Peripheral ganglia in healthy rats as target structures for the evaluation of PSMA imaging agents.

BACKGROUND: The recent implementation of PET with prostate specific membrane antigen (PSMA)-specific radiotracers into the clinical practice has resulted in the significant improvement of accuracy in the detection of prostate carcinoma (PCa). PSMA-expression in ganglia has been regarded as an important pitfall in prostate carcinoma-PET diagnostics but has not found any practical use for diagnosis or therapy. METHODS: We explored this phenomenon and demonstrated the applicability of peripheral ganglia in healthy rats as surrogates for small PSMA positive lesions for the preclinical evaluation of diagnostic PCa PET probes. Healthy rats were measured with PET/CT using the tracers [18F]DCFPyL, [Al18F]PSMA-11 and [68Ga]PSMA-11. Sections of ganglia were stained with an anti-PSMA antibody. [18F]DCFPyL uptake in ganglia was compared to that in LNCaP tumor xenografts in mice. RESULTS: Whereas [18F]DCFPyL and [68Ga]PSMA-11 were stable in vivo and accumulated in peripheral ganglia, [Al18F]PSMA-11 suffered from fast in vivo deflourination resulting in high bone uptake. Ganglionic PSMA expression was confirmed by immunohistochemistry. [18F]DCFPyL uptake and signal-to-noise ratio in the superior cervical ganglion was not significantly different from LNCaP xenografts. CONCLUSIONS: Our results demonstrated the non-inferiority of the novel model compared to conventionally used tumor xenografts in immune compromised rodents with regard to reproducibility and stability of the PSMA signal. Furthermore, the model involves less expense and efforts while it is permanently available and avoids tumor-growth associated animal morbidity and distress. To the best of our knowledge, this is the first tumor-free model suitable for the in vivo evaluation of tumor imaging agents.

Multiscale Approach to the Study of the Electronic Properties of Two Thiophene Curcuminoid Molecules.

We studied the electronic and conductance properties of two thiophene-curcuminoid molecules, 2-thphCCM (1) and 3-thphCCM (2), in which the only structural difference is the position of the sulfur atoms in the thiophene terminal groups. We used electrochemical techniques as well as UV/Vis absorption studies to obtain the values of the HOMO-LUMO band gap energies, showing that molecule 1 has lower values than 2. Theoretical calculations show the same trend. Self-assembled monolayers (SAMs) of these molecules were studied by using electrochemistry, showing that the interaction with gold reduces drastically the HOMO-LUMO gap in both molecules to almost the same value. Single-molecule conductance measurements show that molecule 2 has two different conductance values, whereas molecule 1 exhibits only one. Based on theoretical calculations, we conclude that the lowest conductance value, similar in both molecules, corresponds to a van der Waals interaction between the thiophene ring and the electrodes. The one order of magnitude higher conductance value for molecule 2 corresponds to a coordinate (dative covalent) interaction between the sulfur atoms and the gold electrodes.

Plant-based compositions for the treatment of local and topical bacterial infections: a patent review.

Aim: To examine recent patents related to plants with antimicrobial effects. Methods: Our investigation was carried out using the Espacenet database, searching patents related to International Patent Classification (IPC) codes A61P31/04, and A61K36/00 between 2008 and 2023. Results: The study began with 360 patents, of which 15 were found to be duplicates; 144 were not related to the research topic and six were not available. Then, 48 patents were related to other administration routes. The final selection was 47 patents related to local administration compositions. The potential for these herbal compositions to be marketed as over-the-counter medicines was evident. Conclusion: Developing new plant-origin anti-infective agents could provide promising solutions for combating resistant infections and offer accessible treatment options.

[Box: see text].

Case Report: Duodenal Papillary Stenosis Secondary to Strongyloides stercoralis Infection in a Non-Immunocompromised Host.

