Alzheimer's disease CSF biomarkers correlate with early pathology and alterations in neuronal and glial gene expression.

INTRODUCTION: Normal pressure hydrocephalus (NPH) patients undergoing cortical shunting frequently show early AD pathology on cortical biopsy, which is predictive of progression to clinical AD. The objective of this study was to use samples from this cohort to identify CSF biomarkers for AD-related CNS pathophysiologic changes using tissue and fluids with early pathology, free of post-mortem artifact. METHODS: We analyzed Simoa, proteomic, and metabolomic CSF data from 81 patients with previously documented pathologic and transcriptomic changes. RESULTS: AD pathology on biopsy correlates with CSF ß-amyloid-40/42, neurofilament light chain (NfL), and phospho-tau-181(p-tau181)/ß-amyloid-42, while several gene expression modules correlate with NfL. Proteomic analysis highlights 7 core proteins that correlate with pathology and gene expression changes on biopsy, and metabolomic analysis of CSF identifies disease-relevant groups that correlate with biopsy data.. DISCUSSION: As additional biomarkers are added to AD diagnostic panels, our work provides insight into the CNS pathophysiology these markers are tracking.

A model organism pipeline provides insight into the clinical heterogeneity of TARS1 loss-of-function variants.

Aminoacyl-tRNA synthetases (ARSs) are ubiquitously expressed, essential enzymes that complete the first step of protein translation: ligation of amino acids to cognate tRNAs. Genes encoding ARSs have been implicated in myriad dominant and recessive phenotypes, the latter often affecting multiple tissues but with frequent involvement of the central and peripheral nervous systems, liver, and lungs. Threonyl-tRNA synthetase (TARS1) encodes the enzyme that ligates threonine to tRNATHR in the cytoplasm. To date, TARS1 variants have been implicated in a recessive brittle hair phenotype. To better understand TARS1-related recessive phenotypes, we engineered three TARS1 missense variants at conserved residues and studied these variants in S. cerevisiae and C. elegans models. This revealed two loss-of-function variants, including one hypomorphic allele (R433H). We next used R433H to study the effects of partial loss of TARS1 function in a compound heterozygous mouse model (R432H/null). This model presents with phenotypes reminiscent of patients with TARS1 variants and with distinct lung and skin defects. This study expands the potential clinical heterogeneity of TARS1-related recessive disease, which should guide future clinical and genetic evaluations of patient populations.

Psychedelics in developmental stuttering to modulate brain functioning: a new therapeutic perspective?

Developmental stuttering (DS) is a neurodevelopmental speech-motor disorder characterized by symptoms such as blocks, repetitions, and prolongations. Persistent DS often has a significant negative impact on quality of life, and interventions for it have limited efficacy. Herein, we briefly review existing research on the neurophysiological underpinnings of DS -specifically, brain metabolic and default mode/social-cognitive networks (DMN/SCN) anomalies- arguing that psychedelic compounds might be considered and investigated (e.g., in randomized clinical trials) for treatment of DS. The neural background of DS is likely to be heterogeneous, and some contribution from genetically determinants of metabolic deficiencies in the basal ganglia and speech-motor cortical regions are thought to play a role in appearance of DS symptoms, which possibly results in a cascade of events contributing to impairments in speech-motor execution. In persistent DS, the difficulties of speech are often linked to a series of associated aspects such as social anxiety and social avoidance. In this context, the SCN and DMN (also influencing a series of fronto-parietal, somato-motor, and attentional networks) may have a role in worsening dysfluencies. Interestingly, brain metabolism and SCN/DMN connectivity can be modified by psychedelics, which have been shown to improve clinical evidence of some psychiatric conditions (e.g., depression, post-traumatic stress disorder, etc.) associated with psychological constructs such as rumination and social anxiety, which also tend to be present in persistent DS. To date, while there have been no controlled trials on the effects of psychedelics in DS, anecdotal evidence suggests that these agents may have beneficial effects on stuttering and its associated characteristics. We suggest that psychedelics warrant investigation in DS.

Python tooth-inspired fixation device for enhanced rotator cuff repair.

