Onset Of Symptoms Research Articles

Assessment of palpitations in patients with frequent premature ventricular contractions.

In patients with frequent premature ventricular contractions (PVCs), palpitations may not always be directly caused by PVCs, and therefore, it is essential to establish symptom-rhythm correlations to determine the appropriate treatment. This study aims to analyze the palpitations and related factors in patients with frequent PVCs. The study enrolled patients with frequent PVCs who were not combined with other arrhythmias or structural heart disease. Through face-to-face consultation, patients were divided into symptomatic and asymptomatic groups. For symptomatic patients, the correlation between palpitations and PVC was further evaluated based on the temporal consistency of symptom onset and PVC occurrence. The demographic, clinical, and electrocardiogram features of the patients in each group were compared. Of the 214 patients enrolled, 124(57.9%) experienced palpitations. Compared to the asymptomatic group, the symptomatic group had a higher proportion of females (63.7% vs. 47.8%; p = .020) and a higher proportion of subjects with anxiety (44.4% vs.14.4%; p = .000). Within the symptomatic patients, 72 (33.60%) who had palpitations that were clearly correlated with PVCs were classified as the PVC-relevant group. In this group, the PVC CI ratios were significantly lower (55% [52% -60%] vs. 62% [55% -67%]; p = .001) and the Post-PVC CI were longer (1170 [1027-1270] vs. 1083 [960-1180] ms; p = .018) than in the PVC-irrelevant group. A direct relationship between palpitations and PVCs could be established only in a minority of patients with frequent PVCs. PVCs with a relatively short PVC CI and a long post-PVC CI were more likely to cause palpitations, whereas palpitations lasting only a few seconds were more likely to be directly relevant to PVCs.

Microvascular abnormalities in skin capillaries of individuals with amyotrophic lateral sclerosis

This is the first study aimed to detect morphological abnormalities in vivo in the skin capillaries of amyotrophic lateral sclerosis patients (ALS). Videocapillaroscopy assessed subungueal capillaries in 28 ALS patients (cases) and 35 controls (p = 0.42). The mean age was 61.46 and 61.23 years, respectively (p > 0.99). No statistically significant differences were observed between the groups regarding dominant hand, arterial hypertension, dyslipidemia, diabetes mellitus, active smoker, and former smoker variables. 78.57% of cases had spinal onset and 21.43% bulbar. The median disease duration (time between the onset of symptoms and the date of videocapillarscopy) was 29.71 months. Dilated capillaries were detected in 17.8% of cases and 11.43% of controls (p = 0.49). The median of capillary diameter in cases was 10.15 µm and 8.72 µm in controls (p = 0.011). 35.71% of cases and 2.86% of controls had severe capillary tortuosities (p < 0.001). Ramified capillaries were observed in 46.43% of cases and 11.43% of controls (p < 0.002). Micro-hemorrhages were only observed in 10.71% of cases. No significant correlations were observed between disease duration and dilated capillaries, tortuosity, ramified capillaries, and micro-hemorrhages. The present in vivo study shows abnormalities in the skin capillaries of ALS patients that do not depend on disease duration.

Association of CSF α-synuclein seed amplification assay positivity with disease progression and cognitive decline: A longitudinal Alzheimer's Disease Neuroimaging Initiative study.

Cerebrospinal fluid (CSF) α-synuclein (α-syn) seed amplification assay (SAA) is a sensitive and specific tool for detecting Lewy body co-pathology in Alzheimer's disease. A total of 1637 cross-sectional and 407 longitudinal CSF samples from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were tested with SAA. We examined longitudinal dynamics of amyloid beta (Aβ), α-syn seeds, and phosphorylated tau181 (p-tau181), along with global and domain-specific cognition in stable SAA+, stable SAA-, and those who converted to SAA+ from SAA-. SAA+ individuals had faster cognitive decline than SAA-, notably in mild cognitive impairment, and presented with earlier symptom onset. SAA+ conversion was associated with CSF Aβ42 positivity but did not impact the progression of either CSF Aβ42 or CSF p-tau181 status. CSF Aβ42, p-tau181, and α-syn SAA were all strong predictors of clinical progression, particularly CSF Aβ42. In vitro, CSF α-syn SAA kinetic parameters were associated with participant demographics, clinical profiles, and cognitive decline. These results highlight the interplay between amyloid and α-syn and their association with disease progression. Seed amplification assay (SAA) positivity was associated with greater cognitive decline and earlier symptom onset. Thirty-four Alzheimer's Disease Neuroimaging Initiative (ADNI) individuals progressed from SAA- to SAA+, that is, ≈ 5% conversion. SAA conversion was associated with amyloid beta (Aβ) pathology and greater cognitive decline. SAA status did not impact the progression of either CSF Aβ42 or phosphorylated tau181 biomarkers. Change in clinical diagnosis was associated with both Alzheimer's disease biomarkers and SAA. SAA kinetic parameters were associated with clinical features and progression.

