The ameliorative effects of Nigella sativa, thymoquinone, and bentonite against aflatoxicosis in broilers via AFAR and Nrf2 signalling pathways, and down-regulation of caspase-3.

1. Aflatoxins (AFs) are metabolites which especially have toxic effects on proteins, and are detoxified by the aflatoxin-B1 aldehyde reductase (AFAR) pathway. In this pathway, the aldo-keto reductase family 7, member A2 (AKR7A2) enzyme, which is controlled by nucleic-related erythroid factor 2 (Nrf2), plays an active role. However, data on the efficacy of this critical pathway in broilers is limited.2. The aim of the following study was to investigate the changes in the expression levels of AKR7A2, Nrf2, and caspase-3, and the effects of Nigella sativa seeds (NS), thymoquinone (TMQ), and bentonite (BNT) in broilers exposed to AFs.3. One-hundred broilers were divided into ten groups (control (CNT); AF; NS; TMQ; BNT; AF+TMQ; AF+NS; AF+BNT; AF+BNT+NS; AF+BNT+TMQ) and fed for 28 d. AF, TMQ, NS and BNT were added to diets at levels of 2 mg/kg, 300 mg/kg, 50 g/kg and 10 g/kg respectively.4. The addition of AF to the diet decreased AKR7A2 and Nrf2 levels dramatically, but increased caspase-3 (P < 0.01). TMQ, NS and BNT additions to the diet eliminated all negative effects caused by AF (P < 0.01); and AKR7A2 and Nrf2 were further raised in TMQ and NS groups when compared to the control group. TMQ and NS showed a positive effect on detoxification parameters when given together with BNT.5. Supplementation with NS and TMQ enhanced AF detoxification via the AFAR pathway, by increasing AKR7A2 and Nrf2 levels, in addition to reducing hepatocyte apoptosis.

Label-free electrical detection of pyrophosphate generated from DNA polymerase reactions on field-effect devices.

We introduce a label-free approach for sensing polymerase reactions on deoxyribonucleic acid (DNA) using a chelator-modified silicon-on-insulator field-effect transistor (SOI-FET) that exhibits selective and reversible electrical response to pyrophosphate anions. The chemical modification of the sensor surface was designed to include rolling-circle amplification (RCA) DNA colonies for locally enhanced pyrophosphate (PPi) signal generation and sensors with immobilized chelators for capture and surface-sensitive detection of diffusible reaction by-products. While detecting arrays of enzymatic base incorporation reactions is typically accomplished using optical fluorescence or chemiluminescence techniques, our results suggest that it is possible to develop scalable and portable PPi-specific sensors and platforms for broad biomedical applications such as DNA sequencing and microbe detection using surface-sensitive electrical readout techniques.

Determination of the effects of aflatoxin B1 given in ovo on the proximal tibial growth plate of broiler chickens: histological, histometric and immunohistochemical findings.

Detrimental effects of aflatoxin B1 (AFB1) on the embryonic development of broiler tibia and its proximal growth plate were determined by means of histological, histometric and immunohistochemical methods. For this, 420 fertile eggs from parent stocks of Ross 308 broiler chickens were divided into five groups according to the proposed treatment: a control untreated group, a group injected with 30% ethanol and three further groups to be injected with 5, 15 or 40 ng AFB1. The eggs were injected into the air space prior to incubation. Five eggs from each group were opened at 9, 11, 13, 17, 19 and 21 days of incubation and tibial tissue samples were removed, dissected of muscle and connective tissues, and processed by means of routine histological techniques. The cell proliferation rate of the epiphyseal growth plate cells was determined by immunohistochemical assay of proliferating cell nuclear antigen (PCNA) expression. The results showed that both proliferative and hypertrophic zones narrowed significantly (P<0.05), when compared with the controls, in all of the AFB1-treated groups whereas the transitional zone thickened, especially in the group given 40 ng AFB1 group. The PCNA positivity indices of 15 and 40 ng AFB1-treated groups were significantly higher (P<0.05) on days 11, 13, 17, 19 and 21 of incubation. It was concluded that in ovo-administered AFB1 adversely affected embryonic development of the tibial growth plate, and that affected hatched broilers might also be more susceptible to skeletal disorders during growth.

