Study of late toxicity biomarkers of locally advanced head and neck cancer patients treated with radiotherapy plus cisplatin or cetuximab points to the relevance of skin macrophages (TOX-TTCC-2015-01).

PURPOSE: Radiotherapy (RT) with concomitant cisplatin (CRT) or cetuximab (ERT) are accepted treatment options for locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). Long-term adverse events (AEs) have a vast impact on patients' quality of life. This study explored tissue biomarkers which could help predict late toxicity. METHODS/PATIENTS: Single-institution prospective study including patients aged ≥ 18 with histologically confirmed newly diagnosed LA-SCCHN treated with RT and either concomitant cisplatin q3w or weekly cetuximab, according to institutional protocols. All patients underwent pre- and post-treatment skin biopsies of neck regions included in the clinical target volume. Angiogenesis, macrophages, and extracellular matrix (ECM) markers were evaluated by immunohistochemistry (IHC). RESULTS: From April 15, 2016, to December 11, 2017; 31 patients were evaluated [CRT = 12 (38.7%) and ERT = 19 (61.3%)]. 27 patients (87%) had received induction chemotherapy. All patients finished RT as planned. IHC expression of vasculature (CD34) and collagen (Masson's Trichrome) did not differ significantly between and within CRT and ERT arms. Conversely, an increased CD68 and CD163 macrophage infiltration expression was observed after treatment, without significant impact of treatment modality. Patients with higher late toxicity showed lower expression of macrophage markers in pre-treatment samples compared with those with lower late toxicity, with statistically significant differences for CD68. CONCLUSIONS: Angiogenesis and ECM biomarkers did not differ significantly between CRT and ERT. Macrophage markers increased after both treatments and deserve further investigation as predictors of late toxicity in LA-SCCHN patients. [Protocol code: TOX-TTCC-2015-01/Spanish registry of clinical studies (REec): 2015-003012-21/Date of registration: 27/01/2016].

Advanced Detection of Failed LEDs in a Short Circuit for Automotive Lighting Applications.

This paper addresses the issue of LED short-circuit fault detection in signaling and lighting systems in the automotive industry. The conventional diagnostic method commonly implemented in newer vehicles relies on measuring the voltage drop across different LED branches and comparing it with threshold values indicating faults caused by open circuits or LED short circuits. With this algorithm, detecting cases of a few LEDs short-circuited within a branch, particularly a single malfunctioning LED, is particularly challenging. In this work, two easily implementable algorithms are proposed to address this issue within the vehicle's control unit. One is based on a mathematical prediction model, while the other utilizes a neural network. The results obtained offer a 100% LED short-circuit fault detection rate in the majority of analyzed cases, representing a significant improvement over the conventional method, even in scenarios involving a single malfunctioning LED within a branch. Additionally, the neural network-based model can accurately predict the number of failed LEDs.

Li-Site Defects Induce Formation of Li-Rich Impurity Phases: Implications for Charge Distribution and Performance of LiNi0.5- xMxMn1.5O4 Cathodes (M = Fe and Mg; x = 0.05-0.2).

An understanding of the structural properties that allow for optimal cathode performance, and their origin, is necessary for devising advanced cathode design strategies and accelerating the commercialization of next-generation cathodes. High-voltage, Fe- and Mg-substituted LiNi0.5Mn1.5O4 cathodes offer a low-cost, cobalt-free, yet energy-dense alternative to commercial cathodes. In this work, the effect of substitution on several important structure properties is explored, including Ni/Mn ordering, charge distribution, and extrinsic defects. In the cation-disordered samples studied, a correlation is observed between increased Fe/Mg substitution, Li-site defects, and Li-rich impurity phase formation-the concentrations of which are greater for Mg-substituted samples. This is attributed to the lower formation energy of MgLi defects when compared to FeLi defects. Li-site defect-induced impurity phases consequently alter the charge distribution of the system, resulting in increased [Mn3+] with Fe/Mg substitution. In addition to impurity phases, other charge compensators are also investigated to explain the origin of Mn3+ (extrinsic defects, [Ni3+], oxygen vacancies and intrinsic off-stoichiometry), although their effects are found to be negligible.