Rotator cuff repair surgeries fail frequently, with 20 to 94% of the 600,000 repairs performed annually in the United States resulting in retearing of the rotator cuff. The most common cause of failure is sutures tearing through tendons at grasping points. To address this issue, we drew inspiration from the specialized teeth of snakes of the Pythonoidea superfamily, which grasp soft tissues without tearing. To apply this nondamaging gripping approach to the surgical repair of tendon, we developed and optimized a python tooth-inspired device as an adjunct to current rotator cuff suture repair and found that it nearly doubled repair strength. Integrated simulations, 3D printing, and ex vivo experiments revealed a relationship between tooth shape and grasping mechanics, enabling optimization of the clinically relevant device that substantially enhances rotator cuff repair by distributing stresses over the attachment footprint. This approach suggests an alternative to traditional suturing paradigms and may reduce the risk of tendon retearing after rotator cuff repair.

Factors affecting protein recovery during Hsp40 affinity profiling.

The identification and quantification of misfolded proteins from complex mixtures is important for biological characterization and disease diagnosis, but remains a major bioanalytical challenge. We have developed Hsp40 Affinity Profiling as a bioanalytical approach to profile protein stability in response to cellular stress. In this assay, we ectopically introduce the Hsp40 FlagDNAJB8H31Q into cells and use quantitative proteomics to determine how protein affinity for DNAJB8 changes in the presence of cellular stress, without regard for native clients. Herein, we evaluate potential approaches to improve the performance of this bioanalytical assay. We find that although intracellular crosslinking increases recovery of protein interactors, this is not enough to overcome the relative drop in DNAJB8 recovery. While the J-domain promotes Hsp70 association, it does not affect the yield of protein association with DNAJB8 under basal conditions. By contrast, crosslinking and J-domain ablation both substantially increase relative protein interactor recovery with the structurally distinct Class B Hsp40 DNAJB1 but are completely compensated by poorer yield of DNAJB1 itself. Cellular thermal stress promotes increased affinity between DNAJB8H31Q and interacting proteins, as expected for interactions driven by recognition of misfolded proteins. DNAJB8WT does not demonstrate such a property, suggesting that under stress misfolded proteins are handed off to Hsp70. Hence, we find that DNAJB8H31Q is still our most effective recognition element for the recovery of destabilized client proteins following cellular stress.

The myosin chaperone UNC-45 has an important role in maintaining the structure and function of muscle sarcomeres during adult aging.

C. elegans undergo age-dependent declines in muscle organization and function, similar to human sarcopenia. The chaperone UNC-45 is required to fold myosin heads after translation and is likely used for refolding after thermally- or chemically-induced unfolding. UNC-45's TPR region binds HSP-90 and its UCS domain binds myosin heads. We observe early onset sarcopenia when UNC-45 is reduced at the beginning of adulthood. There is sequential decline of HSP-90, UNC-45, and MHC B myosin. A mutation in age-1 delays sarcopenia and loss of HSP-90, UNC-45, and myosin. UNC-45 undergoes age-dependent phosphorylation, and mass spectrometry reveals phosphorylation of six serines and two threonines, seven of which occur in the UCS domain. Additional expression of UNC-45 results in maintenance of MHC B myosin and suppression of A-band disorganization in old animals. Our results suggest that increased expression or activity of UNC-45 might be a strategy for prevention or treatment of sarcopenia.

CHD2 Regulates Neuron-glioma Interactions in Pediatric Glioma.

High-grade gliomas (HGG) are deadly diseases for both adult and pediatric patients. Recently, it has been shown that neuronal activity promotes progression of multiple subgroups of HGG. However, epigenetic mechanisms that govern this process remain elusive. Here we report that the chromatin remodeler CHD2 regulates neuron-glioma interactions in diffuse midline glioma (DMG) characterized by onco-histone H3.1K27M. Depletion of CHD2 in H3.1K27M DMG cells compromises cell viability and neuron-to-glioma synaptic connections in vitro, neuron-induced proliferation of H3.1K27M DMG cells in vitro and in vivo, activity-dependent calcium transients in vivo, and extends the survival of H3.1K27M DMG-bearing mice. Mechanistically, CHD2 coordinates with the transcription factor FOSL1 to control the expression of axon-guidance and synaptic genes in H3.1K27M DMG cells. Together, our study reveals a mechanism whereby CHD2 controls the intrinsic gene program of the H3.1K27M DMG subtype, which in turn regulates the tumor growth-promoting interactions of glioma cells with neurons.

Fourteen-Year Experience in Burn Eyelid Reconstruction and Complications Recurrence: A Retrospective Cohort Study.

