Hard-Flaccid syndrome: a survey of sexual medicine practitioners' knowledge and experience.

Hard-flaccid syndrome (HFS) is a poorly understood condition of male sexual dysfunction (MSD) that has more recently become a new topic of discussion in online forums and sexual medicine conferences. There has been limited research looking into HFS and consequently there are no evidence-based guidelines for its work-up and management. In order to identify the current level of understanding of HFS in the sexual medicine community, a survey was distributed at a national urologic conference focusing on pertinent management strategies employed by practitioners, and their own thoughts on HFS. This showed that nearly one-third of those surveyed had never seen HFS in their practice. Of those that had, diagnosis was mainly made via clinical history as well as patient self-diagnosis. Additionally, only about half of the respondents who had seen HFS were confident in its legitimacy as a real medical syndrome. This analysis is one of the first of its kind, and highlights the ongoing lack of familiarity of HFS among the sexual medicine community. There were limitations, most notably its survey format as well as low sample size, however, it importantly emphasizes the critical need for continued education and research into HFS to improve diagnostic accuracy, enhance patient care, and develop effective treatment strategies.

Multimodal, PSMA-Targeted, PAMAM Dendrimer-Drug Conjugates for Treatment of Prostate Cancer: Preclinical Evaluation.

Introduction: Prostate cancer (PC) is the second most common cancer and the fifth most frequent cause of cancer death among men. Prostate-specific membrane antigen (PSMA) expression is associated with aggressive PC, with expression in over 90% of patients with metastatic disease. Those characteristics have led to its use for PC diagnosis and therapies with radiopharmaceuticals, antibody-drug conjugates, and nanoparticles. Despite these advancements, none of the current therapeutics are curative and show some degree of toxicity. Here we present the synthesis and preclinical evaluation of a multimodal, PSMA-targeted dendrimer-drug conjugate (PT-DDC), synthesized using poly(amidoamine) (PAMAM) dendrimers. PT-DDC was designed to enable imaging of drug delivery, providing valuable insights to understand and enhance therapeutic response. Methods: The PT-DDC was synthesized through consecutive conjugation of generation-4 PAMAM dendrimers with maytansinoid-1 (DM1) a highly potent antimitotic agent, Cy5 infrared dye for optical imaging, 2,2',2"-(1,4,7-triazacyclononane-1,4,7-triyl)triacetic acid (NOTA) chelator for radiolabeling with copper-64 and positron emission tomography tomography/computed tomography (PET/CT), lysine-urea-glutamate (KEU) PSMA-targeting moiety and the remaining terminal primary amines were capped with butane-1,2-diol. Non-targeted control dendrimer-drug conjugate (Ctrl-DDC) was formulated without conjugation of KEU. PT-DDC and Ctrl-DDC were characterized using high-performance liquid chromatography, matrix assisted laser desorption ionization mass spectrometry and dynamic light scattering. In vitro and in vivo evaluation of PT-DDC and Ctrl-DDC were carried out in isogenic human prostate cancer PSMA+ PC3 PIP and PSMA- PC3 flu cell lines, and in mice bearing the corresponding xenografts. Results: PT-DDC was stable in 1×PBS and human blood plasma and required glutathione for DM1 release. Optical, PET/CT and biodistribution studies confirmed the in vivo PSMA-specificity of PT-DDC. PT-DDC demonstrated dose-dependent accumulation and cytotoxicity in PSMA+ PC3 PIP cells, and also showed growth inhibition of the corresponding tumors. PT-DDC did not accumulate in PSMA- PC3 flu tumors and did not inhibit their growth. Ctrl-DDC did not show PSMA specificity. Conclusion: In this study, we synthesized a multimodal theranostic agent capable of delivering DM1 and a radionuclide to PSMA+ tumors. This approach holds promise for enhancing image-guided treatment of aggressive, metastatic subtypes of prostate cancer.

Early Inflatable penile prosthesis implantation offers superior outcomes compared to delayed insertion following ischemic priapism: a narrative review.

