Facile Peptide Macrocyclization and Multifunctionalization via Cyclen Installation.

Cyclen-peptide bioconjugates are usually prepared in multiple steps that require individual preparation and purification of the cyclic peptide and hydrophilic cyclen derivatives. An efficient strategy is discovered for peptide cyclization and functionalization toward lanthanide probe via three components intermolecular crosslinking on solid-phase peptide synthesis with high conversion yield. Multifunctionality can be conferred by introducing different modular parts or/and metal ions on the cyclen-embedded cyclopeptide. As a proof-of-concept, a luminescent Eu3+ complex and a Gd3+-based contrasting agent for in vitro optical imaging and in vivo magnetic resonance imaging, respectively, are demonstrated through utilizing this preparation of cyclen-embedded cyclic arginylglycylaspartic acid (RGD) peptide.

Incorporation of Fmoc-Dab(Mtt)-OH during solid-phase peptide synthesis: a word of caution.

As a commercially available and orthogonally protected amino acid building block, Fmoc-Dab(Mtt)-OH showed abnormally poor coupling efficiency during solid-phase peptide synthesis (SPPS). Herein, we reveal that Fmoc-Dab(Mtt)-OH undergoes rapid lactamization under a series of conditions with various coupling reagents. Although the complete incorporation of Fmoc-Dab(Mtt)-OH can be achieved using a multi-time and preincubation-free protocol with the coupling reagent DEPBT, alternative orthogonally protected building blocks are suggested to be used for avoiding such a costly and tedious procedure.

Correction: Incorporation of Fmoc-Dab(Mtt)-OH during solid-phase peptide synthesis: a word of caution.

Correction for 'Incorporation of Fmoc-Dab(Mtt)-OH during solid-phase peptide synthesis: a word of caution' by Pak-Lun Lam et al., Org. Biomol. Chem., 2022, DOI: 10.1039/d2ob00070a.

"When the Benign Bleed" Vestibular Schwannomas with Clinically Significant Intratumoral Hemorrhage: A Case Series and Review of the Literature.

Vestibular schwannomas (VSs) are slow-growing benign neoplasms commonly located at the cerebellopontine angle. Although clinically significant hemorrhagic VSs are rarely encountered with only 75 patients previously reported, they could be life threatening. We discuss the presentation and outcomes of three patients with hemorrhagic VS as well as review the literature for this phenomenon. Consecutive adult patients with a histologically proven diagnosis of VS over a 9-year period were retrospectively reviewed. Fifty adult patients were identified with three (6%) having clinically significant intratumoral hemorrhage. This was defined as patients having acute to subacute symptoms with frank radiological evidence of hemorrhage. The mean age of diagnosis was 62 ± 9 years and the male-to female ratio was 2:1. The mean duration of symptoms, namely headache, vertigo, and sensorineural hearing impairment, was 26 ± 4 days with one patient presenting with acute coma. Retrosigmoid craniotomy for tumor resection was performed for all patients. Histopathological examination revealed extensive areas of microhemorrhage with considerable macrophage infiltration. All three patients were discharged with no additional neurological deficit and good functional performance. Clinically significant hemorrhagic VSs are rare, and patients may present with acute to subacute (i.e., within a month) symptoms of hearing loss headache, facial, or trigeminal nerve palsy. Macrophage infiltration is frequently encountered in tumor specimens and reflects the pivotal role of chronic inflammation in their pathophysiology. Surgical resection can lead to good outcomes with timely intervention.

Evidence for Cerebral Embolic Prevention in Transcatheter Aortic Valve Implantation and Thoracic Endovascular Aortic Repair.

BACKGROUND: Embolic stroke is a formidable complication of transcatheter aortic valve implantation (TAVI) and thoracic endovascular aortic repair (TEVAR). Mechanical strategies to reduce the risk of ischemic embolic lesions include embolic protection devices (EPDs) and carbon dioxide flushing (CDF). This study aims to assess the efficacy for EPD and CDF uses in TAVI and TEVAR. METHODS: A literature review was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis. All searches were performed via PubMed, OvidSP, MEDLINE, Web of Science Core Collection, and Cochrane Library. Conference abstracts and proceedings were included. Those that were out of scope of interest and review articles were excluded. RESULTS: Eighteen studies fulfilled the inclusion criteria of the 456 articles searched. Regarding EPD use in TAVI, systematic review comparing EPD with no-EPD showed smaller total volume of cerebral lesions and smaller volume per lesion in patients with EPD in all studies. They also performed better in postoperative neurocognitive assessments but could not demonstrate clinical prevention of embolic stroke in all studies. While for EPD use in TEVAR, capture of embolic debris and absence of early postoperative neurocognitive deficit were demonstrated in all cases of 2 prospective pilot studies. Concerning CDF in TEVAR, significant reduction in gaseous emboli released during stent-graft deployment was shown by 1 in vitro study. Successful CDF application in all patients, with only 1 case of postoperative nondisabling stroke, was also demonstrated by 1 cohort study. CONCLUSIONS: This systematic review of medical literature has demonstrated the safety and feasibility of EPD use in TAVI. Although improvements in clinical outcomes have yet been demonstrated, there was level I evidence showing reduced embolic lesions in imaging. The use of EPD and CDF in TEVAR was suggested, but evidence remained inadequate to support routine clinical use.

