Biochemical, biomechanical and imaging biomarkers of ischemic stroke: Time for integrative thinking.

Stroke is one of the leading causes of adult disability affecting millions of people worldwide. Post-stroke cognitive and motor impairments diminish quality of life and functional independence. There is an increased risk of having a second stroke and developing secondary conditions with long-term social and economic impacts. With increasing number of stroke incidents, shortage of medical professionals and limited budgets, health services are struggling to provide a care that can break the vicious cycle of stroke. Effective post-stroke recovery hinges on holistic, integrative and personalized care starting from improved diagnosis and treatment in clinics to continuous rehabilitation and support in the community. To improve stroke care pathways, there have been growing efforts in discovering biomarkers that can provide valuable insights into the neural, physiological and biomechanical consequences of stroke and how patients respond to new interventions. In this review paper, we aim to summarize recent biomarker discovery research focusing on three modalities (brain imaging, blood sampling and gait assessments), look at some established and forthcoming biomarkers, and discuss their usefulness and complementarity within the context of comprehensive stroke care. We also emphasize the importance of biomarker guided personalized interventions to enhance stroke treatment and post-stroke recovery.

Portal Vein Pull-Through Technique and Thrombectomy for Extensive Portal Vein Thrombosis.

BACKGROUND: Herein, a different technique is presented describing complete dissection of the entire portal vein (PV), superior mesenteric vein (SMV), and splenic vein, thus enabling a complete thrombectomy without the risk of uncontrolled hemorrhage due to blind thrombectomy. METHODS: In cases where a thrombectomy would not be an option because of extensive thrombosis involving the confluence of the PV and SMV, small branches of the SMV, including the inferior mesenteric vein, were divided. Both the SMV and splenic vein were encircled separately. Then, the side branches of the PV above the pancreas, left gastric vein on the left side, and superior pancreatoduodenal vein on the right side were divided. The lateral and posterior part of the PV were dissected within the pancreas both from above and below, allowing the main PV completely free from attachments. At this point, the splenic vein and SMV were clamped, and the main PV was divided above the pancreas and then pulled back through the pancreatic tunnel. The thrombus was easily dissected of the vein under direct visualization, and afterward the PV was redirected to its original position. Then, the liver transplant was carried out in a regular fashion. RESULTS: This technique was applied to 2 patients. The first was a 43-year-old man who underwent a right lobe living donor liver transplant because of hepatitis B virus-related cirrhosis. The patient is still alive and well with stable liver function after 15 years of follow-up. The second was a 69-year-old woman who underwent a right lobe living donor liver transplant because of hepatitis C virus and hepatocellular carcinoma. She survived the procedure and her liver function was entirely normal afterward. She died of pneumonia and sepsis 5 months after transplant. CONCLUSIONS: This technique enables complete dissection of the entire PV, SMV, and splenic vein. Thus, complete thrombectomy under direct visualization without the risk of uncontrolled hemorrhage can be performed.

Prophylactic Cerclage Cabling Decreases the Intraoperative Periprosthetic Fracture Rate during Cement-Less Total Hip Arthroplasty in Patients with Severe Developmental Hip Dysplasia.

