Search Results (1,900)

Background: Comorbid personality disorders (PDs) in patients with anorexia nervosa (AN) are associated with increased psychopathology, higher suicide risk, and poorer treatment response and outcomes. This study aimed to examine associations between gray matter (GM) volume and PDs in female adolescents with AN before and after short-term psychotherapeutic and nutritional therapy. Methods: Eighteen female adolescents with acute AN, mean age 15.9 years, underwent 3T magnetic resonance imaging before and after weight restoration. The average interval between scans was 2.6 months. Structural brain changes were analyzed using voxel-based morphometry. PDs were assessed using the Structured Clinical Interview for DSM-IV Axis II Disorders (SCID II) and the Assessment of Identity Development Questionnaire. Results: SCID-II total scores showed significant positive associations with GM volume in the mid-cingulate cortex at both time points and in the left superior parietal–occipital lobule at baseline. The histrionic subscale correlated with GM volume in the thalamus bilaterally and the left superior parietal–occipital lobule in both assessments, as well as with the mid-cingulate cortex at follow-up. Borderline and antisocial subscales were associated with GM volume in the thalamus bilaterally at baseline and in the right mid-cingulate cortex at follow-up. Conclusions: PDs in female adolescent patients with AN may be specifically related to GM alterations in the thalamus, cingulate, and parieto-occipital regions, which are present during acute illness and persist after weight restoration therapy. Full article

This study describes and validates a novel method for assessing anterior crystalline lens curvature along vertical and horizontal meridians using radial measurements derived from Scheimpflug imaging. The aim was to evaluate whether pupil diameter (PD), anterior lens curvature, and anterior chamber depth (ACD) change during accommodation and whether these changes are age-dependent. A cross-sectional study was conducted on 104 right eyes from healthy participants aged 21–62 years. Sixteen radial images per eye were acquired using the Galilei Dual Scheimpflug Placido Disk Topographer under four accommodative demands (0, 1, 3, and 5 dioptres (D)). Custom software analysed lens curvature by calculating eccentricity in both meridians. Participants were analysed as a total group and by age subgroups. Accommodative amplitude and monocular accommodative facility were inversely correlated with age. Both PD and ACD significantly decreased with higher accommodative demands and age. Relative eccentricity decreased under accommodation, indicating increased lens curvature, especially in younger participants. Significant curvature changes were detected in the horizontal meridian only, although no statistically significant differences between meridians were found overall. The vertical meridian showed slightly higher eccentricity values, suggesting that it remained less curved. By enabling detailed, meridionally stratified in vivo assessment of anterior lens curvature, this novel method provides a valuable non-invasive approach for characterizing age-related biomechanical changes during accommodation. The resulting insights enhance our understanding of presbyopia progression, particularly regarding the spatial remodelling of the anterior lens surface. Full article

It is well established that combining exercise with medication may benefit functionality in individuals with PD (Parkinson’s disease). However, the long-term evolution of gait biomechanics under this combination remains poorly understood. Objectives: This study aims to analyze the evolution of spatiotemporal gait parameters, kinetics, and kinematics throughout a long-term exercise program conducted in water and on dry land. Methods: We have compared the trajectories of biomechanical variables across the treatment phases using statistical parametric mapping (SPM). A cohort of fourteen individuals with PD (mean age: 65.6 ± 12.1 years) participated in 24 sessions of aquatic exercises over three months, followed by a three-month retention phase, and then 24 additional sessions of land-based exercises. Three-dimensional gait data and spatiotemporal parameters were collected before and after each phase. Two-way ANOVA with repeated measures was used to compare spatiotemporal parameters. Results: The walking speed increased while the duration of the double support phase decreased. Additionally, the knee extensor moment consistently increased in the entire interval from midstance to midswing (20% to 70% of the stride period), approaching normal gait patterns. Regarding kinematics, significant increases were observed in both hip and knee flexion angles. Furthermore, the abnormal ankle dorsiflexion observed at the foot strike disappeared. Conclusions: These findings collectively suggest positive adaptations in gait biomechanics during the observation period. Full article

