Search results for: muscle activation

Authors: Ho Sy Nam, Tang Ha Nam Anh

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Background: Rotator cuff tears are a common problem in the aging population. The prevalence of massive rotator cuff tears varies in some studies from 10% to 40%. Of irreparable rotator cuff tears (IRCTs), which are mostly associated with massive tear size, 79% are estimated to have recurrent tears after surgical repair. Recent studies have shown that superior capsule reconstruction (SCR) in massive rotator cuff tears can be an efficient technique with optimistic clinical scores and preservation of stable glenohumeral stability. Superior capsule reconstruction techniques most commonly use either fascia lata autograft or dermal allograft, both of which have their own benefits and drawbacks (such as the potential for donor site issues, allergic reactions, and high cost). We propose a simple technique for superior capsule reconstruction that involves using the long head of the biceps tendon as a local autograft; therefore, the comorbidities related to graft harvesting are eliminated. The long head of the biceps tendon proximal portion is relocated to the footprint and secured as the SCR, serving to both stabilize the glenohumeral joint and maintain vascular supply to aid healing. Objective: The purpose of this study is to assess the clinical outcomes of patients with large to massive RCTs treated by SCR using LHBT. Materials and methods: A study was performed of consecutive patients with large to massive RCTs who were treated by SCR using LHBT between January 2022 and December 2022. We use one double-loaded suture anchor to secure the long head of the biceps to the middle of the footprint. Two more anchors are used to repair the rotator cuff using a single-row technique, which is placed anteriorly and posteriorly on the lateral side of the previously transposed LHBT. Results: The 3 men and 5 women had an average age of 61.25 years (range 48 to 76 years) at the time of surgery. The average follow-up was 8.2 months (6 to 10 months) after surgery. The average preoperative ASES was 45.8, and the average postoperative ASES was 85.83. The average postoperative UCLA score was 29.12. VAS score was improved from 5.9 to 1.12. The mean preoperative ROM of forward flexion and external rotation of the shoulder was 720 ± 160 and 280 ± 80, respectively. The mean postoperative ROM of forward flexion and external rotation were 1310 ± 220 and 630 ± 60, respectively. There were no cases of progression of osteoarthritis or rotator cuff muscle atrophy. Conclusion: SCR using LHBT is considered a treatment option for patients with large or massive RC tears. It can restore superior glenohumeral stability and function of the shoulder joint and can be an effective procedure for selected patients, helping to avoid progression to cuff tear arthropathy.

Keywords: superior capsule reconstruction, large or massive rotator cuff tears, the long head of the biceps, stabilize the glenohumeral joint

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Authors: S. D. N. K. Bathige, G. I. Godahewa, Navaneethaiyer Umasuthan, Jehee Lee

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Kunitz-type serine protease inhibitors (KTIs) are identified in various organisms including animals, plants and microbes. These proteins shared single or multiple Kunitz inhibitory domains link together or associated with other types of domains. Characteristic Kunitz type domain composed of around 60 amino acid residues with six conserved cysteine residues to stabilize by three disulfide bridges. KTIs are involved in various physiological processes, such as ion channel blocking, blood coagulation, fibrinolysis and inflammation. In this study, two Kunitz-type domain containing protein was identified from rock bream database and designated as RbKunitz. The coding sequence of RbKunitz encoded for 507 amino acids with 56.2 kDa theoretical molecular mass and 5.7 isoelectric point (pI). There are several functional domains including MANEC superfamily domain, PKD superfamily domain, and LDLa domain were predicted in addition to the two characteristic Kunitz domain. Moreover, trypsin interaction sites were also identified in Kunitz domain. Homology analysis revealed that RbKunitz shared highest identity (77.6%) with Takifugu rubripes. Completely conserved 28 cysteine residues were recognized, when comparison of RbKunitz with other orthologs from different taxonomical groups. These structural evidences indicate the rigidity of RbKunitz folding structure to achieve the proper function. The phylogenetic tree was constructed using neighbor-joining method and exhibited that the KTIs from fish and non-fish has been evolved in separately. Rock bream was clustered with Takifugu rubripes. The SYBR Green qPCR was performed to quantify the RbKunitz transcripts in different tissues and challenged tissues. The mRNA transcripts of RbKunitz were detected in all tissues (muscle, spleen, head kidney, blood, heart, skin, liver, intestine, kidney and gills) analyzed and highest transcripts level was detected in gill tissues. Temporal transcription profile of RbKunitz in rock bream blood tissues was analyzed upon LPS (lipopolysaccharide), Poly I:C (Polyinosinic:polycytidylic acid) and Edwardsiella tarda challenge to understand the immune responses of this gene. Compare to the unchallenged control RbKunitz exhibited strong up-regulation at 24 h post injection (p.i.) after LPS and E. tarda injection. Comparatively robust expression of RbKunits was observed at 3 h p.i. upon Poly I:C challenge. Taken together all these data indicate that RbKunitz may involve into to immune responses upon pathogenic stress, in order to protect the rock bream.

Keywords: Kunitz-type, rock bream, immune response, serine protease inhibitor

Procedia PDF Downloads 374

Authors: Mohammed Fayez Al Rez

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Nowadays, there is an unmet clinical need for new small-diameter vascular grafts to overcome the drawbacks of traditional methods used for treatment of widespread cardiovascular diseases. Vascular tissue engineering (VTE) is a promising approach that can be utilized to develop viable vascular grafts by in vitro seeding of functional cells onto a scaffold allowing them to attach, proliferate and differentiate. To achieve this purpose, the scaffold should provide cells with the initial necessary extracellular matrix environment and structure until being able to reconstruct the required vascular tissue. Therefore, producing scaffolds with suitable features is crucial for guiding cells properly to develop the desired tissue-engineered vascular grafts for clinical applications. The main objective of this work is fabrication and characterization of tubular small-diameter ( < 6 mm) bilayered scaffolds for VTE. The scaffolds were prepared via mixing electrospinning approach of biodegradable poly(ε-caprolactone) (PCL) polymer – due to its favorable physicochemical properties – to mimic the natural environment-extracellular matrix. Firstly, tubular nanofibrous construct with inner diameter of 3, 4 or 5 mm was electrospun as inner layer, and secondly, microfibrous construct was electrospun as outer layer directly on the first produced inner layer. To improve the biological properties of PCL, a group of the electrospun scaffolds was immersed in type-1 collagen solution. The morphology and structure of the resulting fibrous scaffolds were investigated by scanning electron microscope. The electrospun nanofibrous inner layer contained fibers measuring 219±35 nm in diameter, while the electrospun microfibrous outer layer contained fibers measuring 1011 ± 150 nm. Furthermore, mechanical, thermal and physical tests were conducted with both electrospun bilayered scaffold types where revealed improved properties. Biological investigations using endothelial, smooth muscle and fibroblast cell line showed good biocompatibility of both tested electrospun scaffolds. Better attachment and proliferation were obviously found when cells were cultured on the scaffolds immersed with collagen due to increasing the hydrophilicity of the PCL. The easy, inexpensive and versatile electrospinning approach used in this work was able to successfully produce double layered tubular elastic structures containing both nanofibers and microfibers to imitate the native vascular structure. The PCL – as a suitable and approved biomaterial for many biomedical and tissue engineering applications – can ensure favorable mechanical properties of scaffolds used for VTE. The VTE approach using electrospun bilayered scaffolds offers optimal solutions and holds significant promises for treatment of many cardiovascular diseases.

Keywords: electrospinning, poly(ε-caprolactone) (PCL), tissue-engineered vascular graft, tubular bilayered scaffolds, vascular cells

Procedia PDF Downloads 287

Authors: Gaweł Magdalena, Lipkowska Anna, Olbert Magdalena, Frąckiewicz Ewelina, Librowski Tadeusz, Nowak Gabriel, Pilc Andrzej

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Heme oxygenase-1 (HO-1), also known as heat shock protein 32 (HSP32), has been shown to be implicated in cytoprotection in various organs. Its activation plays a significant role in acute and chronic inflammation, protecting cells from oxidative injury and apoptosis. This inducible isoform of HO catalyzes the first and rate-limiting step in heme degradation to produce equimolar quantities of biologically active products: carbon monoxide (CO), free iron and biliverdin. CO has been reported to possess anti-apoptotic properties. Moreover, it inhibits the production of proinflammatory cytokines and stimulates the synthesis of the anti-inflammatory interleukin-10 (IL-10), as well as promotes vasodilatation at sites of inflammation. The second product of catalytic HO-1 activity, free cytotoxic iron, is promptly sequestered into the iron storage protein ferritin, which lowers the pro-oxidant state of the cell. The third product, biliverdin, is subsequently converted by biliverdin reductase into the bile pigment bilirubin, the most potent endogenous antioxidant among the constituents of human serum, which modulates immune effector functions and suppresses inflammatory response. Furthermore, being one of the so-called stress proteins, HO-1 adaptively responds to different stressors, such as reactive oxygen species (ROS), inflammatory cytokines and heavy metals and thus protects cells against such conditions as ischemia, hemorrhagic shock, heat shock or hypoxia. It is suggested that pharmacologic modulation of HO-1 may represent an effective strategy for prevention of stress and drug-induced gastrointestinal toxicity. HO-1 is constitutively expressed in normal gastric, intestinal and colonic mucosa and up-regulated during inflammation. It has been proven that HO-1 up-regulated by hemin, heme and cobalt-protoporphyrin ameliorates experimental colitis. In addition, the up-regulation of HO-1 partially explains the mechanism of action of 5-aminosalicylic acid (5-ASA), which is used clinically as an anti-colitis agent. In 2009 Ueda et al. has reported for the first time that mucosal protection by Polaprezinc, a chelate compound of zinc and L-carnosine used as an anti-ulcer drug in Japan, is also attributed to induction of HO-1 in the stomach. Since then, inducers of HO-1 are desired subject of research, as they may constitute therapeutically effective anti-ulcer drugs.

