Synthesis, Characterization and Biological Studies of Technetium-99m and Rhenium-188 Peptides

Radiopharmaceuticals are very powerful diagnostic tools for evaluation of a host of medical conditions. These drugs are labeled with radioactive isotopes, which are utilized to create pictures of areas of interest through absorption of the drug. They are currently in high demand due to their ability to image areas that traditional imaging devices cannot. The radioisotope 99mTc, with a half-life of 6.01 hours and a 140 keV gamma emission, is central to many radiopharmaceutical compounds. This isotope is easily obtained from a 99Mo-99mTc generator, through beta decay and column chromatography separations. Very little technetium, less than 6 ng, is needed to label the pharmaceuticals for use in-vivo. Another radioisotope 188Re is also important due to its ability to be used for therapy while being tracked throughout the body. Radiotherapy gives radiopharmaceuticals a huge advantage by their ability to destroy rapidly growing cells. One of the main reasons there is interest in rhenium pharmaceuticals is the chemical similarity between it and technetium. The 188Re isotope also has a considerably short half–life of approximately 17 hours and has emission energy of 155 keV. The 188Re isotope is separated from 188W-188Re generator, analogously to the 99Mo-99mTc generator. The ligand used in this work is a pentapepetide macrocyclic ligand. This ligand, KYCAR (lysyl-tyrosyl-cystyl-alanyl-arginine), has been designed as a potential chelating ligand for imaging and therapeutic in vivo agents. Ligands are chosen based on their in-situ biological behavior, and are used in the complexation with technetium and rhenium. Understanding and exploiting technetium and rhenium chemistry can provide insight into the reaction mechanisms and coordination chemistry of these compounds. The exploration of various oxidation states as a function of the ligands used and the reaction conditions can help develop novel radiopharmaceuticals. The investigations of the manipulation of oxidation states have the possible application to simplify the synthesis of the pharmaceutical. The versatility of the oxidation states of these metals leads to numerous possibilities in developing new radiopharmaceuticals. The coordination chemistry and reaction mechanisms must be efficiently characterized to ensure the reproducibility of the radiopharmaceutical. The current study focuses on technetium and rhenium complexes with peptides. These complexes have become increasing interesting for their use in diagnostic and therapeutic radiopharmaceuticals. The characterization of the complexation of Tc(V), and Rh(V) with the pentapeptide KYCAR (lysyl-tyrosyl-cystyl-alanyl-arginine) will be discussed. Complexes will be characterized by High Performance Liquid Chromatography (HPLC), UV-Visible Spectroscopy, Proton NMR, Circular Dichroism (CD), and Electrospray Ionization Mass Spectroscopy, to compare them to current radiopharmaceuticals. Information on the underlying reactions and coordination will be discussed

Measuring wanting and liking from animals to humans: A systematic review

Animal research has shown it is possible to want a reward that is not liked once obtained. Although these findings have elicited interest, human experiments have produced contradictory results, raising doubts about the existence of separate wanting and liking influences in human reward processing. This discrepancy could be due to inconsistences in the operationalization of these concepts. We systematically reviewed the methodologies used to assess human wanting and/or liking and found that most studies operationalized these concepts in congruency with the animal literature. Nonetheless, numerous studies operationalized wanting in similar ways to those that operationalized liking. These contradictions might be driven by a major source of confound: expected pleasantness. Expected pleasantness underlies cognitive desires and does not correspond to animal liking, a hedonic experience, or to animal wanting, which relies on affective relevance, consisting of the perception of a cue associated with a relevant reward for the organism’s current physiological state. Extending the concept of affective relevance and differentiating it from expected pleasantness might improve measures of human wanting and liking

Lifetime Lubricant Use among a Nationally Representative Sample of Lesbian- and Bisexual-Identified Women in the United States

Introduction The diversity in self-identified lesbian and bisexual women's sexual interactions necessitates better understanding of how and when they integrate personal lubricant into different experiences. However, little is known about lesbian and bisexual women's lifetime lubricant use, particularly at the population level. Aims The aim of this study was to examine the prevalence and characteristics of lubricant use among adult lesbian and bisexual women in the United States. Methods Data were drawn from a subset of lesbian and bisexual participants who participated in the 2012 National Survey of Sexual Health and Behavior, an online questionnaire administered to a nationally representative probability sample of U.S. adults ages 18 and older. Main Outcome Measures We examined socio-demographic characteristics, recent and lifetime lubricant use, lubricant use in associated with specific sexual behaviors and condom use, frequency of use, motivations for use, as well as perception of lubricant when used. Results A majority of lesbian- (60.1%) and bisexual-identified (77.1%) women reported ever using lubricant; 25.7% of lesbian women and 32.7% of bisexual women used it in the last 30 days. Across most age groups, lubricant was commonly used during partnered sexual play, partnered sexual intercourse, or when a vibrator/dildo was used. Lesbian and bisexual women reported using lubricants to increase arousal/sexual pleasure/desire, to make sex more fun, or to increase physical comfort during sex. Conclusions Lubricant use is identified as a part of lesbian and bisexual women's sexual experience across the life span, as a part of both solo and partnered experiences. As part of evolving sexual health assessments, clinicians and health educators may find value in integrating lubricant-focused conversation with their lesbian and bisexual patients and clients, particularly

