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This article investigates hole transport in poly[2-methoxy-5-(2'-ethyl-hexyloxy)-1,4-phenylene vinylene] (MEH-PPV)/CdSe colloidal quantum dot (CQD) nanocomposites using a modified time-of-flight photoconductivity technique. The measured hole drift mobilities are analyzed in the context of Bässler’s Gaussian disorder model and the correlated disorder model in order to determine the polymer internal morphology of hybrid nanocomposite thin films. This work shows that increasing the CdSe CQD concentration decreases the polymer hole mobility from ~5.9 × 10−6 cm2/Vs in an MEH-PPV film to ~8.1 × 10−8 cm2/Vs in a 20:80 (wt%) MEH-PPV:CdSe CQD nanocomposite film (measured at 25 °C and ~2 × 105 V/cm). The corresponding disorder parameters indicate increasing disruption of interchain interaction with increasing CQD concentration. This work quantifies polymer chain morphology in hybrid nanocomposite thin films and provides useful information regarding the optimal use of semiconductor nanocrystals in conjugated polymer-based optoelectronics.

Abstract Background Acute mountain sickness (AMS) is a debilitating condition that individuals may develop on ascent to high altitude. It is characterized by headache, nausea, vomiting, dizziness, and fatigue with the potential to progress to fatal disease. Although the pathophysiology of AMS remains unclear, proposed mechanisms are hypothesized to be similar to migraine. Prochlorperazine, a first-line treatment for acute migraine, has been shown to abort migraine early and thus may be effective in preventing AMS. Its action as a respiratory stimulant additionally makes it a promising novel agent for AMS prevention. Methods In this randomized double-blinded trial, participants will be randomized to receive oral prochlorperazine maleate or placebo for 24 h of three times daily dosing on a rapid ascent to 4348 m. Participants will be adults, aged 18, and older who are unacclimatized. Participants will remain at this elevation overnight. The Lake Louise Questionnaire will be utilized to define the primary outcome and presence of AMS and will be assessed the evening of and morning after ascent to peak altitude. Discussion Currently, acetazolamide is the preferred option for the chemoprophylaxis of AMS, which has been studied and utilized since the 1970s and involves potential prohibitive side effects. Other more efficacious options with more tolerable side effects are needed. Preventing AMS has the potential to limit both the morbidity and mortality associated with developing AMS and more serious diseases (notably high-altitude cerebral edema). Additionally, there is a substantial economic and environmental impact of AMS that could be prevented. Trial registration Clinicaltrial.gov, NCT06450899. Registered on June 2024.

Benign prostatic hyperplasia affects up to 80% of men in their lifetime. It causes bladder outflow obstruction, leading to lower urinary tract symptoms, which can have a large impact on quality of life. Lifestyle modifications and pharmacotherapy are often offered as first-line treatments for patients. These include alpha blockers, 5-alpha-reductase inhibitors, phosphodiesterase-5 inhibitors, anticholinergics, B3-agonists, and desmopressin. While often well tolerated, these pharmacotherapies do have significant side effects, which both clinicians and patients should understand and discuss in order to make an informed treatment decision among alternatives. The purpose of this review is to provide a current overview of the risks and side effects of commonly used medications in benign prostatic hyperplasia management.

Abstract Objective The objective of this study is to determine if Aquablation therapy can maintain its effectiveness in treating men with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) with large‐volume (80–150 cc) prostates at 3 years. Subjects and Methods One hundred one men with moderate‐to‐severe BPH symptoms and prostate volumes between 80 and 150 cc were enrolled in a prospective, nonrandomized, multicenter, international clinical trial in late 2017. Baseline, procedural, and follow‐up parameters were recorded at baseline and scheduled postoperative visits. IPSS, Qmax, and treatment failure are reported at 3 years. Results The mean prostate volume was 107 cc (range 80–150). Mean IPSS improved from 23.2 at baseline to 6.5 at 3 years (16.3‐point improvement, p

