Abstract: Background/Objectives: The physiological basis underlying symptomatic versus asymptomatic premature ventricular contractions (PVC) remains poorly understood. However, symptomatic PVC can significantly impair quality of life. In patients without structural heart disease, symptom intensity is crucial for guiding management strategies and determining the need for medical or surgical intervention. In this study, we aimed for the first time to examine the associations be-tween PVC symptoms and cardiac interoception. Methods: The study included 34 participants with PVC (20 women; median age = 42 years; 17 participants had asymptomatic PVC) without concomitant disorders. Interoception was assessed through interoceptive accuracy (IA) probed by two behavioral tests—mental tracking (MT) and heartbeat detection (HBD)—and the neurophysi-ological marker of cardiac interoception, the heartbeat-evoked potentials (HEPs). Symptom inten-sity scores reported by patients served as the response variable in the regression analysis, with IA and HEP as predictors. Other factors such as sex, age, percent of body fat, trait anxiety, and alexithymia were added to the models as confounding variables. Results: IAMT was significantly higher in patients with symptomatic PVC. IAMT and HEP modulation for the HBD task were asso-ciated with symptom intensity. A combined regression model incorporating both metrics showed the highest predictive accuracy for symptom severity. Adding confounding variables improved model quality (lower AIC); however, only the male sex emerged as a significant negative predictor for symptom intensity. Conclusions: Our findings confirm a significant association between in-teroception and PVC symptom severity. Integrating behavioral and neurophysiological interocep-tion measures enhances symptom prediction accuracy, suggesting new ways to develop diagnos-tic and non-invasive treatment strategies targeting interoception in PVC management.

Abstract: Male infertility is a significant global health issue, comprising approx. 50% of all infertility cases. Semen cryopreservation, a critical component of assisted reproductive technologies (ART), is a method commonly used in a wide range of situations, including gonadotoxic treatments such as radiation or chemotherapy, hazardous occupational exposures, or various medical conditions. Although historically viewed as potentially damaging to sperm, recent findings suggest that cryopreservation, when performed with appropriate techniques, may in fact enhance semen quality by improving the proportion of healthy spermatozoa, particularly in terms of their morphological parameters. The aim of this study was to evaluate the impact of cryopreservation on sperm morphology and viability, utilizing advanced morphological assessments pre- and post-freezing. Semen samples from 97 patients were analyzed, revealing significant improvements in morphology, with increased percentages of normal sperm and reductions in deformation indices post-thaw. The findings indicate that optimized cryopreservation protocols may support the selection of higher-quality sperm, offering valuable benefits for ART applications. These results challenge certain past assumptions regarding the impact of cryopreservation and underscore the need for refined freezing techniques to maintain and potentially enhance semen quality for reproductive use.

Abstract:

Intratumoral microbiota, the diverse community of microorganisms residing within tumor tissues, represent an emerging and intriguing field in cancer biology. These microbial populations are distinct from the well-studied gut microbiota, offering novel insights into tumor biology, cancer progression, and potential therapeutic interventions. Recent studies have explored the use of certain antibiotics to modulate intratumoral microbiota and enhance the efficacy of cancer therapies, showing promising results. Antibiotics can alter intratumoral microbiota’s composition, which may have a major role in promoting cancer progression and immune evasion. Certain bacteria within tumors can promote immunosuppression and resistance to therapies. By targeting these bacteria, antibiotics can help create a more favorable environment for chemotherapy, targeted therapy and immunotherapy to act effectively. Some bacteria within the tumor microenvironment produce immunosuppressive molecules that inhibit the activity of immune cells. The combination of antibiotics and other cancer therapies holds significant promise for creating a synergistic effect and enhancing the immune response against cancer. In this review we analyze several preclinical studies that have been conducted to demonstrate the synergy between antibiotics and other cancer therapies and discuss possible clinical implications.