Electron paramagnetic resonance as a tool to determine the sodium charge storage mechanism of hard carbon.

Hard carbon is a promising negative electrode material for rechargeable sodium-ion batteries due to the ready availability of their precursors and high reversible charge storage. The reaction mechanisms that drive the sodiation properties in hard carbons and subsequent electrochemical performance are strictly linked to the characteristic slope and plateau regions observed in the voltage profile of these materials. This work shows that electron paramagnetic resonance (EPR) spectroscopy is a powerful and fast diagnostic tool to predict the extent of the charge stored in the slope and plateau regions during galvanostatic tests in hard carbon materials. EPR lineshape simulation and temperature-dependent measurements help to separate the nature of the spins in mechanochemically modified hard carbon materials synthesised at different temperatures. This proves relationships between structure modification and electrochemical signatures in the galvanostatic curves to obtain information on their sodium storage mechanism. Furthermore, through ex situ EPR studies we study the evolution of these EPR signals at different states of charge to further elucidate the storage mechanisms in these carbons. Finally, we discuss the interrelationship between EPR spectroscopy data of the hard carbon samples studied and their corresponding charging storage mechanism.

Repeated hypoxic episodes allow hematological and physiological habituation in rainbow trout.

Introduction: Under climate change, the increase in temperature in aquatic environments may induce oxygen depletion. In extreme cases, low oxygen may become a limiting factor for fish, thus generating stress. In addition, consecutive hypoxic episodes may complicate the recovery of individuals and hinder their ability to modulate physiological and biochemical responses to maintain homeostasis. Thus, the aim of this study was to determine the hematological and physiological responses of rainbow trout under a condition of repeated hypoxic and manipulation stresses at three different time points. Methods: Every hypoxic episode consisted of exposing the fish to low dissolved oxygen concentrations (2 mgO2/L for 1 h). Following the exposure, the fish were allowed to recover for 1 h, after which they were sampled to investigate hematological and physiological parameters. Results and discussion: The results showed a pattern of habituation reflected by values of hematocrit, hemoglobin, and mean corpuscular volume, indicating a certain ability of rainbow trout to resist this type of repeated hypoxic events, provided that the fish can have some recovery time between the exposures.

Structural Insight into Protective Alumina Coatings for Layered Li-Ion Cathode Materials by Solid-State NMR Spectroscopy.

Layered transition metal oxide cathode materials can exhibit high energy densities in Li-ion batteries, in particular, those with high Ni contents such as LiNiO2. However, the stability of these Ni-rich materials often decreases with increased nickel content, leading to capacity fade and a decrease in the resulting electrochemical performance. Thin alumina coatings have the potential to improve the longevity of LiNiO2 cathodes by providing a protective interface to stabilize the cathode surface. The structures of alumina coatings and the chemistry of the coating-cathode interface are not fully understood and remain the subject of investigation. Greater structural understanding could help to minimize excess coating, maximize conductive pathways, and maintain high capacity and rate capability while improving capacity retention. Here, solid-state nuclear magnetic resonance (NMR) spectroscopy, paired with powder X-ray diffraction and electron microscopy, is used to provide insight into the structures of the Al2O3 coatings on LiNiO2. To do this, we performed a systematic study as a function of coating thickness and used LiCoO2, a diamagnetic model, and the material of interest, LiNiO2. 27Al magic-angle spinning (MAS) NMR spectra acquired for thick 10 wt % coatings on LiCoO2 and LiNiO2 suggest that in both cases, the coatings consist of disordered four- and six-coordinate Al-O environments. However, 27Al MAS NMR spectra acquired for thinner 0.2 wt % coatings on LiCoO2 identify additional phases believed to be LiCo1-xAlxO2 and LiAlO2 at the coating-cathode interface. 6,7Li MAS NMR and T1 measurements suggest that similar mixing takes place near the interface for Al2O3 on LiNiO2. Furthermore, reproducibility studies have been undertaken to investigate the effect of the coating method on the local structure, as well as the role of the substrate.

