Revealing the relation between job satisfaction and workload: a cross-sectional study in the emergency department.

Job satisfaction is recognized as an essential parameter that affects the performance and quality of medical services provided by emergency department (ED) health professionals. However, little is known about the status of job satisfaction related to workload among ED staff in Saudi Arabia. This study aimed to explore the current level of job satisfaction and to analyze the relationship between job satisfaction and the personal and professional characteristics of ED staff. Methods: A cross-sectional questionnaire-based study was conducted among ED staff, including various job positions, to assess job satisfaction. An online questionnaire was sent electronically to all ED staff. The structured online questionnaire collected information on sociodemographic factors, workload-related factors, and job satisfaction. The data was analyzed using SPSS version 26. Results: The questionnaire used to assess job satisfaction levels demonstrated high internal consistency and reliability using Cronbach's α (0.85). Completed responses were obtained from 103 ED staff members; 58.25% were males, and most of the participants in the survey were either nurse (48.54%) or physicians (28.16%). Most of the respondents (61.16%) had a satisfaction score that was higher than half of the possible attainable score and showed a high level of satisfaction, although 38.84% fell below half of the possible attainable score on the satisfaction parameter and showed a lower level of satisfaction. Conclusion: It may be concluded that ED staff have a higher level of job satisfaction related to workload factors. The level of satisfaction did not change for different age groups, genders, levels of education, levels of experience, or jobs.

Skin healing effects of an innovative polymer-based oil Nigella sativa: a rabbit model experimental study.

OBJECTIVE: Natural wound dressings composed of gelatin (GEL) and chitosan (CH) impregnated with bioactive compounds (Nigella sativa oil) were prepared and characterized to evaluate their potential application. MATERIALS AND METHODS: The formulated composite was subjected to γ-irradiation. In vitro, the ferric-reducing antioxidant power (FRAP) assay and antibiofilm activities were evaluated. In vivo, the tissue wound-healing process was studied by applying GEL-CH-Nigella in dorsal skin rabbit tissue. On days 7 and 14, the biochemical biomarker and histological analysis were determined. RESULTS: At 10 kGy, FRAP assays exhibited the highest antioxidant activity (380 mmol/kg). A significant inhibition of anti-biofilm activity was observed against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) (p<0.01). Fourteen days post-surgery, a significant reduction in thiobarbituric acid-reactive compounds (TBARs) was observed compared to the GEL-CH group. Concerning oxidative stress status, GEL-CH-Nigella significantly improved superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities. A histological analysis revealed that GEL-CH-Nigella accelerated wound closure and improved collagenisation and enhanced epidermal tissue thickness. CONCLUSIONS: These results indicate that GEL-CH-Nigella wound dressing is a promising biomaterial for engineered tissue.

Live stream marketing and consumers' purchase intention: An IT affordance perspective using the S-O-R paradigm.

Recent years have seen a shift in the online retail industry toward a greater emphasis on live marketing. The growth of social media commerce on the internet demonstrates the popularity of Livestream shopping. Although there has been a rise in interest in studying live streaming, a comprehensive model describing why consumers are willing to consistently employ this novel sales format has yet to be developed. Hence, the present study develops a model to determine the factors influencing consumers' live-stream shopping intention by employing the affordance lens and S-O-R model. The online data was collected through the Wenjuanxing website from the users of live-streaming platforms such as Taobao.com, Mogujie.com, and JD.com. Results showed that (N = 434): trust can be enhanced through visibility, metavoicing, trading affordance, guidance shopping and interactivity that consequently affects consumer purchase intention. In addition, this study highlights the theoretical and managerial implications for social commerce.

Preclinical study of vitamin D deficiency in the pathogenesis of metabolic syndrome in rats.