BACKGROUND: Loss of vision and other ocular defects are a concern with eyelid burn sequelae. This most commonly progresses from eyelid contracture to cicatricial ectropion and lagophthalmos. When left untreated, these may lead to exposure keratitis, ulceration, infection, perforation, and loss of vision. In the case of full-thickness eyelid burns, release and grafting are required. However, there is a paucity of studies on outcomes in eyelid burn surgery treatment, despite concern for permanent ocular damage or loss of vision. The aim of the study is to describe the complication rates in burn eyelid reconstruction at a single center for 14 years. METHODS: A retrospective cohort study was performed of all patients who had sustained eyelid burns and required reconstruction between April 2009 and February 2023. Medical records were obtained from patients' charts. Collected data include demographics, medical history, type of injury, indication for surgery, procedure performed, and complications. RESULTS: A total of 14 patients and 25 eyelids underwent eyelid reconstruction of the 901 total patients with burn-related injuries requiring plastic surgery reconstruction. These patients underwent 54 eyelid surgeries with a mean follow-up time of 13.1 ± 17.1 months. Patients were 71% men and 29% women, with a mean age of 45.1 ± 15.6 years. In 53.7% (n = 29) of the cases, the simultaneous reconstruction of both the upper and lower eyelids was necessary. The reconstruction of the upper and lower eyelid alone represented a smaller percentage (25.9% and 20.4%, respectively). On average, the patients received 3.9 ± 3.5 eyelid surgeries. The overall complication rate was 53.7% (n = 29). The most common complication was ectropion (42.6%, n = 23). Other complications included eye injury (25.9%, n = 14), lagophthalmos (24.1%, n = 13), local infection (7.4%, n = 4), and graft loss (5.6%, n = 3). CONCLUSION: Periorbital burns represent a major challenge that may require complex surgical intervention. Full-thickness skin graft remains the standard of care for patients with eyelid burns. However, there is a high incidence of ectropion that may require reoperation. Further studies examining the conditions of successful eyelid burn procedures may provide guidance on when patients may benefit from eyelid reconstruction during their burn treatment.

Predictive modeling provides insight into the clinical heterogeneity associated with TARS1 loss-of-function mutations.

Aminoacyl-tRNA synthetases (ARSs) are ubiquitously expressed, essential enzymes that complete the first step of protein translation: ligation of amino acids to cognate tRNAs. Genes encoding ARSs have been implicated in myriad dominant and recessive phenotypes, the latter often affecting multiple tissues but with frequent involvement of the central and peripheral nervous system, liver, and lungs. Threonyl-tRNA synthetase (TARS1) encodes the enzyme that ligates threonine to tRNATHR in the cytoplasm. To date, TARS1 variants have been implicated in a recessive brittle hair phenotype. To better understand TARS1-related recessive phenotypes, we engineered three TARS1 missense mutations predicted to cause a loss-of-function effect and studied these variants in yeast and worm models. This revealed two loss-of-function mutations, including one hypomorphic allele (R433H). We next used R433H to study the effects of partial loss of TARS1 function in a compound heterozygous mouse model (R433H/null). This model presents with phenotypes reminiscent of patients with TARS1 variants and with distinct lung and skin defects. This study expands the potential clinical heterogeneity of TARS1-related recessive disease, which should guide future clinical and genetic evaluations of patient populations.

Comorbid physical health burden of serious mental health disorders in 32 European countries.

BACKGROUND: Mental health disorders (MHDs) are associated with physical health disparities, but underlying excess risk and health burden have not yet been comprehensively assessed. OBJECTIVE: To assess the burden of comorbid physical health conditions (PHCs) across serious MHDs in Europe. METHODS: We estimated the relative prevalence risk of PHCs associated with alcohol use disorders (AUD), bipolar disorder (BD), depressive disorders (DD) and schizophrenia (SZ) across working-age populations of 32 European countries in 2019 based on a targeted literature review. Excess physical health burden was modelled using population-attributable fractions and country-level prevalence data. FINDINGS: We screened 10 960 studies, of which 41 were deemed eligible, with a total sample size of over 18 million persons. Relative prevalence of PHCs was reported in 54%, 20%, 15%, 5% and 7% of studies, respectively, for SZ, DD, BD, AUD or mixed. Significant relative risk estimates ranged from 1.44 to 3.66 for BD, from 1.43 to 2.21 for DD, from 0.81 to 1.97 for SZ and 3.31 for AUD. Excess physical health burden ranged between 27% and 67% of the total, corresponding to 84 million (AUD), 67 million (BD), 66 million (DD) and 5 million (SZ) PHC diagnoses in Europe. A 1% reduction in excess risk assuming causal inference could result in two million fewer PHCs across investigated MHDs. CONCLUSIONS: This is the first comprehensive study of the physical health burden of serious MHDs in Europe. The methods allow for updates, refinement and extension to other MHDs or geographical areas. CLINICAL IMPLICATIONS: The results indicate potential population health benefits achievable through more integrated mental and physical healthcare and prevention approaches.