Rapid surface uplift and crustal flow in the Central Andes (southern Peru) controlled by lithospheric drip dynamics.

The high flux magmatism, crustal shortening/extension and plateau formation in Cordilleran orogenic systems have been explained by removal of lithosphere (lower crust and the sub-arc mantle lithosphere) that develops beneath the magmatic arc and hinterland regions. However, the primary role of this process driving surface uplift, and crustal deformation is not well understood. Here, reconciling geodynamic model predictions with lithospheric structure and paleoelevation estimates, we suggest that viscous drip-type lithospheric removal from beneath the Central (Peruvian) Andes can explain several tectonic features: (1) "double humped" shaped/axisymmetric topographic profile and rapid surface rise (up to 1.2 km in ~ 4.31 Myrs); (2) thicker crust associated with the lower surface elevation of the Altiplano plateau (Lake Titicaca region) (negative residual topography) and higher topography and thinner crust of Western and Eastern Cordilleras (positive residual topography); and (3) faster wave speed (colder)/sub-Moho anomaly underlying the Altiplano, surrounded by slower speed anomalies on both western arc-forearc areas and parts of the eastern Cordillera and Sub-Andes. Our results emphasize the important role of lithospheric drip and associated mantle dynamics in the transient evolution of Andean orogeny controlling surface uplift and crustal flow and thickening.

Silicon field effect transistors as dual-use sensor-heater hybrids.

We demonstrate the temperature mediated applications of a previously proposed novel localized dielectric heating method on the surface of dual purpose silicon field effect transistor (FET) sensor-heaters and perform modeling and characterization of the underlying mechanisms. The FETs are first shown to operate as electrical sensors via sensitivity to changes in pH in ionic fluids. The same devices are then demonstrated as highly localized heaters via investigation of experimental heating profiles and comparison to simulation results. These results offer further insight into the heating mechanism and help determine the spatial resolution of the technique. Two important biosensor platform applications spanning different temperature ranges are then demonstrated: a localized heat-mediated DNA exchange reaction and a method for dense selective functionalization of probe molecules via the heat catalyzed complete desorption and reattachment of chemical functionalization to the transistor surfaces. Our results show that the use of silicon transistors can be extended beyond electrical switching and field-effect sensing to performing localized temperature controlled chemical reactions on the transistor itself.

High-k dielectric Al2O3 nanowire and nanoplate field effect sensors for improved pH sensing.

Over the last decade, field-effect transistors (FETs) with nanoscale dimensions have emerged as possible label-free biological and chemical sensors capable of highly sensitive detection of various entities and processes. While significant progress has been made towards improving their sensitivity, much is yet to be explored in the study of various critical parameters, such as the choice of a sensing dielectric, the choice of applied front and back gate biases, the design of the device dimensions, and many others. In this work, we present a process to fabricate nanowire and nanoplate FETs with Al(2)O(3) gate dielectrics and we compare these devices with FETs with SiO(2) gate dielectrics. The use of a high-k dielectric such as Al(2)O(3) allows for the physical thickness of the gate dielectric to be thicker without losing sensitivity to charge, which then reduces leakage currents and results in devices that are highly robust in fluid. This optimized process results in devices stable for up to 8 h in fluidic environments. Using pH sensing as a benchmark, we show the importance of optimizing the device bias, particularly the back gate bias which modulates the effective channel thickness. We also demonstrate that devices with Al(2)O(3) gate dielectrics exhibit superior sensitivity to pH when compared to devices with SiO(2) gate dielectrics. Finally, we show that when the effective electrical silicon channel thickness is on the order of the Debye length, device response to pH is virtually independent of device width. These silicon FET sensors could become integral components of future silicon based Lab on Chip systems.

Union of the European Phoniatricians' position statement on the exit strategy of phoniatric and laryngological services: staying safe and getting back to normal after the peak of coronavirus disease 2019 (issued on 25th May 2020).

