Heart-specific NFAT5 knockout suppresses type I interferon signaling and aggravates coxsackievirus-induced myocarditis.

Nuclear factor of activated T cells 5 (NFAT5) is an osmosensitive transcription factor that is well-studied in renal but rarely explored in cardiac diseases. Although the association of Coxsackievirus B3 (CVB3) with viral myocarditis is well-established, the role of NFAT5 in this disease remains largely unexplored. Previous research has demonstrated that NFAT5 restricts CVB3 replication yet is susceptible to cleavage by CVB3 proteases. Using an inducible cardiac-specific Nfat5-knockout mouse model, we uncovered that NFAT5-deficiency exacerbates cardiac pathology, worsens cardiac function, elevates viral load, and reduces survival rates. RNA-seq analysis of CVB3-infected mouse hearts revealed the significant impact of NFAT5-deficiency on gene pathways associated with cytokine signaling and inflammation. Subsequent in vitro and in vivo investigation validated the disruption of the cytokine signaling pathway in response to CVB3 infection, evidenced by reduced expression of key cytokines such as interferon ß1 (IFNß1), C-X-C motif chemokine ligand 10 (CXCL10), interleukin 6 (IL6), among others. Furthermore, NFAT5-deficiency hindered the formation of stress granules, leading to a reduction of important stress granule components, including plakophilin-2, a pivotal protein within the intercalated disc, thereby impacting cardiomyocyte structure and function. These findings unveil a novel mechanism by which NFAT5 inhibits CVB3 replication and pathogenesis through the promotion of antiviral type I interferon signaling and the formation of cytoplasmic stress granules, collectively identifying NFAT5 as a new cardio protective protein.

Accelerated corneal cross-linking (18mW/cm2 for 5 min) with HPMC-riboflavin in progressive keratoconus - 5 years follow-up.

PURPOSE: To evaluate long-term results of accelerated corneal cross-linking (ACXL) in patients with progressive keratoconus, seventy-four eyes of 53 patients with progressive keratoconus (documented Kmax progression > 1D/a) who underwent ACXL (18mW/cm2 for 5 min) were included in a retrospective observational clinical study. The investigation focused on tomographic and keratometric parameters, refractive data, and visual outcomes at 5 years follow-ups. METHODS: Corrected distance visual acuity (CDVA), slit lamp, and Pentacam® examinations were conducted, including assessments of thinnest corneal point (TP), minimum radius (Rmin), corneal astigmatism, and maximum anterior keratometry (Kmax). These examinations were performed two weeks before the surgery and, on average, 56 months after the surgery. In a subgroup of 24 eyes, Pentacam® examination data from an intermediate visit at 12 months until the final visit was evaluated to confirm continuous stability. The ACXL protocol included corneal abrasion, hydroxypropylmethylcellulose (HPMC)-riboflavin eye drops administered every 5 min for a total duration of 30 min, and irradiation with 18mW/cm2 for 5 min using riboflavin eye drops applied every minute during the irradiation process. Intraoperatively, minimal corneal pachymetry of > 400 µm was ensured in every patient. RESULTS: After 56 months, all values exhibited statistically significant changes (paired t-test; CDVA p = 0.002; Kmax p < 0.001; Rmin p < 0.001; astigmatism p = 0.03; TP p < 0.001). In the subgroup analysis of 24 eyes, which included tomographical and keratometric parameters, no statistically significant changes were observed during the last 12 months of observation (paired t-test; Kmax p = 0.72; Rmin p = 0.67; astigmatism p = 0.72). Treatment failure was strictly defined as an increase in Kmax (> 1D) during the 5-year follow-up and was observed in only 3 eyes (4%). CONCLUSIONS: ACXL is an effective and safe treatment for patients with progressive keratoconus. Our results demonstrate improvements in functional and tomographical outcomes even after high-energy ACXL (18mW/cm2 for 5 min) over a long-term period of 56 months. Our analysis indicates stable conditions in previously progressive keratoconus, particularly during the final year of the observation period. The treatment failure rate was 4%.

The effect of Melatonin on Improving the benign Prostatic Hyperplasia Urinary Symptoms, a Randomized Clinical Trial.

