Complete surgical myocardial revascularization in patients with declined renal functions: 12-month outcomes.

INTRODUCTION: This retrospective observational study aimed to evaluate the feasibility and effectiveness of complete revascularization coronary artery bypass grafting (CABG) in patients with multi-vessel disease (MVD)-CAD and declined renal functions, addressing the knowledge gap regarding optimal treatment strategies and outcomes in this specific patient population. METHODS: Between 2020 and 2022, a total of 58 patients underwent on-pump coronary artery bypass grafting surgery for complete myocardial revascularization in this study. To assess overall survival, Kaplan-Meier with the log-rank test was conducted for statistical analysis. RESULTS: The mean age of cohort was 60.7. The findings showed a high prevalence of medical conditions such as hypertension (50.0%), diabetes (50.0%), and anaemia (41.4%) among the participants. Intraoperatively, low cardiac output syndrome was reported in 5.2% of cases, while perioperative outcomes indicated a need for transfusions in 53.5% of cases and an in-hospital mortality rate of 3.4%. At the 12-month follow-up, no redo revascularization or renal replacement therapy was required, but cardiac mortality was 5.2% and all-cause mortality was 6.9%. CONCLUSIONS: The study concluded that complete revascularization is safe for these patients and highlights the potential benefits, emphasizing the need for further research in optimizing revascularization techniques for this population.

Capsular remnant in the rotator cuff footprint is a novel arthroscopic finding may indicate the etiology of the tear.

PURPOSE: The aim of the study was that the capsule remnant is a common indicator of sub-acromial impingement syndrome and bursal side onset rotator cuff tears. METHODS: Sixty-three patients with capsule remnants in the rotator cuff footprint (Study group) were detected, while the 53 patients did not have any remnant on the tendon footprint (Control group) between 2015 and 2020 were included. Demographic data of patients, such as age, gender, and operated side information were obtained from the archive files. Acromion type, presence of osteophytes in the acromioclavicular joint, Acromiohumeral Distance (AHD), Acromial Index (AI), Critical Shoulder Angle (CSA), and Coracoacromial Ligament (CAL) degeneration values were evaluated from preoperative MRI, radiographic images, and arthroscopic video recordings. RESULTS: Severe stages of CAL degeneration were observed in 82.5% of the patients who had capsule remnant (p: 0.001). While type 2 acromion was found in 61.9%, and also acromioclavicular joint osteophyte was found in 58.7% of the patients in the study group. The mean AHD was 8.22 ± 1.56 mm in the study group and 9.2 ± 1.3 mm in the control group. The mean CSA was 43.3 ± 4.9 in the study group and 40.8 ± 4.2 in the control group. The AI was measured as 0.8 ± 0.1 in the study group and 0.8 ± 0.01 in the control group. As a result of these measurements, a statistical difference was found between the two groups in terms of type 2 acromion ratio (p < 0.001), presence of osteophytes in the acromioclavicular joint (p < 0.001), mean acromio-humeral distance (p < 0.001), critical shoulder angle (p = 0.004), and acromial index values (p < 0.001). CONCLUSION: The findings of sub-acromial impingement syndrome were found to be more prominent in patients with full-thickness degenerative tear and findings of capsular remnant in the footprint. If the presence of the current finding is detected during glenohumeral arthroscopy, sub-acromial impingement syndrome should be examined in more detail to reveal the underlying cause and prevent a recurrence.

Can subcoracoid effusion be a more specific finding for subscapularis tear among rotator cuff pathologies on magnetic resonance imaging?

