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6-OHDA Inhibits Platelet Functional Parameters: 6-OHDA enters into platelet and inhibits thrombin-induced platelet adhesion, activation, secretion, aggregation, and retraction, thus explaining the occurrence of reduced stroke frequency in PD. [Display omitted] • Parkinson's disease (PD) is often associated with a reduced stroke frequency. • Platelet is linked to vascular damage and shares similarities with a PD neuron. • 6-OHDA treatment decreased thrombin-induced various platelet functions. • 6-OHDA reduced platelet adhesion, activation, aggregation, secretion & retraction. • This study supports and provides new insights into platelet dysfunctions in PD. Parkinson's disease (PD) is the second-most prevalent neurodegenerative disease worldwide, which worsens with advancing age. It is a common movement disorder and is often associated with several vascular diseases with decreased stroke frequency. Circulating platelets substantially regulate vascular complications, including stroke, and share striking similarities with PD neurons. Although structural alterations in platelets are well-documented in PD, their functional parameters remain unclear. This study aimed to investigate the functional abnormalities in platelets associated with PD by evaluating key functional aspects such as adhesion, activation, secretion, aggregation, and clot retraction. To achieve this, we treated human blood platelets with 6-hydroxydopamine or 6-OHDA, that selectively destroys dopaminergic neurons, thereby creating an in vitro experimental model that closely resembles the pathogenic environment in PD, and examine its impact on platelet functions. In our study, platelet adhesion was assessed and further evaluated by a microplate reader, activation and secretion by a flow cytometer, aggregation by aggregometer, and clot retraction by Sonoclot. Phase-contrast and confocal microscopic studies further verified the results from the above experiments. Our findings showed that 6-OHDA treatment significantly inhibited thrombin (a platelet agonist)-induced functions, including adhesion, activation, aggregation, secretion, and clot retraction in human-washed platelets. In summary, this research provides pioneering evidence that 6-OHDA induces abnormal platelet functions, shedding light on the previously unexplored processes by which 6-OHDA affects platelet activity. [ABSTRACT FROM AUTHOR]

Heparin-induced thrombocytopenia (HIT) is a serious drug induced reaction that may be associated with life threatening complications. Platelet-activating antibodies directed against platelet factor 4 (PF4)/heparin complexes cause the disease. The diagnosis of HIT is challenging, as thrombocytopenia is a frequent finding in intensive care (ICU) patient population, especially during extracorporeal membrane oxygenation. To investigate the performance of a diagnostic algorithm for HIT in ICU patients. ICU patients who developed thrombocytopenia or thrombosis under heparin treatment were included in this study. The pretest probability for HIT was estimated using the 4Ts-score and patient's sera were tested using two rapid immunoassays (RA) LFI-HIT and PaGIA (from Milenia Biotec and DiaMed), and within 72 h using the IgG enzyme immunoassay (EIA) from Hyphen and the heparin induced platelet activation assay (HIPA). 392 consecutive ICU patients with suspected HIT were enrolled in this study, of whom 83/392 (21.2%) patients had extracorporeal circulation. Sera from 120/392 (30.6%) and 98/392 (25.0%) patients revealed positive results in RA and IgG EIA, respectively. The HIPA test revealed heparin-dependent platelet activation in a total of 15/392 (3.8%) ICU patients (3 medical and 12 surgical patients). In addition, sera from 7 patients revealed indeterminate HIPA results, of whom 2 patients had a clinical course compatible with HIT. Data from our study confirm the high frequency of IgG PF4/heparin antibodies in ICU patients under unfractionated heparin and shows that the combination of 4Ts-score and RA does not reduce the laboratory overinvestigation for HIT in these patients. • Diagnostic approach for HIT in ICU – a challenge for clinicians and laboratories • Management and clinical course of 4 cases with uncertain HIT diagnosis • 83/392 included patients had extracorporeal circulation. [ABSTRACT FROM AUTHOR]

