Initial Loss Research Articles

Incidence and progression of erosive tooth wear according to tooth type in schoolchildren of Mexico City.

This study aimed to estimate the cumulative incidence and the progression of erosive tooth wear (ETW) according to tooth type over a follow-up period of 18 months in adolescents living in Mexico City. We examined 10,776 teeth from 424 participants and used the Basic Erosive Wear Examination index (BEWE) to assess ETW. Our results showed that the overall cumulative incidence rate of ETW was 5.9% (587 from 9933 teeth), and the progression of ETW was 10% (85 from 843 teeth). Notably, the cumulative incidence of initial texture loss (BEWE = 1) was 29.1% for maxillary central incisors, and 30.4% of mandibular first molars progressed to loss of hard tissues (BEWE ≥2).

Impact of Initial Body Weight Loss on Prognosis in Advanced Pancreatic Cancer: Insights From a Single-Center Retrospective Study.

Pancreatic cancer (PC) has a poor prognosis, with body weight loss commonly observed at diagnosis. However, the impact on PC prognosis of weight loss at the time of diagnosis on PC prognosis is unknown. This retrospective, single-center study enrolled consecutively patients diagnosed with metastatic or locally advanced PC or resectable PC who were intolerant of or refused surgery. Patients who had lost more than 5% of their body weight or more than 2% and had a body mass index (BMI) of less than 20kg/m2 at diagnosis were classified as experiencing body weight loss. Patients were subclassified into 2 groups: patients with and without weight loss. The study evaluated patient-related and PC-related factors affecting prognosis. Cox proportional hazards models were used to assess factors affecting prognosis. The primary endpoint was overall survival. Additionally, 1:1 propensity score matching was performed to reduce bias. In total, 220 patients were included in the study. The median age of the patients was 74years, and 49.1% were male. Weight loss at diagnosis was observed in 43.2% of patients. There were no significant differences in clinical factors, except for anthropometric parameters, between the groups. The median survival time did not differ between the weight loss and no weight loss groups (149 and 173days, respectively, P = .669). After matching, no significant differences in survival times were observed between the 2 groups. This study found no association between weight loss at diagnosis and prognosis in patients with advanced PC treated with best supportive care or chemotherapy.

AW-NI-6: MINERALOCORTICOID RECEPTOR ACTIVATION LEADS TO HIGH BLOOD PRESSURE DUE TO BODY POTASSIUM AND WATER LOSS

Objective: Mineralocorticoid receptor (MR) activation is known to reduce renal Na+ elimination and increase body fluid, resulting in arterial hypertension. We have reported earlier that high salt intake, chronic renal failure and psoriasis occur blood pressure increases initiated by body water loss. Here we tested the hypothesis that DOCA treatment induces a similar adaptive water conservation response that also causes arterial hypertension. Design and method: Male C57BL/6J mice on the low-salt diet (<0.1% NaCl) were divided into four groups: tap water (control), tap water with subcutaneous 25 mg DOCA (DOCA), 1% NaCl water with DOCA (DOCA salt), 1.44% NaHCO3 water with DOCA (DOCA NaBic). We performed continuous metabolic cage studies. Na+, K+, and water were measured in mice tissue by desiccation and consecutive dry ashing. Blood pressure was measured by telemetry. We also studied body composition, glucocorticoid-receptor (GR) protein/chromatin interaction, skin blood flow perfusion and renal vascular resistance. Metabolome and key enzyme activities of energy production in kidney, skeletal muscle and in liver were compared between four groups. Results: Compared to control mice, DOCA mice showed increased urine volume, lower urine osmolality and increased blood pressure. DOCA salt developed arterial hypertension within 3 days of the experiment (P < 0.001, Fig. 1A). In DOCA salt mice, K+ and water loss occurs in the initiation phase of arterial hypertension (Fig. 1B), indicating solute and water loss from the intracellular space. Further water loss was then prevented by secondary Na+ accumulation, indicating that the initial MR-driven dehydration reverted back to normal body fluid level by means of Na+ accumulation. Additional physiological adaptation to DOCA salt-driven body water loss included increased vascular resistance (Fig. 1C) and catabolic amino acid breakdown (Fig. 1D). DOCA NaBic mice showed similar massive primary K+ loss and secondary Na+ retention, but no arterial hypertension occurred (Fig. 1A). While DOCA salt decreased skin blood flow, DOCA NaBic increased it (Fig. 1C). DOCA salt mice showed renal glutamine catabolism as well as muscle protein catabolism (Fig. 1D). This catabolic state was coupled with glucocorticoid receptor binding in skeletal muscle. Conclusions: DOCA salt leads to pronounced initial K+ and water loss with hypertension. Na+ retention occurs only secondarily and is a compensatory response that reverts initial body water loss back to normal body water levels. Additional NaBic feeding reveals that the blood pressure level in mice with MR activation is determined by changes in blood flow independent of body Na+ or water content.

