Liver cirrhosis is the result of a vicious cycle of both chronic oxidative stress and inflammation. NADPH oxidase-4 (NOX4) and its companion, NOD-like receptor protein 3 (NLRP3) inflammasome, are ...emerging as therapeutic targets of liver fibrosis.
Baicalin (BA), a natural flavone, has been investigated for its therapeutic potential against cirrhosis induced by thioacetamide (TAA) (200 mg/kg, twice/week) for 12 weeks in Sprague-Dawley rats. Two doses of BA were administered (25 and 75 mg/kg/day, orally, a week after TAA was stopped and continued for 4 weeks).
BA was able to reduce fibrosis visualized by Masson trichrome and immunohistochemical staining of the hepatic α-smooth muscle actin (α-SMA) and transforming growth factor-β1. Moreover, BA was able to ameliorate inflammation by reducing hepatic NLRP3 inflammasome subunits, NLRP3 and caspase-1, both parts of the complex responsible for the activation of different interleukins (IL), measured as IL-1β. In addition, BA was able to reduce hepatic nuclear factor kappa B (NF-κB)-driven inflammation through IL-6. BA targeted inflammation through its anti-oxidant ability evidenced by the enhancement of the hepatic superoxide dismutase (SOD) and reduced glutathione (GSH) activity and level, respectively, and the reduction of both hepatic malondialdehyde (MDA) and nitric oxide (NOx) contents. Treatment with BA significantly decreased TAA-induced elevation in hepatic NOX4, a key enzyme for reactive oxygen species (ROS) generation, as well as, inducible nitric oxide synthase (iNOS).
therefore, the study could conclude, the anti-fibrotic effect of BA through TGF- β1/NOX4/NF-κB/NLRP3 pathway, exerting both anti-inflammatory and anti-oxidant effects.
Schematic diagram summarizing the possible mechanisms through which Baicalin (BA) could protect against Thioacetamide (TAA)-induced cirrhosis in rats. ALT: alanine aminotransferase; BA: Baicalin; GSH: reduced glutathione; IL-6: Interleukin-6; iNOS: inducible nitric oxide synthase; MDA: malondialdehyde; NF-κB: nuclear factor Kappa B; NLRP3: NOD-like receptor protein 3; NOx: nitric oxide; NOX: nicotinamide adenine dinucleotide phosphate oxidase; NOX4: NADPH oxidase-4; SOD: superoxide dismutase; ROS: reactive oxygen species; TAA: Thioacetamide; TGF-β: transforming growth factor-β. Display omitted
•Baicalin possessed an anti-fibrotic effect in thioacetamide-induced cirrhosis in Sprague-Dawley rats.•Baicalin decreased inflammation via inhibiting hepatic NF-κB/IL-6 and NF-κB/NLRP3 inflammasome/IL-1β signaling pathway.•Baicalin ameliorated TAA-induced hepatic oxidative stress via inhibiting hepatic NOX4 and the iNOS signaling pathway.
► Potato tuber yield varied widely under different amounts of water and N applied through drip irrigation system. ► Water stress is a more yield limiting factor than N fertilizer for potato ...production. ► The decrease in potato yield in the deficit irrigation treatments was mainly due to a decrease in tuber weight. ► The yield reduction under severe water deficit was much more severe at high N levels. ► Water use efficiency was conditioned by N level, but its effect decreased as the irrigation water increased.
Water and nitrogen supply in potato cropping systems is an essential factor for controlling production level especially in arid and semi-arid regions. Shortage water availability and escalating irrigation costs along with high prices of fertilizers have caused attention to adopt practices to improve water and N use efficiency. The present work was conducted to assess the interaction effect of different amounts of water (W) and nitrogen (N) applied through drip irrigation on potato production, water use efficiency (WUE), nitrogen use efficiency (NUE) and total N uptake in an arid region. Potato plants were subjected to four irrigation treatments, 100% (W1.0), 80% (W0.8), 60% (W0.6) and 40% (W0.4) of crop ET (evapotranspiration) and four N levels, 160 (N160), 220 (N220), 280 (N280) and 340(N340)kgNha−1. Plants grown under full irrigation supply resulted in the highest tuber yield and there were significant reductions in total yield and yield components when applying less amount of water. Tuber weight was more sensitive to water deficit than tuber number, where the decrease in potato yield in the deficit water treatments was mainly due to a decrease in tuber weight (R2=0.982). Except for tuber number per plant, application of N adversely affected yield and yield components, when N level applied above 280kgNha−1 at W0.6, and above 220kgNha−1 at W0.4, respectively. The WUE was improved by N supply, but its effect decreased as the irrigation level increased. The WUE at W1.0, which produced the highest tuber yield, was 146kgha−1mm−1 with N340 but this increased to 195kgha−1mm−1 at W0.4 with N220. The NUE was affected greatly by the applied N amount and increased as the N level was decreased. The highest NUE value 176kgyieldkg−1N was obtained at W1.0 treatment with N160 but this decreased to 136kgyieldkg−1N with N340. The uptake of N increased with increase in the level of N applied up to the highest level but the reverse was true for N recovery. These results suggested that potato in an arid climate region can be cultivated with acceptable yields while saving irrigation water and reducing nitrogen supply but it is essential to exploit the interaction effect between these two factors to maximize resource use efficiency.
