Search results for: peripheral nerve blocking

Authors: Ferreira RC, Simons HZ, Thompson WS, Cutler AJ, Dopico XC, Smyth DJ, Mashar M, Schuilenburg H, Walker NM, Dunger DB, Wallace C, Todd JA, Wicker LS, Pekalski ML

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Type 1 diabetes is caused by autoimmune destruction of insulin-secreting beta cells in the pancreas. T cells are known to play an important role in this immune-mediated destruction; however, there is no general consensus regarding alterations in cytokine production or T cell subsets in peripheral blood of patients with type 1 diabetes. Using polychromatic flow cytometry of peripheral blood mononuclear cells (PBMCs), we assessed production of the proinflammatory cytokines IL-21, IFN-γ and IL-17 by memory CD4 T effector (Teff) cells in 69 patients with type 1 diabetes and 61 healthy donors. We found a 21.9% (95% CI 5.8, 40.2; p = 3.9 × 10(-3)) higher frequency of IL-21(+) CD45RA(-) memory CD4(+) Teffs in patients with type 1 diabetes (geometric mean 5.92% [95% CI 5.44, 6.44]) compared with healthy donors (geometric mean 4.88% [95% CI 4.33, 5.50]). In a separate cohort of 30 patients with type 1 diabetes and 32 healthy donors, we assessed the frequency of circulating T follicular helper (Tfh) cells in whole blood. Consistent with the increased production of IL-21, we also found a 14.9% increase in circulating Tfh cells in the patients with type 1 diabetes (95% CI 2.9, 26.9; p = 0.016). Analysis of IL-21 production by PBMCs from a subset of 46 of the 62 donors immunophenotyped for Tfh showed that frequency of Tfh cells was associated with the frequency of IL-21+ cells (r2 = 0.174, p = 0.004). These results indicate that increased IL-21 production is likely to be an aetiological factor in the pathogenesis of type 1 diabetes that could be considered as a potential therapeutic target.

Keywords: T follicular helper cell, IL-21, IL-17, type 1 diabetes

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Authors: Shujun Xie, Shirong Zhang, Shenglin Ma

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Background: Chronic inflammation might lead to many malignancies, and inadequate resolution could play a crucial role in tumor invasion, progression, and metastases. A randomised, double-blind, placebo-controlled trial shows that IL-1β inhibition with canakinumab could reduce incident lung cancer and lung cancer mortality in patients with atherosclerosis. The process and secretion of proinflammatory cytokine IL-1β are controlled by the inflammasome. Here we showed the correlation of the innate immune system and afatinib, a tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR) in non-small cell lung cancer. Methods: Murine Bone marrow derived macrophages (BMDMs), peritoneal macrophages (PMs) and THP-1 were used to check the effect of afatinib on the activation of NLRP3 inflammasome. The assembly of NLRP3 inflammasome was check by co-immunoprecipitation of NLRP3 and apoptosis-associated speck-like protein containing CARD (ASC), disuccinimidyl suberate (DSS)-cross link of ASC. Lipopolysaccharide (LPS)-induced sepsis and Alum-induced peritonitis were conducted to confirm that afatinib could inhibit the activation of NLRP3 in vivo. Peripheral blood mononuclear cells (PBMCs) from non-small cell lung cancer (NSCLC) patients before or after taking afatinib were used to check that afatinib inhibits inflammation in NSCLC therapy. Results: Our data showed that afatinib could inhibit the secretion of IL-1β in a dose-dependent manner in macrophage. Moreover, afatinib could inhibit the maturation of IL-1β and caspase-1 without affecting the precursors of IL-1β and caspase-1. Next, we found that afatinib could block the assembly of NLRP3 inflammasome and the ASC speck by blocking the interaction of the sensor protein NLRP3 and the adaptor protein ASC. We also found that afatinib was able to alleviate the LPS-induced sepsis in vivo. Conclusion: Our study found that afatinib could inhibit the activation of NLRP3 inflammasome in macrophage, providing new evidence that afatinib could target the innate immune system to control chronic inflammation. These investigations will provide significant experimental evidence in afatinib as therapeutic drug for non-small cell lung cancer or other tumors and NLRP3-related diseases and will explore new targets for afatinib.

Keywords: inflammasome, afatinib, inflammation, tyrosine kinase inhibitor

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Authors: Nazim Mir-Nasiri, Hudyjaya Siswoyo Jo

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The paper describes conceptual design, control strategies, and partial simulation for a new fully autonomous lower limb wearable exoskeleton system for human motion enhancement that can support its weight and increase strength and endurance. Various problems still remain to be solved where the most important is the creation of a power and cost efficient system that will allow an exoskeleton to operate for extended period without batteries being frequently recharged. The designed exoskeleton is enabling to decouple the weight/mass carrying function of the system from the forward motion function which reduces the power and size of propulsion motors and thus the overall weight, cost of the system. The decoupling takes place by blocking the motion at knee joint by placing passive air cylinder across the joint. The cylinder is actuated when the knee angle has reached the minimum allowed value to bend. The value of the minimum bending angle depends on usual walk style of the subject. The mechanism of the exoskeleton features a seat to rest the subject’s body weight at the moment of blocking the knee joint motion. The mechanical structure of each leg has six degrees of freedom: four at the hip, one at the knee, and one at the ankle. Exoskeleton legs are attached to subject legs by using flexible cuffs. The operation of all actuators depends on the amount of pressure felt by the feet pressure sensors and knee angle sensor. The sensor readings depend on actual posture of the subject and can be classified in three distinct cases: subject stands on one leg, subject stands still on both legs and subject stands on both legs but transit its weight from one leg to other. This exoskeleton is power efficient because electrical motors are smaller in size and did not participate in supporting the weight like in all other existing exoskeleton designs.

Keywords: energy efficient system, exoskeleton, motion enhancement, robotics

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Authors: Elham Azimzadeh, Saeedeh Sepehri, Hamidollah Hassanlouei

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Obesity is associated with postural instability, might influence the quality of daily life, and could be considered a potential factor for falling in obese people. The fat body mass especially in the abdominal area may increase body sway. Furthermore, loss of visual feedback may induce a larger postural sway in obese people. Moreover, Muscle fatigue may impair the work capacity of the skeletal muscle and may alter joint proprioception. So, the purpose of this study was to investigate the effect of physical fatigue and visual feedback on body sway and strength of lower extremities in obese people. 12 obese (4 female, 8 male; BMI >30 kg/m2), and 12 normal weight (4 female, 8 male; BMI: 20-25 kg/m2) subjects aged 37- 47 years participated in this study. The postural stability test on the Biodex balance system was used to characterize postural control along the anterior-posterior (AP) and mediolateral (ML) directions in eyes open and eyes closed conditions and maximal voluntary contraction (MVC) of knee extensors and flexors were measured before and after the high-intensity exhausting exercise protocol on the ergometer bike to confirm the presence of fatigue. Results indicated that the obese group demonstrated significantly greater body sway, in all indices (ML, AP, overall) compared with the normal weight group (eyes open). However, when visual feedback was eliminated, fatigue impaired the balance in the overall and AP indicators in both groups; ML sway was higher only in the obese group after exerting the fatigue in the eyes closed condition. Also, maximal voluntary contraction of knee extensors was impaired in the fatigued normal group but, there was no significant impairment in knee flexors MVC in both group. According to the findings, peripheral fatigue was associated with altered postural control in upright standing when eyes were closed, and that mechanoreceptors of the feet may be less able to estimate the position of the body COM over the base of support in the loss of visual feedback. This suggests that the overall capability of the postural control system during upright standing especially in the ML direction could be lower due to fatigue in obese individuals and could be a predictor of future falls.

