Peripheral neuropathies after shoulder arthroscopy: a systematic review.

Purpose: Peripheral neuropathies after shoulder arthroscopy are rare, though likely under-reported. Many resolve spontaneously, but some patients are left with permanent neurological deficits. The purpose of this study was to review the literature to better characterize this patient population, diagnostic tests performed, the timing and type of surgical intervention, and report clinical outcomes. Methods: A systematic literature review was performed. Articles in English were identified from PubMed, EMBASE, and CINAHL in August 2021. Article titles and abstracts were screened for relevance by two authors and discordant abstracts were resolved by the senior author. Data were subsequently extracted from the included articles. Results: Seventeen articles were identified yielding a total of 91 patients. The average age was 53 ± 12 years, and most patients were male (72%). Rotator cuff repair (62%) was the most common procedure performed. A peripheral neuropathy was identified an average of 80 ± 81 days from the index procedure (range, 0-240 days). Most commonly, peripheral nerve injury presented as a mononeuropathy, with the median nerve (39%) and ulnar nerve (17%) affected predominantly. Seventeen percent of patients underwent a secondary surgery at an average of 232 ± 157 days after the index procedure. At the final follow-up, 55% of neuropathies had resolved, 14% partially improved, and 22% showed no clinical improvement. The most proposed etiologies were postoperative immobilization (29%) and intraoperative positioning (20%), but several possible etiologies have been suggested. Conclusions: Peripheral neuropathies after arthroscopic shoulder procedures are rare. While most spontaneously resolve, up to 1 in 5 patients may have persistent neuropathic symptoms. A high index of suspicion should be maintained throughout the postoperative period. When neurologic deficits are identified, patients should undergo a thorough diagnostic workup and be referred to a subspecialist in a timely manner.

Found Down Extremity Compartment Syndrome Secondary to Substance Use: An Observational Multicenter Study.

With the worsening opioid epidemic in America, more patients are developing found down extremity compartment syndrome (FDECS). The purpose of this study was to describe this patient population, including their presenting symptoms, laboratory test results, and clinical outcomes. METHODS: We performed a 2-center retrospective review of adult patients who developed FDECS secondary to substance use from January 2006 to December 2019. Patients were managed operatively or nonoperatively at the surgeon's discretion. Data on patient demographic characteristics, laboratory values, hospital course, and clinical outcomes were collected from electronic medical records. RESULTS: In this study, 91 patients were included: 85 patients were managed operatively, and 6 patients were managed nonoperatively. Most patients were male, and the mean patient age (and standard deviation) was 37 ± 11 years. Opioids were the most common substance used. Patients managed operatively underwent a mean of 4 ± 3 surgical procedures, 44% received a skin graft, 25% developed a wound infection, and 11% underwent limb amputation. Patients managed nonoperatively did not undergo a subsequent fasciotomy or amputation. At a mean follow-up of 2.3 years, persistent weakness (66%), pain (78%), persistent sensory deficits (53%), and contractures (18%) were common. CONCLUSIONS: Patients who develop FDECS secondary to substance use have high surgical complication rates and poor clinical outcomes. We found high rates of wound infection, revision surgical procedures, and amputation, often leaving young adults with lifelong disability. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Applying the Crystalline Sponge Method to Agrochemicals: Obtaining X-ray Structures of the Fungicide Metalaxyl-M and Herbicide S-Metolachlor.

The crystalline sponge method is a technique that provides the ability to elucidate the absolute structure of noncrystalline or hard to crystallize compounds through single-crystal X-ray diffraction by removing the need to obtain crystals of the target compound. In this study the crystalline sponges {[(ZnX2)3(2,4,6-tris(4-pyridyl)-1,3,5-trazine)2].x(solvent)} n (X = I, Br) were used to obtain X-ray structures of the agrochemical active ingredients metalaxyl-M and S-metolachlor. The effect of the temperature used during guest uptake and the influence of changing the host framework ZnX2 nodes on guest encapsulation were investigated. Additionally, three compounds containing chemical fragments similar to those of metalaxyl-M and S-metolachlor (phenylacetaldehyde, N-ethyl-o-toluidine, and methyl phenylacetate) were also encapsulated. This allowed for the effect of guest size on the position that guests occupy within the host frameworks to be examined. The disorder experienced by the guest compounds was documented, and an analysis of the intermolecular host-guest interactions (CH···π and π ···π) used for guest ordering within the host frameworks was also undertaken in this study.

Substance-Related Found-Down Compartment Syndrome: A Systematic Review.