PURPOSE OF THE STUDY Cementless stems in highly dysplastic hips are considered to increase the risk of femoral fracture and associated morbidity. Several authors speculated to use prophylactic cabling in this patient group to prevent intraoperative fractures. This study aims to reveal objective results regarding the perioperative complications in a large and consecutive patient group with respect to use of prophylactic cabling. MATERIAL AND METHODS A retrospective comparative study was planned. A total of 122 consecutive patients with dysplastic hips of Crowe type 3 or 4, operated on with total hip arthroplasty (THA) and shortening osteotomy using a rectangular femoral stem were included. Patients were stratified according to use of a diaphyseal prophylactic cerclage cable. Perioperative complications were recorded. Clinical outcome was measured in terms of Harris Hip Score and Visual Analog Scale (VAS) for pain. All results were compared between the groups. RESULTS The mean follow-up time was 27 months. Two (2%) versus five (14%) patients had a fracture at the diaphyseal level in cabled versus non-cabled groups. Difference between groups was statistically significant (p=0.01). Relative risk of fracture in case of a non-cabling was 5.8 (p=0.03). Eleven (9%) patients had a non-displaced fracture at the metaphyseal level. No significant differences were detected with respect to preoperative clinical outcome scores or change in these scores between groups. CONCLUSIONS Femoral diaphyseal fracture rates are low when cementless, rectangular stems are used in dysplastic high riding hips. Prophylactic cerclage cabling further decreases the fracture risk and eases treatment in case of a fracture without causing additional complications and therefore is recommended. Key words: intraoperative fracture, periprosthetic fracture, total hip arthroplasty, cerclage cabling, developmental hip dysplasia, transverse shortening osteotomy.

Intraoperative testing of passive and active state mechanics of spastic semitendinosus in conditions involving intermuscular mechanical interactions and gait relevant joint positions.

In cerebral palsy (CP) patients suffering pathological knee joint motion, spastic muscle's passive state forces have not been quantified intraoperatively. Besides, assessment of spastic muscle's active state forces in conditions involving intermuscular mechanical interactions and gait relevant joint positions is lacking. Therefore, the source of flexor forces limiting joint motion remains unclear. The aim was to test the following hypotheses: (i) in both passive and active states, spastic semitendinosus (ST) per se shows its highest forces within gait relevant knee angle (KA) range and (ii) due to intermuscular mechanical interactions, the active state forces elevate. Isometric forces (seven children with CP, GMFCS-II) were measured during surgery over a range of KA from flexion to full extension, at hip angle (HA) = 45° and 20°, in four conditions: (I) passive state, (II) individual stimulation of the ST, simultaneous stimulation of the ST (III) with its synergists, and (IV) also with an antagonist. Gait analyses: intraoperative data for KA = 17-61° (HA = 45°) and KA = 0-33° (HA = 20°) represent the loading response and terminal swing, and mid/terminal stance phases of gait, respectively. Intraoperative tests: Passive forces maximally approximated half of peak force in condition II (HA = 45°). Added muscle activations did increase muscle forces significantly (HA = 45°: on average by 42.0% and 72.5%; HA = 20°: maximally by 131.8% and 123.7%, respectively in conditions III and IV, p < 0.01). In conclusion, intermuscular mechanical interactions yield elevated active state forces, which are well above passive state forces. This indicates that intermuscular mechanical interactions may be a source of high flexor forces in CP.

Intraoperative experiments combined with gait analyses indicate that active state rather than passive dominates the spastic gracilis muscle's joint movement limiting effect in cerebral palsy.

BACKGROUND: In cerebral palsy, spastic muscle's passive forces are considered to be high but have not been assessed directly. Although activated spastic muscle's force-joint angle relations were studied, this was independent of gait relevant joint positions. The aim was to test the following hypotheses intraoperatively: (i) spastic gracilis passive forces are high even in flexed knee positions, (ii) its active state forces attain high amplitudes within the gait relevant knee angle range, and (iii) increase with added activations of other muscles. METHODS: Isometric forces (seven children with cerebral palsy, gross motor function classification score = II) were measured during surgery from knee flexion to full extension, at hip angles of 45° and 20° and in four conditions: (I) passive state, after gracilis was stimulated (II) alone, (III) simultaneously with its synergists, and (IV) also with an antagonist. FINDINGS: Directly measured peak passive force of spastic gracilis was only a certain fraction of the peak active state forces (maximally 26%) measured in condition II. Conditions III and IV caused gracilis forces to increase (for hip angle = 45°, by 32.8% and 71.9%, and for hip angle = 20°, by 24.5% and 45.1%, respectively). Gait analyses indicated that intraoperative data for knee angles 61-17° and 33-0° (for hip angles 45° and 20°, respectively) are particularly relevant, where active state force approximates its peak values. INTERPRETATION: Active state muscular mechanics, rather than passive, of spastic gracilis present a capacity to limit joint movement. The findings can be highly relevant for diagnosis and orthopaedic surgery in individuals with cerebral palsy.

