UNASSIGNED: Individuals affected by the post-covid condition (PCC) show an increased fatigue and the so-called post-exertion malaise (PEM) that led health professionals to advise against exercise although accumulating evidence indicates the contrary. The goal of this study is to determine the impact of a closely monitored 8-week mixed exercise program on physical capacity, symptoms, fatigue, systemic oxidative stress and plasma proteomic profiles of PCC cases.
UNASSIGNED: Twenty-five women and men with PCC were assigned sequentially to exercise (n = 15) and non-exercise (n = 10) groups. Individuals with no PCC served as a control group. The exercise program included cardiovascular and resistance exercises. Physical capacity, physical activity level and the presence of common PCC symptoms were measured before and after the intervention. Fatigue was measured the day following each exercise session. Plasma and PBMC samples were collected at the beginning and end of the training program. Glutathione and deoxyguanosine levels in PBMC and plasma proteomic profiles were evaluated.
UNASSIGNED: Bicep Curl (+15% vs 4%; p = 0.040) and Sit-to-Stand test (STS-30 (+31% vs +11%; p = 0.043)) showed improvement in the exercise group when compared to the non-exercise group. An interaction effect was also observed for the level of physical activity (p =0.007) with a positive effect of the program on their daily functioning and without any adverse effects on general or post-effort fatigue. After exercise, glutathione levels in PBMCs increased in women but remained unchanged in men. Discernable changes were observed in the plasma proteomics profile with certain proteins involved in inflammatory response decreasing in the exercise group.
UNASSIGNED: Supervised exercise adapted to the level of fatigue and ability is safe and effective in PCC patients in improving their general physical capacity and wellbeing. Systemic molecular markers that accompany physical improvement can be monitored by analyzing plasma proteomics and markers of oxidative stress. Large-scale studies will help identify promising molecular markers to objectively monitor patient improvement.

UNASSIGNED: Eosinophilic esophagitis (EoE) is a chronic, inflammatory disease of the esophagus leading to symptoms of esophageal dysfunction; dysphagia is the most common symptom experienced by adults and adolescents.
UNASSIGNED: We sought to perform a psychometric evaluation of the Dysphagia Symptom Questionnaire (DSQ), a patient-reported outcome measure for patients with EoE.
UNASSIGNED: Using baseline and week 24 data from the randomized, interventional, multinational phase 3 R668-EE-1774 trial (NCT03633617), the measurement properties of the DSQ-including reliability, construct and known-groups validity, responsiveness, and interpretation of change-were evaluated.
UNASSIGNED: The analysis population comprised 239 patients with EoE (age [mean ± SD], 28.1 ± 13.14 years; 63.6% male; 90.4% White). Intraclass correlation coefficients of 0.92 and 0.97 exceeded the acceptable reliability threshold (≥0.70). Construct validity correlations with EoE symptom and impact measures were moderate at baseline (|r| = 0.44-0.55) and week 24 (|r| = 0.55-0.69), and the DSQ biweekly total score discriminated among groups defined by disease severity. Analyses exploring interpretation of change from baseline on the DSQ biweekly total score indicated thresholds for within-patient improvement ranging from 9 to 23 points; a within-patient improvement from baseline of 13 points or greater could be considered clinically meaningful.
UNASSIGNED: This analysis confirmed that the DSQ has acceptable distributional properties, test-retest reliability, construct validity, and ability to detect change. Therefore, the DSQ is a valid and reliable measure to assess the patient-reported symptom of dysphagia among adult and adolescent patients with EoE in the context of a clinical trial setting.

Fractional flow reserve fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) is currently recommended in the management of patients with stable coronary artery disease (CAD). Pullback pressure gradient (PPG) index is an emerging concept that provides a fully quantitative measure of the longitudinal distribution of CAD. It can be derived from FFR, as well as other non-hyperemic indices, and is a novel metric of assessing the focality or diffuseness of CAD. PPG adds a second domain to the assessment of CAD, beyond ischemia as measured by FFR, and may enable clinicians to better inform their patients about the status of their CAD but may also predict potential outcomes before revascularization. In this article, we will provide an in-depth review on the concept of PPG index and its correlation to pre and post revascularization ischemia. We will assess the relationship between PPG index and plaque characteristics and how this is translated into any difference in procedural and long-term clinical outcomes.