The Development and Management of Neck Burn Scar Contracture Recurrence: A Single-Center Retrospective Cohort Study.

INTRODUCTION: Burn neck contractures pose a great challenge for reconstructive surgeons. A paucity of literature exist regarding long-term outcomes based on different surgical management strategies. The aim of this study was to evaluate the long-term outcomes of the treatment of neck burn scar contractures and evaluate surgical strategies according to their long-term effectiveness and associated complications. METHODS: A retrospective cohort study was conducted to review outcomes of neck contractures release after burn injury. All patients operated on between January 2009 and February 2023 at a single institution were included. RESULTS: A total of 20 patients developed neck burn scar contracture and were included in this study. The mean age was 32.9 ± 20.3 years. The burn injuries were most commonly thermal (n = 19, 95%). All burn injuries were full-thickness burns, with an average neck defect size of 130.5 ± 106.0 cm2. Overall, 45 surgical scar release procedures were performed on the 20 patients who developed a neck contracture. Patients underwent 1.65 ± 1.04 surgeries on average to address neck contracture. Although 25% of patients only received 1 surgery to treat neck contracture, some patients underwent as many as 8 surgeries. Contracture recurrence (CR) was the most common complication and occurred in 28.9% of the cases. The mean percentage total body surface area did not significantly differ in CR patients (26.7% ± 14.9%) and no-CR patients (44.5% ± 30.2%). However, there was a significant difference (P = 0.01) in the average neck defect size between CR patients (198.5 ± 108.3 cm2) and no-CR patients (81.1 ± 75.1 cm2). CONCLUSIONS: This study showed that risk factors for initial burn scar contractures may differ from those associated with CR, highlighting the importance of neck defect size as a predictor. The study also examines various surgical approaches, with Z-plasty showing promise for managing CR. However, the absence of data on neck range of motion is a limitation. This research underscores the complexity of managing CR and emphasizes the need for ongoing postoperative monitoring.

Exploring the incidence of inadequate response to antidepressants in the primary care of depression.

Data from the UK suggests 13-55 % of depression patients experience some level of treatment resistance. However, little is known about how physicians manage inadequate response to antidepressants in primary care. This study aimed to explore the incidence of inadequate response to antidepressants in UK primary care. One-hundred-eighty-four medication-free patients with low mood initiated antidepressant treatment and monitored severity of depression symptoms, using the QIDS-SR16, for 48 weeks. Medication changes, visits to healthcare providers, and health-related quality of life were also recorded. Patients were classified into one of four response types based on their QIDS scores at three study timepoints: persistent inadequate responders (<50 % reduction in baseline QIDS at all timepoints), successful responders (≥50 % reduction in baseline QIDS at all timepoints), slow responders (≥50 % reduction in QIDS at week 48, despite earlier inadequate responses), and relapse (initial ≥50 % reduction in baseline QIDS, but inadequate response by week 48). Forty-eight weeks after initiating treatment 47 % of patients continued to experience symptoms of depression (QIDS >5), and 20 % of patients had a persistent inadequate response. Regardless of treatment response, 96 % (n = 176) of patients did not visit their primary care physician over the 40-week follow-up period. These results suggest that despite receiving treatment, a considerable proportion of patients with low mood remain unwell and fail to recover. Monitoring depression symptoms remotely can enable physicians to identify inadequate responders, allowing patients to be reassessed or referred to secondary services, likely improving patients' quality of life and reducing the socioeconomic impacts of chronic mental illness.

Use of Recommended Neurodiagnostic Evaluation Among Patients With Drug-Resistant Epilepsy.