HYPOTHESIS AND BACKGROUND: Magnetic resonance imaging (MRI) is a well-known, noninvasive diagnostic method for rotator cuff tendon pathologies that are not very sensitive for subscapularis tendon tears. Subcoracoid effusion (SE) is an easily recognizable radiologic sign on MRI. In this study, we aimed to examine the relationship of SE with rotator cuff tear and to investigate whether SE could be a supportive finding in the diagnosis of subscapularis tear in preoperative MRI. Our hypothesis was that SE was a more specific finding of subscapularis tear than other rotator cuff tears. METHODS: The data of patients who underwent shoulder arthroscopy in our clinic between 2017 and 2021 were analyzed retrospectively. Four groups were included in the study: patients with a rotator cuff tear accompanied by a subscapularis tear (group 1, n = 273), patients with isolated subscapularis tear (group 2, n = 57), patients with rotator cuff tear with intact subscapularis tendon (group 3, n = 190), and patients without any rotator cuff pathology (group 4, n = 263). Arthroscopic video records and MRIs of all patients were evaluated retrospectively. Subscapularis tendon tears were classified according to the Lafosse classification. RESULTS: There was a statistically significant difference between the groups in terms of the presence of SE on MRI (P = .001). The presence of SE in group 1 and group 2 was statistically significantly higher than that in both group 3 and group 4 (P = .001), and there was no significant difference between group 3 and group 4 (P > .05). A significant relationship was found between Lafosse classification and SE (P = .001). When the diagnostic powers of the detection of SSC tear and the presence of SE on MRI for SSC tear were compared, Kappa values were 0.615 (P = .001) and 0.701 (P = .001), and overall diagnostic accuracy rates were 80.3% and 85.5%, respectively. CONCLUSION: We conclude that SE is a more specific finding for subscapularis tears than other rotator cuff pathologies. We suggest that SE on MRI should also be considered in patients with a rotator cuff tear in whom a subscapularis tear was not detected in preoperative MRI and that the subscapularis tendon should be carefully evaluated during surgery in cases where the effusion is positive.

An urban air quality assessment based on a meteorological perspective.

An integrated approach to understanding all measured pollutants with multi-discipline in different time scales and understanding the mechanisms hidden under low air quality (AQ) conditions is essential for tackling potential air pollution issues. In this study, the air pollution of Sivas province was analyzed with meteorological and PM2.5 data over six years to assess the city's AQ in terms of PM2.5 pollution and analyze the effect of meteorological factors on it. It was found that the winter period (January-February-November-December) of every year except 2019-which has missing data-is the period with the highest air pollution in the province. In addition, the days exceeding the daily PM2.5 limit values in 2016, 2017, 2020, and 2021 were also seen in the spring and summer months, which inclined the study to focus on additional pollutant sources such as long-range dust transport and road vehicles. The year 2017 has the highest values and was analyzed in detail. Pollution periods with the most increased episodes in 2018 were analyzed with the Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) and Dust Regional Atmospheric Model (DREAM) models. As a result of the study, the average PM2.5 values in 2017 were 31.66 ± 19.2 µg/m3 and a correlation of -0.49 between temperature and PM2.5. As a result of model outputs, it was found that the inversion is intensely observed in the province, which is associated with an increase of PM2.5 during the episodes. Dust transport from northwestern Iraq and northeastern Syria is observed, especially on days with daily average PM2.5 values above 100 µg/m3. Additionally, planetary boundary layer (PBL) data analysis with PM pollution revealed a significant negative correlation (r = -0.61). Air pollutants, particularly PM2.5, were found to be higher during lower PBL levels.

The Correlation of Histopathologic Parameters With Mismatch Repair Protein-deficient Subgroups and MLH1 Methylation in Endometrial Carcinomas.

There are limited data regarding the correlation of clinical and pathologic parameters with mismatch repair (MMR) protein-deficient subgroups and methylation status. In this study, we analyzed the status of MMR proteins in resection specimens of 198 consecutive endometrial carcinomas and the methylation status in tumors with MLH1 and PMS2 deficiency. We, therefore, assessed the correlation of clinical and pathologic parameters with MMR protein-deficient subgroups. Univariate analysis revealed that deeper myometrial invasion and the presence of tumor-associated lymphocytes were more frequently observed in tumors with MMR protein deficiency ( P =0.023 and 0.001, respectively). The multivariate logistic regression analysis revealed that only the presence of tumor-associated lymphocytes was significantly associated with MMR protein deficiency ( P =0.002, odds ratio=2.674, 95% confidence interval=1.418-5.045). We also compared MLH1 and PMS2 deficiency with other protein deficiency regarding clinical and pathologic parameters. Furthermore, we compared MLH1 methylated tumors with MMR protein-deficient nonmethylated tumors regarding clinical and pathologic parameters. MLH1 was methylated in 51 of 54 tumors with MLH1 and PMS2 deficiency. In univariate analysis, a larger tumor size was significantly associated with MLH1 and PMS2 deficiency and with MLH1 methylation ( P =0.004 and 0.005, respectively). The multivariate logistic regression analysis revealed that a larger tumor size was significantly associated with MLH1 and PMS2 deficiency and MLH1 methylation ( P =0.002, odds ratio=14.222, 95% confidence interval=2.560-79.026, P =0.008, odds ratio=22.222, 95% confidence interval=2.220-222.395, respectively). Our results showed a slightly higher rate of MLH1 and PMS2 deficiency (34.3%) than in previous studies. This may likely be due to ethnic differences in frequency of various mutations.

