Low-intensity shockwave therapy improves baseline erectile function: a randomized sham-controlled crossover trial.

Background: Low-intensity shockwave therapy for erectile dysfunction is emerging as a promising treatment option. Aim: This randomized sham-controlled crossover trial assessed the efficacy of low-intensity shockwave therapy in the treatment of erectile dysfunction. Methods: Thirty-three participants with organic erectile dysfunction were enrolled and randomized to shockwave therapy (n = 17) or sham (n = 16). The sham group was allowed to cross over to receive shockwave therapy after 1 month. Outcomes: Primary outcomes were the changes in Sexual Health Inventory for Men (SHIM) score and Erection Hardness Score at 1 month following shockwave therapy vs sham, and secondary outcomes were erectile function measurements at 1, 3, and 6 months following shockwave therapy. Results: At 1 month, mean SHIM scores were significantly increased in the shockwave therapy arm as compared with the sham arm (+3.0 vs -0.7, P = .024). Participants at 6 months posttreatment (n = 33) showed a mean increase of 5.5 points vs baseline (P < .001), with 20 (54.6%) having an increase ≥5. Of the 25 men with an initial Erection Hardness Score <3, 68% improved to a score ≥3 at 6 months. When compared with baseline, the entire cohort demonstrated significant increases in erectile function outcomes at 1, 3, and 6 months after treatment. Clinical Implications: In this randomized sham-controlled crossover trial, we showed that 54.6% of participants with organic erectile dysfunction met the minimal clinically important difference in SHIM scores after treatment with low-intensity shockwave therapy. Strengths and Limitations: Strengths of this study include a sham-controlled group that crossed over to treatment. Limitations include a modest sample size at a single institution. Conclusions: Low-intensity shockwave therapy improves erectile function in men with erectile dysfunction as compared with sham treatment, which persists even 6 months after treatment. Clinical Trial Registration: ClinicalTrials.gov NCT04434352.

Predictors of urinary outcomes following robotic-assisted laparoscopic prostatectomy.

Introduction: Incontinence and urgency are common after prostatectomy. The University of Virginia prostatectomy functional outcomes program (PFOP) was developed to comprehensively assess and optimise continence outcomes following robotic-assisted laparoscopic prostatectomy (RALP). Patients are prospectively evaluated by a Female Pelvic Medicine and Reconstructive Surgery specialist. This study assessed for predictors of 3- and 6-month stress urinary incontinence (SUI) and urgency symptom outcomes following RALP. Methods: We performed a post hoc review of patients from our PFOP receiving a minimum of 6-month follow-up. Urinary symptoms are prospectively assessed using the validated International Consultation on Incontinence Questionnaire-Male Lower Urinary Tract Symptoms (ICIQ-MLUTS) questionnaire and daily pad use (pads per day [PPD]). Primary study outcomes included ICIQ-MLUTS SUI and urgency domain scores and PPD. Multivariable linear regression was performed to identify variables associated with outcomes at 3 and 6 months postoperatively. Variables included patient, oncologic and surgical factors. Each variable was run in a separate model with pelvic floor muscle therapy and surgeon to reduce confounding and prevent overfitting. Results: Forty men were included. In assessment of ICIQ-MLUTS SUI domain score, at 3 months, body mass index (BMI) was associated with worse scores, and at 6 months, BMI, hypertension and estimated blood loss (EBL) were associated with worse scores, whereas bilateral nerve-sparing technique was associated with better scores. For ICIQ-MLUTS Urgency domain score, at 3 months, preoperative use of benign prostatic hyperplasia (BPH) medication was associated with better scores. No covariates predicted 6-month ICIQ-MLUTS Urgency domain scores. For PPD use, at both 3 and 6 months, BMI was a positive predictor, while preoperative use of BPH medication was a negative predictor. Conclusion: Increased BMI, EBL and hypertension are associated with worsened SUI outcomes following RALP, whereas bilateral nerve-sparing technique and preoperative BPH medication are associated with improved SUI outcomes. These data may inform patient counselling and help identify patients who may benefit from closer surveillance and earlier anti-incontinence intervention.

The perceived leaders' authentic leadership, knowledge sharing within the team, and faculty members' creativity: A cross-sectional online survey in nursing academia.

