Procedural learning in schizophrenia can reflect the pharmacologic properties of the antipsychotic treatments.

BACKGROUND: Conventional and atypical antipsychotics have different affinities for D2 receptors, and these receptors are principally located in the striatum. Given that this cerebral structure was previously found to play a major role in procedural learning, the antipsychotic treatment in schizophrenia may be determinant for the procedural learning profile of these patients. OBJECTIVE: The current study was aimed at verifying whether procedural learning differs in patients with schizophrenia treated with conventional antipsychotics and patients treated with atypical antipsychotics. METHOD: Forty-five patients with schizophrenia were divided into 3 different groups according to their pharmacologic treatment: (1) haloperidol, a classical neuroleptic with high D2 receptor affinity; (2) clozapine, an atypical neuroleptic with practically no D2 receptor affinity; and (3) risperidone, an atypical neuroleptic that nevertheless shows high D2 receptor affinity. Patients were compared to 35 control subjects on a visuomotor procedural learning task (mirror drawing). RESULTS: All patients were able to learn the task. However, those treated with haloperidol showed some degree of learning impairment, while those treated with clozapine or risperidone did not show this impairment. In addition, performance per se, regardless of the learning, was found to be affected in the haloperidol and risperidone, but not in the clozapine groups. CONCLUSION: Procedural learning in schizophrenia may be differentially affected, depending on the pharmacologic profiles of the antipsychotics used for the treatment of this illness.     

Plötzlicher Brustschmerz und Unterleibsschmerzen

Notfall + Rettungsmedizin - Der plötzliche Brust- und der plötzliche Unterleibsschmerz gehören zu den häufigsten Gründen, die Patienten in die Notaufnahme führen. Das...     

Contrast-Enhanced Ultrasound Quantifies the Perfusion Within Tibial Non-Unions and Predicts the Outcome of Revision Surgery

Vascularity is one of the factors determining successful bone regeneration. This prospective study focused on quantifying the microperfusion of tibial non-unions with contrast-enhanced ultrasound (CEUS) 12?wk after revision surgery and comparing it with the osseous consolidation at a maximum of 24?mo assessed with standard radiography and computed tomography. Of 36 patients with tibial non-unions, 28 (77.8%) manifested consolidation, and 8 patients required further revision surgery. CEUS revealed significantly higher perfusion in consolidated versus persistent non-unions for all quantification parameters (e.g., wash-in perfusion index p?=?0.036). Receiver operating characteristic analysis revealed a sensitivity of 82.1% and specificity of 75.0% with a wash-in perfusion index cutoff at 19.9 a.u. for diagnosing persisting non-unions. More than 1 y ahead of the final radiologic diagnostic examination, CEUS could predict eventual consolidation based on the osseous perfusion as soon as 12?wk postoperatively. This information can be crucial for the decision-making process for re-revision at an early stage.     

Efficient denoising algorithms for large experimental datasets and their applications in Fourier transform ion cyclotron resonance mass spectrometry