Keywords: maximal voluntary contraction, obesity, peripheral fatigue, postural control, visual feedback

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Authors: Shubham Sharma, Sandra Barkauskaite, Brendan Duffy, Swarna Jaiswal, Amit K. Jaiswal

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Food packaging protects food from temperature, light, and humidity; preserves food and guarantees the safety and the integrity of the food. Advancement in packaging research leads to development of active packaging system with numerous properties such as oxygen scavengers, carbon-dioxide generating systems, antimicrobial active packaging, moisture control packaging, ethylene scavengers etc. In the active packaging, several additives such as essential oils, polyphenols etc. are incorporated into packaging film or within the packaging material to achieve the desired properties. This study investigates the effect on the structural, thermal and functional properties of different poly(lactide) – poly (butylene adipate-co-terephthalate) (PLA-PBAT) blend films incorporated with clove essential oil. The PLA-PBAT films were prepared by a solution casting method and then characterized based on their optical, mechanical properties, surface hydrophobicity, chemical composition, antimicrobial activity against S. aureus and E. coli, and inhibition of biofilm formation of E. coli. Results showed that, the developed packaging film containing clove oil has significant UV-blocking property (80%). However, incorporation of clove oil resulted in reduced transparency and tensile strength of the film as the concentration of clove oil increased. The surface hydrophobicity of packaging film was improved with the increasing concentration of essential oil. Similarly, thickness of the clove oil containing films increased from 36.71 µm to 106.67 µm as the concentration increases. The antimicrobial activity and biofilm inhibition study showed that the clove-incorporated PLA-PBAT composite film was effective against tested bacteria E. coli and S. aureus. This study showed that the PLA-PBAT – Clove oil composite film has significant antimicrobial and UV-blocking properties and can be used as an active food packaging film.

Keywords: active packaging, clove oil, poly(butylene adipate-co-terephthalate), poly(lactide)

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Authors: Saad Al-Shibli, Nasser Amjad, Muna Al Kubaisi, Norra Harun, Shaikh Mizan

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Leptin is a multifunctional hormone produced mainly by adipocyte. Leptin and its receptor have long been found associated with breast cancer. The main aim of this study is to investigate the correlation between Leptin/Leptin receptor and the clinicopathological features of breast cancer. Blood samples for ELISA, tissue samples from tumors and adjacent breast tissue were taken from 51 women with breast cancer with a control group of 40 women with a negative mammogram. Leptin and Leptin receptor in the tissues were estimated by immunohistochemistry (IHC). They were localized at the subcellular level by immunocytochemistry using transmission electron microscopy (TEM). Our results showed significant difference in serum leptin level between control and the patient group, but no difference between pre and post-operative serum leptin levels in the patient group. By IHC, we found that the majority of the breast cancer cells studied, stained positively for leptin and leptin receptors with co-expression of leptin and its receptors. No significant correlation was found between leptin/leptin receptors expression with the race, menopausal status, lymph node metastasis, estrogen receptor expression, progesterone receptor expression, HER2 expression and tumor size. Majority of the patients with distant metastasis were associated with high leptin and leptin receptor expression. TEM views both Leptin and Leptin receptor were found highly concentrated within and around the nucleus of the cancer breast cells, indicating nucleus is their principal seat of actions while the adjacent breast epithelial cells showed that leptin gold particles are scattered all over the cell with much less than that of the cancerous cells. However, presence of high concentration of leptin does not necessarily prove its over-expression, because it could be internalized from outside by leptin receptor in the cells. In contrast, leptin receptor is definitely over-expressed in the ductal breast cancer cells. We conclude that reducing leptin levels, blocking its downstream tissue specific signal transduction, and/or blocking the upstream leptin receptor pathway might help in prevention and therapy of breast cancer.

Keywords: breast cancer, expression, leptin, leptin receptors

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Authors: Emmanuel Kamal Aziz Saba, Hussein Al-Moghazy Sultan

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The aim of this study was to evaluate clinically and electro physiologically the autonomic nervous system changes associated with rheumatoid arthritis (RA). The present study included 25 patients with RA [22 women (88%)] and 30 apparently healthy control subjects [27 women (90%)]. A thorough clinical examination was carried out. Disease activity and functional disability were assessed. Tests for assessment of autonomic functions include active and passive orthostatic stress tests, and sympathetic skin response (SSR). The presence of abnormality in 2 tests or more was a clue for the presence of autonomic neuropathy (AN). Sural sensory nerve conduction study and posterior tibial motor nerve conduction study were done. There was a statistically significant decrease in standing systolic and diastolic blood pressure (BP) components of the active orthostatic stress test and SSR amplitude as well as statistically significant prolongation of SSR latency of RA patients when compared to control. Three patients (12%) had clinical symptoms suggestive of AN; increased to 14 patients (56 %) when orthostatic stress tests and SSR were utilized. There were no statistically significant differences between patients with different disease activity score 28 with 4 variables grades of RA activity and SSR latency and amplitude. There were no statistically significant differences between patients with different Stanford Health Assessment Questionnaire Disability Index grades of RA functional disability and SSR latency and amplitude. In conclusion, autonomic neuropathy is a common extra-articular manifestation of RA affecting sympathetic and parasympathetic fibers.

Keywords: autonomic neuropathy, orthostatic stress test, rheumatoid arthritis, sympathetic skin response

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Authors: Gabriel Cucato, Marilia Correia, Wagner Domingues, Aline Palmeira, Paulo Longano, Nelson Wolosker, Raphael Ritti-Dias

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Women with peripheral arterial disease (PAD) present lower walking capacity in comparison with men. However, whether cardiovascular regulation is also different between genders is unknown. Thus, the aim of this study was to compare walking capacity and cardiovascular regulation between men and women with PAD. A total of 23 women (66±7 yrs) and 31 men (64±9 yrs) were recruited. Patients performed a 6-minute test and the onset claudication distance and total walking distance were measured. Additionally, cardiovascular regulation was assessed by arterial stiffness (pulse wave velocity and augmentation index) and heart rate variability (frequency domain). Independent T test or Mann-Whitney U test were performed. In comparison with men, women present lower onset claudication distance (108±66m vs. 143±50m; P=0.032) and total walking distance (286±83m vs. 361±91 m, P=0.007). Regarding cardiovascular regulation, there were no differences in heart rate variability SDNN (72±160ms vs. 32±22ms, P=0.587); RMSSD (75±209 vs. 25±22ms, P=0.726); pNN50 (11±17ms vs. 8±14ms, P=0.836) in women and men, respectively. Moreover, there were no difference in augmentation index (39±10% vs. 34±11%, P=0.103); pulse pressure (59±17mmHg vs. 56±19mmHg, P=0.593) and pulse wave velocity (8.6±2.6m\s vs. 9.0±2.7m/s, P=0.580). In conclusion, women have impaired walking capacity compared to men. However, sex differences were not observed on cardiovascular regulation in patients with PAD.

