Effect of different levels of single cell protein and probiotic microorganisms on performance, immunological responses, and intestinal histology in laying hens.

An experiment was conducted to evaluate the effects of single-cell protein (SCP), as a valuable by-product and substitute for soybean meal, and multistrain probiotics on the performance, blood biochemistry, intestinal histomorphology, ileal microbiota, and immune responses in laying hens. Leghorn laying hens were randomly assigned to nine experimental treatments with eight replicates of five birds each. Dietary treatments consisted of three levels of replacement of soybean meal with SCP (0.0%, 30%, and 60%) and three levels of probiotics (0.0, 50, 100 mg/kg) offered through 70 days of main recording. The result indicated that replacing 30% soybean meal with SCP in the diet significantly increased the eggshell weight, thickness, and strength; however, hens receiving 60% SCP replacement showed lower productive performance. During the second 35-d trial, hens receiving at least 50 mg/kg probiotics produced higher eggshell weight, thickness, and strength than the control hens. Remarkable lower levels of serum cholesterol content were observed in the SCP and probiotic-supplemented diets. The significant reduction in the ileal pH, Escherichia coli and Clostridium spp. enumerations and a remarkable increase in Lactobacillus count was observed after feeding incremental levels of probiotics. The highest villus height to crypt depth ratio, antibody titer against sheep red blood cells (in secondary response) and Newcastle disease vaccine, as well as egg production and egg mass, were found in the hens that received 30% SCP replacement in combination with 50 or 100 mg/kg probiotic (SCP × Probiotic). The present study concluded that feeding SCP, as a cheap protein alternative source, along with probiotics while reducing production costs can support productive performance via modulating the intestinal microbiomes and health indices and fortifying the immune system in laying hens.

Clinical Comparison of Three Indirect Pulp Capping Restorative Protocols: A Randomized Controlled Prospective Study.

OBJECTIVES: The objective of this prospective double-blind clinical trial was to compare clinical outcomes of indirect pulp capping restorative protocols on permanent teeth over a 12-month period. METHODS AND MATERIALS: Deep carious lesions in permanent teeth (90) were randomly assigned to three indirect pulp capping protocols (n=30: TheraCal LC, Dycal, and no liner). All teeth were restored with resin composite. The outcome measures were pain (VAS scale) and success rate (pulp vitality based on percussion, palpation, cold test, and radiographic findings), collected at screening, intervention, and 24-hour, 7-day, 3-month, 6-month, and 12-month follow-up visits. RESULTS: There was no statistically significant difference in tooth sensitivity among the three indirect pulp capping protocols nor in success rates among the restorative protocols after 1 year of follow-up (p>0.1).The respective success rates, as defined by the tooth remaining vital, after 1 year were: 96.2% for TheraCal LC, 100% for Dycal, and 100% for no liner. CONCLUSIONS: After 12-month evaluation, the success rate of indirect pulp capping therapy on permanent teeth was not affected by the pulp capping restorative protocol.

Toward making a high-quality silage from common reed (Phragmites australis).

The effects of the addition of molasses (5 and 10% of dry matter: DM basis; M5 and M10 respectively) with or without urea (2%; U2, U2 + M5 and U2 + M10) on chemical and mineral composition, silage quality, microbial populations, buffering capacity and fermentation/digestion characteristics of common reed (Phragmites australis) ensiled under anaerobic conditions were investigated. The additives changed the silage quality of common reed compared with the control. Crude protein content was significantly (p < 0.0001) increased in urea-containing silages, whereas ash-free neutral detergent fibre concentration decreased in M10 compared with the control (p = 0.05). Treatment with 2% urea (U2) resulted in the reduction of most measured minerals with a severe decrease in iron concentration. The amount of gas produced after 96 h of incubation was, respectively, higher for U2, M10, U2M10, U2M5 and M5 compared with the control (p < 0.0001). Although the greatest in vitro dry matter digestibility and in vitro organic matter digestibility (96 h) were observed in U2 (p < 0.0001), no significant differences were found between U2 and M10. Supplementation with 10% molasses (M10) significantly increased lactic acid concentration, aerobic stability and total bacteria compared with other treatments (p < 0.0001). Moreover, DM loss (p = 0.0004), total yeast and mould (p < 0.0001) were significantly decreased as a result of 10% molasses treatment. Overall, it can be suggested that treating silage with 10% molasses (M10) has the potential to efficiently improve the nutritive value of common reed.