Live donor liver transplantation for type 1 tyrosinemia: An analysis of 15 patients.

Type 1 tyrosinemia is a rare metabolic disorder of the tyrosine degradation pathway. Due to the rarity of the disease, the best evidence literature offers is limited to guidelines based on expert opinions and optimal treatment is still a debate. LT serves as a definitive treatment of the defective metabolic pathway in the liver along with other serious disease manifestations such as LF and HCC. Nitisinone is a relatively new agent that is currently recommended for the medical management of the disease. Its mechanism of action is well understood, and efficacy is well established when started presymptomatically. This study aims to evaluate outcomes of 15 patients with type 1 tyrosinemia who underwent LT in nitisinone era and discuss its effect on prevention of HCC. A LT database of 1037 patients was reviewed. Data from 15 patients with type 1 tyrosinemia were retrospectively analyzed. All the patients except one were treated with nitisinone prior to LT. Most common indications for LT were LF and suspicious nodules. Seven patients had HCC. Mortality rate was 20% (n = 3). Nitisinone treatment has opened new horizons in the management of type 1 tyrosinemia, but LT still remains the only option for the patients developing LF and in the event of HCC. Neonatal screening programs utilizing blood succinyl acetone as the marker should be encouraged especially in the countries, such as Turkey, with high prevalence of consanguineous marriages.

Prognostic Value of Metastatic Lymph Node Ratio in Pancreatic Cancer.

Lymph node involvement in pancreatic adenocancer is one of the strongest predictors of prognosis. However, the extent of lymph node dissection is still a matter of debate and number of dissected nodes varies widely among patients. In order to homogenize this diverse group of patients and more accurately predict their prognosis, we aimed to analyze the effect of metastatic lymph node ratio as an independent prognostic factor. We retrospectively analyzed medical recordings of 326 patients with pancreatic cancer who were treated in a tertiary medical oncology center over a 10-year period. Both in univariate and multivariate analyses, metastatic lymph node ratio proved to be a strong predictor of prognosis which was unaffected from heterogeneity of our patient population and can be used to facilitate predict prognosis of patients who underwent lymph node dissection to various extents and with future studies it can emerge as a successful tool for creating prognostic subgroups of the disease.

Effects of inter-synergistic mechanical interactions on the mechanical behaviour of activated spastic semitendinosus muscle of patients with cerebral palsy.

Previous physiological experiments and finite element modelling indicate that inter-synergistic epimuscular myofascial force transmission (EMFT) between co-activated muscles has a potential to affect healthy muscle's contribution to joint moment and joint range of movement. This is quite relevant for patients with cerebral palsy (CP) since, amplitude of spastic muscle's force and the joint range of force exertion are central to the joint movement limitation. Stiffness of activated spastic muscle is also a determinant for pathological joint movement. However, assessments of effects of inter-synergistic EMFT on the mechanical behaviour of spastic muscle are lacking. Those assessments require measurement during surgery of activated spastic muscle's forces directly at its tendon and as a function of joint angle. Employing this methodology, the aim was to test the following study hypotheses: added activation of semimembranosus (SM) and gracilis (GRA) muscles of patients with CP changes (1) force, (2) stiffness and (3) joint range of force exertion of activated spastic semitendinosus (ST) due to inter-synergistic EMFT. Isometric spastic ST forces were measured intraoperatively (12 limbs of 7 patients (mean age 8 years 9 months) for knee angles from flexion (120°) to full extension (0°). Conditions I and II: spastic ST was activated alone, and simultaneously with its synergists SM and GRA muscles, respectively. Condition II did increase activated spastic ST's forces significantly (by 33.3%), but did not change its stiffness and joint range of force exertion, confirming only study hypothesis 1. Therefore, we conclude that inter-synergistic EMFT affects forces exerted at spastic ST tendon, but not other characteristics of its angle-force relationship.