BACKGROUND: The following position statement from the Union of the European Phoniatricians, updated on 25th May 2020 (superseding the previous statement issued on 21st April 2020), contains a series of recommendations for phoniatricians and ENT surgeons who provide and/or run voice, swallowing, speech and language, or paediatric audiology services. OBJECTIVES: This material specifically aims to inform clinical practices in countries where clinics and operating theatres are reopening for elective work. It endeavours to present a current European view in relation to common procedures, many of which fall under the aegis of aerosol generating procedures. CONCLUSION: As evidence continues to build, some of the recommended practices will undoubtedly evolve, but it is hoped that the updated position statement will offer clinicians precepts on safe clinical practice.

Localized heating on silicon field effect transistors: device fabrication and temperature measurements in fluid.

We demonstrate electrically addressable localized heating in fluid at the dielectric surface of silicon-on-insulator field-effect transistors via radio-frequency Joule heating of mobile ions in the Debye layer. Measurement of fluid temperatures in close vicinity to surfaces poses a challenge due to the localized nature of the temperature profile. To address this, we developed a localized thermometry technique based on the fluorescence decay rate of covalently attached fluorophores to extract the temperature within 2 nm of any oxide surface. We demonstrate precise spatial control of voltage dependent temperature profiles on the transistor surfaces. Our results introduce a new dimension to present sensing systems by enabling dual purpose silicon transistor-heaters that serve both as field effect sensors as well as temperature controllers that could perform localized bio-chemical reactions in Lab on Chip applications.

Corneal sensitivity and subjective complaints of ocular pain in patients with fibromyalgia.

PurposeFibromyalgia (FM) is a chronic pain disorder associated with pain and hypersensitivity in various parts of the body. The aim of this study was to understand whether changes in corneal sensitivity were associated with the subjective complaints of these patients.Patients and methodsIn this study, we included 36 patients with FM (30 female, 6 male, mean age: 46.7±9.2 years) and 39 healthy control subjects (33 females, 6 males, mean age: 44.3±7.6 years). We performed a detailed ophthalmological examination, measured tear film breakup time (TBUT), and performed Schirmer I test without anesthetic (SIT). Only patients that did not have any eye disease were included in this study. Subjective complaints of the patients were evaluated with ocular surface disease index (OSDI) scores and the corneal sensation was evaluated with Cochet-Bonnet esthesiometer.ResultsThere was no significant difference between the groups for age, sex, and visual acuity. Both SIT (16.1 mm vs 15.3 mm, P=0.36) and TBUT results (17.8 s vs 18.8 s, P=0.40) were similar in FM group and the controls subjects. However, corneal sensations in central (60.0 mm vs 55.0 mm, P=0.03), superior (57.5 mm vs 50.0 mm, P=0.005), and inferior (53.89 mm vs 46.03 mm, P<0.001) regions were significantly increased in FM patients. There was a significant positive correlation between corneal sensation and OSDI scores.ConclusionIn this study, we have demonstrated that the patients with FM have increased corneal sensitivity and have related ocular surface complaints similar to dry eye disease in the absence of it.

Scalable Nanogap Sensors for Non-Redox Enzyme Assays.

Clinical diagnostic assays that monitor redox enzyme activity are widely used in small, low-cost readout devices for point-of-care monitoring (e.g., a glucometer); however, monitoring non-redox enzymes in real-time using compact electronic devices remains a challenge. We address this problem by using a highly scalable nanogap sensor array to observe electrochemical signals generated by a model non-redox enzyme system, the DNA polymerase-catalyzed incorporation of four modified, redox-tagged nucleotides. Using deoxynucleoside triphosphates (dNTPs) tagged with para-aminophenyl monophosphate (pAPP) to form pAP-deoxyribonucleoside tetra-phosphates (AP-dN4Ps), incorporation of the nucleotide analogs by DNA polymerase results in the release of redox inactive pAP-triphosphates (pAPP3) that are converted to redox active small molecules para-aminophenol (pAP) in the presence of phosphatase. In this work, cyclic enzymatic reactions that generated many copies of pAP at each base incorporation site of a DNA template in combination with the highly confined nature of the planar nanogap transducers ( z = 50 nm) produced electrochemical signals that were amplified up to 100,000×. We observed that the maximum signal level and amplification level were dependent on a combination of factors including the base structure of the incorporated nucleotide analogs, nanogap electrode materials, and electrode surface coating. In addition, electrochemical signal amplification by redox cycling in the nanogap is independent of the in-plane geometry of the transducer, thus allowing the nanogap sensors to be highly scalable. Finally, when the DNA template concentration was constrained, the DNA polymerase assay exhibited different zero-order reaction kinetics for each type of base incorporation reaction, resolving the closely related nucleotide analogs.