Keywords: exercise, intermittent claudication, cardiovascular load, arterial stiffness

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Authors: Izuddin Fahmy Abu, Mohamad Haiqal Nizar Mohamad, Muhammad Fattah Fazel, Renu Agarwal, Igor Iezhitsa, Nor Salmah Bakar, Henrik Franzyk, Ian Mellor

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Glaucoma is the global leading cause of irreversible blindness. Currently, the available treatment strategy only involves lowering intraocular pressure (IOP); however, the condition often progresses despite lowered or normal IOP in some patients. N-methyl-D-aspartate receptor (NMDAR) excitotoxicity often occurs in neurodegeneration-related glaucoma; thus it is a relevant target to develop a therapy based on neuroprotection approach. This study investigated the effects of Philanthotoxin-343 (PhTX-343), an NMDAR antagonist, on the neuroprotection of NMDA-induced glaucoma to alleviate visual impairments. Male Sprague-Dawley rats were equally divided: Groups 1 (control) and 2 (glaucoma) were intravitreally injected with phosphate buffer saline (PBS) and NMDA (160nM), respectively, while group 3 was pre-treated with PhTX-343 (160nM) 24 hours prior to NMDA injection. Seven days post-treatments, rats were subjected to visual behavior assessments and subsequently euthanized to harvest their retina and optic nerve tissues for histological analysis and determination of nitrosative stress level using 3-nitrotyrosine ELISA. Visual behavior assessments via open field, object, and color recognition tests demonstrated poor visual performance in glaucoma rats indicated by high exploratory behavior. PhTX-343 pre-treatment appeared to preserve visual abilities as all test results were significantly improved (p < 0.05). H&E staining of the retina showed a marked reduction of ganglion cell layer thickness in the glaucoma group; in contrast, PhTX-343 significantly increased the number by 1.28-folds (p < 0.05). PhTX-343 also increased the number of cell nuclei/100μm2 within inner retina by 1.82-folds compared to the glaucoma group (p < 0.05). Toluidine blue staining of optic nerve tissues showed that PhTX-343 reduced the degeneration changes compared to the glaucoma group which exhibited vacuolation overall sections. PhTX-343 also decreased retinal 3- nitrotyrosine concentration by 1.74-folds compared to the glaucoma group (p < 0.05). All results in PhTX-343 group were comparable to control (p > 0.05). We conclude that PhTX-343 protects against NMDA-induced changes and visual impairments in the rat model by reducing nitrosative stress levels.

Keywords: excitotoxicity, glaucoma, nitrosative stress , NMDA receptor , N-methyl-D-aspartate , philanthotoxin, visual behaviour

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Authors: Sharjeel Abid, Tanveer Hussain, Ahsan Nazir, Abdul Zahir, Nabyl Khenoussi

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Localized application of drug has various advantages and fewer side effects as compared with other methods. Burn patients suffer from swear pain and the major aspects that are considered for burn victims include pain and infection management. Nano-fibers (NFs) loaded with drug, applied on local wound area, can solve these problems. Therefore, this study dealt with the fabrication of drug loaded NFs for better pain management. Two layers of NFs were fabricated with different drugs. Contact layer was loaded with Gabapentin (a nerve painkiller) and the second layer with acetaminophen. The fabricated dressing was characterized using scanning electron microscope, Fourier Transform Infrared Spectroscopy, X-Ray Diffraction and UV-Vis Spectroscopy. The double layered based NFs dressing was designed to have both initial burst release followed by slow release to cope with pain for two days. The fabricated nanofibers showed diameter < 300 nm. The liquid absorption capacity of the NFs was also checked to deal with the exudate. The fabricated double layered dressing with dual drug loading and release showed promising results that could be used for dealing pain in burn victims. It was observed that by the addition of drug, the size of nanofibers was reduced, on the other hand, the crystallinity %age was increased, and liquid absorption decreased. The combination of fast nerve pain killer release followed by slow release of non-steroidal anti-inflammatory drug could be a good tool to reduce pain in a more secure manner with fewer side effects.

Keywords: pain management, burn wounds, nano-fibers, controlled drug release

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Authors: Roya Vakili, Lekaa Elhajjmoussa, Barzin Omidi-Shal, Kim Blake

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Objective: The purpose of this case report is to highlight the successful treatment of a patient with Coloboma, Heart defect, Atresia choanae, Retarded growth and development, Genital hypoplasia, Ear anomalies/deafness, (CHARGE syndrome) using a vagal nerve stimulator (VNS). Background: This is the first documented case report, to the authors' best knowledge, for a patient with CHARGE syndrome, epilepsy, autism, and postural orthostatic tachycardia syndrome (POTS) that was successfully treated with an implanted VNS therapeutic device. Methodology: The study is a case report. Results: This is the case of a 24-year-old female patient with CHARGE syndrome (non-random association of anomalies Coloboma, Heart defect, Atresia choanae, Retarded growth and development, Genital hypoplasia, Ear anomalies/deafness) and several other comorbidities including refractory epilepsy, Patent Ductus Arteriosus (PDA) and POTS who had significant improvement of her symptoms after VNS implantation. She was a VNS candidate given her longstanding history of drug-resistant epilepsy and current disposition secondary to CHARGE syndrome. Prior to VNS implantation, she experienced three generalized seizures a year and daily POTS-related symptoms. She was having frequent lightheadedness and syncope spells due to a rapid heart rate and low blood pressure. The VNS device was set to detect a rapid heart rate and send appropriate stimulation anytime the heart rate exceeded 20% of the patient’s normal baseline. The VNS device demonstrated frequent elevated heart rates and concurrent VNS release every 8 minutes in addition to the programmed events. Following VNS installation, the patient became more active, alert, and communicative and was able to verbally communicate with words she was unable to say prior. Her GI symptoms also improved, as she was able to tolerate food better orally in addition to her G and J tube, likely another result of the vagal nerve stimulation. Additionally, the patient’s seizures and POTS-related cardiac events appeared to be well controlled. She had prolonged electroencephalogram (EEG) testing, showing no significant change in epileptiform activity. Improvements in the patient’s disposition are believed to be secondary to parasympathetic stimulation, adequate heart rate control, and GI stimulation, in addition to behavioral changes and other benefits via her implanted VNS. Conclusion: VNS showed promising results in improving the patient's quality of life and managing her diverse symptoms, including dysautonomia, POTs, gastrointestinal mobility, cognitive functioning as well seizure control.

