Early flexible endoscopic evaluation of swallowing after mechanical thrombectomy in stroke patients.

OBJECTIVE: The aims of the study were to (1) characterize the findings of flexible endoscopic evaluation of swallowing (FEES) in stroke patients undergoing mechanical thrombectomy (MT); (2) analyse the screening performance of the Standardized Swallowing Assessment (SSA); and (3) study the impact of FEES-defined dysphagia on 3-month outcomes. METHODS: This single-centre study was based on a local registry of consecutive acute ischaemic stroke patients undergoing MT during a 1-year period. Patients received FEES within 5 days of admission regardless of the result of dysphagia screening. We compared baseline demographic and clinical characteristics of patients with and without FEES-defined dysphagia. We collected 3-month modified Rankin Scale (mRS) and individual index values of the European Quality of Life 5 Dimensions (EQ-5D-iv). Using univariable and multivariable regression analyses we predicted 3-month outcomes for presence of dysphagia and for FEES-defined dysphagia severity. RESULTS: We included 137 patients with a median age of 74 years, 43.1% were female, median NIHSS was 12 and successful recanalization was achieved in 92.7%. Stroke-associated pneumonia occurred in 8% of patients. FEES-defined dysphagia occurred in 81% of patients. Sensitivity of the SSA as a dysphagia screening was 67%. Presence of dysphagia and increasing severity of dysphagia were independently associated with increasing 3-month mRS score. Increasing dysphagia severity dysphagia was independently associated with lower EQ-5D-iv. INTERPRETATION: Early FEES-defined dysphagia occurs in four in every five patients undergoing MT. SSA has a suboptimal dysphagia screening performance. Presence of dysphagia and increasing dysphagia severity predict worse functional outcome and worse health-related quality-of-life.

Elexacaftor/tezacaftor/ivacaftor improves chronic rhinosinusitis detected by magnetic resonance imaging in children with cystic fibrosis on long-term therapy with lumacaftor/ivacaftor.

INTRODUCTION: Previous studies using magnetic resonance imaging (MRI) demonstrated early onset and progression of chronic rhinosinusitis (CRS) from infancy to school age, and response to lumacaftor/ivacaftor (LUM/IVA) therapy in children with cystic fibrosis (CF). However, the effect of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) on CRS detected by MRI in children with CF and at least one F508del mutation, and potential incremental effects of ELX/TEZ/IVA compared to LUM/IVA in F508del homozygous children have not been studied. METHODS: 30 children with CF with at least one F508del mutation underwent three longitudinal paranasal sinus MRI before (MRI1), without (n = 16) or with LUM/IVA therapy (n = 14, MRI2), and with ELX/TEZ/IVA therapy (MRI3, mean age at therapy initiation 11.1 ± 3.4y, range 6-16y). MRI were evaluated using the CRS-MRI score. RESULTS: After therapy initiation with ELX/TEZ/IVA, the prevalence and in maxillary and sphenoid sinuses the dominance of mucopyoceles decreased (35% vs. 0 %, p<0.001 and 26% vs. 8 %, p < 0.05, respectively). This leads to a reduction in mucopyocele subscore (-3.4 ± 1.9, p < 0.001), and sinus subscores in MRI3 (maxillary sinus: -5.3 ± 3.1, p < 0.001, frontal sinus: -1.0 ± 1.9, p < 0.01, sphenoid subscore: -2.8 ± 3.5, p < 0.001, ethmoid sinus: -1.7 ± 1.9, p < 0.001). The CRS-MRI sum score decreased after therapy initiation with ELX/TEZ/IVA by -9.6 ± 5.5 score points (p < 0.001). The strength in reduction of mucopyoceles subscore and CRS-MRI sum score was independent of a pretreatment with LUM/IVA from MRI1-MRI2 (p = 0.275-0.999). CONCLUSIONS: ELX/TEZ/IVA therapy leads to improvement of CRS in eligible children with CF. Our data support the role of MRI for comprehensive monitoring of CRS disease severity and response to therapy in children with CF.

The relationship between neurogenic dysphagia, stroke-associated pneumonia and functional outcome in a cohort of ischemic stroke patients treated with mechanical thrombectomy.