Evaluation of the relationship between insulin resistance and visceral adiposity index in patients with acne vulgaris.

BACKGROUND: Acne vulgaris (AV) is a chronic inflammatory skin disease that is common among adolescents. Its etiology involves hormones, diet, genetics, and environmental factors. The aim of this study was to investigate the association between acne vulgaris and insulin resistance (IR) and visceral adiposity index (VAI). METHODS: The study included 184 individuals. Participants' height, weight, waist and hip circumference and blood pressure were measured. Morning fasting blood was obtained from all participants for measuring glucose, insulin, triglyceride (TG), and cholesterol levels. The HOMA index and visceral adiposity index were calculated. The collected data were analyzed using statistical methods. RESULTS: The patient and control groups exhibited similar age, gender, and body mass index (p > 0.05). There was no significant difference between the patient and control groups in HOMA index and VAI (p > 0.05). A positive correlation was observed between VAI and glucose, insulin, HOMA index, TG level, and waist circumference, whereas there was a negative correlation with high-density lipoprotein (HDL). DISCUSSION: Our study results demonstrated that IR and VAI were similar both in the AV and healthy control groups. There was no correlation between acne severity score and waist circumference, glucose, insulin, TG, HDL, HOMA index, and VAI. These results indicate that IR and visceral adipose tissue dysfunction alone are not effective in the development of acne.

Multimodal chemical imaging of a single brain tissue section using ToF-SIMS, MALDI-ToF and immuno/histochemical staining.

Cluster ion beam ToF-SIMS and/or MALDI-ToF mass spectrometry imaging (using 1,5-DAN matrix via sublimation) of a single coronal rat brain tissue section followed by classical- or immuno- histochemical staining faclilated a new multimodal chemical imaging workflow allowing complementary correlation of the lipid molecular ion images with the immuno/histological features within cerebellum region of the same brain tisue section.

PD-L1 Expression in Mismatch Repair-deficient Endometrial Carcinoma and Tumor-associated Immune Cells: Differences Between MLH1 Methylated and Nonmethylated Subgroups.

