Assessment of short-term effect of platelet-rich plasma treatment of tendinosis using texture analysis of ultrasound images.

BACKGROUND: Computer-aided diagnosis (i.e., texture analyses) tools are becoming increasingly beneficial methods to monitor subtle tissue changes. The aim of this pilot study was to investigate short-term effect of platelet rich plasma (PRP) treatment in supraspinatus and common extensor of the forearm tendinosis by using texture analysis of ultrasound (US) images as well as by clinical questionnaires. PATIENTS AND METHODS: Thirteen patients (7 male and 6 female, age 36-60 years, mean age 51.2 ± 5.2) were followed after US guided PRP treatment for tendinosis of two tendons (9 patients with lateral epicondylitis and 4 with supraspinatus tendinosis). Clinical and US assessment was performed prior to as well as 3 months after PRP treatment with validated clinical questionnaires. Tissue response in tendons was assessed by using gray level run length matrix method (GLRLM) of US images. RESULTS: All patients improved of tendinosis symptoms after PRP treatment according to clinical questionnaires. Almost all GLRLM features were statistically improved 3 months after PRP treatment. GLRLM-long run high gray level emphasis (LRLGLE) revealed the best moderate positive and statistically significant correlation after PRP (r = 0.4373, p = 0.0255), followed by GLRLM-low gray level run emphasis (LGLRE) (r = 0.3877, p = 0.05). CONCLUSIONS: Texture analysis of tendinosis US images was a useful quantitative method for the assessment of tendon remodeling after minimally invasive PRP treatment. GLRLM features have the potential to become useful imaging biomarkers to monitor spatial and time limited tissue response after PRP, however larger studies with similar protocols are needed.

Therapeutic Dosage of Antipsychotic Drug Aripiprazole Induces Persistent Mitochondrial Hyperpolarisation, Moderate Oxidative Stress in Liver Cells, and Haemolysis.

Aripiprazole has fewer metabolic side effects than other antipsychotics; however, there are some severe ones in the liver, leading to drug-induced liver injury. Repeated treatment with aripiprazole affects cell division. Since this process requires a lot of energy, we decided to investigate the impact of aripiprazole on rat liver cells and mitochondria as the main source of cellular energy production by measuring the mitochondrial membrane potential, respiration, adenosine triphosphate (ATP) production, oxidative stress, antioxidative response, and human blood haemolysis. Here, we report that mitochondrial hyperpolarisation from aripiprazole treatment is accompanied by higher reactive oxygen species (ROS) production and increased antioxidative response. Lower mitochondrial and increased glycolytic ATP synthesis demand more glucose through glycolysis for equal ATP production and may change the partition between the glycolysis and pentose phosphate pathway in the liver. The uniform low amounts of the haemolysis of erythrocytes in the presence of aripiprazole in 25 individuals indicate lower quantities of the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH+H+), which is in accordance with a decreased activity of glucose 6-phosphate dehydrogenase and the lower dehydrogenase activity upon aripiprazole treatment. The lower activity of glucose 6-phosphate dehydrogenase supports a shift to glycolysis, thus rescuing the decreased mitochondrial ATP synthesis. The putative reduction in NADPH+H+ did not seem to affect the oxidised-to-reduced glutathione ratio, as it remained equal to that in the untreated cells. The effect of aripiprazole on glutathione reduction is likely through direct binding, thus reducing its total amount. As a consequence, the low haemolysis of human erythrocytes was observed. Aripiprazole causes moderate perturbations in metabolism, possibly with one defect rescuing the other. The result of the increased antioxidant enzyme activity upon treatment with aripiprazole is increased resilience to oxidative stress, which makes it an effective drug for schizophrenia in which oxidative stress is constantly present because of disease and treatment.

Does intervention with GLP-1 receptor agonist semaglutide modulate perception of sweet taste in women with obesity: study protocol of a randomized, single-blinded, placebo-controlled clinical trial.