Effect of age in women undergoing laparoscopic sacrocolpopexy: A retrospective study.

OBJECTIVE: To determine whether elderly women (≥65 years) have an increased risk of complications and lower success when undergoing laparoscopic sacrocolpopexy (LSC) compared with younger women (<65 years). METHODS: This was a retrospective study of all LSC procedures performed from August 2014 to February 2021 by a single urogynecologic surgeon in an academic affiliated hospital system. Charts were identified through procedure codes. Patient demographics, clinical, surgical, and postoperative data were collected. The primary outcome of this study was to compare complications associated with LSC, including intraoperative and postoperative complications. Secondary outcomes included subjective, objective, and composite success. RESULTS: In total, 312 participants met the criteria. The mean age of the group who were younger than 65 years was 55.7 years (±6.5) and of the group aged 65 years or older was 69.3 years (±3.5). Racial demographics revealed no differences between the two groups. Patients aged 65 years or older had a statistically significant lower body mass index (calculated as weight in kilograms divided by the square of height in meters), a higher rate of hypertension, smaller genital hiatus, and a larger anterior vaginal wall prolapse compared with the younger cohort. They also less often underwent a posterior repair. No statistically significant differences were found with regards to intraoperative and postoperative complications, including 30-day re-admission, between the two age groups. Both groups had high anatomic success rates, with no significant difference (<65 = 96.3%; ≥65 = 98.4%; P = 0.326). Those aged younger than 65 years compared with those aged 65 years or older had lower subjective success that was not significantly different (<65 = 62.8%; ≥65 = 71.0; P = 0.134). Composite success was noted to reach the threshold of a statistically significant difference in the group aged younger than 65 years compared with those aged 65 years or older (60.1% vs 71.0%; P = 0.0499). CONCLUSION: In this study, elderly patients did not have increased intraoperative and postoperative complications after undergoing LSC. Similar rates of anatomic and subjective success were also found with younger patients having a lower composite success. Proper candidates for LSC should not be excluded based upon age.

Long-term outcomes in two adult siblings with Fucosidosis - Diagnostic odyssey and clinical manifestations.

Fucosidosis (OMIN# 230000) is a rare lysosomal storage disorder (LSDs) caused by mutations in the FUCA1 gene, leading to alpha-L-fucosidase deficiency; it is inherited as an autosomal recessive trait. Fucosidosis represents a disease spectrum with a wide variety of clinical features, but most affected patients have slow neurologic deterioration. Many patients die young and the long-term clinical outcomes in adult patients are poorly documented. Here, we report the long-term follow up of two Caucasian siblings, a 31-year-old man and 25-year-old woman. We describe the clinical, biochemical, radiological and genetic findings in two siblings affected by Fucosidosis and the differences between them after 19-years follow up. The dermatological features of the younger sibling have been reported previously by Bharati et al. (2007). Both patients have typical features of Fucosidosis, such as learning difficulties, ataxia, and angiokeratomas with differing severity. Case 1 presents severe ataxia with greater limitation of mobility, multiple dysostoses, angiokeratomas on his limbs, retinal vein enlargement and increased tortuosity in the eye and gastrointestinal symptoms. Biochemical analysis demonstrated a deficiency of alpha-fucosidase in leucocytes. Case 2 has a greater number of angiokeratomas and has suffered three psychotic episodes. The diagnosis of Fucosidosis was confirmed in cultured skin fibroblast at the age of 12 years. Molecular analysis of the FUCA1 gene showed a heterozygous mutation c.998G > A p.(Gly333Asp), with a pathogenic exon 4 deletion in the other allele in both patients. Conclusion. Fucosidosis presents a wide clinical heterogeneity and intrafamilial variability of symptoms. Psychosis and gastrointestinal symptoms have not been reported previously in Fucosidosis.