OBJECTIVE: To explore the impact of vitamin D deficiency (VD-) in the pathogenesis of metabolic syndrome (MetS). MATERIALS AND METHODS: Models of (VD-) and (MetS) were induced in male Wister rats by dividing into four groups, group-I for the development of (VD-) by intraperitoneal injection of paricalcitol for 3 weeks, group II for (MetS) model by adding 10% fructose to their drinking water for 8 weeks, the group III for induction of combined (VD- + MetS) and group-IV as a control. Ultimately, the parameters of (VD-) and (MetS) were assessed at zero time and after 8 weeks. RESULTS: Both (VD-) and (MetS) groups alone displayed a remarkable enhancement of blood pressure, glucose and insulin levels, triglycerides, cholesterol, and low-density lipoproteins with a reduction of high-density lipoproteins. Additionally, all distinguishing features of obesity were substantially increased. Nevertheless, the combined group (VD-+MetS) demonstrated an expeditious and substantial increase in all the aforesaid parameters compared to the (VD-) and (MetS) groups alone. CONCLUSIONS: The hallmark of this study, reinforces a new frontier of awareness of the deleterious effect of (VD-) on each component of (MetS). Eventually, supplementation of vitamin D can circumvent the elements of (MetS) and needs further validation by determination of (VD-) molecular pathway on the parameters of (MetS).

An ounce of prevention or a pound of cure? Multi-level modelling on the antecedents of mobile-wallet adoption and the moderating role of e-WoM during COVID-19.

During the COVID-19 epidemic, personal safety has received increasing attention, leading to behavioral changes. Mobile-wallet (m-wallet) makes it easier for people to keep social distance, which helps stop the spread of the COVID-19 virus. Evolving Internet technology has brought about changes in consumer lifestyle. The current situation of COVID-19 has created a business environment to shift from traditional ways and adopt e-commerce solutions worldwide. Grounded in technology acceptance model (TAM) theory, this study's objective is two-fold: First, this study intends to examine perceived susceptibility to COVID-19, perceived severity of COVID-19, insecurity and discomfort as the predictors of perceived usefulness (PU) and perceived ease of use (PEOU). Second, the current research intends to test the moderating effect of electronic words-of-mouth (eWOM) on the relationship between attitude and usage intention. Using survey methods, 226 usable responses were collected through a mall intercept survey in Pakistan. Data were analyzed using partial least square (PLS). The results revealed that PEOU and PU positively influence attitude toward M-wallet. This study has found that attitude positively influences the usage intention in adopting M-wallet. The results also support the moderating role of eWOM. These findings contribute to the marketing literature in several ways, particularly in Pakistan. This is the first study to use eWOM as a moderating variable in the TAM theory. In addition, this study adds to the current body of knowledge by considering eWOM as a multi-dimensional construct novel in m-wallet literature.

Pharmacological basis of the putative therapeutic effect of Topical Vitamin D3 on the experimental model of atopic dermatitis in mice.

OBJECTIVE: The aim of the study was to explore the effect of topical vitamin D3 in atopic dermatitis (AD) induced by ovalbumin (OVA) in contrast with topical betamethasone in mice. MATERIALS AND METHODS: 35 BALB/c adult male mice, weighing between 25-30 gm were used to induce AD by topically sensitizing the dorsal surface of the skin with the OVA patch. Subsequently, treatments were performed in each group by application of vitamin D3 cream (0.0003%), betamethasone cream (0.1%), or vehicles (QV cream) on the skin. RESULTS: Remarkably, vitamin D3 had a marked improvement in the skin of OVA-induced AD mice. Additionally, vitamin D3 revealed a considerable diminution in the levels of IgE, IL-5, filaggrin, and epidermal thickness, whereas a significant augmentation in the levels of IL-4 and IL-13 was observed when compared with the control group, and histopathological studies had further confirmed these findings. CONCLUSIONS: This study essentially highlighted the anti-inflammatory effect of vitamin D3 by effective alteration in the immunological components responsible for AD. Moreover, this pioneer experimental work represents a new paradigm and sheds a light on the importance of vitamin D3 in the implications of AD. A comprehensive creative approach is crucial to concretely establish and further corroborate vitamin D3 for this therapeutic role.

Impact of Bayesian penalized likelihood reconstruction on quantitative and qualitative aspects for pulmonary nodule detection in digital 2-[18F]FDG-PET/CT.