Keywords: autism, POTs, CHARGE, VNS

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Authors: Allyson Augusta Shrikhande, Alexa Rains, Tayyaba Ahmed, Marjorie Mamsaang, Rakhi Vyas, Janaki Natarajan, Erika Moody, Christian Reutter, Kimberlee Leishear, Yogita Tailor, Sandra Sandhu-Restaino, Lora Liu, Neha James, Rosemarie Filart

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Characterized by consistent difficulty getting and keeping an erection firm enough for intercourse, Erectile Dysfunction may affect up to 15% of adult men. Although awareness and access to treatment have improved in recent years, many patients do not actively seek diagnosis or treatment due to the stigma surrounding this condition. Patients who do seek treatment are often dissatisfied by the efficacy of the medication. The condition inhibits patients’ quality of life by worsening mental health and relationships. The purpose of this study was to test the effectiveness of an outpatient neuromuscular treatment protocol in treating the symptoms of Chronic Pelvic Pain and Erectile Dysfunction, improving pain and function. 56 patients ages 20-79 presented to an outpatient clinic for treatment of pelvic pain and Erectile Dysfunction symptoms. These symptoms had persisted for an average of 4 years. All patients underwent external ultrasound-guided hydro-dissection technique targeted at pelvic peripheral nerves in combination with pelvic floor musculature trigger-point injections. To measure the effects of this treatment, a five question Erectile Dysfunction questionnaire was completed by each patient at their first visit to a clinic and three months after treatment began. Answers were summed for a total score of 5-25, with a higher score indicating optimal function. The average score before treatment was 14.125 (SD 5.411) (a=0.05; CI 12.708-15.542), which increased by 18% to an average of 16.625 (SD 6.423) (a=0.05; CI 14.943-18.307) after treatment (P=0.0004). Secondary outcome variables included a Visual Analogue Scale (VAS) to measure pelvic pain intensity and the Functional Pelvic Pain Scale (FPPS) to measure function across multiple areas. VAS scores reduced by 51% after three months. Before treatment, the mean VAS score was 5.87, and the posttreatment mean VAS score was 2.89. Pelvic pain functionality improved by 34% after three months. Pretreatment FPPS scores averaged at 7.48, decreasing to 4.91 after treatment. These results indicate that this unique treatment was very effective at relieving pain and increasing function for patients with Erectile Dysfunction.

Keywords: chronic pelvic pain, erectile dysfunction, nonsurgical, outpatient, trigger point injections

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Authors: A. Elmajdoub, A. El-Mahmoudy

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The present study was designed to investigate the neurotransmitters that mediate the excitatory response of the circular muscle of final branches of mesenteric artery in bovine calves. Mesentery was dissected and the iliac branches were separated and used. The final mesenteric branches of diameter 400 micrometers and less responded strongly to norepinephrine and moderately to ATP. However, the mesenteric branches of wider diameters were gradually less responsive to norepinephrine and those of diameter 700 micrometers were exclusively nonresponsive. These arteries were strongly responsive to ATP (100 µM). Norepinephrine response was sensitive to phentolamine (3 µM) and prazosin (5 µM) indicating that it is mediated by α1 receptor; while ATP response was sensitive to suramin (200 µM), PPADS (50 µM), but not to cibacron blue (100 µM) indicating that it is mediated via P2X receptor. Further confirmatory experiments were performed including application of α1 and P2X receptor specific agonists which are methoxamine and α,β-methylene ATP. Methoxamine (1 µM) showed effects similar to norepinephrine in final branches and was without effect in wider branches. α,β-methylene ATP (1 µM), exhibited more pronounced effects on both wide and narrow branches but in parallel manner to that of ATP. Agonists for α2 and P2Y receptors as clonidine (10 µM) and 2-meThio ATP (10 µM), respectively, were without effect indicating that involvement of these receptors is unlikely. The neuropeptide-Y (200 nM) did not have any effects on either the narrow or the wide rings. Conclusion: These data may imply that in the most peripheral mesenteric arteries a strong vasopressor power represented by norepinephrine and ATP integration is needed for maintaining peripheral resistance; on the other hand a mild vasopressor power mediated only by ATP is enough to maintain the vascular tone in the relatively central mesenteric branches.

Keywords: ATP, calves, mesenteric artery, norepinephrine

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Authors: Nermeen Elbeltagy, Sara Hassan, Tamer Hosny, Mostafa Abdelaziz

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Introduction: Adequate postoperative analgesia after caesarean section (CS) is crucial as it impacts the distinct surgical recovery needs of the parturient. Over recent years, there has been increased interest in regional nerve block techniques with promising results on efficacy. These techniques reduce the need for additional analgesia, thereby lowering the incidence of drug-related side effects. As postoperative pain after cesarean is mainly due to abdominal incision, the transverses abdomenis plane ( TAP ) block is a relatively new abdominal nerve block with excellent efficacy after different abdominal surgeries, including cesarean section. Objective: The main objective is to compare ultrasound-guided TAP block provided by the anesthesiologist with TAP provided by the surgeon through a caesarean incision regarding the duration of postoperative analgesia, intensity of analgesia, timing of mobilization, and easiness of the procedure. Method: Ninety pregnant females at term who were scheduled for delivery by elective cesarean section were randomly distributed into two groups. The first group (45) received spinal anesthesia and postoperative ultrasound guided TAP block using 20ml on each side of 0.25% bupivacaine which was provided by the anesthesiologist. The second group (45) received spinal anesthesia plus a TAP block using 20ml on each side of 0.25% bupivacaine, which was provided by the surgeon through the cesarean incision. Visual Analogue Scale (VAS) was used for the comparison between the two groups. Results: VAS score after four hours was higher among the TAP block group provided by the surgeon through the surgical incision than the postoperative analgesic profile using ultrasound-guided TAP block provided by the anesthesiologist (P=0.011). On the contrary, there was no statistical difference in the patient’s dose of analgesia after four hours of the TAP block (P=0.228). Conclusion: TAP block provided through the surgical incision is safe and enhances early patient’s mobilization.

Keywords: TAP block, CS, VAS, analgesia

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Authors: Xiao-Yin Liu, Liang-Xue Zhou

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Traumatic brain injury (TBI), as a kind of nerve trauma caused by an external force, affects people all over the world and is a global public health problem. Although there are various clinical treatments for brain injury, including surgery, drug therapy, and rehabilitation therapy, the therapeutic effect is very limited. To improve the therapeutic effect of TBI, scaffolds combined with exosomes are a promising but challenging method for TBI repair. In this study, we examined whether a novel 3D-printed collagen/chitosan scaffold/exosomes derived from neural stem cells (NSCs) pretreated with insulin growth factor-1 (IGF-I) scaffolds (3D-CC-INExos) could be used to improve TBI repair and functional recovery after TBI. Our results showed that composite scaffolds of collagen-, chitosan- and exosomes derived from NSCs pretreated with IGF-I (INExos) could continuously release the exosomes for two weeks. In the rat TBI model, 3D-CC-INExos scaffold transplantation significantly improved motor and cognitive function after TBI, as assessed by the Morris water maze test and modified neurological severity scores. In addition, immunofluorescence staining and transmission electron microscopy showed that the recovery of damaged nerve tissue in the injured area was significantly improved by 3D-CC-INExos implantation. In conclusion, our data suggest that 3D-CC-INExos might provide a potential strategy for the treatment of TBI and lay a solid foundation for clinical translation.