Modern scientific research produces datasets of increasing size and complexity that require dedicated numerical methods to be processed. In many cases, the analysis of spectroscopic data involves the denoising of raw data before any further processing. Current efficient denoising algorithms require the singular value decomposition of a matrix with a size that scales up as the square of the data length, preventing their use on very large datasets. Taking advantage of recent progress on random projection and probabilistic algorithms, we developed a simple and efficient method for the denoising of very large datasets. Based on the QR decomposition of a matrix randomly sampled from the data, this approach allows a gain of nearly three orders of magnitude in processing time compared with classical singular value decomposition denoising. This procedure, called urQRd (uncoiled random QR denoising), strongly reduces the computer memory footprint and allows the denoising algorithm to be applied to virtually unlimited data size. The efficiency of these numerical tools is demonstrated on experimental data from high-resolution broadband Fourier transform ion cyclotron resonance mass spectrometry, which has applications in proteomics and metabolomics. We show that robust denoising is achieved in 2D spectra whose interpretation is severely impaired by scintillation noise. These denoising procedures can be adapted to many other data analysis domains where the size and/or the processing time are crucial.Big data are becoming predominant in modern science, and found in many scientific domains: astrophysics (1), large-scale physics experiments (2), biology (3, 4), or even natural text analysis (5). This introduces a new challenge for data handling and analysis, as it requires special processing approaches, which avoid accessing the whole data at once (6), and make use of adapted algorithms easily parallelized. Such constraints may be difficult to fulfill, even for simple procedures such as noise reduction.Every measurement is corrupted by unwanted noise, which is the combination of the effect of random fluctuations in the sample and the apparatus, but can also originate from external events like environmental noise. Denoising methods focus mainly on removing or reducing as much as possible an additive Gaussian wide sense stationary noise.For stationary signals the optimal linear denoising filter in the mean-square error sense is the Wiener filter. However, it suffers from the requirement of a precise estimate of the signal and noise auto- and cross-correlation functions. Many advanced denoising methods have been developed using linear algebra, which usually requires considerable processing power. One of the main alternative approaches relies on a multiresolution analysis, which sets noise apart from signal components more efficiently than classical orthogonal basis methods. In this respect, wavelets associated with soft thresholding have been considered for denoising purposes (7).Harmonic signals can be modeled as the sum of damped sinusoids. They are typically found in spectroscopies like NMR, Fourier transform mass spectrometry (FT-MS), FTIR but also in seismology, astrophysics, genetics, or financial analysis. They are easily analyzed by Fourier transformation if regularly sampled. For such specific signals, one class of denoising methods is based on modeling a sum of a fixed number of exponentials as devised by Prony (8). This was recently revisited and improved by Beylkin and Monzon (9, 10).There are also statistical methods related to the Karhunen–Loève transform which use adaptive basis instead of a priori basis. Relying on the autoregressive model (AR) (11, 12), a Hankel matrix is built and its rank is then reduced to the number of expected frequencies. Rank reduction by the singular value decomposition (SVD) (13) of this matrix is known as Cadzow’s method (14), also known as singular spectrum analysis (SSA) (15). The advantage is that no assumption about the noise or signal power is required and the number of frequencies is the only parameter.However, the benefits of denoising are balanced by several drawbacks. If the assumed number of frequencies is incorrect, the denoised signal is polluted with spurious artifacts that are indistinguishable from the real signal. Additionally, the SVD decomposition is slow and scales in operations. Alternative rapid SVD algorithms can be used, such as the Lanczos bidiagonalization method (16, 17), the truncated SVD (18), or random projections (19), as was recently applied in seismology (20). However, these algorithms do not solve the artifacts issue.Capitalizing on recent progress in algebra on random projection and probabilistic algorithms (21–24), we present here an efficient approach to denoising which can be easily applied to the large datasets found in Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry experiments, and more generally, to any big data analysis. The main driving idea is to avoid explicit computation of data-derived quantities, but rather estimate the needed values, based on a partial sampling of the data. Extending from previous ideas (19), the denoising algorithm is based on a subsampling of the data-associated matrix. Here, rather than truncating the rank by removing some of the components of the SVD decomposition, we compute a randomized low-rank approximation of the Hankel matrix (24) that retains preferentially more signal than noise.We show that this leads to a substantial improvement of the processing in terms of speed, with little compromise on the quality, allowing gains of 2–3 orders of magnitude in processing time and in memory size. Applications of this approach are demonstrated on the large datasets obtained in FT-ICR mass spectrometry.     

Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) with Low-Dose Cisplatin and Doxorubicin in Gastric Peritoneal Metastasis

Background

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel technique of intraperitoneal chemotherapy. First results obtained with PIPAC in patients with advanced peritoneal metastasis (PM) from gastric cancer (GC) are presented.

Methods

Retrospective analysis: Sixty PIPAC were applied in 24 consecutive patients with PM from GC. 67 % patients had previous surgery, and 79 % previous platinum-based systemic chemotherapy. Mean Peritoneal Carcinomatosis Index (PCI) of 16?±?10 and 18/24 patients had signet-ring GC. Cisplatin 7.5 mg/m² and doxorubicin 1.5 mg/m² were given for 30 min at 37 °C and 12 mmHg at 6 week intervals. Outcome criteria were survival, adverse events, and histological tumor response.

Results

Median follow-up was 248 days (range 105–748), and median survival time was 15.4 months. Seventeen patients had repeated PIPAC, and objective tumor response was observed in 12 (12/24?=?50 %): no vital tumor cells?=?6, major pathological response?=?6, minor response?=?3. Postoperative adverse events?>?CTCAE 2 were observed in 9 patients (9/24, 37.5 %). In 3/17 patients, a later PIPAC could not be performed due to non-access. Two patients (ECOG 3 and 4) died in the hospital due to disease progression.

Conclusion

PIPAC with low-dose cisplatin and doxorubicin was safe and induced objective tumor regression in selected patients with PM from recurrent, platinum-resistant GC. First survival data are encouraging and justify further clinical studies in this indication.

     

Contrast-Enhanced Ultrasound (CEUS) as Predictor for Early Retear and Functional Outcome After Supraspinatus Tendon Repair

Supraspinatus (SSP) tendon tears represent a common indication for shoulder surgery. Yet, prediction of postoperative function and tendon retear remains challenging and primarily relies on morphologic magnetic resonance imaging (MRI)-based parameters, supported by patients' demographic data like age, gender, and comorbidities. Considering continuously high retear rates, especially in patients with larger tears and negative prognostic factors, improved outcome prediction could be of high clinical value. Contrast-enhanced ultrasound (CEUS) enables an assessment of dynamic perfusion of the SSP muscle. As a potential surrogate for muscle vitality, CEUS might reflect functional properties of the SSP and support improved outcome prediction after tendon repair. Fifty patients with isolated SSP tendon tears were prospectively enrolled. Preoperatively, SSP muscle perfusion was quantified by CEUS and conventional morphologic parameters like tear size, fatty infiltration, and tendon retraction were assessed by MRI. At six months follow-up, shoulder function, tendon integrity, and muscle perfusion were reassessed. The predictive value of preoperative CEUS for postoperative shoulder function and tendon integrity was evaluated. 35 patients entered the statistical analysis. Preoperative CEUS-based assessment of SSP perfusion significantly correlated with early postoperative shoulder function (Constant, r = 0.48, p < 0.018) and tendon retear (r = 0.67, p < 0.001). CEUS-based subgroup analysis identified patients with exceptionally high, respectively low risk for tendon retear. CEUS-based assessment of the SSP seemed to predict early shoulder function and tendon retear after SSP repair and allowed to identify patient subgroups with exceptionally high or low risk for tendon retear. © 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 38:1150-1158, 2020     