Background/Objectives: Neurodegenerative proteinopathies, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and dementia with Lewy bodies (DLB), are increasingly prevalent worldwide mainly due to population aging. These conditions are marked by complex etiologies, overlapping pathologies, and progressive clinical decline, with significant consequences for patients, caregivers, and healthcare systems. This review aims to synthesize evidence on the healthcare complexities of major neurodegenerative proteinopathies to highlight current knowledge gaps, and to inform future care models, policies, and research directions. Methods: We conducted a comprehensive literature search in PubMed/MEDLINE using combinations of MeSH terms and keywords related to neurodegenerative diseases, proteinopathies, diagnosis, sex, management, treatment, caregiver burden, and healthcare delivery. Studies were included if they addressed the clinical, pathophysiological, economic, or care-related complexities of aging-related neurodegenerative proteinopathies. Results: Key themes identified include the following: (1) multifactorial and unclear etiologies with frequent co-pathologies; (2) long prodromal phases with emerging biomarkers; (3) lack of effective disease-modifying therapies; (4) progressive nature requiring ongoing and individualized care; (5) high caregiver burden; (6) escalating healthcare and societal costs; and (7) the critical role of multidisciplinary and multi-domain care models involving specialists, primary care, and allied health professionals. Conclusions: The complexity and cost of neurodegenerative proteinopathies highlight the urgent need for prevention-focused strategies, innovative care models, early interventions, and integrated policies that support patients and caregivers. Prevention through the early identification of risk factors and prodromal signs is critical. Investing in research to develop effective disease-modifying therapies and improve early detection will be essential to reducing the long-term burden of these disorders. Full article

This study investigated the effects of six cap management protocols targeting contrasting oxidation-reduction potential (ORP) evolutions during alcoholic fermentation of Pinot noir wines. Treatments included twice-daily punch-downs (PD) and pump-overs (PO), 1 h air or N₂ injections (AirMix, N₂Mix), air injections triggered by ORP ≤ −40 mV (RedoxConAir), and equal N₂ injections concurrent to RedoxConAir wines (RedoxConN₂). AirMix wines maintained ORP values above 0 mV throughout fermentation, showed an oxidatively favored glutathione-to-glutathione disulfide ratio (GSH:GSSG) of 0.3:1, and had 21% lower total phenolics and 24% lower anthocyanins than PD wines. In contrast, N₂Mix wines maintained the lowest ORP, near −100 mV, and showed a reductively favored GSH:GSSG ratio (7:1). PD wines extracted 48% more flavan-3-ols than PO wines, consistent with greater berry integrity disruption and seed submersion. Volatile composition was also impacted: ethyl n-octanoate showed the highest OAV among esters, ranging from 147 in PO wines to 116 in AirMix wines. Results suggest the GSH:GSSG ratio served as an indicator of redox history, with potential implications for color and aroma preservation during aging. Inert gas mixings resulted in equal or greater total phenolic content, while excessive air injections may provide a tool to soften astringency. Full article

