DNA damage response in a 2D-culture model by diffusing alpha-emitters radiation therapy (Alpha-DaRT).

Diffusing alpha-emitters radiation therapy (Alpha-DaRT) is a unique method, in which interstitial sources carrying 224Ra release a chain of short-lived daughter atoms from their surface. Although DNA damage response (DDR) is crucial to inducing cell death after irradiation, how the DDR occurs during Alpha-DaRT treatment has not yet been explored. In this study, we temporo-spatially characterized DDR such as kinetics of DNA double-strand breaks (DSBs) and cell cycle, in two-dimensional (2D) culture conditions qualitatively mimicking Alpha-DaRT treatments, by employing HeLa cells expressing the Fucci cell cycle-visualizing system. The distribution of the alpha-particle pits detected by a plastic nuclear track detector, CR-39, strongly correlated with γH2AX staining, a marker of DSBs, around the 224Ra source, but the area of G2 arrested cells was more widely spread 24 h from the start of the exposure. Thereafter, close time-lapse observation revealed varying cell cycle kinetics, depending on the distance from the source. A medium containing daughter nuclides prepared from 224Ra sources allowed us to estimate the radiation dose after 24 h of exposure, and determine surviving fractions. The present experimental model revealed for the first time temporo-spatial information of DDR occurring around the source in its early stages.

Hand and Wrist trauma: Antimicrobials and Infection Audit of Clinical Practice (HAWAII ACP) protocol.

Aims: Hand trauma, consisting of injuries to both the hand and the wrist, are a common injury seen worldwide. The global age-standardized incidence of hand trauma exceeds 179 per 100,000. Hand trauma may require surgical management and therefore result in significant costs to both healthcare systems and society. Surgical site infections (SSIs) are common following all surgical interventions, and within hand surgery the risk of SSI is at least 5%. SSI following hand trauma surgery results in significant costs to healthcare systems with estimations of over £450 per patient. The World Health Organization (WHO) have produced international guidelines to help prevent SSIs. However, it is unclear what variability exists in the adherence to these guidelines within hand trauma. The aim is to assess compliance to the WHO global guidelines in prevention of SSI in hand trauma. Methods: This will be an international, multicentre audit comparing antimicrobial practices in hand trauma to the standards outlined by WHO. Through the Reconstructive Surgery Trials Network (RSTN), hand surgeons across the globe will be invited to participate in the study. Consultant surgeons/associate specialists managing hand trauma and members of the multidisciplinary team will be identified at participating sites. Teams will be asked to collect data prospectively on a minimum of 20 consecutive patients. The audit will run for eight months. Data collected will include injury details, initial management, hand trauma team management, operation details, postoperative care, and antimicrobial techniques used throughout. Adherence to WHO global guidelines for SSI will be summarized using descriptive statistics across each criteria. Discussion: The Hand and Wrist trauma: Antimicrobials and Infection Audit of Clinical Practice (HAWAII ACP) will provide an understanding of the current antimicrobial practice in hand trauma surgery. This will then provide a basis to guide further research in the field. The findings of this study will be disseminated via conference presentations and a peer-reviewed publication.

Acute Hand Injury in Surfing: A Case Report.

Hand injuries from surfing tend to be severe and require medical attention. Follow-up of a surfing injury is difficult because many patients are visiting and go home after treatment. We report a case of a surfing hand injury sustained abroad, which was treated upon the patient's return, allowing for follow-up. The mechanism of injury was traction and torsion from the surfboard leash while surfing. The patient was initially treated for nailbed injury but presented later back home after persistent pain, for which an unstable distal phalanx fracture in their right ring finger was found by x-ray. This was surgically reduced with K-wire insertion and nailbed repair. Postoperatively, the injured finger was kept in a splint, and the patient had physiotherapy. Pain was significantly reduced, and the patient regained sufficient function. Considering a fracture as a differential for finger injury caused by the surfboard leash may prevent management delays. Injury may be prevented through education and redesign of the surfboard leash.

A Case of Radiation-Induced Brachial Plexopathy Below the Tolerance Dose.

