Search Results (34,217)

Introduction: Scrub typhus is a mite-borne infectious disease caused by “Orientia tsutsugamushi”, a bacterium that was formerly classified under the genus Rickettsia. It is transmitted to humans through the bites of infected chigger mites (larval trombiculid mites). However, clinical data on the cardiac manifestations of scrub typhus and their outcomes remain limited. Methods: This research was retrospectively conducted at a tertiary care hospital in South India. The study included all patients admitted from January 2016 to September 2021 who fulfilled the clinical criteria for a diagnosis of scrub typhus. Data were collected for 426 patients. Patients with previously diagnosed heart disease and mixed infections (leptospirosis, dengue fever, blood culture positivity, and COVID-19 positivity) were excluded. Comprehensive assessments of clinical presentation, electrocardiography (ECG), 2D echocardiography, and outcomes, including all-cause mortality and probable myocarditis, were performed. Multivariate regression analysis was performed to identify independent predictors of all-cause mortality and probable myocarditis. Results: Out of 426 patients, 200 (46.9%) were male and 226 (53.1%) were female. The mean age at presentation was 49.29 ± 14.43 years. A total of 108 (25.4%) patients had diabetes and 82 (19.25%) had hypertension. Sinus tachycardia (29.3%) was the most frequent ECG finding. Echocardiographic evidence of probable myocarditis was observed in 20 (4.7%) patients, while 6 (1.4%) patients had isolated RV dysfunction, 4 (0.9%) had biventricular dysfunction, 7 (1.6%) had significant pulmonary hypertension, and 40 (9.4%) had trivial pericardial effusion. A total of 78 (18.3%) patients had acute respiratory distress syndrome. All-cause mortality was observed in 12 (2.8%) patients. A total of 56 (13.1%) patients developed multiorgan dysfunction syndrome (MODS) during their hospitalization. A total of 78 (18.3%) patients were documented to have acute kidney injury (AKI), and 22 (5.2%) patients underwent hemodialysis. Multivariable binary logistic regression analysis revealed that probable myocarditis and MODS were independent predictors of mortality among patients with scrub typhus, and age, female gender, and LV systolic dysfunction were identified as predictors of overall complications, including mortality, probable myocarditis, congestive heart failure, MODS, AKI, and the need for hemodialysis. Conclusions: Probable myocarditis was the most frequent cardiac manifestation noted in patients with scrub typhus, and in addition to MODS, probable myocarditis was an independent predictor of mortality in this cohort. Thus, it is crucial to maintain clinical vigilance regarding the cardiac status of such patients. Full article

Many recent progresses in the overall quality of life have allowed for an increase in life expectancy, both in humans and in dogs. In addition, long-lived individuals may develop neurodegenerative disorders, and one of the most important in human medicine is Alzheimer’s disease (AD). In veterinary medicine, the AD counterpart is Canine Cognitive Dysfunction Syndrome (CCDS), which, generally, affects elderly dogs from 8 years of age. These cognitive disorders are becoming frequently encountered conditions and, despite researchers’ attention towards pathogenesis, treatment and diagnosis, more efforts are required to outline which clinical and laboratory evaluations must be carried out to reach a presumptive antemortem diagnosis of CCDS. The biggest need is the establishment of standardized protocols and guidelines for a correct clinical and diagnostic approach towards dogs with clinical signs referrable to CCDS. In this narrative review, we examined the up-to-date scientific literature on the topic, focusing our attention on sensitive and reliable markers for clinical antemortem CCDS diagnosis. Even if some parameters analyzed are interesting and promising, more investigations are needed to confirm the results obtained so far. This is crucial because a correct diagnosis is fundamental to determine the best treatment and, thus, to guarantee animals’ health and welfare. Full article