Ischemic priapism is a urological emergency which may lead to irreversible erectile dysfunction. One of the accepted treatments is penile prosthesis implantation. Given the scarcity of studies directly comparing timing of penile prosthesis insertion after ischemic priapism, consensus remains elusive. We aim to compare different studies in the literature concerning advantages and disadvantages of early versus delayed inflatable penile prosthesis following ischemic priapism. We analyzed 8 articles that investigated immediate and delayed inflatable penile prosthesis placement after ischemic priapism. Early inflatable penile prosthesis placement is associated with better outcomes, including pain relief, priapism resolution, penile shortening prevention, and quicker sexual activity resumption. However, it still carries a high risk of complications like edema, infection, and distal perforations. Delayed inflatable penile prosthesis insertion poses surgical challenges due to the potential for extensive corporal fibrosis. Comparative analyses have shown elevated complication rates in patients with ischemic priapism who undergo delayed inflatable penile prosthesis insertion, as opposed to those with early insertion. In studies reporting complications rates, the total complication rate in the early group was 3.37%, significantly lower than the delayed group (37.23%). Most studies support the superiority of early inflatable penile prosthesis placement following ischemic priapism over delayed placement. Further research is, however, needed to establish a global consensus on timing of prosthesis insertion.

Search traffic for inflatable penile prosthesis increased following the COVID-19 pandemic in the United States: a Google Trends analysis.

We aimed to determine the impact of the COVID-19 pandemic on search trends for inflatable penile implants in the US. Search trends for inflatable penile implants ranging from 2016 through 2023 were analyzed utilizing Google Trends. Associations between search trends and US Census Bureau data, including average household income and per capita income, were analyzed. Pre- and post- COVID-19, the interest in inflatable penile implants has been steadily increasing on average in the US. The average household income for counties with the highest interest in inflatable penile implants during the pre-COVID era was $53,136, whereas for the counties with the highest interest in inflatable penile implants in the post-COVID era, the average decreased to $50,940. Similarly, the average per capita median decreased from $35,209 to $34,547. Search traffic for inflatable penile prosthesis increased following the pandemic in the US. Nevertheless, post-pandemic, individuals with lower income levels showed no change in interest in penile implant searches compared to the pre-pandemic period. Understanding this steadiness in interest can inform healthcare professionals and policymakers to tailor interventions and educational efforts to reach a broader audience, ensuring equitable access to information and healthcare resources.

Modification of a Selective NTRK2 Agonist and Confirmation of Activity in a Glaucoma-on-a-Chip Model.

Purpose: RNYK is a selective agonist of the neurotrophic tyrosine kinase receptor type 2 (NTRK2) which has been screened from a phage-displayed peptide library. Its sequence is SGVYKVAYDWQH, similar to a native NTRK2 ligand, that is, brain-derived neurotrophic factor (BDNF). The current study was performed to recognize and confirm critical residues for RNYK activity in a glaucoma-on-a-chip model. Methods: We designed a modified RNYK (mRNYK) peptide based on hotspots of the RNYK sequence identified by alanine scanning. The critical residues consisted of tyrosine, valine, aspartic acid, and tryptophan (YVDW); however, lysine and glutamine were also maintained in the final sequence (YKVDWQ) for forming amide bonds and peptide dimerization. The affinity of mRNYK binding was confirmed by testing against NTRK2 receptors on the surface of ATRA-treated SH-SY5Y cells. The neuroprotective effect of mRNYK was also evaluated in cell culture after elevated pressure insult in a glaucoma-on-a-chip model. Results: The primary amine on the lysine side-chain from one sequence (YKVDWQ) reacted with a γ-carboxamide group of glutamine from the other sequence, forming dimeric mRNYK. In silico, molecular dynamic simulations of the mRNYK-NTRK2 complex showed more stable and stronger interactions as compared to the RNYK-NTRK2 complex. In vitro, mRNYK demonstrated a neuroprotective effect on SH-SY5Y cells under normal and elevated pressure comparable to RNYK. The 50% effective concentration (logEC50) for mRNYK was 0.7009, which was better than RNYK with a logEC50 of 0.8318. Conclusion: The modified peptide studied herein showed improved stability over the original peptide (RNYK) and demonstrated potential for use as a BDNF agonist with neuroprotective properties for treatment of neurodegenerative disorders such as glaucoma.

SegPC-2021: A challenge & dataset on segmentation of Multiple Myeloma plasma cells from microscopic images.