BACKGROUND: There hasn't been much recent research on leaders' authentic leadership, knowledge sharing within the team, and faculty members' creativity. AIM: This study examined the perceived variables and predictors of academic nursing leaders' authentic leadership by their nursing faculty members, knowledge sharing within the team, and nursing faculty members' own creativity. DESIGN: A cross-sectional design using a survey instrument was employed to answer the research questions. METHODS: A convenience snowball sample of 105 academic nursing faculty members who worked at various universities in Jordan was recruited. RESULTS: Academic nursing leaders' authentic leadership, knowledge sharing within the team, and nursing faculty members' creativity were perceived high by nursing faculty members. The highest and lowest means of the three concepts were reported. As evidenced by correlations, knowledge sharing within the team related to nursing faculty members' creativity without affecting academic nursing leaders' authentic leadership. The perceived academic nursing leaders' authentic leadership didn't predict knowledge sharing within the team or faculty members' creativity. CONCLUSIONS: The current research fills critical voids in the reviewed literature. The results augment nursing leadership knowledge in academic settings. Academic nursing leaders' authentic leadership didn't predict knowledge sharing within the team or faculty members' creativity. These findings raise the flag; authentic nursing leadership should be synergized in conducive academic environments with other factors that may promote nursing faculty members' creativity, such as psychological safety and team environment.

Investigating the Prevalence of Computer Vision Syndrome (CVS) Among Undergraduate Nursing Students: A Cross-Sectional Study.

Introduction: During the pandemic, health issues associated with using digital devices and exploring social media, such as Computer Vision Syndrome (CVS), have increased considerably. Objectives: This study looked into CVS and its significance in Jordan and the CVS outcomes of undergraduate nursing students who used digital devices to surf social media during COVID-19. Methods: To assess CVS, a quantitative cross-sectional research design was used. Data were collected in 2022 through an online diagnostic and formative survey utilizing the CVS-Questionnaire (CVS-Q) with 310 undergraduate nursing students from a government and a private university in Jordan. Descriptive statistics and the univariate general linear model were used to analyze the collected data. Results: To report the prevalence of CVS among the studied sample, the median score was 1.80. The median prevalence score was 24.50 (range = 13-31), and 26.75% of participants reported having intense social media searches. For a student in this study to be diagnosed with CVS, they must receive a score of at least 5, and the current sample score was around 2, indicating they didn't have a CVS; however, it was moderate when it occurred. About 26.75% of participants reported having problematic social media searches. Back and neck pain and headaches were the typical signs of CVS. The average daily hours spent using digital devices for social media searches increased during the pandemic utilizing mobile phones, especially among male nursing students. Being a junior student with no social media account and unable to balance study and social media were among the predictors of CVS. Most students used protective tools on their digital devices, such as protective films and phone screens, to prevent or accommodate CVS. Conclusion: There were no prior collected data about CVS in Jordan, and based on the international trend, the COVID-19 pandemic didn't directly contribute to the prevalence of CVS. However, when the CVS occurred, it was moderate, which mandates proactive and prophylactic redesigning of our educational system.

Longitudinal urgency outcomes following robotic-assisted laparoscopic prostatectomy.

PURPOSE: Stress urinary incontinence (SUI) is a well-known adverse outcome following robotic-assisted laparoscopic prostatectomy (RALP). Although postoperative SUI has been extensively studied, little focus has been placed on understanding the natural history and impact of urgency symptoms following RALP. The UVA prostatectomy functional outcomes program (PFOP) was developed to comprehensively assess and optimize continence outcomes following RALP. The present study focuses on assessing urgency outcomes in this cohort. METHODS: PFOP patients with a minimum of 6-months follow up following RALP were included. The PFOP includes prospectively assessed incontinence and quality of life outcomes utilizing ICIQ-MLUTS, Urgency Perception Score (UPS), and IIQ-7 questionnaires. The primary study outcome was urgency urinary incontinence (UUI) as determined by ICIQ-MLUTS UUI domain. Secondary outcomes included urgency (UPS score) and quality of life (IIQ-7). RESULTS: Forty patients were included with median age 63.5 years. Fourteen (35%) patients reported UUI at baseline. UUI and QOL scores worsened compared to baseline at all time-points. Urgency worsened at 3-weeks and 3-months but returned to baseline by 6-months. Notably, 63% of patients without baseline UUI reported de-novo UUI at 6 months. Although QOL was lower in patients with versus without UUI (IIQ-7 score 3.0 vs 0.0, p = 0.009), severity of UUI was not associated with QOL when controlling for SUI severity. CONCLUSION: Our data demonstrate significantly worsened UUI from baseline and a large incidence of de-novo UUI following RALP. Further study is needed to inform how urgency and UUI and its treatment affect health-related quality of life following RALP.

Modulation of ocular surface desiccation in a murine model by histatin-5 application.