Mismatch repair (MMR)-deficient endometrial carcinomas show increased programmed cell death-ligand 1 (PD-L1) expression compared with MMR-intact endometrial carcinomas, but there are limited data regarding PD-L1 expression between sporadic and inherited carcinomas exhibiting MMR loss. Most of the studies investigating PD-L1 expression in endometrial carcinoma have used tissue microarrays and did not examine all tumor blocks. In this study, we analyzed the expression of PD-L1 in resection specimens of 176 consecutive endometrial carcinomas using all tumor blocks; we compared PD-L1 expression in MMR-deficient endometrial carcinomas, including the MLH1 and PMS2-loss subgroup, and the other MMR-loss subgroups (MSH2 and MSH6, isolated PMS2, and isolated MSH6), with the MMR-intact subgroup. MLH1 methylation was performed in tumors with MLH1 and PMS2 loss. Tumor cell (TC) and tumor-associated immune cell (IC) PD-L1 positivity with a 1% cutoff was observed in 21% (n=37) and 66.5% (n=117) of cases, respectively, and with a 5% cutoff in 5.1% (n=9) and 39.8% (n=70) of cases, respectively. MMR protein deficiency was a statistically significant parameter associated with IC PD-L1 positivity, with 1% and 5% cutoffs on multivariate analysis [odds ratio (OR)=5.236, 95% confidence interval (CI)=2.075-13.211, P=0.001, and OR=3.702, 95% CI=1.759-7.791, P=0.001, respectively]. The multivariate analysis showed that IC PD-L1 positivity, using both 1% and 5% cutoffs, was significantly associated with the MLH1 and PMS2 loss compared with the MMR protein-intact subgroup (MLH1 and PMS2 loss for 1% cutoff: OR=5.104, 95% CI=1.876-13.881, P=0.001, and for 5% cutoff: OR=3.322, 95% CI=1.540-7.166, P=0.002). Squamous differentiation was an independent predictor for TC PD-L1 positivity, with a 5% cutoff (OR=6.102, 95% CI=1.280-10.096, P=0.026). Larger tumor size was an independent predictive factor for IC PD-L1 positivity with a 1% cutoff (OR=6.757, 95% CI=1.569-29.109, P=0.010). Overall, 48 (92.3%) of 52 MLH1 methylated tumors showed IC PD-L1 positivity with 1% cutoff, and 34 (65.4%) of 52 MLH1 methylated tumors showed IC PD-L1 positivity with 5% cutoff. Our results show a higher rate of IC PD-L1 positivity than in previous studies. This is likely due in part to the use of all tumor blocks. MLH1 and PMS2 loss was an independent predictive factor for IC PD-L1 positivity, with both 1% and 5% cutoffs. Using univariate analysis, we observed decreased disease-free survival for IC PD-L1 positivity ≥5%. Our study results should now be tested and proven in larger cohorts, with longer follow-up data.

(CO2)n+, (H2O)n+, and (H2O)n+ (CO2) gas cluster ion beam secondary ion mass spectrometry: analysis of lipid extracts, cells, and Alzheimer's model mouse brain tissue.

This work assesses the potential of new water cluster-based ion beams for improving the capabilities of secondary ion mass spectrometry (SIMS) for in situ lipidomics. The effect of water clusters was compared to carbon dioxide clusters, along with the effect of using pure water clusters compared to mixed water and carbon dioxide clusters. A signal increase was found when using pure water clusters. However, when analyzing cells, a more substantial signal increase was found in positive ion mode when the water clusters also contained carbon dioxide, suggesting that additional reactions are in play. The effects of using a water primary ion beam on a more complex sample were investigated by analyzing brain tissue from an Alzheimer's disease transgenic mouse model. The results indicate that the ToF-SIMS results are approaching those from MALDI as ToF-SIMS was able to image lyso-phosphocholine (LPC) lipids, a lipid class that for a long time has eluded detection during SIMS analyses. Gangliosides, sulfatides, and cholesterol were also imaged.

Can Moderate Patient Prosthesis Mismatch Be Tolerated in a Selected Group of Patients with Aortic Valve Replacement?

INTRODUCTION: In this study, we aimed to determine the incidence of patient prosthesis mismatch (PPM) and its effects on ejection fraction (EF), gradients, and late survival. METHODS: 200 patients who underwent isolated mechanical AVR between March 2013 and May 2016 were retrospectively evaluated based on patient records. RESULTS: 200 patients were included in the study. No PPM was detected in 42 (21%) patients, moderate PPM in 122 (61%), and severe PPM in 36 (18%) patients. A significant decrease was found in all groups in terms of mean valve gradients and LVMI (preoperative LVMI compared with postoperative LVMI at the 12th month) (P < .001). A 30% decrease in mean LVMI in the no PPM and moderate PPM groups and a 20% decrease in the severe PPM group were detected at the 6th month. CONCLUSION: In our postoperative data, we found that EF was preserved, the transvalvular gradient reduced, and LVMI decreased. There was no difference in mortality rates between the control (no PPM) group and the moderate PPM group. Taking into account our patient groups, we can say that no-to-moderate PPM has no major effect on left ventricular remodeling in patients with preserved left ventricular functions.