To evaluate the impact of block sequential regularized expectation maximization (BSREM) reconstruction on quantitative and qualitative aspects of 2-[18F]FDG-avid pulmonary nodules compared to conventional ordered subset expectation maximization (OSEM) reconstruction method. Ninety-one patients with 144 2-[18F]FDG-avid pulmonary nodules (all ≤ 20 mm) undergoing PET/CT for oncological (re-)staging were retrospectively included. Quantitative parameters in BSREM and OSEM (including point spread function modelling) were measured, including maximum standardized uptake value (SUVmax). Nodule conspicuity in BSREM and OSEM images was evaluated by two readers. Wilcoxon matched pairs signed-rank test was used to compare quantitative and qualitative parameters in BSREM and OSEM. Pulmonary nodule SUVmax was significantly higher in BSREM images compared to OSEM images [BSREM 5.4 (1.2-20.7), OSEM 3.6 (0.7-17.4); p = 0.0001]. In a size-based analysis, the relative increase in SUVmax was more pronounced in smaller nodules (≤ 7 mm) as compared to larger nodules (8-10 mm, or > 10 mm). Lesion conspicuity was higher in BSREM than in OSEM (p < 0.0001). BSREM reconstruction results in a significant increase in SUVmax and a significantly improved conspicuity of small 2-[18F]FDG-avid pulmonary nodules compared to OSEM reconstruction. Digital 2-[18F]FDG-PET/CT reading may be enhanced with BSREM as small lesion conspicuity is improved.

Potential Nephroprotective Effect of Dorsomorphin Homolog 1 (DMH1) in a rat model of diabetic nephropathy.

OBJECTIVE: Diabetic nephropathy (DN) represents the most common cause of end-stage renal disease. On the other hand, Bone Morphogenetic Protein signaling pathway (BMP/Smad) is one of the most interesting prophylactic targets, since inhibition of this pathway may preserve kidney functions. Therefore, a BMP pharmacological inhibitor, Dorsomorphin Homolog 1 (DMH1) was used to assess the potential nephroprotective effect in an animal model of DN. MATERIALS AND METHODS: STZ-induced diabetic rat was the selected model to assess the nephroprotective effect of DMH1(5 mg/kg) for eight weeks. Rats were divided into normal control (C=10), diabetic control (DC=10), diabetic+vehicle (DV=10) and diabetic DMH1-treated rats (DT=10). Fasting blood glucose (FBG) level was measured on a weekly basis. Then, glycated hemoglobin (HbA1c), serum Creatinine (sCr), Cystatin-C (Cys-C) and Blood Urea Nitrogen (BUN) were measured by the end of the experiment. Furthermore, Tumor Necrosis Factor (TNF-α), Interleukin-6 (IL-6) and Malondialdehyde (MDA) levels were determined in kidney tissues. The histopathological study was also performed using Hematoxylin and Eosin (H&E), Periodic acid Schiff (PAS) and Masson's trichrome stains. RESULTS: DMH1 treatment has significantly reduced HbA1c along with sCr, Cys-C and BUN vs. the diabetic non-treated groups (p < 0.001). Furthermore, TNF-α, IL-6 and MDA levels were also significantly decreased in the DT group compared to the diabetic non-treated groups (p < 0.001). This improvement was further confirmed and found in correspondence with histopathological findings. CONCLUSIONS: The present findings revealed a nephroprotective activity of DMH1 against STZ-induced DN in rats. DMH1 also showed anti-inflammatory and antioxidant activities, which may explain part of the nephroprotective mechanism. This can shed light on the importance of DMH1 and BMP/Smad pathway for further experimental studies.

Low-dose CT from myocardial perfusion SPECT/CT allows the detection of anemia in preoperative patients.

BACKGROUND: To assess whether low-dose CT for attenuation correction of myocardial perfusion single-photon emission computed tomography (SPECT) allows for identification of anemic patients and grading anemia severity. METHODS AND RESULTS: Patients who underwent a preoperative blood-test and low-dose CT scan, as a part of a cardiac SPECT exam, between 01 January 2015 and 31 December 2017 were enrolled in this retrospective study. Hemoglobin (Hb) levels and hematocrit were derived from clinical records. CT images were visually assessed (qualitative analysis) for the detection of inter-ventricular septum sign (IVSS) and aortic rim sign (ARS) and quantitative analysis were performed. The diagnostic accuracy for detecting anemia was compared using Hb values as the standard of reference. A total of 229 patients were included (110 with anemia; 57 mild; 46 moderate; 7 severe). The AUC of IVSS and ARS were 0.830 and 0.669, respectively (p<0.0001). The quantitative analysis outperformed ARS and IVSS; (AUC of 0.893, p=0.29). The optimal anemia cut-off using Youden index was 4.5 HU. CONCLUSION: Quantitative analysis derived from low-dose CT images, as a part of cardiac SPECT exams, have a diagnostic accuracy similar to that of hematocrit for the detection of anemia and may allow discriminating different anemia severities.