Importance: Interdisciplinary practice parameters recommend that patients with drug-resistant epilepsy (DRE) undergo comprehensive neurodiagnostic evaluation, including presurgical assessment. Reporting from specialized centers suggests long delays to referral and underuse of surgery; however, longitudinal data are limited to characterize neurodiagnostic evaluation among patients with DRE in more diverse US settings and populations. Objective: To examine the rate and factors associated with neurodiagnostic studies and comprehensive evaluation among patients with DRE within 3 US cohorts. Design, Setting, and Participants: A retrospective cross-sectional study was conducted using the Observational Medical Outcomes Partnership Common Data Model including US multistate Medicaid data, commercial claims data, and Columbia University Medical Center (CUMC) electronic health record data. Patients meeting a validated computable phenotype algorithm for DRE between January 1, 2015, and April 1, 2020, were included. No eligible participants were excluded. Exposure: Demographic and clinical variables were queried. Main Outcomes and Measures: The proportion of patients receiving a composite proxy for comprehensive neurodiagnostic evaluation, including (1) magnetic resonance or other advanced brain imaging, (2) video electroencephalography, and (3) neuropsychological evaluation within 2 years of meeting the inclusion criteria. Results: A total of 33 542 patients with DRE were included in the Medicaid cohort, 22 496 in the commercial insurance cohort, and 2741 in the CUMC database. A total of 31 516 patients (53.6%) were women. The proportion of patients meeting the comprehensive evaluation main outcome in the Medicaid cohort was 4.5% (n = 1520); in the commercial insurance cohort, 8.0% (n = 1796); and in the CUMC cohort, 14.3% (n = 393). Video electroencephalography (24.9% Medicaid, 28.4% commercial, 63.2% CUMC) and magnetic resonance imaging of the brain (35.6% Medicaid, 43.4% commercial, 52.6% CUMC) were performed more regularly than neuropsychological evaluation (13.0% Medicaid, 16.6% commercial, 19.2% CUMC) or advanced imaging (3.2% Medicaid, 5.4% commercial, 13.1% CUMC). Factors independently associated with greater odds of evaluation across all 3 data sets included the number of inpatient and outpatient nonemergency epilepsy visits and focal rather than generalized epilepsy. Conclusions and Relevance: The findings of this study suggest there is a gap in the use of diagnostic studies to evaluate patients with DRE. Care setting, insurance type, frequency of nonemergency visits, and epilepsy type are all associated with evaluation. A common data model can be used to measure adherence with best practices across a variety of observational data sources.

Surgical Excision of Burn Wounds.

Burn injuries affect patients of all ages, and timely surgical debridement and excision commence to protect dermal vascularity and integrity, improve healing, and minimize scarring. Several tools may be used for burn wound excision, which is performed either tangentially or down to muscular fascia. Once wounds are optimized from a tissue viability and healing standpoint, coverage may be obtained through grafts or secondary intention healing for more superficial injuries. A collaborative team of plastic and general surgeons, anesthesiologists, nutritionists, and therapists can provide improved patient care throughout the perioperative period, leading to improvements in overall patient morbidity and mortality.

A Pilot Feasibility Evaluation of a Heart Rate Variability Biofeedback App to Improve Self-Care in COVID-19 Healthcare Workers.

COVID-19 exacerbated burnout and mental health concerns among the healthcare workforce. Due to high work stress, demanding schedules made attuned eating behaviors a particularly challenging aspect of self-care for healthcare workers. This study aimed to examine the feasibility and acceptability of a heart rate variability biofeedback (HRVB) mobile app for improving well-being among healthcare workers reporting elevated disordered eating during COVID-19. We conducted a mixed methods pre-mid-post single-arm pilot feasibility trial (ClinicalTrials.gov NCT04921228). Deductive content analysis of participants' commentary generated qualitative themes. Linear mixed models were used to examine changes in pre- mid- to post-assessment scores on well-being outcomes. We consented 28 healthcare workers (25/89% female; 23/82% Non-Hispanic White; 22/79% nurses) to use and evaluate an HRVB mobile app. Of these, 25/89% fully enrolled by attending the app and device training; 23/82% were engaged in all elements of the protocol. Thirteen (52%) completed at least 10 min of HRVB on two-thirds or more study days. Most participants (18/75%) reported being likely or extremely likely to continue HRVB. Common barriers to engagement were busy schedules, fatigue, and technology difficulties. However, participants felt that HRVB helped them relax and connect better to their body's signals and experiences. Results suggested preliminary evidence of efficacy for improving interoceptive sensibility, mindful self-care, body appreciation, intuitive eating, stress, resilience, and disordered eating. HRVB has potential as a low-cost adjunct tool for enhancing well-being in healthcare workers through positively connecting to the body, especially during times of increased stress when attuned eating behavior becomes difficult to uphold.