A Fiber-Optical Dosimetry Sensor for Gamma-Ray Irradiation Measurement in Biological Applications.

In this paper, we propose a novel fiber-optical dosimetry sensor for radiation measurement in biological applications. A two-dimensional (2D) fiber-optical dosimeter (FOD) for radiation measurement is considered. The sensors are arranged as a 2D array in a tailored holder. This FOD targets accurate industrial and medical applications which seek more tolerant radiation dosimeters. In this paper, the FOD sensors are subjected to gamma-ray radiation facilities from the 137Cs gamma-ray irradiator type for low doses and 60Co gamma-ray irradiator for high doses. For better evaluation of radiation effects on the FOD sample, the measurements are performed using eight sensors (hollow cylinder shape) with two samples in each dose. The sensors were measured before and after each irradiation. To the author's knowledge, the measurements of FOD transplanted inside animals are presented for the first time in this paper. A 2D simulation program has been implemented for numerical simulation based on the attenuation factors from the absorbed dose inside the in vivo models. A comparison between the FOD and the standard thermo-luminescence detector is presented based on the test of in vivo animal models. The results indicate that the proposed FOD sensor is more stable and has higher sensitivity.

Empirical Dilation of Non-obstructive Dysphagia: Current Understanding and Future Directions.

Non-obstructive dysphagia (NOD) is defined as symptomatic dysphagia in patients with negative endoscopic and radiographic workup. The management of NOD remains controversial as there is a discrepancy between different guidelines and clinical practice. Despite the lack of high-quality studies, empiric dilation for NOD is a common clinical practice among endoscopists and the approach varies between different clinical centers. In this review, we summarize the published literature on empiric dilation for NOD and propose a management algorithm for offering empiric dilation to patients presenting with dysphagia.

The effects of supplementation of Withania coagulans and α-tocopherol acetate in diets containing oxidised oil on growth performance, immune response and antioxidant indices in broiler chickens.

This experiment was designed to study the effects of a hydroalcoholic fruit extract from Withania coagulans (WC) and α-tocopherol acetate (α-Toc) in diets containing oxidised oil on growth performance, immune response and antioxidant indices of broiler chickens. The experiment was arranged 2 × 3 × 2 factorial comprising the oxidised oil (0% and 2% diet), WC (0, 100 and 200 mg/kg diet) and α-Toc (0 and 200 mg/kg diet). A total of 600 1-day-old male broiler chickens of the Ross strain were randomly allocated to 12 treatments with 5 replicates of 10 birds each. On day 42, one bird from each replicate was sacrified to measure the lymphoid organ weights, intestinal morphometric characteristics, and malondialdehyde content in the thigh meat. Dietary inclusion of oxidised oil significantly reduced the body weight gain in birds receiving no dietary WC (p < 0.05). In contrast, dietary supplementation of WC at 100 mg/kg diet in birds fed with the diets lacking in WC and oxidised oil resulted in significant increase in body weight gain (p < 0.05). Dietary supplementation of WC significantly increased the total anti-sheep red blood cell titre (p < 0.01). The birds fed with the dietary oxidised oil revealed significantly higher values of malondialdehyde and lower glutathione peroxidase and superoxide dismutase activities (p < 0.05). Feeding diets containing WC resulted in a significant decrease in malondialdehyde content in thigh meat while conversely, increased the glutathione peroxidase and superoxide dismutase activities (p < 0.05). The findings indicated that the dietary inclusion of WC could be recommended as a potent alternative to synthetic compounds in order to improve broilers performance, immunity and meat quality under oxidative stress conditions.