Associations between ultra-processed food consumption and kidney function in an older adult population with metabolic syndrome.

BACKGROUND & AIMS: Ultra-processed food (UPF) consumption has increased dramatically over the last decades worldwide. Although it has been linked to some cardiometabolic comorbidities, there is limited evidence regarding kidney function. This study aimed to cross-sectionally and longitudinally assess the association between UPF consumption and estimated-glomerular filtration rate (eGFR) based on Cystatin C (CysC). METHODS: Older adults (mean age 65 ± 5.0 years, 46% women) with overweight/obesity and metabolic syndrome (MetS) who had available data of CysC at baseline (n = 1909), at one-year and at 3-years of follow-up (n = 1700) were analyzed. Food consumption was assessed using a validated 143-item semi-quantitative food frequency questionnaire and UPF consumption (% of g/d) at baseline and changes after one-year of follow-up were estimated according to NOVA classification system. Multivariable-adjusted linear and logistic regression models were performed to evaluate the cross-sectional associations between UPF consumption with eGFR levels and decreased kidney function (eGFR <60 ml/min/1.73 m2) at baseline. Multivariable-adjusted mixed-effects linear regression models were fitted to investigate the associations between one-year changes in UPF and eGFR over 3-years of follow-up. RESULTS: Individuals with the highest baseline UPF consumption showed lower eGFR (ß: -3.39 ml/min/1.73 m2; 95% CI: -5.59 to -1.20) and higher odds of decreased kidney function (OR: 1.64; 95% CI: 1.21 to 2.22) at baseline, compared to individuals in the lowest tertile. Participants in the highest tertile of one-year changes in UPF consumption presented a significant decrease in eGFR after one-year of follow-up (ß: -1.45 ml/min/1.73 m2; 95% CI: -2.90 to -0.01) as well as after 3-years of follow-up (ß: -2.18 ml/min/1.73 m2; 95% CI: -3.71 to -0.65) compared to those in the reference category. CONCLUSIONS: In a Mediterranean population of older adults with overweight/obesity and MetS, higher UPF consumption at baseline and one-year changes towards higher consumption of UPF were associated with worse kidney function at baseline and over 3-years of follow-up, respectively. CLINICAL TRIAL REGISTRY NUMBER: ISRCTN89898870.

Association of adiposity and its changes over time with COVID-19 risk in older adults with overweight/obesity and metabolic syndrome: a longitudinal evaluation in the PREDIMED-Plus cohort.

BACKGROUND: Cross-sectionally, older age and obesity are associated with increased coronavirus disease-2019 (COVID-19) risk. We assessed the longitudinal associations of baseline and changes in adiposity parameters with COVID-19 incidence in older adults at high cardiovascular risk. METHODS: This analysis included 6874 men and women (aged 55-75 years) with overweight/obesity and metabolic syndrome in the PREDIMED-Plus lifestyle intervention trial for cardiovascular risk reduction. Body weight, body-mass-index (BMI), waist circumference, waist-to-height ratio (WHtR), and a body shape index (ABSI) were measured at baseline and annual follow-up visits. COVID-19 was ascertained by an independent Event Committee until 31 December 2021. Cox regression models were fitted to evaluate the risk of COVID-19 incidence based on baseline adiposity parameters measured 5-6 years before the pandemic and their changes at the visit prior to censoring. RESULTS: At the time of censoring, 653 incident COVID-19 cases occurred. Higher baseline body weight, BMI, waist circumference, and WHtR were associated with increased COVID-19 risk. During the follow-up, every unit increase in body weight (HRadj (95%CI): 1.01 (1.00, 1.03)) and BMI (HRadj: 1.04 (1.003, 1.08)) was associated with increased COVID-19 risk. CONCLUSIONS: In older adults with overweight/obesity, clinically significant weight loss may protect against COVID-19. TRIAL REGISTRATION: This study is registered at the International Standard Randomized Controlled Trial (ISRCT; http://www.isrctn.com/ISRCTN89898870 ).