Pyroglutamation of amyloid-ßx-42 (Aßx-42) followed by Aß1-40 deposition underlies plaque polymorphism in progressing Alzheimer's disease pathology.

Amyloid-ß (Aß) pathology in Alzheimer's disease (AD) is characterized by the formation of polymorphic deposits comprising diffuse and cored plaques. Because diffuse plaques are predominantly observed in cognitively unaffected, amyloid-positive (CU-AP) individuals, pathogenic conversion into cored plaques appears to be critical to AD pathogenesis. Herein, we identified the distinct Aß species associated with amyloid polymorphism in brain tissue from individuals with sporadic AD (s-AD) and CU-AP. To this end, we interrogated Aß polymorphism with amyloid conformation-sensitive dyes and a novel in situ MS paradigm for chemical characterization of hyperspectrally delineated plaque morphotypes. We found that maturation of diffuse into cored plaques correlated with increased Aß1-40 deposition. Using spatial in situ delineation with imaging MS (IMS), we show that Aß1-40 aggregates at the core structure of mature plaques, whereas Aß1-42 localizes to diffuse amyloid aggregates. Moreover, we observed that diffuse plaques have increased pyroglutamated Aßx-42 levels in s-AD but not CU-AP, suggesting an AD pathology-related, hydrophobic functionalization of diffuse plaques facilitating Aß1-40 deposition. Experiments in tgAPPSwe mice verified that, similar to what has been observed in human brain pathology, diffuse deposits display higher levels of Aß1-42 and that Aß plaque maturation over time is associated with increases in Aß1-40. Finally, we found that Aß1-40 deposition is characteristic for cerebral amyloid angiopathy deposition and maturation in both humans and mice. These results indicate that N-terminal Aßx-42 pyroglutamation and Aß1-40 deposition are critical events in priming and maturation of pathogenic Aß from diffuse into cored plaques, underlying neurotoxic plaque development in AD.

Brain region-specific amyloid plaque-associated myelin lipid loss, APOE deposition and disruption of the myelin sheath in familial Alzheimer's disease mice.

There is emerging evidence that amyloid beta (Aß) aggregates forming neuritic plaques lead to impairment of the lipid-rich myelin sheath and glia. In this study, we examined focal myelin lipid alterations and the disruption of the myelin sheath associated with amyloid plaques in a widely used familial Alzheimer's disease (AD) mouse model; 5xFAD. This AD mouse model has Aß42 peptide-rich plaque deposition in the brain parenchyma. Matrix-assisted laser desorption/ionization imaging mass spectrometry of coronal brain tissue sections revealed focal Aß plaque-associated depletion of multiple myelin-associated lipid species including sulfatides, galactosylceramides, and specific plasmalogen phopshatidylethanolamines in the hippocampus, cortex, and on the edges of corpus callosum. Certain phosphatidylcholines abundant in myelin were also depleted in amyloid plaques on the edges of corpus callosum. Further, lysophosphatidylethanolamines and lysophosphatidylcholines, implicated in neuroinflammation, were found to accumulate in amyloid plaques. Double staining of the consecutive sections with fluoromyelin and amyloid-specific antibody revealed amyloid plaque-associated myelin sheath disruption on the edges of the corpus callosum which is specifically correlated with plaque-associated myelin lipid loss only in this region. Further, apolipoprotein E, which is implicated in depletion of sulfatides in AD brain, is deposited in all the Aß plaques which suggest apolipoprotein E might mediate sulfatide depletion as a consequence of an immune response to Aß deposition. This high-spatial resolution matrix-assisted laser desorption/ionization imaging mass spectrometry study in combination with (immuno) fluorescence staining of 5xFAD mouse brain provides new understanding of morphological, molecular and immune signatures of Aß plaque pathology-associated myelin lipid loss and myelin degeneration in a brain region-specific manner. Read the Editorial Highlight for this article on page 7.

Trypanosomosis prevalence in natural field-based infection: insights into systematic review and meta-analysis of studies from 1980 to 2018 on The Gambian ruminants with special emphasis on cattle.