BACKGROUND: Preclinical studies demonstrated that glucagon-like peptide 1 (GLP-1) is locally synthesized in taste bud cells and that GLP-1 receptor exists on the gustatory nerves in close proximity to GLP-1-containing taste bud cells. This local paracrine GLP-1 signalling seems to be specifically involved in the perception of sweets. However, the role of GLP-1 in taste perception remains largely unaddressed in clinical studies. Whether any weight-reducing effects of GLP-1 receptor agonists are mediated through the modulation of taste perception is currently unknown. METHODS AND ANALYSIS: This is an investigator-initiated, randomized single-blind, placebo-controlled clinical trial. We will enrol 30 women with obesity and polycystic ovary syndrome (PCOS). Participants will be randomized in a 1:1 ratio to either semaglutide 1.0 mg or placebo for 16 weeks. The primary endpoints are alteration of transcriptomic profile of tongue tissue as changes in expression level from baseline to follow-up after 16 weeks of treatment, measured by RNA sequencing, and change in taste sensitivity as detected by chemical gustometry. Secondary endpoints include change in neural response to visual food cues and to sweet-tasting substances as assessed by functional MRI, change in body weight, change in fat mass and change in eating behaviour and food intake. DISCUSSION: This is the first study to investigate the role of semaglutide on taste perception, along with a neural response to visual food cues in reward processing regions. The study may identify the tongue and the taste perception as a novel target for GLP-1 receptor agonists. ETHICS AND DISSEMINATIONS: The study has been approved by the Slovene National Medical Ethics Committee and will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. Results will be submitted for publication in an international peer-reviewed scientific journal. TRIAL REGISTRATION: ClinicalTrials.gov NCT04263415 . Retrospectively registered on 10 February 2020.

Semaglutide reduces fat accumulation in the tongue: A randomized single-blind, pilot study.

AIM: We evaluated the effect of the latest GLP-1 RA semaglutide on tongue fat storage in obese women. DESIGN: We conducted a randomized single-blind, pilot study. METHODS: Twenty-five obese women with polycystic ovary syndrome (PCOS) (33.7 ± 5.3 years, body mass index (BMI) 36.1 ± 3.9 kg/m2, mean ± SD) were randomized to semaglutide 1.0 mg or placebo for 16 weeks. We quantified tongue volume and its fat tissue and fat proportion by magnetic resonance imaging. RESULTS: Tongue fat tissue and fat proportion significantly reduced after semaglutide vs placebo (-1.94 ± 5.51 vs. + 3.12 ± 4.87 cm3, p = 0.022, and -0.02 ± 0.07 vs. 0.04 ± 0.06, p = 0.010, respectively). Correlation analysis revealed that these reductions were associated with those in body weight, BMI and waist circumference (p = 0.010 for all). CONCLUSIONS: This is the first study confirming the beneficial effect of semaglutide on tongue structure in obese women with PCOS. Further studies are needed to assess the clinical importance of such findings.

Review article: Structural brain alterations in prelingually deaf.

Functional studies show that our brain has a remarkable ability to reorganize itself in the absence of one or more sensory modalities. In this review, we gathered all the available articles investigating structural alterations in congenitally deaf subjects. Some concentrated only on specific regions of interest (e.g., auditory areas), while others examined the whole brain. The majority of structural alterations were observed in the auditory white matter and were more pronounced in the right hemisphere. A decreased white matter volume or fractional anisotropy in the auditory areas were the most common findings in congenitally deaf subjects. Only a few studies observed alterations in the auditory grey matter. Preservation of the grey matter might be due to the cross-modal plasticity as well as due to the lack of sensitivity of methods used for microstructural alterations of grey matter. Structural alterations were also observed in the frontal, visual, and other cerebral regions as well as in the cerebellum. The observed structural brain alterations in the deaf can probably be attributed mainly to the cross-modal plasticity in the absence of sound input and use of sign instead of spoken language.

Acute Hyperglycemia and Spatial Working Memory in Adolescents With Type 1 Diabetes.

OBJECTIVE: To investigate the effect of acute hyperglycemia on brain function in adolescents with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: Twenty participants with T1D (aged 14.64 ± 1.78 years) and 20 age-matched healthy control subjects (aged 14.40 ± 2.82 years) performed two functional MRI sessions. Participants with T1D performed the first scanning session under euglycemic and the second under hyperglycemic clamp (20 mmol/L [360 mg/dL]). RESULTS: Lower spatial working memory (sWM) capacity during acute hyperglycemia and significant differences in activation of regions of interest during different stages of the sWM task (P = 0.014) were observed. CONCLUSIONS: Acute hyperglycemia negatively affected sWM capacity in adolescents with T1D, which is relevant for daily functioning and academic performance.

Semi-Automatic Signature-Based Segmentation Method for Quantification of Neuromelanin in Substantia Nigra.