Strongyloides stercoralis infection is a common infection in tropical and subtropical regions and is considered one of the "neglected tropical diseases." Owing to its life cycle, this infection can remain undetectable for years, preventing an early diagnosis and prompt treatment. We report the case of a 65-year-old woman who presented to us with a history of nausea, abdominal pain, bloating, and weight loss and, after initial radiologic and laboratory workup, was diagnosed with a periampullary mass with no secondary spread. She underwent an uneventful pylorus-preserving pancreatoduodenectomy, and on histopathological study of the lesion, a diagnosis of S. stercoralis infection was confirmed. This case stands out because of the importance of keeping S. stercoralis infections as a differential diagnosis of periampullary masses, particularly when the patient comes from regions where S. stercoralis is prevalent.

Positive identity predicts psychological wellbeing in Chilean youth: A double-mediation model.

Positive youth development (PYD) allows the youth to be comprehended from their potential, strengths and assets, in contrast to the traditional deficit view that focuses on their weaknesses. The PYD model promotes constructive behaviours in youth by highlighting the positive attributes usually found during the transition from childhood to adulthood to achieve healthy and optimal development in later life. Overall, PYD comprises five key competence (5C), the flourishing models and forty developmental assets. In the present study, a structural equation model is tested with the Chilean dataset of the PYD project on the premise that Positive Identity is the core internal developmental asset explaining Psychological wellbeing and that Confidence and Character are mediators of the relationship between Positive Identity and Psychological Wellbeing. The sample comprised 261 participants (n Women = 189, n Men = 72), Mean Age = 22 years old, who were approached by an online survey uploaded to Qualtrics. The measures of the study included: The Developmental assets Scale, the Short-form of the Five Cs included in the PYD and the Mental Health Continuum Short-Form. The results indicated a good model fit (ß = 1.74, Z total = 10.63, χ 2 = 424.95, df = 277, χ2/df = 1.53, p < 0.001, Robust CFI = 0.945, Robust RMSEA = 0.049, 90% CI (0.040, 0.058), AIC = 17689.91, saBIC = 17719.08 and SRMR = 0.061), highlighting the relevance of studying Latin-American adolescents and young 's wellbeing in times of COVID-19, as the participants' Positive Identity significantly predicted their Psychological Wellbeing, and simultaneously, this relationship was mediated by both their level of Confidence and Character.

Oxygen saturation as a predictor of mortality in hospitalized adult patients with COVID-19 in a public hospital in Lima, Peru.

INTRODUCTION: Peru is among the top ten countries with the highest number of coronavirus disease 2019 (COVID-19) cases worldwide. The aim of the study was to describe the clinical features of hospitalized adult patients with COVID-19 and to determine the prognostic factors associated with in-hospital mortality. METHODS: We conducted a retrospective cohort study among adult patients with COVID-19 admitted to Hospital Cayetano Heredia; a tertiary care hospital in Lima, Peru. The primary outcome was in-hospital mortality. Multivariate Cox proportional hazards regression was used to identify factors independently associated with in-hospital mortality. RESULTS: A total of 369 patients (median age 59 years [IQR:49-68]; 241 (65.31%) male) were included. Most patients (68.56%) reported at least one comorbidity; more frequently: obesity (42.55%), diabetes mellitus (21.95%), and hypertension (21.68%). The median duration of symptoms prior to hospital admission was 7 days (IQR: 5-10). Reported in-hospital mortality was 49.59%. By multiple Cox regression, oxygen saturation (SaO2) values of less than 90% on admission correlated with mortality, presenting 1.86 (95%CI: 1.02-3.39), 4.44 (95%CI: 2.46-8.02) and 7.74 (95%CI: 4.54-13.19) times greater risk of death for SaO2 of 89-85%, 84-80% and <80%, respectively, when compared to patients with SaO2 >90%. Additionally, age >60 years was associated with 1.88 times greater mortality. CONCLUSIONS: Oxygen saturation below 90% on admission is a strong predictor of in-hospital mortality in patients with COVID-19. In settings with limited resources, efforts to reduce mortality in COVID-19 should focus on early identification of hypoxemia and timely access to hospital care.