Background/Objectives: Heart disease affects 0.1% to 4% of pregnant women, with congenital heart defects being the leading cause in developed countries. While maternal mortality is generally low, pre-existing cardiac conditions substantially increase adverse outcome risks. This report describes the multidisciplinary management of a pregnant patient with a bicuspid aortic valve, severe aortic stenosis, and ascending aortic ectasia. Case Presentation: A 34-year-old pregnant woman, asymptomatic but at high risk (World Health Organization Class III) for hemodynamic decompensation, was closely monitored throughout gestation. At 36 weeks, intrauterine growth restriction was detected, prompting an elective cesarean delivery at 38 weeks. Postpartum, the patient developed pre-eclampsia, which was managed successfully. Imaging revealed progressive aortic dilation, leading to surgical aortic valve replacement and ascending aorta reduction plasty. Post-operatively, atrioventricular reentrant tachycardia from an unrecognized accessory pathway developed; medical therapy effectively controlled the arrhythmia after failed catheter ablation. One year later, both mother and child remained in good health. Discussion: This case illustrates the complexity of managing pregnancy in women with congenital heart disease and significant aortic pathology. The physiological changes of pregnancy can exacerbate underlying lesions, necessitating individualized risk assessment, vigilant monitoring, and timely intervention. Conclusions: A multidisciplinary approach involving cardiology, obstetrics, anesthesiology, and genetics is essential to optimize outcomes for pregnant women with significant heart disease. As advances in care allow more women with congenital heart defects to reach childbearing age, structured care pathways remain vital for ensuring safe pregnancies and long-term cardiovascular health. Full article

Background: Alzheimer’s disease is a progressive neurodegenerative disorder characterized by cognitive decline and memory loss. Gamma (γ) oscillations are closely linked to learning and memory, and recent interest has grown around Gamma ENtrainment Using Sensory stimulation (GENUS) as a non-invasive neuromodulation strategy. However, the therapeutic impact of vibrotactile gamma stimulation under varying physical parameters such as acceleration remains underexplored. Methods: Differentiated SH-SY5Y cells were treated with amyloid-β (Aβ) and exposed to vibrotactile stimulation at 2.2 or 4.0 m/s². In vivo, male C57BL/6N mice (7 weeks old, 35 g) were administered scopolamine to induce neurotoxicity and randomly assigned to sham, scopolamine, donepezil, or vibrotactile stimulation groups (n = 10 each). Behavioral tests, biochemical assays, Western blotting, and immunohistochemistry were performed to evaluate cognitive function, oxidative stress, cholinergic activity, synaptic plasticity, and neuroinflammation. Results: In vitro, SH-SY5Y cells exposed to amyloid-beta (Aβ) were treated with vibrotactile stimulation, resulting in enhanced neuronal marker expression at 2.2 m/s². In vivo, mice receiving stimulation at 2.2 m/s² showed improved cognitive performance, reduced oxidative stress, restored cholinergic function, suppressed neuroinflammation, and enhanced synaptic plasticity. Mechanistically, these effects were associated with activation of the AKT/GSK3β/β-catenin pathway. Conclusions: Our findings demonstrate that vibrotactile gamma stimulation at 2.2 m/s² exerts greater therapeutic efficacy than higher acceleration, highlighting the importance of optimizing stimulation parameters. This work supports the potential of acceleration-tuned, non-invasive GENUS-based therapies as effective strategies for cognitive recovery in neurodegenerative conditions. Full article