• Dandelion root fractions are typified by anti-adhesive and anti-aggregation action. • Phenylacetate inositol esters fraction (C) showed the strongest antiplatelet action. • Hydroxycinnamic acids fractions (D and E) showed the strongest anticoagulant effect. • Fractions A (amino-acid-sesquiterpene lactones) and C showed the highest anti-oxidative action. The effect of dandelion root and its various ingredients on the biological functions of blood platelets has not been well investigated. Thus, the objective of our in vitro study was to examine the five root fractions (A–E), differing in chemical composition, for changes induced in the human platelets' model using selected hemostatic parameters. As a result, the best anti-platelet potential was shown by preparation enriched with hydroxyphenylacaetate inositol esters – PIEs (fraction C). On the other hand, the best overall protective effect against oxidation of lipids and proteins of platelets, and the best inhibitory effect on the generation of O 2 − were observed in the presence of fraction A (SL-amino acid adducts enriched fraction). Thus, PIEs and SLs rich plant organs, such as dandelion root, may be considered as potentially suitable additives for functional food products used in prophylaxis and treatment of cardiovascular diseases associated with hyperactivation of blood platelets. [ABSTRACT FROM AUTHOR]

The primary biological function of platelets is to form hemostatic thrombi that prevent blood loss and maintain vascular integrity. These multi-responding cells are activated by different endogenous, physiological agonists due to the vast number of receptors present on the surface of the platelets. Collagen represents up to 40% of the total protein presented in the vessel wall and is the major activator of the platelets’ response after tissue injury, and is the only matrix protein which supports both platelet adhesion and complete activation. The aim of our study was to determine the effects of three major flavonolignans (silybin, silychristin and silydianin) on collagen-induced blood platelets’ activation, adhesion, aggregation and secretion of PF-4. We observed that depending on the dose, silychristin and silybin have anti-platelet properties observed as inhibition of collagen-induced activation (formation of blood platelet aggregates and microparticles, as well as decreased expression of P-selectin and activation of integrin α IIb β 3 ), aggregation, adhesion and secretion of PF-4. These effects highlight the potential of silybin and silychristin as supplementation to prevent primary and secondary thrombotic events wherein excessive blood platelet response to a physiological agonist is observed. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a progressive neuronal illness often linked to increased cardiovascular complications, such as myocardial infarction, cardiomyopathy, congestive heart failure, and coronary heart disease. Platelets, which are the essential components of circulating blood, are considered potential players in regulating these complications, as platelet dysfunction is evident in PD. These tiny blood cell fragments are supposed to play a crucial role in these complications, but the underlying molecular processes are still obscure. To gain a better understanding of platelet dysfunction in PD, we investigated the impact of 6-hydroxydopamine (6-OHDA), an analog of dopamine that simulates PD by destroying dopaminergic neurons, on human blood platelets. The levels of intraplatelet reactive oxygen species (ROS) were assessed using H 2 DCF-DA (20 μM), while mitochondrial ROS was evaluated using MitoSOX™ Red (5 μM), and intracellular Ca2+ was measured with Fluo-4-AM (5 μM). The data were acquired through the use of both a multimode plate reader and a laser-scanning confocal microscope. Our findings showed that 6-OHDA treatment increased the production of ROS in human blood platelets. The increase in ROS was confirmed by the ROS scavenger, NAC, and was also reduced by inhibiting the NOX enzyme with apocynin. Additionally, 6-OHDA potentiated mitochondrial ROS production in platelets. Furthermore, 6-OHDA triggered the intraplatelet Ca2+ elevation. This effect was mitigated by the Ca2+ chelator BAPTA, which decreased the ROS production triggered by 6-OHDA in human blood platelets, while the IP 3 receptor blocker, 2-APB, reduced the formation of ROS induced by 6-OHDA. Our findings suggest that the 6-OHDA-induced ROS production is regulated by the IP 3 receptor-Ca2+-NOX signaling axis in human blood platelets, where the platelet mitochondria also play a significant role. This observation provides a crucial mechanistic understanding of the altered platelet activities that are commonly observed in PD patients. • 6-OHDA, a dopamine analog, increases ROS production in human blood platelets. • 6-OHDA-mediated mitochondrial ROS augments total cytosolic ROS in platelets. • NOX enzyme regulates 6-OHDA-mediated intra-platelet ROS generation. • Platelet ROS production is dependent on IP 3 receptor-mediated Ca2+ mobilization. • The study proposes molecular mechanism for platelet dysfunction observed in PD. [ABSTRACT FROM AUTHOR]