Effects of gender difference in early cytokine levels in trauma patients.

BACKGROUND: Experimental studies conducted on laboratory animals have demonstrated that gender differences affect the outcome following trauma-hemorrhage but, it is not clear yet whether the manipulation of sex steroids during clinical trauma affects the outcome. This study was designed to determine whether gender based changes occur in cytokine responses after trauma-hemorrhage. METHODS: Plasma cytokine, estradiol, and prolactin levels of 100 consecutive abdominal trauma patients admitted to an emergency unit were measured to determine if there is a gender based difference. RESULTS: There was no significant difference in trauma severity between male and female patients. Plasma interleukin-1beta levels were found to be significantly higher in male patients compared to females following trauma hemorrhage (p = 0.003). On the other hand, there was no significant difference in plasma interleukin-6, tumor necrosis factor-*, and prolactin levels between the male and female patients (p > 0.05). CONCLUSION: These results suggest that the role of sex steroids on immunomodulatory processes following trauma-hemorrhage should be further investigated before studies are undertaken to evaluate the effect of hormonal manipulation in patients with trauma (Tab. 1, Fig. 1, Ref. 26).

Drip tectonics and the enigmatic uplift of the Central Anatolian Plateau.

Lithospheric drips have been interpreted for various regions around the globe to account for the recycling of the continental lithosphere and rapid plateau uplift. However, the validity of such hypothesis is not well documented in the context of geological, geophysical and petrological observations that are tested against geodynamical models. Here we propose that the folding of the Central Anatolian (Kirsehir) arc led to thickening of the lithosphere and onset of "dripping" of the arc root. Our geodynamic model explains the seismic data showing missing lithosphere and a remnant structure characteristic of a dripping arc root, as well as enigmatic >1 km uplift over the entire plateau, Cappadocia and Galatia volcanism at the southern and northern plateau margins since ~10 Ma, respectively. Models show that arc root removal yields initial surface subsidence that inverts >1 km of uplift as the vertical loading and crustal deformation change during drip evolution.

Limbal conjunctival mini-autografting for preventing recurrence after pterygium surgery.

PURPOSE: The aim of the present study was to evaluate limbal conjunctival mini-autografting procedure based on recurrence rates following pterygium surgery. METHODS: A total of 63 eyes (53 patients) with pterygium, of which 60 were primary and 3 were recurrent, underwent surgery for the removal of pterygia with limbal conjunctival mini-autograft. After the pterygium excision, the limbal portion of the graft was oriented and sutured to the limbus at the recipient bed with the epithelial surface upside. Recurrence was defined as fibrovascular tissue of more than 1 mm over the cornea in the area of previous pterygium excision. The mean follow-up period was 12.5 months (ranging between 6 and 29 months). RESULTS: The time required for the surgery was approximately 30 minutes (range 20-40 minutes). Recurrence of pterygium was observed in 6 of 63 eyes (9.52%). No eyes with recurrent pterygium developed recurrence postoperatively. There were no severe complications during the operative and postoperative period. Most patients had temporary graft edema, lasting a few days after the operation, and they experienced and complained of foreign body sensations and epiphora. CONCLUSIONS: Limbal conjunctival mini-autografting appears to be an effective procedure for pterygium surgery resulting in a low recurrence rate.

Evaluation of pathological changes in broilers during chronic aflatoxin (50 and 100 ppb) and clinoptilolite exposure.