Consistent quantification of trypanosomes, the parasite responsible for African animal trypanosomosis, is important for effective surveillance, control, and eradication strategies. Here, we used a rigorously predefined protocol to search and select eligible publications that utilized either microscopy, serology, or molecular methods to investigate prevalence of trypanosomosis based on the presence of any of three most common Trypanosoma spp. (T. congolense, T. vivax, and T. brucei) in the field-based naturally grazed Gambian cattle, sheep, and goats. To combine results of studies on cattle through meta-analysis, sensitivity and subgroup analyses were carried out with the random effects model, and prevalence estimates of each study with 95% confidence intervals (CI) were presented with a forest plot. All the eligible studies utilized the buffy coat technique (BCT) to detect trypanosomes in the blood samples, while the more sensitive serological and molecular detection methods are yet to be widely exploited. Heterogeneity among the studies on cattle was moderate (I2 = 55%), and the pooled trypanosomosis prevalence based on the BCT was 5.2% (95% CI: 4.0-6.4). Meanwhile, estimated prevalence varied according to the trypanosome detection methods, study locations, types of publication, year, and length of observations. We could not pool the trypanosomosis prevalence in sheep and goats through meta-analysis due to small number of studies. The prevalence estimates based on the BCT ranged from 3.2 to 8.1% in goats and 2.8 to 10.6% in sheep. Even though there seems to be a slight decrease in trypanosomosis prevalence in cattle in one of the Gambian districts, there was no consistent trend across the years. It is thought that the literature search and formatting procedures presented in this study contribute to doing systematic reviews on the investigated subject and can be adapted for similar cases.

A BCI Gaze Sensing Method Using Low Jitter Code Modulated VEP.

Visual evoked potentials (VEPs) are used in clinical applications in ophthalmology, neurology, and extensively in brain-computer interface (BCI) research. Many BCI implementations utilize steady-state VEP (SSVEP) and/or code modulated VEP (c-VEP) as inputs, in tandem with sophisticated methods to improve information transfer rates (ITR). There is a gap in knowledge regarding the adaptation dynamics and physiological generation mechanisms of the VEP response, and the relation of these factors with BCI performance. A simple, dual pattern display setup was used to evoke VEPs and to test signatures elicited by non-isochronic, non-singular, low jitter stimuli at the rates of 10, 32, 50, and 70 reversals per second (rps). Non-isochronic, low-jitter stimulation elicits quasi-steady-state VEPs (QSS-VEPs) that are utilized for the simultaneous generation of transient VEP and QSS-VEP. QSS-VEP is a special case of c-VEPs, and it is assumed that it shares similar generators of the SSVEPs. Eight subjects were recorded, and the performance of the overall system was analyzed using receiver operating characteristic (ROC) curves, accuracy plots, and ITRs. In summary, QSS-VEPs performed better than transient VEPs (TR-VEP). It was found that in general, 32 rps stimulation had the highest ROC area, accuracy, and ITRs. Moreover, QSS-VEPs were found to lead to higher accuracy by template matching compared to SSVEPs at 32 rps. To investigate the reasons behind this, adaptation dynamics of transient VEPs and QSS-VEPs at all four rates were analyzed and speculated.

Multimodal Chemical Imaging of Amyloid Plaque Polymorphism Reveals Aß Aggregation Dependent Anionic Lipid Accumulations and Metabolism.

Amyloid plaque formation constitutes one of the main pathological hallmarks of Alzheimer's disease (AD) and is suggested to be a critical factor driving disease pathogenesis. Interestingly, in patients that display amyloid pathology but remain cognitively normal, Aß deposits are predominantly of diffuse morphology suggesting that cored plaque formation is primarily associated with cognitive deterioration and AD pathogenesis. Little is known about the molecular mechanism responsible for conversion of monomeric Aß into neurotoxic aggregates and the predominantly cored deposits observed in AD. The structural diversity among Aß plaques, including cored/compact- and diffuse, may be linked to their distinct Aß profile and other chemical species including neuronal lipids. We developed a novel, chemical imaging paradigm combining matrix assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) and fluorescent amyloid staining. This multimodal imaging approach was used to probe the lipid chemistry associated with structural plaque heterogeneity in transgenic AD mice (tgAPPSwe) and was correlated to Aß profiles determined by subsequent laser microdissection and immunoprecipitation-mass spectrometry. Multivariate image analysis revealed an inverse localization of ceramides and their matching metabolites to diffuse and cored structures within single plaques, respectively. Moreover, phosphatidylinositols implicated in AD pathogenesis, were found to localize to the diffuse Aß structures and correlate with Aß1-42. Further, lysophospholipids implicated in neuroinflammation were increased in all Aß deposits. The results support previous clinical findings on the importance of lipid disturbances in AD pathophysiology and associated sphingolipid processing. These data highlight the potential of multimodal imaging as a powerful technology to probe neuropathological mechanisms.