Spent hop extract (SHE) is hypothesized to possess multifaceted anticoagulant effect and to reduce platelet reactivity in a direct manner and to improve the antiplatelet action of endothelium. The results demonstrated that SHE, rich in flavanols (50% of total phenolic compounds), hydroxycinnamic acids, proanthocyanidin oligomers, flavan-3-ol monomers, and flavonol glycosides, inhibited ADP-induced platelet aggregation up to 11% for 7.5 µg/ml or up to 23% for 15 µg/ml, P  <   0.05. Additionally, SHE ameliorated anticoagulant activity of human endothelial cells to significantly reduce platelet reactivity. This effect could be related to the increased expression/activity of the ecto-ADPase (CD39). ADP-induced platelet reactivity was reduced in the case of platelets incubated with the extract-treated endothelial cells compared to the untreated cells. Diabetic rats fed with SHE demonstrated longer survival time than the group treated with placebo. In conclusion, our study provided evidence for a potential beneficial role of SHE in the regulation of platelet and endothelial function. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD), a progressive neurodegenerative disorder, is considered one of the most common causes of dementia worldwide, accounting for about 80 % of all dementia cases. AD is manifested by the extraneuronal deposition of senile plaques of amyloid beta (Aβ) and intraneuronal accumulation of neurofibrillary tangles of phosphorylated tau. The impaired proteostasis of these filamentous Aβ and tau is significantly regulated by reactive oxygen species (ROS). ROS-induced oxidative stress (OS) is the cardinal cause behind neuroinflammation-triggered neurodegeneration during AD. Besides ROS-induced neuro-inflammation, AD is also associated with cerebrovascular dysfunction, where platelet primarily plays a significant role in blood-vessel integrity and tissue repair. Though platelets are the circulatory cell fragments that play predominant roles in thrombosis and hemostasis, their contributions to other physiological functions are also being elucidated. Surprisingly, platelets contribute about 90 % of the circulatory Aβ and share striking similarities with neurons in several aspects, including different neurotransmitters and their cognate receptors, thus considering platelets as potential peripheral models for AD. Interestingly, platelet structural and functional dysfunctions are evident in AD, where ROS production is associated with platelet hyperactivity. Although activated platelet carries several vital enzymes and immunomodulatory molecules, which can potentially exacerbate OS-mediated neuronal damage, and neurodegeneration, their mechanism of action and mode of progression, are still obscure. Therefore, in this review, we have described the detailed role of OS and platelet in AD, addressing the therapeutic approach and molecular mechanism of platelet-mediated ROS generation as a contributing factor in aggravating the disease. [Display omitted] • Alzheimer's disease (AD) is associated with reactive oxygen species (ROS) that induce oxidative stress (OS). • AD is linked with vascular dysfunction, where platelet plays a crucial role, and shares striking resemblance with a neuron. • Structural and functional alterations of blood platelets, including mitochondrial dysfunction, are observed in AD. • Proteasomal dysfunction, calcium mobilization, and mitochondrial impairment are found in AD platelets. • Platelet ROS could be the potential target for the development of plausible therapeutics for AD management. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is the second-most-common neurodegenerative disease characterized by motor and non-motor dysfunctions, which currently affects about 10 million people worldwide. Gradual death and progressive loss of dopaminergic neurons in the pars compacta region of substantia nigra result in striatal dopamine deficiency in PD. Specific mutation with further aggregation of α‐synuclein in the intraneuronal inclusion bodies is considered the neuropathological hallmark of this disease. PD is often associated with various organelle dysfunctions inside a dopaminergic neuron, including mitochondrial damage, proteasomal impairment, and production of reactive oxygen species, thus causing subsequent neuronal death. Apart from several genetic and non-genetic risk factors, emerging research establishes an association between cardiovascular diseases, including coronary heart disease, myocardial infarction, congestive heart failure, and ischemic stroke with PD. The majority of these cardiovascular diseases have an origin from atherosclerosis, where endothelial dysfunction following thrombus formation is significantly regulated by blood platelet. This non-nucleated cell fragment expresses not only neuron-specific molecules and receptors but also several PD-specific biomarkers such as α-synuclein, parkin, PTEN-induced kinase-1, tyrosine hydroxylase, dopamine transporter, thus making platelet a suitable peripheral model for PD. Besides its similarity with a dopaminergic neuron, platelet structural alterations, as well as functional abnormalities, are also evident in PD. However, the molecular mechanism behind platelet dysfunction is still elusive and quite controversial. This state-of-the-art review describes the detailed mechanism of platelet impairment in PD, addressing the novel platelet-associated therapeutic drug candidates for plausible PD management. • Parkinson's disease (PD) affects the dopaminergic neurons in the pars compacta region of the substantia nigra. • PD is associated with cardiovascular diseases including myocardial infarction, ischemic stroke, and coronary heart disease. • Atherosclerosis occurs nearly in all cardiovascular diseases, where tiny blood platelets play an essential role. • Platelets express several PD-specific proteins and miRNAs, thus considering them the peripheral models of PD. • Platelet impairment happens during PD, and antiplatelet drugs could be the potential therapeutic options for PD. [ABSTRACT FROM AUTHOR]