Thrombotic characteristics of extracellular vesicles derived from prostate cancer cells.

BACKGROUND: Prostate cancer (PC) patients in advanced stages of the disease have high risk of blood coagulation complications. The procoagulant molecule Tissue factor (TF), and the fibrinolysis inhibitor plasminogen activator inhibitor-1 PAI-1 play important role in this complication. Extracellular vesicles (EV) shed from cancer cells may contribute to the regulation of TF and PAI-1. The procoagulant activity of EV can be associated with the oncogenic and metastatic characteristics of their cells. METHODS: We have expressed EGFRvIII in DU145 cells to assess the role of this oncogene in the procoagulant activity of EV. The intercellular exchange of TF via EV was assessed by downregulating its expression in DU145 cells using shRNA vector, and determining the transfer of TF via EV enriched with the protein. Two PC cell lines with different metastatic potential were used to assess the correlation between the procoagulant activity of EV and the metastatic potential of PC cells. Photometric assays were used to determine FXa-activity and thrombin generation as indicators for the procoagulant activity of EV. Double-tagged proteinase-activated receptor 1(PAR-1) expressed in CHO cells to assess its activation by EV. RESULTS: The expression of EGFRvIII in DU145 cells led to increased mRNA levels for TF and PAI-1, but the increase in these proteins expression was detected mostly in the EV. EV with enhanced levels of TF protein conferred higher TF procoagulant activity on the acceptor cells by intercellular exchange of this protein. Procoagulant activity of EV, assessed by FXa activity, and thrombin generation, was correlated with the oncogenic and metastatic potential of PC cells. The ability of EV to generate thrombin led to the activation of PAR-1, which was evident by the truncation of tagged-PAR-1. CONCLUSION: The active oncogene EGFRvIII increases the concentration of TF and PAI-1 in EV. The procoagulant activity of EV is associated with the oncogenic and metastatic characteristics of their PC cells. Also, EV may contribute to the high procoagulant activity in the tumour microenvironment by the intercellular exchange of TF. Finally, through the generation of thrombin, EV can activate PAR-1, which evidently contributes to cancer progression, linking the coagulation system to tumor progression.

On the scattering directionality of a dielectric particle dimer of High Refractive Index.

Low-losses and directionality effects exhibited by High Refractive Index Dielectric particles make them attractive for applications where radiation direction control is relevant. For instance, isolated metallo-dielectric core-shell particles or aggregates (dimers) of High Refractive Index Dielectric particles have been proposed for building operational switching devices. Also, the possibility of using isolated High Refractive Index Dielectric particles for optimizing solar cells performance has been explored. Here, we present experimental evidence in the microwave range, that a High Refractive Index Dielectric dimer of spherical particles is more efficient for redirecting the incident radiation in the forward direction than the isolated case. In fact, we report two spectral regions in the dipolar spectral range where the incident intensity is mostly scattered in the forward direction. They correspond to the Zero-Backward condition (also observed for isolated particles) and to a new condition, denoted as "near Zero-Backward" condition, which comes from the interaction effects between the particles. The proposed configuration has implications in solar energy harvesting devices and in radiation guiding.

Primary healthcare policy implementation in the Eastern Mediterranean region: Experiences of six countries.