This study was conducted to evaluate the pathological changes in broilers fed a diet containing low-levels of aflatoxin (AF) and clinoptilolite (CLI) until 42 days of age. A total of 576 one-day-old Ross-308 type broiler chicks were treated with varying levels of AF and CLI (15 g kg(-1)). The gross and histopathological changes in the liver, kidneys, spleen, thymus and bursa of Fabricius were investigated and relative organ weights were calculated. Compared to controls, significant changes (P<0.05), such as slight to moderate hydropic degeneration and/or fatty change (8 cases of 10), bile-duct hyperplasia (7 of 10) and periportal fibrosis (5 of 10), were found in chicks fed 100 ppb AF-containing diet. No gross-pathological changes were observed in any treatments. The addition of CLI to the 100 ppb AF-containing diet significantly decreased the number of affected broilers and/or the severity of lesions (hydropic degeneration and bile-duct hyperplasia) in the livers (P<0.05). The addition of CLI to the AF-free diet did not produce any significant lesions compared with the controls.

Comparison of peritoneal closure techniques in laparoscopic transabdominal preperitoneal inguinal hernia repair: a prospective randomized study.

PURPOSE: We aimed to compare tacker and suture techniques for peritoneal closure with respect to patient outcomes. METHODS: A total of 64 patients were included in the study, 32 being in the tacker group and 32 in the suture group. All patients underwent laparoscopic TAPP inguinal hernia repair. Both groups were compared with respect to age, sex, duration of peritoneal closure and the operation, hernia type, the number of tackers used for mesh fixation, postoperative complication rate, visual analogue scale (VAS) scores on 1st, 7th, and 30th days, duration of follow-up, and recurrence rates. RESULTS: Duration of peritoneal closure and the operation was significantly shorter in the tacker group compared to the suture group (p < 0.001, p = 0.008, respectively). Statistical analysis with the two-way analysis of variance method revealed that mesh fixation with one or two tackers did not influence postoperative pain. VAS 1 was significantly lower in patients with peritoneal closure with suture compared to the patients undergoing peritoneal closure with tacker (p = 0.027). VAS 7 and VAS 30 were lower for peritoneal closure with suture versus tacker, although the difference did not reach statistical significance (p = 0.064, p = 0.294, respectively). We observed no recurrence at an average of 21-month follow-up. CONCLUSIONS: Tacker and suture appeared to have a comparable safety for peritoneal closure in laparoscopic TAPP inguinal hernia operation. It can be suggested that peritoneal closure with tacker increased short-term pain, independent of the number of tackers used for mesh fixation. Long-term pain was similar in both groups.

The effect of high-dose methylprednisolone treatment on GM-CSF level in children with acute leukemia: a pilot study.

High-dose methylprednisolone therapy (HDMP) induces acceleration of leukocyte recovery in acute lymphoblastic leukemia (ALL) and the differentiation of myeloblasts to mature granulocytes in acute myeloblastic leukemia (AML). These effects of corticosteroids have been shown to be due to the enhanced colony-stimulating activity (CSA) and responses to corticosteroids in some patients with aplastic anemia and myelodysplastic syndromes (MDS) have been related to increased CSA activity. We measured the serum (granulocyte-macrophage colony-stimulating factor (GM-CSF) levels by a sandwich linked immunoabsorbent assay (ELISA) in patients with ALL and AML at presentation and following high-dose methylprednisolone (HDMP) therapy. Serum GM-CSF levels at presentation in the ten cases studied ranged between 160 and 700 pg/ml (mean 418.5 +/- 252.5). One week following HDMP therapy GM-CSF levels increased to between 260 and 950 pg/ml (733.5 +/- 203.2). Four weeks after therapy the GM-CSF levels increased to between 470 and 1350 pg/ml (911 +/- 278.7). GM-CSF levels were markedly elevated one week after HDMP in the patients with ALL, suggesting that in addition to the lymphotoxic effects on leukemic blasts, the acceleration in neutrophil recovery may be due to release of GM-CSF induced by HDMP and its effects on myeloid progenitors.