Glucocorticoid receptor (NR3C1) genetic polymorphisms and the outcomes of sudden sensorineural hearing loss

BackgroundThe glucocorticoid receptor gene (NR3C1) encodes the receptor to which cortisol and other glucocorticoids bind. Steroids in either oral, intratympanic, or intravascular forms are the treatment of choice for sudden sensorineural hearing loss (SSNHL), but the outcome varies. The outcomes of SSNHL have been investigated for related factors, including age, initial hearing loss severity and pattern, vertigo, genetic variations, and the time between onset and treatment. The objective of the present study was to analyze the association of genetic polymorphisms of NR3C1 with the outcomes of SSNHL.Materials and methodsWe conducted a comparison study of 93 cases with a poor outcome (control) and 100 cases with a good outcome (case) in SSNHL patients. Six single nucleotide polymorphisms (SNPs) were selected. The genotypes were determined using TaqMan technology.ResultsThe heterozygous AT genotype of rs17100289 was associated with a poor outcome in comparison with the major homozygous AA genotype after adjustments for age and sex (OR = 0.50; 95% CI 0.26–0.95; P = 0.035) in SSNHL patients. The CT genotype of rs4912912 was also associated with a poor outcome compared with the major homozygous TT genotype after the adjustments (OR = 0.47; 95% CI 0.24–0.92; P = 0.026).ConclusionThese results suggest that NR3C1 genetic polymorphisms may influence the outcomes of SSNHL.Graphical

The Predictors of Posttraumatic Stress Symptoms in Recovered COVID-19 Patients: Illness-Related Factors, Depressive and Anxiety Symptoms, Alexithymia and Social Support

Objective: The COVID-19 pandemic had a profound impact on millions of people, affecting their biological, psychological, and social well-being. The biological effects of SARS-CoV-2 have reportedly been linked to cognitive, emotional, and behavioral symptoms. Traumatic experiences associated with the disease and treatment procedures are regarded as potential risk factors for the emergence of posttraumatic stress symptoms (PTSS); as a result, the severity of the disease and the experience of hospitalization can significantly influence the mental well-being of individuals who have contracted COVID-19. This study aims to assess the factors that influence the development of PTSS among individuals who have recovered from COVID-19. Method: Sociodemographic features, hospitalization status, and physical symptoms of COVID-19 were assessed and PTSS, alexithymia, perceived social support, anxiety, and depression were examined with validated self-report questionnaires (Impacts of Events Scale-Revised, Toronto Alexithymia Scale-20, The Multidimensional Scale of Perceived Social Support, Hospital Anxiety and Depression Scale) in a sample with 105 inpatients and 107 outpatients. Results: PTSS and depression scores of inpatients and outpatients were not significantly different (t(210)=1.246, p=0.214, and t(210)=-0.493, p=0.623, respectively), however, anxiety scores of outpatients were higher (t(209.880)=-2.938, p=0.004). Hospitalization did not significantly affect avoidance and hyperarousal symptoms but was associated with increased intrusion symptoms (t(210)=2.095, p=0.037). In a hierarchical regression model, predictors of PTSS were identified; in step 3 sleep disturbance and initial loss of smell and taste were significant factors (β=0.282, p<0.010; β=0.163, p=0.019, respectively). In step 4, the effects of depression, anxiety, and alexithymia were superior to all other variables (β=0.211, β=0.318, β=0.261, respectively, p<0.010) and initial loss of smell and taste and sleep disturbance did not remain significant in the final model. The final results indicated that psychological assessments made a distinctive contribution to the overall variation in Impacts of Events Scale-Revised scores, extending beyond demographic characteristics, individual variations, and COVID-19 symptoms. Additionally, social support had an indirect impact on PTSS, which was mediated by anxiety, depression, and alexithymia (total bunstd=-0.446, S.E.boot=0.057, CIboot 95% (-0.563, -0.338)). The direct effect of social support on PTSS was non-significant (cunstd=-0.004, S.E.=0.072, CI 95% (-0.146, 0.137)). Conclusion: This study contributes to the literature about the worldwide effects of COVID-19 on mental trauma by establishing the possible predictors for PTSS; and highlights the importance of reflecting on the COVID-19 history of patients and providing appropriate support.

