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First-in-human Evaluation of a Prostate-specific Membrane Antigen-targeted Near-infrared Fluorescent Small Molecule for Fluorescence-based Identification of Prostate Cancer in Patients with High-risk Prostate Cancer Undergoing Robotic-assisted Prostatectomy

Eur Urol Oncol. 2023 Jul 27:S2588-9311(23)00146-3. doi: 10.1016/j.euo.2023.07.004. Online ahead of print.

ABSTRACT

BACKGROUND: Men with high-risk prostate cancer undergoing surgery likely recur due to failure to completely excise regional and/or local disease.

OBJECTIVE: The first-in-human evaluation of safety, pharmacokinetics, and exploratory efficacy of IS-002, a novel near-infrared prostate-specific membrane antigen (PSMA)-targeted fluorescence imaging agent, designed for intraoperative prostate cancer visualization.

DESIGN, SETTING, AND PARTICIPANTS: A phase 1, single-center, dose-escalation study was conducted in 24 men with high-risk prostate cancer scheduled for robotic-assisted radical prostatectomy with (extended) pelvic lymph node dissection using the da Vinci surgical system.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Adverse events (AEs), vital signs, complete blood count, complete metabolic panel, urinalysis, and electrocardiogram were assessed over a 14-d period and compared with baseline. The pharmacokinetic profile of IS-002 was determined. Diagnostic accuracy was assessed for exploratory efficacy.

RESULTS AND LIMITATIONS: AEs predominantly included discoloration of urine (n = 22/24; expected, related, grade 1). There were no grade ≥2 AEs. IS-002 Cmax and area under the curve increased with increasing dose. Plasma concentrations declined rapidly in a biphasic manner, with the median terminal half-lives ranging from 5.0 to 7.6 h, independent of dose and renal function. At 25 μg/kg, the exploratory efficacy readouts for the negative and positive predictive values were, 97% and 45% for lymph nodes, and 100% and 80% for residual/locoregional disease detection, respectively.

CONCLUSIONS: IS-002 is safe and well tolerated, and has the potential to enable intraoperative tumor detection that could not be identified using standard imaging.

PATIENT SUMMARY: IS-002 is a new imaging agent that specifically targets the prostate-specific membrane antigen receptor. In this study, we tested IS-002 for the first time in men with high-risk prostate cancer undergoing surgery and found that IS-002 is safe, is cleared from the body quickly, and potentially allows identification of prostate cancer in areas that would not be identified by conventional white light imaging.

PMID:37516587 | DOI:10.1016/j.euo.2023.07.004

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Nevin Manimala Statistics

Nursing students’ attitudes towards sexuality before training in sexual and reproductive health

Nurs Open. 2023 Jul 29. doi: 10.1002/nop2.1959. Online ahead of print.

ABSTRACT

AIM: To know the attitudes towards sexuality of nursing students and those sociodemographic and cultural factors that can influence it.

DESIGN: An observational study was carried out on Nursing degree students. One hundred and eighteen nursing degree students who were going to take the sexual and reproductive health nursing course.

METHODS: A self-administered online questionnaire. This questionnaire had several parts specifically designed to collect sociodemographic variables. In order to determine the attitudes towards sexuality, the questionnaire based on the ATSS (Attitudes Towards Sexuality Scale). The Double Standard Scale (DSS) was also used. This scale evaluates double standards within the area of sexuality. The Rape Supportive Attitude Scale (RSAS), was included to determine beliefs about rape, rapists and their victims.

RESULTS: The ATSS shows a statistically significant association with religious beliefs (p = 0.005), with mean scores of 113.84 (SD = 9.81) for non-believers (no religion), 108.36 (SD = 15.68) for non-practicing believers and 102.32 (SD = 17.87) for believers (those who practice their faith). The mean score in the DSS shows a statistically significant association with alcohol consumption (p = 0.001). The mean score on the RSAS is statistically significantly associated with the place of residence (p = 0.050), the means were 44.32 (SD = 9.26) for those who lived in the city, 34.94 (SD = 19.21) if the place of residence was between 10,000 and 5000 inhabitants and 32.54 (SD = 15.01) if the family home was in a town with less than 5000 inhabitants.

CONCLUSION: Religious beliefs reduce liberalism and positive attitudes towards sexuality, whereas sporadic alcohol consumption increases them.

PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

PMID:37515451 | DOI:10.1002/nop2.1959

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The influence of radio frequency-based toothbrush on the accumulation of calculus and periodontal health: A randomized double-blind controlled prospective study

Clin Exp Dent Res. 2023 Jul 29. doi: 10.1002/cre2.770. Online ahead of print.