This case report details a rare instance of radiation-induced brachial plexopathy (RIBP) occurring below the typical tolerance dose in a 55-year-old woman following chemoradiotherapy for apical non-small cell lung carcinoma. Despite receiving a radiation dose considered safe (47-48 Gray in 25 fractions), she developed sensory abnormalities and motor weakness in the right upper limb. The diagnostic distinction between RIBP and tumor recurrence was achieved using MRI, which showed characteristic features of radiation-induced damage. The patient's medical history included smoking and rheumatoid arthritis, highlighting the role of patient-specific factors in the development of RIBP. The case underscores the importance of recognizing RIBP as a potential diagnosis in patients with new-onset brachial plexopathy post-radiation therapy, even when radiation exposure is within conventional safety limits. This report contributes to the literature by demonstrating that RIBP can occur at lower-than-expected radiation doses, especially in the presence of contributing factors like neurotoxic chemotherapy and individual patient risks. It emphasizes the need for careful assessment and management in such cases to distinguish between RIBP and cancer recurrence.

CRUMPLED LEAF supports plastid OUTER ENVELOPE PROTEIN OF 80 KDA complex formation in Arabidopsis.

Embedded ß-barrel proteins in the outer envelope membrane mediate most cellular trafficking between the cytoplasm and plastids. Although the TRANSLOCON AT THE OUTER ENVELOPE MEMBRANE OF CHLOROPLASTS 75-V (TOC75-V)/OUTER ENVELOPE PROTEIN OF 80 KDA (OEP80) complex has been implicated in the insertion and assembly of ß-barrel proteins in the outer envelope membrane of Arabidopsis (Arabidopsis thaliana) chloroplasts, relatively little is known about this process. CRUMPLED LEAF (CRL) encodes a chloroplast outer envelope membrane-localized protein, and its loss-of-function mutation results in pleiotropic defects, including altered plant morphogenesis, growth retardation, suppression of plastid division, and spontaneous light intensity-dependent localized cell death. A suppressor screen conducted on mutagenized crl mutants revealed that a missense mutation in OEP80 suppresses the pleiotropic defects of crl. Furthermore, we found that OEP80 complex formation is compromised in crl. Additionally, we demonstrated that CRL interacts with OEP80 in vivo and that a portion of CRL is present at the same molecular weight as the OEP80 complex. Our results suggest that CRL interacts with OEP80 to facilitate its complex formation. CRL is involved in plastid protein import; therefore, the pleiotropic defects in crl are likely due to the combined effects of decreased plastid protein import and altered membrane integration of ß-barrel proteins in the outer envelope membrane. This study sheds light on the mechanisms that allow ß-barrel protein integration into the plastid outer envelope membrane and the importance of this finding for plant cellular processes.

Feasibility of accelerated partial breast irradiation with strut-adjusted volume implant brachytherapy in Japan focusing on dosimetry and acute toxicity: a Japanese multi-institutional prospective study.

BACKGROUND: A Japanese multi-institutional prospective study was initiated to investigate the effectiveness and safety of accelerated partial breast irradiation (APBI) using strut-adjusted volume implant (SAVI) brachytherapy, with subjects registered between 2016 and 2021. Herein, we report the preliminary results on the feasibility of this treatment modality in Japan, focusing on the registration process, dosimetry, and acute toxicities. PATIENTS AND METHODS: Primary registration was conducted before breast-conserving surgery (BCS) and the eligibility criteria included the following: age ≥ 40 years, tumor unifocal and unicentric, ≤ 3 cm in diameter, cN0M0, proven ductal, mucinous, tubular, medullary, or lobular carcinoma by needle biopsy. Secondary registration was conducted after BCS had been performed leaving a cavity for device implantation and pathological evaluations, and the eligibility criteria were as follows: negative surgical margin, tumor ≤ 3 cm in diameter on gross pathological examination, histologically confirmed ductal, mucinous, tubular medullary, colloid, or lobular carcinoma, pN0, L0V0, no extensive ductal component, no initiation of chemotherapy within 2 weeks of the brachytherapy APBI planning with SAVI was performed for the patients successfully entered in the study by the secondary registration process, and the treatment was administered at the dose of 34 Gy in 10 fractions administered twice daily. RESULTS: Between 2016 and 2021, 64 women were enrolled in the study through primary registration, of which 19 were excluded from the secondary registration process, and in one, it was deemed impossible to comply with the dose constraints established during treatment planning. After the exclusion of these latter 20 patients, we treated the remaining 44 patients by APBI with SAVI. The dose constraints could be adhered to in all the patients, but re-planning was necessitated in 3 patients because of applicator movement during the treatment period. Grade 2 acute toxicities were observed in 18% of all patients, but more severe acute toxicities than Grade 2 were not observed in any of the patients. CONCLUSION: APBI with SAVI brachytherapy is feasible in Japan from the aspects of compliance with dose constraints and frequency of acute toxicities.