Background/Objectives: Restored CD4 absolute counts (CD4AC) and CD4/CD8 ratio in the setting of continuous antiretroviral treatment (ART) do not exclude a low-level immune activation associated with HIV reservoirs, microbial translocation, or the side effects of ART itself, which accelerates the aging of people living with HIV (PLHIV). To delineate biomarkers of incomplete immune restoration in PLHIV on successful ART, we evaluated T-lymphocyte mitochondrial parameters in relation to phenotypic markers of immune exhaustion and senescence. Methods: PLHIV with sustained viral suppression, CD4AC > 500 and CD4/CD8 ratio >0.9 on ART (n = 39) were compared to age-matched ART-naïve donors (n = 27) and HIV(–) healthy controls (HC, n = 35). CD4 and CD8 differentiation and effector subsets (CCR7/CD45RA and CD27/CD28), activation, exhaustion, and senescence markers (CD38, CD39 Treg, CD57, TIGIT, and PD-1) were determined by flow cytometry. Mitochondrial mass (MM) and membrane potential (MMP) of CD8 and CD4 T cells were evaluated with MitoTracker Green and Red flow cytometry dyes. Results: ART+PLHIV differed from HC by increased CD4 TEMRA (5.3 (2.1–8.8) vs. 3.2 (1.6–4.4), p < 0.05), persistent TIGIT+CD57–CD27+CD28– CD8+ subset (53.9 (45.5–68.9) vs. 40.1 (26.7–58.5), p < 0.05), and expanding preapoptotic TIGIT–CD57+CD8+ effectors (9.2 (4.3–21.8) vs. 3.0 (1.5–7.3), p < 0.01) in correlation with increased CD8+ MMP (2527 (1675–4080) vs.1477 (1280–1691), p < 0.01). These aberrations were independent of age, time to ART, or ART duration, and were combined with increasing CD4 T cell MMP and MM. Conclusions: In spite of recovered CD4AC and CD4/CD8 ratio, the increased CD8+ MMP, combined with elevated markers of exhaustion and senescence in ART+PLHIV, signals a malfunction of the CD8 effector pool that may compromise viral reservoir latency. Full article

In this study, we report the synthesis of Te and Ag₂Te micron-sized rods (MRs) via a controlled hot-injection-based quenching process, enabling the control of rod morphology and enhanced crystallinity. Structural analysis confirmed that the synthesized Te MRs exhibit a trigonal phase, growing along the (110) direction, while Ag₂Te MRs undergo a phase transformation into a monoclinic structure upon Ag doping. A simple and scalable photodetector (PD) was fabricated by drop-casting Te and Ag₂Te MRs onto PET plastic films, followed by the application of Ag paste electrodes. The PD demonstrated room-light-induced photocurrent responses, which increased significantly upon mechanical bending due to the formation of additional conductive pathways between MRs. The Ag₂Te-based bending sensor exhibited a fivefold enhancement in photocurrent compared to its Te counterpart and maintained high stability over 1000 bending cycles. These results highlight the potential of Te and Ag₂Te MRs for use in flexible and wearable motion-sensing technologies, offering a simple yet effective approach for integrating 1D telluride nanostructures into scalable optoelectronic applications. Full article

Background/Objectives: Depression, anxiety and apathy are often associated with subjective cognitive complaints (SCCs) in people with Parkinson’s disease (PwPD) without cognitive impairment. Cognitive reserve (CR) enhances emotional resilience, allowing people to better cope with stress and emotional challenges, factors affecting quality of life. We aimed to explore the relationship between CR and mood/anxiety in cognitively intact PwPD with and without SCCs. Methods: In this cross-sectional study we enrolled 133 PwPD and normal cognitive function (age 59.8 ± 6.7 years; disease duration 9.0 ± 5.5 years; male/female 84/49). We assessed cognitive reserve (CR scale), subjective cognitive complaints (with PD-CFRS), QoL (PDQ8), mood, anxiety and apathy (BDI-II; STAI, PAS, Apathy scales). We used a t-test to compare groups (with/without SCC; M/F); correlations and moderation analysis to evaluate the relation between CR and behavioral features and the interplay between CR, behavioral discomfort and QoL. Results: The group with SCCs had significantly (p < 0.05) higher scores in PDQ8, Apathy, STAI, PAS-C and BDI-II scales than those with no SCCs. Males with SCCs had higher scores in PDQ8, Apathy scale and BDI-II while females differed in PDQ8 and Apathy scale scores. In the SCC group, late-life CR was negatively correlated with PAS-C (avoidance behavior) and BDI-II; correlations were confirmed in the male group where CR also correlated with PDQ-8 and PAS persistent anxiety. Conclusions: PwPD and SCCs are more depressed and anxious compared to people without SCCs. Furthermore, we found a relationship between depressive symptoms, anxiety and CR: PwPD with SCCs may rely on cognitive reserve to better cope with the feeling of anxiety and depression, especially in male gender. Full article