INTRODUCTION: Mechanical thrombectomy (MT) is an established treatment approach in acute ischemic stroke patients with large vessel occlusion (LVO). Recent studies suggest that the prevalence of dysphagia and pneumonia risk is increased in this patient population. The aim of this study was to systematically evaluate the prevalence, predictors, and influence of neurogenic dysphagia for 3-month outcome in a large population of patients receiving MT and to elucidate the relationship between dysphagia, stroke-associated pneumonia (SAP) and medium-term functional outcome. MATERIALS AND METHODS: Data of a prospective collected registry of patients with LVO and MT between 2016 and 2019 were analyzed retrospectively. Binary logistic regression was carried out to determine predictors for dysphagia and 3-month outcome as measured by the modified Rankin Scale, respectively. A mediation analysis was performed to investigate the mediating influence of intercurrent SAP. RESULTS: A total of 567 patients were included in the study. Mean age was 73.4 years, 47.8% of the patients were female, and median NIHSS was 15.0. The prevalence of dysphagia was 75.1% and 23.3% of all patients developed SAP. In the regression analysis, dysphagia was one of the main independent predictors for poor functional outcome at 3 months. The mediator analysis revealed that the effect of dysphagia on the functional outcome at 3 months was not mediated by the occurrence of SAP. DISCUSSION: The prevalence of dysphagia is high and exerts both negative short- and medium-term effects on patients with large vessel occlusion who undergo MT.

Renewable carbon sources to biochemicals and -fuels: contributions of the smut fungi Ustilaginaceae.

The global demand for food, fuels, and chemicals increases annually. Using renewable C-sources (i.e. biomass, CO2, and organic waste) is a prerequisite for a future free of fossil carbon. The smut fungi Ustilaginaceae naturally produce a versatile spectrum of valuable products, such as organic acids, polyols, and glycolipids, applicable in the food, energy, chemistry, and pharmaceutical sector. Combined with the use of alternative (co-)substrates (e.g. acetate, butanediol, formate, and glycerol), these microorganisms offer excellent potential for industrial biotechnology, thereby overcoming central challenges humankind faces, including CO2 release and land use. Here, we provide insight into fundamental production capacities, present genetic modifications that improve the biotechnical application, and review recent high-performance engineering of Ustilaginaceae toward relevant platform chemicals.

The decidual expression of Interleukin-7 is upregulated in early pregnancy loss.

BACKGROUND: Maternal immunological rejection of the semi-allogenic fetus is discussed as one of the significant factors involved in early pregnancy loss. An array of cytokines secreted by both maternal and fetal cells is involved in generating a delicate maternal immune tolerance. Interleukin-7 (IL-7) is discussed to play a key role in pro-inflammatory processes, but there is still limited insight into the pathophysiological input on placentation and embryonic development in early pregnancy loss. PATIENTS AND METHODS: Cytokine level differences were identified with quantitative real-time PCR in placental tissue from spontaneous abortions (SA) (n = 18), recurrent spontaneous abortions (RSA) (n = 15), and healthy pregnancies (n = 15) at gestational weeks 7 to 14. Protein expression of IL-7 in the decidua was investigated by immunohistochemistry. IL-7-expressing cells were identified with double-immunofluorescence. RESULTS: Decidua of women with RSA expressed almost 51-times higher values of IL-7 in gene expression analysis. Immunohistochemistry identified a significant upregulation of IL-7 in the decidua of RSA specimens (p = .013) and in the decidua of women with SA (p = .004). Double-immunofluorescence confirmed decidual stroma cells as IL-7-expressing cells. CONCLUSION: Significantly elevated IL-7 values in the decidua of spontaneous and recurrent miscarriages imply a crucial role of the cytokine in the signaling at the feto-maternal interface of the placenta. An overexpression of IL-7 could result in early pregnancy loss by inducing a pro-inflammatory environment. Proven to be valuable in other autoimmune diseases, targeting IL-7 signaling therapeutically may prove to be a very beneficial treatment option for RSA patients.

Serial whole-body cryotherapy in fibromyalgia is effective and alters cytokine profiles.

