-traumatic reasons were retrospectively recruited and randomly selected. Presenting complaint (PC), demographic variables, Relevant radiological findings (RRF) on the urgent cranial-CT and Relevant clinical-radiological findings (RCRF: admission need or RRF detection on the urgent cranial-CT or cranial CT/MRI in the following three months) were recruited. RESULTS: We recruited 702 patients, with median age 62 [47-76] years, 363 (51.7%) females. RCRF were observed in 404 (57.55%); of these, 352 (50.1%) required admission. RRF were detected in 190 (27.06%): 36 acute ischemic and 27 acute hemorrhagic lesions, 115 masses, 9 edema, and 27 hydrocephalus. Predictive PC for urgent cranial-CT were motor, speech, sensory deficits, sudden alteration of mental status, epileptic seizure, cognitive impairment, neurological symptoms in cancer patients, acute headache without a prior history and with meningeal signs; nausea, vomiting, or hypertensive crisis; visual deficits, and dizziness. This algorithm provided sensitivity, specificity, positive predictive value, and negative predictive value (NPV, 95%CI in brackets) of 92.1% (89-94.5%), 27.5% (22.5-33.0%), 63.3% (59.2-67.2%), and 71.9% (62.7-80.0%), to diagnose RCRF, and 97.4% (93.4-99.1%), 21.3% (17.8-25.1%), 31.5% (27.7-35.4%), and 95.6% (90.1-98.6%), to diagnose RRF. In patients not requiring admission (n = 350), the NPV for RRF was 98.8% (93.6-100%); the negative likelihood ratio 0.08 (0.01-0.57), and sensitivity remained at 97.8% (82.2-99.9%). Applying it would have avoided performing 85/350 urgent cranial-CT (24.29%). To find one RRF, we would have gone from performing 7.8 (350/45) to 5.9 (265/45) CTs, failing to diagnose 1/45 (2.2%) RRF. CONCLUSIONS: This proposed clinical scale could potentially decrease 24% of urgent cranial-CT.

Palladium(II) and Platinum(II) Complexes Bearing ONS-Type Pincer Ligands: Synthesis, Characterization and Catalytic Investigations.

This work describes the synthesis of eight new Pd(II) and Pt(II) complexes with the general formula [M(TSC)Cl], where TSC represents the 4N-monosubstituted thiosemicarbazone derived from 2-acetylpyridine N-oxide with the substituents CH3 (H4MLO), C2H5 (H4ELO), phenyl (H4PLO) and (CH3)2 (H4DMLO). These complexes have been characterized by elemental analysis, molar conductivity, IR spectroscopy, 1H, 13C, 195Pt and ESI-MS. The complexes exhibit a square planar geometry around the metallic center coordinated by a thiosemicarbazone molecule acting as a donor ONS-type pincer ligand and by a chloride, as confirmed by the molecular structures of the complexes, [Pd(4ELO)Cl] (3) and [Pd(4PLO)Cl] (5), determined by single-crystal X-ray diffraction. The 195Pt NMR spectra of the complexes of formulae [Pt(4PLO)Cl] (6) and [Pt(4DMLO)Cl] (8) in DMSO show a single signal at -2420.4 ppm, confirming the absence of solvolysis products. Complexes 3 and 5 have been tested as catalysts in the Suzuki-Miyaura cross-coupling reactions of aryl bromides with phenylboronic acid, with yields of between 50 and 90.

Synthesis, Structural Characterisation, and Electrochemical Properties of Copper(II) Complexes with Functionalized Thiosemicarbazones Derived from 5-Acetylbarbituric Acid.

The reaction between 5-acetylbarbituric acid and 4-dimethylthiosemicarbazide or 4-hexamethyleneiminyl thiosemicarbazide produces 5-acetylbarbituric-4-dimethylthiosemicarbazone (H2AcbDM) and 5-acetylbarbituric-4N-hexamethyleneiminyl thiosemicarbazone (H2Acbhexim). Eight new complexes with different copper(II) salts have been prepared and characterized using elemental analysis, molar conductance, UV-Vis, ESI-HRMS, FT-IR, magnetic moment, EPR, and cyclic voltammetry. In addition, three-dimensional molecular structures of [Cu(HAcbDM)(H2O)2](NO3)·H2O (3a), [Cu(HAcbDM)(H2O)2]ClO4 (4), and [Cu(HAcbHexim)Cl] (6) were determined by single crystal X-ray crystallography, and an analysis of their supramolecular structure was carried out. The H-bonded assemblies were further studied energetically using DFT calculations and MEP surface and QTAIM analyses. In these complexes, the thiosemicarbazone coordinates to the metal ion in an ONS-tridentate manner, in the O-enolate/S-thione form. The electrochemical behavior of the thiosemicarbazones and their copper(II) complexes has been investigated at room temperature using the cyclic voltammetry technique in DMFA. The Cu(II)/Cu(I) redox system was found to be consistent with the quasi-reversible diffusion-controlled process.