Keywords: heme oxygenase-1, gastric lesions, gastroprotection, Polaprezinc

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Authors: M. H. A. D. de Silva, R. P. Hewawasam, M. A. G. Iresha

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Macrosomia is common in infants born to not only women diagnosed with gestational diabetes mellitus but also non-diabetic obese women. Maternal Body Mass Index (BMI) correlates with the incidence of large for gestational age infants. Obesity has reached epidemic levels in modern societies. During the past two decades, obesity in children and adolescents has risen significantly in Asian populations including Sri Lanka. There is increasing evidence to believe that infants who are born large for gestational age are more likely to be obese in childhood and adolescence and are at risk of cardiovascular and metabolic complications later in life. It is also established that Asians have lower skeletal muscle mass, low bone mineral content and excess body fat for a given BMI indicating a genetic predisposition in the occurrence of obesity. The objective of this study is to determine the effect of maternal weight, weight gain during pregnancy, c-peptide and insulin concentrations in the cord blood on the birth of appropriate for and large for gestational age infants in a tertiary care center in Southern Sri Lanka. Umbilical cord blood was collected from 90 newborns (Male 40, Female 50; gestational age 35-42 weeks) after double clamping the umbilical cord before separation of the placenta and the concentration of insulin and C-peptide were measured by ELISA technique. Anthropometric parameters of the newborn such as birth weight, length, ponderal index, occipital frontal, chest, hip and calf circumferences were measured, and characteristics of the mother were collected. The relationship between insulin, C-peptide and anthropometrics were assessed by Spearman correlation. The multiple logistic regression analysis examined influences of maternal weight, weight gain during pregnancy, C-peptide and insulin concentrations in cord blood as covariates on the birth of large for gestational age infants. A significant difference (P<0.001) was observed between the insulin levels of infants born large for gestational age (18.73 ± 0.52 µlU/ml) and appropriate for gestational age (13.08 ± 0.56 µlU/ml). Consistently, A significant decrease in concentration (41.68%, P<0.001) was observed between C-peptide levels of infants born large for gestational age and appropriate for gestational age. Cord blood insulin and C-peptide levels had a significant correlation with birth weight (r=0.35, P<0.05) of the newborn at delivery. Maternal weight and BMI which are indicators of maternal nutrition were proven to be directly correlated with birth weight and length. To our knowledge, this relationship was investigated for the first time in a Sri Lankan setting and was also evident in our results. This study confirmed the fact that insulin and C-peptide play a major role in regulating fetal growth. According to the results obtained in this study, we can suggest that the increased BMI of the mother has a direct influence on increased maternal insulin secretion, which may subsequently affect cord insulin and C-peptide levels and also birth weight of the infant.

Keywords: C-peptide, insulin, large for gestational age, maternal weight

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Authors: Tayo P. Ogundunmade, Adedayo A. Adepoju

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Terrorist attacks in liberal democracies bring about a few pessimistic results, for example, sabotaged public support in the governments they target, disturbing the peace of a protected environment underwritten by the state, and a limitation of individuals from adding to the advancement of the country, among others. Hence, seeking for techniques to understand the different factors involved in terrorism and how to deal with those factors in order to completely stop or reduce terrorist activities is the topmost priority of the government in every country. This research aim is to develop an efficient deep learning-based predictive model for the prediction of future terrorist activities in Nigeria, addressing low-quality prediction accuracy problems associated with the existing solution methods. The proposed predictive AI-based model as a counterterrorism tool will be useful by governments and law enforcement agencies to protect the lives of individuals in society and to improve the quality of life in general. A Heterogeneous Bayesian Neural Network (HETBNN) model was derived with Gaussian error normal distribution. Three primary transfer functions (HOTTFs), as well as two derived transfer functions (HETTFs) arising from the convolution of the HOTTFs, are namely; Symmetric Saturated Linear transfer function (SATLINS ), Hyperbolic Tangent transfer function (TANH), Hyperbolic Tangent sigmoid transfer function (TANSIG), Symmetric Saturated Linear and Hyperbolic Tangent transfer function (SATLINS-TANH) and Symmetric Saturated Linear and Hyperbolic Tangent Sigmoid transfer function (SATLINS-TANSIG). Data on the Terrorist activities in Nigeria gathered through questionnaires for the purpose of this study were used. Mean Square Error (MSE), Mean Absolute Error (MAE) and Test Error are the forecast prediction criteria. The results showed that the HETFs performed better in terms of prediction and factors associated with terrorist activities in Nigeria were determined. The proposed predictive deep learning-based model will be useful to governments and law enforcement agencies as an effective counterterrorism mechanism to understand the parameters of terrorism and to design strategies to deal with terrorism before an incident actually happens and potentially causes the loss of precious lives. The proposed predictive AI-based model will reduce the chances of terrorist activities and is particularly helpful for security agencies to predict future terrorist activities.

Keywords: activation functions, Bayesian neural network, mean square error, test error, terrorism

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Authors: Ankita Singh, Chandan Gorain, Amirul I. Mallick

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Successful adherence of the mucosal epithelial cells is the key early step for Campylobacter jejuni pathogenesis (C. jejuni). A set of Surface Exposed Colonization Proteins (SECPs) are among the major factors involved in host cell adherence and invasion of C. jejuni. Among them, constitutively expressed surface-exposed lipoprotein adhesin of C. jejuni, JlpA, interacts with intestinal heat shock protein 90 (hsp90α) and contributes in disease progression by triggering pro-inflammatory response via activation of NF-κB and p38 MAP kinase pathway. Together with its ability to express in the bacterial surface, higher sequence conservation and predicted predominance of several B cells epitopes, JlpA protein reserves its potential to become an effective vaccine candidate against wide range of Campylobacter sps including C. jejuni. Given that chickens are the primary sources for C. jejuni and persistent gut colonization remain as major cause for foodborne pathogenesis to humans, present study explicitly used chickens as model to test the immune-protective efficacy of JlpA protein. Taking into account that gastrointestinal tract is the focal site for C. jejuni colonization, to extrapolate the benefit of mucosal (intragastric) delivery of JlpA protein, a food grade Nisin inducible Lactic acid producing bacteria, Lactococcus lactis (L. lactis) was engineered to express recombinant JlpA protein (rJlpA) in the surface of the bacteria. Following evaluation of optimal surface expression and functionality of recombinant JlpA protein expressed by recombinant L. lactis (rL. lactis), the immune-protective role of intragastric administration of live rL. lactis was assessed in commercial broiler chickens. In addition to the significant elevation of antigen specific mucosal immune responses in the intestine of chickens that received three doses of rL. lactis, marked upregulation of Toll-like receptor 2 (TLR2) gene expression in association with mixed pro-inflammatory responses (both Th1 and Th17 type) was observed. Furthermore, intragastric delivery of rJlpA expressed by rL. lactis, but not the injectable form, resulted in a significant reduction in C. jejuni colonization in chickens suggesting that mucosal delivery of live rL. lactis expressing JlpA serves as a promising vaccine platform to induce strong immune-protective responses against C. jejuni in chickens.

Keywords: chickens, lipoprotein adhesion of Campylobacter jejuni, immuno-protection, Lactococcus lactis, mucosal delivery

Procedia PDF Downloads 133

Authors: Beate Englich, Linda Schlittenbauer, Christiane Pfeifer, Isabel Kratochvil, Michael Borte, Gabriele I. Stangl, Martin von Bergen, Thorsten Reemtsma, Irina Lehmann, Kristin M. Junge

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The worldwide production of endocrine disrupting compounds (EDC) has risen dramatically over the last decades, as so has the prevalence for obesity. Many EDCs are believed to contribute to this obesity epidemic, by enhancing adipogenesis or disrupting relevant metabolism. This effect is most tremendous in the early prenatal period when priming effects find a highly vulnerable time window. Therefore, we investigate the impact of parabens on childhood overweight development and adipogenesis in general. Parabens are ester of 4-hydroxy-benzoic acid and part of many cosmetic products or food packing. Therefore, ubiquitous exposure can be found in the westernized world, with exposure already starting during the sensitive prenatal period. We assessed maternal cosmetic product consumption, prenatal paraben exposure and infant BMI z-scores in the prospective German LINA cohort. In detail, maternal urinary concentrations (34 weeks of gestation) of methyl paraben (MeP), ethyl paraben (EtP), n-propyl paraben (PrP) and n-butyl paraben (BuP) were quantified using UPLC-MS/MS. Body weight and height of their children was assessed during annual clinical visits. Further, we investigated the direct influence of those parabens on adipogenesis in-vitro using a human mesenchymal stem cell (MSC) differentiation assay to mimic a prenatal exposure scenario. MSC were exposed to 0.1 – 50 µM paraben during the entire differentiation period. Differentiation outcome was monitored by impedance spectrometry, real-time PCR and triglyceride staining. We found that maternal cosmetic product consumption was highly correlated with urinary paraben concentrations at pregnancy. Further, prenatal paraben exposure was linked to higher BMI Z-scores in children. Our in-vitro analysis revealed that especially the long chained paraben BuP stimulates adipogenesis by increasing the expression of adipocyte specific genes (PPARγ, ADIPOQ, LPL, etc.) and triglyceride storage. Moreover, we found that adiponectin secretion is increased whereas leptin secretion is reduced under BuP exposure in-vitro. Further mechanistic analysis for receptor binding and activation of PPARγ and other key players in adipogenesis are currently in process. We conclude that maternal cosmetic product consumption is linked to prenatal paraben exposure of children and contributes to the development of infant overweight development by triggering key pathways of adipogenesis.