Optimal tuning of sigmoid PID controller using Nonlinear Sine Cosine Algorithm for the Automatic Voltage Regulator system.

Automatic Voltage Regulator (AVR) is fabricated to sustain the voltage level of a synchronous generator spontaneously. Several control strategies have been introduced into the AVR system with the aim of gaining a better dynamic response. One of the most universally utilized controllers is the Proportional-Integral-Derivative (PID) controller. Despite the PID controller having a relatively high dynamic response, there are still further possibilities to improve in order to obtain more appropriate responses. This paper designed a sigmoid-based PID (SPID) controller for the AVR system in order to allow for an accelerated settling to rated voltage, as well as increasing the control accuracy. In addition, the parameters of the proposed SPID controller are obtained using an enhanced self-tuning heuristic optimization method called Nonlinear Sine Cosine Algorithm (NSCA), for achieving a better dynamic response, particularly with regards to the steady-state errors and overshoot of the system. A time-response specifications index is used to validate the proposed SPID controller. The obtained simulation results revealed that the proposed method was not only highly effective but also greatly improved the AVR system transient response in comparison to those with the modern heuristic optimization based PID controllers.

Cryptic footprints of rare earth elements on natural resources and living organisms.

BACKGROUND: Rare earth elements (REEs) are gaining attention due to rapid rise of modern industries and technological developments in their usage and residual fingerprinting. Cryptic entry of REEs in the natural resources and environment is significant; therefore, life on earth is prone to their nasty effects. Scientific sectors have expressed concerns over the entry of REEs into food chains, which ultimately influences their intake and metabolism in the living organisms. OBJECTIVES: Extensive scientific collections and intensive look in to the latest explorations agglomerated in this document aim to depict the distribution of REEs in soil, sediments, surface waters and groundwater possibly around the globe. Furthermore, it draws attention towards potential risks of intensive industrialization and modern agriculture to the exposure of REEs, and their effects on living organisms. It also draws links of REEs usage and their footprints in natural resources with the major food chains involving plants, animals and humans. METHODS: Scientific literature preferably spanning over the last five years was obtained online from the MEDLINE and other sources publishing the latest studies on REEs distribution, properties, usage, cycling and intrusion in the environment and food-chains. Distribution of REEs in agricultural soils, sediments, surface and ground water was drawn on the global map, together with transport pathways of REEs and their cycling in the natural resources. RESULTS: Fourteen REEs (Ce, Dy, Er, Eu, Gd, Ho, La, Lu, Nd, Pr, Sm, Tb, Th and Yb) were plighted in this study. Wide range of their concentrations has been detected in agricultural soils (<15.9-249.1 µg g-1) and in groundwater (<3.1-146.2 µg L-1) at various sites worldwide. They have strong tendency to accumulate in the human body, and thus associated with kidney stones. The REEs could also perturb the animal physiology, especially affecting the reproductive development in both terrestrial and aquatic animals. In plants, REEs might affect the germination, root and shoot development and flowering at concentration ranging from 0.4 to 150 mg kg-1. CONCLUSIONS: This review article precisely narrates the current status, sources, and potential effects of REEs on plants, animals, humans health. There are also a few examples where REEs have been used to benefit human health. However, still there is scarce information about threshold levels of REEs in the soil, aquatic, and terrestrial resources as well as living entities. Therefore, an aggressive effort is required for global action to generate more data on REEs. This implies we prescribe an urgent need for inter-disciplinary studies about REEs in order to identify their toxic effects on both ecosystems and organisms.

Competing magnetic effects due to the incorporation of oxygen in thin films of (ZnCo)O.

We have investigated the magnetic properties of ZnCoO thin films grown by pulsed laser deposition from targets made from pure ZnO combined with metallic Co, CoO or Co3O4 as a function of oxygen pressure in the deposition chamber. We find that the structural and magnetic properties of films grown from targets containing CoO or Co3O4 are similar and can be mapped on to each other by assuming that the films made from CoO require some additional oxygen to make them the same as those grown from Co3O4. The data suggest that the magnetism in these films is due to oxygen vacancies. Radically different properties are seen for the films grown with metallic Co in the target. In this case, there is structural evidence for the production of Zn vacancies as oxygen was added during deposition and this was accompanied by a strong increase of the magnetisation. In contrast, there was very little difference seen between the magnetic properties of the targets, which were all found to be paramagnetic, even after further annealing in air.