Li2Se as cathode additive to prolong the next generation high energy lithium-ion batteries

The initial lithium loss caused by the formation of solid electrolyte interface (SEI) is a critical issue that reduces the energy density of lithium-ion batteries (LIBs). In order to offset the initial capacity loss, herein we propose lithium selenide (Li2Se) as an effective cathode prelithiation agent, which has a high “donor” Li-ion capacity, poor reversibility, relatively low delithiation potential and good compatibility to the existing cell fabrication processes. In a LiNi0.8Co0.1Mn0.1O2 (NCM)/ Si-C-Gr full cell, a high initial charge capacity of 250 mAh/g is obtained with 7% Li2Se additive, and the discharge capacity is 188.2 mAh/g (10.3 mAh/g higher than that of the pristine counterpart). The released capacity from Li2Se can offset the initial capacity loss during the SEI formation, confirmed by the enhanced discharged capacity. In addition, it can serve as a “lithium bank” to compensate the Li loss caused by the ongoing SEI breakage and reformation of Si-C-Gr anodes, leading to an improved cycling stability. The reversible capacity of the full cell with Li2Se prelithiation additives remains 152 mAh/g after 150 cycles at 0.3C, with an increase of 37.1% as compared to the counterpart without the additive. Li2Se is a promising cathode prelithiation agent especially for future advanced battery systems involving high specific capacity anodes with large initial irreversible capacity and poor cycling performance.

Improvement of cycling stability of high energy density LiNi0.83Co0.12Mn0.05O2/silicon-graphite batteries via cathode prelithiation agent

Li2NiO2 is used as cathode prelithiation additive to improve the electrochemical performance of high energy density LiNi0.83Co0.12Mn0.05O2/silicon-graphite (NCM811/SiG) batteries. Li2NiO2 (LNO) provides an irreversible capacity of 294.7 mAh/g with a columbic efficiency of 30.8%. Comparative tests show that Li2NiO2 additive can reduce the initial Li loss, stabilize the layered structure and inhibit the dissolution of transition metal ions of LiNi0.83Co0.12Mn0.05O2 cathode. NCM811/SiG pouch cell (6 A h) with an optimized addition level of 8 wt% LNO exhibits an excellent electrochemical performance, delivering an initial discharge capacity of 6.13 A h with a capacity retention of 80.9% after 700 cycles at 1C.

In Situ Surface Coating and Oxygen Vacancy Dual Strategy Endowing a Li-Rich Li1.2Mn0.55Ni0.11Co0.14O2 Cathode with Superior Lithium Storage Performance

Lithium-rich Mn-based cathode materials are widely regarded as the next-generation cathode materials for high-energy-density lithium-ion batteries owing to their low cost and high specific capacity. Nonetheless, their commercial application is seriously hindered by low initial Coulombic efficiency, capacity loss, and voltage drop during long-term cycling. Herein, surface phosphorus doping and a mixture protective layer with oxygen vacancies (OVs) which consists of Li3PO4 and LiMnPO4 as a surface-coating layer on the Li1.2Mn0.55Ni0.11Co0.14O2 cathode material through a facile solid–gas reaction treatment, which can simultaneously optimize the surface chemical structure and deplete lithium impurity, is proposed. What is more, the dual strategy of surface engineering and OVs can improve electronic conductivity and regulate the ion diffusion rate. The dual-modified sample expresses a discharge capacity of 180.9 mA h g–1 with a capacity retention of 89.2% at 0.5 C after 250 cycles, which is better than that of the pristine sample (63.7%). This work provides a facile and effective method for surface coating design to improve other Li-rich manganese-based cathodes for rechargeable batteries.

