Search

Perineal recurrence after brachytherapy is an exceedingly rare complication. Moreover, ductal adenocarcinoma is a rare histological variant of prostate cancer. Herein, we describe a case of perineal recurrence from ductal adenocarcinoma of prostate after low-dose-rate brachytherapy (LDR-BT) in a 65-year-old male patient. The patient had localized prostate cancer, for which he received LDR-BT; however, he experienced perineal recurrence 2 years after receiving LDR-BT. Surgical excision was attempted, but we were unable to remove the whole tumor, owing to invasion to surrounding tissue. Pathological examination of resected tumor showed ductal adenocarcinoma of the prostate. External beam radiation therapy and high-dose-rate brachytherapy (HDR-BT) were performed for residual tumor. Mild mediastinal lymph node swelling was observed during clinical course of the disease. Hence, androgen deprivation therapy was administered with abiraterone after radiation therapy, and prostate-specific antigen level decreased to undetectable level. Biochemical failure after transperineal brachytherapy for prostate cancer should be considered as a perineal recurrence.

Summary: The PTEN gene is highly mutated in many cancers, including hepatocellular carcinoma. The PTEN protein is located at different subcellular regions—PTEN at the plasma membrane suppresses PI3-kinase signaling in cell growth, whereas PTEN in the nucleus maintains genome integrity. Here, using nuclear PTEN-deficient mice, we analyzed the role of PTEN in the nucleus in hepatocellular carcinoma that is induced by carcinogen and oxidative stress-producing hepatotoxin. Upon oxidative stress, PTEN was accumulated in the nucleus of the liver, and this accumulation promoted repair of DNA damage in wild-type mice. In contrast, nuclear PTEN-deficient mice had increased DNA damage and accelerated hepatocellular carcinoma formation. Both basal and oxidative stress-induced localization of PTEN in the nucleus require ubiquitination of lysine 13 in PTEN. Taken together, these data suggest the critical role of nuclear PTEN in the protection from DNA damage and tumorigenesis in vivo.

Introduction Familial hypercholesterolaemia (FH) is an autosomal-dominant inherited genetic disease. It carries an extremely high cardiovascular risk associated with significantly elevated low-density lipoprotein (LDL) cholesterol. The diagnostic rate of this disease in some European nations is quite high, due to the presence of multiple prospective registries. On the other hand, few data—and in particular multicentre data—exist regarding this issue among Japanese subjects. Therefore, this study intends to assemble a multicentre registry that aims to comprehensively assess cardiovascular risk among Japanese FH patients while taking into account their genetic backgrounds.Methods and analysis The Hokuriku-plus FH registry is a prospective, observational, multicentre cohort study, enrolling consecutive FH patients who fulfil the clinical criteria of FH in Japan from 37 participating hospitals mostly in Hokuriku region of Japan from April 2020 to March 2024. A total of 1000 patients will be enrolled into the study, and we plan to follow-up participants over 5 years. We will collect clinical parameters, including lipids, physical findings, genetic backgrounds and clinical events covering atherosclerotic and other important events, such as malignancies. The primary endpoint of this study is new atherosclerotic cardiovascular disease (ASCVD) events. The secondary endpoints are as follows: LDL cholesterol, secondary ASCVD events and the occurrence of other diseases including hypertension, diabetes and malignancies.Ethics and dissemination This study is being conducted in compliance with the Declaration of Helsinki, the Ethical Guidelines for Medical and Health Research Involving Human Subjects, and all other applicable laws and guidelines in Japan. This study protocol has been approved by the Institutional Review Board at Kanazawa University. We will disseminate the final results at international conferences and in a peer-reviewed journal.Trial registration number UMIN000038210.