Abstract:

Objectives: To evaluate the impact of diabetes mellitus (DM) on the outcome of Schlemm’s canal based minimally invasive glaucoma surgery (MIGS). Methods: In a retrospective interventional cohort study, post- operative intraocular pressure (IOP) and intracameral bleeding were analyzed in 25 diabetic and 84 non-diabetic patients with primary open angle glaucoma (POAG) or ocular hypertension (OH). Results: The mean follow-up period for all 109 eyes was 35.3±24.8 months. There was no significant difference in pre-operative IOP between diabetic and non-diabetic cohorts. However, the post-surgical IOP between 3 months and 2 years was significantly higher in the diabetic cohort (P=0.019 to 0.001). The 3-year survival probability of achieving an IOP≦15 mmHg was 17.8±0.09% in diabetic patients, significantly lower than the 30.4±0.06% observed in non- diabetic patients (P=0.042 Log-rank test). The 3-year survival probability of achieving an IOP≦18 mmHg was 56.7±0.12% in diabetic patients compared to 79.5±0.05% in non-diabetic patients, indicating a marginally significant difference between diabetic and non-diabetic cohorts (P=0.065). When the random effect of diabetes mellitus (DM) was analyzed alongside the fixed effects of preoperative IOP, age, refractive error and extent of canal opening using a multivariate linear mixed model, DM emerged as a significant risk factor for higher postoperative IOP at both 6 and 12 months (P<0.001). Conclusions: Diabetes mellitus is a significant risk factor for poor outcomes following Schlemm’s canal based MIGS, particularly in achieving lower postoperative IOP.

Abstract: A 2-year-old male neutered domestic shorthair cat was presented with a progressive history of tetraparesis, ataxia, and inappetence over 4 days. A physical exam revealed mucopurulent nasal discharge and stertor. Neurologic exam revealed a multifocal neurolocalization. The cat was non-ambulatory tetraparetic and developed seizures while in-hospital. Hematologic assessment revealed anemia, hypoalbuminemia and hyperglobulinemia. Magnetic resonance imaging (MRI) of the brain revealed multifocal meningeal contrast enhancement in the brainstem and cervical spine, as well as mandibular and retropharyngeal lymphadenopathy. Cerebrospinal fluid revealed marked neutrophilic pleocytosis, no infectious organisms were seen. Toxoplasma IgG/IgM and cryptococcus antigen latex agglutination were negative. Mandibular and abdominal lymph nodes were aspirated, and cytology revealed mixed inflammation. Nanopore sequencing specifically identified FCoV-1 RNA in spinal fluid and anal swab, but not in urine. This method serves as a novel and rapid PCR sequencing technique for the antemortem diagnosis of feline infectious peritonitis. The cat was treated with anticonvulsants (phenobarbital and levetiracetam), an antibiotic (ampicillin/clavulanic acid), and GS-441524. Neurologic signs did not improve on an antibiotic alone but improved significantly after two subcutaneous injections of GS-441524. The cat received an 84-day course of GS-441524 and, at the time of manuscript preparation (over 12 months after diagnosis), remained ambulatory and seizure-free without recurrence of neurologic signs and no detectable viral shedding in feces.

Abstract: Background: Hyperkalemia is a common electrolyte disorder in patients with heart failure and reduced ejection fraction (HFrEF). Renin-angiotensin-aldosterone system inhibitors (RAASi) have been shown to improve survival and decrease hospitalization rates, although they may increase the serum potassium levels. Hyperkalemia has significant clinical and economic implications, and is associated with increased healthcare resource utilization. The main objective of this study was to analyze the management of hyperkalemia and the associated medical costs in a cohort of patients with HFrEF. Methods: An observational, longitudinal, retrospective, single-center retrospective study was made in patients with HFrEF who started follow-up in a specialized heart failure unit between 2010 and 2021. Results: The study population consisted of 1181 patients followed-up on for 64.6 ± 38.8 months. During follow-up, 11,059 control visits were conducted, documenting 438 episodes of hyperkalemia in 262 patients (22.2%). Of the hyperkalemia episodes, 3.0% required assistance in the Emergency Department, 1.4% required hospitalization, and only 0.2% required admission to the Intensive Care Unit. No episode required renal replacement therapy. Reduction or withdrawal of RAASi was necessary in 69.9% of the hyperkalemia episodes. The total cost of the 438 hyperkalemia episodes was €89,178.82; the expense during the first year accounted for 48.8% of the total cost. Conclusions: Hyperkalemia is common in patients with HFrEF. It is often accompanied by a modification of treatment with RAASi. Hyperkalemia generates substantial costs in terms of healthcare resources and medical care, especially during the first year.