Intra-operatively measured spastic semimembranosus forces of children with cerebral palsy.

The knee kept forcibly in a flexed position is typical in cerebral palsy. Using a benchmark, we investigate intra-operatively if peak spastic hamstring force is measured in flexed knee positions. This tests the assumed shift of optimal length due to adaptation of spastic muscle and a decreasing force trend towards extension. Previously we measured spastic gracilis (GRA) and semitendinosus (ST) forces. Presently, we studied spastic semimembranosus (SM) and tested the following hypotheses: spastic SM forces are (1) high in flexed and (2) low in extended positions. We compared the data to those of GRA and ST to test (3) if percentages of peak force produced in flexed positions are different. During muscle lengthening surgery of 8 CP patients (9years, 4months; GMFCS levels=II-IV; limbs tested=13) isometric SM forces were measured from flexion (120°) to full extension (0°). Spastic SM forces were low in flexed knee positions (only 4.2% (3.4%) and 10.7% (9.7%) of peak force at KA=120° and KA=90° respectively, indicating less force production compared to the GRA or ST) and high in extended knee positions (even 100% of peak force at KA=0°). This indicates an absence of strong evidence for a shift of optimal muscle length of SM towards flexion.

Intraoperative experiments show relevance of inter-antagonistic mechanical interaction for spastic muscle's contribution to joint movement disorder.

BACKGROUND: Recent intra-operative knee angle-muscle force data showed no abnormal muscular mechanics (i.e., a narrow joint range of muscle force exertion and peak muscle force availability at flexed joint positions), if the spastic gracilis muscle was stimulated alone. This can limit inter-muscular mechanical interactions, which have been shown to affect muscular mechanics substantially. We aimed at testing the hypothesis that the knee angle-muscle force curves of the spastic gracilis muscle activated simultaneously with a knee extensor are representative of joint movement disorder. METHODS: Experiments were performed during remedial surgery of spastic cerebral palsy patients (n=6, 10 limbs tested). Condition-I: muscle forces were measured in flexed knee positions (120° and 90°) after activating the gracilis exclusively. Condition-II: knee angle-muscle force data were measured from 120° to full extension after activating the vastus medialis, simultaneously. FINDINGS: Condition-II vs. I: Inter-antagonistic interaction did not consistently cause a gracilis force increase. Condition-II: Peak muscle force=mean 47.92 N (SD 22.08 N). Seven limbs showed availability of high muscle force in flexed knee positions (with minimally 84.8% of peak force at 120°). Knee angle-muscle force curves of four of them showed a local minimum followed by an increasing force (explained by an increasing passive force, indicating muscle lengths unfavorable for active force exertion). High active gracilis forces measured at flexed knee positions and narrow operational joint range of force exertion do indicate abnormality. The remainder of the limbs showed no such abnormality. INTERPRETATION: Our hypothesis is confirmed for most, but not all limbs tested. Therefore, tested inter-antagonistic mechanical interaction can certainly, but not exclusively be a factor for abnormal mechanics of the spastic muscle.

The relationship of insulin resistance and metabolic syndrome with known breast cancer prognostic factors in postmenopausal breast cancer patients.

