Replication Stress Induced by the Ribonucleotide Reductase Inhibitors Guanazole, Triapine, and Gemcitabine in Fission Yeast

Replication stress can be produced by various exogenous or endogenous factors that perturb the movement of replication forks. To overcome the stress, the cells provoke the DNA replication checkpoint to mobilize several pathways to protect the forks, maintain genome integrity, and promote cell survival. Defects in the replication checkpoint cause forks collapse, leading to chromosomal DNA damage or cell death. Although the replication checkpoint is crucial for genome integrity in all eukaryotes, the underlying mechanisms remains to be fully understood. To investigate the mechanisms of DRC, hydroxyurea (HU), an established inhibitor of ribonucleotide reductase (RNR), has been widely used in laboratories as an inducer of the replication stress. It depletes dNTP pools, slows down the movement of DNA polymerase at the forks, and thus activates the replication checkpoint pathway in yeasts and in mammalian cells. Unfortunately, HU also targets other cellular components, which may complicate the studies, leading to ambiguous description of the checkpoint mechanisms. The purpose of this study is to find an RNR inhibitor that produces the replication stress more specifically than HU in the fission yeast Schizosaccharomyces pombe. We examined three RNR inhibitors guanazole, triapine, and gemcitabine under several experimental conditions that are commonly used in the laboratories for checkpoint studies. We found that among the three drugs, guanazole and triapine produce the replication stress more specifically than HU under the chronic drug exposure conditions such as the spot assay. Under acute drug treatment conditions, however, guanazole and triapine cause other cellular stresses more significantly than HU. Therefore, using guanazole and triapine in chronic drug exposure conditions and HU in acute treatment can produce a specific replication stress under various experimental conditions and thus benefits the checkpoint studies in S. pombe and possibly the research in other model systems

Post-tonsillectomy hemorrhage after bipolar diathermy vs. cold dissection surgical techniques in Alahsa region, Saudi Arabia

Introduction: Tonsillectomy is a common surgical procedure done by  totolaryngologists. Tonsillectomy is a relatively simple procedure. The concept of implementing it as a day case operation has become increasingly popular.Material and Methods: This is a cross sectional study done in Alahsa city, eastern province, Saudi Arabia during the period from January 2014 to March 2015,This study reported the postoperative hemorrhage after Bipolar diathermy and Cold dissection surgical techniques to evaluate the incidence of the hemorrhage and to identify the possible risk factors associated with its occurrence.Results: Postoperative bleeding occurred in 45 (3.6%) out of 1232 patients. Post-tonsillectomy hemorrhage according to operation technique was significantly higher among patients who underwent bipolar diathermy than cold dissection technique (p< 0.05).Conclusion: Bleeding after operation by bipolar diathermy technique was occurring more frequently within the first five days. Hemoglobin level was significantly decreased in posttonsillectomy hemorrhage

Langendorff’s isolated perfused rat heart technique: a review

The Langendorff’s isolated perfused small mammalian heart represents the optimal compromise in the conflict between the quantity and quality of data that can be acquired from an experimental model versus its clinical relevance, especially in relation to ischemia-reperfusion injury. We analyzed the important recent, as well as standard older articles to highlight the importance of Langendorff’s isolated heart technique using the rat as an experimental animal model. The retrograde perfusion of isolated rat heart preparation is the most commonly used technique in cardiovascular research experiments with many advantages. The longevity of this preparation is one of the main advantages. From the moment an ex vivo preparation is established, it starts to deteriorate and the rate will depend on number of factors such as the skill of the operator, the species of animal, age, initial heart rate, choice and composition of the perfusion fluid, flow rate, presence or absence of various drugs, preload pressure, and the temperature at which the studies are carried out. Recently, various techniques and variables measured have undergone modifications. This review article has attempted to address many of the issues, developments, and applications which will assist investigators to make the best possible use of this experimental model using the rat

Wind Energy Assessment Using Weibull Distribution with Different Numerical Estimation Methods: A Case Study