ABSTRACT

OBJECTIVES: The use of a toothbrush with radio frequency (RF) has shown to be of benefit regarding the reduction of plaque, calculus, and dental staining and improving teeth shade compared to conventional powered and manual toothbrushes.

AIM: To evaluate the efficacy of the RF toothbrush in the reduction of calculus accumulation and its effect on periodontal parameters as well as subject satisfaction as compared to an identical sham-tooth brush.

MATERIALS AND METHODS: Patients who are under a strict maintenance program were included. Patients were allocated to test (RF toothbrush) or control (sham) randomly and were examined at baseline, one and three months. Clinical photos were taken and a consequential calculus assessment via ImageJ software. Clinical assessment included the following: plaque index (PI), bleeding on probing (BOP), probing pocket depth (PPD), and recession (REC). Patient satisfaction was assessed via a questionnaire.

RESULTS: Fifty-eight patients (29 control, 29 test) were included. At baseline mean PPD, BOP, PI, REC, and calculus accumulation were similar between the groups. Mean buccal calculus was lower in the test group at one month 4.0% versus 6.7%, p < .05. Calculus accumulation within the groups was lower in the test group at 1 and 3 months when compared to baseline at the buccal aspect (2.8% vs. 8.9%, p < .05% and 3.8% vs. 8.9%, p < .05) and lingual aspect (6.7% vs. 16.5%, p < .05% and 8.9% vs. 16.5%, p < .05). No statistically significant results were found regarding periodontal parameters PPD, BOP, PI, and REC. No difference was found between groups regarding patient satisfaction.

CONCLUSION: RF seems to have an additive effect on preventing calculus accumulation on the buccal aspect of anterior mandibular teeth at 1 month. Nevertheless, at 3 months, no difference between the toothbrushes is seen regarding calculus formation and maintaining periodontal health (ClinicalTrials.gov, Identifier NCT04640857).

PMID:37515446 | DOI:10.1002/cre2.770

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Nevin Manimala Statistics

The Reflection Room®: Moving from Death-Avoiding to Death-Discussing

Omega (Westport). 2023 Jul 29:302228231192163. doi: 10.1177/00302228231192163. Online ahead of print.

ABSTRACT

We developed, implemented, and evaluated a participatory arts-based storytelling initiative called the Reflection Room project. Our aim was to investigate if visiting a Reflection Room, (1) creates opportunities for disclosing emotions and processing thoughts, (2) increases comfort discussing dying and death, and (3) supports advance care planning (ACP), conversations. In the pilot phase of the Reflection Room project, a Reflection Room was installed in 25 sites across Canada from 2016-2017. Data collection included reflection cards (n = 463), and surveys completed by visitors upon exiting a room (n = 271) and 3 months later (n = 50). Analysis involved theoretically driven coding, inductive content analysis, and descriptive statistics. We found reflections contained both emotional disclosures and reflective processing. Survey data indicated visiting a Reflection Room increased comfort in thinking and talking about dying and death as well as the likelihood of engaging in ACP. In the future, we will explore the extent to which the project fosters social connections and well-being.

PMID:37515417 | DOI:10.1177/00302228231192163

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Association between the use of lipid-lowering drugs and the risk of inflammatory bowel disease

Eur J Clin Invest. 2023 Jul 28:e14067. doi: 10.1111/eci.14067. Online ahead of print.

ABSTRACT

BACKGROUND: Observational studies have suggested an association between lipid-lowering drugs and inflammatory bowel disease (IBD) risk. This study aimed to assess the causal influence of lipid-lowering agents on IBD risk using Mendelian randomization analysis.

METHOD: In a population of 173,082 individuals of European ancestry, 55 single-nucleotide polymorphisms were identified as instrumental variables for 6 lipid-lowering drug targets (HMGCR, NPC1LC, PCSK9, LDLR, CETP and APOB). Summary statistics for the genome-wide association study of IBD, ulcerative colitis (UC) and Crohn’s disease (CD) were obtained from the FinnGen consortium, Program in Complex Trait Genomics and UK Biobank. Inverse-variance weighted was employed as the primary MR method, and odds ratios (ORs) with 95% confidence intervals were reported as the results. Sensitivity analyses using conventional MR methods were conducted to assess result robustness.