OBJECTIVE: To characterize the patient population with substance-related found-down extremity compartment syndrome (FDECS) and report on their treatment and outcome. DATA SOURCE: This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Articles in English language were identified by searching 3 online databases, EMBASE, PubMed Publisher, and Cochrane Central, in September 2019. STUDY SELECTION: Studies involving substance-related FDECS were included. Exclusion criteria were as follows: patient age <18 years, not original studies, no full text available, technical reports, traumatic acute extremity compartment syndrome, chronic exertional compartment syndrome, and vascular acute extremity compartment syndrome. DATA EXTRACTION: There were 61 studies included with 166 cases of FDECS. Two investigators screened and extracted data independently according to a standardized template. Disagreements were addressed by an attempt to reach a consensus, and involvement of a third reviewer. Studies were quality assessed with "Quality Assessment tool for Case Series Studies." DATA SYNTHESIS: Descriptive statistics were reported using Excel. CONCLUSION: Substance-related FDECS is often occurring in young adults. Data from this review found that most of the patients were already diagnosed with substance use disorders and/or psychiatric disorders. There should be a high index of suspicion of FDECS in patients presenting after prolonged immobilization. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Rotator cuff repair with biological graft augmentation causes adverse tissue outcomes.

Background and purpose - Biological patches can be used to augment rotator cuff tendon repair in an attempt to improve healing and reduce rates of re-rupture. However, little is known about the in vivo tissue response to these patches. We assessed native rotator cuff tissue response after surgical repair and augmentation with 2 commercially available extracellular matrix (ECM) patches. Patients and methods - Patients underwent a rotator cuff repair augmented with either GraftJacket (Wright Medical), Permacol (Zimmer Biomet), or no patch (Control), applied using an onlay technique. A sample of supraspinatus tendon was collected intraoperatively and 4 weeks post-surgery, using ultrasound-guided biopsy. Histology and immunohistochemistry were performed on all samples. Results - The Permacol group (n = 3) and GraftJacket group (n = 4) demonstrated some changes in native tendon ECM compared with the control group (n = 3). Significant disruption of the extracellular matrix of the repaired native supraspinatus, underlying both patches, was observed. The patches did not generally increase cellularity, foreign body giant cell count, or vascularity compared to the control group. 1 patient in the Permacol group had an adverse tissue immune response characterized by extensive infiltration of IRF5+, CD68+, and CD206+ cells, suggesting involvement of macrophages with a pro-inflammatory phenotype. No significant differences in protein expression of CD4, CD45, CD68, CD206, BMP7, IRF5, TGFß, and PDPN were observed among the groups. Interpretation - Histological and immunohistochemical analysis of native tendon tissue after patch augmentation in rotator cuff repair raises some concerns about a lack of benefit and potential for harm from these materials.

Fully resolved array of simulations investigating the influence of the magnetic Prandtl number on magnetohydrodynamic turbulence.

We explore the effect of the magnetic Prandtl number Pm on energy and dissipation in fully resolved direct numerical simulations of steady-state, mechanically forced, homogeneous magnetohydrodynamic turbulence in the range 1/32

Localization of Contextual and Context Removed Auditory Fear Memory within the Basolateral Amygdala Complex.

Debilitating and persistent fear memories can rapidly form in humans following exposure to traumatic events. Fear memories can also be generated and studied in animals via Pavlovian fear conditioning. The current study was designed to evaluate basolateral amygdala complex (BLC) involvement following the formation of different fear memories (two contextual fear memories and one adjusted auditory fear memory). Fear memories were created in the same context with five 1.0 mA (0.50 s) foot-shocks and, where necessary, five auditory tones (5 kHz, 75 dB, 20 s). The adjusted auditory fear conditioning protocol was employed to remove background contextual fear and produce isolated auditory fear memories. Immunofluorescent labeling was utilized to identify neurons expressing immediate early genes (IEGs). We found the two contextual fear conditioning (CFC) procedures to produce similar levels of fear-related freezing to context. Contextual fear memories produced increases in BLC IEG expression with distinct and separate patterns of expression. These data suggest contextual fear memories created in slightly altered contexts, can produce unique patterns of amygdala activation. The adjusted auditory fear conditioning procedure produced memories to a tone, but not to a context. This group, where no contextual fear was present, had a significant reduction in BLC IEG expression. These data suggest background contextual fear memories, created in standard auditory fear conditioning protocols, contribute significantly to increases in amygdala activation.

Chaotic Properties of a Turbulent Isotropic Fluid.

By tracking the divergence of two initially close trajectories in phase space in an Eulerian approach to forced turbulence, the relation between the maximal Lyapunov exponent λ and the Reynolds number Re is measured using direct numerical simulations, performed on up to 2048^{3} collocation points. The Lyapunov exponent is found to solely depend on the Reynolds number with λ∝Re^{0.53} and that after a transient period the divergence of trajectories grows at the same rate at all scales. Finally a linear divergence is seen that is dependent on the energy forcing rate. Links are made with other chaotic systems.

Characterizing the macro and micro mechanical properties of scaffolds for rotator cuff repair.