PURPOSE: The aim of this study was to investigate the effect of metabolic syndrome and insulin resistance at the time of diagnosis on the known prognostic factors of breast cancer in postmenopausal breast cancer patients. METHODS: The study included 71 patients with a recent diagnosis of postmenopausal breast cancer, admitted at the Medical Oncology outpatient clinic of the Izmir Ataturk Training and Research Hospital between June 2010 and June 2011. We determined whether the patients had metabolic syndrome and insulin resistance at diagnosis, and recorded known prognostic factors, such as tumor size, axillary lymph node involvement, presence of distant metastasis, tumor grade, estrogen receptor (ER), progesterone receptor (PR), and CerbB-2 status. RESULTS: Among 71 patients, 25 (35%) had metabolic syndrome at the time of diagnosis, and 33 (46%) had insulin resistance with Homeostasis Model of Assessment-Insulin Resistance (HOMA-IR)>2.7. No statistically significant difference was found in the prognostic values of breast cancer, i.e. tumor size, axillary lymph node involvement, distant metastasis, tumor grade, ER, PR, and CerbB-2 status between the patients with and without metabolic syndrome. There was no statistically significant difference in the prognostic factors of breast cancer at the time of diagnosis between 33 patients with insulin resistance and 38 patients without insulin resistance. CONCLUSION: Several previous studies showed a negative relationship between metabolic syndrome and insulin resistance and prognostic factors of breast cancer in postmenopausal breast cancer patients. However, our study failed to show such a relationship. The relationship between metabolic syndrome and insulin resistance and postmenopausal breast cancer was not well demonstrated due to the small number of patients, unknown duration of the metabolic syndrome and insulin resistance, and shorter follow-up period. Further studies are required to demonstrate the effect of metabolic syndrome and insulin resistance on the prognosis of breast cancer, including larger number of patients and longer follow-up periods.

Muscle lengthening surgery causes differential acute mechanical effects in both targeted and non-targeted synergistic muscles.

Epimuscular myofascial force transmission (EMFT) is a major determinant of muscle force exerted, as well as length range of force exertion. Therefore, EMFT is of importance in remedial surgery performed, e.g., in spastic paresis. We aimed to test the following hypotheses: (1) muscle lengthening surgery (involving preparatory dissection (PD) and subsequent proximal aponeurotomy (AT)) affects the target muscle force exerted at its distal and proximal tendons differentially, (2) forces of non-operated synergistic muscles are affected as well, (3) PD causes some of these effects. In three conditions (control, post-PD, and post-AT exclusively on m. extensor digitorum longus (EDL)), forces exerted by rat anterior crural muscles were measured simultaneously. Our results confirm hypotheses (1-2), and hypothesis (3) in part: Reduction of EDL maximal force differed by location (i.e. 26.3% when tested distally and 44.5% when tested proximally). EDL length range of active force exertion increased only distally. Force reductions were shown also for non-operated tibialis anterior (by 11.9%), as well as for extensor hallucis longus (by 8.4%) muscles. In tibialis anterior only, part of the force reduction (4.9%) is attributable to PD. Due to EMFT, remedial surgery should be considered to have differential effects for targeted and non-targeted synergistic muscles.

The association of hematologic parameters on the prognosis of patients with metastatic renal cell carcinoma.

PURPOSE: Metastatic renal cell carcinoma (mRCC) bears a poor prognosis. We investigated the prognostic significance of some hematologic parameters of patients with mRCC. METHODS: We retrospectively reviewed the records of 53 patients with mRCC . The mean follow up time was 34 months (range 5-142).We assessed the prognostic value of hematologic parameters (leukocytes ,neutrophils, lymphocytes, platelets, neutrophil to lymphocyte ratio/NLR, platelet to lymphocyte ratio/PLR), and other clinical parameters with univariate and multivariate analysis. RESULTS: Memorial Sloan-Kettering Cancer Center (MSKCC) risk group , lung metastases, sunitinib treatment, lymphocyte count, NLR, and anemia significantly correlated with median overall survival (OS) on univariate analysis. The median OS in patients with a NLR < 3.4 was 32.2 months , significantly higher than the 13.9 months in patients with a ratio ≥ 3.4 (p = 0.006). Multivariate analysis revealed that MSKCC risk group and the NLR were independent predictors of OS. CONCLUSION: Hematologic parameters may be associated with OS in mRCC. However, further studies are needed to establish their routine use.