IN-HOSPITAL OUTCOMES AMONG PATIENTS PRESENTED WITH ST-ELEVATION MYOCARDIAL INFARCTION TREATED WITH PRIMARY PERCUTANEOUS CORONARY INTERVENTION

Primary Percutaneous Coronary Intervention (PCI) is considered the gold standard treatment for patients with ST-elevation myocardial Infarction (STEMI). Prompt intervention, aimed at restoring blood flow, plays a critical role in improving survival and minimizing complications in these patients. Objective: The objective of this study was to evaluate in-hospital outcomes among patients diagnosed with STEMI and treated with Primary PCI. Methods: This cross-sectional study was conducted in the Cardiology Department over one year. The study included patients aged 50 years and older who were diagnosed with STEMI based on electrocardiographic criteria and presented within 12 hours of symptom onset. Demographic information, clinical characteristics, comorbidities, and in-hospital outcomes were recorded. Statistical analyses were performed using relevant descriptive measures. Results: A total of 150 patients were included in the study. The mean age of patients was 60.89 ± 5.65 years, with 64.4% being male. The average door-to-balloon time was 89.93 ± 18.12 minutes. Successful reperfusion, defined as achieving a TIMI grade 3 flow, was observed in 87.8% of the patients. In-hospital mortality was recorded at 4.4%, while 3.3% of patients developed infections during their hospital stay. Conclusion: The study demonstrated favourable in-hospital outcomes for STEMI patients treated with Primary PCI, with a high success rate in achieving TIMI grade 3 flow and a relatively low in-hospital mortality rate. These findings underscore the efficacy of timely PCI in improving survival and procedural outcomes in STEMI patients, particularly when door-to-balloon time is minimized.

Demographic characteristics, clinical manifestations, and treatment outcomes of May-Thurner Syndrome: a five-year retrospective analysis using computed tomography venography in a Chinese population

Objective This study aimed to analyze the demographic characteristics, symptoms, and treatment outcomes of patients diagnosed with May-Thurner syndrome (MTS) using computed tomography venography (CTV). Methods Medical records of patients diagnosed with MTS through CTV at Hebei General Hospital of China between April 1, 2017, and May 31, 2022, were reviewed. The data collected included: (1) gender, age, body mass index (BMI), and smoking and drinking habits; (2) time of onset and symptoms of MTS, as well as other accompanying symptoms; (3) additional diagnoses, length of hospital stay (days), treatment methods, treatment success, and the occurrence of post-treatment bleeding or recurrence. Descriptive statistics were used, with mean ± standard deviation and median values reported. The t-test/u-test and Chi-square test (including the exact probability method) were used to compare means and rates, respectively, with a significance level set at α = 0.05. Results Out of 402 patients (233 males, 169 females), 118 (29.4%) were diagnosed with MTS, with 47 (21.1%) males and 71 (39.7%) females. The incidence of MTS was significantly higher in females than males (χ2 proportion = 16.545, χ2 composition = 9.763, P < 0.05). The average ages of male and female MTS patients were 56.4 and 59.9 years, respectively, with mean BMIs of 27.05 and 27.09 kg/m2. Among male patients, 27.7% (13) were smokers, and 17.0% (8) consumed alcohol. Inferior vena cava (IVC) thrombosis was notable in 59.3% of MTS patients, with a significantly higher proportion in females (70.4%) than in males (42.6%) (χ2 = 9.102, P < 0.05). Lower limb swelling without pain was reported by 70.3% of patients, with 53.4% (44.7% male, 59.2% female) experiencing swelling on the left side only, which was significantly more common than swelling on the right side only or both sides (χ2 = 44.554, P < 0.05). Additionally, 12.7% of patients reported both swelling and pain, with left-side symptoms being more prevalent than right-side or both sides. The average ages at symptom onset were 51.3 ± 17.1 years in males and 57.1 ± 13.2 years in females. All treatments for MTS were successful without bleeding or recurrence. The most common treatment method was balloon dilation combined with stent placement (57.6%). Conclusion CTV is highly effective in detecting and facilitating the successful treatment of MTS. It should be fully utilized to promote early diagnosis and treatment of MTS. Female MTS patients need more medical resources for diagnosis and treatment.