The coronary sinus reducer (CSR), a minimally invasive device, has emerged as a promising alternative for improving myocardial perfusion in these patients. This meta-analysis evaluated the effectiveness of CSR implantation in patients with refractory angina. A comprehensive search of PubMed, EMBASE, and Web of Science databases identified 10 relevant studies with a pooled sample size of 799 patients. The analysis focused on changes in the Canadian Cardiovascular Society (CCS) classification score, Seattle Angina Questionnaire (SAQ) score, and six-minute walk distance (6MWD) from baseline to follow-up. Results showed significant improvements across all measured outcomes. CCS scores decreased significantly post-CSR implantation, indicating reduced angina severity. SAQ scores improved across all domains, including physical limitation, anginal stability, anginal frequency, treatment satisfaction, and quality of life, suggesting enhanced overall well-being. The 6MWD also increased significantly, reflecting improved functional capacity. These findings highlight CSR\'s potential as an effective treatment option for patients with refractory angina who have exhausted traditional therapies. CSR implantation appears to alleviate angina symptoms, improve quality of life, and enhance exercise tolerance. Future research should prioritize larger, multi-center randomized controlled trials to validate these findings. Long-term follow-up studies are needed to assess sustained benefits and potential risks.

Children\'s mental health symptoms\' development can be characterized by both continuity and discontinuity. However, existing studies ignore the potential discontinuity in children\'s internalizing symptoms\' development. Hence, the current study examines continuous and discontinuous developmental trajectories using representative data from a sample of 2792 children (49.10% females) from the Growing Up in Australia cohort assessed seven times (ages 4, 6, 8, 10, 12, 14, 16). Longitudinal measurement invariance analyses revealed that internalizing symptoms were comparable over time. Linear, quadratic, and piecewise latent growth curve models were deployed to estimate the trajectory of internalizing symptoms from early childhood to late adolescence. The analyses showed that internalizing symptoms were characterized by a quadratic-quadratic piecewise growth curve comprising two distinct phases of upward concave growth. Internalizing scores reduced steadily between ages 4 and 8 years but exhibited a slight upward curvature between ages 8 and 10 years. By age 14 years, the trajectory remained relatively stable but spiked between age 14 and 16 years. The two phases of internalizing symptoms\' development were largely unrelated. Overall, the study adds to the knowledge about the development of internalizing mental health from early childhood to late adolescence and highlights the need for additional support in late adolescence.

Despite enormous recent advances in stage IV melanoma treatment, it continues to have a significant mortality. Five-years survival is below 50% even when granted full access to effective therapeutic regimens. Considering the real world, mostly with low or medium-income countries like Brazil, where 75% of population depends on public health system receiving ineffective Dacarbazine chemotherapy, more than 95% of stage IV patients are dead before 5 years. Knowing the survival process of melanoma end-of-life time is imperative to help physicians to establish better symptoms control and improve the quality of death of these patients.
METHODS: Relative caregiver of melanoma end of life patients were invited to participate in a specific interview answering questions for the purpose of gathering information regarding symptoms and patients\' complaints at the last 30 days, 7 days and at the day of death.
RESULTS: Although melanoma has a highest propensity for brain dissemination, seizure and focal neurological deficits were not a major complaint. Most of dying melanoma symptoms are shared among other solid terminality tumor process and get worse from 30 days to 7 days, but the majority of symptoms kept unchanged from 7 days till time to death. Wound bleeding and bad odor were the only complaints that got worse during the whole terminality process and could be improved with better commitment of assistant team.
CONCLUSIONS: although a strong effort is made to control brain metastasis, local and regional open wound metastasis represents a major remediable complaint that should receive more attention at end-of-life melanoma patients.