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, spread rapidly across the globe in 2020, with most countries experiencing two distinct waves of infection. In Brazil, the second wave was marked by the emergence of the P.1 (Gamma) variant, which disproportionately affected younger individuals and was associated with increased mortality. This study aimed to evaluate the epidemiological profile and post mortem histopathological lung findings, correlate them with laboratory results, and compare the first and second waves of COVID-19. To investigate neutrophil extracellular traps (NETs), we performed immunohistochemistry for citrullinated histone H3 (cit-H3) and myeloperoxidase (MPO). Our cohort included patients who died in the intensive care unit (ICU) of a single center in southern Brazil. The study included 42 patients, 24 from the first wave and 18 from the second, who died between March 2020 and August 2021. Laboratory data included complete blood counts and D-dimer levels. Histopathological analyses were conducted using H&E-stained slides and reviewed independently by two blinded pathologists. MPO and cit-H3 immunohistochemistry were performed to evaluate NETs markers. All cases exhibited varying degrees of inflammation and diffuse alveolar damage (DAD), with frequent microvascular thrombi. Neutrophilic infiltration was significantly higher in the second wave. Additionally, cases with intense neutrophilic infiltration showed a stronger association with thrombosis. NETs were identified in 10 cases. No significant correlation was found between histopathological findings, NETs, and laboratory blood count results. The histopathological findings were consistent with those reported globally. The second wave of COVID-19 showed higher neutrophilic infiltrate in the lung tissue. Neutrophils play a key role in the inflammatory response and NET formation might indicate an increased risk of mortality. Further studies can consider NET-targeted therapies as potential strategies. Full article

Introduction: The decline of serum estrogen in postmenopausal women leads to several changes in the vulvovaginal and vesicourethral areas, resulting in the genitourinary syndrome of menopause (GSM), characterized by bothersome symptoms such as vaginal atrophy, lack of lubrication, dyspareunia, urgency, dysuria, and recurrent urinary tract infections. Nevertheless, this condition could also be experienced by younger women affected by hormone-dependent tumors. Although topical estrogens are considered “the gold standard”, hormonal treatments cannot be indicated in cancer survivors. As a result, energy-based devices using radiofrequency and laser technologies have emerged as alternative options. This prospective study aimed to evaluate the benefits of non-invasive monopolar radiofrequency (RF) in women affected by GSM who have contraindications to, did not respond to, or declined local estrogen therapy. Methods: The patients underwent five weekly sessions of second-generation monopolar RF. At baseline and at the fifth session, two validated questionnaires were administered to the patients: the Visual Analogue Scale (VAS) and the Female Sexual Function Index (FSFI-19). On the other hand, the vaginal mucosa status was evaluated by clinicians through the Vaginal Health Index (VHI). At the end of the cycle, the Patient Global Impression of Improvement (PGI-I) questionnaire was collected. Results: Based on 44 patients who completed five sessions of radiofrequency, a significant improvement was observed in sexual function according to the FSFI scale (22.9 vs. 38.6; p < 0.001) and in VVA atrophy symptoms, as documented by the VAS score (223 vs. 125; p < 0.001). The mean VHI score increased by 3 points (p < 0.001). Moreover, according to PGI-I, 96% of patients reported a perceived improvement (PGI-I score ≤ 3). Conclusions: Radiofrequency could provide an innovative and safe therapeutic approach for patients suffering from GSM and VVA, especially when hormonal strategies are unsuitable. Full article

Chronic kidney disease (CKD) prevalence is rising worldwide and is projected to become the fifth leading cause of death globally by 2040. The high proportion of undiagnosed early-staged CKD and delayed diagnosis is of significant concern. The access to diagnosis and treatment is also limited in low-resource settings. The majority of individuals with kidney disease succumb to cardiovascular disease complications. Furthermore, heart failure and CKD are closely interconnected, with each condition significantly increasing the risk of developing the other. They share common risk factors, such as high blood pressure and diabetes, and their coexistence worsens prognosis and raises mortality rates. The bidirectional relationship between the heart and kidneys becomes even more complex and challenging in the context of cardiorenal syndrome. Emerging medications, such as sodium–glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists, have shown remarkable efficacy in slowing the progression of kidney disease, surpassing the benefits of traditional treatments. This article summarizes the evidence on the early detection of CKD and real-world opportunities to slow the progression of CKD by optimizing cardiorenal guideline-directed medical therapy. Full article