Keywords: adipogenesis, endocrine disruptors, paraben, prenatal exposure

Procedia PDF Downloads 268

Authors: Weiliang Gong, Lissa Gomes, Lucile Raymond, Hui Xu, Werner Lutze, Ian L. Pegg

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Alkali-activated materials, particularly geopolymers, have attracted much interest in academia. Commercial applications are on the rise, as well. Geopolymers are produced typically by a reaction of one or two aluminosilicates with an alkaline solution at room temperature. Fly ash is an important aluminosilicate source. However, using low-Ca fly ash, the byproduct of burning hard or black coal reacts and sets slowly at room temperature. The development of mechanical durability, e.g., compressive strength, is slow as well. The use of fly ashes with relatively high contents ( > 6%) of unburned carbon, i.e., high loss on ignition (LOI), is particularly disadvantageous as well. This paper will show to what extent these impediments can be mitigated by mixing the fly ash with one or two more aluminosilicate sources. The fly ash used here is generated at the Orlando power plant (Florida, USA). It is low in Ca ( < 1.5% CaO) and has a high LOI of > 6%. The additional aluminosilicate sources are metakaolin and blast furnace slag. Binary fly ash-metakaolin and ternary fly ash-metakaolin-slag geopolymers were prepared. Properties of geopolymer pastes before and after setting have been measured. Fresh mixtures of aluminosilicates with an alkaline solution were studied by Vicat needle penetration, rheology, and isothermal calorimetry up to initial setting and beyond. The hardened geopolymers were investigated by SEM/EDS and the compressive strength was measured. Initial setting (fluid to solid transition) was indicated by a rapid increase in yield stress and plastic viscosity. The rheological times of setting were always smaller than the Vicat times of setting. Both times of setting decreased with increasing replacement of fly ash with blast furnace slag in a ternary fly ash-metakaolin-slag geopolymer system. As expected, setting with only Orlando fly ash was the slowest. Replacing 20% fly ash with metakaolin shortened the set time. Replacing increasing fractions of fly ash in the binary system by blast furnace slag (up to 30%) shortened the time of setting even further. The 28-day compressive strength increased drastically from < 20 MPa to 90 MPa. The most interesting finding relates to the calorimetric measurements. The use of two or three aluminosilicates generated significantly more heat (20 to 65%) than the calculated from the weighted sum of the individual aluminosilicates. This synergetic heat contributes or may be responsible for most of the increase of compressive strength of our binary and ternary geopolymers. The synergetic heat effect may be also related to increased incorporation of calcium in sodium aluminosilicate hydrate to form a hybrid (N,C)A-S-H) gel. The time of setting will be correlated with heat release and maximum heat flow.

Keywords: alkali-activated materials, binary and ternary geopolymers, blends of fly ash, metakaolin and blast furnace slag, rheology, synergetic heats

Procedia PDF Downloads 111

Authors: Inbal Zuriely, Yonit Weiss, Hilla Zaharoni, Hadas Lewkowicz, Tatiana Vander, Tarif Bader

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early active movement, along with adjusting optimal nutrition, prevents aggravation of muscle degeneracy and functional decline. Eating is a basic activity of daily life, which reflects the patient's independence. When eating and feeding are experienced successfully, they lead to a sense of pleasure and satisfaction. However, when they are experienced as a difficulty, they might evoke feelings of helplessness and frustration. This stresses the essential process of gradual weaning off the enteral feeding tube. the work describes the collaboration of a dietitian, determining the nutritional needs of patients undergoing enteral tube weaning as part of the rehabilitation process, with the suited treatment of an occupational therapist. Occupational therapy intervention regarding eating capabilities focuses on improving the required motor and cognitive components, along with environmental adjustments and aids, imparting eating strategies and training to patients and their families. The project was conducted in the long-term, ventilated patients’ department at the Herzfeld Rehabilitation Geriatric Medical Center on patients undergoing enteral tube weaning with the staff’s assistance. Establishing continuous collaboration between the dietician and the occupational therapist, starting from the beginning of the feeding-tube weaning process: 1.The dietician updates the occupational therapist about the start of the process and the approved diet. 2.The occupational therapist performs cognitive, motor, and functional assessments and treatments regarding the patient’s eating capabilities and recommends the required adjustments for independent eating according to the FIM (Functional Independence Measure) scale. 3.The occupational therapist closely follows up on the patient’s degree of independence in eating and provides a repeated update to the dietician. 4.The dietician accordingly guides the ward staff on whether and how to feed the patient or allow independent eating. The project aimed to promote patients toward independent feeding, which leads to a sense of empowerment, enjoyment of the eating experience, and progress of functional ability, along with performing active movements that will motivate mobilization. From the beginning of 2022, 26 patients participated in the project. 79% of all patients who started the weaning process from tube feeding achieved different levels of independence in feeding (independence levels ranged from supervision (FIM-5) to complete independence (FIM-7). The integration of occupational therapy and dietary treatment is based on a patient-centered approach while considering the patient’s personal needs, preferences, and goals. This interdisciplinary partnership is essential for meeting the complex needs of prolonged mechanically ventilated patients and promotes independent functioning and quality of life.

Keywords: dietary, mechanical ventilation, occupational therapy, tube feeding weaning

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Authors: Tiziana Pepe, Gerardo Manfreda, Adriana Ianieri, Aniello Anastasio

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The sustainable exploitation of marine biological resources is among the most important objectives of the EU's Common Fisheries Policy (CFP). Currently, Europe imports about 65% of its fish products, indicating that domestic production does not meet consumer demand. Despite the availability of numerous commercially significant fish species, European consumption is concentrated on a limited number of products (e.g., sea bass, sea bream, shrimp). Many native species, present in large quantities in the Mediterranean Sea, are little known to consumers and are therefore considered ‘fishing by-products’. All the data presented so far indicate a significant waste of local resources and the overexploitation of a few fish stocks. It is therefore necessary to develop strategies that guide the market towards sustainable conversion. The objective of this work was to valorize underutilized fish species of the Mediterranean Sea through a multidisciplinary approach. To this end, three fish species were sampled: Atlantic Horse Mackerel (Trachurus trachurus), Bogue (Boops boops), and Common Dolphinfish (Coryphaena hippurus). Nutritional properties (water %, fats, proteins, ashes, salts), physical/chemical properties (TVB-N, histamine, pH), and rheological properties (color, texture, viscosity) were analyzed. The analyses were conducted on both fillets and processing by-products. Additionally, mitochondrial DNA (mtDNA) was extracted from the muscle of each species. The mtDNA was then sequenced using the Illumina NGS technique. The analysis of nutritional properties classified the fillets of the sampled species as lean or semi-fat, as they had a fat content of less than 3%, while the by-products showed a higher lipid content (2.7-5%). The protein percentage for all fillets was 22-23%, while for processing by-products, the protein concentration was 18-19% for all species. Rheological analyses showed an increase in viscosity in saline solution in all species, indicating their potential suitability for industrial processing. High-quality and quantity complete mtDNA was extracted from all analyzed species. The complete mitochondrial genome sequences were successfully obtained and annotated. The results of this study suggest that all analyzed species are suitable for both human consumption and feed production. The sequencing of the complete mtDNA and its availability in international databases will be useful for accurate phylogenetic analysis and proper species identification, even in prepared and processed products. Underutilized fish species represent an important economic resource. Encouraging their consumption could limit the phenomenon of overfishing, protecting marine biodiversity. Furthermore, the valorization of these species will increase national fish production, supporting the local economy, cultural, and gastronomic tradition, and optimizing the exploitation of Mediterranean resources in accordance with the CFP.

Keywords: mtDNA, nutritional analysis, sustainable fisheries, underutilized fish species

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Authors: I. Witbooi, J. De Smidt, A. Oelofse

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Negative emotions that are common in depression are coupled with the activation of the corrugator supercilli and procerus muscles in the glabellar region of the face. This research investigated the impact of OnabotulinumtoxinA (BOTOX) in the improvement of emotional states in depressed subjects by relaxing the mentioned muscles. The aim of the study was to investigate the effectiveness of BOTOX treatment for glabellar frown lines as an adjunctive therapy for Major Depressive Disorder (MDD) and to improve the quality of life and self-esteem of the subjects. It is hypothesized that BOTOX treatment for glabellar frown lines reduces depressive symptoms significantly and therefore augment conventional antidepressant medication. Forty-five (45) subjects diagnosed with MDD were assigned to a treatment (n = 15), placebo (n = 15), and control (n = 15) group. The treatment group received BOTOX injection, while the placebo group received saline injection into the Procerus and Corrugator supercilli muscles with follow-up visits every 3 weeks (weeks 3, 6 and 12 respectively). The control group received neither BOTOX nor saline injections and were only interviewed again on the 12th week. To evaluate the effect of BOTOX treatment in the glabellar region on depressive symptoms, the Montgomery-Asberg Depression Rating (MADRS) scale and the Beck Depression Inventory (BDI) were used. The Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) and Rosenberg Self-Esteem Scale (RSES) were used in the assessment of self-esteem and quality of life. Participants were followed up for a 12 week period. The expected primary outcome measure is the response to treatment, and it is defined as a ≥ 50% reduction in MADRS score from baseline. Other outcome measures include a clinically significant decrease in BDI scores and the increase in quality of life and self-esteem respectively. Initial results show a clear trend towards such differences. Results showed trends towards expected differences. Patients in the Botox group had a mean MADRS score of 14.0 at 3 weeks compared to 20.3 of the placebo group. This trend was still visible at 6 weeks with the Botox and placebo group scoring an average of 10 vs. 18 respectively. The mean difference in MDRS scores from baseline to 3 weeks were 9.3 and 2.0 for the Botox and placebo group respectively. Similarly, the BDI scores were lower in the Botox group (17.25) compared to the placebo group (19.43). The two self-esteem questionnaires showed expected results at this stage with the RSES 19.1 in the Botox group compared to 18.6 in the placebo group. Similarly, the Botox patients had a higher score for the Q-LES-Q-SF of 49.2 compared to 46.1 for the placebo group. Conclusions: Initial results clearly demonstrated that the use of Botox had positive effects on both scores of depressions and that of self-esteem when compared to a placebo group.