Time to Pain Relapse After Palliative Radiotherapy for Bone Metastasis: A Prospective Multi-institutional Study.

BACKGROUND/AIM: Low risk asymptomatic bone metastasis (LRABM) without gross osteolytic changes tends to be out of indication for radiotherapy. The aim of this study was to evaluate the time between the end of palliative radiotherapy of bone metastasis (BM) until the start of new pain, in patients with painful BM. PATIENTS AND METHODS: Patients with BM were prospectively assessed for location and strength of pain every month for one year after radiotherapy. The correlation of pain relapse at irradiated site, and pain onset outside the irradiated site was evaluated with sex, age, primary tumor, pathology of tumor, visceral metastases, baseline scores for Eastern Cooperative Oncology Group performance status (PS), and baseline verbal rating scale (VRS). RESULTS: A hundred and thirty-two patients were included (79 males and 53 females). Median age was 66 years. Primary sites were lung (n=60), breast (n=17), colon (n=12), prostate (n=11), and others (n=33) (one patient had two primary sites). Median follow-up was 185 days. Pain relief was observed in 92 patients (86.0%). Out of them, pain progression was observed in 69.6%. Median time to pain progression was 75.5 days. Pain onset outside the irradiated site was observed in 57 patients (43.2%). Median time to pain onset was 109 days. Out of the 57 patients, 13 (22.8%) had LRABM which existed before the start of radiotherapy. There were 54 patients with LRABM in this study and because many patients had more than one LRABM, the total LRABM sites were 123. Out of them, pain onset was observed within one year after irradiation in 44 (36%) lesions. Median time to pain onset was 67 days, which was the shortest of the three: irradiated site, out of the irradiated site, and LRABM site. Risk factors for high probability of pain onset within one year in LRABM lesions were female sex (showing a trend in univariate analysis), and pelvic, skull and spine metastasis (significant in multivariate analysis). CONCLUSION: Time to pain onsets in LRABM are relatively short, especially in female patients with pelvic, skull and spine metastasis. In these patients, prophylactic radiotherapy could be an option to consider.

253 J at 0.2†Hz, LD pumped cryogenic helium gas cooled Yb:YAG ceramics laser.

A 253 J with 26 ns at 0.2 Hz laser performance was demonstrated using a LD pumped cryogenically cooled Yb:YAG ceramics laser amplifier. A high energy storage of 344 J was achieved with a stored energy density of 0.58 J/cm3 using a 1 kJ output multidirectional-pumping system. High energy-extraction efficiency of 56.5% was achieved with high energy fluence of 4.63 J /cm2. To the best of our knowledge, this is the highest output energy obtained with a repetitive nanosecond pulse by LD pumped solid-state laser. This paper presented a design of 1 kJ amplifier based on experimentally proven numerical data.

Retrograde Migration of an Au-198 Grain to the Submandibular Gland Post Brachytherapy Treatment of Floor of Mouth Cancer.

At our institution, radiation oncologists routinely treat early-stage oral cancer with low-dose-rate brachytherapy (LDR-BRT) using Au-198 grains. In this report, we show a unique case of a patient with a gold grain located within the submandibular gland, found incidentally during follow-up after LDR-BRT for floor of mouth cancer. One month after the implant, he showed sialadenitis-like symptoms, but the pain resolved two months later. All the grains were detected around the anterior sublingual area by computed tomography (CT) four months after the implant. Unexpectedly, 11 months after the implant, CT revealed that a grain was located in an intraglandular site of the submandibular gland. This finding clearly demonstrates that the grain entered Wharton's duct and retrogradely migrated to the submandibular gland through the duct. As a mechanism of the calculus formation within Wharton's duct, retrograde migration of foreign bodies to the inside of the duct has been proposed. Our incidental finding after LDR-BRT highlights the need for monitoring post-LDR-BRT using Au-198 grains for the treatment of floor of mouth cancer and sheds additional light on retrograde theory within Wharton's duct.