The relationship between seminal plasma and serum trace elements and semen parameters of dromedary camels (Camelus dromedarius).

A total of 14 camels of known fertility (controls) at the Camel Research Centre, King Faisal University and 41 infertile dromedaries brought to the Veterinary Teaching Hospital were used in this study during the breeding season. Seminal plasma and serum were obtained from all males, and stored at -80°C until analysis. Concentrations of six trace elements (manganese [Mn], zinc [Zn], iron [Fe], selenium [Se], copper [Cu] and chromium [Cr]) were estimated in the seminal plasma and serum using an atomic absorption spectrophotometer. Results showed significant (p < 0.05 and p < 0.01) differences in semen pH and sperm motility, concentration and abnormalities between the control and infertile dromedaries. In seminal plasma, a significant (p < 0.01) difference in Fe concentrations (7.792 ± 1.567 vs. 61.259 ± 11.967 mg/L) and significant (p < 0.05) differences in Zn (24.763 ± 8.206 vs. 83.981 ± 4.972 mg/L) and Cu (1.653 ± 0.348 vs. 7.905 ± 1.134 mg/L) concentrations existed between the control and infertile dromedaries, respectively. In serum, there were significant (p < 0.05) differences in Fe (6.237 ± 0.695 vs. 151.121 ± 27.604 mg/L) and Cu (24.703 ± 4.195 vs. 6.375 ± 0.644 mg/L) concentrations and a significant (p < 0.01) difference in Zn concentrations (17.086 ± 1.606 vs. 90.422 ± 4.347 mg/L) between the fertile and infertile camels, respectively. There were significant (p < 0.05) positive (r = 0.51) and negative (r = -0.54) correlations between Zn concentrations in seminal plasma and both sperm motility and sperm abnormalities, respectively. In conclusion, seminal plasma and serum trace elements of Fe, Zn and Cu influenced the semen parameters and fertility of dromedary camels. Low concentrations of Fe, Zn and Cu in the seminal plasma were associated with normal fertility in dromedaries.

Assessment of oxidative stress of platelets among chronic heroin and hashish addicts.

INTRODUCTION: Illicit drugs abuse is associated with several clinical life-threatening consequences that are primarily mediated by oxidative damage to multiple cellular components with a subsequent cellular dysfunction and death. Primarily, this study aimed to investigate oxidative stress to protein and lipid components of circulatory platelets among chronic heroin and hashish addicts. METHODS: Platelet lysates were prepared from 20 chronic intravenously administrated heroin addicts and 20 chronic smoked hashish addicts. For comparative purposes, two control groups of 20 cigarette smokers and 20 nonsmokers were included in the study. Oxidative stress to platelet's proteins and lipids was investigated using carbonyl group contents assay and thiobarbituric acid reactive substances (TBARS) assay, respectively. RESULTS: In comparison to control groups, carbonyl group contents and TBARS concentration were significantly higher among heroin addicts but not among hashish addicts. Both of these markers were significantly correlated to the duration of addiction but not to the daily administrated dose. While in regard of the timing of the latest administrated dose (TLAD), only carbonyl group contents were significantly correlated to the TLAD. CONCLUSIONS: Considering the contribution of drug's route of administration, drug's pharmacokinetics, and kinetics of circulatory platelet, we concluded that chronic heroin addiction is associated with significant levels of oxidative stress to platelet's proteins and lipids. Due to the high proteomic contents of platelets, protein's oxidative stress is more prominent compared to lipids. Chronic hashish smoking is not associated with significant levels of oxidative stress in platelet's proteins and lipids.

The impact of multiple blood donations on the risk of cardiovascular diseases: Insight of lipid profile.