UNASSIGNED: Research data show the impact of the endocannabinoid system on psychosis through its neurotransmission homeostatic functions. However, the effect of the endocannabinoid system genetic variability on the relationship between cannabis use and psychosis has been unexplored, even less in first-episode patients. Here, through a case-only design, we investigated the effect of cannabis use and the genetic variability of endocannabinoid receptors on clinical and cognitive outcomes in first-episode psychosis (FEP) patients.
UNASSIGNED: The sample comprised 50 FEP patients of European ancestry (mean age (sd) = 26.14 (6.55) years, 76% males), classified as cannabis users (58%) or cannabis non-users. Two Single Nucleotide Polymorphisms (SNP) were genotyped at the cannabinoid receptor type 1 gene (CNR1 rs1049353) and cannabinoid receptor type 2 gene (CNR2 rs2501431). Clinical (PANSS, GAF) and neuropsychological (WAIS, WMS, BADS) assessments were conducted. By means of linear regression models, we tested the main effect of cannabis use and its interaction with the polymorphic variants on the clinical and cognitive outcomes.
UNASSIGNED: First, as regards cannabis effects, our data showed a trend towards more severe positive symptoms (PANSS, p = 0.05) and better performance in manipulative abilities (matrix test-WAIS, p = 0.041) among cannabis users compared to non-users. Second, concerning the genotypic effects, the T allele carriers of the CNR1 rs1049353 presented higher PANSS disorganization scores than CC homozygotes (p = 0.014). Third, we detected that the observed association between cannabis and manipulative abilities is modified by the CNR2 polymorphism (p = 0.022): cannabis users carrying the G allele displayed better manipulative abilities than AA genotype carriers, while the cannabis non-users presented the opposite genotype-performance pattern. Such gene-environment interaction significantly improved the overall fit of the cannabis-only model (Δ-R2 = 8.4%, p = 0.019).
UNASSIGNED: Despite the preliminary nature of the sample, our findings point towards the role of genetic variants at CNR1 and CNR2 genes in the severity of the disorganized symptoms of first-episode psychosis and modulating cognitive performance conditional to cannabis use. This highlights the need for further characterization of the combined role of endocannabinoid system genetic variability and cannabis use in the understanding of the pathophysiology of psychosis.

Background All over the world, millions die of hypertension (HTN) every year. Given the influence of healthcare expenses, HTN represents a serious public health issue in developed and developing countries. HTN is common in Pakistan; however, there are several myths about the symptoms of raised blood pressure that need to be identified. Objective The objective of this study is to compare the frequency of high blood pressure-associated symptoms in normotensive and hypertensive adult populations in Karachi, Pakistan. Methodology A community-based cross-sectional observational study was conducted among 277 patients aged 18 years and above who were attending the OPD of different community health centers in Karachi, with and without HTN. Ethical approval was obtained, and data were collected using a convenient sampling technique on a predesigned questionnaire and analyzed using IBM SPSS Statistics for Windows, Version 20.0 (Released 2011; IBM Corp., Armonk, NY, USA). Results Out of the total study population, 88 (31.65%) were normotensive, and 189 (67.98%) were hypertensive. In the hypertensive group, approximately 100 (52.9%) were men and 89 (47.1%) were women. The mean ages of normotensives and hypertensives were 44.13 + 11.0 and 49.2 + 13.1 years, respectively. Mean age, heart rate, and smoking status were significantly different between the two groups. Among several perceived blood pressure symptoms like vision problems, sleep apnea, and abnormal heartbeat was significantly higher in the hypertensive group. Conversely, although headache, vertigo, edema, and epistaxis were more frequent in the hypertensive group, the difference was not statistically significant. Conclusions In our study, >65% of patients visiting OPD had high blood pressure. Several symptoms were found to be more prevalent in hypertensive individuals compared with non-hypertensive ones. More large-scale studies are recommended to further explore the common symptoms associated with HTN in our population.