BACKGROUND: Primary healthcare (PHC) is essential for equitable access and cost-effective healthcare. This makes PHC a key factor in the global strategy for universal health coverage (UHC). Implementing PHC requires an understanding of the health system under prevailing circumstances, but for most countries, no data are available. OBJECTIVES: This paper describes and analyses the health systems of Bahrain, Egypt, Lebanon, Qatar, Sudan and the United Arab Emirates, in relation to PHC. METHODS: Data were collected during a workshop at the WONCA East Mediterranean Regional Conference in 2017. Academic family physicians (FP) presented their country, using the WONCA framework of 11 PowerPoint slides with queries of the country demographics, main health challenges, and the position of PHC in the health system. RESULTS: All six countries have improved the health of their populations, but currently face challenges of non-communicable diseases, aging populations and increasing costs. Main concerns were a lack of trained FPs in community settings, underuse of prevention and of equitable access to care. Countries differed in the extent to which this had resulted in coherent policy. CONCLUSION: Priorities were (i) advocacy for community-based PHC to policymakers, including the importance of coordination of healthcare at the community level, and UHC to respond to the needs of populations; (ii) collaboration with universities to include PHC as a core component of every medical curriculum; (iii) collaboration with communities to improve public understanding of PHC; (iv) engagement with the private sector to focus on PHC and UHC.

Microvesicles Contribute to the Bystander Effect of DNA Damage.

Genotoxic treatments elicit DNA damage response (DDR) not only in cells that are directly exposed but also in cells that are not in the field of treatment (bystander cells), a phenomenon that is commonly referred to as the bystander effect (BE). However, mechanisms underlying the BE remain elusive. We report here that etoposide and ultraviolet (UV) exposure stimulate the production of microvesicles (MVs) in DU145 prostate cancer cells. MVs isolated from UV-treated DU145 and A431 epidermoid carcinoma cells as well as etoposide-treated DU145 cells induced phosphorylation of ataxia-telangiectasia mutated (ATM) at serine 1981 (indicative of ATM activation) and phosphorylation of histone H2AX at serine 139 (γH2AX) in naïve DU145 cells. Importantly, neutralization of MVs derived from UV-treated cells with annexin V significantly reduced the MV-associated BE activities. Etoposide and UV are known to induce DDR primarily through the ATM and ATM- and Rad3-related (ATR) pathways, respectively. In this regard, MV is likely a common source for the DNA damage-induced bystander effect. However, pre-treatment of DU145 naïve cells with an ATM (KU55933) inhibitor does not affect the BE elicited by MVs isolated from etoposide-treated cells, indicating that the BE is induced upstream of ATM actions. Taken together, we provide evidence supporting that MVs are a source of the DNA damage-induced bystander effect.

Electromagnetic polarization-controlled perfect switching effect with high-refractive-index dimers and the beam-splitter configuration.

Sub-wavelength particles made from high-index dielectrics, either individual or as ensembles, are ideal candidates for multifunctional elements in optical devices. Their directionality effects are traditionally analysed through forward and backward measurements, even if these directions are not convenient for in-plane scattering practical purposes. Here we present unambiguous experimental evidence in the microwave range that for a dimer of HRI spherical particles, a perfect switching effect is observed out of those directions as a consequence of the mutual particle electric/magnetic interaction. The binary state depends on the excitation polarization. Its analysis is performed through the linear polarization degree of scattered radiation at a detection direction perpendicular to the incident direction: the beam-splitter configuration. The scaling property of Maxwell's equations allows the generalization of our results to other frequency ranges and dimension scales, for instance, the visible and the nanometric scale.

Pattern of childhood brucellosis in Najran, south Saudi Arabia in 2013-2017.