Validation of Rates of Mean Deviation Change as Clinically Relevant End Points for Glaucoma Progression

To investigate whether rates of standard automated perimetry (SAP) mean deviation (MD) over an initial 2-year follow-up period were predictive of events of visual field progression over an extended follow-up. Longitudinal, prospective, observational study. Two hundred forty-six eyes of 168 patients with glaucoma followed up every 6 months for up to 5 years. Patients were required to have a minimum of 5 reliable SAP tests during the first 2 years of follow-up. Events of progression were evaluated using 2 methods: Guided Progression Analysis (GPA; Carl Zeiss Meditec, Inc) and a United States Food and Drug Administration (FDA)-suggested end point. The date of the first test showing progression after the first 2 years was considered to be the event date. Rates of change in SAP MD were calculated for the first 2 years of follow-up, and joint longitudinal survival models were used to assess the risk of faster initial MD loss for subsequent progression based on each event analysis. Risk of having an event of progression based on initial rates of SAP MD change. Fifty-six eye (22.8%) showed an event of progression by the GPA and 51 eyes (20.7%) did so by the FDA end point. Each 0.1-dB/year faster rate of SAP MD loss in the first 2 years was associated with a 26% increase in risk of a GPA progression end point developing (R2= 76%) and 32% risk of an FDA-based end point developing (R2= 83%). A reduction of 30% in the rate of MD change in the first 2 years was associated with a 20% reduction in the cumulative probability of a progression event developing over 5 years of follow-up. Rates of SAP MD change for eyes with glaucoma calculated over the initial 2 years of follow-up were strongly predictive of events of progression over subsequent follow-up. Our findings give support for the use of slopes of MD change as suitable end points of progression in clinical trials. Proprietary or commercial disclosure may be found after the references.

Electrochemical characterization of evolving ionomer/electrocatalyst interactions throughout accelerated stress tests

The degradation of polymer electrolyte membrane fuel cells (PEMFCs) catalyst layers used for heavy-duty vehicles was examined using a catalyst-specific accelerated stress test (AST). High surface area carbon supported dispersed Pt (Pt/HSC), annealed Pt (a-Pt/HSC) and PtCo (PtCo/HSC) alloy catalysts were examined over the course of 90,000 cycles by measuring changes in mass activity, O2 transport resistance, electrochemical active surface area (ECSA), catalyst accessibility and ionomer-electrocatalyst interactions. Compared to a-Pt/HSC and Pt/HSC catalyst, the PtCo/HSC showed better initial mass activity, a larger initial mass transport loss, and faster degradation after the first 30k AST cycles, as a large portion of Co leached out during potential cycling. Pt/HSC showed higher initial performance relative to a-Pt/HSC but had faster degradation. STEM characterizations show that the ECSA losses are largely related to Pt dissolution resulting in either catalyst particle growth via the Ostwald ripening mechanism or redeposition in the membrane. Catalyst accessibility measurements showed decreased RH sensitivity for all three samples, while CO impedance measurements revealed a decrease in both Pt-water and carbon-water interactions. This implies that, Pt is either preferentially redepositing on the exterior of the carbon support, or that the ionomer is undergoing morphological changes enabling the enhanced intrusion of mesopores.

Clinical Value of a Novel Magnetic Resonance Imaging Protocol and Prognostic Model Establishment for Sudden Sensorineural Hearing Loss: A Prospective Study