Er-Doped Nanostructured BaTiO3 for NIR to Visible Upconversion.

Photoluminescent mechanisms in erbium-doped barium titanate nanoparticle systems were studied. Er3+ ions were introduced into the BaTiO3 lattice by the sol-gel method. The resulting Er3+ concentration was between 0% and 5%, with Ba/Ti ratios of 1.008 and 0.993. The stoichiometry of Ba and Ti concentrations in the lattice influenced the doping mechanism and placement of erbium ions in the lattice structure. Our research shows the existence of a strong correlation between Ba/Ti ratios, erbium concentration, phase structure and doping site location on the upconversion photoluminescence mechanisms. Competing upconversion emissions ²H11/2/4S3/2→4I15/2 at 523 and 548 nm respectively and other photoluminescent mechanisms as 4I9/2→4I11/2 around 4000 nm (2500 cm-1) were studied using Raman and emission spectroscopy. The upconversion process is predominant over other photoluminescent decay when the material presents high distortion in the surrounding activator.

Costs of medical care for acute myocardial infarction attributable to tobacco consumption.

BACKGROUND: Tobacco consumption is the principal modifiable risk factor causally associated with acute myocardial infarction (AMI). AMI has been an increasing and important cause of death in Mexico since 1980. METHODS: To estimate the direct health care costs of AMI, we carried out a cost of illness (COI) analysis, using data derived from an expert panel consensus and from medical chart review. We used the smoking attributable fraction (SAF) estimates to derive costs of tobacco consumption. We also estimated the benefits of a "Smoke-free Workplace" tobacco control policy in terms of avoidable deaths and health care costs savings. RESULTS: We estimated an annual average costs of 6,420 US dollars and 9,216 US dollars for non-ST segment elevation AMI (NSTEMI) and ST segment elevation AMI (STEMI), respectively. The total annual health care costs estimated for incident AMI for the IMSS state-level division of Morelos reached 2.9 million US dollars, of which 1.6 million US dollars was directly attributed to tobacco consumption. CONCLUSIONS: Our results confirm the high costs associated with smoking and show the potential benefits resulting from a tobacco control policy. Our estimates are only applicable to social security in the state-level division of Morelos and more likely represent a lower boundary of the total costs of cardiovascular diseases attributed to tobacco, because we based the costs estimation on incident cases, and we did not take into consideration the costs derived from prevalent cases, indirect costs or other intangibles.

Caspofungin therapy of neonates with invasive candidiasis.

BACKGROUND: Invasive candidiasis is an increasing problem in neonatal intensive care units worldwide and is an important cause of morbidity, mortality and prolongation of hospital stay. Despite administration of amphotericin B, invasive candidiasis in neonates is sometimes complicated by persistent fungemia and refractory invasive candidiasis. The problem has been augmented by the increasing prevalence of non-albicans species that often are resistant to fluconazole and to amphotericin B. POPULATION AND METHODS: The population consisted of 1 term and 9 premature neonates with invasive candidiasis caused by Candida albicans (n = 4), Candida parapsilosis (n = 3), Candida tropicalis (n = 2) and Candida glabrata (n = 1). Despite initial therapy with deoxycholate amphotericin B, blood cultures remained positive in all patients for 13-49 days. Invasive candidiasis progressed to meningitis and enlarging renal Candida bezoars in the kidney of one patient and an enlarging atrial vegetation in another. Another patient developed severe hypokalemia refractory to potassium supplementation. Two of the C. albicans and all of the non-albicans Candida isolates were resistant to fluconazole; the C. glabrata isolate was resistant to amphotericin B. Amphotericin B was discontinued and caspofungin initiated in all patients in a dosage of 1 mg/kg/d for 2 days followed by 2 mg/kg/d. RESULTS: All positive blood cultures cleared between 3 and 7 days after initiation of caspofungin, the atrial vegetation resolved and the renal Candida bezoars disappeared. Renal and hepatic function tests did not show any values above normal throughout caspofungin therapy. There were no attributable clinical adverse events during the administration of caspofungin in any of the patients. CONCLUSIONS: Caspofungin was effective, safe and well-tolerated as an alternative therapy for persistent and progressive candidiasis in those neonates who were unresponsive to or intolerant of deoxycholate amphotericin B.