Keywords: adjunctive therapy, depression, glabellar area, OnabotulinumtoxinA

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Authors: Matthew E. Potter, Daniel J. Stewart, Lindsay M. Armstrong, Pier J. A. Sazio, Robert R. Raja

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Rising CO₂ levels in the atmosphere means that CO₂ is a highly desirable feedstock. This requires specific catalysts to be designed to activate this inert molecule, combining a catalytic site tailored for CO₂ transformations with a support that can readily adsorb CO₂. Metal organic frameworks (MOFs) are regularly used as CO₂ sorbents. The organic nature of the linker molecules, connecting the metal nodes, offers many post-synthesis modifications to introduce catalytic active sites into the frameworks. However, the metal nodes may be coordinatively unsaturated, allowing them to bind to organic moieties. Imidazoles have shown promise catalyzing the formation of cyclic carbonates from epoxides with CO₂. Typically, this synthesis route employs toxic reagents such as phosgene, liberating HCl. Therefore an alternative route with CO₂ is highly appealing. In this work we design active sites for CO₂ activation, by tethering substituted-imidazole organocatalytic species to the available Cr3+ metal nodes of a Cr-MIL-101 MOF, for the first time, to create a tailored species for carbon capture utilization applications. Our tailored design strategy combining a CO₂ sorbent, Cr-MIL-101, with an anchored imidazole results in a highly active and selective multifunctional catalyst, achieving turnover frequencies of over 750 hr-1. These findings demonstrate the synergy between the MOF framework and imidazoles for CO₂ utilization applications. Further, the effect of substrate variation has been explored yielding mechanistic insights into this process. Through characterization, we show that the structural and compositional integrity of the Cr-MIL-101 has been preserved on functionalizing the imidazoles. Further, we show the binding of the imidazoles to the Cr3+ metal nodes. This can be seen through our EPR study, where the distortion of the Cr3+ on binding to the imidazole shows the CO₂ binding site is close to the active imidazole. This has a synergistic effect, improving catalytic performance. We believe the combination of MOF support and organocatalyst allows many possibilities to generate new multifunctional catalysts for CO₂ utilisation. In conclusion, we have validated our design procedure, combining a known CO₂ sorbent, with an active imidazole species to create a unique tailored multifunctional catalyst for CO₂ utilization. This species achieves high activity and selectivity for the formation of cyclic carbonates and offers a sustainable alternative to traditional synthesis methods. This work represents a unique design strategy for CO₂ utilization while offering exciting possibilities for further work in characterization, computational modelling, and post-synthesis modification.

Keywords: carbonate, catalysis, MOF, utilisation

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Authors: Magdalena Jablonska, Andrzej Falkowski

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The negativity effect is one of the most intriguing and well-studied psychological phenomena that can be observed in many areas of human life. The aim of the following study is to investigate how valence framing and positive and negative information about political candidates affect judgments about similarity to an ideal and bad politician. Based on the theoretical framework of features of similarity, it is hypothesized that negative features have a stronger effect on similarity judgments than positive features of comparable value. Furthermore, the mediating role of affect is tested. Method: One hundred sixty-one people took part in an experimental study. Participants were divided into 6 research conditions that differed in the reference point (positive vs negative framing) and the number of favourable and unfavourable information items about political candidates (a positive, neutral and negative candidate profile). In positive framing condition, the concept of an ideal politician was primed; in the negative condition, participants were to think about a bad politician. The effect of independent variables on similarity judgments, affective evaluation, and voting intention was tested. Results: In the positive condition, the analysis showed that the negative effect of additional unfavourable features was greater than the positive effect of additional favourable features in judgements about similarity to the ideal candidate. In negative framing condition, ANOVA was insignificant, showing that neither the addition of positive features nor additional negative information had a significant impact on the similarity to a bad political candidate. To explain this asymmetry, two mediational analyses were conducted that tested the mediating role of affect in the relationship between similarity judgments and voting intention. In both situations the mediating effect was significant, but the comparison of two models showed that the mediation was stronger for a negative framing. Discussion: The research supports the negativity effect and attempts to explain the psychological mechanism behind the positive-negative asymmetry. The results of mediation analyses point to a stronger mediating role of affect in the relationship between cognitive evaluation and voting intention. Such a result suggests that negative comparisons, leading to the activation of negative features, give rise to stronger emotions than positive features of comparable strength. The findings are in line with positive-negative asymmetry, however, by adopting Tversky’s framework of features of similarity, the study integrates the cognitive mechanism of the negativity effect delineated in the contrast model of similarity with its emotional component resulting from the asymmetrical effect of positive and negative emotions on decision-making.

Keywords: affect, framing, negativity effect, positive-negative asymmetry, similarity judgements

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Authors: Christine P. Gibson, Ramona Alex, Michael Farney, Johana Vallejo-Elias, Mitra Esfandiarei

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Aortic aneurysm is the leading cause of death in Marfan syndrome (MFS), a connective tissue disorder caused by mutations in fibrillin-1 gene (FBN1). MFS aneurysm is characterized by weakening of the aortic wall due to elastin fibers fragmentation and disorganization. The above-average height and distinct physical features make young adults with MFS desirable candidates for competitive sports; but little is known about the exercise limit at which they will be at risk for aortic rupture. On the other hand, aerobic cardiovascular exercise has been shown to have protective effects on the heart and aorta. We have previously reported that mild aerobic exercise can delay the formation of aortic aneurysm in a mouse model of MFS. In this study, we aimed to investigate the effects of various levels of exercise intensity on the progression of aortic aneurysm in the mouse model. Starting at 4 weeks of age, we subjected control and MFS mice to different levels of exercise intensity (8m/min, 10m/min, 15m/min, and 20m/min, corresponding to 55%, 65%, 75%, and 85% of VO2 max, respectively) on a treadmill for 30 minutes per day, five days a week for the duration of the study. At 24 weeks of age, aortic tissue were isolated and subjected to structural and functional studies using histology and wire myography in order to evaluate the effects of different exercise routines on elastin fragmentation and organization and aortic wall elasticity/stiffness. Our data shows that exercise training at the intensity levels between 55%-75% significantly reduces elastin fragmentation and disorganization, with less recovery observed in 85% MFS group. The reversibility of elasticity was also significantly restored in MFS mice subjected to 55%-75% intensity; however, the recovery was less pronounced in MFS mice subjected to 85% intensity. Furthermore, our data shows that smooth muscle cells (SMCs) contractilion in response to vasoconstrictor agent phenylephrine (100nM) is significantly reduced in MFS aorta (54.84 ± 1.63 mN/mm2) as compared to control (95.85 ± 3.04 mN/mm2). At 55% of intensity, exercise did not rescue SMCs contraction (63.45 ± 1.70 mN/mm2), while at higher intensity levels, SMCs contraction in response to phenylephrine was restored to levels similar to control aorta [65% (81.88 ± 4.57 mN/mm2), 75% (86.22 ± 3.84 mN/mm2), and 85% (83.91 ± 5.42 mN/mm2)]. This study provides the first time evidence that high intensity exercise (e.g. 85%) may not provide the most beneficial effects on aortic function (vasoconstriction) and structure (elastin fragmentation, aortic wall elasticity) during the progression of aortic aneurysm in MFS mice. On the other hand, based on our observations, medium intensity exercise (e.g. 65%) seems to provide the utmost protective effects on aortic structure and function in MFS mice. These findings provide new insights into the potential capacity, in which MFS patients could participate in various aerobic exercise routines, especially in young adults affected by cardiovascular complications particularly aortic aneurysm. This work was funded by Midwestern University Research Fund.