Effects of rosiglitazone on serum paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus

Human serum paraoxonase contributes to the anti-atherogenic effect of high-density lipoprotein cholesterol (HDL-C) and has been shown to protect both low-density lipoprotein cholesterol (LDL-C) and HDL-C against lipid peroxidation. We investigated the effects of rosiglitazone on paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus [50 patients (30 males, 20 females); mean±SD age: 58.7±9.2 years, body mass index: 28.2±4.1'kg/m2], in whom glucose control could not be achieved despite treatment with metformin, sulphonylurea, and/or insulin. The patients were given 4'mg/day rosiglitazone for 3 months in addition to their usual treatment. Serum paraoxonase activity, malondialdehyde, homocysteine, and lipid profile were measured at the time of initiation and at the end of therapy with rosiglitazone. After rosiglitazone therapy, serum levels of HDL-C, apolipoprotein A-1, and paraoxonase activity increased significantly (P<0.05) and malondialdehyde, homocysteine, lipoprotein(a), and glucose levels decreased significantly (P<0.05), but no significant changes in levels of total cholesterol and apolipoprotein B were observed. Triglyceride levels also increased significantly (P<0.05). Rosiglitazone treatment led to an improvement in glycemic control and to an increase in paraoxonase activity and HDL-C levels. Although rosiglitazone showed favorable effects on oxidant/antioxidant balance and lipid profile, further studies are needed to determine the effect of rosiglitazone on cardiovascular risk factors and cardiovascular morbidity and mortality.

Human spastic Gracilis muscle isometric forces measured intraoperatively as a function of knee angle show no abnormal muscular mechanics.

BACKGROUND: To show whether mechanics of activated spastic muscle are representative of the functional deficiencies clearly apparent in the joints, our goal was to test the following hypotheses: (1) The muscle's joint range of force exertion is narrow, and (2) high muscle forces are available at low muscle length. METHODS: During remedial surgery, we measured the forces of the Gracilis muscle of spastic cerebral palsy patients (n=7, 10 limbs tested) as a function of knee joint angle from flexion (120°) to full extension (0°). FINDINGS: The spastic Gracilis exerted non-zero forces for the entire knee angles studied. For four limbs, the peak force was exerted at the highest length. For the remainder limbs, the closest knee angle of peak force exertion to 120° was 66°. Maximally 79.1%, and for most limbs only a much lower percentage (minimally 22.4%) of peak Gracilis force (mean 41.59N (SD 41.76N)) was available at 120° knee flexion. Moreover, a clinical metric was obtained showing that the occurrence of a contracture was not correlated significantly with key determinants of knee angle-Gracilis force characteristics. INTERPRETATION: Our hypotheses are rejected: the spastic Gracilis has no narrow operational joint range of force exertion and no supreme active resistance capacity to stretch at low length. We conclude that if activated alone, spastic muscle shows no abnormal mechanics representative of joint movement disorder. Simultaneous stimulation of other muscles as in daily activities may change this situation.

In muscle lengthening surgery multiple aponeurotomy does not improve intended acute effects and may counter-indicate: an assessment by finite element modelling.

The goal was to assess the effects of multiple aponeurotomy on mechanics of muscle with extramuscular myofascial connections. Using finite element modelling, effects of combinations of the intervention carried out at a proximal (P), an intermediate (I) and a distal (D) location were studied: (1) Case P, (2) Case P-I, (3) Case P-D and (4) Case P-I-D. Compared to Case P, the effects of multiple interventions on muscle geometry and sarcomere lengths were sizable for the distal population of muscle fibres: e.g. at high muscle length (1) summed gap lengths between the cut ends of aponeurosis increased by 16, 25 and 27% for Cases P-I, P-D and P-I-D, respectively, (2) characteristic substantial sarcomere shortening became more pronounced (mean shortening was 26, 29, 30 and 31% for Cases P, P-I, P-D and P-I-D, respectively) and (3) fibre stresses decreased (mean stress equalled 0.49, 0.39, 0.38 and 0.33 for Cases P, P-I, P-D and P-I-D, respectively). In contrast, no appreciable effects were shown for the proximal population. The overall change in sarcomere length heterogeneity was limited. Consequently, the effects of multiple aponeurotomy on muscle length-force characteristics were marginal: (1) a limited reduction in active muscle force (maximal 'muscle weakening effect' remained between 5 and 11%) and (2) an even less pronounced change in slack to optimum length range of force exertion (maximal 'muscle lengthening effect' distally was 0.2% for Case P-I-D) were shown. The intended effects of the intervention were dominated by the one intervention carried out closer to the tendon suggesting that aponeurotomies done additionally to that may counter-indicated.