Keywords: traumatic brain injury, exosomes, insulin growth factor-1, neural stem cells, collagen, chitosan, 3D printing, neural regeneration, angiogenesis, functional recovery

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Authors: Luciana P. Mazur, Tatiana A. Pozdniakova, Rui A. R. Boaventura, Vitor J. P. Vilar

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The principal mechanism of metal ions sequestration by brown algae involves the formation of complexes between the metal ion and functional groups present on the cell wall of the biological material. To understand the role of functional groups on copper(II) uptake by Ascophyllum nodosum, some functional groups were chemically modified. The esterification of carboxylic groups was carried out by suspending the biomass in a methanol/HCl solution under stirring for 48 h and the blocking of the sulfonic groups was performed by repeating the same procedure for 4 cycles of 48 h. The methylation of amines was conducted by suspending the biomass in a formaldehyde/formic acid solution under shaking for 6 h and the chemical modification of sulfhydryl groups on the biomass surface was achieved using dithiodipyridine for 1 h. Equilibrium sorption studies for Cu2+ using the raw and esterified algae were performed at pH 2.0 and 4.0. The experiments were performed using an initial copper concentration of 300 mg/L and algae dose of 1.0 g/L. After reaching the equilibrium, the metal in solution was quantified by atomic absorption spectrometry. The biological material was analyzed by Fourier Transform Infrared Spectroscopy and Potentiometric Titration techniques for functional groups identification and quantification, respectively. The results using unmodified algae showed that the maximum copper uptake capacity at pH 4.0 and 2.0 was 1.17 and 0.52 mmol/g, respectively. At acidic pH values most carboxyl groups are protonated and copper sorption suffered a significant reduction of 56%. Blocking the carboxylic, sulfonic, amines and sulfhydryl functional groups, copper uptake decreased by 24/26%, 69/81%, 1/23% and 40/27% at pH 2.0/4.0, respectively, when compared to the unmodified biomass. It was possible to conclude that the carboxylic and sulfonic groups are the main functional groups responsible for copper binding (>80%). This result is supported by the fact that the adsorption capacity is directly related to the presence of carboxylic groups of the alginate polymer, and the second most abundant acidic functional group in brown algae is the sulfonic acid of fucoidan that contributes, to a lower extent, to heavy metal binding, particularly at low pH.

Keywords: biosorption, brown marine macroalgae, copper, ion-exchange

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Authors: Tansa Nisan Gunerhan

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Dementia comes in different forms, including Alzheimer's disease. The most common dementia diagnosis among elderly individuals is Alzheimer's disease. On average, for patients with Alzheimer’s, life expectancy is around 4-8 years after the diagnosis; however, expectancy can go as high as twenty years or more, depending on the shrinkage of the brain. Normally, along with aging, the brain shrinks at some level but doesn’t lose a vast amount of neurons. However, Alzheimer's patients' neurons are destroyed rapidly; hence problems with loss of memory, communication, and other metabolic activities begin. The toxic changes in the brain affect the stability of the neurons. Beta-amyloid and tau are two proteins that are believed to play a role in the development of Alzheimer's disease through their toxic changes. Beta-amyloid is a protein that is produced in the brain and is normally broken down and removed from the body. However, in people with Alzheimer's disease, the production of beta-amyloid increases, and it begins to accumulate in the brain. These plaques are thought to disrupt communication between nerve cells and may contribute to the death of brain cells. Tau is a protein that helps to stabilize microtubules, which are essential for the transportation of nutrients and other substances within brain cells. In people with Alzheimer's disease, tau becomes abnormal and begins to accumulate inside brain cells, forming neurofibrillary tangles. These tangles disrupt the normal functioning of brain cells and may contribute to their death, forming amyloid plaques which are deposits of a protein called amyloid-beta that build up between nerve cells in the brain. The accumulation of amyloid plaques and neurofibrillary tangles in the brain is thought to contribute to the shrinkage of brain tissue. As the brain shrinks, the size of the brain may decrease, leading to a reduction in brain volume. Brain atrophy in Alzheimer's disease is often accompanied by changes in the structure and function of brain cells and the connections between them, leading to a decline in brain function. These toxic changes that accumulate can cause symptoms such as memory loss, difficulty with thinking and problem-solving, and changes in behavior and personality.

Keywords: Alzheimer, amyloid-beta, brain atrophy, neuron, shrinkage

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Authors: Ju-Hong Lee, Ching-Wei Liao

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Adaptive beamforming using antenna array of sensors is useful in the process of adaptively detecting and preserving the presence of the desired signal while suppressing the interference and the background noise. For conventional adaptive array beamforming, we require a prior information of either the impinging direction or the waveform of the desired signal to adapt the weights. The adaptive weights of an antenna array beamformer under a steered-beam constraint are calculated by minimizing the output power of the beamformer subject to the constraint that forces the beamformer to make a constant response in the steering direction. Hence, the performance of the beamformer is very sensitive to the accuracy of the steering operation. In the literature, it is well known that the performance of an adaptive beamformer will be deteriorated by any steering angle error encountered in many practical applications, e.g., the wireless communication systems with massive antennas deployed at the base station and user equipment. Hence, developing effective signal processing techniques to deal with the problem due to steering angle error for array beamforming systems has become an important research work. In this paper, we present an effective signal processing technique for constructing an adaptive beamformer against the steering angle error. The proposed array beamformer adaptively estimates the actual direction of the desired signal by using the presumed steering vector and the received array data snapshots. Based on the presumed steering vector and a preset angle range for steering mismatch tolerance, we first create a matrix related to the direction vector of signal sources. Two projection matrices are generated from the matrix. The projection matrix associated with the desired signal information and the received array data are utilized to iteratively estimate the actual direction vector of the desired signal. The estimated direction vector of the desired signal is then used for appropriately finding the quiescent weight vector. The other projection matrix is set to be the signal blocking matrix required for performing adaptive beamforming. Accordingly, the proposed beamformer consists of adaptive quiescent weights and partially adaptive weights. Several computer simulation examples are provided for evaluating and comparing the proposed technique with the existing robust techniques.