PURPOSE: To determine the efficacy of Histatin-5 (Hst5) peptide treatment in ameliorating dry eye disease (DED) phenotype in an in-vivo mouse model of scopolamine and desiccating stress (SDS) dry eye. METHODS: SDS was induced in female C57BL/6 mice by subcutaneous injections of scopolamine hydrobromide and exposure to low relative humidity and forced air draft for five days. Mouse eyes were topically treated with synthetic Hst5 peptide or balanced salt solution (BSS) twice a day for four days. Control mice were not exposed to SDS induction and did not receive any treatments. Oregon green dextran (OGD) staining was used to evaluate corneal permeability. Histologically, staining with periodic acid schiff (PAS), immunohistochemistry (IHC) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), were used to quantify the number of goblet cells (GC), CD45+ immune cells and apoptotic cells respectively in formalin fixed paraffin embedded (FFPE) mouse whole eye sections. RESULTS: Compared to treatment with BSS, Hst5 treatment significantly lowered corneal epithelial permeability, prevented conjunctival epithelial GC loss, decreased conjunctival CD45+ immune cell infiltration and reduced conjunctival epithelial cell apoptosis. CONCLUSIONS: Hst5 peptide topical treatment significantly improves the clinical parameters observed in SDS experimental model of DED. This is the first report of the efficacy of Hst5 treatment of dry eye phenotype, and potential novel treatment for DED in the clinic. Hst5 represents a new class of efficacious therapeutic agents, demonstrating pro-epithelial and anti-inflammatory activities at the ocular surface.

A narrative review of pelvic floor muscle training in the management of incontinence following prostate treatment.

Background and Objective: Urinary incontinence following prostate treatment (IPT) is a common complication with corresponding negative impacts on quality of life. Pelvic floor muscle training (PFMT) is a non-invasive treatment strategy to treat combat this clinical issue, and has been recognized by medical associations globally and increasingly supported by large bodies of literature. Accordingly, many studies demonstrate a significant benefit of pelvic floor muscle training to continence status and quality of life in men with incontinence following prostate treatment. However, related research is limited by variety in treatment regimens, outcome measures, and study designs, with unclear impact on treatment success. We aim to provide a brief overview of pathology and incidence of incontinence following prostate surgery and an understanding how PFMT is currently used to treat and prevent this clinical consequence. Methods: A comprehensive literature search was conducted utilizing PubMed, Medline, and Google Scholar. Search criteria included systematic reviews and randomized control trials published in the year 2000 to present. References of resulting studies were further analyzed to identify further articles of relevance. Keywords searched included: "post-prostatectomy incontinence", "pelvic muscle strengthening", "Benign Prostatic Hyperplasia", and "pelvic floor muscle training". Peer-reviewed publications that demonstrated a novel addition to the existing body of literature on this subject were included. Key Content and Findings: Upon review of the current research landscape, PFMT is largely supported in treatment of IPT. Analysis of current literature on this subject demonstrates heterogeneity in protocols, measures of treatment success, and patient numbers. Nevertheless, benefits to continence and quality of life are noted across an expansive body of literature and as such, PFMT is therefore recommended as an important part of the treatment algorithm following radical prostatectomy. Conclusions: PFMT is an important and effective part of the treatment algorithm in the prevention and treatment of IPT. Additional research is needed to more extensively assess PFMT's role in treating this clinical consequence, especially following other prostate surgeries.

Histatin-1 Attenuates LPS-Induced Inflammatory Signaling in RAW264.7 Macrophages.

Macrophages play a critical role in the inflammatory response to environmental triggers, such as lipopolysaccharide (LPS). Inflammatory signaling through macrophages and the innate immune system are increasingly recognized as important contributors to multiple acute and chronic disease processes. Nitric oxide (NO) is a free radical that plays an important role in immune and inflammatory responses as an important intercellular messenger. In addition, NO has an important role in inflammatory responses in mucosal environments such as the ocular surface. Histatin peptides are well-established antimicrobial and wound healing agents. These peptides are important in multiple biological systems, playing roles in responses to the environment and immunomodulation. Given the importance of macrophages in responses to environmental triggers and pathogens, we investigated the effect of histatin-1 (Hst1) on LPS-induced inflammatory responses and the underlying molecular mechanisms in RAW264.7 (RAW) macrophages. LPS-induced inflammatory signaling, NO production and cytokine production in macrophages were tested in response to treatment with Hst1. Hst1 application significantly reduced LPS-induced NO production, inflammatory cytokine production, and inflammatory signaling through the JNK and NF-kB pathways in RAW cells. These results demonstrate that Hst1 can inhibit LPS-induced inflammatory mediator production and MAPK signaling pathways in macrophages.

Histatin-1 is an endogenous ligand of the sigma-2 receptor.