In Parkinson's disease (PD), there is a reduction of neuromelanin (NM) in the substantia nigra (SN). Manual quantification of the NM volume in the SN is unpractical and time-consuming; therefore, we aimed to quantify NM in the SN with a novel semi-automatic segmentation method. Twenty patients with PD and twelve healthy subjects (HC) were included in this study. T1-weighted spectral pre-saturation with inversion recovery (SPIR) images were acquired on a 3T scanner. Manual and semi-automatic atlas-free local statistics signature-based segmentations measured the surface and volume of SN, respectively. Midbrain volume (MV) was calculated to normalize the data. Receiver operating characteristic (ROC) analysis was performed to determine the sensitivity and specificity of both methods. PD patients had significantly lower SN mean surface (37.7 ± 8.0 vs. 56.9 ± 6.6 mm2) and volume (235.1 ± 45.4 vs. 382.9 ± 100.5 mm3) than HC. After normalization with MV, the difference remained significant. For surface, sensitivity and specificity were 91.7 and 95 percent, respectively. For volume, sensitivity and specificity were 91.7 and 90 percent, respectively. Manual and semi-automatic segmentation methods of the SN reliably distinguished between PD patients and HC. ROC analysis shows the high sensitivity and specificity of both methods.

Effects of NH4CL application and removal on astrocytes and endothelial cells.

BACKGROUND: Hepatic encephalopathy (HE) is a complex disorder associated with increased ammonia levels in the brain. Although astrocytes are believed to be the principal cells affected in hyperammonemia (HA), endothelial cells (ECs) may also play an important role by contributing to the vasogenic effect of HA. METHODS: Following acute application and removal of NH4Cl on astrocytes and endothelial cells, we analyzed pH changes, using fluorescence imaging with BCECF/AM, and changes in intracellular Ca2+ concentration ([Ca2+]i), employing fluorescence imaging with Fura-2/AM. Using confocal microscopy, changes in cell volume were observed accompanied by changes of [Ca2+]i in astrocytes and ECs. RESULTS: Exposure of astrocytes and ECs to 1 - 20 mM NH4Cl resulted in rapid concentration-dependent alkalinization of cytoplasm followed by slow recovery. Removal of the NH4Cl led to rapid concentration-dependent acidification, again followed by slow recovery. Following the application of NH4Cl, a transient, concentration-dependent rise in [Ca2+]i in astrocytes was observed. This was due to the release of Ca2+ from intracellular stores, since the response was abolished by emptying intracellular stores with thapsigargin and ATP, and was still present in the Ca2+-free bathing solution. The removal of NH4Cl also led to a transient concentration-dependent rise in [Ca2+]i that resulted from Ca2+ release from cytoplasmic proteins, since removing Ca2+ from the bathing solution and emptying intracellular Ca2+ stores did not eliminate the rise. Similar results were obtained from experiments on ECs. Following acute application and removal of NH4Cl no significant changes in astrocyte volume were detected; however, an increase of EC volume was observed after the administration of NH4Cl, and EC shrinkage was demonstrated after the acute removal of NH4Cl. CONCLUSIONS: This study reveals new data which may give a more complete insight into the mechanism of development and treatment of HE.

Structural alterations of brain grey and white matter in early deaf adults.

Functional and structural brain alterations in the absence of the auditory input have been described, but the observed structural brain changes in the deaf are not uniform. Some of the previous researchers focused only on the auditory areas, while others investigated the whole brain or other selected regions of interest. Majority of studies revealed decreased white matter (WM) volume or altered WM microstructure and preserved grey matter (GM) structure of the auditory areas in the deaf. However, preserved WM and increased or decreased GM volume of the auditory areas in the deaf have also been reported. Several structural alterations in the deaf were found also outside the auditory areas, but these regions differ between the studies. The observed differences between the studies could be due to the use of different single-analysis techniques, or the diverse population sample and its size, or possibly due to the usage of hearing aids by some participating deaf subjects. To overcome the aforementioned limitations four different image-processing techniques were used to investigate changes in the brain morphology of prelingually deaf adults who have never used hearing aids. GM and WM volume of the Heschl's gyrus (HG) were measured using manual volumetry, while whole brain GM volume, thickness and surface area were assessed by voxel-based morphometry (VBM) and surface-based analysis. The microstructural properties of the WM were evaluated by diffusion tensor imaging (DTI). The data were compared between 14 congenitally deaf adults and 14 sex- and age-matched normal hearing controls. Manual volumetry revealed preserved GM volume of the bilateral HG and significantly decreased WM volume of the left HG in the deaf. VBM showed increased cerebellar GM volume in the deaf, while no statistically significant differences were observed in the GM thickness or surface area between the groups. The results of the DTI analysis showed WM microstructural alterations between the groups in the bilateral auditory areas, including the superior temporal gyrus, the HG, the planum temporale and the planum polare, which were more extensive in the right hemisphere. Fractional anisotropy (FA) was significantly reduced in the right and axial diffusivity (AD) in the left auditory areas in the deaf. FA and AD were significantly reduced also in several other brain areas outside the auditory cortex in the deaf. The use of four different methods used in our study, although showing changes that are not directly related, provides additional information and supports the conclusion that in prelingually deaf subjects structural alterations are present both in the auditory areas and elsewhere. Our results support the findings of those studies showing that early deafness results in decreased WM volume and microstructural WM alterations in the auditory areas. As we observed WM microstructural alteration also in several other areas and increased GM volume in the cerebellum in the deaf, we can conclude that early deafness results in widespread structural brain changes. These probably reflect atrophy or degradation as well as compensatory cross-modal reorganisation in the absence of the auditory input and the use of the sign language.