Objective Cardiovascular mortality increases after menopause in women. Nitric oxide is essential for proper platelet function inhibiting its aggregation and maintaining vascular haemostasis. Here, we investigated whether platelet function and intraplatelet l -arginine–nitric oxide pathway are impaired in postmenopausal women. Study design Cross-sectional. Main outcomes measures Blood was collected from 16 premenopausal and 12 postmenopausal women without any additional risk factor for cardiovascular disease. Platelet reactivity was measured by light transmission aggregometry. l -Arginine–nitric oxide pathway was assessed measuring transmembrane l -[ 3 H]-arginine transport, nitric oxide synthase activity by the citrulline assay, and arginase activity by the conversion of l -[ 14 C]arginine to l -[ 14 C]-urea. The activity of antioxidant enzymes was measured by spectrophotometric assays. Protein expression was determined by Western blotting. Results Platelet aggregation was increased in postmenopausal compared to premenopausal women. Postmenopausal women demonstrated reduced plasma levels of l -arginine, a lower nitric oxide synthase activity, similar endothelial and inducible nitric oxide synthase expression, and a compensatory increase in l -arginine transmembrane transport. Arginase expression and activity did not differ between groups. In regard to oxidative stress, no differences between groups were observed NAPDH oxidase subunits expression and protein carbonylation. However, the activity of the antioxidant enzyme superoxide dismutase and catalase protein levels in platelets were higher in postmenopausal women. Conclusion Postmenopausal women present increased platelet reactivity, which may be due to a reduction in intraplatelet nitric oxide synthesis. Platelet hyperaggregability is known to be associated with arterial and venous thromboembolic event; therefore, it may contribute to the heightened risk of cardiovascular adverse events in this population. [ABSTRACT FROM AUTHOR]

Carbon monoxide (CO) is an odorless, colorless and non-irritating gas. Even a small amount of CO exposure is possibly associated with specific toxic effects. CO is also produced endogenously in the body as a byproduct of heme degradation catalyzed by heme oxygenase. More recently CO has been identified as a gasotransmitter in various biological systems. However, the biological role and the therapeutic potential of carbon monoxide is not clear. This review summarizes the negative and the positive functions of carbon monoxide in various biological systems, including cardiovascular system. [ABSTRACT FROM AUTHOR]

Abstract: Recent evidences include mitochondrial dysfunctions in pathophysiology of mood disorders. We examined association between depressive disorders and mitochondrial respiration using both intact and permeabilized blood platelets. In intact platelets, physiological respiration, maximal capacity of electron transport system and respiratory rate after complex I inhibition were decreased in depressive patients, who reached partial remission, compared to healthy controls. Respiratory rates were unchanged in several respiratory states in permeabilized platelets. Results indicate that changes in respiratory rate in intact platelets can be used as biological marker of depressive disorder. The hypothesis that decreased mitochondrial respiratory rate participate in pathophysiology of depression was supported. [Copyright &y& Elsevier]

Abstract: The phenolic fraction and the crude extract from Tribulus pterocarpus have different biological activity, including antiplatelet–antiadhesive properties. Since it is demonstrated that hyperhomocysteinemia may act as stimulator of blood platelet activation (platelet adhesion, aggregation, and secretion), but various antiplatelet compounds are able to reduce hyperactivation of blood platelets induced by hyperhomocysteinemia. The aim of our present experiments was to investigate in vitro one of the step in platelet activation process – platelet adhesion to collagen induced by the model of severe hyperhomocyateinemia in the presence of the phenolic fraction and the crude extract from T. pterocarpus. Severe hyperhomocysteinemia was induced by reduced form of Hcy in the concentrations 0.1mM and 1mM, or using HTL in the concentrations 0.1, 0.5 and 1μM. Adhesion of blood platelets to collagen was determined according to Tuszynski and Murphy. We observed that the phenolic fraction and the crude extract from T. pterocarpus have the inhibitory effect on platelet adhesion during severe hyperhomocysteinemia. The action of tested phenolic and crude extract was concentration-dependent, but the phenolic fraction was stronger antiadhesive action than the crude extract. We suggest that T. pterocarpus may be good source of antiplatelet compounds during hyperhomocysteinemia. [Copyright &y& Elsevier]