Background
Urinary schistosomiasis and its severe complications, mainly bladder cancer, are scarce in non-endemic areas. The deficiency in knowledge and clinical experience of schistosomiasis may ...lead to inadequate management. Highlighting these topics may be of value, especially with the increased immigration from endemic low-/middle-income countries (LMIC) to non-endemic high-income countries (HIC). Schistosomiasis is a parasitic infection endemic in many low- and middle-income countries. It can affect various systems but is best known for its effect on the urinary system.
Main Body
PubMed, Scopus, Google Scholar, and the Cochrane Library databases were searched for urinary schistosomiasis and its related bladder cancer published from 1980 till 2020.
Schistosoma haematobium
(SH) infecting the urinary bladder was considered by the IARC as group 1 definitive biological carcinogenic agent. Several carcinogenic pathways have been postulated but the exact mechanism(s) are not defined yet. A more thorough understanding of the parasite life cycle was explored to help eradicate the infection especially for the immigrants from endemic areas. This may prevent or slow down the process of carcinogenesis that leads to Schistosoma-associated bladder cancer (SA-BC), which is usually, but not conclusively, squamous cell carcinoma. Treatment of SA-BC generally follows the same guidelines as urothelial Schistosoma-non-associated bladder cancer (SNA-BC) management; however, prospective trials to confirm and refine the treatment approach for SA-BC have been relatively limited.
Conclusion
The available data showed that despite some etiologic and carcinogenic differences, the oncologic outcomes are generally comparable for SA-BC and NSA-BC when adjusting for stage, risk status, and comorbidities.
Local-regional failure for patients with ≥pT3 urothelial carcinoma after radical cystectomy is a significant clinical challenge. Prospective randomised trials have failed to show that chemotherapy ...reduces the risk of local-regional recurrences. Salvage treatment for local failures is difficult and often unsuccessful. There is promising evidence, particularly from a recent Egyptian National Cancer Institute trial, that radiation therapy plus chemotherapy can significantly reduce local recurrences compared with chemotherapy alone, and that this improvement in local-regional control may translate to meaningful improvements in disease-free and overall survival with acceptable toxicity. In light of the high rates of local failure following cystectomy for locally advanced disease and the progress that has been made in identifying patients at high risk of failure and the patterns of failure in the pelvis, the National Comprehensive Cancer Network guidelines were revised to include postoperative radiotherapy as an option to consider for patients with ≥pT3 disease. Here we review the problem of local-regional failure after cystectomy, identify patients who would probably benefit from adjuvant radiotherapy, review the patterns of pelvic failure after cystectomy, discuss technical details of radiation treatment and review the modern literature on this topic. Adjuvant radiotherapy should be considered as a treatment option for patients with locally advanced disease, especially those with positive margins or squamous cell carcinoma.
Workplace factors are important predictors of occurrence of musculoskeletal pain among different occupational populations. In healthcare, a psychologically unsafe work environment can negatively ...affect the emotional, physical and psychological well-being of physicians. This study aimed to examine the relationship between workplace violence, sexual harassment and musculoskeletal pain among Egyptian physicians in their years of residency.
We distributed an online self-administered questionnaire to 101 residents working in various healthcare sectors in Egypt. It included sections on demographic data, working conditions, widespread pain index (WPI), pain interference short-form, workplace violence and harassment questionnaire, psychosocial safety climate questionnaire (PSC) and sexual harassment climate questionnaire.
All residents had at least one painful site on the WPI (range 1-11). The mean WPI was 3.5 ± 2.4, and 39.6% satisfied the criteria of having widespread pain by having at least 4 pain sites. Widespread pain index showed a weak statistically significant negative correlation with workplace PSC score (rho = - 0.272, p = 0.006), and a statistically significant weak positive correlation with the calculated total abuse index (rho = 0.305, p = 0.002). Workplace violence and abuse, as measured by a calculated abuse index was the only significant predictors of widespread pain among residents.
WPV was found to be a predictor of musculoskeletal pain among medical residents. Healthcare organizations need to address WPV by employing preventive strategies to minimize its hazardous effects and ensure a safe working environment for physicians.
During the Neogene, the Western Mediterranean subduction‐related orogen developed under differing modes and senses of subduction, resulting in the formation of the Apennines, Maghrebides, Rif, and ...Betics. In this work, we present the Neogene kinematic evolution of the Rif, based on literature data and new results from structural‐stratigraphic analyses and biostratigraphic investigations carried out in the External Zone of the Rif. We analyzed three stratigraphic sections: Dar Zhirou, Saf Lahmame, and Seguedla. The results of these analyses allow us to reconstruct a wide Tortonian‐Messinian wedge‐top basin in the Tanger‐Al Manzla area, when the leading edge of the Rif was at the frontal thrust of the Prerif. The presence of this wedge‐top basin points to a Tortonian‐Messinian compressional deformation that affected a wide area of the Rif, including the Prerif, Mesorif, and Intrarif. The late Miocene compressional deformation that affected the Mesorif and Intrarif occurred as out‐of‐sequence thrusting, due to renewed compressional tectonics in the internal zone of the chain triggered by the collision of the Rif accretionary wedge with the North African Margin. In the Neogene evolution of the Western Mediterranean subduction‐related orogen, the late Miocene was a major pulse in the interplay between African and European plates, as evidenced by the increase in migration rates of some segments of the circum‐Mediterranean fold‐and‐thrust belt, the out‐of‐sequence thrusting in the Rif, as well as the occurrence of late Miocene imbricate thrust structures in oceanic fracture zones of the African Plate (Central Atlantic Ocean).