The RhoGAP RRC-1 is required for the assembly or stability of integrin adhesion complexes and is a member of the PIX pathway in muscle.

GTPases cycle between active GTP bound and inactive GDP bound forms. Exchange of GDP for GTP is catalyzed by guanine nucleotide exchange factors (GEFs). GTPase activating proteins (GAPs) accelerate GTP hydrolysis, to promote the GDP bound form. We reported that the RacGEF, PIX-1, is required for assembly of integrin adhesion complexes (IAC) in striated muscle of Caenorhabditis elegans. In C. elegans, IACs are found at the muscle cell boundaries (MCBs), and bases of sarcomeric M-lines and dense bodies (Z-disks). Screening C. elegans mutants in proteins containing RhoGAP domains revealed that loss of function of rrc-1 results in loss of IAC components at MCBs, disorganization of M-lines and dense bodies, and reduced whole animal locomotion. RRC-1 localizes to MCBs, like PIX-1. The localization of RRC-1 at MCBs requires PIX-1, and the localization of PIX-1 requires RRC-1. Loss of function of CED-10 (Rac) shows lack of PIX-1 and RRC-1 at MCBs. RRC-1 exists in a complex with PIX-1. Transgenic rescue of rrc-1 was achieved with wild type RRC-1 but not RRC-1 with a missense mutation in a highly conserved residue of the RhoGAP domain. Our results are consistent with RRC-1 being a RhoGAP for the PIX pathway in muscle.

In Vivo Porcine Model of Acute Iliocaval Deep Vein Thrombosis.

CLINICAL IMPACT: The study establishes a rapid, technically straightforward, and reproducible porcine large animal model for acute iliocaval deep vein thrombosis (DVT). The procedure can be performed with basic endovascular skillsets. With its procedural efficiency and consistency, the platform is promising for comparative in vivo testing of venous thrombectomy devices in a living host, and for future verification and validation studies to determine efficacy of novel thrombectomy devices relative to predicates.

Critical Care Nurses' Moral Resilience, Moral Injury, Institutional Betrayal, and Traumatic Stress After COVID-19.

BACKGROUND: Traumatic stress and moral injury may contribute to burnout, but their relationship to institutional betrayal and moral resilience is poorly understood, leaving risk and protective factors understudied. OBJECTIVES: To examine traumatic stress symptoms, moral injury symptoms, moral resilience, and institutional betrayal experienced by critical care nurses and examine how moral injury and traumatic stress symptoms relate to moral resilience, institutional betrayal, and patient-related burnout. METHODS: This cross-sectional study included 121 critical care nurses and used an online survey. Validated instruments were used to measure key variables. Descriptive statistics, regression analyses, and group t tests were used to examine relationships among variables. RESULTS: Of participating nurses, 71.5% reported significant moral injury symptoms and/or traumatic stress. Both moral injury symptoms and traumatic stress were associated with burnout. Regression models showed that institutional betrayal was associated with increased likelihood of traumatic stress and moral injury. Increases in scores on Response to Moral Adversity subscale of moral resilience were associated with a lower likelihood of traumatic stress and moral injury symptoms. CONCLUSIONS: Moral resilience, especially response to difficult circumstances, may be protective in critical care environments, but system factors (eg, institutional betrayal) must also be addressed systemically rather than relying on individual-level interventions to address nurses' needs.

Open-source microscope add-on for structured illumination microscopy.

Super-resolution techniques expand the abilities of researchers who have the knowledge and resources to either build or purchase a system. This excludes the part of the research community without these capabilities. Here we introduce the openSIM add-on to upgrade existing optical microscopes to Structured Illumination super-resolution Microscopes (SIM). The openSIM is an open-hardware system, designed and documented to be easily duplicated by other laboratories, making super-resolution modality accessible to facilitate innovative research. The add-on approach gives a performance improvement for pre-existing lab equipment without the need to build a completely new system.