Small animal imaging and examination by micro-CT.

Micro-computed tomography imaging technology allows for the whole-mount investigation of skeletal structures in preclinical specimens at both fetal and postnatal time points. The imaging process is nondestructive to the specimen and can be performed at various resolutions to derive the region of interest information most relevant to individual researchers. In addition to qualitative imaging of skeletal samples, accurate and desirable metrics such as bone mineral density (BMD), discrete cortical and trabecular bone analysis, and milligrams hydroxyapatite per unit volume (mgHA/cc) are also achievable depending upon scanner platform. Additional benefits to the method include digitally archivable files, in vivo and ex vivo scanning options, and volumetric or slice-thru presentation of data in standard histological or oblique orientations. Some drawbacks to the method include long scan times at higher spatial resolutions, large file sizes, and limitation to imaging of highly dense biological structures (i.e., bone), though several groups have attempted to expand the modality to include soft tissue imaging in ex vivo specimens.

A volumetric method for quantifying atherosclerosis in mice by using microCT: comparison to en face.

Precise quantification of atherosclerotic plaque in preclinical models of atherosclerosis requires the volumetric assessment of the lesion(s) while maintaining in situ architecture. Here we use micro-computed tomography (microCT) to detect ex vivo aortic plaque established in three dyslipidemic mouse models of atherosclerosis. All three models lack the low-density lipoprotein receptor (Ldlr(-/-)), each differing in plaque severity, allowing the evaluation of different plaque volumes using microCT technology. From clearly identified lesions in the thoracic aorta from each model, we were able to determine plaque volume (0.04-3.1 mm(3)), intimal surface area (0.5-30 mm(2)), and maximum plaque (intimal-medial) thickness (0.1-0.7 mm). Further, quantification of aortic volume allowed calculation of vessel occlusion by the plaque. To validate microCT for future preclinical studies, we compared microCT data to intimal surface area (by using en face methodology). Both plaque surface area and plaque volume were in excellent correlation between microCT assessment and en face surface area (r(2) = 0.99, p<0.0001 and r(2) = 0.95, p<0.0001, respectively). MicroCT also identified internal characteristics of the lipid core and fibrous cap, which were confirmed pathologically as Stary type III-V lesions. These data validate the use of microCT technology to provide a more exact empirical measure of ex vivo plaque volume throughout the entire intact aorta in situ for the quantification of atherosclerosis in preclinical models.

Optimization of microCT imaging and blood vessel diameter quantitation of preclinical specimen vasculature with radiopaque polymer injection medium.

Vascular networks within a living organism are complex, multi-dimensional, and challenging to image capture. Radio-angiographic studies in live animals require a high level of infrastructure and technical investment in order to administer costly perfusion mediums whose signals metabolize and degrade relatively rapidly, diminishing within a few hours or days. Additionally, live animal specimens must not be subject to long duration scans, which can cause high levels of radiation exposure to the specimen, limiting the quality of images that can be captured. Lastly, despite technological advances in live-animal specimen imaging, it is quite difficult to minimize or prevent movement of a live animal, which can cause motion artifacts in the final data output. It is demonstrated here that through the use of postmortem perfusion protocols of radiopaque silicone polymer mediums and ex-vivo organ harvest, it is possible to acquire a high level of vascular signal in preclinical specimens through the use of micro-computed tomographic (microCT) imaging. Additionally, utilizing high-order rendering algorithms, it is possible to further derive vessel morphometrics for qualitative and quantitative analysis.