Empirical model to assess leaching of pesticides in soil under a steady-state flow and tropical conditions.

Abstract: An empirical model of leaching of pesticides was developed to simulate the concentration of fungicides throughout unsaturated soil. The model was based on chemical reactions and the travel time of a conservative tracer to represent the travel time required for water to flow between soil layers. The model's performance was then tested using experimental data from dimethomorph and pyrimethanil applied to the soil under field and laboratory conditions. The empirical model simulated fungicide concentration on soil solids and in soil solution at different depths over time (mean square error between 2.9 mg2 kg-2 and 61mg2 kg-2) using sorption percentages and degradation rates under laboratory conditions. The sorption process was affected by the organic carbon, clay, and the effective cation exchange capacity of the soil. The degradation rate values of dimethomorph (0.039 d-1-0.009 d-1) and pyrimethanil (0.053 d-1-0.004 d-1) decreased from 0 to 40 cm and then remained constant in deeper soil layers (60-80 cm). Fungicide degradation was a critical input in the model at subsurface layers. The model was determined to be a reliable mathematical tool to estimate the leachability of pesticides in tropical soil under a steady-state flow. It may be extended to other substances and soils for environmental risk assessment projects. Supplementary Information: The online version contains supplementary material available at 10.1007/s13762-023-05038-w.

Mechanistic Insights on Pd-Catalyzed Three-Component Reactions of Alkynols, Methyl Orthoformate, and Salicylaldehyde Derivatives. Application to the Synthesis of Steroid Chroman Ketals and Spiroketals with Antioxidant Activity.

Contrary to our previous report in which a Pd-catalyzed three-component reaction of a steroid alkynol, trimethyl orthoformate, and salicylaldehyde exclusively produced chroman ketals, the same reaction employing 2,5-dihydroxysalicylaldehyde led to a mixture of a chroman ketal and a spiroketal. Provided that both courses of the reaction imply a 4 + 2 inverse demand cycloaddition between an o-quinone methide and an enol ether, density functional theory calculations revealed that the chroman ketal/spiroketal selectivity is governed by both, the rate of the formation of the o-quinone methide and the isomerization of the initially produced exocyclic enol ether─that led to the spiroketal─to its endocyclic partner that produces the chroman ketal. Remarkably, Lewis catalysis is central to the observed reactivity, and the availability of plausible catalytic species controls the overall chemoselectivity. The methodology herein applied and scrutinized enriches the palette of reactions, leading to increased molecular complexity, as demonstrated in the obtained products, whose antioxidant activity and detailed NMR characterization are presented.

Digital tomosynthesis improves chest radiograph accuracy and reduces microbiological false negatives in COVID-19 diagnosis.

PURPOSE: Diagnosing pneumonia by radiograph is improvable. We aimed (a) to compare radiograph and digital thoracic tomosynthesis (DTT) performances and agreement for COVID-19 pneumonia diagnosis, and (b) to assess the DTT ability for COVID-19 diagnosis when polymerase chain reaction (PCR) and radiograph are negative. METHODS: Two emergency radiologists with 11 (ER1) and 14 experience-years (ER2) retrospectively evaluated radiograph and DTT images acquired simultaneously in consecutively clinically suspected COVID-19 pneumonia patients in March 2020-January 2021. Considering PCR and/or serology as reference standard, DTT and radiograph diagnostic performance and interobserver agreement, and DTT contributions in unequivocal, equivocal, and absent radiograph opacities were analysed by the area under the curve (AUC), Cohen's Kappa, Mc-Nemar's and Wilcoxon tests. RESULTS: We recruited 480 patients (49 ± 15 years, 277 female). DTT increased ER1 (from 0.76, CI95% 0.7-0.8 to 0.79, CI95% 0.7-0.8; P=.04) and ER2 (from 0.77 CI95% 0.7-0.8 to 0.80 CI95% 0.8-0.8, P=.02) radiograph-AUCs, sensitivity, specificity, predictive values, and positive likelihood ratio. In false negative microbiological cases, DTT suggested COVID-19 pneumonia in 13% (4/30; P=.052, ER1) and 20% (6/30; P=.020, ER2) more than radiograph. DTT showed new or larger opacities in 33-47% of cases with unequivocal opacities in radiograph, new opacities in 2-6% of normal radiographs and reduced equivocal opacities by 13-16%. Kappa increased from 0.64 (CI95% 0.6-0.8) to 0.7 (CI95% 0.7-0.8) for COVID-19 pneumonia probability, and from 0.69 (CI95% 0.6-0.7) to 0.76 (CI95% 0.7-0.8) for pneumonic extension. CONCLUSION: DTT improves radiograph performance and agreement for COVID-19 pneumonia diagnosis and reduces PCR false negatives.