The demand for electrical energy is increasing every day, which is one of the critical challenges facing the world today. Hence, the necessity of turning to clean renewable energy sources that are not harmful to the environment as an alternative to the traditional generation based on fossil fuels has become more important than ever before. Wind power is one of the renewable sources that provides a clean solution to generate electricity. In this context, the Kingdom of Saudi Arabia announces renewable energy projects to generate 9 GW from wind in 2032. Hence, the aim of this paper is to investigate the most suitable method of Weibull parameter estimation in order to predict wind characteristics and employ it for wind energy assessment in the Qassim region located in the center of the country. In this study, wind data is collected from NASA's forecasts of global energy resources for 2010–2015 based on their availability at altitudes of 10m and 50m and analyzed by using six different methods for Weibull parameter estimation: the graphical method (GM), standard deviation method (SDM), energy pattern factor method (EPF), moment method (MM), alternative maximum likelihood method (AMLM), and novel energy pattern factor method (NEPF). The efficiency of each method is tested by calculating the root mean square error (RMSE) and the relative wind power density error (RPDE). The comparison shows that the most appropriate method for estimating wind power density in the country is the Moment Method (MM), with the lowest RPDE ratio equal to 0.2018%. It has been found that the wind power density in the Qassim region falls into the class 1 category, as it is less than 100 W/m2 at a height of 10m and less than 200 W/m2at an altitude of 50m. The results show the region is only suitable for small off-grid projects. Doi: 10.28991/ESJ-2023-07-06-024 Full Text: PD

Ophthalmic short- and long-term outcomes for premature infants: Results of an extended follow-up program in Saudi Arabia

AbstractPurposeStudy the ophthalmic morbidities for infants born prematurely at a Tertiary care center in Riyadh city.MethodsRetrospective, longitudinal cohort study at King Fahad Medical City for premature infants born at gestational age (GA) ⩽32weeks or birth weight (BW) ⩽1500g during the study period from January 1, 2007, until the end of December 2009 was conducted. Short term outcome was diagnosis with Retinopathy of Prematurity (ROP) and long-term outcome was ophthalmic findings at age 18–24months.ResultsThe cumulative incidence of ROP was 30%. Infants diagnosed with ROP had a mean GA of 27weeks (23–35weeks) and mean BW of 907g (530–1730g). Risk factors other than GA and BW for ROP, identified in the predictive logistic regression model, were blood transfusion [odds ratio (OR) 1.27] and diagnosis with intraventricular hemorrhage (OR=2.90). Strabismus was identified in 14% of the study cohort. Diagnosis of hyperopia (spherical equivalent ⩾+0.75D) was equal in both ROP and no-ROP groups (p=0.56). Myopia (spherical equivalent ⩾−0.75D) and astigmatism ⩾1.00D were diagnosed more frequently in the ROP group (p<0.0001 and 0.04, respectively).ConclusionsA higher incidence of ROP was observed in this cohort compared to some Saudi Arabian centers. It is recommended that the screening criteria be maintained and that the effects of further control of blood transfusion be assessed in a prospective study. The authors recommend an extra ophthalmic evaluation at the age of 18–24months for all premature infants born with GA⩽32weeks

A unified model of post-stroke language deficits including discourse production and their neural correlates.

The clinical profiles of individuals with post-stroke aphasia demonstrate considerable variation in the presentation of symptoms. Recent aphasiological studies have attempted to account for this individual variability using a multivariate data-driven approach (principal component analysis) on an extensive neuropsychological and aphasiological battery, to identify fundamental domains of post-stroke aphasia. These domains mainly reflect phonology, semantics and fluency; however, these studies did not account for variability in response to different forms of connected speech, i.e. discourse genres. In the current study, we initially examined differences in the quantity, diversity and informativeness between three different discourse genres, including a simple descriptive genre and two naturalistic forms of connected speech (storytelling narrative, and procedural discourse). Subsequently, we provided the first quantitative investigation on the multidimensionality of connected speech production at both behavioural and neural levels. Connected speech samples across descriptive, narrative, and procedural discourse genres were collected from 46 patients with chronic post-stroke aphasia and 20 neurotypical adults. Content analyses conducted on all connected speech samples indicated that performance differed across discourse genres and between groups. Specifically, storytelling narratives provided higher quantities of content words and lexical diversity compared to composite picture description and procedural discourse. The analyses further revealed that, relative to neurotypical adults, patients with aphasia, both fluent and non-fluent, showed reduction in the quantity of verbal production, lexical diversity, and informativeness across all discourses. Given the differences across the discourses, we submitted the connected speech metrics to principal component analysis alongside an extensive neuropsychological/aphasiological battery that assesses a wide range of language and cognitive skills. In contrast to previous research, three unique orthogonal connected speech components were extracted in a unified model, reflecting verbal quantity, verbal quality, and motor speech, alongside four core language and cognitive components: phonological production, semantic processing, phonological recognition, and executive functions. Voxel-wise lesion-symptom mapping using these components provided evidence on the involvement of widespread cortical regions and their white matter connections. Specifically, left frontal regions and their underlying white matter tracts corresponding to the frontal aslant tract and the anterior segment of the arcuate fasciculus were particularly engaged with the quantity and quality of fluent connected speech production while controlling for other co-factors. The neural correlates associated with the other language domains align with existing models on the ventral and dorsal pathways for language processing