RSTNCOVID Burns: A multi-centre service evaluation and stakeholder survey of the impact of COVID-19 on burns care in England, Wales and Northern Ireland.

As the UK entered the first wave of the COVID-19 pandemic, the National Health Service published consensus guidance to the UK burns services advising changes to the acute management of burns to allow the continuation of safe care while protecting limited hospital resources. We aimed to describe the demographics of burns service users, changes to clinical pathways and experiences of the burns team during the first wave of the COVID-19 pandemic. All burns services in the UK were invited to participate in a national collaborative, trainee-led study supported by the Reconstructive Surgery Trials Network. The study consisted of (1) a service evaluation of patients receiving burns treatment during the COVID-19 pandemic; (2) a multidisciplinary team survey. Analyses were descriptive and narrative depending on data types. Collaborators from 18 sites contributed data from burns MDT surveys and 512 patients. Patient demographics were consistent with typical burns patterns in the UK. The delayed presentation occurred in 20% of cases, with 24 patients developing complications. MDT surveys indicated substantial adaptations and challenges as a result of the pandemic. Access to theatres and critical care were limited, yet a comprehensive acute burns service was maintained. Telemedicine was utilised heavily to reduce patient footfall. Adaptations in the provision of burns care, including greater outpatient care and telemedicine, have emerged out of necessity with reported success. The impact of reduced scar therapy and psychological interventions for burns patients during the pandemic requires longer-term follow-up. Lessons from the UK experience can be used to strategise for future pandemics.

Efficacy and Safety of Induction Chemotherapy and/or External Beam Radiotherapy Followed by Brachytherapy in Patients With Tongue Cancer.

BACKGROUND/AIM: To evaluate the outcomes of induction chemotherapy and/or external beam radiotherapy (EBRT) followed by brachytherapy (BT) in patients with tongue cancer who had a waiting period for BT or a large tumor that was not suitable for BT. PATIENTS AND METHODS: As an induction therapy, chemotherapy with tegafur/gimeracil/oteracil (S-1), EBRT or both S-1 chemotherapy and EBRT was prescribed. BT was performed using Au-198 grains or Ir-192 pins. Local control (LC), lymph node metastasis-free survival (LNMFS), overall survival (OS), and complication rates were calculated. RESULTS: Forty-nine patients were enrolled in this study. The 3-year LC, LNMFS, and OS rates for cT1-2 patients were 84%, 45%, and 69%, respectively. The 3-year LC, LNMFS, and OS rates for cT3 patients were 77%, 58%, and 79%, respectively. The incidence of Grade 3 or 4 complications was 6%. CONCLUSION: Induction therapy contributed to the efficacy of the subsequent BT in LC rate.

Complete one-to-one correspondence between magnifying endoscopic and histopathologic images: the KOTO method II.

Recent advances in magnifying endoscopy with narrow-band imaging/blue laser imaging have aided in the diagnosis of gastrointestinal lesions. However, it requires knowledge of the relationship between magnifying endoscopic and histopathological images. We propose a novel method which makes possible a complete correspondence between magnifying endoscopic and histopathological images at the single glandular duct level. The KOTO method II enables three-dimensional visualization of the correlation between the endoscopic surface pattern of the mucosa and histopathological images. This method may be helpful in the development of diagnosis using magnifying endoscopy.

PolliRS: A 3D-printed Pollicization Retractor System that Improves Access and Autonomy during the Surgical Procedure.