Keywords: aerobic exercise, aortic aneurysm, aortic wall elasticity, elastin fragmentation, Marfan syndrome

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Authors: A. Pallavi, N. Vijay Mohan

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A nation can be economically progressive only when the citizens have sufficient capacity to work efficiently to increase the productivity. So, good health must be regarded as a primary need of the community. This helps the growth and development of the body and the mind, which in turn leads to progress and prosperity of the nation. An optimum growth is a necessity for an efficient existence in a biologically adverse and economically competitive world. It is also necessary for the execution of daily routine work. Yoga is a method or a system for the complete development of the personality in a human being. It can be further elaborated as an all-around and complete development of the body, mind, morality, intellect and soul of a being. Sri Aurobindo defines yoga as 'a methodical effort towards self-perfection by the development of the potentialities in the individual.' Aerobic exercise as any activity that uses large muscle groups, can be maintained continuously, and is rhythmic I nature. It is a type of exercise that overloads the heart and lungs and causes them to work harder than at rest. The important idea behind aerobic exercise today, is to get up and get moving. There are more activities that ever to choose from, whether it is a new activity or an old one. Find something you enjoy doing that keeps our heart rate elevated for a continuous time period and get moving to a healthier life. Middle aged selected and served as the subjects for the purpose of this study. The selected subjects were in the age group of 30 to 40 years. By going through the literature and after consulting the experts in yoga and aerobic training, the investigator had chosen the variables which are specifically related to the middle-aged men. The selected physiological variables are pulse rate, diastolic blood pressure, systolic blood pressure; percent body fat and vital capacity. The selected psychological variables are job anxiety, occupational stress. The study was formulated as a random group design consisting of aerobic exercise and yogic exercises groups. The subjects (N=60) were at random divided into three equal groups of twenty middle-aged men each. The groups were assigned the names as follows: 1. Experimental group I- aerobic exercises group, 2. Experimental group II- yogic exercises, 3. Control group. All the groups were subjected to pre-test prior to the experimental treatment. The experimental groups participated in their respective duration of twenty-four weeks, six days in a week throughout the study. The various tests administered were: prior to training (pre-test), after twelfth week (second test) and twenty-fourth weeks (post-test) of the training schedule.

Keywords: pulse rate, diastolic blood pressure, systolic blood pressure; percent body fat and vital capacity, psychological variables, job anxiety, occupational stress, aerobic exercise, yogic exercise

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Authors: Orkide Donma, Mustafa M. Donma

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Association between insulin resistance (IR) and hematological parameters has long been a matter of interest. Within this context, body mass index (BMI), red blood cells, white blood cells and platelets were involved in this discussion. Parameters related to platelets associated with IR may be useful indicators for the identification of IR. Platelet indices such as mean platelet volume (MPV), platelet distribution width (PDW) and plateletcrit (PCT) are being questioned for their possible association with IR. The aim of this study was to investigate the association between platelet (PLT) count as well as PLT indices and the surrogate indices used to determine IR in morbid obese (MO) children. A total of 167 children participated in the study. Three groups were constituted. The number of cases was 34, 97 and 36 children in the normal BMI, MO and metabolic syndrome (MetS) groups, respectively. Sex- and age-dependent BMI-based percentile tables prepared by World Health Organization were used for the definition of morbid obesity. MetS criteria were determined. BMI values, homeostatic model assessment for IR (HOMA-IR), alanine transaminase-to-aspartate transaminase ratio (ALT/AST) and diagnostic obesity notation model assessment laboratory (DONMA-lab) index values were computed. PLT count and indices were analyzed using automated hematology analyzer. Data were collected for statistical analysis using SPSS for Windows. Arithmetic mean and standard deviation were calculated. Mean values of PLT-related parameters in both control and study groups were compared by one-way ANOVA followed by Tukey post hoc tests to determine whether a significant difference exists among the groups. The correlation analyses between PLT as well as IR indices were performed. Statistically significant difference was accepted as p-value < 0.05. Increased values were detected for PLT (p < 0.01) and PCT (p > 0.05) in MO group compared to those observed in children with N-BMI. Significant increases for PLT (p < 0.01) and PCT (p < 0.05) were observed in MetS group in comparison with the values obtained in children with N-BMI (p < 0.01). Significantly lower MPV and PDW values were obtained in MO group compared to the control group (p < 0.01). HOMA-IR (p < 0.05), DONMA-lab index (p < 0.001) and ALT/AST (p < 0.001) values in MO and MetS groups were significantly increased compared to the N-BMI group. On the other hand, DONMA-lab index values also differed between MO and MetS groups (p < 0.001). In the MO group, PLT was negatively correlated with MPV and PDW values. These correlations were not observed in the N-BMI group. None of the IR indices exhibited a correlation with PLT and PLT indices in the N-BMI group. HOMA-IR showed significant correlations both with PLT and PCT in the MO group. All of the three IR indices were well-correlated with each other in all groups. These findings point out the missing link between IR and PLT activation. In conclusion, PLT and PCT may be related to IR in addition to their identities as hemostasis markers during morbid obesity. Our findings have suggested that DONMA-lab index appears as the best surrogate marker for IR due to its discriminative feature between morbid obesity and MetS.

Keywords: children, insulin resistance, metabolic syndrome, plateletcrit, platelet indices

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Authors: Evanka Madan, Madhu Puri, Dan Zilberstein, Rohini Muthuswami, Rentala Madhubala

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The extensive interaction between the host and pathogen metabolic networks decidedly shapes the outcome of infection. Utilization of arginine by the host and pathogen is critical for determining the outcome of pathogenic infection. Infections with L. donovani, an intracellular parasite, will lead to an extensive competition of arginine between the host and the parasite donovani infection. One of the major amino acid (AA) sensing signaling pathways in mammalian cells are the mammalian target of rapamycin complex I (mTORC1) pathway. mTORC1, as a sensor of nutrient, controls numerous metabolic pathways. Arginine is critical for mTORC1 activation. SLC38A9 is the arginine sensor for the mTORC1, being activated during arginine sufficiency. L. donovani transport arginine via a high-affinity transporter (LdAAP3) that is rapidly up-regulated by arginine deficiency response (ADR) in intracellular amastigotes. This study, to author’s best knowledge, investigates the interaction between two arginine sensing systems that act in the same compartment, the lysosome. One is important for macrophage defense, and the other is essential for pathogen virulence. We hypothesize that the latter modulates lysosome arginine to prevent host defense response. The work presented here identifies an upstream regulatory role of LdAAP3 in regulating the expression of SLC38A9-mTORC1 pathway, and consequently, their function in L. donovani infected THP-1 cells cultured in 0.1 mM and 1.5 mM arginine. It was found that in physiological levels of arginine (0.1 mM), infecting THP-1 with Leishmania leads to increased levels of SLC38A9 and mTORC1 via an increase in the expression of RagA. However, the reversal was observed with LdAAP3 mutants, reflecting the positive regulatory role of LdAAP3 on the host SLC38A9. At the molecular level, upon infection, mTORC1 and RagA were found to be activated at the surface of phagolysosomes which was found to form a complex with phagolysosomal localized SLC38A9. To reveal the relevance of SLC38A9 under physiological levels of arginine, endogenous SLC38A9 was depleted and a substantial reduction in the expression of host mTORC1, its downstream active substrate, p-P70S6K1 and parasite LdAAP3, was observed, thereby showing that silencing SLC38A9 suppresses ADR. In brief, to author’s best knowledge, these results reveal an upstream regulatory role of LdAAP3 in manipulating SLC38A9 arginine sensing in host macrophages. Our study indicates that intra-macrophage survival of L. donovani depends on the availability and transport of extracellular arginine. An understanding of the sensing pathway of both parasite and host will open a new perspective on the molecular mechanism of host-parasite interaction and consequently, as a treatment for Leishmaniasis.

Keywords: arginine sensing, LdAAP3, L. donovani, mTORC1, SLC38A9, THP-1

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Authors: R. Pussinen, V. Jankovic, U. Herzberg, M. Cerrada-Gimenez, T. Huhtala, A. Nurmi, T. Ahtoniemi

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Targeted over-expression of human α-synuclein using viral-vector mediated gene delivery into the substantia nigra of rats and non-human primates has been reported to lead to dopaminergic cell loss and the formation of α-synuclein aggregates reminiscent of Lewy bodies. We have previously shown how AAV-mediated expression of α-synuclein is seen in the chronic phenotype of the rats over 16 week follow-up period. In the context of these findings, we attempted to further characterize this long term PD related functional and motor deficits as well as neurochemical and neuropathological changes in AAV-mediated α-synuclein transfection model in rats during chronic follow-up period. Different titers of recombinant AAV expressing human α-synuclein (A53T) were stereotaxically injected unilaterally into substantia nigra of Wistar rats. Rats were allowed to recover for 3 weeks prior to initial baseline behavioral testing with rotational asymmetry test, stepping test and cylinder test. A similar behavioral test battery was applied again at weeks 5, 9,12 and 15. In addition to traditionally used rat PD model tests, MotoRater test system, a high speed kinematic gait performance monitoring was applied during the follow-up period. Evaluation focused on animal gait between groups. Tremor analysis was performed on weeks 9, 12 and 15. In addition to behavioral end-points, neurochemical evaluation of dopamine and its metabolites were evaluated in striatum. Furthermore, integrity of the dopamine active transport (DAT) system was evaluated by using 123I- β-CIT and SPECT/CT imaging on weeks 3, 8 and 12 after AAV- α-synuclein transfection. Histopathology was examined from end-point samples at 3 or 12 weeks after AAV- α-synuclein transfection to evaluate dopaminergic cell viability and microglial (Iba-1) activation status in substantia nigra by using stereological analysis techniques. This study focused on the characterization and validation of previously published AAV- α-synuclein transfection model in rats but with the addition of novel end-points. We present the long term phenotype of AAV- α-synuclein transfected rats with traditionally used behavioral tests but also by using novel fine motor analysis techniques and tremor analysis which provide new insight to unilateral effects of AAV α-synuclein transfection. We also present data about neurochemical and neuropathological end-points for the dopaminergic system in the model and how well they correlate with behavioral phenotype.