Abstract: Surface microroughness can induce contact osteogenesis (bone formation initiated at the implant surface) around oral implants, which may result from different mechanisms, such as blood platelet–biomaterial interactions and/or interaction with (pre-)osteoblast cells. We have developed a computational model of implant endosseous healing that takes into account these interactions. We hypothesized that the initial attachment and growth factor release from activated platelets is crucial in achieving contact osteogenesis. In order to investigate this, a computational model was applied to an animal experiment that looked at the effect of surface microroughness on endosseous healing. Surface-specific model parameters were implemented based on in vitro data (Lincks et al. Biomaterials 1998;19:2219–32). The predicted spatio-temporal patterns of bone formation correlated with the histological data. It was found that contact osteogenesis could not be predicted if only the osteogenic response of cells was up-regulated by surface microroughness. This could only be achieved if platelet–biomaterial interactions were sufficiently up-regulated as well. These results confirmed our hypothesis and demonstrate the added value of the computational model to study the importance of surface-mediated events for peri-implant endosseous healing. [Copyright &y& Elsevier]

Abstract: Blood platelets are emerging as important immunomodulatory cells, but complement interaction with platelets is not well understood. Several platelet structures have been described as complement protein 1q (C1q) binding receptors, such as C1qRp/CD93 and gC1qR. However, there are conflicting results whether these receptors are C1q binding structures, or even at all expressed on the cell surface. Recently, the collagen-binding integrin αIIβI was reported to bind C1q on mast cells, and this receptor is also present on platelets. The aim of this study was to further characterize the effects of C1q on platelets, by quantifying the platelet surface expression of P-selectin (CD62P) and monitoring the formation of platelet–neutrophil aggregates. Using flow cytometry, we found that C1q dose-dependently triggered a rapid but moderate and transient up-regulation of P-selectin already within 5s of C1q exposure. Pre-incubation with an antibody directed against gC1qR significantly inhibited (with 57% compared to control) the up-regulation, whereas an antibody towards the αIIβI-integrin showed no effect. Stimulation with C1q did not change the cytosolic calcium-levels, as measured with the fluorescent ratiometric probe Fura-2, however, a protein kinase C inhibitor (GF109203x) blocked the C1q-induced P-selectin expression. Furthermore, pre-incubation of platelets with C1q diminished both the collagen as well as the collagen-related peptide-induced up-regulation of P-selectin, most evident after 90s of stimulation. This indicates that C1q may regulate platelet activation via the GPVI receptor, which is a novel finding. Moreover, C1q antagonized the collagen-induced formation of platelet–neutrophil aggregates, indicating a reduced interaction between platelet P-selectin and neutrophil P-selectin glycoprotein ligand-1(PSGL-1/CD162). In summary, C1q induces a moderate rapid platelet P-selectin expression, modulates subsequent collagen and collagen-related peptide stimulation of platelets, and inhibits the formation of platelet–neutrophil aggregates. These immuno-regulatory effects of C1q may have a crucial role in innate immunity and inflammation. [Copyright &y& Elsevier]

Abstract: Hemostasis is required to maintain vascular system integrity, but thrombosis, formation of a clot in a blood vessel, is one of the largest causes of morbidity and mortality in the industrialized world. Novel clinical and research tools for characterizing the hemostatic system are of continued interest, and the object of this research is to test the hypothesis that clinically relevant platelet function can be monitored using an electromechanical sensor. A piezoelectric thickness shear mode (TSM) biosensor coated with collagen-I fibers to promote platelet activation and adhesion was developed and tested for sensitivity to detect these primary events. Magnitude and frequency response of the sensor were monitored under static conditions at 37°C, using platelet-rich plasma (PRP), and PRP with adenosine diphosphate (ADP), a clinical aggregation inhibitor (abciximab), or a collagen binding inhibitor. Sensors loaded with PRP exhibited a 3-stage response; no significant change in response for the first 20min (Stage-1), followed by a larger drop in response (Stage-2) and subsequently, response gradually increased (Stage-3). Exogenous ADP stimulated an immediate Stage-2 response, while abciximab delayed and reduced the magnitude change of Stage-2. In the presence of collagen inhibitor, Stage-2 response was similar to that of control but was delayed by an additional 20min. The obtained results, supported by epifluorescence and complementary SEM studies, demonstrated the selective sensitivity of TSM electromechanical biosensors to monitor platelet function and inhibition, particularly aggregation. [Copyright &y& Elsevier]