Introduction: Sudden sensorineural hearing loss (SSNHL) is one of the most common acute symptoms in the otolaryngology department. Etiological diagnosis is the premise of effective treatment of SSNHL, and prognostic evaluation is the key. However, most of the patients are diagnosed as idiopathic due to a lack of overall assessment, while prognostic factors of SSNHL are numerous and controversial. Our purpose was to validate the potential value of a novel three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) MR protocol in SSNHL and to establish a clinical-image prognostic model for unilateral SSNHL. Methods: This prospective study included consecutive patients from May 2019 to November 2021. Pathogenic diagnosis relied on expertise-based estimation and the associations of MR findings with clinical features of unilateral SSNHL were assessed. The prognostic evaluation of unilateral SSNHL was adopted for recovery and no recovery groups and complete and incomplete recovery groups. Significant clinical and MR features were compared and screened out by single-factor analyses. The primary clinical-image prognosis assessment model was built by multifactor logistic regression analyses. Results: A total of 101 patients were enrolled in our study who acquired the correct etiological diagnosis based on the novel 3D-FLAIR MR combined with clinical examination. Among the 93 patients with unilateral SSNHL, 30.1% (28/93) showed labyrinthine abnormalities on 3D-FLAIR images. The severity of initial hearing loss in the MR+ group was worse than that in the MR− group (p < 0.05), and patients with positive MR findings tended to have poor recovery. An excellent prognostic model was built for hearing complete recovery and no recovery. The combination of three independent risk factors, including abnormal distortion products otoacoustic emission and transient evoked otoacoustic emission, the period from onset to treatment, and PTA at the onset, was adopted for hearing recovery/no recovery (accuracy = 90.2%, AUC = 0.820). Furthermore, adding the factor of positive MRI findings could improve the confidence for the judgment of hearing no recovery. The only independent risk factor, PTA at the onset, was adopted for complete/incomplete hearing recovery (accuracy = 86.1%, AUC = 0.874). Conclusion: The novel MR protocol had a good advantage in pathogenic diagnosis. Labyrinthine MR 3D-FLAIR signal abnormalities were related to the severity of an initial hearing loss and had a greater tendency to be found in patients with no recovery. A prognostic model with two main steps of unilateral SSNHL, mainly for SSNHL with no recovery and complete recovery, was built successfully and needed further verification by larger series of patients.

Feasibility of Prelithiation in LiFePO4

AbstractLithium iron phosphate (LiFePO4) is widely applied as the cathode material for the energy storage Li‐ion batteries due to its low cost and high cycling stability. However, the low theoretical specific capacity of LiFePO4 makes its initial capacity loss more concerning. Therefore, lithium compensation by way of prelithiation and applications of sacrificial Li‐rich additives in LiFePO4 is imminent in elevating the energy density and/or prolonging the lifetime of the LiFePO4‐based Li‐ion batteries (LIBs). Prelithiation in LiFePO4 is herein carried out by electrochemical and chemical methods and its feasibility is proved on the basis of the electrochemical evaluations such as the initial charge capacity and the cycling stability. In addition, the site of the pre‐intercalated Li‐ions is found via comprehensive physical characterizations and the density functional theory (DFT) calculations. These findings open a new avenue for elevating the energy density and/or prolonging the lifetime of the high‐energy‐density batteries.

Toward Models of Impact and Recovery of the US Western Grid from Earthquake Events

A Cascadia Subduction Zone (CSZ) earthquake will cause widespread damage to numerous lifelines and infrastructure along the northern US west coast. The goal of the presented research is to provide a bottom up estimate of the impact on and subsequent recovery of a Cascadia Subduction Zone earthquake on the US western grid to supplement and enhance the expert opinion estimates provided to date. The scope is limited to only consideration of shaking damage to utility substation equipment components of a power system model. The analysis utilizes probabilistic models of damage and recovery for substation power system assets, along with graph techniques for modeling connectivity, and Monte Carlo quasi steady state power flow solutions. The results show that a conservative estimate of the initial damage and loss of load is approximately 4000 MW, with a recovery estimate of 230 days.

Insufficient sleep predicts poor weight loss maintenance after 1 year.