Keywords: adeno-associated virus, alphasynuclein, animal model, Parkinson’s disease

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Authors: Mitakshara Sharma, S. K. Nema, Sanjeev Narang

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Diabetes mellitus (DM) is a group of metabolic disorders characterized by metabolic abnormalities, chronic hyperglycaemia and long term macrovascular & microvascular complications. Vascular complications are due to platelet hyperactivity and dysfunction, increased inflammation, altered coagulation and endothelial dysfunction. Large proportion of patients with Type II DM suffers from preventable vascular angiopathies, and there is need to develop risk factor modifications and interventions to reduce impact of complications. These complications are attributed to platelet activation, recognised by increase in Platelet Volume Indices (PVI) including Mean Platelet Volume (MPV) and Platelet Distribution Width (PDW). The current study is prospective analytical study conducted over 2 years. Out of 1100 individuals, 930 individuals fulfilled inclusion criteria and were segregated into three groups on basis of glycosylated haemoglobin (HbA1C): - (a) Diabetic, (b) Non-Diabetic and (c) Subjects with Impaired fasting glucose (IFG) with 300 individuals in IFG and non-diabetic groups & 330 individuals in diabetic group. Further, diabetic group was divided into two groups on the basis of presence or absence of known diabetes related vascular complications. Samples for HbA1c and PVI were collected using Ethylene diamine tetraacetic acid (EDTA) as anticoagulant and processed on SYSMEX-X-800i autoanalyser. The study revealed gradual increase in PVI from non-diabetics to IFG to diabetics. PVI were markedly increased in diabetic patients. MPV and PDW of diabetics, IFG and non diabetics were (17.60 ± 2.04)fl, (11.76 ± 0.73)fl, (9.93 ± 0.64)fl and (19.17 ± 1.48)fl, (15.49 ± 0.67)fl, (10.59 ± 0.67)fl respectively with a significant p value 0.00 and a significant positive correlation (MPV-HbA1c r = 0.951; PDW-HbA1c r = 0.875). MPV & PDW of subjects with diabetes related complications were higher as compared to those without them and were (17.51±0.39)fl & (15.14 ± 1.04)fl and (20.09 ± 0.98) fl & (18.96 ± 0.83)fl respectively with a significant p value 0.00. There was a significant positive correlation between PVI and duration of diabetes across the groups (MPV-HbA1c r = 0.951; PDW-HbA1c r = 0.875). However, a significant negative correlation was found between glycaemic levels and total platelet count (PC- HbA1c r =-0.164). This is multi-parameter and comprehensive study with an adequately powered study design. It can be concluded from our study that PVI are extremely useful and important indicators of impending vascular complications in all patients with deranged glycaemic control. Introduction of automated cell counters has facilitated the availability of PVI as routine parameters. PVI is a useful means for identifying larger & active platelets which play important role in development of micro and macro angiopathic complications of diabetes leading to mortality and morbidity. PVI can be used as cost effective markers to predict and prevent impending vascular events in patients with Diabetes mellitus especially in developing countries like India. PVI, if incorporated into protocols for management of diabetes, could revolutionize care and curtail the ever increasing cost of patient management.

Keywords: diabetes, IFG, HbA1C, MPV, PDW, PVI

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Authors: Abdulaziz Alakeel, Roaa Alamri, Abdulrahman Alomair, Mohammed Fouda

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Introduction: Ibrutinib is a selective, potent, and irreversible small-molecule inhibitor of Bruton's tyrosine kinase (BTK). It forms a covalent bond with a cysteine residue (CYS-481) at the active site of Btk, leading to inhibition of Btk enzymatic activity. The drug is indicated to treat certain type of cancers such as mantle cell lymphoma (MCL), chronic lymphocytic leukaemia and Waldenström's macroglobulinaemia (WM). Cardiac failure is a condition referred to inability of heart muscle to pump adequate blood to human body organs. There are multiple types of cardiac failure including left and right-sided heart failure, systolic and diastolic heart failures. The aim of this review is to evaluate the risk of cardiac failure associated with the use of ibrutinib and to suggest regulatory recommendations if required. Methodology: Signal Detection team at the National Pharmacovigilance Center (NPC) of Saudi Food and Drug Authority (SFDA) performed a comprehensive signal review using its national database as well as the World Health Organization (WHO) database (VigiBase), to retrieve related information for assessing the causality between cardiac failure and ibrutinib. We used the WHO- Uppsala Monitoring Centre (UMC) criteria as standard for assessing the causality of the reported cases. Results: Case Review: The number of resulted cases for the combined drug/adverse drug reaction are 212 global ICSRs as of July 2020. The reviewers have selected and assessed the causality for the well-documented ICSRs with completeness scores of 0.9 and above (35 ICSRs); the value 1.0 presents the highest score for best-written ICSRs. Among the reviewed cases, more than half of them provides supportive association (four probable and 15 possible cases). Data Mining: The disproportionality of the observed and the expected reporting rate for drug/adverse drug reaction pair is estimated using information component (IC), a tool developed by WHO-UMC to measure the reporting ratio. Positive IC reflects higher statistical association while negative values indicates less statistical association, considering the null value equal to zero. The results of (IC=1.5) revealed a positive statistical association for the drug/ADR combination, which means “Ibrutinib” with “Cardiac Failure” have been observed more than expected when compared to other medications available in WHO database. Conclusion: Health regulators and health care professionals must be aware for the potential risk of cardiac failure associated with ibrutinib and the monitoring of any signs or symptoms in treated patients is essential. The weighted cumulative evidences identified from causality assessment of the reported cases and data mining are sufficient to support a causal association between ibrutinib and cardiac failure.

Keywords: cardiac failure, drug safety, ibrutinib, pharmacovigilance, signal detection

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Authors: Angela U. Makolo

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Protein-coding and Non-coding regions determine the biology of a sequenced transcriptome. Research advances have shown that Non-coding regions are important in disease progression and clinical diagnosis. Existing bioinformatics tools have been targeted towards Protein-coding regions alone. Therefore, there are challenges associated with gaining biological insights from transcriptome sequence data. These tools are also limited to computationally intensive sequence alignment, which is inadequate and less accurate to identify both Protein-coding and Non-coding regions. Alignment-free techniques can overcome the limitation of identifying both regions. Therefore, this study was designed to develop an efficient sequence alignment-free model for identifying both Protein-coding and Non-coding regions in sequenced transcriptomes. Feature grouping and randomization procedures were applied to the input transcriptomes (37,503 data points). Successive iterations were carried out to compute the gradient vector that converged the developed Protein-coding and Non-coding Region Identifier (PNRI) model to the approximate coefficient vector. The logistic regression algorithm was used with a sigmoid activation function. A parameter vector was estimated for every sample in 37,503 data points in a bid to reduce the generalization error and cost. Maximum Likelihood Estimation (MLE) was used for parameter estimation by taking the log-likelihood of six features and combining them into a summation function. Dynamic thresholding was used to classify the Protein-coding and Non-coding regions, and the Receiver Operating Characteristic (ROC) curve was determined. The generalization performance of PNRI was determined in terms of F1 score, accuracy, sensitivity, and specificity. The average generalization performance of PNRI was determined using a benchmark of multi-species organisms. The generalization error for identifying Protein-coding and Non-coding regions decreased from 0.514 to 0.508 and to 0.378, respectively, after three iterations. The cost (difference between the predicted and the actual outcome) also decreased from 1.446 to 0.842 and to 0.718, respectively, for the first, second and third iterations. The iterations terminated at the 390th epoch, having an error of 0.036 and a cost of 0.316. The computed elements of the parameter vector that maximized the objective function were 0.043, 0.519, 0.715, 0.878, 1.157, and 2.575. The PNRI gave an ROC of 0.97, indicating an improved predictive ability. The PNRI identified both Protein-coding and Non-coding regions with an F1 score of 0.970, accuracy (0.969), sensitivity (0.966), and specificity of 0.973. Using 13 non-human multi-species model organisms, the average generalization performance of the traditional method was 74.4%, while that of the developed model was 85.2%, thereby making the developed model better in the identification of Protein-coding and Non-coding regions in transcriptomes. The developed Protein-coding and Non-coding region identifier model efficiently identified the Protein-coding and Non-coding transcriptomic regions. It could be used in genome annotation and in the analysis of transcriptomes.

Keywords: sequence alignment-free model, dynamic thresholding classification, input randomization, genome annotation

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Authors: Sebastiano Candamano, Antonio Iorfida, Patrizia Frontera, Anastasia Macario, Fortunato Crea

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Alkali-activated materials are promising binders obtained by an alkaline attack on fly-ashes, metakaolin, blast slag among others. In order to guarantee the highest ecological and cost efficiency, a proper selection of precursors and alkaline activators has to be carried out. These choices deeply affect the microstructure, chemistry and performances of this class of materials. Even if, in the last years, several researches have been focused on mix designs and curing conditions, the lack of exhaustive activation models, standardized mix design and curing conditions and an insufficient investigation on shrinkage behavior, efflorescence, additives and durability prevent them from being perceived as an effective and reliable alternative to Portland. The aim of this study is to develop alkali-activated cements mortars containing high amounts of industrial by-products and waste, such as ground granulated blast furnace slag (GGBFS) and ashes obtained from the combustion process of forest biomass in thermal power plants. In particular, the experimental campaign was performed in two steps. In the first step, research was focused on elucidating how the workability, mechanical properties and shrinkage behavior of produced mortars are affected by the type and fraction of each precursor as well as by the composition of the activator solutions. In order to investigate the microstructures and reaction products, SEM and diffractometric analyses have been carried out. In the second step, their durability in harsh environments has been evaluated. Mortars obtained using only GGBFS as binder showed mechanical properties development and shrinkage behavior strictly dependent on SiO2/Na2O molar ratio of the activator solutions. Compressive strengths were in the range of 40-60 MPa after 28 days of curing at ambient temperature. Mortars obtained by partial replacement of GGBFS with metakaolin and forest biomass ash showed lower compressive strengths (≈35 MPa) and shrinkage values when higher amount of ashes were used. By varying the activator solutions and binder composition, compressive strength up to 70 MPa associated with shrinkage values of about 4200 microstrains were measured. Durability tests were conducted to assess the acid and thermal resistance of the different mortars. They all showed good resistance in a solution of 5%wt of H2SO4 also after 60 days of immersion, while they showed a decrease of mechanical properties in the range of 60-90% when exposed to thermal cycles up to 700°C.