BACKGROUND: Retearing after rotator cuff surgery is a major clinical problem. Numerous scaffolds are being used to try to reduce retear rates. However, few have demonstrated clinical efficacy. We hypothesize that this lack of efficacy is due to insufficient mechanical properties. Therefore, we compared the macro and nano/micro mechanical properties of 7 commercially available scaffolds to those of the human supraspinatus tendons, whose function they seek to restore. METHODS: The clinically approved scaffolds tested were X-Repair, LARS ligament, Poly-Tape, BioFiber, GraftJacket, Permacol, and Conexa. Fresh frozen cadaveric human supraspinatus tendon samples were used. Macro mechanical properties were determined through tensile testing and rheometry. Scanning probe microscopy and scanning electron microscopy were performed to assess properties of materials at the nano/microscale (morphology, Young modulus, loss tangent). RESULTS: None of the scaffolds tested adequately approximated both the macro and micro mechanical properties of human supraspinatus tendon. Macroscale mechanical properties were insufficient to restore load-bearing function. The best-performing scaffolds on the macroscale (X-Repair, LARS ligament) had poor nano/microscale properties. Scaffolds approximating tendon properties on the nano/microscale (BioFiber, biologic scaffolds) had poor macroscale properties. CONCLUSION: Existing scaffolds failed to adequately approximate the mechanical properties of human supraspinatus tendons. Combining the macroscopic mechanical properties of a synthetic scaffold with the micro mechanical properties of biologic scaffold could better achieve this goal. Future work should focus on advancing techniques to create new scaffolds with more desirable mechanical properties. This may help improve outcomes for rotator cuff surgery patients.

Inflammation activation and resolution in human tendon disease.

Improved understanding of the role of inflammation in tendon disease is required to facilitate therapeutic target discovery. We studied supraspinatus tendons from patients experiencing pain before and after surgical subacromial decompression treatment. Tendons were classified as having early, intermediate, or advanced disease, and inflammation was characterized through activation of pathways mediated by interferon (IFN), nuclear factor κB (NF-κB), glucocorticoid receptor, and signal transducer and activator of transcription 6 (STAT-6). Inflammation signatures revealed expression of genes and proteins induced by IFN and NF-κB in early-stage disease and genes and proteins induced by STAT-6 and glucocorticoid receptor activation in advanced-stage disease. The proresolving proteins FPR2/ALX and ChemR23 were increased in early-stage disease compared to intermediate- to advanced-stage disease. Patients who were pain-free after treatment had tendons with increased expression of CD206 and ALOX15 mRNA compared to tendons from patients who continued to experience pain after treatment, suggesting that these genes and their pathways may moderate tendon pain. Stromal cells from diseased tendons cultured in vitro showed increased expression of NF-κB and IFN target genes after treatment with lipopolysaccharide or IFNγ compared to stromal cells derived from healthy tendons. We identified 15-epi lipoxin A4, a stable lipoxin isoform derived from aspirin treatment, as potentially beneficial in the resolution of tendon inflammation.

Feminisation of UK General Practice: a challenge for the Defence Medical Services?

BACKGROUND: The Defence Medical Services (DMS) primarily recruits its trained General Practitioners (GPs) from the NHS and since 1970, the number of men entering medicine has doubled whereas the number of women has increased 10-fold; female GPs will outnumber their male counterparts by 2017. This study performs a quantitative assessment of the potential impact of feminisation of UK General Practice upon the DMS recruitment and workforce planning. METHODS: General Medial Council General Practice Certificate of Completion of Training (GMC GP CCT) data were analysed to identify any change in the percentage of male and female GP Specialty Training Registrars successfully completing GP vocational training between 2007 and 2012, thus becoming potentially recruitable into the DMS as independent GPs. RESULTS: A 3% increase was seen in the number of women achieving GMC GP CCT between 2007 and 2012 (p=0.015). The percentage of DMS GP Specialty Training Registrars (GPStRs) gaining their GMC GP CCT in 2012 who were women (25%) was about half that seen nationally (59%). A lack of 2007 by-sex GMC GP CCT data for DMS GPStRs prevented a comparison with 2012. CONCLUSIONS: The national increase of only 3% infers feminisation of UK General Practice is not an immediate challenge for the DMS. Nevertheless, as feminisation of the UK GP workforce is expected to continue, the future cohort from whom the DMS will recruit its GPs is likely to contain increasing numbers of women. With the return to contingency, the DMS may wish to consider the implications of increasing numbers of female GPs upon service delivery in the UK and overseas, and explore more flexible medical employment models.

Antiproton induced DNA damage: proton like in flight, carbon-ion like near rest.