Insufficient sleep may attenuate weight loss, but the role of sleep in weight loss maintenance is unknown. Since weight regain after weight loss remains a major obstacle in obesity treatment, we investigated whether insufficient sleep predicts weight regain during weight loss maintenance. In a randomized, controlled, two-by-two factorial study, 195 adults with obesity completed an 8-week low-calorie diet and were randomly assigned to 1-year weight loss maintenance with or without exercise and liraglutide 3.0 mg/day or placebo. Sleep duration and quality were measured before and after the low-calorie diet and during weight maintenance using wrist-worn accelerometers (GENEActiv) and Pittsburgh Sleep Quality Index (PSQI). To test associations between insufficient sleep and weight regain, participants were stratified at randomization into subgroups according to sleep duration (</≥6 h/night) or sleep quality (PSQI score ≤/>5). After a diet-induced 13.1 kg weight loss, participants with short sleep duration at randomization regained 5.3 kg body weight (p = .0008) and had less reduction in body fat percentage compared with participants with normal sleep duration (p = .007) during the 1-year weight maintenance phase. Participants with poor sleep quality before the weight loss regained 3.5 kg body weight compared with good quality sleepers (p = .010). During the weight maintenance phase, participants undergoing liraglutide treatment displayed increased sleep duration compared with placebo after 26 weeks (5 vs. -15 min/night) but not after 1 year. Participants undergoing exercise treatment preserved the sleep quality improvements attained from the initial weight loss. Short sleep duration or poor sleep quality was associated with weight regain after weight loss in adults with obesity.

VATS in Thorax Trauma

Since the early 1990s, video-assisted thoracoscopy (VATS) has been increasingly established for a variety of indications in the treatment of patients with thoracic trauma. During this time, one premise for the use of thoracoscopy has not changed. Its use is consistently recommended only for trauma patients with stable circulation and respiration. To define the indications of VATS for use in thoracic trauma, the Pulmonary Injury Group - as part of the Working Committee for Thoracic Trauma of the German Society for Thoracic Surgery (DGT) and the German Society for Trauma Surgery (DGU) - has developed treatment recommendations based on a current literature review (based on the PRISMA Checklist/here: MEDLINE via PubMed from 1993 to 2022). In the present study, after reviewing the available literature, the indications for VATS in the care of thoracic trauma were identified, in order to formulate clinical recommendations for the use of VATS in thoracic trauma. The analysis of 1679 references identified a total of 4 randomised controlled trials (RCTs), 4 clinical trials, and 5 meta-analyses or systematic reviews and 39 reviews, which do not allow a higher level of recommendation than consensual recommendations, due to the low evidence of the available literature. Over the past 30 years, stabilisation options in the care of trauma patients have improved significantly, allowing expansion of indications for the use of VATS. Moreover, the recommendation for more than 50 years to thoracotomise trauma patients in case of an initial blood loss ≥1500ml via the inserted chest drainage or in case of continuous blood loss ≥250ml/h over 4h is now only relative with today's better stabilisation measures. For unstable/non-stabilisable patients with a thoracic injury requiring emergency treatment, thoracotomy remains the method of choice, while VATS is recommended for a wide range of indications in the diagnosis and treatment of stable patients with a penetrating or blunt thoracic trauma. The indications for VATS are persistent haemothorax, treatment of injuries and haemorrhages to the lung, diaphragm, thoracic wall and other organ injuries, and in the secondary phase, treatment of thoracic sequelae of injury (empyema, persistent pulmonary fistula, infected atelectasis, etc.).

Abutment removal torque and implant conical surface morphological changes after standardized artificial aging: An in vitro study

Statement of problemZirconia abutments have become popular as they provide favorable esthetic outcomes. However, studies investigating how abutment material affects abutment screw torque performance and implant conical surface morphological changes in internal conical connection systems are scarce. PurposeThe purpose of this in vitro study was to investigate the influence of abutment material on abutment removal torque and implant conical surface morphological changes in internal conical connection implant–abutment assemblies of 2 diameters after simulated long-term oral use. Material and methodsThirty abutments of 3 materials (1-piece titanium, 1-piece zirconia, zirconia with alloy base) and 2 diameters (regular, narrow) made by the original manufacturer were connected to internal conical connection implants and subjected to a standardized artificial aging process consisting of thermal cycling and mechanical cyclic loading with parameters corresponding to anterior and posterior mastication scenarios simulating long-term oral use. An abutment removal torque test was done before and after aging. Morphological changes in the implant conical contact surface were observed with a scanning electron microscope (SEM). Initial and after-aging torque loss values were calculated and analyzed separately with 1-way ANOVA and Tukey HSD post hoc tests (α=.05). ResultsAll specimens survived artificial aging. For initial and after-aging torque loss, the 1-piece zirconia groups showed significantly greater values (P<.001) for both diameters. In the SEM observation, the 1-piece zirconia groups showed distinct widespread surface damage while the other groups exhibited only minor damages. ConclusionsRegardless of diameter, 1-piece zirconia abutments tend to induce more abutment removal torque loss and implant conical surface morphological changes than those with metal connections, both initially and after simulated long-term oral use. Zirconia abutments with an alloy base performed similarly to 1-piece titanium abutments.