Comparison of the cardiovascular protection by omapatrilat and lisinopril treatments in DOCA-salt hypertension

OBJECTIVE: To compare the cardiovascular protection provided by omapatrilat and lisinopril in an experimental model of hypertension. METHODS: Four-week deoxycorticosterone acetate (DOCA)-salt hypertensive (HT) and age-matched normotensive (NT) rats were treated either with omapatrilat (40 mg/kg per day) or lisinopril (20 mg/kg per day) for 2 weeks before sacrifice, and compared with untreated HT and NT rats sacrificed at ages corresponding to either before or after the drug regimens. RESULTS: Systolic arterial pressure (SAP) of 2 and 4 week HT rats was increased in comparison to age-matched NT rats (P <0.05). Treatment with omapatrilat or lisinopril reduced SAP in HT (P <0.05) similarly by about 10%. Cardiac interstitial collagen, perivascular collagen and media/lumen ratio of coronary arterioles were increased in HT rats. Both treatments partially prevented the rise in perivascular collagen and completely corrected the increased media/lumen ratio in small arterioles from HT (P <0.05). In contrast to NT rats, only a weak coronary dilatation to bradykinin was observed in Langendorff hearts isolated from untreated-HT. This response was slightly improved by lisinopril and markedly improved by omapatrilat (P <0.05). The coronary dilatation to SNP which was reduced in 4-week HT (P <0.05), was partially improved by omapatrilat treatment but not by lisinopril. The enhanced superoxide anion production in aorta from HT rats was partially corrected with omapatrilat and lisinopril. Finally, omapatrilat, unlike lisinopril, markedly reduced mortality in a more severe form of DOCA-salt hypertension. CONCLUSIONS: Omapatrilat and lisinopril regressed coronary remodelling and cardiac collagen deposition, and reduced vascular oxidative stress in DOCA-salt hypertensive rats. However, despite similar antihypertensive efficacy, omapatrilat was superior to lisinopril in improving the endothelial-dependent coronary dilatation, suggesting a better vascular protection in the DOCA-salt model of hypertension.     

Prenatal and Postnatal Serum PCB Concentrations and Cochlear Function in Children at 45 Months of Age

Background: Some experimental and human data suggest that exposure to polychlorinated biphenyls (PCBs) may induce ototoxicity, though results of previous epidemiologic studies are mixed and generally focus on either prenatal or postnatal PCB concentrations exclusively.Objectives: Our aim was to evaluate the association between pre- and postnatal PCB concentrations in relation to cochlear status, assessed by distortion product otoacoustic emissions (DPOAEs), and to further clarify the critical periods in development where cochlear status may be most susceptible to PCBs.Methods: A total of 351 children from a birth cohort in eastern Slovakia underwent otoacoustic testing at 45 months of age. Maternal pregnancy, cord, and child 6-, 16-, and 45-month blood samples were collected and analyzed for PCB concentrations. At 45 months of age, DPOAEs were assessed at 11 frequencies in both ears. Multivariate, generalized linear models were used to estimate the associations between PCB concentrations at different ages and DPOAEs, adjusting for potential confounders.Results: Maternal and cord PCB-153 concentrations were not associated with DPOAEs at 45 months. Higher postnatal PCB concentrations at 6-, 16-, and 45-months of age were associated with lower (poorer) DPOAE amplitudes. When all postnatal PCB exposures were considered as an area-under-the-curve metric, an increase in PCB-153 concentration from the 25th to the 75th percentile was associated with a 1.6-dB SPL (sound pressure level) decrease in DPOAE amplitude (95% CI: –2.6, –0.5; p = 0.003).Conclusions: In this study, postnatal rather than maternal or cord PCB concentrations were associated with poorer performance on otoacoustic tests at age 45 months.Citation: Jusko TA, Sisto R, Iosif AM, Moleti A, Wimmerová S, Lancz K, Tihányi J, Šovčíková E, Drobná B, Palkovičová L, Jurečková D, Thevenet-Morrison K, Verner MA, Sonneborn D, Hertz-Picciotto I, Trnovec T. 2014. Prenatal and postnatal serum PCB concentrations and cochlear function in children at 45 months of age. Environ Health Perspect 122:1246–1252; http://dx.doi.org/10.1289/ehp.1307473