BACKGROUND: With more than 500,000 new cases annually, human brucellosis is the commonest zoonotic disease worldwide. In some endemic countries, its prevalence is more than 10 per 100,000 population. OBJECTIVE: The aim of this study was to determine the magnitude of the problem and the clinical features, laboratory findings, treatment given and complications seen in children with brucellosis in Najran City, Kingdom of Saudi Arabia. METHODS: This is a case-series study by analysis of data of children known or diagnosed to have brucellosis for the last 4 years in Najran City. Data was obtained by reviewing the hospital records of the Maternity and Children Hospital and Najran Armed Forces Hospital in Najran during the period from 2013 to 2017. The statistical analysis was carried out using SPSS version 16.0. Since it was the first report of brucellosis on the study population, we used descriptive statistics (frequency, proportion, mean, and standard deviation) for presenting the findings. RESULTS: We studied 57 diagnosed cases of child brucellosis throughout the past 4 years in Najran, south Saudi Arabia with an average number of about 12 cases per year. Of the cases, 15.8% reported a history of ingestion of raw milk and dairy product and only 1.8% of them reported a history of animal contact while 82.4% confirmed unknown mode of transmission. Fever was the only finding in 36.8%, fever and arthralgia 21.1%, and fever and myalgia 19.3%. Two thirds of the cases were diagnosed by standard agglutination test (SAT). Hepatosplenomegaly was found in 10.5%. Rifampicin was the antibiotic of choice and 70.2% of cases have been cured but 3.5% relapsed and 1.8% died from complications. CONCLUSIONS: Results suggest brucellosis be considered in every child living in an endemic area, showing symptoms of fever and having a history of ingestion of raw milk and dairy product and/or animal contact.Prevention should rely on health education of the public about different issues of the disease including boiling raw milk.

Sterol Regulatory Element Binding Protein (SREBP)-1 is a novel regulator of the Transforming Growth Factor (TGF)-ß receptor I (TßRI) through exosomal secretion.

Accumulation of matrix in the glomerulus is a classic hallmark of diabetic nephropathy. The profibrotic cytokine transforming growth factor beta 1 (TGF-ß1) plays a central role in the development of glomerular sclerosis. Recent studies have demonstrated that the transcription factor sterol regulatory element binding protein (SREBP)-1 is an important regulator of glomerular sclerosis through both induction of TGF-ß1 as well as facilitation of its signaling. Here we have identified that SREBP-1 is also a novel regulator of TGF-ß receptor I (TßRI) expression in kidney mesangial cells. Inhibition of SREBP activation with fatostatin or downregulation of SREBP-1 using siRNA inhibited the expression of the receptor. SREBP-1 did not regulate TßRI transcription, nor did it induce its proteasomal or lysosomal degradation or proteolytic cleavage. Disruption of lipid rafts with cyclodextrin, however, prevented TßRI downregulation. This was not dependent on caveolae since SREBP-1 inhibition could induce TßRI downregulation in caveolin-1 knockout mesangial cells. SREBP-1 associated with TßRI, and SREBP-1 inhibition led to the secretion of TßRI in exosomes. Thus, we have identified a novel role for SREBP-1 as a cell surface retention factor for TßRI in mesangial cells, preventing its secretion in exosomes. Inhibition of SREBP-1 in vivo may thus provide a novel therapeutic strategy for diabetic nephropathy which targets multiple aspects of TGFß signaling and matrix upregulation.

Nuclear transportation of exogenous epidermal growth factor receptor and androgen receptor via extracellular vesicles.

Epidermal growth factor receptor (EGFR) plays a central role in the progression of several human malignancies. Although EGFR is a membrane receptor, it undergoes nuclear translocation, where it has a distinct signalling pathway. Herein, we report a novel mechanism by which cancer cells can directly transport EGFR to the nucleus of other cells via extracellular vesicles (EVs). The transported receptor is active and stimulates the nuclear EGFR pathways. Interestingly, the translocation of EGFR via EVs occurs independently of the nuclear localisation sequence that is required for nuclear translocation of endogenous EGFR. Also, we found that the mutant receptor EGFRvIII could be transported to the nucleus of other cells via EVs. To assess the role of EVs in the regulation of an actual nuclear receptor, we studied the regulation of androgen receptor (AR). We found that full-length AR and mutant variant ARv7 are secreted in EVs derived from prostate cancer cell lines and could be transported to the nucleus of AR-null cells. The EV-derived AR was able to bind the androgen-responsive promoter region of prostate specific antigen, and recruit RNA Pol II, an indication of active transcription. The nuclear-translocated AR via EVs enhanced the proliferation of acceptor cells in the absence of androgen. Finally, we provide evidence that nuclear localisation of AR could occur in vivo via orthotopically-injected EVs in male SCID mice prostate glands. To our knowledge, this is the first study showing the nuclear translocation of nuclear receptors via EVs, which significantly extends the role of EVs as paracrine transcriptional regulators.