RESULTS: Gene-proxied inhibition of Niemann-Pick C1-like 1 (NPC1L1) was associated with an increased IBD risk (OR [95% CI]: 2.31 [1.38, 3.85]; p = .001), particularly in UC (OR [95% CI]: 2.40 [1.21, 4.74], p = .012), but not in CD. This finding was replicated in the validation cohort. Additionally, gene-proxied inhibition of low-density lipoprotein receptor was associated with reduced IBD (OR [95% CI]: .72 [.60, .87], p < .001) and UC risk (OR [95% CI]: .74 [.59, .92], p = .006), although this result was not replicated in the validation cohort. Other drug targets did not show significant associations with IBD, UC or CD risk.

CONCLUSION: Inhibition of the lipid-lowering drug-target NPC1L1 leads to an increased IBD risk, mainly in the UC population.

PMID:37515404 | DOI:10.1111/eci.14067

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Microvascular complications of obesity and diabetes-Role of bariatric surgery

Obes Rev. 2023 Jul 29:e13602. doi: 10.1111/obr.13602. Online ahead of print.

ABSTRACT

Bariatric surgery in people with obesity can lead to long-term remission of type 2 diabetes mellitus (T2DM) and a reduction in the incidence of macrovascular complications. The impact of bariatric surgery on microvascular complications is less clear. In this narrative review, we sought to evaluate the effect of bariatric surgery on microvascular complications in patients with and without diabetes. The risk of developing microvascular complications is increased in people with obesity, and this is amplified in those with T2DM. The impact of metabolic surgery on microvascular complications is limited to a subgroup analysis of studies or statistical modeling to predict the glycemia-independent effect of bariatric surgery. While bariatric surgery halts the progression of retinopathy in those with minimal retinopathy, it may worsen in those with advanced retinopathy. Bariatric surgery improves proteinuria and major renal outcomes, regardless of the severity of renal impairment. Bariatric surgery in patients with obesity with or without diabetes is associated with an improvement in neuropathic symptoms and regeneration of small nerve fibers. In conclusion, bariatric surgery is associated with an improvement in microvascular complications. Further studies are needed to elucidate the underlying mechanisms for the favorable effect of bariatric surgery on microvascular outcomes.

PMID:37515402 | DOI:10.1111/obr.13602

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Increased rate of significant findings on brain MRI during the early stage of the COVID-19 pandemic

Neuroradiol J. 2023 Jul 28:19714009231193161. doi: 10.1177/19714009231193161. Online ahead of print.

ABSTRACT

OBJECTIVES: To assess the effect of the COVID-19 pandemic on the proportion of abnormal paediatric neuroimaging findings as a surrogate marker for potential underutilisation.

METHODS: Consecutive paediatric brain MRIs performed between March 27th and June 19th 2019 (Tbaseline) and March 23rd and June 1st 2020 (Tpandemic) were reviewed and classified according to presence or absence and type of imaging abnormality, and graded regarding severity on a 5-point Likert scale, where grade 4 was defined as abnormal finding requiring non-urgent intervention and grade 5 was defined as acute illness prompting urgent medical intervention. Non-parametric statistical testing was used to assess for significant differences between Tpandemic vs. Tbaseline.

RESULTS: Fewer paediatric MRI brains were performed during Tpandemic compared to Tbaseline (12.2 vs 14.7 examinations/day). No significant difference was found between the two time periods regarding sex and age (Tbaseline: 557 females (44.63%), 7.95 ± 5.49 years, Tpandemic: 385 females (44.61%), 7.64 ± 6.11 years; p = 1 and p = .079, respectively). MRI brain examinations during Tpandemic had a higher likelihood of being abnormal, 41.25% vs. 25.32% (p<.0001). Vascular abnormalities were more frequent during Tpandemic (11.01% vs 8.01%, p = .02), congenital malformations were less common (8.34% vs 12.34%, p = .004). Severity of MRI brain examinations was significantly different when comparing group 4 and group 5 individually and combined between Tbaseline and Tpandemic (p = .0018, p < .0001, and p <.0001, respectively).

CONCLUSIONS: The rate of abnormality and severity found on paediatric brain MRI was significantly higher during the early phase of the pandemic, likely due to underutilisation.

PMID:37515380 | DOI:10.1177/19714009231193161

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A novel method for age identification of mountain-cultivated ginseng

Microsc Res Tech. 2023 Jul 28. doi: 10.1002/jemt.24393. Online ahead of print.