Two-Year Changes in Physical Activity and Concurrent Changes in Cognitive Function in a Cohort of Adults with Metabolic Syndrome.

BACKGROUND: It has been proposed that physical activity (PA) could prevent cognitive decline. OBJECTIVE: To evaluate the association between changes in PA and changes in cognitive function in a cohort of adults with metabolic syndrome. METHODS: Longitudinal observational study including 5,500 adults (mean age 65 years, SD = 5; women = 49.3% ) with metabolic syndrome. Participants underwent physical activity measurements and cognitive evaluation at baseline and at two-years of follow-up. PA was quantified using the Minnesota questionnaire-shortened version. Cognitive function was evaluated using a battery of tests: Mini-Mental Test Examination, Clock Drawing Test, Trail Making Test A and B, Verbal Fluency Test, and Digit Span. The primary outcome was two-year change in cognition, measured through the Global Composite Score (GCS) of all neuropsychological tests. Multivariable-adjusted linear regression models were fitted with baseline PA and their changes as the main exposures and changes in cognitive function as the outcome. RESULTS: No significant association was found between PA levels (or their changes) in the GCS of cognitive function. A greater increase in PA levels was associated with a more favorable two-year change in the Trail Making Test A (Q4 versus Q1: b = - 2.24s, 95% CI -4.36 to -0.12s; p-trend = 0.020). No significant association was found for other neuropsychological test. CONCLUSION: Our results do not support an association between increases in PA and the evolution of the global cognitive function at two-year in an intervention trial which included PA promotion in one of its two randomized arms, but they suggested a possible beneficial effect of PA on attentional function in older adults.

Capacitive platform for real-time wireless monitoring of liquid wicking in a paper strip.

Understanding the phenomenon of liquid wicking in porous media is crucial for various applications, including the transportation of fluids in soils, the absorption of liquids in textiles and paper, and the development of new and efficient microfluidic paper-based analytical devices (µPADs). Hence, accurate and real-time monitoring of the liquid wicking process is essential to enable precise flow transport and control in microfluidic devices, thus enhancing their performance and usefulness. However, most existing flow monitoring strategies require external instrumentation, are generally bulky and unsuitable for portable systems. In this work, we present a portable, compact, and cost-effective electronic platform for real-time and wireless flow monitoring of liquid wicking in paper strips. The developed microcontroller-based system enables flow and flow rate monitoring based on the capacitance measurement of a pair of electrodes patterned beneath the paper strip along the liquid path, with an accuracy of 4 fF and a full-scale range of 8 pF. Additionally to the wired transmission of the monitored data to a computer via USB, the liquid wicking process can be followed in real-time via Bluetooth using a custom-developed smartphone application. The performance of the capacitive monitoring platform was evaluated for different aqueous solutions (purified water and 1 M NaCl solution), various paper strip geometries, and several custom-made chemical valves for flow retention (chitosan-, wax-, and sucrose-based barriers). The experimental validation delivered a full-scale relative error of 0.25%, resulting in an absolute capacitance error of ±10 fF. In terms of reproducibility, the maximum uncertainty was below 10 nl s-1 for flow rate determination in this study. Furthermore, the experimental data was compared and validated with numerical analysis through electrical and flow dynamics simulations in porous media, providing crucial information on the wicking process, its physical parameters, and liquid flow dynamics.

Prognostic Factors Associated with Acute Heart Failure in Patients Admitted for COVID-19: Analysis of the SEMI-COVID-19 Registry.