Keywords: adaptive beamforming, robustness, signal blocking, steering angle error

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Authors: Ae Ra Han, Seoung Eun Huh, Ji Yeon Kim, Joanne Kwak-Kim, Sung Ki Lee

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Objective: Prevalence of osteoporosis, cardiovascular disorders, and Alzheimer's disease rapidly increase after menopause. Immune activation and inflammation are suggested as an important pathogenesis of these serious diseases. Several pro-inflammatory cytokines are increased in women with surgical or natural menopause. However, the little is known about IL-17 producing T cells and Foxp3+ regulatory T (Treg) cells in post-menopause. Methods: A total of 34 postmenopausal women, who had no active cardiovascular, endocrine and infectious disorders were recruited as study group and healthy premenopausal women participated as controls. Peripheral blood mononuclear cells were isolated. Immuno-morphologic (CD3, CD4, CD8, CD19, CD56/CD16), intracellular cytokine (TNF-alpha, IFN-gamma, IL-10, IL-17), and Treg cell (Foxp3) studies were carried out using flow cytometry. The proportion of peripheral lymphocytes, including IL-17 producing and Foxp3+ Treg cells immune cell in each group were statistically analyzed. Results: The proportion of NK cells was significantly increased in menopausal women as compared to that of controls (P=.005). The ratios of TNF-alpha/IL-10 producing CD3+CD4+ T cells were increased in postmenopausal women. CD3+IL-17+ T cell level was higher in postmenopausal women and CD4+ Foxp3+ Treg cells was lower than that of controls. The ratios of CD3+IL-17+ T cell to CD3+Foxp3+ and to CD4+Foxp3+ Treg cells were significantly increased in postmenopausal women (P=.001). Conclusions: We found enhanced innate immunity and Th1- and Th17-mediated adaptive immunity in postmenopausal women. This may explain increasing prevalence of chronic inflammatory diseases after menopause. Further studies are needed to elucidate what factors contribute to this inflammatory shift in the postmenopause.

Keywords: inflammation, immune cell, menopause, Th17, regulatory T cell

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Authors: Kantha Siddhanth Gujjari, Shaani Singhal, Robert Andrew Danks, Adrian Praeger

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Background: Trigeminal neuralgia (TN) is a heterogenous pain syndrome characterised by short paroxysms of lancinating facial pain in the distribution of the trigeminal nerve, often triggered by usually innocuous stimuli. TN has a low prevalence of less than 0.1%, of which 80% to 90% is caused by compression of the trigeminal nerve from an adjacent artery or vein. The root entry zone of the trigeminal nerve is most sensitive to neurovascular conflict (NVC), causing dysmyelination. Whilst microvascular decompression (MVD) is an effective treatment for TN with NVC, all patients do not achieve long-term pain relief. Pre-operative scoring systems by Panczykowski and Hardaway have been proposed but have not been externally validated. These pre-operative scoring systems are composite scores calculated according to a subtype of TN, presence and degree of neurovascular conflict, and response to medical treatments. There is discordance in the assessment of NVC identified on pre-operative magnetic resonance imaging (MRI) between neurosurgeons and radiologists. To our best knowledge, the prognostic impact for MVD of this difference of interpretation has not previously been investigated in the form of a composite scoring system such as those suggested by Panczykowski and Hardaway. Aims: This study aims to identify prognostic factors and externally validate the proposed scoring systems by Panczykowski and Hardaway for TN. A secondary aim is to investigate the prognostic difference between a neurosurgeon's interpretation of NVC on MRI compared with a radiologist’s. Methods: This retrospective cohort study included 95 patients who underwent de novo MVD in a single neurosurgical unit in Melbourne. Data was recorded from patients’ hospital records and neurosurgeon’s correspondence from perioperative clinic reviews. Patient demographics, type of TN, distribution of TN, response to carbamazepine, neurosurgeon, and radiologist interpretation of NVC on MRI, were clearly described prospectively and preoperatively in the correspondence. Scoring systems published by Panczykowski et al. and Hardaway et al. were used to determine composite scores, which were compared with the recurrence of TN recorded during follow-up over 1-year. Categorical data analysed using Pearson chi-square testing. Independent numerical and nominal data analysed with logistical regression. Results: Logistical regression showed that a Panczykowski composite score of greater than 3 points was associated with a higher likelihood of pain-free outcome 1-year post-MVD with an OR 1.81 (95%CI 1.41-2.61, p=0.032). The composite score using neurosurgeon’s impression of NVC had an OR 2.96 (95%CI 2.28-3.31, p=0.048). A Hardaway composite score of greater than 2 points was associated with a higher likelihood of pain-free outcome 1 year post-MVD with an OR 3.41 (95%CI 2.58-4.37, p=0.028). The composite score using neurosurgeon’s impression of NVC had an OR 3.96 (95%CI 3.01-4.65, p=0.042). Conclusion: Composite scores developed by Panczykowski and Hardaway were validated for the prediction of response to MVD in TN. A composite score based on the neurosurgeon’s interpretation of NVC on MRI, when compared with the radiologist’s had a greater correlation with pain-free outcomes 1 year post-MVD.

Keywords: de novo microvascular decompression, neurovascular conflict, prognosis, trigeminal neuralgia

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Authors: Aneta Binkowska, Grzegorz Michalak, Slawomir Pilip, Lukasz Bondaruk, Daniel Celinski, Robert Slotwinski

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Post-traumatic mortality rates are still very high and show an increasing tendency. Early identification of patients at high risk of severe complications has a significant impact on treatment outcomes. The aim of the study was to better understand the early pathological inflammatory response to injury and infection and to determine the usefulness of the assessment of TNF-α and sTNFR1 concentrations in the peripheral blood as early indicators of severe post-traumatic complications. The study was carried out in a group of 51 patients after trauma treated in the ED, including 32 patients that met inclusion criteria for immunological analysis. Patients were divided into two groups using the ISS scale (group A with ISS ≥20, group B with ISS <20). Serum levels of TNF-α and sTNFR1 were determined after admission to the ED and after 3, 6, 12 and 24 hours. The highest TNF-α and sTNFR1 concentrations in both groups were recorded at admission and were significantly higher in group A compared to group B (A vs B TNF-α 2.46 pg/ml vs 1.78 pg/ml; sTNFR1 1667.5 pg/ml vs 875.2 p<0.005). The concentration of sTNFR1 in patients with severe complications was significantly higher compared to patients without complications and preceded clinical symptoms of complications ( C+ vs C- 1561.5 pg/ml vs 930.6 pg/ml). Spearman's correlation showed a statistically significant positive correlation between the baseline concentrations of IL-6 (r=0.38, p<0.043) and sTNFR1 (r=0.59, p=0.001) and the ISS scores. The high diagnostic sensitivity calculated from the ROC (receiver operating characteristic) curves was found for the concentrations of both cytokines: TNF α (AUC=0.91, p=0.004) and sTNFR1 (AUC=0.86, p=0.011). Elevated levels of sTNFR1, determined in the peripheral blood shortly after injury, is significantly associated with the occurrence of later complications, which in some patients lead to death. In contrast, high levels of TNF-α shortly after injury are associated with high mortality.