Objective: Many erectile dysfunction (ED) cases are attributed to vascular endothelial dysfunction and impaired blood flow due to arteriosclerotic changes. In this study, we examined the association among the erection hardness score (EHS), pulse wave velocity (PWV), and the presence of carotid artery plaques. Subjects and Methods: The study enrolled 67 patients who visited our hospital with the chief complaint of ED. Based on the history at the first visit, 28 of the 67 patients were categorized into the EHS 3–4 group and the remaining 39 into the EHS 0–2 group. The two groups were retrospectively analyzed. Results: The PWV points were significantly higher in the EHS 0–2 group than in the EHS 3–4 group (P = 0.047). In consideration for error in age, the modified points (PWV at the first visit – reference PWV by age) were significantly higher in the EHS 0–2 group than in the EHS 3–4 group (P = 0.026). This group also showed a higher detection rate of plaques by carotid ultrasound (66.7%). Conclusion: This study showed that patients with lower points of EHS had higher PWV and were more likely to have carotid artery plaques. While ED has occasionally been considered as an early risk marker for the onset of cardiovascular events; this study suggests that the hardness of the penis can be an easier-to-measure and more sensitive index.

Dynamin-related protein 1 (Drp1) divides mitochondria as a mechano-chemical GTPase. However, the function of Drp1 beyond mitochondrial division is largely unknown. Multiple Drp1 isoforms are produced through mRNA splicing. One such isoform, Drp1ABCD, contains all four alternative exons and is specifically expressed in the brain. Here, we studied the function of Drp1ABCD in mouse neurons in both culture and animal systems using isoform-specific knockdown by shRNA and isoform-specific knockout by CRISPR/Cas9. We found that the expression of Drp1ABCD is induced during postnatal brain development. Drp1ABCD is enriched in dendritic spines and regulates postsynaptic clathrin-mediated endocytosis by positioning the endocytic zone at the postsynaptic density, independently of mitochondrial division. Drp1ABCD loss promotes the formation of ectopic dendrites in neurons and enhanced sensorimotor gating behavior in mice. These data reveal that Drp1ABCD controls postsynaptic endocytosis, neuronal morphology and brain function.

Taha and Nielsen have developed a multi-stage calculus {\lambda}{\alpha} with a sound type system using the notion of environment classifiers. They are special identifiers, with which code fragments and variable declarations are annotated, and their scoping mechanism is used to ensure statically that certain code fragments are closed and safely runnable. In this paper, we investigate the Curry-Howard isomorphism for environment classifiers by developing a typed {\lambda}-calculus {\lambda}|>. It corresponds to multi-modal logic that allows quantification by transition variables---a counterpart of classifiers---which range over (possibly empty) sequences of labeled transitions between possible worlds. This interpretation will reduce the "run" construct---which has a special typing rule in {\lambda}{\alpha}---and embedding of closed code into other code fragments of different stages---which would be only realized by the cross-stage persistence operator in {\lambda}{\alpha}---to merely a special case of classifier application. {\lambda}|> enjoys not only basic properties including subject reduction, confluence, and strong normalization but also an important property as a multi-stage calculus: time-ordered normalization of full reduction. Then, we develop a big-step evaluation semantics for an ML-like language based on {\lambda}|> with its type system and prove that the evaluation of a well-typed {\lambda}|> program is properly staged. We also identify a fragment of the language, where erasure evaluation is possible. Finally, we show that the proof system augmented with a classical axiom is sound and complete with respect to a Kripke semantics of the logic.

Tse and Zdancewic have formalized the notion of noninterference for Abadi et al.'s DCC in terms of logical relations and given a proof of noninterference by reduction to parametricity of System F. Unfortunately, their proof contains errors in a key lemma that their translation from DCC to System F preserves the logical relations defined for both calculi. In fact, we have found a counterexample for it. In this article, instead of DCC, we prove noninterference for sealing calculus, a new variant of DCC, by reduction to the basic lemma of a logical relation for the simply typed lambda-calculus, using a fully complete translation to the simply typed lambda-calculus. Full completeness plays an important role in showing preservation of the two logical relations through the translation. Also, we investigate relationship among sealing calculus, DCC, and an extension of DCC by Tse and Zdancewic and show that the first and the last of the three are equivalent.