PURPOSE: to investigate the effect of melatonin along with tamsulosin in improving BPH urinary symptoms. MATERIALS AND METHODS: A total of 108 men with BPH symptoms, age of ≥ 50 years, and International Prostate Symptom Score (IPSS) ≥ 8 entered into the parallel group randomized, double-blind clinical trial with balanced randomization. The treatment group received of 3mg melatonin plus 0.4mg tamsulosin and the control group received placebo plus 0.4mg tamsulosin. Patients and physicians were concealed by sealed and opaque envelopes. Symptoms were assessed at baseline and 1 month after treatment. Finally all scores at the initial and end of the study were compared and analyzed using SPSS software. RESULTS: This study showed that adding melatonin to the classic treatment of BPH patients with tamsulosin could significantly reduce the likelihood of nocturia by 2.39 times (95% CI: 1.07-5.32, OR = 2.39, p = 0.033) and could also reduce the frequency of urination by 2.59 times (95% CI: 1.15-5.84, OR = 2.59, p = 0.021). There was no statistically significant difference between the two groups in IPSS, intermittency, incomplete emptying, straining, urgency, and weak stream. CONCLUSION: Melatonin plus tamsulosin treatment is associated with a significant improvement of nocturia and frequency in patients with benign proststic hyperplasia. However, it is necessary to do more studies.

[iOCT in clinical use : Correlation of intraoperative morphology and postoperative visual outcome in patients with full thickness macular hole]. / iOCT in der klinischen Anwendung : Korrelation von intraoperativer Morphologie und postoperativem Ergebnis bei Patienten mit durchgreifendem Makulaforamen.

BACKGROUND: Due to intraoperative optical coherence tomography (iOCT), observation of retinal morphological changes during surgery has become possible. OBJECTIVE: To analyze the intraoperative morphology of full thickness macular holes (FTMH) and the correlation with the postoperative function, a retrospective, observational clinical study was performed analyzing 32 eyes of patients treated at the hospital of the technical university of Munich. MATERIAL AND METHODS: Using iOCT in 32 eyes of 32 consecutive patients, the operative morphology was analyzed during surgery. These findings were then correlated with the postoperative visual outcome. RESULTS: After posterior vitreous detachment (PVD) the macular hole index (MHI) decreased by -0.05 (p = 0.01) and the base diameter (BD) increased by +99.4 µm (SD = 197.8 µm; p = 0.04). Closure rate was 100% at the first visit after a mean time of 73 days and the postoperative best corrected visual acuity (BCVA) significantly improved (p < 0.05). There were significant correlations between intraoperative morphology and postoperative results indicating a relation between low MHI and better postoperative BCVA (SCC = 0.50; p = 0.02), large BD and better postoperative BCVA (SCC = 0.43; p = 0.05) and large aperture after PVD and higher improvement of BCVA (SCC = 0.44; p = 0.03). CONCLUSION: Flattening and broadening of the FTMH occurred as a result of reduction of vitreoretinal traction. The significant correlation between a large operative BD and improved BCVA reveals the importance of intraoperative retinal relaxation.

Processing-Aware Real-Time Rendering for Optimized Tissue Visualization in Intraoperative 4D OCT.

Intraoperative Optical Coherence Tomography (iOCT) has advanced in recent years to provide real-time high resolution volumetric imaging for ophthalmic surgery. It enables real-time 3D feedback during precise surgical maneuvers. Intraoperative 4D OCT generally exhibits lower signal-to-noise ratio compared to diagnostic OCT and visualization is complicated by instrument shadows occluding retinal tissue. Additional constraints of processing data rates upwards of 6GB/s create unique challenges for advanced visualization of 4D OCT. Prior approaches for real-time 4D iOCT rendering have been limited to applying simple denoising filters and colorization to improve visualization. We present a novel real-time rendering pipeline that provides enhanced intraoperative visualization and is specifically designed for the high data rates of 4D iOCT. We decompose the volume into a static part consisting of the retinal tissue and a dynamic part including the instrument. Aligning the static parts over time allows temporal compounding of these structures for improved image quality. We employ a translational motion model and use axial projection images to reduce the dimensionality of the alignment. A model-based instrument segmentation on the projections discriminates static from dynamic parts and is used to exclude instruments from the compounding. Our real-time rendering method combines the compounded static information with the latest iOCT data to provide a visualization which compensates instrument shadows and improves instrument visibility. We evaluate the individual parts of our pipeline on pre-recorded OCT volumes and demonstrate the effectiveness of our method on a recorded volume sequence with a moving retinal forceps.

[Intraoperative Optical Coherence Tomography in Vitreoretinal Surgery: Clinical Experiences and Future Developments]. / Die intraoperative optische Kohärenztomografie in der Netzhaut-Glaskörper-Chirurgie. Aktuelle Erfahrungen und Ausblick auf künftige Entwicklungsschritte.