Background/Objectives: Accurate visualization of the Achilles tendon enthesis is critical for distinguishing mechanical, degenerative, and inflammatory pathologies. Although ultrasonography is the first-line modality for suspected enthesis disease, recent technical advances may expand the role of magnetic resonance imaging (MRI). This study evaluated the utility of ultra-short echo time (UTE) and zero echo time (ZTE) sequences versus proton density-weighted imaging (PD-WI) for depicting the enthesis organ in healthy volunteers. Methods: In this institutional review board (IRB)-approved prospective single-center study, 50 asymptomatic adult volunteers underwent 3-Tesla hindfoot MRI with fat-suppressed PD-WI, UTE, and ZTE between 2018 and 2023. Four radiologists assessed image quality, signal-to-noise ratio, visibility, and abnormal high signal intensities (SIs) of the periost, sesamoid, and enthesis fibrocartilages (PCa, SCa, and ECa, respectively). Statistical tests included Chi-square, McNemar, paired Wilcoxon, and Benjamini–Hochberg adjustments for multiple comparisons. Results: The median age was 36 years (range: 20–51); 58% women were included. PD-WI and ZTE sequences were always available while UTE was unavailable in 24% of patients. PD-WI consistently failed to concomitantly visualize all fibrocartilages. ZTE and UTE visualized all fibrocartilages in 72% and 92.1% of volunteers, respectively, with significant differences favoring ZTE and UTE over PD-WI (p < 0.0001) and UTE over ZTE (p = 0.027). Inter-rater agreement exceeded 80% except for SCa on ZTE (68%, 95%CI: 53.2–80.1). Abnormal SCa findings in asymptomatic patients were more frequent with UTE (23.7%) and ZTE (34%) than with PD-WI (2%) (p = 0.0045). Conclusions: At 3-Tesla, UTE and ZTE sequences reliably depict the enthesis organ of the Achilles tendon, outperforming PD-WI. However, the high sensitivity of these sequences also presents challenges in interpretation. Full article

Sporadic Parkinson’s Disease (PD) affects 3% of people over 65 years of age. People are living longer, thanks in large part to improvements in global health technology and health access for non-neurological diseases. Consequently, neurological diseases of senescence, such as PD, are representing an ever-increasing share of global disease burden. There is an intensifying research focus on the processes that underlie these conditions in the hope that neurological decay may be arrested at the earliest time point. The concept of neuronal death linked to ageing- neural senescence- first emerged in the 1800s. By the late 20th century, it was recognized that neurodegeneration was common to all ageing human brains, but in most cases, this process did not lead to clinical disease during life. Conditions such as PD are the result of accelerated neurodegeneration in particular brain foci. In the case of PD, degeneration of the substantia nigra pars compacta (SNpc) is especially implicated. Why neural degeneration accelerates in these particular regions remains a point of contention, though current evidence implicates a complex interplay between a vast array of neuronal cell functions, bioenergetic failure, and a dysfunctional brain immunological response. Their complexity is a considerable barrier to disease modification trials, which seek to intercept these maladaptive cell processes. This paper reviews current evidence in the domain of neurodegeneration in Parkinson’s disease, focusing on alpha-synuclein accumulation and deposition and the role of oxidative stress and inflammation in progressive brain changes. Recent approaches to disease modification are discussed, including the prevention or reversal of alpha-synuclein accumulation and deposition, modification of oxidative stress, alteration of maladaptive innate immune processes and reactive cascades, and regeneration of lost neurons using stem cells and growth factors. The limitations of past research methodologies are interrogated, including the difficulty of recruiting patients in the clinically quiescent prodromal phase of sporadic Parkinson’s disease. Recommendations are provided for future studies seeking to identify novel therapeutics with disease-modifying properties. Full article