INTRODUCTION: Whole-body cryotherapy (WBC) has shown to be beneficial in the treatment of fibromyalgia (FM). There is cumulative evidence that cytokines play a crucial role in FM. It's unknown whether clinical effects of WBC can be demonstrated at the molecular level and how long the effects last. METHODS: We compared effects of serial WBC (6 sessions (- 130 °C in 6 weeks) in FM patients and healthy controls (HC). Primary outcome was the change in pain level (visual analogue scale 0-100 mm) after 6 sessions. Secondary outcomes were a change in disease activity (revised Fibromyalgia Impact Questionnaire) and pain after 3 sessions and 3 months after discontinued therapy and in cytokine levels (interleukin (IL-)1, IL-6, tumor necrosis factor α (TNF-α) and IL-10). The patients' opinions on the satisfaction, effectiveness and significance of WBC were evaluated. RESULTS: Twenty-three FM patients and 30 HC were enrolled. WBC resulted in a significant reduction in pain and disease activity after 3 and 6 sessions. No clinical benefit could be measured 3 months after discontinued treatment. Overall, probands were satisfied with WBC and considered WBC to be important and effective. FM patients had significantly different levels of IL-1, IL-6, TNF-α and IL-10 at each reading point compared to HC. Levels of IL-1, IL-6 and IL-10 were significantly altered over time in FM patients. Compared to HC FM patients showed a significantly different response of IL1, - 6 and - 10 to WBC. CONCLUSION: Serial WBC is a fast acting and effective treatment for FM. Proven effects of WBC may be explained by changes in cytokines.

Cytosolic Phosphoenolpyruvate Carboxykinase Deficiency: Cause of Hypoglycemia-Induced Seizure and Death.

Cytosolic phosphoenolpyruvate carboxykinase (PEPCK) deficiency (MIM 261680, EC 4.1.1.32, encoded by PCK1) is a rare disorder of gluconeogenesis presenting with recurrent hypoglycemia, hepatic dysfunction, and lactic acidosis. We report on a previously healthy 3-year-old boy who was initially admitted under the suspicion of a febrile seizure during an upper airway infection. Diagnostic workup revealed hypoglycemia as well as a cerebral edema and ruled out an infection. After a complicated course with difficult to treat symptomatic seizures, the child died on the 5th day of admission due to progressive cerebral edema. The metabolic screening showed elevated urinary lactate and Krebs cycle intermediates in line with a primary or secondary energy deficit. Due to the unclear and fatal course, trio exome sequencing was initiated postmortem ("molecular autopsy") and revealed the diagnosis of cytosolic PEPCK deficiency based on the compound heterozygosity of a known pathogenic (c.925G > A, p.(Gly309Arg)) and a previously unreported (c.724G > A, p.(Gly242Arg)) variant in PCK1 (NM_002591.3). Sanger sequencing ruled out the disease and carrier status in three older brothers. Molecular autopsy was performed due to the unclear and fatal course. The diagnosis of a cytosolic PEPCK deficiency not only helped the family to deal with the grief, but especially took away the fear that the siblings could be affected by an unknown disease in the same manner. In addition, this case increases the genetic and phenotypic spectrum of cytosolic PEPCK deficiency.

High level production of itaconic acid at low pH by Ustilago maydis with fed-batch fermentation.

The metabolically engineered plant pathogen Ustilago maydis MB215 Δcyp3 Petefria1 has been cultivated to produce more than 80 g/L itaconate in 16 L scale pH and temperature controlled fermentation, in fed-batch mode with two successive feedings. The effect of pH as well as successive rounds of feeding has been quantified via elemental balances. Volumetric itaconic acid productivity gradually decreased with successive glucose feedings with increasing itaconic titers, with nearly constant product yield. Extracellular pH was decreased from 6 down to 3.5 and the fermentation was characterized in specific uptake, production, and growth rates. Notable is that the biomass composition changes significantly from growth phase to itaconic acid production phase, carbon content increases from 42% to around 62%. Despite the gradual decrease in itaconic acid levels with decreasing pH (nearly 50% decrease in itaconic acid at pH 3.5, compared to pH 6), significant itaconate production is still observed at pH 4 (around 63 g/L). Biomass yield remained nearly constant until pH 4. Taken together, these results strongly illustrate the potential of engineered Ustilago maydis in itaconate production at commercial levels.

Serial whole-body cryotherapy in fibromyalgia is effective and alters cytokine profiles