Inappropriate requests for cranial CT scans in emergency departments increase overuse and reduce test performance.

PURPOSE: The number of non-traumatic urgent cranial computed tomography (NT-UCCT) is exponentially increasing but limited research has been conducted on the quality of clinical justification. Accordingly, we aimed (1) to assess how clinical information in the electronic NT-UCCT request agreed with that provided in the patient's emergency department discharge summary and (2) to analyze the potential effect of those discrepancies on the NT-UCCT overload. MATERIAL AND METHODS: Patients undergoing NT-UCCT in 2017-2021 were randomly selected for this retrospective research-board-approved study. Signs and symptoms (S/S) in electronic request and emergency department discharge summary, acute and relevant computed tomography (CT) findings (acute ischemia or hemorrhage, masses, brain edema, or previously undetected hydrocephalus), and final diagnosis at emergency department discharge summary were collected. Concordance between digital request and emergency department discharge summary and their association with both acute and relevant CT findings and final diagnosis were analyzed. RESULTS: We recruited 156 patients: 80 men; mean age, 55. Acute, relevant CT findings were detected in 28 cases (17.9%). The final diagnosis was neurological disease, non-neurological disease, and no definitive diagnosis in 46 (29.5%), 58 (37.2%), and 51 (32.7%) cases, respectively. Full agreement between the electronic request and emergency department discharge summary occurred in only 36 patients (23.1%). Motor deficit was the most frequent false positive electronic request S/S (18; 11.54%), having low positive predictive value (30.30%; 95%CI 15.59-48.71%) and worst association with acute relevant CT findings than when true positive (OR 2.54; 95%CI 0.04-6.21 vs. OR 6.26, 95%CI 2.21-17.78). Nausea/vomiting was the third most common false negative electronic request S/S (13; 10.26%) and reduced the likelihood of acute and relevant CT findings (OR 0.126; 95%CI 0.016-0.971; p = 0.020). False S/S in electronic request predominated in non-neurological diseases (50-60.2% vs. 33-39.8%; p = 0.068). CONCLUSION: Discrepancies between electronic request and emergency department discharge summary were observed in >75% of patients, leading to unnecessary NT-UCCT tests.

Impact of Probiotics on the Prevention and Treatment of Gastrointestinal Diseases in the Pediatric Population.

Despite the high prevalence of gastrointestinal disorders (GIDs) in infants and children, especially those categorized as functional GIDs (FGIDs), insufficient knowledge about their pathophysiology has limited both symptomatic diagnosis and the development of optimal therapies. Recent advances in the field of probiotics have made their potential use as an interesting therapeutic and preventive strategy against these disorders possible, but further efforts are still needed. In fact, there is great controversy surrounding this topic, generated by the high variety of potential probiotics strains with plausible therapeutic utility, the lack of consensus in their use as well as the few comparative studies available on probiotics that record their efficacy. Taking into account these limitations, and in the absence of clear guidelines about the dose and timeframe for successful probiotic therapy, our review aimed to evaluate current studies on potential use of probiotics for the prevention and treatment of the most common FGIDs and GIDs in the pediatric population. Furthermore, matters referring to know major action pathways and key safety recommendations for probiotic administration proposed by major pediatric health agencies shall also be discussed.

The effect of pulp volume and impact direction on the stress and strain distribution during an impact.