INTRODUCTION: Since the beginning of the COVID-19 pandemic in March 2020, an intimate relationship between this disease and cardiovascular diseases has been seen. However, few studies assess the development of heart failure during this infection. This study aims to determine the predisposing factors for the development of heart failure (HF) during hospital admission of COVID-19 patients. METHODOLOGY: A retrospective and multicenter study of patients with HF admitted for COVID-19 in 150 Spanish hospitals (SEMI-COVID-19 Registry). A bivariate analysis was performed to relate the different variables evaluated in patients developing heart failure during hospital admission. A multivariate analysis including the most relevant clinical variables obtained in bivariate analyses to predict the outcome of heart failure was performed. RESULTS: A total of 16.474 patients hospitalized for COVID-19 were included (57.5% men, mean age 67 years), 958 of them (5.8%) developed HF during hospitalization. The risk factors for HF development were: age (odds ratio [OR]): 1.042; confidence interval 95% (CI 95%): 1.035-1.050; p < 0.001), atrial fibrillation (OR: 2.022; CI 95%: 1.697-2.410; p < 0.001), BMI > 30 kg/m2 (OR: 1.460 CI 95%: 1.230-1.733; p < 0001), and peripheral vascular disease (OR: 1.564; CI 95%: 1.217-2.201; p < 0.001). Patients who developed HF had a higher rate of mortality (54.1% vs. 19.1%, p < 0.001), intubation rate (OR: 2,36; p < 0.001), and ICU admissions (OR: 2.38; p < 0001). CONCLUSIONS: Patients who presented a higher risk of developing HF were older with cardiovascular risk factors. The risk factors for HF development were age, atrial fibrillation, obesity, and peripheral vascular disease. In addition, patients who developed HF more frequently required to be intubated or admitted to the ICU.

System Based on an Inertial Measurement Unit for Accurate Flight Time Determination in Vertical Jumps.

The world of elite sports has always been characterized by intense competition, where victories are often determined by minimal differences. This means that every little detail in the preparation of top-level athletes is crucial to their performance at the highest level. One of the most significant aspects to monitor is the jumping capacity, as it enables the measurement of performance, progression, and helps prevent injuries. Herein, we present the development of a system capable of measuring the flight time and height reached by the user, reporting the results through a smartphone using an Android ad-hoc application, which handles all the data processing. The system consists of an affordable and portable circuit based on an accelerometer. It communicates with the smartphone via UART using a Bluetooth module, and its battery provides approximately 9 h of autonomy, making it suitable for outdoor operations. To evaluate the system's precision, we conducted performance tests (counter-movement jumps) with seven subjects. The results confirmed the system's potential for monitoring high-level sports training sessions, as the average deviation obtained was only 2.1% (~0.01 s) in the analysis of flight time and 4.6% (~0.01 m) in jump height.

Single cell transcriptomic analysis of Graves' disease thyroid glands reveals the broad immunoregulatory potential of thyroid follicular and stromal cells and implies a major re-interpretation of the role of aberrant HLA class II expression in autoimmunity.

The study of the immune response in thyroid autoimmunity has been mostly focused on the autoantibodies and lymphocytes, but there are indications that intrinsic features of thyroid tissue cells may play a role in disrupting tolerance that needs further investigation. The overexpression of HLA and adhesion molecules by thyroid follicular cells (TFC) and our recent demonstration that PD-L1 is also moderately expressed by TFCs in autoimmune thyroid indicates that TFCs they may activate but also inhibit the autoimmune response. Intriguingly, we have recently found that in vitro cultured TFCs are able to suppress the proliferation of autologous lymphocyte T in a contact-dependent manner which is independent of the PD-1/PD-L1 signaling pathway. To get a more comprehensive picture of TFC activating and inhibitory molecules/pathways driving the autoimmune response in the thyroid glands, preparations of TFCs and stromal cells from five Graves' disease (GD) and four control thyroid glands were compared by scRNA-seq. The results confirmed the previously described interferon type I and type II signatures in GD TFCs and showed unequivocally that they express the full array of genes that intervene in the processing and presentation of endogenous and exogeneous antigens. GD TFCs lack however expression of costimulatory molecules CD80 and CD86 required for priming T cells. A moderate overexpression of CD40 by TFCs was confirmed. GD Fibroblasts showed widespread upregulation of cytokine genes. The results from this first single transcriptomic profiling of TFC and thyroid stromal cells provides a more granular view of the events occurring in GD. The new data point at an important contribution of stromal cells and prompt a major re-interpretation of the role of MHC over-expression by TFC, from deleterious to protective. Most importantly this re-interpretation could also apply to other tissues, like pancreatic beta cells, where MHC over-expression has been detected in diabetic pancreas.

