High-content fluorescence bioassay investigates pore formation, ion channel modulation and cell membrane lysis induced by venoms.

Venoms comprise highly sophisticated bioactive molecules modulating ion channels, receptors, coagulation factors, and the cellular membranes. This array of targets and bioactivities requires advanced high-content bioassays to facilitate the development of novel envenomation treatments and biotechnological and pharmacological agents. In response to the existing gap in venom research, we developed a cutting-edge fluorescence-based high-throughput and high-content cellular assay. This assay enables the simultaneous identification of prevalent cellular activities induced by venoms such as membrane lysis, pore formation, and ion channel modulation. By integrating intracellular calcium with extracellular nucleic acid measurements, we have successfully distinguished these venom mechanisms within a single cellular assay. Our high-content bioassay was applied across three cell types exposed to venom components representing lytic, ion pore-forming or ion channel modulator toxins. Beyond unveiling distinct profiles for these action mechanisms, we found that the pore-forming latrotoxin α-Lt1a prefers human neuroblastoma to kidney cells and cardiomyocytes, while the lytic bee peptide melittin is not selective. Furthermore, evaluation of snake venoms showed that Elapid species induced rapid membrane lysis, while Viper species showed variable to no activity on neuroblastoma cells. These findings underscore the ability of our high-content bioassay to discriminate between clades and interspecific traits, aligning with clinical observations at venom level, beyond discriminating among ion pore-forming, membrane lysis and ion channel modulation. We hope our research will expedite the comprehension of venom biology and the diversity of toxins that elicit cytotoxic, cardiotoxic and neurotoxic effects, and assist in identifying venom components that hold the potential to benefit humankind.

Anterior locking plate fixation versus cast immobilization for acceptably reduced extra- articular distal radial fractures: long-term follow-up of a randomized controlled trial.

This study reports the long-term results of a randomized controlled trial comparing anterior locking plate fixation with cast immobilization for extra-articular distal radial fractures. After 5.3 years of follow-up, no clinically relevant functional differences were found.

Outcomes of Flexor Pollicis Longus Reconstruction for Volar Plate Related Ruptures.

Aim A rare complication following volar plate fixation of a distal radius fracture is flexor pollicis longus (FPL) rupture. This study aims primarily to analyze the radiographic features and secondly to report the patient-reported outcomes of FPL reconstruction after volar plate fixation. Methods Ten patients were retrospectively identified and contacted for follow-up. Seven patients participated in the study and completed the numeric rating scale (NRS) for pain, patient-reported outcome measurement information system-upper extremity (PROMIS-UE), and quick disability of arm, shoulder, and hand (QuickDASH) questionnaires at a median of 3.4 years following FPL reconstruction. Soong grade was determined on preoperative radiographs. Results Six patients were classified as Soong grade 1 and two patients had a screw or wire protruding volarly. The median time to tendon rupture was 21.6 months. At final follow-up, the median NRS pain score was 0 (range: 0-7); the median PROMIS-UE score was 47.1 (range: 25.9-61); and the median QuickDASH-score was 12.5 (range: 4.5-75). Conclusions The outcome of FPL reconstruction after volar plate fixation is highly variable. All ruptures in our cohort occurred in patients with plate positioning classified as Soong grade 1 and occurred at up to 3 years following distal radius fixation.

Concomitant ligament injuries can be left untreated during surgery of distal radial fractures.

Instability of the distal radioulnar joint and scapholunate dissociation may cause pain, functional impairment and subsequent arthrosis. There is no consensus about whether these injuries should be treated acutely in patients undergoing surgery for distal radial fractures. We conducted a prospective cohort study to determine whether concomitant distal radioulnar joint instability or scapholunate dissociation negatively influence patient-related outcomes in these patients. The primary outcome was the patient-reported wrist/hand evaluation at 6 and 12 months after surgery. Out of 62 patients, 58% and 27% had intraoperative distal radioulnar joint instability and scapholunate dissociation, respectively. No significant differences were found in patient-reported scores at follow-up between patients with stable and unstable distal radioulnar joints, nor between patients with and without scapholunate dissociation. Sixty-three per cent of patients with an unstable distal radioulnar joint during surgery were stable on retesting after 6 months. Our study suggests that a wait-and-see policy in these patients therefore seems reasonable.Level of evidence: III.

Quantitative Analysis of the Volar Ulnar Corner of the Distal Radius: A Reference for Intraoperative Distal Radius Fracture Reduction.