Caffeine Use in Huntington's Disease: A Single Center Survey.

Anecdotal evidence suggests paradoxical caffeine overuse in individuals with Huntington's disease (HD). A small retrospective study associated caffeine intake over 190 grams daily to earlier onset of HD symptoms. However, specific data on consumption habits is limited. This study aims to gather pilot data on caffeine use in people with HD, exploring motivations and consequences. Thirty adults with HD completed a survey on daily caffeine intake, its impact on symptoms, and consumption motivations through multiple-choice and open-ended questions. Descriptive statistics were used to analyze findings and compare them to general population data. Caffeine intake ranged from 0 to 1400.4 mg/day, with a median of 273.2 mg/day and a mean of 382.5 mg/day. Seventy percent of participants with HD consumed more caffeine than the average for their age group in the general population. Additionally, 20% of participants and 38% of family members believed caffeine influenced HD symptoms, primarily anxiety. People with HD typically consume more caffeine than the general U.S. population. Contrary to the hypothesis, higher caffeine intake was not associated with significant subjective worsening of HD symptoms. Further research with objective measures and multiple HD centers is necessary to guide screening and counseling on caffeine use in this population. Participants with Huntington's disease (HD) had increased caffeine intake compared to the general population, supporting previous anecdotal observations. Anxiety was the most affected HD symptom. Further research using objective measures of symptom burden and including multiple HD centers can help inform screening and counseling regarding caffeine use in this population.

Alice in Wonderland Syndrome in Children With Severe Acute Respiratory Syndrome SARS-CoV-2 Infection: A Case Series of Two Patients in an Italian Hospital

BackgroundAlice in Wonderland syndrome (AIWS) is a disorienting neurological condition that affects human perception to the senses of vision, hearing, touch, and sensation and the phenomenon of time. Herein we report two pediatric cases of AIWS temporally related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Case presentationAn eight-year-old-girl without history of migraine or epilepsy experienced some episodes of visual distortions (micropsia, macropsia, and teleopsia) and misperception of sound, sometimes associated with headache. The onset of symptoms began at the occurrence of fever (38°C), during SARS-CoV-2 infection. Another six-year-old girl, with no history of migraine or epilepsy, experienced short-term episodes of visual (metamorphopsia) and color disturbance (chromatopsia), during an otherwise asymptomatic SARS-CoV-2 infection. In both cases, clinical examination was unremarkable; surface electroencephalography showed normal findings, without any correlation between visual phenomena and cortical activity; and brain magnetic resonance was normal. The patients were given symptomatic treatment, consisting of anti-inflammatory drugs on demand. The frequency of episodes decreased progressively following a negative SARS-CoV-2 test, with full remission in a few weeks. At the moment of hospital admission, none of the patients had completed the two-dose vaccination schedule for SARS-CoV-2. ConclusionBased on our clinical experience, we believe SARS-CoV-2 may be responsible for AIWS, in addition to other neurological symptoms more frequently documented in the literature. Pathogenesis is multifactorial and arises from the activation of inflammatory pathways. We therefore suggest also searching for SARS-CoV-2, among other viruses linked with AIWS, in children presenting with visual and/or auditory hallucinations, even as isolated symptoms.

Ion Channel Diseases as a Cause of Sudden Cardiac Death in Young People: Aspects of Their Diagnosis, Treatment, and Pathogenesis.

Sudden cardiac death (SCD) is the death of an apparently healthy person within one hour of the onset of symptoms, or within 24 hours of last being seen alive and well-with no evidence of an extra-cardiac cause. In autopsied cases, SCD is defined as the natural unexpected death of unknown or cardiac cause. The reported incidence figures for SCD vary widely. This review is based on clinical registry studies, meta-analyses, randomized controlled trials, systematic reviews, and current guidelines that were retrieved by a selective search in PubMed employing the key words "channelopathy," "Brugada syndrome," "long QT syndrome," "catecholaminergic polymorphic ventricular tachycardia," "short QT syndrome," and "early repolarization." Approximately 18% of cases of SCD in young persons are associated with cardiac channelopathy. The most common ion channel diseases affecting the heart are long QT syndrome and Brugada syndrome. The diagnosis is established by specific ECG abnormalities in the absence of structural heart disease. These can be unmasked by various maneuvers, e.g., the administration of sodium-channel blockers in Brugada syndrome. Imaging studies such as echocardiography, coronary angiography, and computed tomography are used to rule out structural heart disease and coronary artery disease. Long-term ECG and risk stratification scores can be useful aids to therapeutic decision-making. For some of these diseases, it is advisable for the patient to avoid particular triggers of ECG changes and cardiac arrhythmias in his or her everyday life. The near relatives of persons with congenital ion channel diseases should undergo clinical and genetic screening to protect them from SCD. The affected families should be investigated systematically so that appropriate diagnoses and treatments can be established.