Medical students' perception of the proposal for theme-based integrated multi-disciplinary objective structured practical examination in Saudi Arabia / 보건의료교육평가

This study aimed to find the opinion of preclinical medical students concerning a new suggested approach for practical assessment. Fifty-three female students agreed to participate in this study, out of 87 registered students in years 2 and 3 of the basic science phase of the College of Medicine, Qassim University, Kingdom of Saudi Arabia. Full explanation was made to the students of theme-based integrated objective structured practical examination (TBI-OSPE), followed by distribution of a questionnaire to collect the students' opinions. The study was conducted in January 2015. Results showed that 78% of respondents were accepting of this new approach, and that only 5.7% rejected it. This difference was statistically significant (P<0.05). This study suggested a new model for assessment of preclinical students' competencies using the proposed tool (TBI-OSPE) rather than standard classical OSPE, particularly in curricula involving high levels of integration and theme-based problems. This form of assessment would more positively enhance learning.

A study on biomarkers, cytokines, and growth factors in children with burn injuries.

Background. Burns are a unique injury which not only is devastating for the patients but also puts a great burden on society by consuming enormous health care resources. Despite improvements in burn wound care and treatment, understanding the role of pro-inflammatory and anti-inflammatory cytokines as well as the mechanisms responsible for the healing process remains to be clarified. Although leptin is regarded as a circulating hormone, it can exert a direct effect on T cells and monocytes, causing the release of cytokines. It may induce angiogenesis or influence angiogenic factors. The aim of the present work is to determine serum levels of leptin, tumour necrosis factor a (TNFa), interleukin-6 (IL-6), basic fibroblast growth factor (bFGF), procalcitonin (PCT), and C-reactive protein (CRP) in a group of children with thermal burns and to determine the changes in these parameters in relation to the duration of hospital stay, the presence of infection, and the total body surface area (TBSA) burned. Patients and methods. The study included 42 children with burns (22 males and 20 females; age range, 2 months to 7 years). The study also included 26 age-matched controls. Besides full clinical assessment, including assessment of TBSA burned and the presence or absence of sepsis, all the patients and controls had the following investigations performed: complete blood count, CRP, IL-6, TNFa, PCT, serum leptin, bFGF, and transforming growth factor a (TGFa). Results. The fatality rate in this study was 28.6%. Burn cases as a whole showed significantly higher values of white blood cells (WBC), CRP, PCT, TNFa, IL-6, leptin, bFGF, and TGFa than controls. Cases with sepsis showed significantly higher values of WBC, CRP, PCT, TNFa, and IL-6 than cases without sepsis. They showed significantly lower values of TGFa than cases without sepsis. Patients with larger TBSA (>30%) showed significantly higher levels of WBC, CRP, PCT, TNFa, IL-6, and leptin than cases with smaller TBSA. They showed significantly lower levels of bFGF and TGFa than patients with smaller TBSA. Non-survivors showed significantly higher levels of WBC, CRP, PCT, TNFa, and IL-6 than survivors. They showed significantly lower levels of leptin, bFGF, and TGFa than survivors. Correlation studies showed a significant positive correlation between TBSA and each of IL-6, TNFa, and leptin. Conclusions. Cytokines and leptin increased in severely burned patients, cases associated with sepsis, and in fatal cases, while bFGF and TGFa levels were lower in severe cases. This may point to impaired healing in such cases and to their poorer prognosis. Recommendations. It is highly recommended to monitor immunological parameters such as PCT and/or IL-6 for early detection of infectious complications following thermal injury. Leptin can be regarded as a novel treatment modality to diminish burn-induced inflammation, reduce post-burn immune dysfunction, and enhance burn healing.