Multiple Myeloma (MM) is an emerging ailment of global concern. Its diagnosis at the early stages is critical for recovery. Therefore, efforts are underway to produce digital pathology tools with human-level intelligence that are efficient, scalable, accessible, and cost-effective. Following the trend, a medical imaging challenge on "Segmentation of Multiple Myeloma Plasma Cells in Microscopic Images (SegPC-2021)" was organized at the IEEE International Symposium on Biomedical Imaging (ISBI), 2021, France. The challenge addressed the problem of cell segmentation in microscopic images captured from the slides prepared from the bone marrow aspirate of patients diagnosed with Multiple Myeloma. The challenge released a total of 775 images with 690 and 85 images of sizes 2040×1536 and 1920×2560 pixels, respectively, captured from two different (microscope and camera) setups. The participants had to segment the plasma cells with a separate label on each cell's nucleus and cytoplasm. This problem comprises many challenges, including a reduced color contrast between the cytoplasm and the background, and the clustering of cells with a feeble boundary separation of individual cells. To our knowledge, the SegPC-2021 challenge dataset is the largest publicly available annotated data on plasma cell segmentation in MM so far. The challenge targets a semi-automated tool to ensure the supervision of medical experts. It was conducted for a span of five months, from November 2020 to April 2021. Initially, the data was shared with 696 people from 52 teams, of which 41 teams submitted the results of their models on the evaluation portal in the validation phase. Similarly, 20 teams qualified for the last round, of which 16 teams submitted the results in the final test phase. All the top-5 teams employed DL-based approaches, and the best mIoU obtained on the final test set of 277 microscopic images was 0.9389. All these five models have been analyzed and discussed in detail. This challenge task is a step towards the target of creating an automated MM diagnostic tool.

CRISPR-Based Diagnostics and Microfluidics for COVID-19 Point-of-Care Testing: A Review of Main Applications.

An ongoing pandemic of coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). So far, there have been various approaches for SARS-CoV-2 detection, each having its pros and cons. The current gold-standard method for SARS-CoV-2 detection, which offers acceptable specificity and sensitivity, is the quantitative reverse transcription-PCR (qRT-PCR). However, this method requires considerable cost and time to transport samples to specialized laboratories and extract, amplify, and detect the viral genome. On the other hand, antigen and antibody testing approaches that bring rapidity and affordability into play have lower sensitivity and specificity during the early stages of COVID-19. Moreover, the immune response is variable depending on the individual. Methods based on clustered regularly interspaced short palindromic repeats (CRISPR) can be used as an alternative approach to controlling the spread of disease by a high-sensitive, specific, and low-cost molecular diagnostic system. CRISPR-based detection systems (CRISPR-Dx) target the desired sequences by specific CRISPR-RNA (crRNA)-pairing on a pre-amplified sample and a subsequent collateral cleavage. In the present article, we have reviewed different CRISPR-Dx methods and presented their benefits and drawbacks for point-of-care testing (POCT) of suspected SARS-CoV-2 infections at home or in small clinics.

Laplacian-Former: Overcoming the Limitations of Vision Transformers in Local Texture Detection.

Vision Transformer (ViT) models have demonstrated a breakthrough in a wide range of computer vision tasks. However, compared to the Convolutional Neural Network (CNN) models, it has been observed that the ViT models struggle to capture high-frequency components of images, which can limit their ability to detect local textures and edge information. As abnormalities in human tissue, such as tumors and lesions, may greatly vary in structure, texture, and shape, high-frequency information such as texture is crucial for effective semantic segmentation tasks. To address this limitation in ViT models, we propose a new technique, Laplacian-Former, that enhances the self-attention map by adaptively re-calibrating the frequency information in a Laplacian pyramid. More specifically, our proposed method utilizes a dual attention mechanism via efficient attention and frequency attention while the efficient attention mechanism reduces the complexity of self-attention to linear while producing the same output, selectively intensifying the contribution of shape and texture features. Furthermore, we introduce a novel efficient enhancement multi-scale bridge that effectively transfers spatial information from the encoder to the decoder while preserving the fundamental features. We demonstrate the efficacy of Laplacian-former on multi-organ and skin lesion segmentation tasks with +1.87% and +0.76% dice scores compared to SOTA approaches, respectively. Our implementation is publically available at GitHub.

An Evaluation of CXCR4 Targeting with PAMAM Dendrimer Conjugates for Oncologic Applications.