Demographic and Outcome Trends in a Naturopathic Teaching Clinic

Naturopathic Doctors (NDs) are trained to treat patients using an individualized approach combining dietary and lifestyle changes, botanical and nutritional medicines, homeopathic medicines, and counseling techniques. In order to effectively study naturopathic medicine, it is beneficial to use whole systems research rather than standardized protocols. In our study, we monitored 27 patients treated individually with wholistic naturopathic medicine for various chief concerns over the course of 12 weeks in the UB Naturopathic Clinic. These patients were given surveys at baseline, 6 weeks, and 12 weeks pertaining to their health-related quality of life (HRQoL), which is considered by the CDC to be an effective tool for predicting mortality and morbidity compared to many objective measures. We used the PROMIS Global Health Scale questionnaire, a validated tool for monitoring HRQoL, for these measures. We also collected demographic data at baseline, including gender, chief medical concerns, age, ethnicity, income level, and education. In our study population, 38.5% of patients were seeking care for depression/anxiety and 15.4% of patients were seeking care for fatigue. 46.2% of participants are aged 50-69 years old, and 71.8% are female. 28.2% have an income under $29,999 per year, and 51.3% are Caucasian. PROMIS Global Health Measures are divided into Physical Health and Mental Health T-scores, and a T-score of 50 is considered an average score for a control population sampled by PROMIS. GPH scores started at 44.652 and increased to 47.8 at 6 weeks and declined to 45.324 at 12 weeks (average SD +/- 7.94). GMH scores started at 45.5259 at baseline, increased to 46.5185 at 6 weeks, and increased to 47.356 at 12 weeks (average SD +/- 8.40). While not statistically significant, our research helps us to understand the type of patients who visit a naturopathic clinic and to perform future research to target treatments for this particular population. A trend towards improved GMH scores was noted over 12 weeks

Optimizing sequencing protocols for leaderboard metagenomics by combining long and short reads.

As metagenomic studies move to increasing numbers of samples, communities like the human gut may benefit more from the assembly of abundant microbes in many samples, rather than the exhaustive assembly of fewer samples. We term this approach leaderboard metagenome sequencing. To explore protocol optimization for leaderboard metagenomics in real samples, we introduce a benchmark of library prep and sequencing using internal references generated by synthetic long-read technology, allowing us to evaluate high-throughput library preparation methods against gold-standard reference genomes derived from the samples themselves. We introduce a low-cost protocol for high-throughput library preparation and sequencing

Dialogue on the Impact of Coronavirus on Research and Publishing: Monday 22nd June 2020

This roundtable took place via Microsoft Teams on Monday 22nd June 2020 to discuss the impact of COVID-19 on Research and Publishing in the U

Excess Risk of Temporomandibular Disorder Associated With Cigarette Smoking in Young Adults

Evidence suggests that the effect of cigarette smoking on chronic pain is stronger in younger than older adults. This case control study investigated whether age modified an effect of smoking on temporomandibular disorder (TMD) in 299 females aged 18–60 years. It also investigated the extent to which this relationship was explained by psychological profile, inflammatory response and allergy. Cases were defined using the Research Diagnostic Criteria for Temporomandibular Disorders based on clinical examination. Psychological profile was evaluated using standardized instruments. Inflammatory response was evaluated with 11 cytokines isolated in plasma. History of allergy conditions was self-reported. Odds ratios (OR) for the effect of smoking were calculated using binary logistic regression. Stratified analyses and the likelihood ratio test examined effect modification by smoking. Compared to non-smokers, ever smokers aged <30 years had higher odds of TMD (OR =4.14, 95% CI: 1.57, 11.35) than older adults (OR =1.23, 95% CI: 0.55, 2.78) (P (effect modification) =0.038). Adjustment for psychological profile, cytokines and history of allergy-like conditions attenuated the effect by 45% to statistical non-significance. The main finding was reproduced with secondary analyses of two nationally-representative surveys of adults conducted in the U.S. and Australia