Magnetic resonance imaging for rapid screening for the nephrotoxic and hepatotoxic effects of microcystins.

In vivo visualization of kidney and liver damage by Magnetic Resonance Imaging (MRI) may offer an advantage when there is a need for a simple, non-invasive and rapid method for screening of the effects of potential nephrotoxic and hepatotoxic substances in chronic experiments. Here, we used MRI for monitoring chronic intoxication with microcystins (MCs) in rat. Male adult Wistar rats were treated every other day for eight months, either with MC-LR (10 µg/kg i.p.) or MC-YR (10 µg/kg i.p.). Control groups were treated with vehicle solutions. T1-weighted MR-images were acquired before and at the end of the eight months experimental period. Kidney injury induced by the MCs presented with the increased intensity of T1-weighted MR-signal of the kidneys and liver as compared to these organs from the control animals treated for eight months, either with the vehicle solution or with saline. The intensification of the T1-weighted MR-signal correlated with the increased volume density of heavily injured tubuli (R2 = 0.77), with heavily damaged glomeruli (R2 = 0.84) and with volume density of connective tissue (R2 = 0.72). The changes in the MR signal intensity probably reflect the presence of an abundant proteinaceous material within the dilated nephrons and proliferation of the connective tissue. T1-weighted MRI-is a valuable method for the in vivo screening of kidney and liver damage in rat models of intoxication with hepatotoxic and nephrotoxic agents, such as microcystins.

Segmentation priors from local image properties: without using bias field correction, location-based templates, or registration.

We present a novel approach for generating information about a voxel's tissue class membership based on its signature--a collection of local image textures estimated over a range of neighborhood sizes. The approach produces a form of tissue class priors that can be used to initialize and regularize image segmentation. The signature-based approach is a departure from current location-based methods, which derive tissue class likelihoods based on a voxel's location in standard template space. To use location-based priors, one needs to register the volume in question to the template space, and estimate the image intensity bias field. Two optimizations, over more than a thousand parameters, are needed when high order nonlinear registration is employed. In contrast, the signature-based approach is independent of volume orientation, voxel position, and largely insensitive to bias fields. For these reasons, the approach does not require the use of population derived templates. The prior information is generated from variations in image texture statistics as a function of spatial scale, and an SVM approach is used to associate signatures with tissue types. With the signature-based approach, optimization is needed only during the training phase for the parameter estimation stages of the SVM hyperplanes, and associated PDFs; a training process separate from the segmentation step. We found that signature-based priors were superior to location-based ones aligned under favorable conditions, and that signature-based priors result in improved segmentation when replacing location-based ones in FAST (Zhang et al., 2001), a widely used segmentation program. The software implementation of this work is freely available as part of AFNI http://afni.nimh.nih.gov.

Increased cognitive load during simple and complex motor tasks in acute stage after stroke.

UNLABELLED: The aim of this study was to assess the activation of primary motor cortex, prefrontal cortex and parietal cortex during simple and complex motor tasks performed with the hemiparetic and non-hemiparetic hand. METHODS: Seven patients after stroke in the left brain hemisphere were included in the study. Functional magnetic resonance imaging (fMRI) was performed in the first and third week, and in three patients also three months after the stroke. RESULTS: Performance of both the simple and the complex tasks with the hemiparetic or non-hemiparetic hand resulted in activations of the motor cortex, prefrontal cortex and parietal cortex in majority of the consecutive fMRI sessions. Three months after the stroke fMRI data revealed reduced activation of primary motor cortex and parietal cortex in the contralesional hemisphere during the performance of the simple task by the hemiparetic hand. During the complex task, the reduction of activation was less prominent. CONCLUSIONS: Results of the present study suggest that in mildly impaired stroke patients a bilateral activation of prefrontal and parietal cortex may participate in the recovery process from stroke. The potential for measurement of cortical rehabilitation is discussed.