Keywords: alkali activated cement, biomass ash, durability, shrinkage, slag

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Authors: Lorenzo Petrucci

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This paper is intended to give insight into the potential use of small-scale off-grid trigeneration systems powered by biogas generated in a dairy farm. The off-grid plant object of analysis comprises a dual-fuel Genset as well as electrical and thermal storage equipment and an adsorption machine. The loads are the different apparatus used in the dairy farm, a household where the workers live and a small electric vehicle whose batteries can also be used as a power source in case of emergency. The insertion in the plant of an adsorption machine is mainly justified by the abundance of thermal energy and the simultaneous high cooling demand associated with the milk-chilling process. In the evaluated operational scenario, our research highlights the importance of prioritizing specific small loads which cannot sustain an interrupted supply of power over time. As a consequence, a photovoltaic and thermal panel is included in the plant and is tasked with providing energy independently of potentially disruptive events such as engine malfunctioning or scarce and unstable supplies of fuels. To efficiently manage the plant an energy dispatch strategy is created in order to control the flow of energy between the power sources and the thermal and electric storages. In this article we elaborate on models of the equipment and from these models, we extract parameters useful to build load-dependent profiles of the prime movers and storage efficiencies. We show that under reasonable assumptions the analysis provides a sensible estimate of the generated energy. The simulations indicate that a Diesel Generator sized to a value 25% higher than the total electrical peak demand operates 65% of the time below the minimum acceptable load threshold. To circumvent such a critical operating mode, dump loads are added through the activation and deactivation of small resistors. In this way, the excess of electric energy generated can be transformed into useful heat. The combination of PVT and electrical storage to support the prioritized load in an emergency scenario is evaluated in two different days of the year having the lowest and highest irradiation values, respectively. The results show that the renewable energy component of the plant can successfully sustain the prioritized loads and only during a day with very low irradiation levels it also needs the support of the EVs’ battery. Finally, we show that the adsorption machine can reduce the ice builder and the air conditioning energy consumption by 40%.

Keywords: hybrid power plants, mathematical modeling, off-grid plants, renewable energy, trigeneration

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Authors: Kseniya Gladun

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Tactile stimulation of a dorsal side of the wrist can have a strong impact on our attitude toward physical objects such as pleasant and unpleasant impact. This study explored different aspects of tactile perception to investigate atypical touch sensitivity in children with autism spectrum disorder (ASD). This study included 40 children with ASD and 40 healthy children aged 5 to 9 years. We recorded rsEEG (sampling rate of 250 Hz) during 20 min using EEG amplifier “Encephalan” (Medicom MTD, Taganrog, Russian Federation) with 19 AgCl electrodes placed according to the International 10–20 System. The electrodes placed on the left, and right mastoids served as joint references under unipolar montage. The registration of EEG v19 assignments was carried out: frontal (Fp1-Fp2; F3-F4), temporal anterior (T3-T4), temporal posterior (T5-T6), parietal (P3-P4), occipital (O1-O2). Subjects were passively touched by 4 types of tactile stimuli on the left wrist. Our stimuli were presented with a velocity of about 3–5 cm per sec. The stimuli materials and procedure were chosen for being the most "pleasant," "rough," "prickly" and "recognizable". Type of tactile stimulation: Soft cosmetic brush - "pleasant" , Rough shoe brush - "rough", Wartenberg pin wheel roller - "prickly", and the cognitive tactile stimulation included letters by finger (most of the patient’s name ) "recognizable". To designate the moments of the stimuli onset-offset, we marked the moment when the moment of the touch began and ended; the stimulation was manual, and synchronization was not precise enough for event-related measures. EEG epochs were cleaned from eye movements by ICA-based algorithm in EEGLAB plugin for MatLab 7.11.0 (Mathwork Inc.). Muscle artifacts were cut out by manual data inspection. The response to tactile stimuli was significantly different in the group of children with ASD and healthy children, which was also depended on type of tactile stimuli and the severity of ASD. Amplitude of Alpha rhythm increased in parietal region to response for only pleasant stimulus, for another type of stimulus ("rough," "thorny", "recognizable") distinction of amplitude was not observed. Correlation dimension D2 was higher in healthy children compared to children with ASD (main effect ANOVA). In ASD group D2 was lower for pleasant and unpleasant compared to the background in the right parietal area. Hilbert transform changes in the frequency of the theta rhythm found only for a rough tactile stimulation compared with healthy participants only in the right parietal area. Children with autism spectrum disorders and healthy children were responded to tactile stimulation differently with specific frequency distribution alpha and theta band in the right parietal area. Thus, our data supports the hypothesis that rsEEG may serve as a sensitive index of altered neural activity caused by ASD. Children with autism have difficulty in distinguishing the emotional stimuli ("pleasant," "rough," "prickly" and "recognizable").

Keywords: autism, tactile stimulation, Hilbert transform, pediatric electroencephalography

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Authors: Safaa S. Hassan, Mohammed H. Elbakry, Safwat A. Mangoura, Zainab M. Omar

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Background: Liver fibrosis is the main reason for increased mortality in chronic liver disease. It has no standard treatment. Antioxidants from a variety of sources are capable of slowing or preventing oxidation of other molecules. Aim: to evaluate the hepatoprotective effect of vit. C, vit. E and gallic acid in comparison to silymarin in the rat model of carbon tetrachloride induced liver fibrosis and their possible mechanisms of action. Material& Methods: A total number of 60 adult male albino rats 160-200gm were divided into six equal groups; received subcutaneous (s.c) injection for 8 weeks. Group I: as control. Group II: received 1.5 mL/kg of CCL4 .Group III: CCL4 and co- treatment with silymarin 100mg/kg p.o. daily. Group IV: CCL4 and co-treatment with vit. C 50mg/kg p.o. daily. Group V: CCL4 and co-treatment with vit. E 200mg/kg. p.o. Group VI: CCL4 and co-treatment with Gallic acid 100mg/kg. p.o. daily. Liver was processed for histological and immunohistochemical examination. Levels of AST, ALT, ALP, reduced GSH, MDA, SOD and hydroxyproline concentration were measured and evaluated statistically. Results: Light and electron microscopic examination of liver of group II exhibited foci of altered cells with dense nuclei and vacuolated, granular cytoplasm, mononuclear cell infiltration in portal areas, profuse collagen fiber deposits were found around portal tract, more intense staining α-SMA-positive cells occupied most of the liver fibrosis tissue, electron lucent areas in the cytoplasm of the hepatocytes, margination of nuclear chromatin. Treatment by any of the antioxidants variably reduced the hepatic structural changes induced by CCL4. Biochemical analysis showed that carbon tetrachloride significantly increased the levels of serum AST, ALT, ALP, hepatic malondialdehyde and hydroxyproline content. Moreover, it decreased the activities of superoxide dismutase and glutathione. Treatment with silymarin, gallic acid, vit. C and vit. E decreased significantly the AST, ALT, and ALP levels in plasma, MDA and hydroxyproline and increased the activities of SOD and glutathione in liver tissue. The effect of administration of CCl4 was improved with the used antioxidants in variable degrees. The most efficient antioxidant was silymarin followed by gallic acid and vit. C then vit. E. It is possibly due to their antioxidant effect, free radical scavenging properties and the reduction of oxidant dependent activation and proliferation of HSCs. Conclusion: So these antioxidants can be a promising drugs candidate for ameliorating liver fibrosis better than the use of the drugs and their side effects.