ABSTRACT

Panax ginseng, a slow-growing perennial herb, is the most praised and popular traditional medicinal herb. Mountain-cultivated ginseng (MCG) and cultivated ginseng (CG) both belong to Panax ginseng C. A. Meyer. The market price and medical effects of this popular health product are closely related to its age. It is widely acknowledged that CG is typically harvested after 4-6 years of growth, but MCG is often collected after 10 years. Until now, the age identification of MCG or mountain wild ginseng (MWG) has remained a major challenge. In this study, we established a novel and rapid method for staining xylem vessels with phloroglucinol and identifying the “annual growth rings” of ginseng by utilizing a stereoscope, which serves as a reliable indicator of the age of MCG. Statistical analysis of the ring radius and the ring density of MCG aged from 1 to 20 years shows that the secondary xylem of MCG increases rapidly in the first 3 years but then gradually slows down from 4 to 10 years, and minor fluctuation is observed in the next 10 years. Meanwhile, the space between the growth rings (ring density) becomes increasingly small with age. This straightforward staining approach can reveal the age of MCG with remarkable clarity and can distinguish MCG from CG. RESEARCH HIGHLIGHTS: A novel rapid staining method for Panax ginseng was established. The age of mountain-cultivated ginseng (MCG) can be identified by microscopic techniques. MCG and cultivated ginseng (CG) can be discriminated by microstructure characteristics.

PMID:37515361 | DOI:10.1002/jemt.24393

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Burnout, Fat Intake, and Body Mass Index in Health Professionals Working in a Public Hospital: A Cross-Sectional Study

Inquiry. 2023 Jan-Dec;60:469580231189601. doi: 10.1177/00469580231189601.

ABSTRACT

Burnout can have a negative influence on dietary intake, promoting unhealthy eating behaviors in health care workers. This study determined the association between burnout, saturated fat intake, and body mass index (BMI) in a group of health care workers. A cross-sectional study was conducted in 300 health professionals residing in Rioja, Department of San Martin, Peru. Data were collected through an online and face-to-face survey. Burnout was assessed using a scale adapted and validated in the Peruvian population. Additionally, a validated food frequency questionnaire (FFQ) was used to assess habitual fat intake. Both instruments were validated and adapted to the Peruvian population. Data were analyzed using Pearson correlation coefficients and multivariate logistic regression. Values of P < .05 were considered statistically significant. In the adjusted model, it was found that, for each extra point on intake scale, an average of 1.10 (95% CI, 0.57-1.62, P < .001) points increased burnout scale; these results persisted when compared by gender, 1.17 0.49 1.85, and 1.08 0.16 2.00, respectively female male genders. there no association between bmi (P > .05). Future programs and interventions should be considered to minimize the effects of burnout on unhealthy food intake in health care workers in Peru to ensure better medical care by health care professionals on behalf of patients.

PMID:37515358 | DOI:10.1177/00469580231189601

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Dectin-1 Multimerization and Signaling Depends on Fungal β-Glucan Structure and Exposure

Biophys J. 2023 Jul 27:S0006-3495(23)00473-3. doi: 10.1016/j.bpj.2023.07.021. Online ahead of print.

ABSTRACT

Dectin-1A is a C-type Lectin innate immunoreceptor that recognizes β-(1,3;1,6)-glucan, a structural component of Candida species cell walls. β-glucans can adopt solution structures ranging from random coil to insoluble fiber due to tertiary (helical) and quaternary structure. Fungal β-glucans of medium and high molecular weight (MMW, HMW) are highly structured, but low MW glucan (LMW) is much less structured. Despite similar affinity for Dectin-1, the ability of glucans to induce Dectin-1A-mediated signaling correlates with degree of structure. Glucan denaturation experiments showed that glucan structure determines agonistic potential, but not receptor binding affinity. We explored the impact of glucan structure on molecular aggregation of Dectin-1A. Stimulation with glucan signaling decreased Dectin-1A diffusion coefficient. Fluorescence measurements provided direct evidence of ligation-induced Dectin-1A aggregation, which positively correlated with increasing glucan structure content. In contrast, Dectin-1A is predominantly in a low aggregation state in resting cells. Molecular aggregates formed during interaction with highly structured, agonistic glucans did not exceed relatively small (<15 nm) clusters of a few engaged receptors. Finally, we observed increased molecular aggregation of Dectin-1A at fungal particle contact sites in a manner that positively correlated with the degree of exposed glucan on the particle surface. These results indicate that Dectin-1A senses the solution conformation of β-glucans through their varying ability to drive receptor dimer/oligomer formation and activation of membrane proximal signaling events.

PMID:37515324 | DOI:10.1016/j.bpj.2023.07.021