Abstract Introduction: Whole-body cryotherapy (WBC) has shown to be beneficial in the treatment of fibromyalgia (FM). There is cumulative evidence that cytokines play a crucial role in FM. It's unknown whether clinical effects of WBC can be demonstrated at the molecular level and how long the effects last. Methods: We compared effects of serial WBC (6 sessions (- 130 °C in 6 weeks) in FM patients and healthy controls (HC). Primary outcome was the change in pain level (visual analogue scale 0-100 mm) after 6 sessions. Secondary outcomes were a change in disease activity (revised Fibromyalgia Impact Questionnaire) and pain after 3 sessions and 3 months after discontinued therapy and in cytokine levels (interleukin (IL-)1, IL-6, tumor necrosis factor α (TNF-α) and IL-10). The patients' opinions on the satisfaction, effectiveness and significance of WBC were evaluated. Results: Twenty-three FM patients and 30 HC were enrolled. WBC resulted in a significant reduction in pain and disease activity after 3 and 6 sessions. No clinical benefit could be measured 3 months after discontinued treatment. Overall, probands were satisfied with WBC and considered WBC to be important and effective. FM patients had significantly different levels of IL-1, IL-6, TNF-α and IL-10 at each reading point compared to HC. Levels of IL-1, IL-6 and IL-10 were significantly altered over time in FM patients. Compared to HC FM patients showed a significantly different response of IL1, - 6 and - 10 to WBC. Conclusion: Serial WBC is a fast acting and effective treatment for FM. Proven effects of WBC may be explained by changes in cytokines.(AU)

Modulating the Heat Sensitivity of Prostate Cancer Cell Lines In Vitro: A New Impact for Focal Therapies.

Focal therapies such as high-intensity focused ultrasound (HiFU) are an emerging therapeutic option for prostate cancer (PCA). Thermal or mechanical effects mediate most therapies. Moreover, locally administered drugs such as bicalutamide or docetaxel are new focal therapeutic options. We assessed the impact of such focal medical treatments on cell viability and heat sensitivity by pre-treating PCA cell lines and then gradually exposing them to heat. The individual heat response of the cell lines tested differed largely. Vertebral-Cancer of the Prostate (VCaP) cells showed an increase in metabolic activity at 40-50 °C. Androgen receptor (AR)-negative PC3 cells showed an increase at 51.3 °C and were overall more resistant to higher temperatures. Pre-treatment of VCaP cells with testosterone (VCaPrev) leads to a more PC3-like kinetic of the heat response. Pre-treatment with finasteride and bicalutamide did not cause changes in heat sensitivity in any cell line. Mitoxantrone treatment, however, shifted heat-induced proliferation loss to lower temperature in VCaP cells. Further analysis via RNAseq identified a possible correlation of heat resistance with H3K27me3-dependent gene regulation, which could be related to an increase in the histone methyltransferase EZH2 and a possible neuroendocrine differentiation. Pre-treatment with mitoxantrone might be a perspective for HiFU treatment. Further studies are needed to evaluate possible combinations with Hsp90 or EZH2 inhibitors.

Increased Diagnostic Certainty of Periprosthetic Joint Infections by Combining Microbiological Results with Histopathological Samples Gained via a Minimally Invasive Punching Technique.

BACKGROUND: The diagnosis of low-grade infections of endoprostheses is challenging. There are still no unified guidelines for standardised diagnostic approaches, recommendations are categorised into major and minor criteria. Additional histopathological samples might sustain the diagnosis. However, ambulatory preoperative biopsy collection is not widespread. METHOD: 102 patients with hip or knee endoprosthesis and suspected periprosthetic joint infection (PJI) were examined by arthrocentesis with microbiological sample and histopathological punch biopsy. The data were retrospectively analysed for diagnosis concordance. RESULTS: Preoperative microbiology compared to intraoperative results was positive in 51.9% (sensitivity 51.9%, specificity 97.3%). In comparison of preoperative biopsy to intraoperative diagnostic results 51.9% cases were positive (sensitivity 51.9%, specificity 100.0%). The combination of preoperative biopsy and microbiology in comparison to intraoperative results was positive in 70.4% of the cases (sensitivity 70.4%, specificity 97.3%). CONCLUSION: The diagnosis of PJI is complex. One single method to reliably detect an infection is currently not available. With the present method histopathological samples might be obtained quickly, easily and safely for the preoperative detection of PJI. A combination of microbiological and histopathological sampling increases the sensitivity up to 18.5% to detect periprosthetic infection.

An Optimized Ustilago maydis for Itaconic Acid Production at Maximal Theoretical Yield.