Keywords: antioxidant, ccl4, gallic acid, liver fibrosis

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Authors: Rashmi Shukla, Yamini Bhusan Tripathi

Abstract:

Diabetic nephropathy (DN) is characterized as diabetic kidney disease which involves many pathways e.g. hyperactivated protein kinase c (PKC), polyol pathway, excess production of advanced glycation end product (AGEs) & free radical accumulation etc. All of them results to hypoxia followed by apoptosis of podocytes, glomerulosclerosis, extracellular matrix (ECM) accumulation and fibrosis resulting to irreversible changes in kidney. This is continuously rising worldwide and there are not enough specific drugs, to retard its progress. Due to increasing side effects of allopathic drugs, interest in herbal remedies is growing. Earlier, we have reported that PTY-2 (a phytomedicine, derived from Pueraria tuberosa Linn.) inhibits the accumulation of extracellular matrix (ECM) through activation of MMP-9. Present study exhibited the therapeutic potential of Pueraria tuberosa in the prevention of podocytes apoptosis and modulation of nephrin expression in streptozotocin (STZ) induced DN rats. DN rats were produced by maintaining persistent hyperglycemia for 8 weeks by intra-peritoneal injection of 55 mg/kg streptozotocin (STZ). These rats were randomly divided in 2 groups, i.e. DN control, and DN+ water extract of Pueraria tuberosa (PTW). One group of age-matched normal rats served as non-diabetic control (group-1), The STZ induced DN rats (group-2) and DN+PTW treated rats (group-3). The PTW was orally administered (0.3g/kg) daily to group-2 rats and drug vector (1 ml of 10% tween 20) in control rats. The treatments were continued for 20 days and blood and urine samples were collected. Rats were then sacrificed to investigate the expression Bcl2, Bax and nephroprotective protein i.e. nephrin in kidney glomerulus. The effect of PTW was evaluated, we have found that the PTW significantly(p < .001) reversed the raised serum urea, serum creatinine, urine protein and improved the creatinine clearance in STZ induce diabetic nephropathy in rats and also significantly(p < .001) prevented the rise in urine albumin excretion. The Western blot analysis of kidney tissue homogenate showed increased expression of Bcl2 in PTW treated rats. The RT-PCR showed the increased expression and accumulation of nephrin mRNA. The confocal photomicrographs also supported the reduction of Bax and a simultaneous increase in Bcl2 and nephrin in glomerular podocytes. Hence, our finding suggests that the nephroprotective role of PTW is mediated via restoration of nephrin thus prevents the podocytes apoptosis and ameliorates diabetic nephropathy. The clinical trial of PTW would prove to be a potential food supplement/ drug of alternative medicine for patients with diabetic nephropathy in early stage.

Keywords: Pueraria tuberosa, diabetic nephropathy, anti-apoptosis, nephrin

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Authors: Soheila Zhaeentan, Anders Von Heijne, Elisabet Hagert, André Stark, Björn Salomonsson

Abstract:

Recommended treatment for traumatic rotator cuff tear (TRCT) is surgery within a few weeks after injury if the diagnosis is made early, especially if a functional impairment of the shoulder exists. This may lead to the assumption that a poor outcome then can be expected in delayed surgical treatment, when the patient is diagnosed at a later stage. The aim of this study was to investigate if a surgical repair later than three months after injury may result in successful outcomes and patient satisfaction. There is evidence in literature that good results of treatment can be expected up to three months after the injury, but little is known of later treatment with cuff repair. 73 patients (75 shoulders), 58 males/17 females, mean age 59 (range 34-­‐72), who had undergone surgical intervention for TRCT between January 1999 to December 2011 at our clinic, were included in this study. Patients were assessed by MRI investigation, clinical examination, Western Ontario Rotator Cuff index (WORC), Oxford Shoulder Score, Constant-­‐Murley Score, EQ-­‐5D and patient subjective satisfaction at follow-­‐up. The patients treated surgically within three months ( < 12 weeks) after injury (39 cases) were compared with patients treated more than three months ( ≥ 12 weeks) after injury (36 cases). WORC was used as the primary outcome measure and the other variables as secondary. A senior consultant radiologist, blinded to patient category and clinical outcome, evaluated all MRI-­‐images. Rotator cuff integrity, presence of arthritis, fatty degeneration and muscle atrophy was evaluated in all cases. The average follow-­‐up time was 56 months (range 14-­‐149) and the average time from injury to repair was 16 weeks (range 3-­‐104). No statistically significant differences were found for any of the assessed parameters or scores between the two groups. The mean WORC score was 77 (early group, range 25-­‐ 100 and late group, range 27-­‐100) for both groups (p= 0.86), Constant-­‐Murley Score (p= 0.91), Oxford Shoulder Score (p= 0.79), EQ-­‐5D index (p= 0.86). Re-­‐tear frequency was 24% for both groups, and the patients with re-­‐tear reported less satisfaction with outcome. Discussion and conclusion: This study shows that surgical repair of TRCT performed later than three months after injury may result in good functional outcomes and patient satisfaction. However, this does not motivate an intentional delay in surgery when there is an indication for surgical repair as that delay may adversely affect the possibility to perform a repair. Our results show that surgeons may safely consider surgical repair even if a delay in diagnosis has occurred. A retrospective cohort study on 75 shoulders shows good functional result after traumatic rotator cuff tear (TRCT) treated surgically up to one year after the injury.

Keywords: traumatic rotator cuff injury, time to surgery, surgical outcome, retrospective cohort study

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Authors: Shahid Noor, Kazim Najjad, Muhammad Nasir, Irshad Bhutto, Abdul Samad Memon, Khurram Anwar, Tehseen Riaz, Mian Muhammad Hanif, Nauman A. Mallik, Saeed Ahmed, Israr Ahmed, Ali Yasir

Abstract:

Background: Musculoskeletal pain is the most common complaint presented to the health practitioner. It is well known that untreated or under-treated pain can have a significant negative impact on an individual’s quality of life (QoL). Objectives: This study was conducted across 10 sites in six (6) major cities of Pakistan to evaluate the tolerability, safety, and the clinical response of Nuberol Forte® (Paracetamol 650 mg + Orphenadrine 50 mg) to musculoskeletal pain in routine Pakistani practice and its impact on improving the patient’s QoL. Design & Methods: This NFORT-EFFECT observational, prospective multicenter study was conducted in compliance with Good Clinical Practice guidelines and local regulatory requirements. The study sponsor was "The Searle Company Limited, Pakistan. To maintain the GCP compliances, the sponsor assigned the CRO for the site and data management. Ethical approval was obtained from an independent ethics committee. The IEC reviewed the progress of the study. Written informed consent was obtained from the study participants, and their confidentiality was maintained throughout the study. A total of 399 patients with known prescreened musculoskeletal conditions and pain who attended the study sites were recruited, as per the inclusion/exclusion criteria (clinicaltrials.gov ID# NCT04765787). The recruited patients were then prescribed Paracetamol (650 mg) and Orphenadrine (50 mg) combination (Nuberol Forte®) for 7 to 14 days as per the investigator's discretion based on the pain intensity. After the initial screening (visit 1), a follow-up visit was conducted after 1-2 weeks of the treatment (visit 2). Study Endpoints: The primary objective was to assess the pain management response of Nuberol Forte treatment and the overall safety of the drug. The Visual Analogue Scale (VAS) scale was used to measure pain severity. Secondary to pain, the patients' health-related quality of life (HRQoL) was also assessed using the Muscle, Joint Measure (MJM) scale. The safety was monitored on the first dose by the patients. These assessments were done on each study visit. Results: Out of 399 enrolled patients, 49.4% were males, and 50.6% were females with a mean age of 47.24 ± 14.20 years. Most patients were presented with Knee Osteoarthritis (OA), i.e., 148(38%), followed by backache 70(18.2%). A significant reduction in the mean pain score was observed after the treatment with the combination of Paracetamol and Orphenadrine (p<0.05). Furthermore, an overall improvement in the patient’s QoL was also observed. During the study, only ten patients reported mild adverse events (AEs). Conclusion: The combination of Paracetamol and Orphenadrine (Nuberol Forte®) exhibited effective pain management among patients with musculoskeletal conditions and also improved their QoL.

Keywords: musculoskeletal pain, orphenadrine/paracetamol combination, pain management, quality of life, Pakistani population

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Authors: Ismaila Haruna

Abstract:

The global downfall in fossil energy prices and dwindling oil reserves in Nigeria has ignited interest in the search for alternative sources of foreign income for the country. Solid minerals, particularly Uranium and other base metals like Lead and Zinc have been considered as potentially good options. Several occurrences of this mineral have been discovered in both the sedimentary and granitic rocks of the Hawal and Adamawa Massifs as well as in the adjoining Benue Trough in northeastern Nigeria. However, the paucity of geochemical data and consequent poor petrogenetic knowledge of the granitoids in this region has made exploration works difficult. Song, a small area within the Hawal Massif, was mapped and the collected samples chemically determined in Activation Laboratory, Canada through fusion dissolution technique of Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Field mapping results show that the area is underlain by Granites, diorites with pockets of gneisses and pegmatites and that these rocks consists of microcline, quartz, plagioclase, biotite, hornblende, pyroxene and accessory apatite, zircon, sphene, magnetite and opaques in various proportions. Geochemical data show continous compositional variation from diorite to granites within silica range of 52.69 to 76.04 wt %. Plot of the data on various Harker variation diagrams show distinct evolutionary trends from diorites to granites indicated by decreasing CaO, Fe2O3, MnO, MgO, Ti2O, and increasing K2O with increasing silica. This pattern is reflected in trace elements data which, in general, decrease from diorite to the granites with rising Rb and K. Tectonic, triangular and other diagrams, indicate high-K calc-alkaline trends, syn-collisional granite signatures, I-type characteristics, with CNK/A of less than 1.1 (minimum of 0.58 and maximum of 0.94) and strong potassic character (K2O/Na2O˃1). However, only the granites are slightly peraluminous containing high silica percentage (68.46 to 76.04), K2O (2.71 to 6.16 wt %) with low CaO (1.88 on the average). Chondrite normalised rare earth elements trends indicate strongly fractionated REEs and enriched LREEs with slightly increasing negative Eu anomaly from the diorite to the granite. On the basis of field and geochemical data, the granitoids are interpreted to be high-K calc-alkaline, I-type, formed as a result of hybridization between mantle-derived magma and continental source materials (probably older meta-sediments) in a syn-collisional tectonic setting.

Keywords: geochemistry, granite, Hawal Massif, Nigeria, petrogenesis, song

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