Abstract: The effects of resveratrol (trans-3,4′,5-trihydroxystilbene) on activation responses and the polyphosphoinositide metabolism in human blood platelets have been studied. Resveratrol partially inhibited secretory responses (liberation of dense granule nucleotides and lysosomal acid hydrolases), microparticle formation and protein phosphorylations induced by thrombin. The effects of resveratrol on phosphoinositide metabolites, phosphatidate (PtdOH), phosphatidylinositol (PtdIns), phosphatidylinositol-4-phosphate (PtdIns-4(5)-P), phosphatidylinositol 4,5-bisphosphate (PtdIns-4,5-P 2 ), phosphatidylinositol-3,4-bisphosphate (PtdIns-3,4-P 2 ) and phosphatidylinositol-3,4,5-trisphosphate (PtdIns-3,4,5-P 3 ) were monitored in blood platelets prelabelled with [32P]Pi. Resveratrol not only inhibited the marked increase in levels of PtdOH in platelets activated by thrombin (0.1 U/ml) but it decreased the steady state levels of the other polyphosphoinositide metabolites. The distribution of 32P in phosphoinositides in activated platelets was consistent with inhibition of CDP-DAG inositol transferase and a weak inhibition of PtdIns-4(5)-P kinase. These observations show that resveratrol has a profound effect on phospholipids, particularly on polyphosphoinositide metabolism, and may decrease the amount of PtdIns-4,5-P 2 available for signalling in these cells. [Copyright &y& Elsevier]

Resveratrol (3, 4′, 5-trihydroxystilbene), a natural polyphenol, is found in some plants that are used in human nutrition. Grapes are a major source for resveratrol, and a significant amount can also be found in red wine. Several experimental studies have demonstrated biological properties of resveratrol, especially its anti-inflammatory, antioxidant, anti-platelet and antitumor effects. In the present study, we investigated the first step of platelet activation—platelet adhesion stimulated by lipopolysaccharide (LPS) from Proteus mirabilis (weak stimulator) and thrombin (strong activator) in the presence of resveratrol. Our studies show that endotoxin (0.3 μg/108 platelets), like thrombin (0.2 U/108 platelets), induced the adhesion of platelets (expressed as absorbance of cell attached proteins) to collagen and fibrinogen. Preincubation of washed platelets with resveratrol at physiological plasma concentrations (25–100 μg/ml, 30 min, 37 °C) had an inhibitory effect on adhesion of platelets to collagen after activation by LPS alone or LPS with thrombin. The strongest effect on this process was caused by resveratrol at the concentration of 100 μg/ml. Pretreatment of platelets with resveratrol (25–100 μg/ml, 30 min, 37 °C) had also inhibitory effects on adhesion of platelets to fibrinogen after stimulation of these cells by LPS alone or by LPS with thrombin at the same concentration. In conclusion, we suggest that resveratrol present in human diet may be an important compound responsible for the reduction of platelet adhesion and changed reactivity of blood platelets in inflammatory process. [Copyright &y& Elsevier]

Supply and demand uncertainties combined with very short lifetime of blood platelets has led to significant wastage of the total blood collected from the donors. Conversely, great shortage of platelets may be obtained due to the limited number of donors and emergency demands. Therefore, it is of utmost importance to develop appropriate inventory management model to simultaneously minimize both shortage and wastage along the blood supply chain. To achieve this purpose, this paper presents an Inventory Management model for Age-differentiated platelets under supply/demand Uncertainties (IMAU) for Blood Supply Chains with Lateral Transshipment (BSCLT), resulting a new model named IMAU-BSCLT. The proposed model is solved using whale optimization algorithm considering the costs of ordering from blood centers and lateral transshipment, transportation, inventory holding, shortage, and wastage. In order to validate the proposed methodology, a case study of blood supply chain is used to show the usability of the proposed model and claim its benefits over existing models. Simulation results demonstrate that lateral transshipment between different demand nodes has a major impact on load balancing leads to simultaneously reduce both shortage and wastage costs. According to the obtained results, shortage rate (total shortage per total demands) and wastage rate (total wastage per total supply) of the proposed method are 3.4 % and 4.8 %, respectively. [ABSTRACT FROM AUTHOR]