The chemokine receptor 4 (CXCR4) is a promising diagnostic and therapeutic target for the management of various cancers. CXCR4 has been utilized in immunotherapy, targeted drug delivery, and endoradiotherapy. Poly(amidoamine) [PAMAM] dendrimers are well-defined polymers with unique properties that have been used in the fabrication of nanomaterials for several biomedical applications. Here, we describe the formulation and pharmacokinetics of generation-5 CXCR4-targeted PAMAM (G5-X4) dendrimers. G5-X4 demonstrated an IC50 of 0.95 nM to CXCR4 against CXCL12-Red in CHO-SNAP-CXCR4 cells. Single-photon computed tomography/computed tomography imaging and biodistribution studies of 111In-labeled G5-X4 showed enhanced uptake in subcutaneous U87 glioblastoma tumors stably expressing CXCR4 with 8.2 ± 2.1, 8.4 ± 0.5, 11.5 ± 0.9, 10.4 ± 2.6, and 8.8 ± 0.5% injected dose per gram of tissue at 1, 3, 24, 48, and 120 h after injection, respectively. Specific accumulation of [111In]G5-X4 in CXCR4-positive tumors was inhibited by the peptidomimetic CXCR4 inhibitor, POL3026. Our results demonstrate that while CXCR4 targeting is beneficial for tumor accumulation at early time points, differences in tumor uptake are diminished over time as passive accumulation takes place. This study further confirms the applicability of PAMAM dendrimers for imaging and therapeutic applications. It also emphasizes careful consideration of image acquisition and/or treatment times when designing dendritic nanoplatforms for tumor targeting.

Deep Learning Prediction of Response to Anti-VEGF among Diabetic Macular Edema Patients: Treatment Response Analyzer System (TRAS).

Diabetic macular edema (DME) is the most common cause of visual impairment among patients with diabetes mellitus. Anti-vascular endothelial growth factors (Anti-VEGFs) are considered the first line in its management. The aim of this research has been to develop a deep learning (DL) model for predicting response to intravitreal anti-VEGF injections among DME patients. The research included treatment naive DME patients who were treated with anti-VEGF. Patient's pre-treatment and post-treatment clinical and macular optical coherence tomography (OCT) were assessed by retina specialists, who annotated pre-treatment images for five prognostic features. Patients were also classified based on their response to treatment in their post-treatment OCT into either good responder, defined as a reduction of thickness by >25% or 50 µm by 3 months, or poor responder. A novel modified U-net DL model for image segmentation, and another DL EfficientNet-B3 model for response classification were developed and implemented for predicting response to anti-VEGF injections among patients with DME. Finally, the classification DL model was compared with different levels of ophthalmology residents and specialists regarding response classification accuracy. The segmentation deep learning model resulted in segmentation accuracy of 95.9%, with a specificity of 98.9%, and a sensitivity of 87.9%. The classification accuracy of classifying patients' images into good and poor responders reached 75%. Upon comparing the model's performance with practicing ophthalmology residents, ophthalmologists and retina specialists, the model's accuracy is comparable to ophthalmologist's accuracy. The developed DL models can segment and predict response to anti-VEGF treatment among DME patients with comparable accuracy to general ophthalmologists. Further training on a larger dataset is nonetheless needed to yield more accurate response predictions.

First-in-human neuroimaging of soluble epoxide hydrolase using [18F]FNDP PET.

PURPOSE: Soluble epoxide hydrolase (sEH) is an enzyme with putative effect on neuroinflammation through its influence on the homeostasis of polyunsaturated fatty acids and related byproducts. sEH is an enzyme that metabolizes anti-inflammatory epoxy fatty acids to the corresponding, relatively inert 1,2-diols. A high availability or activity of sEH promotes vasoconstriction and inflammation in local tissues that may be linked to neuropsychiatric diseases. We developed [18F]FNDP to study sEH in vivo with positron emission tomography (PET). METHODS: Brain PET using bolus injection of [18F]FNDP followed by emission imaging lasting 90 or 180 min was completed in healthy adults (5 males, 2 females, ages 40-53 years). The kinetic behavior of [18F]FNDP was evaluated using a radiometabolite-corrected arterial plasma input function with compartmental or graphical modeling approaches. RESULTS: [18F]FNDP PET was without adverse effects. Akaike information criterion favored the two-tissue compartment model (2TCM) in all ten regions of interest. Regional total distribution volume (VT) values from each compartmental model and Logan analysis were generally well identified except for corpus callosum VT using the 2TCM. Logan analysis was assessed as the choice model due to stability of regional VT values from 90-min data and due to high correlation of Logan-derived regional VT values with those from the 2TCM. [18F]FNDP binding was higher in human cerebellar cortex and thalamus relative to supratentorial cortical regions, which aligns with reported expression patterns of the epoxide hydrolase 2 gene in human brain. CONCLUSION: These data support further use of [18F]FNDP PET to study sEH in human brain.