Diastolic heart failure, also referred to as heart failure with preserved ejection fraction (HFpEF), is a complex cardiovascular clinical syndrome that is a growing health burden worldwide. Patients present with high abnormal left ventricular filling pressures but normal ejection fraction that can progress to diastolic heart failure and death. The causes of diastolic dysfunction are varied, and pharmacotherapies are limited to managing the symptoms of the disease. At the level of the myocyte, cytoskeletal disarray and mitochondrial dysfunction are common features associated with diastolic disease. Understanding the mechanisms of abnormal diastolic filling pressures is necessary to identify novel treatments, which remains an area of significant unmet need. In this article, we discuss the mechanisms of maladaptive feedback contributing to increased extracellular stiffness, cytoskeletal disarray, and mitochondrial dysfunction in diastolic heart failure. Since the mechanisms are complex, understanding the contributing factors provides opportunities for the development of novel drug targets. These will be discussed and examined in the context of current therapy. Full article

Congenital hypothyroidism (CH) is a heterogeneous condition present at birth, resulting in severe-to-mild thyroid hormone deficiency. This condition is difficult to recognize shortly after birth. Therefore, many countries worldwide have implemented newborn screening (NBS) programs for CH since the 1970s. The most recent European guidelines strongly recommend screening for primary CH, as well as for central CH when financial resources are available. However, no consensus has been reached yet to screen more rare forms of CH, such as Allan–Herndon–Dudley syndrome (AHDS), an X-linked condition linked to mutations in the gene encoding a transmembrane monocarboxylate transporter (MCT8), resistance to thyroid hormone beta (RTHβ), and resistance to thyroid hormone alfa (RTHα). The combined measurement of thyroid-stimulating hormone (TSH) and total thyroxine (TT4) on DBS currently allows the recognition of central CH (TSH low/normal and low TT4 without defects in transport proteins). With the introduction of liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) for measurement of free triiodothyronine (FT3) and free thyroxine (FT4), it would be possible to screen for RTHβ (TSH normal/high and high FT4). More complicated would be the method to screen RTHα. It would require the combined measurement of FT4 and FT3 and the determination of FT3/FT4 ratio, while the combined measurement of FT3 and reverse T3 (rT3) to calculate FT3/rT3 ratio would be useful to screen AHDS. In this article, we provide some reflections on expanding NBS for primary CH also to other rare forms of CH. Full article

Background: Antithrombotic therapy plays an important role in acute coronary syndrome (ACS). The combination of anticoagulant and antiplatelet therapy resulted in fewer complications and stronger potency compared to traditional monotherapy. Our net meta-analysis aimed to compare and rank the safety of different treatments used in patients with ACS. Method: We conducted a search for trials in three prominent databases. The main objective of our investigation was to assess hemorrhage. Additional outcomes included mortality, myocardial infarction, stroke, and embolism. We used a frequentist network meta-analysis with a random-effects model to, directly and indirectly, compare safety across different antithrombotic strategies. Result: A total of 30 randomized clinical trials were included in this net meta-analysis with 135,471 ACS patients. In these eight different antithrombotic therapies, SAPT (single-agent platelet inhibitor therapy) showed the lowest risk of bleeding (SUCRA = 0.5%). The highest risk of bleeding was observed in VKA (vitamin K antagonists) + DAPT (dual antiplatelet therapy) (SUCRA = 99.8%). Bleeding among NOAC (non-vitamin K antagonist oral anticoagulants) + DAPT was found to be higher than DAPT (OR = 1.94, 95% CI = 1.42–2.65). NOAC + SAPT significantly reduced the embolism (OR = 1.50, 95% CI = 1.16–1.94) and myocardial infarction (OR = 1.22, 95% CI = 1.08–1.37) events compared with SAPT. In addition, VKA significantly reduced the rate of stroke compared with SAPT (OR = 3.45, 95% CI = 1.17–10.18). However, no significant difference was observed in death events among these eight antithrombotic therapies. Conclusions: We advise against the use of SAPT in ACS due to its elevated risk of embolism, myocardial infarction, and stroke. It is important to mention that the combination of NOAC and SAPT has a lower incidence of myocardial infarction, bleeding and embolism problems. Therefore, the combination of NOAC and SAPT may be the optimal approach to achieve a balance between the risks of bleeding and embolism. This meta-analysis was registered in PROSPERO with the registration number CRD42024542826. Full article