PURPOSE: The reduction of distal radius fractures using volar locking plate fixation can be performed by securing the plate to the distal fragments and then levering the plate to the radial shaft. Oblique placement of the plate on the radial shaft may lead to malreduction. The aim of this study was to evaluate parameters that can be used for the assessment of intraoperative distal radius fracture reduction using "distal-first" volar plate fixation, especially the geometry of the ulnar corner. The prevalence of Tolat distal radioulnar joint (DRUJ) types was determined, and the angles of the volar corner were quantitatively described. METHODS: Three hundred seventy-five adult patients with a conventional wrist radiograph in their medical chart were identified. From this cohort, 50 radiographs of each Tolat DRUJ type were quantitatively analyzed using 4 angles. The probability density of each angle was described using Kernel density estimation graphs. A multivariable analysis was used to study the association between the 4 angles and Tolat DRUJ types and other patient factors. RESULTS: One hundred fifty-one patients (40%) had a wrist with type 1 DRUJ, 147 (39%) had a wrist with type 2 DRUJ, and 77 (21%) had a wrist with type 3 DRUJ. The measurements of the distal ulnar corner, volar ulnar corner, and DRUJ angulation were significantly different among each Tolat DRUJ type. The median lunate facet inclination, relative to the axis of the radial shaft, measured 14° (interquartile range, 12°-16°) across all the Tolat DRUJ types. CONCLUSIONS: The prevalence of Tolat type 1, 2, and 3 DRUJ was 40%, 39%, and 21%, respectively. The angles of the volar ulnar corner varied with each DRUJ type. CLINICAL RELEVANCE: Because the lunate facet inclination was relatively consistent among all the Tolat DRUJ types, this angle may be useful as a reference for "distal-first" distal radius volar plating.

Comparison of extra-articular radiographic parameters of distal radius fractures on plain radiographs and CT scans.

The aim of this study was to compare extra-articular radiographic parameters of distal radial fractures measured on plain radiographs and CT scans. Two researchers independently measured four extra-articular radiographic parameters (dorsal tilt, carpal alignment, radial inclination and ulnar variance) on both radiographs and CT scans in 85 patients. Inter-observer reliability for both techniques was assessed, along with the agreement between CT scans and radiographs using the intraclass correlation coefficient and Bland-Altman plots. The results showed that dorsal tilt, carpal alignment, radial inclination and ulnar variance can be measured reliably on both radiographs and CT scans. At a patient level, carpal alignment, radial inclination and ulnar variance CT scan measurements are an acceptable alternative to plain radiograph measurements in the vast majority of patients. In contrast, dorsal tilt CT scan measurements are not comparable with radiographs in 40% of the cases. Therefore, caution should be taken in measuring dorsal tilt on CT scans.

[A man with a red umbilicus]. / Een man met een rode navel.

A 76-year-old man was sent to the dermatology department because of a red, sore belly button since 3 weeks. Based on histology, a CT-scan and increased Cancer Antigen 19-9 levels, this was interpreted as a pancreas carcinoma metastasis. This type of metastasis is also called a 'Sister Mary Joseph's nodule'.

Increased in vivo efficacy of lenalidomide by addition of piroctone olamine.

BACKGROUND: It was recently confirmed that the antifungal agent ciclopirox olamine inhibits Wnt/beta catenin signaling in myeloma. Piroctone olamine (PO) has very similar chemical features to ciclopirox olamine. MATERIALS AND METHODS: This study investigated the antitumor effect of PO in vitro and in vivo in a murine myeloma model. RESULTS: PO demonstrated a major apoptotic activity in various human and murine myeloma and lymphoma cell lines, as well as in human primary cells. In vivo, tumor growth, as well as overall survival, was significantly reduced in mice treated with PO as compared to untreated mice. Interestingly, concerning tumor growth and survival of the animals, a significant additive effect was seen by the combination of lenalidomide plus PO as compared to single application. CONCLUSION: These results reveal a significant selective induction of apoptosis by PO and suggest a significant in vivo effect against myeloma.

In vivo efficacy of griseofulvin against multiple myeloma.

We recently confirmed that ciclopirox olamine inhibits Wnt/beta catenin signalling in myeloma. Griseofulvin (GF) has similar chemical features as compared to ciclopirox olamine. In this study the anti-tumor effect of GF was investigated. GF demonstrated a major apoptotic activity in various human and murine myeloma and lymphoma cell lines as well as in human primary cells. In vivo, tumor growth as well as overall survival were significantly reduced in mice treated with GF as compared to untreated mice. In conclusion, our results reveal a significant selective induction of apoptosis by GF and suggest a significant in vivo effect against myeloma.