Detection of cardiac amyloidosis on routine bone scintigraphy:an important gatekeeper role for the nuclear medicine physician

Cardiac amyloidosis (CA)—mostly transthyretin-related (ATTR-CA)—has recently gained interest in cardiology. Bone scintigraphy (BS) is one of the main screening tools for ATTR-CA but also used for various other reasons. The objective was to evaluate whether all CA cases are detected and what happens during follow-up. All routine BS performed at the Maastricht University Medical Center (May 2012–August 2020) were screened for the presence of CA. Scans performed for suspected CA were excluded. A Perugini stage ≥1 was classified as positive necessitating further examination. The electronic medical record system was evaluated for any contact with cardiology or other specialists until 2021. Of the 2738 BS evaluated, 40 scans (1.46%; median age 73.5 [IQR: 65.8–79.5], 82.5% male) were positive (Perugini grade 1: 31/77.5%, grade 2: 6/15%, grade 3: 3/7.5%); the potential diagnosis ATTR-CA was not seen in 38 patients (95%) by the nuclear medicine specialist. During follow-up, 19 out of those 40 patients (47.5%) underwent cardiac evaluation without diagnosing CA. Available echocardiograms of patients with a positive BS showed left ventricular hypertrophy, a preserved ejection fraction, and diastolic dysfunction ≥2 in 9/47%, 10/53%, and 4/21% of patients, respectively. Additionally, 20 (50%) patients presented to at least one specialty with symptoms indicative of cardiac amyloidosis. The prevalence of a positive BS indicating potential CA in an unselected population is low but substantial. The majority was not detected which asks for better awareness for CA of all involved specialists to ensure appropriate treatment and follow-up. Graphical abstract: (Figure presented.)</p

Detection of cardiac amyloidosis on routine bone scintigraphy:an important gatekeeper role for the nuclear medicine physician

Cardiac amyloidosis (CA)—mostly transthyretin-related (ATTR-CA)—has recently gained interest in cardiology. Bone scintigraphy (BS) is one of the main screening tools for ATTR-CA but also used for various other reasons. The objective was to evaluate whether all CA cases are detected and what happens during follow-up. All routine BS performed at the Maastricht University Medical Center (May 2012–August 2020) were screened for the presence of CA. Scans performed for suspected CA were excluded. A Perugini stage ≥1 was classified as positive necessitating further examination. The electronic medical record system was evaluated for any contact with cardiology or other specialists until 2021. Of the 2738 BS evaluated, 40 scans (1.46%; median age 73.5 [IQR: 65.8–79.5], 82.5% male) were positive (Perugini grade 1: 31/77.5%, grade 2: 6/15%, grade 3: 3/7.5%); the potential diagnosis ATTR-CA was not seen in 38 patients (95%) by the nuclear medicine specialist. During follow-up, 19 out of those 40 patients (47.5%) underwent cardiac evaluation without diagnosing CA. Available echocardiograms of patients with a positive BS showed left ventricular hypertrophy, a preserved ejection fraction, and diastolic dysfunction ≥2 in 9/47%, 10/53%, and 4/21% of patients, respectively. Additionally, 20 (50%) patients presented to at least one specialty with symptoms indicative of cardiac amyloidosis. The prevalence of a positive BS indicating potential CA in an unselected population is low but substantial. The majority was not detected which asks for better awareness for CA of all involved specialists to ensure appropriate treatment and follow-up. Graphical abstract: (Figure presented.)</p

Metabolic biomarkers assessed with PET/CT predict sex-specific longitudinal outcomes in patients with diffuse large B-cell lymphoma

In many cancers, including lymphoma, males have higher incidence and mortality than females. Emerging evidence demonstrates that one mechanism underlying this phenomenon is sex differences in metabolism, both with respect to tumor nutrient consumption and systemic alterations in metabolism, i.e., obesity. We wanted to determine if visceral fat and tumor glucose uptake with fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) could predict sex-dependent outcomes in patients with diffuse large B-cell lymphoma (DLBCL). We conducted a retrospective analysis of 160 patients (84 males; 76 females) with DLBCL who had imaging at initial staging and after completion of therapy. CT-based relative visceral fat area (rVFA), PET-based SUVmax normalized to lean body mass (SULmax), and end-of-treatment FDG-PET 5PS score were calculated. Increased rVFA at initial staging was an independent predictor of poor OS only in females. At the end of therapy, increase in visceral fat was a significant predictor of poor survival only in females. Combining the change in rVFA and 5PS scores identified a subgroup of females with visceral fat gain and high 5PS with exceptionally poor outcomes. These data suggest that visceral fat and tumor FDG uptake can predict outcomes in DLBCL patients in a sex-specific fashion