Ustilago maydis, a member of the Ustilaginaceae family, is a promising host for the production of several metabolites including itaconic acid. This dicarboxylate has great potential as a bio-based building block in the polymer industry, and is of special interest for pharmaceutical applications. Several itaconate overproducing Ustilago strains have been generated by metabolic and morphology engineering. This yielded stabilized unicellular morphology through fuz7 deletion, reduction of by-product formation through deletion of genes responsible for itaconate oxidation and (glyco)lipid production, and the overexpression of the regulator of the itaconate cluster ria1 and the mitochondrial tricarboxylate transporter encoded by mttA from Aspergillus terreus. In this study, itaconate production was further optimized by consolidating these different optimizations into one strain. The combined modifications resulted in itaconic acid production at theoretical maximal yield, which was achieved under biotechnologically relevant fed-batch fermentations with continuous feed.

An Ustilago maydis chassis for itaconic acid production without by-products.

Ustilago maydis is a promising yeast for the production of a range of valuable metabolites, including itaconate, malate, glycolipids and triacylglycerols. However, wild-type strains generally produce a potpourri of all of these metabolites, which hinders efficient production of single target chemicals. In this study, the diverse by-product spectrum of U. maydis was reduced through strain engineering using CRISPR/Cas9 and FLP/FRT, greatly increasing the metabolic flux into the targeted itaconate biosynthesis pathway. With this strategy, a marker-free chassis strain could be engineered, which produces itaconate from glucose with significantly enhanced titre, rate and yield. The lack of by-product formation not only benefited itaconate production, it also increases the efficiency of downstream processing improving cell handling and product purity.

Integrated strain- and process design enable production of 220 g L-1 itaconic acid with Ustilago maydis.

BACKGROUND: Itaconic acid is an unsaturated, dicarboxylic acid which finds a wide range of applications in the polymer industry and as a building block for fuels, solvents and pharmaceuticals. Currently, Aspergillus terreus is used for industrial production, with titers above 100 g L-1 depending on the conditions. Besides A. terreus, Ustilago maydis is also a promising itaconic acid production host due to its yeast-like morphology. Recent strain engineering efforts significantly increased the yield, titer and rate of production. RESULTS: In this study, itaconate production by U. maydis was further increased by integrated strain- and process engineering. Next-generation itaconate hyper-producing strains were generated using CRISPR/Cas9 and FLP/FRT genome editing tools for gene deletion, promoter replacement, and overexpression of genes. The handling and morphology of this engineered strain were improved by deletion of fuz7, which is part of a regulatory cascade that governs morphology and pathogenicity. These strain modifications enabled the development of an efficient fermentation process with in situ product crystallization with CaCO3. This integrated approach resulted in a maximum itaconate titer of 220 g L-1, with a total acid titer of 248 g L-1, which is a significant improvement compared to best published itaconate titers reached with U. maydis and with A. terreus. CONCLUSION: In this study, itaconic acid production could be enhanced significantly by morphological- and metabolic engineering in combination with process development, yielding the highest titer reported with any microorganism.

ASAP-HSQC-TOCSY for fast spin system identification and extraction of long-range couplings.

Based on Ernst-angle-type excitation and Acceleration by Sharing Adjacent Polarization (ASAP), a fast HSQC-TOCSY experiment is introduced. In the approach, the DIPSI-2 isotropic mixing period of the ASAP-HSQC is simply shifted, which provides a TOCSY period without additional application of rf-energy. The ASAP-HSQC-TOCSY allows the acquisition of a conventional 2D in about 30 s. Alternatively, it allows the acquisition of highly carbon-resolved spectra (several Hz digital resolution) on the order of minutes. An ASAP-HSQC-TOCSY-IPAP variant, finally, allows the sign-sensitive extraction of heteronuclear long-range coupling constants from a pair of highly resolved spectra in less than an hour. Pulse sequences, several example spectra, and a discussion of results are given.

Rapid two-dimensional ALSOFAST-HSQC experiment for metabolomics and fluxomics studies: application to a 13C-enriched cancer cell model treated with gold nanoparticles.

Isotope labeling enables the use of 13C-based metabolomics techniques with strongly improved resolution for a better identification of relevant metabolites and tracing of metabolic fluxes in cell and animal models, as required in fluxomics studies. However, even at high NMR-active isotope abundance, the acquisition of one-dimensional 13C and classical two-dimensional 1H,13C-HSQC experiments remains time consuming. With the aim to provide a shorter, more efficient alternative, herein we explored the ALSOFAST-HSQC experiment with its rapid acquisition scheme for the analysis of 13C-labeled metabolites in complex biological mixtures. As an initial step, the parameters of the pulse sequence were optimized to take into account the specific characteristics of the complex samples. We then applied the fast two-dimensional experiment to study the effect of different kinds of antioxidant gold nanoparticles on a HeLa cancer cell model grown on 13C glucose-enriched medium. As a result, 1H,13C-2D correlations could be obtained in a couple of seconds to few minutes, allowing a simple and reliable identification of various 13C-enriched metabolites and the determination of specific variations between the different sample groups. Thus, it was possible to monitor glucose metabolism in the cell model and study the antioxidant effect of the coated gold nanoparticles in detail. Finally, with an experiment time of only half an hour, highly resolved 1H,13C-HSQC spectra using the ALSOFAST-HSQC pulse sequence were acquired, revealing the isotope-position-patterns of the corresponding 13C-nuclei from carbon multiplets. Graphical abstract Fast NMR applied to metabolomics and fluxomics studies with gold nanoparticles.