L-5F, an apolipoprotein A-I mimetic, inhibits tumor angiogenesis by suppressing VEGF/basic FGF signaling pathways.

We recently reported that apolipoprotein A-I (apoA-I) and apoA-I mimetic peptides inhibit tumor growth and improve survival in a mouse model of ovarian cancer. The current study was designed to examine whether inhibition of angiogenesis is one of the mechanisms for the observed anti-tumorigenic effects. The apoA-I mimetic peptide L-5F had no affect on proliferation and cell viability of human umbilical vascular endothelial cells (HUVECs) in the basal state; however, treatment with L-5F at 1, 3, and 10 µg ml(-1), dose-dependently inhibited both vascular endothelial growth factor (VEGF)- and basic fibroblast growth factor (bFGF)-induced proliferation, cell viability, migration, invasion and tube formation in HUVECs. L-5F inhibited VEGF- and bFGF-induced activation of their corresponding receptors, VEGFR2 and FGFR1, as well as downstream signaling pathways, including Akt and ERK1/2. MicroCT scanning and immunohistochemistry staining demonstrated that daily injection of L-5F (10 mg kg(-1)) decreased both the quantity and size of tumor vessels in mice. L-5F treated mice showed significantly reduced levels of VEGF in both tumor tissue and the circulation, which is consistent with in vitro data showing that L-5F inhibited production and secretion of VEGF from mouse and human ovarian cell lines in the absence and presence of exogenously added lysophosphatidic acid, a potent tumor promoter. In conclusion, our data that L-5F inhibits angiogenesis suggests that apoA-I mimetic peptides may serve as novel anti-angiogenesis agents for the treatment of angiogenesis-associated diseases, including cancer.

A theoretical study of conformational aspects and energy transfer between terthiophene and quinquethiophene in perhydrotriphenylene inclusion compounds.

A theoretical study of models with supramolecular architecture of co-inclusion compounds based on the host perhydrotriphenylene and guests terthiophene and quinquethiophene (PHTP:T3,T5) is carried out to elucidate in detail the conformational aspects of the oligomeric guest species in the PHTP matrix host. The factors that direct the geometry, location and separation of terthiophene and quinquethiophene within the channels of the PHTP host have been studied using semi-empirical and ab initio calculations. The movement of the guests inside the channel is subject to constraints preventing free rotations or axial displacements along the nanochannel. Optimal arrangement and the general trend of the relative order between T3 and T5 in the (PHTP:T3,T5) co-inclusion compound is obtained. Furthermore, excited state calculations allow the explanation of the spectral shifts of the included species in terms of the planarization of their geometries. An analysis of the energy transfer processes between the T3-T5 donor-acceptor pair based on the configurational details of the co-inclusion compound conclude that efficient transfer proceeds only through two different and perpendicular windows for the T3 --> T5 transfer. The results emphasize the importance for better understanding of the directional details of the energy transfer mechanisms in this kind of one-dimensional systems.

Optimization of volumetric computed tomography for skeletal analysis of model genetic organisms.

Forward and reverse genetics now allow researchers to understand embryonic and postnatal gene function in a broad range of species. Although some genetic mutations cause obvious morphological change, other mutations can be more subtle and, without adequate observation and quantification, might be overlooked. For the increasing number of genetic model organisms examined by the growing field of phenomics, standardized but sensitive methods for quantitative analysis need to be incorporated into routine practice to effectively acquire and analyze ever-increasing quantities of phenotypic data. In this study, we present platform-independent parameters for the use of microscopic x-ray computed tomography (microCT) for phenotyping species-specific skeletal morphology of a variety of different genetic model organisms. We show that microCT is suitable for phenotypic characterization for prenatal and postnatal specimens across multiple species.