Key Points
The analyses performed allow us to reconstruct a wide Tortonian‐Messinian wedge‐top basin in the Tanger‐Al Manzla area
The Tanger‐Al Manzla wedge‐top basin demonstrates that the Intrarif was affected by compressional tectonics during the late Miocene
The collision of the late Miocene Rifian accretionary wedge with the Meseta induced out‐of‐sequence thrusting in the Mesorif and Intrarif
We aimed to study the clinical state and prognosis of patients with unilateral retinoblastoma who were being treated at a paediatric comprehensive cancer centre in a limited-resource country, to ...assess the different phases of treatment and the success of different, more complex real-life models.
In this retrospective study, we created a snapshot of our retinoblastoma database for the period between 2007 and 2015. Patients whose data were included in the study were followed up until 2016. Out of a total of 744 screened patients, we included data of 248 patients who had been diagnosed with unilateral retinoblastoma.
As classified as per the International Retinoblastoma Classification, 1 patient presented with group A, 21 with group B, 39 with group C, 104 with group D and 83 with group E retinoblastoma. Chemotherapy was the initial line of treatment in 115 patients and enucleation in 133 others. Later, 141 patients (56.9%) required further management. Patients had a mean ocular survival time of 20.8 months. Nine patients developed extraocular disease at a later stage of management: five after upfront enucleation and four after neoadjuvant chemotherapy. Mean overall survival time stood at 90.2 months. Four and three deaths were recorded in groups D and E, respectively. A single patient died in the initial chemotherapy arm, while six passed away in the initial enucleation arm.
Our study highlights the importance of initial chemotherapy and close follow-up after enucleation of classes D and E affected eyes even in absence of germline mutations.
Huntington's disease (HD) is a fatal, neurodegenerative disorder in which patients suffer from mobility, psychological and cognitive impairments. Existing therapeutics are only symptomatic and do not ...significantly alter the disease progression or increase life expectancy. HD is caused by expansion of the CAG trinucleotide repeat region in exon 1 of the Huntingtin gene (HTT), leading to the formation of mutant HTT transcripts (muHTT). The toxic gain-of-function of muHTT protein is a major cause of the disease. In addition, it has been suggested that the muHTT transcript contributes to the toxicity. Thus, reduction of both muHTT mRNA and protein levels would ideally be the most useful therapeutic option. We herein present a novel strategy for HD treatment using oligonucleotides (ONs) directly targeting the HTT trinucleotide repeat DNA. A partial, but significant and potentially long-term, HTT knock-down of both mRNA and protein was successfully achieved. Diminished phosphorylation of HTT gene-associated RNA-polymerase II is demonstrated, suggestive of reduced transcription downstream the ON-targeted repeat. Different backbone chemistries were found to have a strong impact on the ON efficiency. We also successfully use different delivery vehicles as well as naked uptake of the ONs, demonstrating versatility and possibly providing insights for in vivo applications.
Aim
To assess whether expatriate‐specific factors were associated with nurses’ overall job dissatisfaction after controlling for known factors.
Background
Current evidence about job dissatisfaction ...among nurses in Saudi Arabia is not specific to expatriate nurses. Specific aspects such as job insecurity, fear of litigation, and language barriers have not been assessed in the context of job dissatisfaction.
Introduction
The majority of nurses in the Arab Gulf countries are expatriate. The motive for employment here is purely financial because there is no path to permanent residency.
Methods
This was a cross‐sectional electronic survey of 977 expatriate nurses in Al‐Qassim, Saudi Arabia. The survey included questions on demography, job dissatisfaction (overall and related to salary, workload, and teamwork), job characteristics, job duration as an expatriate, communication issues with patients and doctors, fear of litigation, and job insecurity. We used a hierarchical logistic regression to evaluate whether unique factors were associated with overall job dissatisfaction either as a group, or individually.
Results
The mean age of the nurses was 32 years, and 19% reported overall job dissatisfaction. The unique expatriate factors as a group contributed significantly to the model. Job insecurity, patient communication problems, and shorter job duration were significantly associated with higher overall job dissatisfaction.
Conclusions
Job insecurity, job duration, and patient communication were significant correlates of overall job dissatisfaction among expatriate nurses.
Implications for nursing policy
A longer job contract and organizational initiatives to help new expatriate nurses acculturate will likely decrease feelings of job insecurity and increase job satisfaction.
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