Keywords: cytokine, SIRS, MODS, trauma

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Authors: Marina Fomina

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The paper focuses on the category of semantic subject within the framework of a functional approach to linguistics. The semantic subject is related to similar notions such as the grammatical subject and the bearer of predicative feature. It is the multifaceted nature of the category of subject that 1) triggers a number of issues that, syntax-wise, remain to be dealt with (cf. semantic vs. syntactic functions / sentence parts vs. parts of speech issues, etc.); 2) results in a variety of approaches to the category of subject, such as formal grammatical, semantic/syntactic (functional), communicative approaches, etc. Many linguists consider the prototypical approach to the category of subject to be the most instrumental as it reveals the integrity of denotative and linguistic components of the conceptual category. This approach relates to subject as a source of non-passive predicative feature, an element of subject-predicate-object situation that can take on a variety of semantic roles, cf.: 1) an agent (He carefully surveyed the valley stretching before him), 2) an experiencer (I feel very bitter about this), 3) a recipient (I received this book as a gift), 4) a causee (The plane broke into three pieces), 5) a patient (This stove cleans easily), etc. It is believed that the variety of roles stems from the radial (prototypical) structure of the category with some members more central than others. Translation-wise, the most “treacherous” subject types are the peripheral ones. The paper 1) features a peripheral status of spatial impersonal sentence models such as U menia v ukhe zvenit (lit. I-Gen. in ear buzzes) within the category of semantic subject, 2) makes a structural and semantic analysis of the models, 3) focuses on their Russian-English translation patterns, 4) reveals non-prototypical features of subjects in the English equivalents.

Keywords: bearer of predicative feature, grammatical subject, impersonal sentence model, semantic subject

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Authors: Tomomi Uchiyama, Tomoko Okayama, Yukio Ide

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This study is concerned with the development of a micro-hydraulic turbine for power generation installed in sewer pipes. The runner has a circular hollow around the central (rotating) axis so that solid materials included in water can be easily flow through the runner without blocking the turbine. The laboratory experiments are also conducted. The hollow is very effective to make polyester fibers pass through the turbine. The guide vane is useful to heighten the turbine performance. But it is easily blocked by the fibers, making the turbine lose the function.

Keywords: micro-hydraulic turbine, power generation, sewage, sewer pipe

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Authors: B. Gonzalez-Yebra, H. Barajas, P. Palomares, M. Hernandez, O. Torres, M. Ayala, A. L. González, G. Vazquez-Ortiz, M. L. Guzman

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Leukemia arises by molecular alterations of the normal hematopoietic stem cell (HSC) transforming it into a leukemic stem cell (LSC) with high cell proliferation, self-renewal, and cell differentiation. Chronic myeloid leukemia (CML) originates from an LSC-leading to elevated proliferation of myeloid cells and acute lymphoblastic leukemia (ALL) originates from an LSC development leading to elevated proliferation of lymphoid cells. In both cases, LSC can be identified by multicolor flow cytometry using several antibodies. However, to date, LSC levels in peripheral blood (PB) are not established well enough in ALL and CML patients. On the other hand, the detection of the minimal residue disease (MRD) in leukemia is mainly based on the identification of the mRNA bcr-abl gene in CML patients and some other genes in ALL patients. There is no a properly biomarker to detect MDR in both types of leukemia. The objective of this study was to determine mRNA bcr-abl and the percentage of LSC in peripheral blood of patients with CML and ALL and identify a possible association between the amount of LSC in PB and clinical data. We included in this study 19 patients with Leukemia. A PB sample was collected per patient and leukocytes were obtained by Ficoll gradient. The immunophenotype for LSC CD34+ was done by flow cytometry analysis with CD33, CD2, CD14, CD16, CD64, HLA-DR, CD13, CD15, CD19, CD10, CD20, CD34, CD38, CD71, CD90, CD117, CD123 monoclonal antibodies. In addition, to identify the presence of the mRNA bcr-abl by RT-PCR, the RNA was isolated using TRIZOL reagent. Molecular (presence of mRNA bcr-abl and LSC CD34+) and clinical results were analyzed with descriptive statistics and a multiple regression analysis was performed to determine statistically significant association. In total, 19 patients (8 patients with ALL and 11 patients with CML) were analyzed, 9 patients with de novo leukemia (ALL = 6 and CML = 3) and 10 under treatment (ALL = 5 and CML = 5). The overall frequency of mRNA bcr-abl was 31% (6/19), and it was negative in ALL patients and positive in 80% in CML patients. On the other hand, LSC was determined in 16/19 leukemia patients (%LSC= 0.02-17.3). The Novo patients had higher percentage of LSC (0.26 to 17.3%) than patients under treatment (0 to 5.93%). The amount of LSC was significantly associated with the amount of LSC were: absence of treatment, the absence of splenomegaly, and a lower number of leukocytes, negative association for the clinical variables age, sex, blasts, and mRNA bcr-abl. In conclusion, patients with de novo leukemia had a higher percentage of circulating LSC than patients under treatment, and it was associated with clinical parameters as lack of treatment, absence of splenomegaly and a lower number of leukocytes. The mRNA bcr-abl detection was only possible in the series of patients with CML, and molecular detection of LSC could be identified in the peripheral blood of all leukemia patients, we believe the identification of circulating LSC may be used as biomarker for the detection of the MRD in leukemia patients.

Keywords: stem cells, leukemia, biomarkers, flow cytometry

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Authors: Chanya Inprasit, Yi-Wen Lin

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Inflammation causes changes of peripheral and central nervous system properties, affecting both neuronal and non-neuronal cells, resulting in inflammatory pain. Acupoint injection (AI) was developed in the 1950s and has been widely used for relieving pain. It is an acupoint-stimulating technique that utilizes anatomically based meridians derived from Chinese medicine theory. AI has been accepted as an effective treatment and is thought to display superior results when compared to traditional acupuncture methods. However, the mechanism of AI needs to be ratified by more scientific evidence in order to support the theory and its therapeutic development. In this study, we explored the effect of AI on the comorbidity of chronic pain and depression. Mice hindpaw was injected by complete Freund’s adjuvant (CFA) to induce the condition of chronic pain. Measurements of mechanical and thermal hyperalgesia and depression-like behavior were analyzed. The results indicated a positive tendency to AI treatment. The comorbidity of chronic pain and depression was investigated with relation to transient receptor potential V1 (TRPV1) mechanism through the use of TRPV1 gene deletion. The expression of nociceptors such as voltage-gated sodium channels (Navs) or TRPV1, was significantly down-regulated by AI. The expression of inflammation-activated molecules: astrocytic marker glial fibrillary acidic protein (GFAP), the microglial marker Iba-1, S100B, and related kinases, were reversed by AI in both the peripheral and central nervous system. Taken together, these data provided a detailed molecular mechanism of AI-induced analgesia and anti-inflammatory properties. This finding may be utilized for clinical practice to treat chronic pain and depression comorbidity.