Corneal Endothelial Changes in Chinese Patients with Fuchs’ Uveitis Syndrome

ABSTRACT Purpose To analyze the changes of corneal endothelial cells in Chinese patients with unilateral Fuchs’ uveitis syndrome (FUS) and investigate the factors relevant to these changes. Methods Bilateral specular microscopic examination was performed in 459 Chinese patients with unilateral FUS from April 2008 to April 2023. The affected eyes constituted the study group, while the contralateral eyes served as controls. Results The median values of endothelial cell density (ECD), cell count, total cell size, and hexagonality were significantly lower in the FUS eyes compared to the control eyes (p < 0.001). The median values of average cell size, maximum cell size, SD of cell size, and CV were significantly higher in the FUS eyes compared to the control eyes (p < 0.001). Central ECD showed a negative correlation with age (r = −0.339; p < 0.001), maximum IOP (r = −0.127; p = 0.006), and the interval since symptom onset (r = −0.172; p < 0.001). The ECD was lower in eyes with ocular hypertension compared to those without ocular hypertension (p < 0.001). Eyes with KPs distributed on the central corneal endothelium had a significantly lower ECD than those with KPs distributed diffusely or KPs distributed triangularly on the inferior corneal endothelium (p = 0.006). Conclusion Our findings suggest decreased ECD, increased cell size, and morphological alterations in the affected eyes of Chinese patients with FUS. The reduction in ECD is correlated with age, elevated IOP, the interval since symptom onset, and the distribution of KPs.

Comparison of central precocious puberty frequency before and during COVID-19: a systematic review and meta-analysis

ObjectiveThe current systematic review and meta-analysis assessed the prevalence of central precocious puberty (CPP) throughout the novel coronavirus disease 2019 (COVID-19) pandemic.DesignA systematic review and meta-analysis were carried out following the principles outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA, 2020).Data sourcesPubMed, Embase, Web of Science, and WANFANG databases were searched from January 1, 2019, to March 30, 2023.Eligibility criteria for selecting studies(1) children and adolescents ≤ 15 years; (2) studies with the outcome of frequency of central precocious puberty, measured prior to and throughout the COVID-19 pandemic; (3) a novel CPP diagnosis was created depending on all of the following criteria: girls with a chronological age < 8 years and boys with a chronological age < 9 years at the onset of symptoms, basal luteinizing hormone (LH) levels > 0.3 UI/L, and/or GnRH-stimulated peak LH levels > 5 IU/L.Data extraction and synthesisThe process of extracting data and evaluating the likelihood of bias was carried out by two independent reviewers. The data were pooled employing the generic inverse-variance method and presented as mean differences (MDs) with 95% CIs. The evaluation of heterogeneity was conducted employing the Cochran Q statistic, and the degree of heterogeneity was measured employing the I2 statistic.ResultsThis meta-analysis included 17 studies. In contrast to the same period prior to the COVID-19 pandemic, the occurrence of CPP elevated (OR = 2.57; 95% CI, 1.85–3.56). Moreover, body mass index standard deviation score (BMI SDS) differences between CPP patients prior to COVID-19 and throughout the pandemic follow-up was 0.12 (95% CI − 0.01 to 0.25 P = 0.06).ConclusionOverall, CPP frequency significantly elevated throughout the COVID-19 pandemic. Given the restricted number of cohort investigations in this meta-analysis, additional research may be conducted on larger groups of children in order to establish a correlation between the observed rise in precocious puberty and specific pathogenic factors.