PURPOSE: High resolution optical coherence tomography (OCT) enables better visualization of ophthalmic microstructures than conventional imaging. When using an ophthalmic microscope, integrated optical coherence tomography (iOCT) high resolution real time visualization is possible. METHODS: We report on the first 110 patients operated on using a microscope integrated OCT (iOCT) during surgical procedures for the treatment of various posterior segment pathologies. RESULTS: Microstructural changes that appeared during surgery were depicted precisely by iOCT, and the morphology visualized before and after each surgical step was used to help deciding how to adapt the surgical flow. The iOCT data and real-time imaging of retinal anatomy gives the surgeon the possibility of deploying patient- and operation-specific interventional procedures. DISCUSSION: To date, iOCT is only available in standing microscopes with no measurement or tracking features. Moreover, metal instruments currently obscure the scanned images. In the future, non-metal, transparent instruments (OCT-friendly surgical tools), tracking features, an autofocus and higher resolution could enable full and immediate intraoperative SD-OCT diagnostics in real time.

Structure-function relationship comparison between retinal nerve fibre layer and Bruch's membrane opening-minimum rim width in glaucoma.

AIM: To evaluate and compare structural optical coherence tomography (OCT)-based parameters, such as Bruch's membrane opening-minimum rim width (BMO-MRW), and retinal nerve fiber layer (RNFL) thickness in glaucoma patients with visual field (VF) defects, and to correlate both to mean deviation (MD) values of obtained standard achromatic perimetry (SAP) examinations. METHODS: Patients with glaucoma and glaucomatous VF defects were enrolled in this prospective study and compared to age-matched healthy individuals. All study participants underwent a full ophthalmic examination and VF testing with SAP. Peripapillary RNFL thickness and BMO-MRW were acquired with SD-OCT. Correlation analyses between obtained global functional and global as well as sectorial structural parameters were calculated. RESULTS: A consecutive series of 30 glaucomatous right eyes of 30 patients were included and compared to 36 healthy right eyes of 36 individuals in the control group. Global MD of values correlated significantly with global RNFL (Pearson corr. coeff: 0.632, P=0.001) and global BMO-MRW (Pearson corr. coeff: 0.746, P<0.001) values in the glaucoma group. Global MD and sectorial RNFL or BMO-MRW values correlated less significantly. In the control group, MD values did not correlate with RNFL or BMO-MRW measurements. A subgroup analysis of myopic patients (>4 diopters) within the glaucoma group (n=6) revealed a tendency for higher correlations between MD and BMO-MRW than MD and RNFL measurements. CONCLUSION: In a clinical setting, RNFL thickness and BMO-MRW correlate similarly with global VF sensitivity in glaucoma patients with BMO-MRW showing higher correlations in myopic glaucoma patients.

The efficacy of intramuscular calcitonin injection in the management of lumbar spinal stenosis.

STUDY DESIGN: A prospective, cross-sectional, non-randomized study. PURPOSE: To assess the effectiveness of intramuscular calcitonin injection in the treatment of lumbar spinal stenosis (LSS). OVERVIEW OF LITERATURE: LSS, manifesting as chronic low back pain and neurogenic claudication, is a chronic condition with an increasing incidence in the elderly population having inadequate effective conservative treatment options. METHODS: In this study, 36 patients with LSS who were diagnosed based on the clinical findings and magnetic resonance imaging were included. Patients received 100 IU of calcitonin per week for one month and were evaluated before and after treatment using the Oswestry disability index (ODI) questionnaire and visual analogue scale (VAS). Before treatment, the patients were divided into two subgroups based on their ODI results: patients with mild to moderate low back pain (disability, 0%-40%) and patients with severe or very severe low back pain (disability, 40%-100%). RESULTS: In patients with mild to moderate low back pain, there were no significant changes in the ODI and VAS after calcitonin injection. But in patients with severe or very severe low back pain, pain severity, personal functions, ability to lift and carry objects, time interval between standing and initiation of pain, social life, disability percentage, and VAS were significantly improved after treatment with calcitonin. CONCLUSIONS: It seems that an intramuscular injection of low dose of calcitonin may have some beneficial effects on the pain due to LSS, especially in patients who suffer from severe or very severe low back pain.

Correlation between Radiologic Sign of Lumbar Lordosis and Functional Status in Patients with Chronic Mechanical Low Back Pain.