Background: Studies have suggested a synergism between lenalidomide (LEN) and ibrutinib (IBR) in multiple myeloma (MM). Both downregulate IRF4, a key target and master transcriptional factor regulating myeloma cell survival. Method: A 3 + 3 phase I trial was conducted to determine the maximum tolerated dose (MTD) of IBR in combination with LEN + dexamethasone (DEX) in patients with relapsed/refractory (RR) MM who had at least one prior line of therapy. Three dose levels (DLs) were planned. The cycle length was 28 days. IBR was administered orally daily in doses of 560 mg on DL1-2 and 840 mg on DL3, LEN was administered orally on days 1–21 in doses of 15 mg on DL1 and 25 mg on DL2-3, and DEX was administered orally on days 1, 8, 15, and 22 in a dose of 40 mg if age < 75 years or in a dose of 20 mg if it was ≥75 years for DL1-3. Patients with a glomerular filtration rate (GFR) <60 but ≥30 mL/min were treated in accordance with the manufacturer’s instructions with LEN 10 mg. Dose-limiting toxicities (DLTs) included the following: grade 4 neutropenia lasting more than 5 days, thrombocytopenia, febrile neutropenia, nausea, vomiting or diarrhea; grade 3 thrombocytopenia with bleeding or platelet transfusion; and grade 3–4 hyperglycemia or a thrombotic/embolic event, and other nonhematologic toxicities. The overall response rate (ORR) was defined as the percentage of patients with a partial response (PR), very good partial response (VGPR), or complete response (CR) according to IMWG criteria on two consecutive evaluations at least 4 weeks apart. The clinical benefit rate (CBR) was defined as the percentage of patients with stable disease (SD) or a better outcome on two consecutive evaluations at weeks apart. Results: Fourteen patients (DL1: six patients; DL2: three patients; DL3: five patients) were registered for the study from March 2019 to May 2023, prior to its closure due to limited accrual. Thirteen patients are included in the summary of toxicities and response as one patient on DL3 halted participation prior to the start of the treatment. Two patients on DL3 were excluded from the determination of MTD: one having discontinued cycle 1 treatment due to COVID-19 infection and the another having mistakenly taken 280 mg/day of IBR instead of the assigned 840 mg/day dose during cycle 1. Only one patient developed a DLT, on DL1 with grade 3 non-viral hepatitis. The median number of cycles administered was 4 (range: 1–56). Severe toxicities reported included grade 4 lymphocytopenia (1), grade 4 thrombocytopenia (1), and grade 5 sepsis in the setting of PD (1). Disease responses included a VGPR on DL1 and CR on DL3. Thus, the ORR was 15.4% (90% CI: 2.8–41.0%). One patient on DL1 maintained SD for 4.6 years before discontinuing the treatment to undergo an alternative therapy. Another five patients maintained SD for ≥ 2 consecutive cycles. Thus, the CBR was 61.5% (90% CI: 35.5–83.4%). Conclusions: The combination of LEN with IBR in RR MM proved feasible, with manageable toxicities and the majority of discontinuations being due to disease progression. Full article

ATP13A2 is a lysosomal polyamine transporter with loss of function mutations linked to multiple neurodegenerative disorders including Parkinson’s disease (PD). Knockout of ATP13A2 in mice leads to age-related sensorimotor impairments and in the brain lipofuscinosis, gliosis, and modest alpha-synuclein (αSyn) pathology. However, few studies have included ATP13A2 heterozygous mice as a comparison. In the present study, the effect of reduced or complete loss of ATP13A2 function on behavior, αSyn, gliosis, dopamine, and polyamines were determined in mice. Male and female ATP13A2 wildtype (WT), heterozygous (Het), and knockout (KO) mice were assessed behaviorally at 3, 12, and 18 months of age. In the brain, αSyn, phosphorylated αSyn, and GFAP were measured in the prefrontal cortex, striatum, ventral midbrain, and cerebellum. Polyamine and neurotransmitter analyses were performed in the same brain regions. Similar to previous studies, KO mice developed motor impairments and widespread gliosis in the brain. In addition, polyamine content was altered in Het and KO mice. In contrast, Het mice showed impairments in cognitive function and an age-related increase in αSyn in the brain. These results indicate potentially different pathological mechanisms when ATP13A2 is reduced compared to when it is knocked out and may have important implications for disease modification in synucleinopathies including PD. Full article