A study to determine a capillary alternative to the gold standard oral glucose tolerance test - Protocol

Type 1 diabetes (T1D) is a chronic condition caused by the immune destruction of the pancreatic beta cells. T1D has recognised asymptomatic pre-clinical stages, providing an opportunity for early diagnosis, education and treatment which may delay the onset of symptoms. The oral glucose tolerance test (OGTT) is the gold standard method to stage and monitor early-stage T1D, which can be poorly tolerated and may contribute to marked loss to follow-up. Our study aims to test the accuracy, feasibility, and acceptability of a capillary alternative (‘GTT@home’ test kit) to the gold standard OGTT. We will invite 45 children and young people (CYP) across the spectrum of glycaemia with or without diabetes, from established research platforms or clinical care, to have a standard 2-hour OGTT, with capillary samples collected alongside their venous samples, at 0 and 120 minutes. A subgroup (n=20) will also have 60-minute capillary and venous samples collected. We will also invite 45 CYP from established research platforms, who are known to have two or more islet autoantibodies and are not on insulin, to undergo a capillary OGTT at home, using the GTT@home kit. We will assess the agreement of capillary and venous glucose and measure diagnostic accuracy by calculating the sensitivity and specificity of capillary measures at established diagnostic thresholds (fasting [5.6 mmol/L, 7.0 mmol/L], 60 minutes post glucose load [11.1 mmol/L] and 120 minutes post glucose load [7.8 mmol/L and 11.1 mmol/L]), using venous glucose as the gold standard. These studies will inform our understanding of whether the GTT@home device can be used in CYP in routine clinical care.

Expression study of Krabbe Disease GALC missense variants - Insights from quantification profiles of residual enzyme activity, secretion and psychosine levels.

Krabbe disease (KD) is an autosomal recessive lysosomal storage disorder caused by loss-of-function mutations in the GALC gene, which encodes for the enzyme galactosylceramidase (GALC). GALC is crucial for myelin metabolism. Functional deficiency of GALC leads to toxic accumulation of psychosine, dysfunction and death of oligodendrocytes, and eventual brain demyelination. To date, 46 clinically-relevant, pathogenic GALC missense mutations (MMs) have been identified in KD patients. These MMs are present in ∼70% of KD cases reported over 8 published studies between 1996 - 2019. However, the mechanisms by which these MMs lead to GALC functional deficiency and their correlations with clinical phenotype remain poorly understood. To address this, we generated a GALC -knockout human oligodendrocytic cell line (MO3.13/ GALC -KO) using CRISPR-Cas9 method to assess GALC function and GALC secretion. We evaluated 5 polymorphic and 31 clinically-relevant MM variants (MMVs) using transient expression assays. Our results showed that 26 MMVs, including 10 co-variants with p.I562T, reduced GALC activity by 92% - 100% compared to wild-type GALC (WT-GALC). MMVs from infantile-onset KD patients produced < 2% of WT activity, whereas those associated with juvenile- and adult-onset cases retained up to 7% of WT activity. Residual GALC activity was correlated with mature, lysosomal GALC protein levels (Pearson r = 0.93, P<0.0001). Many low-activity MMVs did not correspondingly impair GALC secretion. Twenty-one of the 26 low-activity MMVs showed a 21% - 100% reduction in sec-GALC levels, indicating varying degrees of GALC mis-trafficking among these variants. Importantly, GALC activity among MMVs strongly correlates with clinical disease severity, based on the age of symptom onset in patients with either homozygous MM (Pearson r = 0.98, P<0.0001, n = 7) or compound heterozygous (Pearson r = 0.94, P<0.0001, n = 12) MM-null mutation genotypes. Thus, our data suggests that GALC activity could serve as a prognostic disease indicator under specific experimental conditions. We further investigated the impact of pathogenic MMVs on psychosine accumulation, a key biomarker for KD. Psychosine levels were 21-fold higher in mock control cells compared to WT-GALC transfected cells (mock = 0.349 pmol/mg, WT-GALC = 0.016 pmol/mg), but negatively correlated with GALC activity among pathogenic MMVs (Pearson r = -0.63, P < 0.01, n = 15). Although psychosine levels were higher in most MMVs associated with infantile-onset KD, no significant correlations with clinical onset were detected. Overall, our study provides a comprehensive quantitative analysis of the functional deficits and mis-trafficking associated with clinically-relevant GALC MMVs, enhancing our understanding of the molecular genetics and genotype-phenotype correlations of the GALC gene in Krabbe disease.