OBJECTIVES: The reduction in blood viscosity and iron store were proposed to be connected to the reduction in the risk of cardiovascular disease (CVD) among multiple blood donors. Herein, we evaluated the modulation of serum lipids levels in accordance with donation events. Furthermore, atherogenic impacts on the risk of CVD were investigated. MATERIALS AND METHODS: A total of 100 voluntarily male donors were included in the study. Fifty donors were multiple time donors (MTD) and 50 were single time donors (STD). Levels of serum lipids were determined and atherogenic indices including TG/HDL and CHO/HDL ratios were calculated. QRISK2 parameters were determined to evaluate the 10-years risk of developing CVD. RESULTS: Among MTD, there were significantly higher serum levels of triglycerides (TG) and very low-density lipoproteins (VLDL) combined with significantly lower HDL level. These modulations were significantly correlated to the extent of donation. Both CHO/HDL and TG/HDL ratios were also significantly higher among MTD. However, only TG/HDL ratio was strongly correlated to the donation extent even when controlled for age, BMI and smoking status. Despite the significant difference in QRISK2 parameters between study groups, none of these parameters was correlated to the extent of donation when controlling for age, BMI and smoking status. CONCLUSION: We demonstrate that multiple blood donation is associated with an unfavorable modulation of serum levels of lipids that is influenced by donation extent. This modulation is not associated with an increased risk of CVD but may weakly contribute in a higher risk for coronary heart disease (CHD).

A hypothetical model to solve the controversy over the involvement of UCP2 in palmitate-induced ß-cell dysfunction.

The aim of this article is to solve an existing controversy over the involvement of uncoupling protein-2 in the impairment of glucose-stimulated insulin secretion induced by chronic exposure of ß-cells to palmitate. We analyzed and compared the results of studies that support and that deny the involvement of uncoupling protein-2 in this impairment. We observed that this impairment could occur in multiple stages. We provide a model in which palmitate-induced impairment of glucose-stimulated insulin secretion is proposed to occur in two stages, early stage and late stage, depending on the integrity of electron supply (glycolysis and Krebs cycle) and transport system through electron transport chain after palmitate treatment. Prolonged exposure of ß-cells to palmitate can impair this system. Early-stage impairment occurs due to uncoupling by uncoupling protein-2 when this system is still intact. When this system becomes impaired, late-stage impairment occurs mainly due to reduced glucose-stimulated adenosine triphosphate production independent of uncoupling by uncoupling protein-2. The change in glucose-stimulated oxygen uptake after palmitate treatment reflects the integrity of this system and can be used to differentiate between the two stages. Some ß-cells lines and islets appear to be more resistant to palmitate-induced impairment of electron supply and transport system than others, and therefore early stage is prominent in the more resistant cell lines and less prominent or absent in the less resistant cell lines. This may help to resolve the pathogenesis of diabetes and to monitor the progression of palmitate-induced ß-cell dysfunction.

Protective Effect of Guggulipid in High Fat Diet and Middle Cerebral Artery Occlusion (MCAO) Induced Ischemic Cerebral Injury in Rats.

AIM: The role of guggulipid was evaluated in high fat diet and middle cerebral artery occlusion (MCAO) induced ischemic cerebral dysfunctions in rats of either sex. MATERIALS AND METHODS: Ethyl acetate extract of guggul known as guggulipid was prepared and administered to rats. Animals were divided into 9 groups, consisting 6 rats, each receiving different treatments per orally for 8 weeks. Control group rats received normal control diet while rest of the other groups animals were fed high fat diet (HFD) for 8 weeks. Cerebral ischemia was induced for 2 h followed by reperfusion for 22 h. Locomotor activity and grip strength tests were performed immediately after 24 h of reperfusion followed by biochemical estimations and histopathology. RESULTS: Locomotor activity and grip strength were significantly decreased in HFD and HFD fed MCAO groups and improved significantly in pretreatment groups. Cerebral infarction, thiobarbituric acid reactive substances (TBARs), nitric oxide and tumor necrosis factor alfa (TNFα) levels were increased, pretreatment of guggulipid alone and with aspirin significantly reduced these markers. Reduced glutathione (GSH), superoxide dismutase (SOD) and catalase, levels were decreased but all drug pretreated groups showed significant improvement in those markers. CONCLUSION: Guggulipid demonstrated neuroprotection owing to its hypolipidemic, antioxidant, anti-inflammatory and anti-thrombotic activities but further research is warranted to confirm its role in cerebral ischemia.

Effect of Sarcosine (a Glycine Transport 1 Inhibitor) and Risperidone (an Atypical antipsychotic Drug) on MK-801 Induced Learning and Memory Deficits in Rats.