BACKGROUND/AIM: Dentoalveolar trauma has a high incidence in different age groups, including the extremes, children, and older people. Mouth aging leads to some changes, one of them being the pulp volume reduction. The aim of this study was to evaluate the influence of different pulp cavity volumes and the impact direction on the stress and strain distribution of a maxillary central incisor. MATERIAL AND METHODS: Twenty cone beam computed tomography sets of images were selected and the pulp cavity volume was measured by ITK-SNAP software. The mean pulp cavity volume for age group of 10- to 12-year-olds was calculated to obtain the largest one. Subsequent reductions (25%, 50%, 75% and 100%) in the pulp volume values were made to simulate the aging process. The maxilla anterior segment was modeled in the Rhinoceros 5.0 software. The three-dimensional volumetric mesh was generated using the Patran software (MSC. Software), with isoparametrics, 4-noded tetrahedral elements, and exported to Marc/Mentat (MSC. Software) as element number 134. A non-linear dynamic impact analysis was performed in which a steel ball reached the central incisor at a speed of 5 m/s in the horizontal or vertical direction. The stresses were evaluated by modified von Mises stresses. The strains and the total displacement were also recorded. RESULTS: The pulp volume mean value for the age group of 10- to 12-year-olds was 65.05 mm3 . Stress concentrations were slightly different for the different pulp volumes. Impact directions resulted in different stress distribution. Higher stress values were present with the horizontal impact (range between 25.18 MPa and 24.08 MPa for enamel and 38.89 MPa and 37.03 for dentin) when compared to vertical impact (range between 15.30 MPa and 14.58 for enamel and 24.77 to 22.03 MPa for dentin). Total displacement was different for the two impact directions and higher for the horizontal impact. CONCLUSION: Pulp volume did not significantly affect the stress, strain, and total displacement during the impact but the impact direction did affect the evaluated parameters during impact.

[Performance in prognostic capacity and efficiency of the Thoracic Care Suite GE AI tool applied to chest radiography of patients with COVID-19 pneumonia]. / Eficacia de la capacidad y la eficiencia pronósticas de la herramienta de inteligencia artificial Thoracic Care Suite de GE aplicada a la radiografía torácica de pacientes con neumonía por COVID-19.

OBJECTIVE: Rapid progression of COVID-19 pneumonia may put patients at risk of requiring ventilatory support, such as non-invasive mechanical ventilation or endotracheal intubation. Implementing tools that detect COVID-19 pneumonia can improve the patient's healthcare. We aim to evaluate the efficacy and efficiency of the artificial intelligence (AI) tool GE Healthcare's Thoracic Care Suite (featuring Lunit INSIGHT CXR, TCS) to predict the ventilatory support need based on pneumonic progression of COVID-19 on consecutive chest X-rays. METHODS: Outpatients with confirmed SARS-CoV-2 infection, with chest X-ray (CXR) findings probable or indeterminate for COVID-19 pneumonia, who required a second CXR due to unfavorable clinical course, were collected. The number of affected lung fields for the two CXRs was assessed using the AI tool. RESULTS: One hundred fourteen patients (57.4 ± 14.2 years, 65 -57%- men) were retrospectively collected. Fifteen (13.2%) required ventilatory support. Progression of pneumonic extension ≥ 0.5 lung fields per day compared to pneumonia onset, detected using the TCS tool, increased the risk of requiring ventilatory support by 4-fold. Analyzing the AI output required 26 seconds of radiological time. CONCLUSIONS: Applying the AI tool, Thoracic Care Suite, to CXR of patients with COVID-19 pneumonia allows us to anticipate ventilatory support requirements requiring less than half a minute.

Experimental and Theoretical Evidence of a Pb⋠⋠⋠Pb Ditetrel Bond Without a σ-Hole.

The crystal structure of a newly synthesized compound, [PbL(Ac)]2 , (where L=2 (amino(pyrazin-2-yl) methylene) hydrazinecarbothioamide, Ac=acetate anion) exhibits a close contact between pairs of Pb atoms, suggesting a ditetrel bond, in addition to two Pb⋅⋅⋅O tetrel bonds, and two C-H⋅⋅⋅O H-bonds. The presence of this ditetrel bond as an attractive component is confirmed by various quantum chemical methods. This novelty of this particular bond is its existence even in the absence of a σ-hole on the Pb atom, which is typically considered a prerequisite for a bond of this type. From a wider perspective, a survey of the Cambridge Structural Database suggests this bond may be more common than was hitherto thought, with 44 examples of Pb⋅⋅⋅Pb contacts amongst a total number of 219 examples of T⋅⋅⋅T interactions in general (T=Si, Ge, Sn, Pb).

A Visible Light Ru-Catalyzed Photoredox Access to Substituted Dihydrofurans.

An efficient, visible light Ru(bpy)3Cl2-catalyzed method for the preparation of 2,3-dihydrofurans is reported. This approach employs 2-bromoketoesters as radical precursors and alkyl enol ethers as acceptors. The photoredox cycle furnishes an oxonium ion that is captured by an internal nucleophile to render the corresponding dihydrofurans. Moreover, the obtained products contain a versatile acetal moiety at C-2, allowing its transformation into a diverse variety of heteroaromatic and nonaromatic compounds. This method could serve as an important tool in the synthesis of complex tetrahydro- and dihydrofurans as well as heteroaromatic structures.

Development and psychometric properties of the human papillomavirus-quality of life (HPV-QoL) questionnaire to assess the impact of HPV on women health-related-quality-of-life.