Abstract: Canine high-grade glioma (HGG) is among the deadliest and most treatment-resistant forms of canine cancer. Successful, widespread treatment is challenged by heterogeneity in tumor cells and the tumor microenvironment and tumor evolution following treatment. Immunotherapy is theoretically a strong novel therapy, since HGG-generated immunosuppression is a substantial malignancy mechanism. Immunotherapy has improved survival times overall, but has been associated with extremely poor outcomes in French bulldogs. Given this breed-specific observation, we hypothesized that within the French bulldog breed, there are key transcriptomic differences when compared to other breeds, and that their tumors change differently in response to immunotherapy. Using bulk RNA sequencing, French bulldog tumors were confirmed to differ substantially from boxer and Boston terrier tumors, with only 15.9% overlap in significant differentially expressed genes (DEGs). In upregulated DEGs, the magnitude of changes in expression post-treatment compared to pre-treatment was markedly greater in French bulldogs. Gene set enrichment analysis confirmed that following treatment, French bulldog tumors showed enrichment of key immune-associated pathways previously correlated with poor prognosis. Overall, this study confirmed that French bulldog HGG transcriptomes differ from boxer and Boston terrier transcriptomes, further refining description of the canine glioma transcriptome and providing important information to guide novel therapy development.

Abstract: Flea-borne typhus (FBT), due to Rickettsia typhi and R. felis, is an infection typically causing fever, headache, rash, hepatitis, and thrombocytopenia. About one-quarter of patients suffer pulmonary, neurologic, hematologic, renal, hepatic, cardiac, ocular or other complications. In the 21st century, the incidence of FBT has increased in both Texas and California compared to the 1990s. In this paper, county-level epidemiological data for the number of cases of FBT occurring in Texas for two decades, 1990-1999 and 2010-2019, were compared with respect to county of residence, urbanization, and climatic region. Human population growth in Texas has promoted FBT by increased urbanization and abundance of pet dogs and cats, stray/feral dogs and cats, and opossums. Increasing temperatures in Texas in the new millennium has increased the flea-borne transmission of FBT by promoting host infestation and flea feeding and defecation, accelerating the flea life cycle, and increasing rickettsial replication within the flea. Increased opossums and stray cats and dogs in the urban/suburban landscape has increased the risk of flea transfer to humans and their pets.

Abstract:

Aim: This study aimed to explore the correlation between the FIB-5 and FIB-4 indices, which assess liver fibrosis, and the grouped duration of heart failure (HF) in a cohort of subjects from the National Health and Nutrition Examination Survey (NHANES) 2015-2020. Methods: The study included 468 participants categorized into three groups based on HF duration: Group 1 (≤1 year, n=91), Group 2 (1-5 years, n=87), and Group 3 (>5 years, n=290). Data were analyzed using Pearson and Spearman correlation analyses to assess relationships between FIB-5, FIB-4, and HF duration. Clinical variables such as age, BMI, ALT, AST, albumin, and platelet count were also considered.Results: The analysis revealed significant correlation between FIB-5 with age (Pearson correlation (r) = -0.29, p<0.0001) but not for HF duration across groups (Spearman correlation (ρ) = -0.010, p=0.8217). The FIB-4 index did not show significant associations with the HF duration group (p=0.6326). The regression analysis also showed no significant predictive relationship between FIB-5 or FIB-4 and the duration of heart failure, further supporting the lack of association between fibrosis indices and HF duration in this cohort.Conclusion: The study found no significant correlation between the FIB-5 and FIB-4 indices and the duration of heart failure in this cohort. These findings suggest that while these fibrosis scores are useful in liver assessment, they may not directly reflect the duration of heart failure in this population. Further studies are needed to explore other potential biomarkers for HF duration.

Abstract: Classic health-related quality of life (HRQOL) metrics are cumbersome, time-intensive, and subject to biases based on the subject’s native language, educational level, and cultural values. Natural language processing (NLP) converts text into quantitative metrics. Sentiment analysis enables subject matter experts to construct domain-specific lexicons that assign a value of either negative (-1) or positive (1) to certain words. The growth of telehealth provides opportunities to apply sentiment analysis to transcripts of adult spinal deformity patient visits to derive a novel and less biased HRQOL metric. In this study, we demonstrate the feasibility of constructing a spine-specific lexicon for sentiment analysis to derive an HRQOL metric for adult spinal deformity patients from their preoperative telehealth visit transcripts. We asked each of twenty-five (25) adult patients seven open-ended questions about their spinal conditions, treatment, and quality of life during telehealth visits. We analyzed the Pearson correlation between our sentiment analysis HRQOL metric and established HRQOL metrics (Scoliosis Research Society-22 questionnaire [SRS-22], 36-Item Short Form Health Survey [SF-36], and Oswestry Disability Index [ODI]). The results show statistically significant correlations (0.43–0.74) between our sentiment analysis metric and the conventional metrics. This provides evidence that applying NLP techniques to patient transcripts can yield effective HRQOL metrics.