The Sigma-2 receptor (S2R) (a.k.a TMEM97) is an important endoplasmic reticular protein involved in cancer, cholesterol processing, cell migration, and neurodegenerative diseases, including Niemann-Pick Type C. While several S2R pharmacologic agents have been discovered, its recent (2017) cloning has limited biological investigation, and no endogenous ligands of the S2R are known. Histatins are a family of endogenous antimicrobial peptides that have numerous important effects in multiple biological systems, including antifungal, antibacterial, cancer pathogenesis, immunomodulation, and wound healing. Histatin-1 (Hst1) has important roles in epithelial wound healing and cell migration, and is the primary wound healing agent in saliva. Little is understood about the downstream machinery that underpins the effects of histatins, and no mammalian receptor is known to date. In this study, we show, using biophysical methods and functional assays, that Hst1 is an endogenous ligand for S2R and that S2R is a mammalian receptor for Hst1.

Juvenile xanthogranuloma in Noonan syndrome.

Noonan syndrome (NS) is one of the common RASopathies. While the clinical phenotype in NS is variable, it is typically characterized by distinctive craniofacial features, cardiac defects, reduced growth, bleeding disorders, learning issues, and an increased risk of cancer. Several different genes cause NS, all of which are involved in the Ras/mitogen-activated protein kinase (Ras/MAPK) pathway. Juvenile xanthogranuloma (JXG) is an uncommon, proliferative, self-limited cutaneous disorder that affects young individuals and may be overlooked or misdiagnosed due to its transient nature. A RASopathy that is known to be associated with JXG is neurofibromatosis type 1 (NF1). JXG in NF1 has also been reported in association with a juvenile myelomonocytic leukemia (JMML). As RASopathies, both NS and NF1 have an increased incidence of JMML. We report a 10-month-old female with NS who has a PTPN11 pathogenic variant resulting in a heterozygous SHP2 p.Y62D missense mutation. She was found to have numerous, small, yellow-pink smooth papules that were histopathologically confirmed to be JXG. In understanding the common underlying pathogenetic dysregulation of the Ras/MAPK pathway in both NS and NF1, this report suggests a possible molecular association for why NS individuals may be predisposed to JXG.

Are antioxidants a viable treatment option for male infertility?

Oxidative stress is caused by an imbalance between ROS and antioxidants, which plays a significant role in the pathophysiology of many human diseases. There is extensive evidence highlighting the role of oxidative stress in male infertility due to elevated levels of sperm DNA fragmentation and abnormal semen parameters. The use of antioxidants is a potential therapeutic option to reduce ROS and improve semen quality. The appeal is that antioxidants can be easily obtained over the counter and are considered all-natural and therefore healthy. The hypothesis has been that by decreasing oxidative stress, antioxidants may be used for the treatment of male infertility. While initial studies of antioxidant supplementation suggested a beneficial role in the management of male subfertility, additional research has questioned the benefit of these therapies. The focus of this article is to present recent evidence assessing the viability of antioxidant therapy in the treatment of male infertility.

Wound Healing Properties of Histatin-5 and Identification of a Functional Domain Required for Histatin-5-Induced Cell Migration.

Histatin peptides are endogenous anti-microbial peptides that were originally discovered in the saliva. Aside from their broad anti-microbial properties, these peptides play an important role in multiple biological systems. Different members of this family are thought to have relative specializations, with histatin-5 originally being thought to have mostly anti-fungal properties, and histatin-1 having strong wound healing properties. In this report, we describe the robust wound healing properties of histatin-5 and elucidate a functional domain, which is necessary and sufficient for promoting wound healing. We demonstrate these findings in multiple different cell types in vitro and with a standardized murine corneal wound healing model. Discovery of this wound healing domain and description of this functional role of histatin-5 will support developing therapies.

Prior inhibition of AKT phosphorylation by BX795 can define a safer strategy to prevent herpes simplex virus-1 infection of the eye.