PURPOSE: The HPV-Quality-of-Life (HPV-QoL) questionnaire was developed to determine the impact of Human-Papillomavirus (HPV) infection and related interventions on women health-related quality-of-life. This study provides the development and preliminary psychometric properties of a novel HPV-QoL questionnaire for adult women with HPV. METHODS: After reviewing literature and cognitive debriefing interviews in women who had experienced HPV-related conditions, instrument items and domains were developed. A draft questionnaire was pilot tested for comprehension and ease of completion. Psychometric evaluation of the final HPV-QoL scale was conducted in a psychometric study including 252 adult women derived to our centre by a positive HPV test in the cervical cancer screening program and/or presenting genital warts. RESULTS: The present study reveals that the HPV-QoL questionnaire, structured in four domains: general well-being [including psychological well-being and social well-being subdomains], health, contagiousness and sexuality, showed good metric properties of feasibility irrespective of age or educational level, and time to administer was less than 5 min. Internal consistency and temporal stability (reliability) showed values above the acceptable standards. The instrument showed its concurrent validity by means of a significant correlation with mental and sexual existing instruments; GHQ-12 and FSFI questionnaires, respectively, and also known groups validity showing significant differences among the subgroups regarding either sexual dysfunction or mental deterioration. CONCLUSION: This study provides an HPV-QoL questionnaire with an innovative patient-reported outcomes specific measurement tool to assess HRQoL in women with HPV infection. The present study suggests this questionnaire has satisfactory psychometric properties, including validity and reliability. Results support the use of the HPV-QoL questionnaire as a HRQoL measurement instrument for daily medical practice and clinical research.

Do Mammalian Cells Really Need to Export and Import Heme?

Heme is a cofactor that is essential to almost all forms of life. The production of heme is a balancing act between the generation of the requisite levels of the end-product and protection of the cell and/or organism against any toxic substrates, intermediates and, in this case, end-product. In this review, we provide an overview of our understanding of the formation and regulation of this metallocofactor and discuss new research on the cell biology of heme homeostasis, with a focus on putative transmembrane transporters now proposed to be important regulators of heme distribution. The main text is complemented by a discussion dedicated to the intricate chemistry and biochemistry of heme, which is often overlooked when new pathways of heme transport are conceived.

Transferrin receptor 1 controls systemic iron homeostasis by fine-tuning hepcidin expression to hepatocellular iron load.

Transferrin receptor 1 (Tfr1) mediates uptake of circulating transferrin-bound iron to developing erythroid cells and other cell types. Its critical physiological function is highlighted by the embryonic lethal phenotype of Tfr1-knockout (Tfrc-/-) mice and the pathologies of several tissue-specific knockouts. We generated TfrcAlb-Cre mice bearing hepatocyte-specific ablation of Tfr1 to explore implications in hepatocellular and systemic iron homeostasis. TfrcAlb-Cre mice are viable and do not display any apparent liver pathology. Nevertheless, their liver iron content (LIC) is lower compared with that of control Tfrcfl/fl littermates as a result of the reduced capacity of Tfr1-deficient hepatocytes to internalize iron from transferrin. Even though liver Hamp messenger RNA (mRNA) and serum hepcidin levels do not differ between TfrcAlb-Cre and Tfrcfl/fl mice, Hamp/LIC and hepcidin/LIC ratios are significantly higher in the former. Importantly, this is accompanied by modest hypoferremia and microcytosis, and it predisposes TfrcAlb-Cre mice to iron-deficiency anemia. TfrcAlb-Cre mice appropriately regulate Hamp expression following dietary iron manipulations or holo-transferrin injection. Holo-transferrin also triggers proper induction of Hamp mRNA, ferritin, and Tfr2 in primary TfrcAlb-Cre hepatocytes. We further show that these cells can acquire 59Fe from 59Fe-transferrin, presumably via Tfr2. We conclude that Tfr1 is redundant for basal hepatocellular iron supply but essential for fine-tuning hepcidin responses according to the iron load of hepatocytes. Our data are consistent with an inhibitory function of Tfr1 on iron signaling to hepcidin via its interaction with Hfe. Moreover, they highlight hepatocellular Tfr1 as a link between cellular and systemic iron-regulatory pathways.

Radiomics for prediction of survival in lower-grade gliomas-it's time to move beyond the crystal ball.

KEY POINTS: • Radiomics might help predict survival of patients with lower-grade gliomas.• Several different models using different radiomics features have been proposed with only little overlap in included features.• Prospective trials and validation studies are needed to establish which models offer clinical benefit and which do not.