Background: Surgical options are limited when treating large (>80 cm3) prostates for lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). Open simple prostatectomy remains the most common procedure performed for large prostates. There is a need for novel surgical approaches with shorter learning curves and effective treatment. Aquablation could be this novel tool. Objective: To compare the outcome of Aquablation for 30–80-cm3 prostates with the outcome for 80–150-cm3 prostates at 2-yr follow-up. Design, setting, and participants: We used data from two trials. WATER is a prospective, double-blind, multicenter, international clinical trial comparing the safety and efficacy of Aquablation and transurethral resection of the prostate in the treatment of LUTS/BPH in men aged 45–80 yr with a prostate of 30–80 cm3. WATER II is a prospective, multicenter, single-arm international clinical trial of Aquablation in men with a prostate of 80–150 cm3. Intervention: Aquablation, an ultrasound-guided, robotically executed waterjet ablative procedure. Outcome measurements and statistical analysis: We compared 24-mo outcomes between 116 WATER and 101 WATER II study subjects. Student’s t test or a Wilcoxon test was used to compare continuous variables and Fisher’s test for categorical variables. Results and limitations: The International Prostate Symptom Score (IPSS) reductions at 24 mo was 14.5 points for WATER and 17.4 points for WATER II (p = 0.31). At baseline, the maximum urinary flow rate (Qmax) was 9.4 and 8.7 cm3/s in WATER and WATER II, improving to 20.5 and 18.2 cm3/s, respectively (p = 0.60) at 24 mo. Improvements in both IPSS and Qmax were immediate and sustained throughout follow-up. At 2 yr, the surgical retreatment rate was 4% in WATER and 2% in WATER II. Conclusions: Aquablation is effective in patients with a prostate of 30–80 cm3 and patients with a prostate of 80–150 cm3 treated for LUTS/BPH, with comparable outcomes in both groups. It has low complication and retreatment rates at 2 yr of follow-up, with durable improvements in functional outcome. Patient summary: Outcomes of Aquablation for both small-to-moderately-sized and large prostates are similar and sustainable at 2 yr of follow-up.

Abstract Background Retroperitoneal fibrosis (RPF) is characterized by the proliferation of fibrous tissue in the retroperitoneum. The majority of RPF cases are due to idiopathic or IgG4-related disease. Recent studies on IgG4-related disease have shown rituximab to be an effective treatment. The current first-line treatment for idiopathic RPF (iRPF) is glucocorticoid therapy. Relapse rates vary widely in the literature, and DMARDs remain poorly studied. We sought to evaluate the efficacy of rituximab in idiopathic RPF by quantifying changes in iRPF diameter on imaging pre- and post-rituximab therapy and response by lab parameters in 10 iRPF patients. Methods We selected 10 patients diagnosed with iRPF and previously treated with rituximab (1000 mg) in two doses approximately 2 weeks apart. Pre- and post-therapy contrast enhanced cross-sectional abdomen and pelvis imaging were compared. In all patients, the thickest portion of the peri-aortic disease was measured in the axial and coronal planes. The presence of acute or long standing back pressure related renal findings were documented. Details of clinical visits including patient demographics and laboratory evaluations were collected pre- and post-therapy. Statistical analysis was performed using a Wilcoxon signed rank test. Results The RPF diameter around the aorta before and after therapy decreased from a mean of 15.9 ± 4.9 mm to 10.6 ± 6.1 mm, respectively (p

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Neuropathic pain remains poorly treated, with most new drugs falling through the translational gap. The traditional model of bench-to-bedside research has relied on identifying new mechanisms/targets in animal models and then developing clinical applications. Several have advocated bridging the translational gap by beginning with clinical observations and back-translating to animal models for further investigation of mechanisms. There is good evidence that phenotyping of patients through quantitative sensory testing can lead to improved treatment selection and hence improved patient outcomes. This practice has been widely adopted in clinical investigations, but its application in preclinical research is not mainstream. In this review, we retrospectively examine our historical rodent data sets with the aim of reconsidering drug effects on sensory neuronal endpoints, their alignment with clinical observations, and how these might guide future clinical studies.