Changes in core depressive symptoms over time in peripartum women: A network analysis

Perinatal depression (PND) is a prevalent mental health condition that affects women during pregnancy and after childbirth. Distinct clinical subtypes of PND exist, with the timing of symptom onset being a pivotal element in the classification of these subtypes. However, the specific manifestations of PND across the various stages of pregnancy and the postpartum period remain to be elucidated. This study aimed to explore the changes in depression symptoms with the stage of pregnancy. Women in their second (n = 161) and third trimesters (n = 248) of pregnancy as well as those in their first 6 weeks of the postpartum period (n = 110) were recruited. Each patient was evaluated using the Edinburgh Postnatal Depression Scale. A network analysis approach was used to explore the interconnections among depressive symptoms across the different time periods. Women in the postpartum period exhibited the most pronounced prevalence of PND and severity of depressive symptoms. In the second and third trimesters, &amp;ldquo;sadness and misery&amp;rdquo; was the most central symptom. However, its prominence diminished after childbirth. &amp;ldquo;Fear and panic&amp;rdquo; was the predominant symptom in the postpartum network. The structural integrity of PND symptom networks was maintained across all three periods, with consistent strength and closeness. This study demonstrates the temporal evolution of PND&amp;rsquo;s central symptoms in women during and after pregnancy, transitioning from depression-centric to anxiety-centric manifestations. These findings advocate for symptom-specific interventions to enhance the mental well-being of mothers and their offspring. Furthermore, this study offers clinical insights into the biological underpinnings of PND subtypes, facilitating precise diagnosis and targeted treatment strategies.

A multicenter, randomized, double-blind, placebo-controlled trial to evaluate the effect of Tongmai Yangxin pill on ventricular remodeling in acute anterior STEMI patients after primary PCI

BackgroundAcute ST-segment elevation myocardial infarction (STEMI) is a severe form of coronary heart disease and a leading cause of mortality and morbidity. This can mainly be ascribed to adverse ventricular remodeling (VR). However, the efficacy of existing treatment strategies for STEMI is not entirely satisfactory. Tongmai Yangxin Pill (TMYX), a patented traditional Chinese medicine (TCM), has been approved for treating various cardiovascular diseases. PurposeThe purpose was to assess the effect of TMYX on VR in acute STEMI patients undergoing primary percutaneous coronary intervention (PPCI). Study DesignA multicenter, randomized, double-blinded, and placebo-controlled trial conducted across 11 hospitals in China. MethodA total of 270 patients with acute anterior STEMI, undergoing PPCI within 10 days of symptom onset were enrolled and randomly assigned to receive either a placebo or TMYX, in addition to guideline-directed treatments for STEMI. The primary endpoint was a change in left ventricular end-diastolic volume index (LVEDVI) at 12 weeks. ResultAmong the 270 randomized patients, 218 (TMYX: 109 and placebo: 109) were included in the per-protocol analysis. At 4 and 12 weeks, TXMY significantly improved LVEDVI than the placebo group ([-2.17(-9.24, 8.28) vs. 3.76(-2.38, 11.48), p < 0.05] and [-1.17 (-12.19, 12.88) vs. 4.46 (-2.89, 11.99), p < 0.05]). Changes in left ventricular end-diastolic volume (LVEDV) at 4 weeks were superior in the TMYX group than the placebo group (-4.37 (-17, 13.99) vs. 7.41 (-4.56, 21.79), p < 0.05). Cardiac magnetic resonance imaging (CMRI) showed that left ventricular ejection fraction (LVEF) was significantly greater in the TMYX group than in the placebo group at 4 weeks. There were no statistically significant differences between groups for left ventricular end-systolic volume (LVESV), left ventricular end-systolic volume index (LVESVI), 6 min walking distance (6MWD), and major adverse cardiac and cerebrovascular events (MACCEs) (p > 0.05). ConclusionTMYX, as an adjunctive therapy in addition to STEMI guideline-directed treatments, significantly delayed VR in patients with acute anterior STEMI undergoing PPCI within 10 days of symptom onset.

Erosive Tarsal Conjunctival Lesions Following Immunogenic Events in Early Development of Ocular Graft-vs-Host Disease.