On-Tissue Chemical Derivatization of Catecholamines Using 4-( N-Methyl)pyridinium Boronic Acid for ToF-SIMS and LDI-ToF Mass Spectrometry Imaging.

The analysis of small polar compounds with ToF-SIMS and MALDI-ToF-MS have been generally hindered by low detection sensitivity, poor ionization efficiency, ion suppression, analyte in-source fragmentation, and background spectral interferences from either a MALDI matrix and/or endogenous tissue components. Chemical derivatization has been a well-established strategy for improved mass spectrometric detection of many small molecular weight endogenous compounds in tissues. Here, we present a devised strategy to selectively derivatize and sensitively detect catecholamines with both secondary ion ejection and laser desorption ionization strategies, which are used in many imaging mass spectrometry (IMS) experiments. Chemical derivatization of catecholamines was performed by a reaction with a synthesized permanent pyridinium-cation-containing boronic acid molecule, 4-( N-methyl)pyridinium boronic acid, through boronate ester formation (boronic acid-diol reaction). The derivatization facilitates their sensitive detection with ToF-SIMS and LDI-ToF mass spectrometric techniques. 4-( N-Methyl)pyridinium boronic acid worked as a reactive matrix for catecholamines with LDI and improved the sensitivity of detection for both SIMS and LDI, while the isotopic abundances of the boron atom reflect a unique isotopic pattern for derivatized catecholamines in MS analysis. Finally, the devised strategy was applied, as a proof of concept, for on-tissue chemical derivatization and GCIB-ToF-SIMS (down to 3 µm per pixel spatial resolution) and LDI-ToF mass spectrometry imaging of dopamine, epinephrine, and norepinephrine in porcine adrenal gland tissue sections. MS/MS using collision-induced dissociation (CID)-ToF-ToF-SIMS was subsequently employed on the same tissue sections after SIMS and LDI mass spectrometry imaging experiments, which provided tandem MS information for the validation of the derivatized catecholamines in situ. This methodology can be a powerful approach for the selective and sensitive ionization/detection and spatial localization of diol-containing molecules such as aminols, vic-diols, saccharides, and glycans along with catecholamines in tissue sections with both SIMS and LDI/MALDI-MS techniques.

Synthesis and Characterization of the Hemi-Salen Ligands and Their Triboron Complexes: Spectroscopy and Examination of Anticancer Properties.

The synthesis, spectroscopic properties, and in vitro cytotoxicity activity of a series of various salen-based triboron complexes have been designed and prepared from hemi-salen (L1 H3  - L4 H3 ) ligands and BF3 ·Et2 O or BPh3 under simple reaction conditions. The hemi-salen (L1 H3  - L4 H3 ) ligands and their BF2 or BPh2 chelating triboron complexes were characterized by means of NMR (1 H, 13 C, 19 F, and 11 B) spectra, FT-IR spectra, UV/VIS spectra, fluorescence spectra, mass spectra, melting point, as well as elemental analysis. The triboron [L(1 - 4) (BF2 )3 ] and [L(1 - 4) (BPh2 )3 ] complexes were investigated for their absorption and emission properties, and these complexes are also good chelates towards boron(III) fragments such as BF2 or BPh2 quantum yield in solution reaching up to 38%. The hemi-salen (L1 H3  - L4 H3 ) ligands and their BF2 or BPh2 chelating triboron complexes were tested for the in vitro anticancer activity against various cancer and normal cells (HeLa, DLD-1, ECC-1, PC-3, PNT-1A, and CRL-4010), and it was found that the cell viability of cancer cells was decreased while most of the healthy cells could still be viable. Also, the cytotoxicity studies showed that anticancer activity of hemi-salen (L1 H3  - L4 H3 ) ligands is higher than that of triboron [L(1 - 4) (BF2 )3 ] and [L(1 - 4) (BPh2 )3 ] complexes. The hemi-salen (L1 H3  - L4 H3 ) ligands showing the strongest cytotoxic effect in PC-3 cells were found to exhibit anticancer activity with apoptosis by increasing the level of ROS in the PC-3 cells.

