In this work the selective uptake of native horse spleen ferritin and apoferritin loaded with MRI contrast agents has been assessed in human breast cancer cells (MCF-7 and MDA-MB-231). The higher ...expression of L-ferritin receptors (SCARA5) led to an enhanced uptake in MCF-7 as shown in T2 and T1 weighted MR images, respectively. The high efficiency of ferritin internalization in MCF-7 has been exploited for the simultaneous delivery of curcumin, a natural therapeutic molecule endowed with antineoplastic and anti-inflammatory action, and the MRI contrast agent Gd-HPDO3A. This theranostic system is able to treat selectively breast cancer cells over-expressing ferritin receptors. By entrapping in apoferritin both Gd-HPDO3A and curcumin, it was possible to deliver a therapeutic dose of 167 μg ml(-1) (as calculated by MRI) of this natural drug to MCF-7 cells, thus obtaining a significant reduction of cell proliferation.
To capture the perspective of prospective urology applicants experiencing unique challenges in the context of COVID-19.
A voluntary, anonymous survey was distributed online, assessing the impact of ...COVID-19 on a large sample of US medical students planning to apply to urology residencies. Themes of (1) specialty discernment, (2) alterations to medical education, and (3) the residency application process were explored.
A total of 238 medical students, 87% third and fourth years, responded to the survey. While 85% indicated that the pandemic had not deterred their specialty choice, they noted substantial impacts on education, including 82% reporting decreased exposure to urology. Nearly half of students reported changes to required rotations and 35% reported changes to urology-specific rotations at their home institutions. Students shared concerns about suspending in-person experiences, including the impact on letters of recommendation (68% “very concerned) and program choice (73% “very concerned”). Looking to the possibility of virtual interactions, students identified the importance of small group and one-on-one communication with residents (83% “very important”) and opportunities to learn about hospital facilities (72% “very important”).
Despite the impacts of COVID-19 on medical education, prospective urology applicants appear to remain confident in their specialty choice. Students’ biggest concerns involve disruption of away rotations, including impacts on obtaining letters of recommendation and choosing a residency program.
Purpose Active surveillance of prostate cancer has emerged as a viable treatment option for men with features of low risk disease. Five prospective studies have enrolled patients for active ...surveillance with varying inclusion criteria. We evaluated the pathological outcomes of men meeting published criteria for active surveillance who elected immediate radical prostatectomy to assess the risk of under grading and under staging in candidates for active surveillance. Materials and Methods Data were extracted from our institutional urological oncology database for all men who underwent radical prostatectomy between 1996 and 2007. The primary outcome was pathological up staging, defined as the occurrence of extracapsular extension or seminal vesicle involvement. Pathological upgrading was identified as a secondary outcome. We determined the proportion of men who would have qualified for each published active surveillance study and the respective rates of upgrading and up staging in each group. Results We identified 1,097 men who underwent radical prostatectomy with a mean age of 59 years. Overall 28% of the men experienced a Gleason upgrade, 21% had extracapsular extension and 11% had seminal vesicle involvement. In men qualifying based on published active surveillance inclusion criteria, rates of upgrading varied between 23% and 35%, the incidence of extracapsular extension ranged from 7% to 19% and seminal vesicle involvement ranged from 2% to 9%. Conclusions Varying entry criteria for active surveillance show different rates of adverse pathological features at radical prostatectomy. Predictably fewer men met the more stringent criteria but these men had a lower incidence of seminal vesicle involvement and extracapsular extension. Such data can be used to advise men of the risks of active surveillance.
As couples are increasingly delaying parenthood, the effect of the aging men and women on reproductive outcomes has been an area of increased interest. Advanced paternal age has been shown to ...independently affect the entire spectrum of male fertility as assessed by reductions in sperm quality and fertilization (both assisted and unassisted). Moreover, epidemiological data suggest that paternal age can lead to higher rates of adverse birth outcomes and congenital anomalies. Mounting evidence also suggests increased risk of specific pediatric and adult disease states ranging from cancer to behavioral traits. While disease states associated with advancing paternal age have been well described, consensus recommendations for neonatal screening have not been as widely implemented as have been with advanced maternal age.
Background and purpose
The prevalence of fatigue and its relation with clinical, neuropsychological and brain magnetic resonance imaging (MRI) variables in a large cohort of multiple sclerosis (MS) ...patients was investigated.
Method
The Modified Fatigue Impact Scale and its subdomains were collected from 725 healthy controls and 366 MS patients 238 relapsing–remitting (RRMS) and 128 progressive (PMS). For the Modified Fatigue Impact Scale global and subdomains, MS patients were classified as fatigued (F‐MS) or non‐fatigued (NF‐MS) according to cut‐off values provided by logistic regression models with a specificity of 90% (i.e. a 10% false‐positive rate in classifying healthy controls). MS patients underwent neurological, neuropsychological and MRI evaluations. Clinical and MRI measures were compared between F‐MS and NF‐MS patients using age‐, sex‐ and phenotype‐adjusted linear models. Heterogeneities between phenotypes were tested with specific interaction terms.