Ocular graft-versus-host disease (oGVHD) affects more than half of the patients following allogeneic hematopoietic stem cell transplantation (HSCT). The disease onset and the pathogenesis of oGVHD are not well understood. We hope to identify the triggers and explore the clinical signs and symptoms of oGVHD development at the early stages. The records of post-HSCT patients seen consecutively in a 1-year span in a single provider's clinic were reviewed. The history, symptoms, and clinical findings of the patients with erosive tarsal conjunctival lesions (ETCLs) were analyzed. Out of the 228 patients screened, 19 had clinically witnessed ETCL in at least one eye during the period. Twelve (63%) patients had a never-before-described nodular erosion on the subtarsal conjunctiva; seven (37%) had previously described pseudomembranous erosions. The ocular symptom onset was within 1 month after immunosuppression (IS) taper, vaccination, or donor lymphocyte infusion (DLI) in 16 of the 19 patients. While 16 (84%) patients reported painless mucous discharge, only 9 (47%) reported dryness as the initial symptom. Within 6 months, only 4 (21%) had discharge but 15 (82%) patients endorsed dryness. Subepithelial conjunctival fibrosis followed ETCL immediately in situ. Corneal punctate staining increased with time, while aqueous tear production decreased. The ETCL described is likely one of the earliest detectable findings of oGVHD and triggered by certain immunogenic events. The ocular symptoms of wet mucous discharge should be considered a warning sign for oGVHD onset, particularly when it occurs shortly after prominently immunogenic events.

Parkinson’s families project: a UK-wide study of early onset and familial Parkinson’s disease

The Parkinson’s Families Project is a UK-wide study aimed at identifying genetic variation associated with familial and early-onset Parkinson’s disease (PD). We recruited individuals with a clinical diagnosis of PD and age at motor symptom onset ≤45 years and/or a family history of PD in up to third-degree relatives. Where possible, we also recruited affected and unaffected relatives. We analysed DNA samples with a combination of single nucleotide polymorphism (SNP) array genotyping, multiplex ligation-dependent probe amplification (MLPA), and whole-genome sequencing (WGS). We investigated the association between identified pathogenic mutations and demographic and clinical factors such as age at motor symptom onset, family history, motor symptoms (MDS-UPDRS) and cognitive performance (MoCA). We performed baseline genetic analysis in 718 families, of which 205 had sporadic early-onset PD (sEOPD), 113 had familial early-onset PD (fEOPD), and 400 had late-onset familial PD (fLOPD). 69 (9.6%) of these families carried pathogenic variants in known monogenic PD-related genes. The rate of a molecular diagnosis increased to 28.1% in PD with motor onset ≤35 years. We identified pathogenic variants in LRRK2 in 4.2% of families, and biallelic pathogenic variants in PRKN in 3.6% of families. We also identified two families with SNCA duplications and three families with a pathogenic repeat expansion in ATXN2, as well as single families with pathogenic variants in VCP, PINK1, PNPLA6, PLA2G6, SPG7, GCH1, and RAB32. An additional 73 (10.2%) families were carriers of at least one pathogenic or risk GBA1 variant. Most early-onset and familial PD cases do not have a known genetic cause, indicating that there are likely to be further monogenic causes for PD.

Association between husband's participation in household work and the onset of depressive symptoms in married women: A population-based longitudinal study in South Korea

An unequal distribution of household work by gender is prevalent. This study explored the association between husbands' participation in household work and the onset of depressive symptoms among married Korean women. A nationwide sample of 7024 married women was repeatedly followed up at 2-year intervals from 2014 to 2022 (20,343 observations). The daily household work hours of both the participants and their husbands were self-reported. Satisfaction with husbands' participation in household work was classified as satisfactory, neutral, or dissatisfactory. Depressive symptoms were assessed using the 10-item version of the Center for Epidemiologic Studies Depression. A generalized estimating equation was employed to determine how household work participation was associated with the onset of depressive symptoms in married women at the 2-year follow-up. The risk ratios (RRs) and 95% confidence intervals (CIs) were calculated. The mean daily hours spent on household work were 2.62 h for married women and 0.35 h for husbands. A 1-h increase in the husbands' daily time spent on household work was negatively associated with the risk of onset of depressive symptoms in married women (RR: 0.88, 95% CI: 0.80–0.98). Compared with individuals with neutral responses, those satisfied with their husband's household work had a lower risk of depressive symptom onset (RR: 0.82, 95% CI: 0.74–0.90), whereas dissatisfaction was linked to increased risk (RR: 1.15, 95% CI: 1.04–1.27). Husbands' participation in household work was associated with a reduced risk of depressive symptom onset among married women. Achieving gender equality in the division of household work is important for women's mental health.

Intervention Development for Tailored Education for Aging and Cognitive Health (TEACH) for Dementia Prevention in Midlife Adults: Protocol for a Randomized Controlled Trial.