Experience with the ketogenic diet in premature neonates.

The ketogenic diet is a time-tested, potent, nonpharmacological treatment of epilepsy. However, the use of the ketogenic diet in premature neonates with epilepsy has not been previously reported. We share our experience with the use of ketogenic diet therapy in two premature neonates. Two identical twin premature neonates with SCN2A-related developmental and epileptic encephalopathy, whose seizures were refractory to multiple anti-seizure medications, were started on the classic ketogenic diet at the conceptual age of 35 weeks. Ketosis was achieved and maintained (range 2-5 mmol/L of serum beta-hydroxybutyrate level). Seizure frequency was significantly reduced (>90% reduction in both patients), and some anti-seizure medications were able to be discontinued. Initial transient weight loss and one episode of asymptomatic hypoglycemia were observed and corrected. The ketogenic diet was found to be a safe, well-tolerated, and effective treatment for seizures in two premature neonates. The side effects are tolerable and correctable. The ketogenic diet, therefore, is a treatment option for refractory seizures in this age group, when administered under expert guidance.

Two progression patterns in Alzheimer's disease identified from structural MRI in a memory clinic‐based cohort

AbstractBackgroundAlzheimer’s disease (AD) is known to be heterogeneous in pathobiology and clinical manifestation. Most previous studies demarcating AD subtypes rely on data‐driven clustering methods that are likely confounded by interindividual differences in disease progression within samples. Addressing this problem, we aim to identify and characterize distinct AD atrophy progression patterns in a memory clinic‐based cohort.Method N = 914 subjects (296 cognitively unimpaired, 366 with subjective cognitive impairment, 153 with mild cognitive impairment, and 99 with AD dementia) from the multicenter observational DZNE Longitudinal Cognitive Impairment and Dementia Study (DELCODE) were included. The Subtype and Stage Inference algorithm (Young et al., 2018, Nat. Commun.) was applied to ROI‐based cortical thickness and gray matter volume data obtained from T1w and T2w 3T‐MRI using FreeSurfer. Subtypes were characterized in demographics, ApoE genotype, various fluid biomarkers, and cognition.ResultTwo atrophy subtypes were identified. A limbic‐predominant subtype exhibited initial volume loss in the amygdala and hippocampus, followed by cortical thinning in the medial temporal, temporal, frontal, parietal, and occipital lobes. Contrary, in a hippocampal‐sparing subtype, cortical thinning first occured in the frontal, parietal, and occipital lobes before the temporal and medial temporal lobes, hippocampus, and amygdala were affected. Compared to the hippocampal‐sparing subtype, the limbic‐predominant subtype included subjects who were older, reported fewer years of education, and tended to have more ApoE e4 alleles, higher risk of vascular pathology, and higher plasma neurofilament light levels. The subtypes differed in their CSF biomarker profiles indicating higher β‐amyloid and tau burden in the limbic‐predominant subtype. In the limbic‐predominant subtype, cognitive impairment was accentuated in the learning and memory as well as language domains. Belonging to the hippocampal‐sparing subtype was associated with an impairment in executive functions and processing speed, visuospatial functions, and working memory.ConclusionWe provide evidence on atrophy heterogeneity that is largely in line with previous theoretical and empirical contributions while overcoming key limitations that are commonly faced in earlier studies. Heterogeneity may have substantial impact even in cohort studies designed to primarily include “typical” amnestic AD which highlights the need for optimized and subtype‐specific measures of early detection and disease progression.