Background/Objectives: Patients with inappropriate sinus tachycardia (IST) and postural orthostatic tachycardia syndrome (POTS) exhibit complex clinical profiles due to autonomic dysfunction. While sinus node sparing (SNS) hybrid ablation is emerging as a promising therapy, there are no established guidelines worldwide for post-procedure patient management and care is mainly based on telemonitoring. In contrast, our hybrid cardiac rehabilitation (HCR) program integrates inpatient care and home-based telerehabilitation. We aim to evaluate the implementation of the HCR program, patient acceptance and adherence, and the effectiveness of the Malmö POTS scoring system in monitoring disease progression and rehabilitation outcomes. Methods: Patients underwent a personalized HCR program after SNS. The program included early mobilization, psychological support, respiratory therapy, and structured exercise. Clinical outcomes were assessed using symptom burden (Malmö POTS score), ECG parameters, exercise duration, perceived exertion, and rehabilitation adherence. Results: All patients completed the inpatient phase, and 87% completed the home-based phase. In the early postoperative period, pericarditis, anemia, and benign rhythm disturbances were mild and self-limiting. The Malmö POTS score decreased from 65.3 to 25.7. Lower perceived exertion early in the program correlated with clinical improvement. At the 2-month follow-up, 81% of patients no longer met the clinical criteria for IST/POTS without the use of medications. The program was evaluated as safe, feasible, and well-tolerated, with high patient satisfaction. Conclusions: A well-organized hybrid cardiac rehabilitation program after SNS is feasible, safe, and well-tolerated in IST/POTS patients. The Malmö POTS score may support outcome monitoring. The integration of individualized training and telemedicine represents a promising development for patients post-SNS ablation. While this study demonstrates feasibility and potential benefits, further controlled studies are needed to evaluate its impact on long-term recovery and symptom control. Full article

Vitamins A, D, E, K, B2, B12, and C play a key role in regulating metabolism and oxidative stress, significantly impacting cardiometabolic health. This review uniquely integrates mechanistic and epidemiological data to examine sex-specific differences in the bioavailability, metabolism, and physiological effects of these vitamins. By linking hormonal and genetic factors with oxidative stress modulation, lipid metabolism, and endothelial function, we outline how individualized vitamin intake strategies may help prevent cardiovascular and metabolic disorders. The paper also identifies natural dietary sources and optimal intake recommendations for each vitamin, emphasizing the importance of tailoring supplementation to sex-related needs. This sex-focused perspective provides a basis for developing personalized nutrition approaches to optimize cardiometabolic outcomes. Full article

Post-translational modifications (PTMs) of proteins, as the core mechanism for dynamically regulating follicular development, affect the maintenance of mammalian fertility by precisely coordinating granulosa cell–oocyte interaction, metabolic reprogramming, and epigenetic remodeling. Dysregulation of these modifications directly contributes to major reproductive diseases, including polycystic ovary syndrome (PCOS) and premature ovarian insufficiency (POI). Post-translational modifications regulate follicular development through intricate mechanisms. Thus, this review systematically synthesizes recent advances in PTMs, encompassing traditional ones such as phosphorylation, ubiquitination, and acetylation, alongside emerging modifications including lactylation, SUMOylation, and ISGylation, thereby constructing a more comprehensive PTM landscape of follicular development. Furthermore, this study dissects the molecular interaction networks of these PTMs during follicular activation, maturation, and ovulation, and uncovers the common mechanisms through which PTM dysregulation contributes to pathological conditions, including hyperandrogenism in PCOS and follicular depletion in POI. Finally, this review ultimately provides a theoretical basis for improving livestock reproductive efficiency and precise intervention in clinical ovarian diseases. Full article