Prostate-specific membrane antigen (PSMA)-targeted photodynamic therapy enhances the delivery of PSMA-targeted magnetic nanoparticles to PSMA-expressing prostate tumors.

Enhanced vascular permeability in tumors plays an essential role in nanoparticle delivery. Prostate-specific membrane antigen (PSMA) is overexpressed on the epithelium of aggressive prostate cancers (PCs). Here, we evaluated the feasibility of increasing the delivery of PSMA-targeted magnetic nanoparticles (MNPs) to tumors by enhancing vascular permeability in PSMA(+) PC tumors with PSMA-targeted photodynamic therapy (PDT). Method: PSMA(+) PC3 PIP tumor-bearing mice were given a low-molecular-weight PSMA-targeted photosensitizer and treated with fluorescence image-guided PDT, 4 h after. The mice were then given a PSMA-targeted MNP immediately after PDT and monitored with fluorescence imaging and T2-weighted magnetic resonance imaging (T2-W MRI) 18 h, 42 h, and 66 h after MNP administration. Untreated PSMA(+) PC3 PIP tumor-bearing mice were used as negative controls. Results: An 8-fold increase in the delivery of the PSMA-targeted MNPs was detected using T2-W MRI in the pretreated tumors 42 h after PDT, compared to untreated tumors. Additionally, T2-W MRIs revealed enhanced peripheral intra-tumoral delivery of the PSMA-targeted MNPs. That finding is in keeping with two-photon microscopy, which revealed higher vascular densities at the tumor periphery. Conclusion: These results suggest that PSMA-targeted PDT enhances the delivery of PSMA-targeted MNPs to PSMA(+) tumors by enhancing the vascular permeability of the tumors.

Countermeasures for Preventing and Treating Opioid Overdose.

The only medication available currently to prevent and treat opioid overdose (naloxone) was approved by the US Food and Drug Administration (FDA) nearly 50 years ago. Because of its pharmacokinetic and pharmacodynamic properties, naloxone has limited utility under some conditions and would not be effective to counteract mass casualties involving large-scale deployment of weaponized synthetic opioids. To address shortcomings of current medical countermeasures for opioid toxicity, a trans-agency scientific meeting was convened by the US National Institute of Allergy and Infectious Diseases/National Institutes of Health (NIAID/NIH) on August 6 and 7, 2019, to explore emerging alternative approaches for treating opioid overdose in the event of weaponization of synthetic opioids. The meeting was initiated by the Chemical Countermeasures Research Program (CCRP), was organized by NIAID, and was a collaboration with the National Institute on Drug Abuse/NIH (NIDA/NIH), the FDA, the Defense Threat Reduction Agency (DTRA), and the Biomedical Advanced Research and Development Authority (BARDA). This paper provides an overview of several presentations at that meeting that discussed emerging new approaches for treating opioid overdose, including the following: (1) intranasal nalmefene, a competitive, reversible opioid receptor antagonist with a longer duration of action than naloxone; (2) methocinnamox, a novel opioid receptor antagonist; (3) covalent naloxone nanoparticles; (4) serotonin (5-HT)1A receptor agonists; (5) fentanyl-binding cyclodextrin scaffolds; (6) detoxifying biomimetic "nanosponge" decoy receptors; and (7) antibody-based strategies. These approaches could also be applied to treat opioid use disorder.

A lab-on-a-chip model of glaucoma.