Abstract Background Malaria is an important cause of morbidity and mortality in malaria-endemic areas. Indoor residual spray is an effective intervention to control malaria, but high community-level coverage is needed to maximize its impact. Methods and results Using thirty-four two-stage cluster surveys (e.g., demographic and health surveys) and lot quality assurance sampling, indoor residual spray was estimated at the community level (i.e. enumeration-area) across sub-Saharan Africa since 2010. For communities receiving indoor residual spray a logistic regression predicted whether community-level coverage exceeded 50% or not. Household-level coverage was equitable both in terms of wealth and urban/rural, with poorer and rural houses more likely to be sprayed than richer and urban houses. Coverage of indoor residual spray at the community level is poor across the continent, with 54% of communities receiving the intervention not reaching 50% coverage. Having >50% coverage at the community-level was not associated with increasing the number of houses sprayed in the country. Conclusions Implementation and monitoring of indoor residual coverage at small geographical scales need to improve greatly to receive maximum benefit of the intervention.

Abstract. Introduction:. Drugs that counteract nociceptive transmission in the spinal dorsal horn preferentially after nerve injury are being pursued as possible neuropathic pain treatments. In a previous behavioural study, the peptide toxin Tx3-3, which blocks P/Q- and R-type voltage-gated calcium channels, was effective in neuropathic pain models. Objectives:. In the present study, we aimed to investigate the effect of Tx3-3 on dorsal horn neuronal responses in rats under physiological conditions and neuropathic pain condition induced by spinal nerve ligation (SNL). Methods:. In vivo electrophysiological recordings of dorsal horn neuronal response to electrical and natural (mechanical and thermal) stimuli were made in rats under normal physiological state (naive rats) or after the SNL model of neuropathic pain. Results:. Tx3-3 (0.3–100 pmol/site) exhibited greater inhibitory effect on electrical-evoked neuronal response of SNL rats than naive rats, inhibiting nociceptive C-fibre and Aδ-fibre responses only in SNL rats. The wind-up of neurones, a measurement of spinal cord hyperexcitability, was also more susceptible to a dose-related inhibition by Tx3-3 after nerve injury. Moreover, Tx3-3 exhibited higher potency to inhibit mechanical- and thermal-evoked neuronal response in conditions of neuropathy. Conclusion:. Tx3-3 mediated differential inhibitory effect under physiological and neuropathic conditions, exhibiting greater potency in conditions of neuropathic pain.

An understanding of human responses to hypoxia is important for the health of millions of people worldwide who visit, live, or work in the hypoxic environment encountered at high altitudes. In spite of dozens of studies over the last 100 years, the basic mechanisms controlling acclimatization to hypoxia remain largely unknown. The AltitudeOmics project aimed to bridge this gap. Our goals were 1) to describe a phenotype for successful acclimatization and assess its retention and 2) use these findings as a foundation for companion mechanistic studies. Our approach was to characterize acclimatization by measuring changes in arterial oxygenation and hemoglobin concentration [Hb], acute mountain sickness (AMS), cognitive function, and exercise performance in 21 subjects as they acclimatized to 5260 m over 16 days. We then focused on the retention of acclimatization by having subjects reascend to 5260 m after either 7 (n = 14) or 21 (n = 7) days at 1525 m. At 16 days at 5260 m we observed: 1) increases in arterial oxygenation and [Hb] (compared to acute hypoxia: PaO2 rose 9±4 mmHg to 45±4 while PaCO2 dropped a further 6±3 mmHg to 21±3, and [Hb] rose 1.8±0.7 g/dL to 16±2 g/dL; 2) no AMS; 3) improved cognitive function; and 4) improved exercise performance by 8±8% (all changes p

A. schaalii is a rare uropathogen. We report urosepsis with Actinobaculum schaalii detected serendipitously in blood and urine culture in a 79-year-old with urinary tract obstruction. This paper illuminates the flaws in our current system in detecting A. schaalii and raises awareness among clinicians and laboratory teams.