Beer is one of the most widely consumed alcoholic beverages in the world; however, traditional - and non-alcoholic beer consumption appear to have different effects on the cardiovascular system. In this short work, we review a base of recent papers to confirm whether, or not, moderate consumption of beer and its non-alcoholic components have a beneficial effect of cardiovascular system. Moreover, the present work reviews recently published papers regarding the influence of beer components on the hemostasis, cardiovascular system, and cardiovascular diseases (CVDs). Although most nutritional guidelines recommend a maximum of one beer per day for women and two for men, individual ideals may vary according to age, sex, genetics and body type, as well as drug or supplement use. Moreover, the recommendations for the moderate consumption of beer are often based on individual case reports and often small clinical experiments. In addition, as the health-related effects of beer consumption may also depend on the presence of other dietary components, as well as the type of beer, it is difficult to determine whether moderate consumption is universally safe and beneficial for the cardiovascular system. More randomized clinical trials are needed to determine this. Well-designed clinical trials are also required to determine the influence of various beer components on hemostasis and CVDs, and their effects in combination with drug or supplement therapy. • Beer is one of the most widely-consumed alcoholic beverages in the world. • Traditional- and non-alcoholic beer consumption appear to have different effects on the cardiovascular system. • The health-related effects of beer consumption depends on the presence of dietary components, and the type of beer. • It is difficult to determine whether moderate consumption is universally safe and beneficial for the cardiovascular system. [ABSTRACT FROM AUTHOR]

• IRT inspection is non-invasive and can compensate for the invasiveness of cell molecular detection. • IRT can evaluate ITP children from the perspective of skin temperature distribution objectively. • The degree of skin temperature distribution confusion can be quantified by the TDSNU feature. • The trunk part of children with ITP has high TDSNU feature, which prove the results of previous research objectively. • The TDSNU feature of IRT has high specificity and sensitivity to ITP. Idiopathic thrombocytopenic purpura (ITP) is an immune disease with complex pathogenesis. However, the diagnosis of ITP lacks of specificity test index, the diagnosis is still at an exclusive diagnosis level. Clinical studies have found that ITP can cause a disorder of the skin temperature distribution due to the spontaneous immune response. Human skin temperature can be collected by infrared thermography (IRT), and we can speculate on the severity of the immune response by extracting the temperature distribution characteristics. In this paper we will explore the value of IRT for the diagnosis and evaluation on ITP, and try to add new non-invasive inspection tools for ITP laboratory inspection. According to the human metabolic function status, a spatial heterogeneity algorithm for skin temperature distribution was proposed in this paper based on infrared thermography. The algorithm was used to quantify the degree of confusion in a target region. Thirty-three subjects were divided into a control group, an ITP1 group and an ITP2 group in this study. The temperature distribution spatial non-uniformity, average temperature and maximum temperature characteristics of 14 ROI regions were extracted from the infrared thermal imaging of every subject. Six target regions with smaller P value were selected and single-dimensional evaluation parameter was extracted by the method of area weighting. At the same time, the sensitivity and specificity of the parameter to ITP were examined. The 6 target regions selected by the non-uniformity feature had significant differences (P < 0.05) among the three groups with the statistical method of ANOVA, but there were no significantly statistical difference on the regions extracted by average temperature and maximum temperature. It can be found from the ROC curve that the evaluation method proposed in this paper has higher sensitivity and specificity, than the common methods. The skin temperature distribution characteristics of the ITP children can be displayed by an infrared thermography. All of the 6 target regions screened by the spatial non-uniformity algorithm proposed in this paper are torso parts, which match the conclusions of relevant literature research. The method presented in this paper has high sensitivity and specificity to ITP. Although there are some limitations, it can non-invasively and objectively describe the disease state and add a new tool for ITP laboratory examinations. This paper also provides a new method and idea for the medical evaluation of infrared thermography. [ABSTRACT FROM AUTHOR]