Intrinsic and Extrinsic Methods for Augmenting Fracture Healing in the Hand and Wrist.

This review examines intrinsic and extrinsic augmentation techniques for uniting hand and upper extremity fractures, including bone morphogenic proteins (BMPs), platelet-rich plasma (PRP), low-intensity pulsed ultrasound (LIPUS), and pulsed electromagnetic fields (PEMF). While BMPs, PRP, LIPUS, and PEMF show potential in accelerating bone healing and reducing nonunion rates, their clinical adoption is limited by high costs and inconsistent results. This paper focuses on understanding the efficacy of these techniques, their drawbacks, and potential next steps for the field.

High-throughput identification of repurposable neuroactive drugs with potent anti-glioblastoma activity.

Glioblastoma, the most aggressive primary brain cancer, has a dismal prognosis, yet systemic treatment is limited to DNA-alkylating chemotherapies. New therapeutic strategies may emerge from exploring neurodevelopmental and neurophysiological vulnerabilities of glioblastoma. To this end, we systematically screened repurposable neuroactive drugs in glioblastoma patient surgery material using a clinically concordant and single-cell resolved platform.

Quantitative 3D histochemistry reveals region-specific amyloid-β reduction by the antidiabetic drug netoglitazone.

A hallmark of Alzheimer's disease (AD) is the extracellular aggregation of toxic amyloid-beta (Aβ) peptides in form of plaques. Here, we identify netoglitazone, an antidiabetic compound previously tested in humans, as an Aβ aggregation antagonist. Netoglitazone improved cognition and reduced microglia activity in a mouse model of AD.

[28-year-old male patient with headaches on the left side and facial pain].

A 28-year-old male suffers for two weeks from new-onset very severe headache located on his left temple radiating to his jaw. He also complains about left sided retroorbital pain and chewing aggravated symptoms. In addition, nausea and emesis in the mornings during the past six months were reported.

Understanding Variations in the Management of Displaced Distal Radius Fractures With Satisfactory Reduction.

Background: The American Academy of Orthopaedic Surgeons has set forth Clinical Practice Guidelines (CPGs) to help guide management of closed, displaced distal radius fractures (DRFs). There still exists variation in practice regarding operative vs nonoperative decision-making. This study aims to identify which factors influence the decision to treat DRFs not indicated for surgery by the CPGs after initial closed reduction.

Time-resolved single-cell transcriptomics defines immune trajectories in glioblastoma.

Deciphering the cell-state transitions underlying immune adaptation across time is fundamental for advancing biology. Empirical in vivo genomic technologies that capture cellular dynamics are currently lacking. We present Zman-seq, a single-cell technology recording transcriptomic dynamics across time by introducing time stamps into circulating immune cells, tracking them in tissues for days.

B cell depletion attenuates CD27 signaling of T helper cells in multiple sclerosis.

Multiple sclerosis is a chronic inflammatory disease of the central nervous system. Whereas T cells are likely the main drivers of disease development, the striking efficacy of B cell-depleting therapies (BCDTs) underscore B cells' involvement in disease progression. How B cells contribute to multiple sclerosis (MS) pathogenesis-and consequently the precise mechanism of action of BCDTs-remains elusive.

IL-12 sensing in neurons induces neuroprotective CNS tissue adaptation and attenuates neuroinflammation in mice.

Interleukin-12 (IL-12) is a potent driver of type 1 immunity. Paradoxically, in autoimmune conditions, including of the CNS, IL-12 reduces inflammation. The underlying mechanism behind these opposing properties and the involved cellular players remain elusive.

Targeted delivery of tumor necrosis factor in combination with CCNU induces a T cell-dependent regression of glioblastoma.

Glioblastoma is the most aggressive primary brain tumor with an unmet need for more effective therapies. Here, we investigated combination therapies based on L19TNF, an antibody-cytokine fusion protein based on tumor necrosis factor that selectively localizes to cancer neovasculature. Using immunocompetent orthotopic glioma mouse models, we identified strong anti-glioma activity of L19TNF in combination with the alkylating agent CCNU, which cured the majority of tumor-bearing mice, whereas monotherapies only had limited efficacy.

Stener-Like Lesions in the Hand: A Qualitative Review.

A Stener-like lesion is defined as the interposition of the sagittal band between the torn collateral ligament of the metacarpophalangeal (MCP) joint of a finger and its origin or insertion. Owing to the rarity of this injury, standardized protocols on the diagnosis and care of these injuries are not currently available. PubMed Central and Google Scholar were searched for published studies from 1962 to 2022.

Whole-brain microscopy reveals distinct temporal and spatial efficacy of anti-Aβ therapies.

Many efforts targeting amyloid-β (Aβ) plaques for the treatment of Alzheimer's Disease thus far have resulted in failures during clinical trials. Regional and temporal heterogeneity of efficacy and dependence on plaque maturity may have contributed to these disappointing outcomes. In this study, we mapped the regional and temporal specificity of various anti-Aβ treatments through high-resolution light-sheet imaging of electrophoretically cleared brains.

Successful Non-operative Management of Metacarpophalangeal Collateral Ligament and Sagittal Band Rupture of the Long Finger: A Case Report.

The metacarpophalangeal (MCP) joint is surrounded by various structures critical to its stability and function. Though the ligamentous injury to the digits is common, rupture of the metacarpophalangeal collateral ligament and a sagittal band of the same finger is not well represented in the literature. We report a chronic case of a concurrent metacarpophalangeal collateral ligament and sagittal band injury.