Identification of novel parasitophorous vacuole proteins in P. falciparum parasites using BioID.

Malaria blood stage parasites develop within red blood cells where they are contained in a vacuolar compartment known as the parasitophorous vacuole (PV). This compartment holds a key role in the interaction of the parasite with its host cell. However, the proteome of this compartment has so far not been comprehensively analysed. Here we used BioID in asexual blood stages of the most virulent human malaria parasite Plasmodium falciparum to identify new proteins of the PV. The resulting proteome contained many of the already known PV proteins and validation by GFP-knock-in of 10 previously in P. falciparum uncharacterised hits revealed 5 new PV proteins and two with a partial PV localisation. This included proteins peripherally attached to the inner face of the PV membrane as well as proteins anchored in the parasite plasma membrane that protrude into the PV. Using selectable targeted gene disruption we generated mutants for 2 of the 10 candidates. In contrast we could not select parasites with disruptions for another 3 candidates, strongly suggesting that they are important for parasite growth. Interestingly, one of these included the orthologue of UIS2, a protein previously proposed to regulate protein translation in the parasite cytoplasm but here shown to be an essential PV protein. This work extends the number of known PV proteins and provides a starting point for further functional analyses of this compartment.

Improvements, extensions, and practical aspects of rapid ASAP-HSQC and ALSOFAST-HSQC pulse sequences for studying small molecules at natural abundance.

Previously we introduced two novel NMR experiments for small molecules, the so-called ASAP-HSQC and ALSOFAST-HSQC (Schulze-Sünninghausen et al., 2014), which allow the detection of heteronuclear one-bond correlations in less than 30s at natural abundance. We propose an improved symmetrized pulse scheme of the basic experiment to minimize artifact intensities and the combination with non-uniform sampling to enable the acquisition of conventional HSQC spectra in as short as a couple of seconds and extremely 13C-resolved spectra in less than ten minutes. Based on steady state investigations, a first estimate to relative achievable signal intensities with respect to conventional, ASAP-, and ALSOFAST-HSQC experiments is given. In addition, we describe several extensions to the basic pulse schemes, like a multiplicity-edited version, a revised symmetrized CLIP-ASAP-HSQC, an ASAP-/ALSOFAST-HSQC sequence with broadband BIRD-based 1H,1H decoupling, and a symmetrized sequence optimized for water suppression. Finally, RF-power considerations with respect to the high duty cycle of the experiments are given.

Laser ablation ICP-MS: Application in biomedical research.

In the last decade, the development of diverse bioanalytical methodologies based on mass spectrometry imaging has increased, as has their application in biomedical questions. The distribution analysis of elements (metals, semimetals, and non-metals) in biological samples is a point of interest in life sciences, especially within the context of metallomics, which is the scientific field that encompasses the global analysis of the entirety of elemental species inside a cell or tissue. Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been efficiently employed to generate qualitative and quantitative maps of elemental distribution in thin tissue sections of a variety of biological samples, for example, brain, cartilage, spinal cord, etc. The combination of elemental with molecular mass spectrometry allows obtaining information about the elements bound to proteins, when they are previously separated by gel electrophoresis (metalloproteomics), and also adding a new dimension to molecular mass spectrometry imaging by the correlation of molecular and elemental distribution maps in definite regions in a biological tissue. In the present review, recent biomedical applications in LA-ICP-MS imaging as a stand-alone technique and in combination with molecular mass spectrometry imaging techniques are discussed. Applications of LA-ICP-MS in the study of neurodegenerative diseases, distribution of contrast agents and metallodrugs, and metalloproteomics will be focused in this review. © 2015 Wiley Periodicals, Inc. Mass Spec Rev 36:47-57, 2017.