Chronic inflammation plays a central role in the progression and complications of chronic kidney disease (CKD). The nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome pathway has emerged as a crucial mediator of the inflammatory response in CKD. This cross-sectional study evaluated the expression of NLRP3 in patients with CKD undergoing different treatments. Blood samples were collected from 32 non-dialysis (ND) patients [63 (11.2) years, estimated glomerular filtration rate, 43.5 (22.0) mL/min, BMI, 29.5 (10.0) kg/m²)], 50 hemodialysis (HD) patients [48.5 (16.5) years, 60.5 (50) months on HD, BMI, 24.2 (4.9) kg/m²)], and 8 peritoneal dialysis (PD) patients [56.5 (8.5) years, 40.5 (41.2) months on PD, BMI, 28.8 (2.6) kg/m²)]. The mRNA expression level of NLRP3 was measured using real-time PCR. The cytokines and the malondialdehyde (MDA) levels were also assessed. The results indicated that the mRNA level of NLRP3 was significantly elevated in patients undergoing HD (1.23, IQR = 0.95) compared with that in non-dialysis patients (0.79, IQR = 0.35) and in patients undergoing PD (0.77, IQR = 0.38) after adjusting for confounding variables, including age, sex, BMI, and dialysis duration. Furthermore, the MDA levels were significantly higher in HD patients. NLRP3 is upregulated in HD patients, and the results suggested that the inflammasome may be associated with oxidative stress in patients with CKD. Full article

In a previous article, an estimation procedure for calculating the liquidus and solidus lines of binary equilibrium phase diagrams was presented. In this article, keeping the thermodynamic basics, the estimation method for the approximate calculation of the liquidus and solidus surfaces of ternary phase diagrams was further developed. It is shown that the procedure has a hierarchical structure, and the ternary functions contain the binary functions. The applicability of the method is checked by calculating the liquidus and solidus surfaces of the Ag-Au-Pd isomorphous ternary equilibrium phase diagram. The application of each level of the developed four-level procedure depends on the data available and the aim. It is shown that in the case of a concentration range close to the base alloy pure element, the liquidus and solidus surfaces of the ternary equilibrium phase diagram can be calculated from the liquidus and solidus functions of the binary equilibrium phase diagrams with a few K errors, which is 0.2 at% at 10 K/at% slope. The equilibrium phase diagrams were available in graphical form, so the data obtained via digitalisation of the diagrams for the calculations was used. The functions describe the slope of the surfaces, and the approximate method developed for the calculation of the partition ratios is also shown. Full article

Background: The atherogenic index of plasma (AIP), a prognostic indicator for cardiovascular disease, has not been fully explored in relation to clinical outcomes in patients receiving peritoneal dialysis. This study aims to elucidate the relationship between baseline AIP levels and all-cause mortality, cardiovascular mortality, and the peritonitis risk in this population. Methods: This retrospective cohort study included incident peritoneal dialysis patients in our center from 1 January 2006 through 31 December 2021. The end of the follow-up time was 31 December 2023. The participants were stratified by baseline AIP levels. Kaplan–Meier curves, Cox regression analyses, and subgroup analyses were used to evaluate associations with clinical outcomes. Results: The average age of the 2460 participants in this study was 45.9 years, and 1456 (59.2%) of them were men. Diabetic nephropathy (19.5%) was the second most common kidney disease, after primary glomerulonephritis (60.8%). The higher AIP tertile group was significantly associated with increased risks of all-cause mortality, cardiovascular mortality, and peritonitis compared to the lowest AIP group, as evidenced by the Kaplan–Meier curves and the multivariate analyses. Continuous AIP levels also showed a positive correlation with the all-cause mortality and peritonitis risk, even after controlling for covariates. Conclusions: Our study highlights AIP as a predictive marker for adverse outcomes in PD patients, emphasizing its potential utility in risk stratification and clinical management. Full article