AIMS: We developed a glaucoma-on-a-chip model to evaluate the viability of retinal ganglion cells (RGCs) against high pressure and the potential effect of neuroprotection. METHODS: A three-layered chip consisting of interconnecting microchannels and culture wells was designed and fabricated from poly-methyl methacrylate sheets. The bottom surface of the wells was modified by air plasma and coated with different membranes to provide a suitable extracellular microenvironment. RGCs were purified from postnatal Wistar rats by magnetic assisted cell sorting up to 70% and characterized by flow cytometry and immunocytochemistry. The cultured RGCs were exposed to normal (15 mmHg) or elevated pressure (33 mmHg) for 6, 12, 24, 36, and 48 hr, with and without adding brain-derived neurotrophic factor (BDNF) or a novel BDNF mimetic (RNYK). RESULTS: Multiple inlet ports allow culture media and gas into the wells under elevated hydrostatic pressure. PDL/laminin formed the best supporting membrane. RGC survival rates were 85%, 78%, 70%, 67%, and 61% under normal pressure versus 40%, 22%, 18%, 12%, and 10% under high pressure at 6, 12, 24, 36, and 48 hr, respectively. BDNF and RNYK separately reduced RGC death rates about twofold under both normal and elevated pressures. CONCLUSION: This model recapitulated the effects of elevated pressure over relatively short time periods and demonstrated the neuroprotective effects of BDNF and RNYK.

cis-4-[18F]fluoro-L-proline Molecular Imaging Experimental Liver Fibrosis.

Introduction: Early-stage liver fibrosis is potentially reversible, but difficult to diagnose. Clinical management would be enhanced by the development of a non-invasive imaging technique able to identify hepatic injury early, before end-stage fibrosis ensues. The analog of the amino acid proline, cis-4-[18F]fluoro-L-proline ([18F]fluoro-proline), which targets collagenogenesis in hepatic stellate cells (HSC), was used to detect fibrosis. Methods: Acute steatohepatitis was induced in experimental animals by liquid ethanol diet for 8 weeks, intra-gastric binge feedings every 10th day along with lipopolysaccharide (LPS) injection. The control animals received control diet for 8 weeks and an equivalent volume of saline on the same schedule as the acute steatohepatitis model. First, in vitro cellular experiments were carried out to assess [3H]proline uptake by HSC, hepatocytes and Kupffer cells derived from rats with acute steatohepatitis (n = 14) and controls (n = 14). Next, ex vivo liver experiments were done to investigate unlabeled proline-mediated collagen synthesis and its associated proline transporter expression in acute steatohepatitis (n = 5) and controls (n = 5). Last, in vivo dynamic and static [18F]fluoro-proline micro-PET/CT imaging was performed in animal models of acute steatohepatitis (n = 7) and control (n = 7) mice. Results: [3H]proline uptake was 5-fold higher in the HSCs of steatohepatitis rats than controls after incubation of up to 60 min. There was an excellent correlation between [3H]proline uptake and liver collagen expression (r-value > 0.90, p < 0.05). Subsequent liver tissue studies demonstrated 2-3-fold higher proline transporter expression in acute steatohepatitis animals than in controls, and proline-related collagen synthesis was blocked by this transporter inhibitor. In vivo micro-PET/CT studies with [18F]fluoro-proline showed 2-3-fold higher uptake in the livers of acute steatohepatitis mice than in controls. There was an excellent correlation between [18F]fluoro-proline uptake and liver collagen expression in the livers of acute steatohepatitis mice (r-value = 0.97, p < 0.001). Conclusion: [18F]fluoro-proline localizes in the liver and correlates with collagenogenesis in acute steatohepatitis with a signal intensity that is sufficiently high to allow imaging with micro-PET/CT. Thus, [18F]fluoro-proline could serve as a PET imaging biomarker for detecting early-stage liver fibrosis.

Bladder Lymphangioma Treated by Holmium Laser: Extremely Rare Case Report.

Introduction: Lymphangioma is a sporadic benign tumor of the bladder. It is a congenital disorder and based on the size of lymphatic spaces, it is divided into 3 types of capillary, cavernous, and cystic. Case Report: In this paper, we presented a 40-year-old woman with microscopic hematuria and a normal urinary ultrasound. Urethrocystoscopy showed a flat 4 mm highlighted strawberry-like lesion on the right lateral wall of the bladder. After a cold cup biopsy, the lesion was coagulated by the holmium: YAG (Ho: YAG) laser. Conclusion: In Bladder Lymphangioma Based on the size of the lesion, partial cystectomy or minimally invasive surgeries such as laser modality would be the principal treatment.