UNASSIGNED: To assess associations of dry eye disease (DED) severity of symptoms and signs with the quality of life in patients with moderate-to-severe DED.
UNASSIGNED: At baseline, 6 and 12 months, participants (N=535) were assessed for DED symptoms using Ocular Surface Disease Index (OSDI) and signs using conjunctival staining, corneal staining, tear breakup time (TBUT), Schirmer\'s testing, meibomian gland dysfunction, and tear osmolarity. Quality of life was evaluated using the Short Form Health Survey (SF-36), consisting of Physical Component Summary (PCS) and Mental Component Summary (MCS). Spearman correlation coefficients (rho) were used to evaluate correlations between the severity of DED and SF-36.
UNASSIGNED: At baseline, Worse DED symptoms indicated by higher OSDI total score were correlated with worse PCS (rho=-0.13, P=0.002) and MCS (rho=-0.09, P=0.03) of SF-36. The worse vision-related function was correlated with a worse PCS score (rho=-0.18, P<0.0001), and worse ocular symptoms were correlated with a worse MCS score (rho=-0.15, P<0.001). More severe DED signs including corneal staining (rho=-0.22, P<0.001), Schirmer test (rho=0.11, P=0.01), TBUT (rho=0.14, P<0.001), and tear osmolarity (rho=-0.12, P=0.02) were correlated with worse PCS score but were not correlated with MCS score (P≥0.39). ln longitudinal analysis, only worsening of ocular symptoms was significantly correlated with worsening of MCS score (rho=-0.09, P=0.04).
UNASSIGNED: In patients with moderate-to-severe DED, there were significant yet weak correlations between dry eye severity of symptoms/signs and physical or mental components of SF-36. Healthcare professionals should offer DED symptom relief and support for the emotional and practical challenges in their daily lives.

UNASSIGNED: In obstructive hypertrophic cardiomyopathy (HOCM), disopyramide is used in patients who remain symptomatic despite β-blockers or verapamil. However, effectiveness of disopyramide therapy has not been clearly established due to inconsistent definition of responders and the insufficient length of follow-ups reported in literature. To address these shortcomings, we have conducted a retrospective analysis from detailed databases with long follow-up, from two HCM Referral Centers.
UNASSIGNED: 62 symptomatic HOCM patients (43% women, age 52 ± 14 years) with left ventricular (LV) outflow tract gradient (LVOTG) ≥ 50 mmHg at rest or during provocation, were recruited from two Italian Centers. Disopyramide was added as second-line therapy in the patients in whom symptoms persisted despite classic pharmacologic treatment. Patients in NYHA class > II at baseline who reached NYHA class II or I, and patients in NYHA class II at baseline who reached NYHA class I or symptoms stabilization were defined as responders.
UNASSIGNED: At follow-up, (mean 4.4 years, IQR 1.1-6.6 years), 47 patients (76%) were responders, whereas 15 (24%) were no-responders. Responders showed larger LV diastolic volume index (LVEDVi) at baseline as compared to no-responders (61 ± 14 vs. 49 ± 16 ml, respectively, p = 0.018), and, at follow-up, reached lower LVOTG than no-responders (43 ± 32 vs. 66 ± 28 mmHg, respectively, p = 0.013), with a LVOTG <50 mmHg more represented in responders than in no-responders (75% vs. 25%, respectively; p = 0.004). No side effects requiring discontinuation of the therapy were recorded.
UNASSIGNED: HOCM patients treated with disopyramide as second-line therapy in a quite long-follow-up showed a significant improvement of symptoms, which avoided SRT in up to 70% of them. Moreover, our data suggest that a larger LVEDVi at baseline identify the subgroup of patients who benefit the most from the therapy in terms of symptoms and reduction of LVOTG below 50 mmHg during treatment. We will discuss specific situations where disopyramide may be preferred over myosin inhibition to ensure that effective therapeutic options are fully considered and not prematurely dismissed.