Thyrotropin stimulating hormone response to thyrotropin releasing hormone in patients with panic disorder.

OBJECTIVE: The aim of this study is to assess thyrotropin stimulating hormone (TSH) response to thyrotropin releasing hormone (TRH) in patients with panic disorder (PD). METHOD: The effects of TRH administration on the release of TSH were examined in 15 patients who met DSM-III-R criteria for PD and compared their test results with those of 15 normal control subjects. Blood samples were taken before TRH administration (baseline values) and at 15, 30 and 60 min. RESULTS: delta max TSH values were lower in the panic disorder patients than in the control subjects. Using the criterion of delta max TSH < or = 7 mlU/l, nine of the 15 panic disorder patients and four of the 15 control subjects had a blunted TSH response to TRH. CONCLUSIONS: These results confirm the findings from earlier reports that patients with PD show blunted TSH response to TRH which is similar to that seen in depressed patients.

Great cervical vein invasion of thyroid carcinoma.

Intraluminal tumor thrombus in great cervical veins as a result of thyroid carcinoma is extremely rare. Three patients (2 Hürthle cell, 1 papillary carcinoma) were surgically treated for thyroid carcinoma associated with tumor thrombus in the great cervical veins. Tumor thrombus in the internal jugular vein due to extension of thyroid carcinoma was found in these 3 patients. Segmental resection of the internal jugular vein was performed in all cases and a tumor thrombectomy from subclavian vein was accomplished in 1 patient. Histological examination verified intraluminal tumor thrombus resulting from invasion of thyroid carcinoma in all patients. The postoperative follow-up period ranged from 1 to 2 years. Of 2 patients undergoing completion thyroidectomy, 1 died of distant metastasis, the other underwent reoperation for local recurrence. The patient who had a definitive primary surgical procedure is free of recurrence. Appropriate initial surgical procedure in rare cases of thyroid carcinoma associated with intraluminal tumor thrombus in great cervical veins seems to improve the clinical outcome of the disease.

The height and radius of the tear meniscus and methods for examining these parameters.

PURPOSE: To investigate the relationship between the radius of tear meniscus curvature (TMR) and tear meniscus height (TMH). METHODS: Twenty-nine eyes of dry-eye patients (all left eyes; two males, 27 females, aged 26 to 85 years [mean +/- SD; 60 +/- 14.4]) were enrolled in the study. TMR was measured at the tear meniscus of the central lower lid with a newly developed videomeniscometer. At the same region of the eye, TMHs were measured without fluorescein (TMH-M) and after 5 minutes with fluorescein (TMH-MF), using a slit lamp equipped with a micrometer. TMHs were also measured on cross-sectional photographs of the fluorescein-stained meniscus (TMH-P). RESULTS: The values of TMR, TMH-M, TMH-MF, and TMH-P (mean +/- SD, mm) were 0.22 +/- 0.09, 0.19 +/- 0.09, 0.21 +/- 0.14, and 0.24 +/- 0.09, respectively. There was significant correlation between TMR and TMH-M, TMH-MF, and TMH-P values (TMR versus TMH-M: r = 0.596, p = 0.0005; TMR versus TMH-MF: r = 0.587, p = 0.0006; TMR versus TMH-P: r = 0.605, p = 0.0003). CONCLUSION: There is a significant correlation between TMR and TMH. Videomeniscometry has some merits over conventional methods for obtaining tear meniscus parameters.

Prolactin response to TRH in patients with panic disorder.

The effects of TRH administration (400 microg, i.v.) on the release of prolactin were examined in 15 patients who met DSM-III-R criteria for panic disorder and 15 normal control subjects. Four hundred micrograms TRH was given via IV route. Blood samples were taken before TRH administration (baseline values) and at 15, 30 and 60 min. The results demonstrate that prolactin responses to TRH did not differ between panic disorder patients and normal control subjects. When only women were evaluated, the findings indicate that women with PD tend to show excessive prolactin responses to TRH. The findings are discussed in view of findings from earlier reports.