We demonstrate the design, manufacture, and deployment of the first custom-made 3-dimensional (3D)-printed hand retractor for the pollicization procedure. Radiological images of the patient's hand were taken preoperatively to measure anatomical dimensions and guide the design of the device in a patient-precise manner. The 3D-printed, sterilizable, device was autoclaved and successfully used on a patient that underwent a pollicization procedure in our unit. The radiolucency of the device and the fluency enabled by the ability to exchange between different positions demonstrated the potential of this device in increasing the overall autonomy afforded to the lead-surgeon during the operation and demonstrated the potential of rapid-prototyping techniques such as 3D printing for producing patient-precise tools on-the-fly that taken account the specific needs of the patient.

Disseminating Hand Surgery Research Using Social Media: The Relationship Between Altmetrics and Citations.

PURPOSE: Social media adds to the traditional methods of research dissemination. It allows researchers and publishers to immediately share content directly with interested end users on a global scale. Alternative metrics (altmetrics) are new bibliometrics that describe article-level activity on platforms such as Twitter, Wikipedia, and online news media. Altmetrics are strongly associated with citation counts in numerous medical disciplines. The aim of this study was to investigate the relationship of altmetrics to citation counts in the field of hand surgery. METHODS: Altmetric Explorer was used to extract data on altmetrics and citation rates for articles published in 2017 in 6 prominent hand surgery journals. Multivariable negative binomial regression was used to estimate the relationship between citation counts and predictors (presented as the incidence rate ratio with a 95% confidence interval [CI]). RESULTS: Overall, 624 articles were included. Mentions on social media platforms were independently associated with more citations (adjusted incidence rate ratio 1.04 [95% CI 1.02-1.05]). The factor that most influenced the rate of citations was the journal in which the article was published; articles in the Journal of Hand Surgery had at least 1 more citation than articles published elsewhere (median difference 3 [interquartile range {IQR} 2-3]) and had a median Altmetric Attention Score which was 3 points higher (IQR 2-3) than articles published elsewhere. CONCLUSIONS: The dissemination of hand surgery research through social media channels is associated with substantial and measurable improvements in short-term citation rates CLINICAL RELEVANCE: Social media appears to be a valuable tool for communicating important research directly to hand surgeons in a timely and succinct manner.

Reduced Hippocampal Subfield Volume in Schizophrenia and Clinical High-Risk State for Psychosis.

Magnetic resonance imaging (MRI) studies in schizophrenia demonstrated volume reduction in hippocampal subfields divided on the basis of specific cytoarchitecture and function. However, it remains unclear whether this abnormality exists prior to the onset of psychosis and differs across illness stages. MRI (3 T) scans were obtained from 77 patients with schizophrenia, including 24 recent-onset and 40 chronic patients, 51 individuals with an at-risk mental state (ARMS) (of whom 5 subsequently developed psychosis within the follow-up period), and 87 healthy controls. Using FreeSurfer software, hippocampal subfield volumes were measured and compared across the groups. Both schizophrenia and ARMS groups exhibited significantly smaller volumes for the bilateral Cornu Ammonis 1 area, left hippocampal tail, and right molecular layer of the hippocampus than the healthy control group. Within the schizophrenia group, chronic patients exhibited a significantly smaller volume for the left hippocampal tail than recent-onset patients. The left hippocampal tail volume was positively correlated with onset age, and negatively correlated with duration of psychosis and duration of medication in the schizophrenia group. Reduced hippocampal subfield volumes observed in both schizophrenia and ARMS groups may represent a common biotype associated with psychosis vulnerability. Volumetric changes of the left hippocampal tail may also suggest ongoing atrophy after the onset of schizophrenia.

Rhodium-Catalyzed ortho-Olefination of Sterically Demanding Benzamides: Application to the Asymmetric Synthesis of Axially Chiral Benzamides.

It has been established that an unsubstituted cyclopentadienyl rhodium(III) (CpRhIII ) complex is a highly active catalyst for the aerobic oxidative ortho C-H bond olefination of sterically demanding ortho-substituted benzamides with alkenes. This catalysis was successfully applied to the diastereoselective synthesis of axially chiral N,N-dialkylbenzamides. The combination of the ruthenium(II)-catalyzed enantioselective hydrogenation and the CpRhIII -catalyzed diastereoselective ortho C-H bond olefination enabled the asymmetric synthesis of axially chiral N,N-dialkylbenzamide derivatives with high ee values.