Toxigenic potential of Fusarium graminearum isolated from maize of northwest Argentina

Twenty six isolates of Fusarium graminearum from grains of maize hybrids harvested in ±west Argentina were grown on autoclaved rice grain to assess their ability to produce type B trichothecenes. Chemical analysis indicated that 38% of isolates were nivalenol (NIV) producers only, 31% were major NIV producers with high DON(deoxynivalenol)/NIV ratios, 8% were major DON producers with minor NIV production, and 23% were DON producers only. Isolates showed a high variability in their toxigenic potential which was not related to fungal biomass. The distribution of the different chemotypes as well as the high and the low trichothecene-producing Fusarium isolates could not be associated to a geographical origin. Our results confirmed for the first time that isolates of Fusarium graminearum from maize of northwest Argentina are able to produce DON and NIV. A substancial contamination with both NIV and DON is likely in maize from northwest Argentina. Their contents should be quantified in regional surveillances for mycotoxin contamination.

A novel nutritional supplement containing chromium picolinate, phosphatidylserine, docosahexaenoic acid, and boron activates the antioxidant pathway Nrf2/HO-1 and protects the brain against oxidative stress in high-fat-fed rats.

AIMS: A novel nutritional supplement complex (N21 #125) composed of four well-known compounds (chromium picolinate, phosphatidylserine, docosahexaenoic acid, and boron) was designed to improve memory function and maintain brain health. The present study evaluated the complex's potential mechanism of action and its role in reducing oxidative stress in the brain of obese rats fed a high-fat diet (HFD). METHODS: Male Wistar rats (n = 40, 8-week-old) were divided into four groups. Group I was fed a standard diet; Group II was fed a standard diet and supplemented with N21 } Group III was fed an HFD; and Group IV was fed an HFD and supplemented with N21 #125 for 12 weeks. RESULTS: Rats fed HFD had greater serum C-reactive protein (CRP) and tumor necrosis factor alpha (TNF-α) and brain malondialdehyde (MDA) concentrations than rats fed the control diet. Supplementation of N21 #125 decreased CRP, TNF-α, and MDA concentration in rats fed HFD. The levels of brain nuclear factor-E2-related factor-2 (Nrf2), heme oxygenase, extracellular signal-regulated kinases and protein kinase B were lower in rats fed the control diet than for rats fed the HFD. These parameters were increased by supplementation of N21 #125. DISCUSSION: The data indicate that N21 #125 protected the brain from oxidative damage and inflammation induced by the HFD. This effect may be through up-regulation of the transcription factor Nrf2 expression.

Digitally adjusting chromogenic dye proportions in brightfield microscopy images.

We present an algorithm to adjust the contrast of individual dyes from colour (red-green-blue) images of dye mixtures. Our technique is based on first decomposing the colour image into individual dye components, then adjusting each of the dye components and finally mixing the individual dyes to generate colour images. Specifically in this paper, we digitally adjust the staining proportions of hematoxylin and eosin (H&E) chromogenic dyes in tissue images. We formulate the physical dye absorption process as a non-negative mixing equation, and solve the individual components using non-negative matrix factorisation (NMF). Our NMF formulation includes camera dark current in addition to the mixing proportions and the individual H and E components. The novelty of our approach is to adjust the dye proportions while preserving the color of nonlinear dye interactions, such as pigments and red blood cells. In this paper we present results for only H&E images, our technique can easily be extended to other staining techniques.