A total of 12 modifiable risk factors account for 40% of dementia cases globally, yet population adherence to health behaviors associated with these factors is low. Midlife is a critical window for dementia prevention, as brain pathology often begins to accumulate years or decades before the onset of symptoms. Although multidomain behavioral interventions have been efficacious in reducing the risk of cognitive decline, adherence is low. Intrapersonal factors, such as health beliefs, are known mediators of the relationship between knowledge and health behavior. In keeping with stage I of the National Institutes of Health (NIH) Stage Model for Behavioral Intervention Development, this study will use mixed methods to (1) develop an enhanced health education intervention, including an explanatory method for communicating information about dementia risk and personal health beliefs, and (2) conduct a pilot randomized controlled trial (n=20 per intervention arm) over 8 weeks to assess the feasibility of delivering the enhanced intervention versus basic health education alone. Phase 1 will involve focus groups and individual qualitative interviews. Focus groups will be analyzed using (1) a descriptive framework matrix analysis and (2) interpretive data review by the research team. Individual qualitative interviews will be coded using applied thematic analysis using a phenomenographic approach. Phase 2 will involve a pilot randomized controlled trial. Proximal outcomes (measured at baseline, 4 weeks, and 8 weeks) include the perceived threat of Alzheimer disease, dementia awareness, and self-efficacy. This project was funded in August 2022. Data collection began in 2023 and is projected to be completed in 2025. Study findings will reveal the feasibility of delivering an 8-week multidomain health education intervention for primary prevention of dementia in midlife and will provide preliminary evidence of mechanisms of change. ClinicalTrials.gov NCT05599425; https://clinicaltrials.gov/study/NCT05599425. DERR1-10.2196/60395.

Immune effector cell-associated enterocolitis following chimeric antigen receptor T-cell therapy in multiple myeloma

We report 14 cases of immune effector cell (IEC)-associated enterocolitis following chimeric antigen receptor T-cell (CAR-T) therapy in multiple myeloma, with a 1.2% incidence overall (0.2% for idecabtagene vicleucel and 2.2% for ciltacabtagene autoleucel). Patients developed acute-onset symptoms (typically non-bloody Grade 3+ diarrhea) with negative infectious workup beginning a median of 92.5 days (range: 22–210 days) after CAR-T therapy and a median of 85 days after cytokine release syndrome resolution. Gut biopsies uniformly demonstrated inflammation, including intra-epithelial lymphocytosis and villous blunting. In one case where CAR-specific immunofluorescence stains were available, CAR T-cell presence was confirmed within the lamina propria. Systemic corticosteroids were initiated in 10 patients (71%) a median of 25.5 days following symptom onset, with symptom improvement in 40%. Subsequent infliximab or vedolizumab led to improvement in 50% and 33% of corticosteroid-refractory patients, respectively. Five patients (36%) have died from bowel perforation or treatment-emergent sepsis. In conclusion, IEC-associated enterocolitis is a distinct but rare complication of CAR-T therapy typically beginning 1–3 months after infusion. Thorough diagnostic workup is essential, including evaluation for potential T-cell malignancies. The early use of infliximab or vedolizumab may potentially hasten symptom resolution and lower reliance on high-dose corticosteroids during the post-CAR-T period.

Non-Invasive Detection of Nitrogen Deficiency in Cannabis sativa Using Hand-Held Raman Spectroscopy

Proper crop management requires rapid detection methods for abiotic and biotic stresses to ensure plant health and yield. Hemp (Cannabis sativa L.) is an emerging economically and environmentally sustainable crop capable of yielding high biomass. Nitrogen deficiency significantly reduces hemp plant growth, affecting photosynthetic capacity and ultimately decreasing yield. When symptoms of nitrogen deficiency are visible to humans, there is often already lost yield. A real-time, non-destructive detection method, such as Raman spectroscopy, is therefore critical to identify nitrogen deficiency in living hemp plant tissue for fast, precise crop remediation. A two-part experiment was conducted to investigate portable Raman spectroscopy as a viable hemp nitrogen deficiency detection method and to compare the technique’s predictive ability against a handheld SPAD (chlorophyll index) meter. Raman spectra and SPAD readings were used to train separate nitrogen deficiency discrimination models. Raman scans displayed characteristic spectral markers indicative of nitrogen deficiency corresponding to vibrational modes of carotenoids, essential pigments for photosynthesis. The Raman-based model consistently predicted nitrogen deficiency in hemp prior to the onset of visible stress symptoms across both experiments, while SPAD only differentiated nitrogen deficiency in the second experiment when the stress was more pronounced. Our findings add to the repertoire of plant stresses that hand-held Raman spectroscopy can detect by demonstrating the ability to provide assessments of nitrogen deficiency. This method can be implemented at the point of cultivation, allowing for timely interventions and efficient resource use.