Multiscale optical and optoacoustic imaging of amyloid-β deposits in mice.

Deposits of amyloid-β (Aβ) in the brains of rodents can be analysed by invasive intravital microscopy on a submillimetre scale, or via whole-brain images from modalities lacking the resolution or molecular specificity to accurately characterize Aβ pathologies. Here we show that large-field multifocal illumination fluorescence microscopy and panoramic volumetric multispectral optoacoustic tomography can be combined to longitudinally assess Aβ deposits in transgenic mouse models of Alzheimer's disease. We used fluorescent Aβ-targeted probes (the luminescent conjugated oligothiophene HS-169 and the oxazine-derivative AOI987) to transcranially detect Aβ deposits in the cortex of APP/PS1 and arcAβ mice with single-plaque resolution (8 μm) and across the whole brain (including the hippocampus and the thalamus, which are inaccessible by conventional intravital microscopy) at sub-150 μm resolutions.

Postoperative Immobilization of Scaphoid Fractures: A Comprehensive Review of the Literature.

The optimal protocol for postoperative immobilization following operative treatment of scaphoid fractures remains controversial. Reports of successful management with brief postoperative immobilization suggest that earlier restoration of function may be achieved by limiting the duration of immobilization. However, the risk of nonunion and its associated complications suggest that a more conservative approach with extended immobilization could optimize fracture healing.

Posttraumatic Ulnar Translocation of the Carpus: A Case Report and Brief Review of the Literature.

We report a case of posttraumatic ulnar translocation of the carpus, which resulted after a fall from a six-foot ladder. This patient presented with multiple injuries to the skull bones, face, and limbs. A diagnosis of ulnar translocation of the carpus was missed on initial radiographs.

Brain metastases: Not all tumors are created equal.

Metastases are the main cause of death in cancer patients. In a recent issue of Cell, Gonzalez et al. (2022) analyze gene expression on the single-cell level in brain metastases from various primary tumors.

LGR5 expressing skin fibroblasts define a major cellular hub perturbed in scleroderma.

Systemic sclerosis (scleroderma, SSc) is an incurable autoimmune disease with high morbidity and mortality rates. Here, we conducted a population-scale single-cell genomic analysis of skin and blood samples of 56 healthy controls and 97 SSc patients at different stages of the disease. We found immune compartment dysfunction only in a specific subtype of diffuse SSc patients but global dysregulation of the stromal compartment, particularly in a previously undefined subset of LGR5-scleroderma-associated fibroblasts (ScAFs).

Observation of Collagen-Containing Lesions After Hematoma Resolution in Intracerebral Hemorrhage.

Background And Purpose: The classic presentation of chronic (stage III) hemorrhagic stroke lesions is a fluid-filled cavity. In one of the most commonly used animal models of intracerebral hemorrhage (ICH), we noticed additional solid material within the chronic lesion. We examined the composition of those chronic ICH lesions and compared them with human autopsy cases.

Intracerebral endotheliitis and microbleeds are neuropathological features of COVID-19.

Coronavirus disease 19 (COVID-19) is a rapidly evolving pandemic caused by the coronavirus Sars-CoV-2. Clinically manifest central nervous system symptoms have been described in COVID-19 patients and could be the consequence of commonly associated vascular pathology, but the detailed neuropathological sequelae remain largely unknown. A total of six cases, all positive for Sars-CoV-2, showed evidence of cerebral petechial hemorrhages and microthrombi at autopsy.

Developmental divergence of sensory stimulus representation in cortical interneurons.

Vasocative-intestinal-peptide (VIP) and somatostatin (SST) interneurons are involved in modulating barrel cortex activity and perception during active whisking. Here we identify a developmental transition point of structural and functional rearrangements onto these interneurons around the start of active sensation at P14. Using in vivo two-photon Ca imaging, we find that before P14, both interneuron types respond stronger to a multi-whisker stimulus, whereas after P14 their responses diverge, with VIP cells losing their multi-whisker preference and SST neurons enhancing theirs.

Large and Small Cerebral Vessel Involvement in Severe COVID-19: Detailed Clinical Workup of a Case Series.

Background And Purpose: Case series indicating cerebrovascular disorders in coronavirus disease 2019 (COVID-19) have been published. Comprehensive workups, including clinical characteristics, laboratory, electroencephalography, neuroimaging, and cerebrospinal fluid findings, are needed to understand the mechanisms.

Methods: We evaluated 32 consecutive critically ill patients with COVID-19 treated at a tertiary care center from March 9 to April 3, 2020, for concomitant severe central nervous system involvement.

The mesoSPIM initiative: open-source light-sheet microscopes for imaging cleared tissue.

Light-sheet microscopy is an ideal technique for imaging large cleared samples; however, the community is still lacking instruments capable of producing volumetric images of centimeter-sized cleared samples with near-isotropic resolution within minutes. Here, we introduce the mesoscale selective plane-illumination microscopy initiative, an open-hardware project for building and operating a light-sheet microscope that addresses these challenges and is compatible with any type of cleared or expanded sample ( www.mesospim.

Eight autopsy cases of melanoma brain metastases showing angiotropism and pericytic mimicry. Implications for extravascular migratory metastasis.

Background: Metastatic tumor spread is a complex multistep process. Due to the blood-brain barrier, metastasis to the central nervous system is restrictive with a distinct predilection for certain tumor types. In melanoma patients, brain metastasis is a common endpoint with the majority showing evidence of widespread disease at autopsy.