Rhodium-Catalyzed ortho-Bromination of O-Phenyl Carbamates Accelerated by a Secondary Amide-Pendant Cyclopentadienyl Ligand.

It has been established that a newly developed cyclopentadienyl rhodium(III) [CpA RhIII ] complex, bearing an acidic secondary amide moiety on the Cp ring, is able to catalyze the ortho-bromination of O-phenyl carbamates with N-bromosuccinimide (NBS) at room temperature. The presence of the acidic secondary amide moiety on the CpA ligand accelerates the bromination by the hydrogen bond between the acidic NH group of the CpA ligand and the carbonyl group of NBS.

The Wakayama-Immediate Stroke Life Support Course: Achieving Successful Training on the Stroke Emergency System without using Mechanical Medical Training Simulators.

BACKGROUND: The Immediate Stroke Life Support (ISLS) course run in Wakayama (Wakayama-ISLS course) is an off-the-job training course for understanding the initial treatment of acute stroke. A total of 22 Wakayama-ISLS courses have been held in Wakayama Prefecture since 2008. To begin with, the case presentation was performed using human-like, mechanical manikins for simulation training. However, as the course progressed, we found the students paying great attention to the display monitor, and less to the patients' neurological status. METHODS: From the fourth Wakayama-ISLS course onward, we conducted the group work with the facilitators pretending to be patients, i.e., without medical training manikins. RESULTS: When the facilitators acted as patients, the students gained a more realistic and expressive perception of neurological symptoms. As a result, they expressed a high level of satisfaction with the course in the questionnaire sent immediately afterwards, regardless of their profession or prior experience. Moreover, as we did not need to transfer medical training simulators, we were able to carry out three ISLS courses at locations some distance from Wakayama city on a low-cost basis. This also enabled the regional medical staff in rural hospitals to participate in the courses easily. CONCLUSION: The Wakayama-ISLS course without medical training manikins is an entirely feasible off-the-job training course, which provides training on fast and excellent treatment of acute stroke problems based on clinical practice. The course has the potential to spread not only across Japan but throughout the world, including to developing countries, given the cost perspective.

Aerobic Oxidative Cross-Coupling of Substituted Acrylamides with Alkenes Catalyzed by an Electron-Deficient CpRhIII Complex.

It has been established that an electron-deficient CpRhIII complex, bearing two ester moieties on the Cp ring, [CpERhIII], catalyzes the aerobic oxidative cross coupling of substituted acrylamides with both activated and unactivated alkenes, leading to (2Z,4E)-dienamides, at relatively low temperature (80 °C). Importantly, tertiary, secondary, and primary amide directing groups could equally be used in this catalysis. The mechanistic studies revealed that the electron-deficient nature of the CpERhIII complex facilitates the turnover-limiting vinylic C-H bond cleavage of the acrylamides.

Outcomes of radiotherapy in advanced external auditory canal cancer.

External auditory canal cancer (EACC) is a rare malignant tumor. In the present study, we retrospectively evaluated the treatment results in patients with advanced EACC who were treated using external-beam radiotherapy (EBRT) combined with chemotherapy or radical surgery. Overall, 21 patients with Stage III (n = 8) or Stage IV (n = 13) EACC who underwent initial treatment at our hospital between 2003 and 2016 were enrolled in this study. The 2-year overall survival (OS) and locoregional control (LRC) rates of all patients were 62% and 71%, respectively. The 2-year OS and LRC rates in patients who had received EBRT and concurrent chemotherapy with docetaxel, cisplatin and 5-fluorouracil (TPF, n = 6) were 100%. These results were higher than the 2-year OS and LRC rates of 62% and 69%, respectively, in patients who had received radical surgery and EBRT (n = 13). The rates were 0% in those who had neither received TPF nor undergone surgery in addition to EBRT (n = 2). Grade 3 bone or soft tissue necrosis was observed in 2 patients who had undergone surgery and postoperative EBRT. Our data suggest that the combination therapy of EBRT and surgery and/or chemotherapy may be the most effective treatment options for advanced EACC, and EBRT with concurrent chemotherapy with TPF is potentially the most acceptable.