Background: Functional Neurological Disorder (FND) encompasses a spectrum of symptoms—including motor, cognitive, and seizure-like manifestations—that are not fully explained by structural neurological disease. Accumulating evidence suggests that comorbid psychiatric and somatic conditions significantly influence the clinical course, diagnostic complexity, and treatment response in FND. Objective: This study systematically explores psychiatric and medical comorbidities across major FND subtypes—Functional Cognitive Disorder (FCD), Functional Movement Disorder (FMD), and Psychogenic Non-Epileptic Seizures (PNES)—with an emphasis on subtype-specific patterns and shared vulnerabilities. Methods: We conducted a narrative review of the published literature, guided by systematic principles for transparency, covering both foundational and contemporary sources to examine comorbid conditions in patients with FCD, FMD, PNES, PPPD and general (mixed) FND populations. Relevant studies were identified through structured research and included based on methodological rigor and detailed reporting of comorbidities (PRISMA). Extracted data were organized by subtype and comorbidity type (psychiatric or medical/somatic). Results: Across all FND subtypes, high rates of psychiatric comorbidities were observed, particularly depression, anxiety, PTSD, and dissociative symptoms. FCD was predominantly associated with internalizing symptoms, affective misattribution, and heightened cognitive self-monitoring. FMD demonstrated strong links with trauma, emotional dysregulation, and personality vulnerabilities. PNES was characterized by the highest burden of psychiatric illness, with complex trauma histories and dissociation frequently reported. Somatic comorbidities—such as fibromyalgia, chronic pain, irritable bowel syndrome, and fatigue—were also prevalent across all subtypes, reflecting overlapping mechanisms involving interoception, central sensitization, and functional symptom migration. Conclusions: Comorbid psychiatric and medical conditions are integral to understanding the presentation and management of FND. Subtype-specific patterns underscore the need for individualized diagnostic and therapeutic approaches, while the shared biopsychosocial mechanisms suggest benefits of integrated care models across the FND spectrum. Full article

CD9 protein belongs to a family of proteins called tetraspanins, so named for their four-transmembrane-spanning architectures. These proteins are located in domains in the plasmatic membrane, called tetraspanin-enriched microdomains (TEMs). Several proteases and cellular receptors for virus entry cluster into TEMs, suggesting that TEMs are preferred virus entry portals. Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein mediates virus attachment and entry into cells by binding to human angiotensin-converting enzyme 2 (ACE-2). In addition, the secretory, type-I membrane-bound SARS-CoV-2 S protein is synthesized as a precursor (proS) that undergoes posttranslational cleavages by host cell proteases, such as furin and TMPRSS2. Moreover, it has been shown that neuropilin-1 (NRP1), which is known to bind furin-cleaved substrates, potentiates SARS-CoV-2 infectivity. Our results indicate that CD9 facilitates SARS-CoV-2 infection. In addition, we show how knocking out CD9 leads to a decrease in the expression of NRP1, a protein that improves SARS-CoV-2 infection. Furthermore, we show that CD9 colocalizes with ACE-2, NRP1, furin, and TMPRSS2 at the plasma membrane; that the absence of CD9 decreases the expression of these proteins on the plasma membrane CD9-enriched microdomains, and that CD9 interacts with ACE2. In conclusion, our data suggest that CD9 facilitates SARS-CoV-2 infection and that CD9 brings together different host proteins involved in SARS-CoV-2 attachment and entry into host cells, such as ACE2, NRP1, furin, and TMPRSS2. Importantly, the fact that a blocking antibody targeting CD9 can effectively reduce SARS-CoV-2 titers highlights not only the mechanistic role of CD9 in viral entry but also offers translational potential, suggesting that tetraspanin-targeting antibodies could be developed as therapeutic agents against SARS-CoV-2 and possibly other coronaviruses, with meaningful implications for clinical intervention. Full article