Possible Points of Ulnar Nerve Entrapment in the Arm and Forearm: An Ultrasound, Anatomical, and Histological Study.

BACKGROUND: Ulnar nerve entrapment is one of the most common entrapment neuropathies, usually occurring in the cubital tunnel of the elbow and in Guyon's canal of the wrist. However, it can also occur at other anatomical locations. PURPOSE: Our aim was to review other possible locations of ulnar nerve entrapment in an ultrasound and anatomical study. MATERIAL AND METHODS: Eleven upper limbs from eight adult corpses were ultrasonographically examined and subsequently dissected in a dissection laboratory. Four specific anatomical points were analysed, and any anatomical variations were documented. Moreover, six samples of the nerve were taken for histological analysis. RESULTS: Distinct anatomical relationships were observed during ultrasound and dissection between the ulnar nerve and the medial intermuscular septum, the triceps aponeurosis, Osborne's fascia at the elbow, the arcuate ligament of Osborne and the intermuscular aponeurosis between the flexor carpi ulnaris and the flexor digitorum superficialis muscles. A statistical study showed that these locations are potential areas for ulnar nerve compression. In addition, a fourth head of the triceps brachii muscle was found in some specimens. CONCLUSION: Results demonstrate that ultrasound is a good tool to investigate ulnar nerve entrapment neuropathy and to identify other anatomical points where the nerve can remain compressed.

Uncovering genetic causes of hypophosphatemia.

BACKGROUND: Chronic hypophosphatemia can result from a variety of acquired disorders, such as malnutrition, intestinal malabsorption, hyperparathyroidism, vitamin D deficiency, excess alcohol intake, some drugs, or organ transplantation. Genetic disorders can be a cause of persistent hypophosphatemia, although they are less recognized. We aimed to better understand the prevalence of genetic hypophosphatemia in the population. METHODS: By combining retrospective and prospective strategies, we searched the laboratory database of 815,828 phosphorus analyses and included patients 17-55 years old with low serum phosphorus. We reviewed the charts of 1287 outpatients with at least 1 phosphorus result ≤2.2 mg/dL. After ruling out clear secondary causes, 109 patients underwent further clinical and analytical studies. Among them, we confirmed hypophosphatemia in 39 patients. After excluding other evident secondary causes, such as primary hyperparathyroidism and vitamin D deficiency, we performed a molecular analysis in 42 patients by sequencing the exonic and flanking intronic regions of a panel of genes related to rickets or hypophosphatemia (CLCN5, CYP27B1, dentin matrix acidic phosphoprotein 1, ENPP1, FAM20C, FGFR1, FGF23, GNAS, PHEX, SLC34A3, and VDR). RESULTS: We identified 14 index patients with hypophosphatemia and variants in genes related to phosphate metabolism. The phenotype of most patients was mild, but two patients with X-linked hypophosphatemia (XLH) due to novel PHEX mutations had marked skeletal abnormalities. CONCLUSION: Genetic causes should be considered in children, but also in adult patients with hypophosphatemia of unknown origin. Our data are consistent with the conception that XLH is the most common cause of genetic hypophosphatemia with an overt musculoskeletal phenotype.

Nanoarchitecture factors of solid electrolyte interphase formation via 3D nano-rheology microscopy and surface force-distance spectroscopy.