Role of Müller cells in cone mosaic rearrangement and retinal remodelling in photoreceptor degenerations

AbstractPhotoreceptor degenerative diseases (e.g., retinitis pigmentosa or age‐related macular degeneration) are currently one of the leading causes of irreversible blindness in the world. Although their pathophysiological mechanisms may vary, they all share some features such as initial photoreceptor loss associated with glial activation and subsequent retinal remodelling. It is well known that glial activation is an early feature of photoreceptor degenerations that is involved in retinal remodelling, which, in turn, is thought to be the cause of the secondary death of the retinal ganglion cells. The mammalian retina contains three types of glial cells. Two types of macroglial cells: astrocytes and Müller cells, and microglial cells. Of them, Müller cells appear to be involved in the reorganization of the photoreceptor mosaic in empty rings of photoreceptor degeneration in the early stages of photoreceptor loss. Müller cells are the principal glial cells in the retina with a wide range of physiological and retinal structural support functions. The basic morphological scheme of Müller cells consists of a soma located in the inner nuclear layer from which an inner and an outer trunk emerge. The inner trunk contributes to the formation of the inner limiting membrane, and the outer trunk divides into complex rootlets spanning photoreceptor nuclei and finally forming the outer limiting membrane of the retina. In the early stages of photoreceptor degeneration, macroglial cell reactivity, namely increased expression of glial fibrillary acidic protein (GFAP) and Müller cells hypertrophy, leads to the formation of a glial scar or glial seal by hypertrophic Müller cell processes in the outer retina that may be related to the formation of empty rings of photoreceptor degeneration. Interestingly, Müller cells extend their external processes horizontally and radially within the rings of photoreceptor degeneration, filling the empty space left by dead photoreceptors. These rings become larger as photoreceptor loss increases, which suggests that they are the result of photoreceptor loss. As rings increase in size and, eventually, merge, the increased expression in the processes of Müller cells continues in the periphery of the rings. Perhaps in an attempt to complete the glial seal to isolate the remnant of the neural retina from the retinal pigment epithelium and choroid which, in turn, may represent a physical barrier to axonal regrowth and migration and therefore may impede the success of therapies aimed at replacing or substituting photoreceptors. Indeed, as photoreceptor loss progresses, the glial sea is more evident, covering large areas of the retina. Although the exact function of the glial seal is not known at this stage, it is thought that it may have a mechanical function in conferring some stability to the retina during the course of degeneration, but also a protective function, since in the later stages of retinal remodelling, focal gaps in the glial seal may allow the migration of retinal pigment epithelium cells to the inner retina, triggering a series of progressive events that eventually cause retinal ganglion cell death.

Association of short-term and long-term weight loss with the risk of major adverse cardiovascular disease: Community-based cohort study

BackgroundThis study evaluated temporal association of changes in BMI over time with major adverse cardiovascular event (MACE) in Korean middle-aged adults. MethodsBetween 2001 and 2002, 6855 individuals from the Korean Genome and Epidemiology Study were included and followed up until 2014. The main predictor was the change in BMI determined using group-based trajectory modelling (decreasing, stable, and increasing) from the baseline to 4-, 6-, and 8-years of follow-up. The primary outcome was the occurrence of MACE. ResultsDuring the mean 10.2 years follow-up, MACEs occurred in 350 (5.1 %) individuals. The median (interquartile rage) age of study population was 50 (44–59) years. In primary analysis with 4-year trajectory model, decreasing BMI trajectory was associated with a 1.41-fold higher risk of the MACEs (hazard ratio [HR], 1.41; 95 % confidence interval [CI], 1.06–1.91) compared with stable BMI trajectory. In secondary analyses with 6- and 8-year trajectory models, this association disappeared, and the corresponding HRs (95 % CIs) were 1.14 (0.81–1.61) and 0.98 (0.65–1.49), respectively. There were concomitant improvements in cardiometabolic risk factors in decreasing BMI group, but unfavorable risk burden remained up to 4 to 6 years. ConclusionsThe initial 4-year weight loss was paradoxically associated with a higher risk of MACEs, probably due to residual cardiovascular burden. However, this association became null in participants with sustained weight loss ≥ 6 years, suggesting a possible lag effect of weight loss on MACEs.