Histology-Compatible MALDI Mass Spectrometry Based Imaging of Neuronal Lipids for Subsequent Immunofluorescent Staining.

Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) enables acquisition of spatial distribution maps for molecular species in situ. This can provide comprehensive insights on the pathophysiology of different diseases. However, current sample preparation and MALDI-IMS acquisition methods have limitations in preserving molecular and histological tissue morphology, resulting in interfered correspondence of MALDI-IMS data with subsequently acquired immunofluorescent staining results. We here investigated the histology compatibility of MALDI-IMS to image neuronal lipids in rodent brain tissue with subsequent immunohistochemistry and fluorescent staining of histological features. This was achieved by sublimation of a low ionization energy matrix compound, 1,5-diaminonapthalene (1,5-DAN), minimizing the number of low-energy laser shots. This yielded improved lipid spectral quality and speed of data acquisition and reduced matrix cluster formation along with preservation of specific histological information at cellular levels. This gentle, histology-compatible MALDI-IMS protocol also diminished thermal effects and mechanical stress created during nanosecond laser ablation processes that were prominent in subsequent immunofluorescent staining images but not with classical hematoxylin and eosin (H&E) staining on the same tissue section. Furthermore, this methodology proved to be a powerful strategy for investigating ß-amyloid (Aß) plaque-associated neuronal lipids as exemplified by performing high-resolution MALDI-IMS with subsequent fluorescent amyloid staining in a transgenic mouse model of Alzheimer's disease (tgSwe).

Probing amyloid-ß pathology in transgenic Alzheimer's disease (tgArcSwe) mice using MALDI imaging mass spectrometry.

The pathological mechanisms underlying Alzheimer's disease (AD) are still not understood. The disease pathology is characterized by the accumulation and aggregation of amyloid-ß (Aß) peptides into extracellular plaques, however the factors that promote neurotoxic Aß aggregation remain elusive. Imaging mass spectrometry (IMS) is a powerful technique to comprehensively elucidate the spatial distribution patterns of lipids, peptides and proteins in biological tissues. In the present study, matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS)-based imaging was used to study Aß deposition in transgenic mouse brain tissue and to elucidate the plaque-associated chemical microenvironment. The imaging experiments were performed in brain sections of transgenic Alzheimer's disease mice carrying the Arctic and Swedish mutation of amyloid-beta precursor protein (tgArcSwe). Multivariate image analysis was used to interrogate the IMS data for identifying pathologically relevant, anatomical features based on their chemical identity. This include cortical and hippocampal Aß deposits, whose amyloid peptide content was further verified using immunohistochemistry and laser microdissection followed by MALDI MS analysis. Subsequent statistical analysis on spectral data of regions of interest revealed brain region-specific differences in Aß peptide aggregation. Moreover, other plaque-associated protein species were identified including macrophage migration inhibitory factor suggesting neuroinflammatory processes and glial cell reactivity to be involved in AD pathology. The presented data further highlight the potential of IMS as a powerful approach in neuropathology. Hanrieder et al. described an imaging mass spectrometry based study on comprehensive spatial profiling of C-terminally truncated Aß species within individual plaques in tgArcSwe mice. Here, brain region-dependent differences in Aß truncation and other plaque-associated proteins, such as macrophage migration inhibitory factor, were observed. The data shed further light on plaque-associated molecular mechanisms implicated in Alzheimer's pathogenesis. Cover image for this issue: doi: 10.1111/jnc.13328.