Biological validation of new radiotherapy modalities is essential to understand their therapeutic potential. Antiprotons have been proposed for cancer therapy due to enhanced dose deposition provided by antiproton-nucleon annihilation. We assessed cellular DNA damage and relative biological effectiveness (RBE) of a clinically relevant antiproton beam. Despite a modest LET (~19 keV/µm), antiproton spread out Bragg peak (SOBP) irradiation caused significant residual γ-H2AX foci compared to X-ray, proton and antiproton plateau irradiation. RBE of ~1.48 in the SOBP and ~1 in the plateau were measured and used for a qualitative effective dose curve comparison with proton and carbon-ions. Foci in the antiproton SOBP were larger and more structured compared to X-rays, protons and carbon-ions. This is likely due to overlapping particle tracks near the annihilation vertex, creating spatially correlated DNA lesions. No biological effects were observed at 28-42 mm away from the primary beam suggesting minimal risk from long-range secondary particles.

Spatiotemporal investigations of DNA damage repair using microbeams.

Cellular response to radiation damage is made by a complex network of pathways and feedback loops whose spatiotemporal organisation is still unclear despite its decisive role in determining the fate of the damaged cell. Revealing the dynamic sequence of the repair proteins is therefore critical in understanding how the DNA repair mechanisms work. There are also still open questions regarding the possible movement of damaged chromatin domains and its role as trigger for lesion recognition and signalling in the DNA repair context. The single-cell approach and the high spatial resolution offered by microbeams provide the perfect tool to study and quantify the dynamic processes associated with the induction and repair of DNA damage. We have followed the development of radiation-induced foci for three DNA damage markers (i.e. γ-H2AX, 53BP1 and hSSB1) using normal fibroblasts (AG01522), human breast adenocarcinoma cells (MCF7) and human fibrosarcoma cells (HT1080) stably transfected with yellow fluorescent protein fusion proteins following irradiation with the QUB X-ray microbeam (carbon X-rays <2 µm spot). The size and intensity of the foci has been analysed as a function of dose and time post-irradiation to investigate the dynamics of the above-mentioned DNA repair processes and monitor the remodelling of chromatin structure that the cell undergoes to deal with DNA damage.

A multipotent neural crest-derived progenitor cell population is resident within the oral mucosa lamina propria.

Wounds within the oral mucosa, similarly to fetal wounds, exhibit rapid healing with reduced scarring. We hypothesized that a progenitor population resident within the oral mucosal lamina propria (OMLP) contributes to this preferential healing. Progenitor cells (PC) were reliably isolated from the OMLP by differential adhesion to fibronectin. Isolated colonies originating from a single cell demonstrated a rapid initial phase of proliferation, completing in excess of 50 population doublings (PDs) before entering cellular senescence. These data were supported by the expression of active telomerase within both developing colonies and expanded clones as assessed by immunocytochemistry (ICC) and the quantitative telomeric repeat amplification protocol. FACS analysis confirmed expression of the stem cell markers CD44, CD90, CD105, and CD166, but negative expression of CD34 and CD45 ruling out a hematopoietic or fibrocyte origin for these progenitors. A neural crest origin was confirmed by increased colony-forming efficiency (CFE) in the presence of Jagged 1 and the expression of a number of neural crest markers within the developing colonies by ICC and serially passaged clones by Western blotting. The multipotency of this novel PC population was demonstrated by differentiation of the cells down both mesenchymal (chondrogenic, osteoblastic, and adipogenic) and neuronal (neuron and Schwann-like cells) cell lineages. This article reports for the first time, the isolation and characterization of a novel, clonally derived PC population resident within the OMLP. The attributes of this adult stem cell (ASC) population and its accessibility lends itself to future therapeutic applications.

Low frequency of CHEK2 1100delC allele in Australian multiple-case breast cancer families: functional analysis in heterozygous individuals.

A protein-truncating variant of CHEK2, 1100delC, is associated with a moderate increase in breast cancer risk. We have determined the prevalence of this allele in index cases from 300 Australian multiple-case breast cancer families, 95% of which had been found to be negative for mutations in BRCA1 and BRCA2. Only two (0.6%) index cases heterozygous for the CHEK2 mutation were identified. All available relatives in these two families were genotyped, but there was no evidence of co-segregation between the CHEK2 variant and breast cancer. Lymphoblastoid cell lines established from a heterozygous carrier contained approximately 20% of the CHEK2 1100delC mRNA relative to wild-type CHEK2 transcript. However, no truncated CHK2 protein was detectable. Analyses of expression and phosphorylation of wild-type CHK2 suggest that the variant is likely to act by haploinsufficiency. Analysis of CDC25A degradation, a downstream target of CHK2, suggests that some compensation occurs to allow normal degradation of CDC25A. Such compensation of the 1100delC defect in CHEK2 might explain the rather low breast cancer risk associated with the CHEK2 variant, compared to that associated with truncating mutations in BRCA1 or BRCA2.