The present study was carried out to evaluate whether the combined administration of sarcosine with risperidone possess any advantageous effects on dopaminergic and NMDA receptor-mediated glutamatergic neurotransmissions as compared to single drug administration in rats. The Wistar rats were divided into 7 groups each with different treatments. MK-801 (0.1 mg/kg, i.p.) was injected as single dose on 14th day for inducing learning and memory deficits in animals. Sarcosine (300 and 600 mg/kg, i.p.) and risperidone (0.2 mg/kg, i.p.) were administered daily for 14 days. Spatial habituation learning and hole board tests were performed on 14th day followed by measurement of GABA and 5-HT levels in brain tissues of rats. Pretreatment of sarcosine (600 mg/kg, i.p.) non-significantly improved learning and memory deficits induced by non-competitive NMDA receptor antagonist MK-801, significantly increased the GABA and decreased the 5-HT levels (p<0.05). Combined administration of sarcosine (300 mg/kg, i.p.) with risperidone (0.1 mg/kg, i.p.) synergistically improved cognitive deficits significantly, decreased % errors in hole board learning test, and increased centre time, corner time in spatial habituation learning test (p<0.05). The combined administration also potentiated the GABA and decreased 5-HT levels, indicating that the increased synaptic glycine concentrations may enhance NMDA receptor function which is directly linked with increased GABAergic transmission in striatum region and decreased 5-HT levels showed antagonistic action hence, enhancing the cognition. Our results suggest that combined administration of sarcosine with risperidone may strengthen glutamatergic tone in striatum. Thus, it may be a novel regime to improve psychotic symptoms and cognitive deficit in schizophrenia.

Effects of the knockdown of death-associated protein 3 expression on cell adhesion, growth and migration in breast cancer cells.

The death-associated protein 3 (DAP3) is a highly conserved phosphoprotein involved in the regulation of autophagy. A previous clinical study by our group suggested an association between low DAP3 expression and clinicopathological parameters of human breast cancer. In the present study, we intended to determine the role of DAP3 in cancer cell behaviour in the context of human breast cancer. We developed knockdown sub-lines of MCF7 and MDA-MB-231, and performed growth, adhesion, invasion assays and electric cell-substrate impedance sensing (ECIS) studies of post-wound migration of the cells. In addition, we studied the mRNA expression of caspase 8 and 9, death ligand signal enhancer (DELE), IFN-ß promoter stimulator 1 (IPS1), cyclin D1 and p21 in the control and knockdown sub-lines. The knockdown sub-lines of MCF7 and MDA-MB-231 had significantly increased adhesion and decreased growth when compared to the controls. Furthermore, invasion and migration were significantly increased in the MDA-MB-231DAP3kd cells vs. the controls. The expression of caspase 9 and IPS1, known components of the apoptosis pathway, were significantly reduced in the MCF7DAP3kd cells (p=0.05 and p=0.003, respectively). We conclude that DAP3 silencing contributes to breast carcinogenesis by increasing cell adhesion, migration and invasion. It is possible that this may be due to the activity of focal adhesion kinase further downstream of the anoikis pathway. Further research in this direction would be beneficial in increasing our understanding of the mechanisms underlying human breast cancer.

Calcium-sensing receptor 20 years later.

The calcium-sensing receptor (CaSR) has played an important role as a target in the treatment of a variety of disease states over the past 20 plus years. In this review, we give an overview of the receptor at the cellular level and then provide details as to how this receptor has been targeted to modulate cellular ion transport mechanisms. As a member of the G protein-coupled receptor (GPCR) family, it has a high degree of homology with a variety of other members in this class, which could explain why this receptor has been identified in so many different tissues throughout the body. This diversity of locations sets it apart from other members of the family and may explain how the receptor interacts with so many different organ systems in the body to modulate the physiology and pathophysiology. The receptor is unique in that it has two large exofacial lobes that sit in the extracellular environment and sense changes in a wide variety of environmental cues including salinity, pH, amino acid concentration, and polyamines to name just a few. It is for this reason that there has been a great deal of research associated with normal receptor physiology over the past 20 years. With the ongoing research, in more recent years a focus on the pathophysiology has emerged and the effects of receptor mutations on cellular and organ physiology have been identified. We hope that this review will enhance and update the knowledge about the importance of this receptor and stimulate future potential investigations focused around this receptor in cellular, organ, and systemic physiology and pathophysiology.