Results
Global fatigue affected 174 (47.5%) MS patients, being more prevalent in PMS (PMS 64.1% vs. RRMS 38.7%, P < 0.001). For all dichotomizations, F‐MS were older (P from <0.001 to 0.012) and more depressed (P < 0.001) than NF‐MS patients. Compared to NF‐MS, cognitive F‐MS patients had lower education (P = 0.035). Compared to NF‐MS, patients with global and physical fatigue had higher Expanded Disability Status Scale only for RRMS (P < 0.001). Only RRMS patients with physical fatigue had lower brain (P = 0.05), white matter (P = 0.039) and thalamic volumes (P = 0.022) compared to NF‐MS patients.
Conclusions
In MS, fatigue is associated with older age, lower education and higher depression. Only in RRMS, fatigue is associated with Expanded Disability Status Scale and brain atrophy. A plateauing effect of disability and structural damage can explain the lack of associations in PMS.
Abstract
GRB 221009A is a long gamma-ray burst among the most energetic and nearest (
z
= 0.151) detected so far. The energy fluence of the burst was so large to cause ionization of the upper layers ...of Earth’s atmosphere and also observable signals in satellite-borne particle detectors. Electron signals, with the same GRB time development, can arise from the interaction of energetic photons with the particle detector and support structures. This effect was previously reported for the HEPP-L on board the China Seismo-Electromagnetic Satellite. We searched for the same effect on the particle detectors on board five POES and MetOp satellites. Electron signals in coincidence with the gamma-ray emission of the burst were found in three satellites, which were well illuminated by the GRB. The properties of the found electron signals are reported and discussed.
Aim
To investigate the relationship between apical periodontitis and atherosclerosis in rats by lipid profile and carotid artery intima tunic measurement, and histological and histometric evaluation ...of periapical lesions.
Methodology
Forty male Wistar rats were allocated into four groups: control (C), with apical periodontitis (AP), with atherosclerosis (AT) and with AP and AT (AP + AT). Atherosclerosis was induced using a high‐lipid diet associated with a surgical ligature in the carotid artery and a super dosage of vitamin D3. AP was induced via pulp exposure to the oral environment. At 45 and 75 days, serum levels of total cholesterol (TC), triglycerides (TG), high‐density lipoprotein cholesterol (HDL‐C) and low‐density lipoprotein cholesterol (LDL‐C) were measured. The maxillary and mandibular jaws and carotid artery were collected and processed for histological analysis. The Kruskal–Wallis or Mann–Whitney test was performed for nonparametric data, and the Tukey’s or Student’s t‐test was performed for parametric data (P < 0.05).
Results
In nonatherosclerotic animals, the induction of apical periodontitis increased TG levels significantly, from 63.1 ± 11.4 mg dL−1 in group C to 88.2 ± 7.9 mg dL−1 in the AP group (P < 0.05). The induction of AP was associated with a trend for higher TC and LDL‐C levels in atherosclerotic animals (P > 0.05); however, it only significantly increased TG levels, from 93.2 ± 18.0 mg dL−1 in AT group to 121.9 ± 14.5 mg dL−1 in the AP + AT group (P < 0.05). Animals in the AP + AT group had a 36.5% increase in the thickness of the carotid intima tunic when compared with the AT group (P < 0.05). The intensity of the inflammatory infiltrate was significantly larger in the AP + AT group when compared with AP group (P < 0.05). The AP + AT group exhibited significantly greater alveolar bone loss, with a periapical lesion size of 206.4 ± 56.3 × 104 μm2, compared with 151.4 ± 49.1 × 104 μm2 in the AP group (P < 0.05).
Conclusion
Apical periodontitis influenced triglyceride levels, increasing them even in the absence of atherosclerosis, and influenced the increase in the thickness of the carotid artery intima tunic in the presence of atherosclerosis. Atherosclerosis intensified the inflammatory reaction and increased bone resorption in periapical lesions.
PNX was described as an uncommon complication in COVID-19 patients but clinical risk predictors and the potential role in patient's outcome are still unclear. We assessed prevalence, risk predictors ...and mortality of PNX in hospitalized COVID- 19 with severe respiratory failure performing a retrospective observational analysis of 184 patients admitted to our COVID-19 Respiratory Unit in Vercelli from October 2020 to March 2021. We compared patients with and without PNX reporting prevalence, clinical and radiological features, comorbidities, and outcomes. Prevalence of PNX was 8.1% and mortality was >86% (13/15) significantly higher than in patients without PNX (56/169) (P < 0.001). PNX was more likely to occur in patients with a history of cognitive decline (HR: 31.18) who received non-invasive ventilation (NIV) (p < 0.0071) and with low P/F ratio (HR: 0.99, p = 0.004). Blood chemistry in the PNX subgroup compared to patients without PNX showed a significant increase in LDH (420 U/L vs 345 U/L, respectively p = 0.003), ferritin (1111 mg/dl vs 660 mg/dl, respectively p = 0.006) and decreased lymphocytes (HR: 4.440, p = 0.004). PNX may be associated with a worse prognosis in terms of mortality in COVID patients. Possible mechanisms may include the hyperinflammatory status associated with critical illness, the use of NIV, the severity of respiratory failure and cognitive impairment. We suggest, in selected patients showing low P/F ratio, cognitive impairment and metabolic cytokine storm, an early treatment of systemic inflammation in association with high-flow oxygen therapy as a safer alternative to NIV in order to avoid fatalities connected with PNX.
•A correction of the Author's affiliation was done because there was a mistake in the original proof.•One version of the abstract was selected.•Answers to Reviewers were addressed in the specific file.•All text additions/corrections are highlighted in yellow.•All deleted words/sentences in the text are marked with a black line.
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