The solid electrolyte interphase in rechargeable Li-ion batteries, its dynamics and, significantly, its nanoscale structure and composition, hold clues to high-performing and safe energy storage. Unfortunately, knowledge of solid electrolyte interphase formation is limited due to the lack of in situ nano-characterization tools for probing solid-liquid interfaces. Here, we link electrochemical atomic force microscopy, three-dimensional nano-rheology microscopy and surface force-distance spectroscopy, to study, in situ and operando, the dynamic formation of the solid electrolyte interphase starting from a few 0.1 nm thick electrical double layer to the full three-dimensional nanostructured solid electrolyte interphase on the typical graphite basal and edge planes in a Li-ion battery negative electrode. By probing the arrangement of solvent molecules and ions within the electric double layer and quantifying the three-dimensional mechanical property distribution of organic and inorganic components in the as-formed solid electrolyte interphase layer, we reveal the nanoarchitecture factors and atomistic picture of initial solid electrolyte interphase formation on graphite-based negative electrodes in strongly and weakly solvating electrolytes.

Intrinsic Defects and Their Role in the Phase Transition of Na-Ion Anode Na2Ti3O7.

The development of high-power anode materials for Na-ion batteries is one of the primary obstacles due to the growing demands for their use in the smart grid. Despite the appealingly low cost and non-toxicity, Na2Ti3O7 suffers from low electrical conductivity and poor structural stability, which restricts its use in high-power applications. Viable approaches for overcoming these drawbacks reported to date are aliovalent doping and hydrogenation/hydrothermal treatments, both of which are closely intertwined with native defects. There is still a lack of knowledge, however, of the intrinsic defect chemistry of Na2Ti3O7, which impairs the rational design of high-power titanate anodes. Here, we report hybrid density functional theory calculations of the native defect chemistry of Na2Ti3O7. The defect calculations show that the insulating properties of Na2Ti3O7 arise from the Na and O Schottky disorder that act as major charge compensators. Under high-temperature hydrogenation treatment, these Schottky pairs of Na and O vacancies become dominant defects in Na2Ti3O7, triggering the spontaneous partial phase transition to Na2Ti6O13 and improving the electrical conductivity of the composite anode. Our findings provide an explanation on the interplay between intrinsic defects, structural phase transitions, and electrical conductivity, which can aid understanding of the properties of composite materials obtained from phase transitions.

Lessons learnt from the implementation of a colorectal cancer screening programme for lynch syndrome in a tertiary public hospital.

BACKGROUND: Lynch syndrome (LS) is the first cause of inherited colorectal cancer (CRC), being responsible for 2-4% of all diagnoses. Identification of affected individuals is important as they have an increased lifetime risk of multiple CRC and other neoplasms, however, LS is consistently underdiagnosed at the population level. We aimed to evaluate the yield of LS screening in CRC in a single-referral centre and to identify the barriers to its effective implementation. METHODS: LS screening programme included individuals with CRC < 70 years, multiple CRC, or endometrial cancer at any age. Mismatch repair (MMR) protein immunohistochemistry (IHC) analysis was performed in routine practice on the surgical specimen and, if MLH1 IHC was altered, MLH1 gene promoter methylation was analysed. Results were collected in the CRC multidisciplinary board database. LS suspected individuals (altered MMR IHC without MLH1 promoter methylation) were referred to the Cancer Genetic Counselling Unit (CGCU). If accepted, a genetic study was performed. Two checkpoints were included: review of the pathology data and verification of patient referral by a genetic counsellor. RESULTS: Between 2016 and 2019, 381 individuals were included. MMR IHC analysis was performed in 374/381 (98.2 %) CRC cases and MLH1 promoter methylation in 18/21 (85.7 %). Seventeen of the 20 LS suspected individuals were invited for referral at the CGCU. Two cases were not invited and the remaining patient died of cancer before completion of tumour screening. Fifteen individuals attended and a genetic analysis was performed in 15/20 (75 %) LS suspected individuals. Ten individuals were diagnosed with LS, in concordance with the IHC profile (2.7 % of the total cohort). This led to cascade testing in 58/75 (77.3 %) of the available adult relatives at risk, identifying 26 individuals with LS. CONCLUSIONS: Establishing a standardized institutional LS screening programme with checkpoints in the workflow is key to increasing the yield of LS identification.