PURPOSE: To evaluate the prophylactic antiviral efficacy, corneal tolerance and toxicity of topically dosed BX795, a non-nucleoside small-molecule inhibitor of herpes simplex virus type-1 (HSV-1). METHODS: Prophylactic treatment with BX795 was performed both in-vitro on human corneal epithelial cells and in-vivo on mice prior to HSV-1 challenge. Viral burden was evaluated using a standard plaque assay. In a separate experiment, mice were treated topically 3-times daily for 4-weeks with BX795 to evaluate corneal tolerance and toxicity. Phenol-red thread measurements, fluorescein staining and optical coherence tomography (OCT) were used to evaluate tear production, dryness and corneal structural changes. Corneal sensitivity and intraocular pressure were measured using esthesiometery and tonometery respectively. RESULTS: Both in-vitro and in-vivo results showed a robust suppression of HSV-1 infection when treated prophylactically with BX795. The fluorescein stain and phenol-red results for the BX795-treated eyes did not show signs of corneal surface dryness when compared to trifluridine (TFT), an FDA-approved topical antiviral. The OCT measurements showed no signs of structural changes to the cornea suggesting that BX795 treatment was well tolerated without any apparent signs of toxicity or inflammation. The corneal sensitivity of BX795-treated eyes was not significantly different from TFT-treated eyes. No significant increase in the intraocular pressure of BX795-treated mice was observed. CONCLUSIONS: Prophylactic treatment with BX795 protects corneal cells from HSV-1 infection. The antiviral is well-tolerated on murine corneas without any detectable toxicity.

Presence of Histatin-1 in Human Tears and Association with Aqueous Deficient Dry Eye Diagnosis: A Preliminary Study.

The aims of this study were to determine if histatin-1 (H1) is present in normal human tears and whether tear levels of H1 varied between normal patients and those with aqueous deficient dry eye disease (ADDE). Patient samples were obtained from 11 normal patients and 11 severe ADDE patients. Relevant patient characteristics, including age, sex, and dry eye disease (DED) diagnostic parameters were collected. Multiple qualitative and quantitative methods were used to compare the concentration of H1 between patient groups. Mixed linear modeling was used to compare H1 levels between groups, and diagnostic performance was assessed using the receiver-operator-characteristic (ROC). ADDE patients had significantly lower H1 concentrations (85.9 ± 63.7 ng/ml) than the normal group (891.6 ± 196.5 ng/ml) (p < 0.001), while controlling for age and sex. ROC analysis indicated that H1 concentration is potentially a biomarker for ADDE (area under curve = 0.96). Reclassification of patients by DED parameters including, Ocular Surface Disease Index (OSDI) (≤13, >13) and Schirmer I (without anesthesia) (<10 mm, ≥10 mm) showed significant differences in H1 level (OSDI, p = 0.004) and Schirmer I ((p = 0.010). In conclusion, this is the first preliminary report of the presence of H1 in human tears. H1 concentrations are lower in ADDE patients and H1 may have diagnostic potential in evaluation ADDE patients.

Strategies for Regenerating the Lacrimal Gland.

PURPOSE OF REVIEW: Aqueous deficient dry eye disease, a significant cause of morbidity worldwide, is due to dysfunction of the main and accessory lacrimal glands. Recent advances in efforts to regenerate lacrimal gland are reviewed. RECENT FINDINGS: Several strategies are being explored: ex vivo culture models of human and non-human lacrimal gland epithelial and myoepithelial cells, isolation and characterization of adult precursor cells within lacrimal glands, directed differentiation of stem cells to lacrimal gland cells, and organogenesis and engraftment techniques. SUMMARY: Conditions for primary cell culture and expansion are being established and will help in the characterization of lacrimal cells. Presumed adult precursor cells have been isolated, laying down foundations for regeneration. Stem cells have been induced to express features of lacrimal gland cells. Engraftment of ex vivo cultured lacrimal tissue is proof of concept that lacrimal gland regeneration and repopulation is possible.

Testing for Noonan syndrome after increased nuchal translucency.

OBJECTIVE: The aim of this study was to report the prevalence of Noonan syndrome (NS) in a cohort of fetuses that presented with increased nuchal translucency (NT) thickness in the first trimester of pregnancy. METHODS: This is a retrospective chart review. INCLUSION CRITERIA: (1) first trimester NT measurement ≥3 mm, (2) normal karyotype by either a CVS or an amniocentesis procedure, and (3) prenatal molecular genetic testing for NS completed. Results with known pathogenic variants were considered positive, while those with variants of unknown clinical significance, or with no variants, were considered negative. RESULTS: A total of 804 fetuses had an NT measurement of ≥3 mm, with a median NT thickness of 3.6 mm. Of these, 302 had karyotyping by CVS or amniocentesis, 200 (66.23%) with normal results. Of fetuses with a normal karyotype, 39 with a median NT thickness of 4.0 mm had a NS gene sequencing panel done, and 161 fetuses with a mean NT thickness of 4.3 mm were not tested for NS (p = 0.05). Of the 39 fetuses who were tested for NS, four (10.3%) had variants consistent with this diagnosis. CONCLUSION: In euploid fetuses, increased NT is associated with a 10% risk of NS. © 2017 John Wiley & Sons, Ltd.