Keywords: inflammatory pain, acupoint injection, TRPV1, GFAP, S100B

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Authors: Azza M. Atya, Mahmoud M. Nasser

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Background/ /Significance: Peripheral neuropathy is one of the long term serious complications of diabetes, which may attribute to postural instability and alteration of planter pressure. Whole body vibration (WBV) is a somatosensory stimulation type of exercise that has been emerged in sport training and rehabilitation of neuromuscular disorders. Purpose: The aim of this study was to investigate the effect of whole Body Vibration on antroposterior (AP), mediolateral (ML) posture stability and planter foot pressure in patients with diabetic neuropathy. Subjects: forty diabetic patients with moderate peripheral neuropathy aged from 35 to 50 years, were randomly assigned to WBV group (n=20) and control group (n=20). Methods and Materials: the WBV intervention consisted of three session weekly for 8 weeks (frequency 20 Hz, peak-to peak displacement 4mm, acceleration 3.5 g). Biodex balance system was used for postural stability assessment and the foot scan plate was used to measure the mean peak pressure under the first and lesser metatarsals. The main Outcome measures were antroposterior stability index (APSI), mediolateral stability index (MLSI), overall stability index (OSI),and mean peak foot pressure. Analyses: Statistical analysis was performed using the SPSS software package (SPSS for Windows Release 18.0). T-test was used to compare between the pre- and post-treatment values between and within groups. Results: For the 40 study participants (18male and 22 females) there were no between-group differences at baseline. At the end of 8 weeks, Subjects in WBV group experienced significant increase in postural stability with a reduction of mean peak of planter foot pressure (P<0.05) compared with the control group. Conclusion: The result suggests that WBV is an effective therapeutic modality for increasing postural stability and reducing planter pressure in patients with diabetic neuropathy.

Keywords: whole body vibration, diabetic neuropathy, posture stability, foot pressure

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Authors: Stephanie PB Caligiuri, Harold M Aukema, Delfin Rodriguez-Leyva, Amir Ravandi, Randy Guzman, Grant N. Pierce

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Background: Hypertension leads to cardiac and cerebral events and therefore is the leading risk factor attributed to death in the world. Oxylipins may be mediators in these events as they can regulate vascular tone and inflammation. Oxylipins are derived from fatty acids. Dietary flaxseed is rich in the n3 fatty acid, alpha-linolenic acid, and, therefore, may have the ability to change the substrate profile of oxylipins. As a result, this could alter blood pressure. Methods: A randomized, double-blinded, controlled clinical trial, the Flax-PAD trial, was used to assess the impact of dietary flaxseed on blood pressure (BP), and to also assess the relationship of plasma oxylipins to BP in 81 patients with peripheral arterial disease (PAD). Patients with PAD were chosen for the clinical trial as they are at an increased risk for hypertension and cardiac and cerebral events. Thirty grams of ground flaxseed were added to food products to consume on a daily basis for 6 months. The control food products contained wheat germ, wheat bran, and mixed dietary oils instead of flaxseed. Central BP, which is more significantly associated to organ damage, cardiac, and cerebral events versus brachial BP, was measured by pulse wave analysis at baseline and 6 months. A plasma profile of 43 oxylipins was generated using solid phase extraction, HPLC-MS/MS, and stable isotope dilution quantitation. Results: At baseline, the central BP (systolic/diastolic) in the placebo and flaxseed group were, 131/73 ± 2.5/1.4 mmHg and 128/71 ± 2.6/1.4 mmHg, respectively. After 6 months of intervention, the flaxseed group exhibited a decrease in blood pressure of 4.0/1.0 mmHg. The 6 month central BP in the placebo and flaxseed groups were, 132/74 ± 2.9/1.8 mmHg and 124/70 ± 2.6/1.6 mmHg (P<0.05). Correlation and logistic regression analyses between central blood pressure and oxylipins were performed. Significant associations were observed between central blood pressure and 17 oxylipins, primarily produced from arachidonic acid. Every 1 nM increase in 16-hydroxyeicosatetraenoic acid (HETE) increased the odds of having high central systolic BP by 15-fold, of having high central diastolic BP by 6-fold and of having high central mean arterial pressure by 15-fold. In addition, every 1 nM increase in 5,6-dihydroxyeicosatrienoic acid (DHET) and 11,12-DHET increased the odds of having high central mean arterial pressure by 45- and 18-fold, respectively. Flaxseed induced a significant decrease in these as well as 4 other vasoconstrictive oxylipins. Conclusion: Dietary flaxseed significantly lowered blood pressure in patients with PAD and hypertension. Plasma oxylipins were strongly associated with central blood pressure and may have mediated the flaxseed-induced decrease in blood pressure.

Keywords: hypertension, flaxseed, oxylipins, peripheral arterial disease

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Authors: Rachel Shukrun, Szilvia Baron, Victoria Fidel, Anna Shusterman, Osnat Sher, Netanya Kollender, Dror Levin, Yair Peled, Yair Gortzak, Yoav Ben-Shahar, Revital Caspi, Sagi Gordon, Michal Manisterski, Ronit Elhasid

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Ewing sarcoma (EWS) is a highly aggressive cancer with a survival rate of 70–80% for patients with localized disease and under 30% for those with metastatic disease. Tumor-infiltrating neutrophils (TIN) can generate extracellular net-like DNA structures known as neutrophil extracellular traps (NETs). However, little is known about the presence and prognostic significance of tumor-infiltrating NETs in EWS. Herein, we investigated 46 patients diagnosed with EWS and treated in the Tel Aviv Medical Center between 2010 and 2021. TINs and NETs were identified in diagnostic biopsies of EWS by immunofluorescent. In addition, NETs were investigated in neutrophils isolated from peripheral blood samples of EWS patients at diagnosis and following neoadjuvant chemotherapy. The relationships between the presence of TINs and NETs, pathological and clinical features, and outcomes were analyzed. Our results demonstrate that TIN and NETs at diagnosis were higher in EWS patients with metastatic disease compared to those with local disease. High NETs formation at diagnosis predicted poor response to neo-adjuvant chemotherapy, relapse, and death from disease (P < .05). NETs formation in peripheral blood samples at diagnosis was significantly elevated among patients with EWS compared to pediatric controls and decreased significantly following neoadjuvant chemotherapy. In conclusion, NETs formation seems to have a role in the EWS immune microenvironment. Their presence can refine risk stratification, predict chemotherapy resistance and survival, and serve as a therapeutic target in patients with EWS.

Keywords: Ewing sarcoma, tumor microenvironment, neutrophil, neutrophil extracellular traps (NETs), prognosis

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Authors: Vladimir V. Iakovlev, Erin T. Carey, John Steege

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The use of polypropylene mesh devices for Pelvic Organ Prolapse (POP) spread rapidly during the last decade, yet our knowledge of the mesh-tissue interaction is far from complete. We aimed to perform a thorough pathological examination of explanted POP meshes and describe findings that may explain mechanisms of complications resulting in product excision. We report a spectrum of important findings, including nerve ingrowth, mesh deformation, involvement of detrusor muscle with neural ganglia, and polypropylene degradation. Analysis of these findings may improve and guide future treatment strategies.

Keywords: transvaginal, mesh, nerves, polypropylene degradation

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Authors: Hadj Abd El Kader Benghenia, Fethi Bereksi Reguig

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In clinical medicine, blood pressure, raised blood hemodynamic monitoring is rich pathophysiological information of cardiovascular system, of course described through factors such as: blood volume, arterial compliance and peripheral resistance. In this work, we are interested in analyzing these signals to propose a detection algorithm to delineate the different sequences and especially systolic blood pressure (SBP), diastolic blood pressure (DBP), and the wave and dicrotic to do their analysis in order to extract the cardiovascular parameters.

Keywords: blood pressure, SBP, DBP, detection algorithm

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