STUDY DESIGN: A cross-sectional study. PURPOSE: To describe the correlation between lumbar lordosis angle and functional status of patients with chronic mechanical low back pain (CMLBP). OVERVIEW OF LITERATURE: There are different and conflicting opinions regarding the relationship between the degree of lumbar lordosis and functional status of patients with low back pain. Nonetheless, the severity of lordosis is still one of the routine physical exams considered in rehabilitation clinics. METHODS: The degree of lumbar lordosis of 150 patients with CMLBP was measured by means of Cobb's method using sagittal standing spinal radiographs. Subjects with probable secondary causes of low back pain (trauma, congenital anomaly, spinal infection, rheumatologic problems and history of spinal surgery) were excluded. Besides recording demographic data, their score of functional disability was estimated using Oswestry Disability Questionnaire, one of the most useful and reliable questionnaires. Comparison between these data was made regarding different age and gender groups. RESULTS: In this study, 119 subjects were female and 31 male, with an age range of 19-85 years. The average degree of lumbar lordosis was 44.69±11.43 and that of Oswestry disability index (ODI) 30.52%. Although we found a significant direct relationship between age and degree of lumbar lordosis (Pearson's correlation coefficient, p=0.016, r=0.197), while insignificant correlation was seen between the degree of lumbar lordosis and ODI (p=0.129). CONCLUSIONS: There was no significant correlation between the degree of lumbar lordosis and the score of functional disability with regards to different age groups and gender.

Sympathetic skin response in patients with vascular erectile dysfunction.

PURPOSE: We aimed to investigate the utility of sympathetic skin response (SSR) test for evaluating vasculogenic erectile dysfunction (ED) which is the most common type of impotence. MATERIALS AND METHODS: Men in the age group of 28 to 60 years and suffering from vasculogenic ED, as confirmed by a papaverin test and color Doppler sonography, at least for 6 months referred from our university urology department were included. We used the International Index of Erectile Function (IIEF-5) for grading severity of dysfunction and recorded the SSR of every patient from the median, tibial, and dorsal nerves of the penis. One-way analysis of variance (ANOVA), independent t-test and Pearson's correlation coefficient were used for comparing quantitative variables, and Fisher's Exact test was used for comparing qualitative variables. The Mann-Whitney U Test and the Kruskal-Wallis test were performed for analysis of data that were not normally distributed. A p value of less than 0.05 was considered significant. RESULTS: Forty-two patients were recruited for the study. We found a strong statistical relationship between the IIEF score and the pathologic SSR registered from every mentioned nerve. Patients with abnormal SSR had more severe ED according to IIEF score (p<0.001). In addition, the IIEF score had a significantcorrelation with diabetes mellitus and cardiovascular disease (t-test; p<0.05). CONCLUSIONS: Our results confirmed the presence of autonomic dysfunction in patients with vasculogenic impotence via an SSR test. We suggest evaluating the efficacy of the SSR test in patients with vascular impotence for treatment response monitoring in future studies.

Comparison the effect of lateral wedge insole and acupuncture in medial compartment knee osteoarthritis: a randomized controlled trial.

BACKGROUND: There is lack of well-designed trials evaluating structural benefits of non-pharmacologic therapies in knee osteoarthritis (OA). In this parallel-group randomized controlled trial, we aim to compare the possible advantages of lateral wedge insole and acupuncture in patients with medial knee OA. METHOD: Patients with grade two or three of medial knee OA were randomly allocated to group one who received an in shoe lateral wedge and group two who underwent acupuncture. We assessed patients' pain, function and knee joint cartilage thickness before and after intervention. Paired t-test and independent samples t-test were used for in group and between group analyses. ( LEVEL OF EVIDENCE: 2.) RESULTS: Twenty patients in each group were recruited in the study. Pain significantly decreased after therapy in both groups one and two (paired t test, P<0.001, 95% CI: 1.62-3.25 and 1.58-3.20 respectively). Function improved in each group (paired t test, P=0.001, 95% CI of 0.94-2.38 in group one and 0.97-2.43 in group two). A non-clinically statistically significant difference regarding the femoral and tibial cartilage thickness was obtained in both groups one (P=0.005, CI: -0.43-0.82 and P=0.037, CI: -0.44-0.80 respectively) and two (P=0.025, CI: -0.45-0.79 and P=0.035, CI: -0.29-0.96 respectively). Between groups analysis showed no significant difference regarding abovementioned measures. CONCLUSION: Both lateral wedge insole and acupuncture can be effective in the treatment of medial knee osteoarthritis without any superiority of one over the other. Iranian Registry of Clinical Trials: IRCT201201108235N1. URL: http://irct.ir/searchen.php.