The impact of palliative care training for oncologists and integrative palliative service in a public-funded hospital cluster-a retrospective cohort study.

PURPOSE: Oncological care of advanced cancer patients was provided by multiple departments in Hong Kong. One of these departments, the clinical oncology department (COD), introduced systematic palliative care training for its oncologists since 2002. The COD was recognized as a European Society for Medical Oncology (ESMO) Designated Centre of Integrated Oncology and Palliative Care since 2009. This retrospective cohort study aims to review the impact of integrative training and service on palliative care coverage and outcome. METHODS: Clinical information, palliative service provision, and end-of-life outcomes of patients who passed away from lung, colorectal, liver, stomach, or breast cancer in the Hong Kong West public hospital network during July 2015 to December 2015 were collected. RESULTS: A total of 307 patients were analyzed. Around half (49.2%) were attended primarily by COD, and 68.9% received palliative service. There are significantly fewer patients referred to palliative care from other departments (p < 0.001), with only 19.9% of this patient group receiving palliative referral. COD patients had longer palliative coverage before death (median 65 days versus 24 days, p < 0.001), higher chance of receiving end-of-life care at hospice units (36.4 versus 21.2%, p = 0.003), lower ICU admission (0.66 versus 5.1%, p = 0.02), and higher percentage of receiving strong opioid in the last 30 days of life (51.0 versus 28.9%, p < 0.001) compared to other departments. In multivariable analysis, COD being the primary care team (odds ratio 12.2, p < 0.001) was associated with higher palliative care coverage. CONCLUSION: The study results suggested that systematic palliative care training of oncologists and integrative palliative service model was associated with higher palliative service coverage and improved palliative care outcomes.

A Cross Sectional Study on Knowledge, Attitude and Practice related to Human Papillomavirus Vaccination for Cervical Cancer Prevention between Medical and Non-Medical Students in Hong Kong

Background: One of the most important aetiologies of cervical cancer is Human Papillomavirus (HPV) infection. While vaccination is an effective way in preventing high risk HPV infection, HPV vaccine uptake rate in Hong Kong has been low. Considering the proven effectiveness of HPV vaccination and the low vaccination uptake rate in Hong Kong, this study was conducted to compare the knowledge, attitude and practice towards HPV vaccination for cervical cancer prevention between medical and non-medical students in the University of Hong Kong. Methods: A total of 420 full time undergraduates from the University of Hong Kong were recruited and evaluated. Questionnaires covering demographics, sexual risk profile, knowledge, attitude and practice towards HPV vaccination were applied, with the Chi-square test analysis. Results: Medical students had more comprehensive knowledge than their non-medical counterparts on HPV vaccination, including the carcinogenicity of HPV (P<0.001), available vaccines on the market (P<0.001) and the outcome of vaccination (P<0.001). In particular, senior medical students (Year 3 or above) were shown to be more knowledgeable than their juniors (below Year 3) with statistical significance (P<0.001). Positive attitudes toward HPV vaccination were observed more frequently among medical students when compared to non-medical students, especially regarding the usefulness of HPV vaccination in males (P<0.001). However, there was no significant difference in the vaccination rate between medical and non-medical students (P=0.671), suggesting an importance for factors other than knowledge, such as cost of vaccination and anxiety of side effects. Conclusions: Medical students in Hong Kong, especially those in senior years, had more comprehensive knowledge and positive attitudes towards HPV vaccination than non-medical students. Yet, there was no significant difference in the practice of HPV vaccination between medical and non-medical students. In addition to medical education, other factors such as health beliefs, risk perception and financial considerations, may have a role in determining HPV vaccination for cervical cancer prevention.