Caspase-Based PET for Evaluating Pro-Apoptotic Treatments in a Tuberculosis Mouse Model.

PURPOSE: Despite recent advances in antimicrobial treatments, tuberculosis (TB) remains a major global health threat. Mycobacterium tuberculosis proliferates in macrophages, preventing apoptosis by inducing anti-apoptotic proteins leading to necrosis of the infected cells. Necrosis then leads to increased tissue destruction, reducing the penetration of antimicrobials and immune cells to the areas where they are needed most. Pro-apoptotic drugs could be used as host-directed therapies in TB to improve antimicrobial treatments and patient outcomes. PROCEDURE: We evaluated [18F]-ICMT-11, a caspase-3/7-specific positron emission tomography (PET) radiotracer, in macrophage cell cultures and in an animal model of pulmonary TB that closely resembles human disease. RESULTS: Cells infected with M. tuberculosis and treated with cisplatin accumulated [18F]-ICMT-11 at significantly higher levels compared with that of controls, which correlated with levels of caspase-3/7 activity. Infected mice treated with cisplatin with increased caspase-3/7 activity also had a higher [18F]-ICMT-11 PET signal compared with that of untreated infected animals. CONCLUSIONS: [18F]-ICMT-11 PET could be used as a noninvasive approach to measure intralesional pro-apoptotic responses in situ in pulmonary TB models and support the development of pro-apoptotic host-directed therapies for TB.

High Availability of the α7-Nicotinic Acetylcholine Receptor in Brains of Individuals with Mild Cognitive Impairment: A Pilot Study Using 18F-ASEM PET.

Emerging evidence supports a hypothesized role for the α7-nicotinic acetylcholine receptor (α7-nAChR) in the pathophysiology of Alzheimer's disease. 18F-ASEM (3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-6-18F-fluorodibenzo[b,d]thiophene 5,5-dioxide) is a radioligand for estimating the availability of α7-nAChR in the brain in vivo with PET. Methods: In this cross-sectional study, 14 patients with mild cognitive impairment (MCI), a prodromal stage to dementia, and 17 cognitively intact, elderly controls completed 18F-ASEM PET. For each participant, binding in each region of interest was estimated using Logan graphical analysis with a metabolite-corrected arterial input function. Results: Higher 18F-ASEM binding was observed in MCI patients than in controls across all regions, supporting higher availability of α7-nAChR in MCI. 18F-ASEM binding was not associated with verbal memory in this small MCI sample. Conclusion: These data support use of 18F-ASEM PET to examine further the relationship between α7-nAChR availability and MCI.

Persian version of Patient-Reported Outcome Measure for Urethral Stricture Surgery (USS-PROM) Questionnaire, Validation and Adaptation Study.

PURPOSE: The aim of the present study was translation, cross cultural adaptation and face validity evaluation of the Persian version of Patient-Reported Outcome Measure for Urethral Stricture Surgery (USS-PROM) Questionnaire. MATERIALS AND METHODS: This study was assessed: translation, translation quality, reverse translation and comparison of the english version, Content validity, internal consistency and stability. Content validity presents by index of content validity (CVI) and the content validity ratio (CVR). Internal consistency reliability was tested by Cronbach's ?, and test-retest reliability was evaluated by Intraclass Correlation Coefficient (ICC) assessed by Guttman two way mixed absolute agreements. RESULT: Frothy males with history urethroplasty and mean age of 41.4±9.08 (range of 19 to 52) years old; enrolled.  In the case of mean scores of difficulty from the 16 translated items, 80% had easy translation. In terms of translation quality, 92% were the satisfactorily clear. In terms of similar concept, 92% were satisfactory. The overall quality of the translation was satisfactory at 88%. The translated questionnaire has a good internal consistency (Cronbach's alpha as 0.84). CVI and the CVR, test-retest ICC evaluation were appropriate/acceptable in all questions. The questionnaire ICC was .791(CI 95%, .678-.876). Two main different aspects of the questionnaire consisted of urinary symptoms (question 1-10) and Quality of life (question 11-15) Cronbach's alpha were .800 and .671 respectively. CONCLUSION: The Persian version of the questionnaire has acceptable cultural adaptation and face Validity. Further studies should be done using this translated tool to determine its applicability in the urethroplasty patients.