Development of self-repair nano-rod scaffold materials for implantation of osteosarcoma affected bone tissue

Osteosarcoma is the most widely recognized fatal bone disease in children and young adults. The osteosarcoma affected places of bone implant materials lose their activity after a period of time due to the possibility of regenerating sarcoma cells. Hence, the complete recovery of this disease is very challenging. Subsequently, new helpful methodologies, including natural antioxidant loaded bone implant materials, are effectively used to treat osteosarcoma cells. In this regard, nano-hydroxyapatite reinforced with a xylitol based poly(xylitol sebacate) PXS co-polymer together with a capsaicin loaded scaffold was investigated on osteosarcoma cells. The physicochemical properties of the scaffold were evaluated by FT-IR (Fourier transform infrared spectroscopy), SEM (scanning electron microscopy), TEM (transmission electron microscopy), and XRD (X-ray diffraction). The in vitro release and antioxidant activity of the capsaicin loaded nHAP/PXS/CAP scaffold were evaluated by UV-Visible spectroscopy. Cytotoxicity against the Saos-2 cancer line and cell viability in the osteoblast cell MG63 are reported. Eventually, the composite enlarges the creation of reactive oxygen species (ROS) in Saos-2 cells

Donated human milk use and subsequent feeding pattern in neonatal units

Background: Donated human milk (DHM) is a safe alternative in the absence of mother’s own milk (MOM); however, specific clinical indications for DHM use and its impact on subsequent feeding practice remain unclear. We aimed to audit local DHM use and explore the impact of the introduction of DHM as the first enteral feed on subsequent MOM availability. Methods: We retrospectively audited DHM recipients nursed in Royal Hospital for Children, Glasgow from 2014 to 2016 against local guidelines. Data were collected from an operational electronic database. Descriptive data analysis was performed to describe DHM use. To explore the association between the first human milk feed with subsequent MOM availability Kruskal Wallis test was used. Adjustments for confounding variables were performed using analysis of variance (ANOVA). Results: A total of 165 recipients of DHM (5.3% of all admission to RHC) were identified. The majority of recipients (69%) were born &lt; 32 weeks of gestation. The main indication for DHM was prematurity, other indications included congenital anomalies of bowel and heart. The local guideline was adhered to in 87% of cases. The median interquartile range (IQR) at DHM introduction was 6 days (3, 17) and the duration of use was 12 days (6, 22). In those born &lt; 32 weeks of gestation the type of human milk (DHM and/ or MOM) used as first feed did not influence the subsequent median IQR days of feeding with any MOM [DHM 40 (9, 51); MOM 28 (17, 49), MOM &amp; DHM 17 (10, 26) p value = 0.465] after adjusting for birthweight and length of hospital stay. Conclusions: In our unit, DHM is mainly used in preterm neonates in accordance with existing local guidance. Using DHM as first milk feed did not affect subsequent MOM availability

Early versus delayed fortification of human milk in preterm infants: a systematic review

Expressed breast milk (EBM) is commonly supplemented with commercially prepared human milk fortifier to meet the additional nutritional needs of preterm infants. The optimal milk intake at which to introduce fortification is unknown. The objective of this systematic review was to compare the effect of early fortification (EF) versus that of delayed introduction of human milk fortifier (DF) on short-term outcomes including growth, feeding intolerance, length of hospital stay, and maturity at discharge in very-low-birth-weight infants. The search was carried out until March 2019 using 5 electronic databases (PubMed, Ovid Medline, Web of Science, Ovid Embase, and the Cochrane Library). The search was supplemented with a search of the clinical trial registry and reference lists. Eligible studies involved randomized controlled trials that had been designed to compare EF against DF using multi-nutrient fortifier for infants of a birth weight of &lt;1,500 g who were fed exclusively or predominantly EBM. Four authors independently screened the studies for eligibility. A total of 1,972 articles were screened; 2 studies met the inclusion criteria and were included with a total number of participants of 171. The definition of EF and DF was not consistent between the 2 studies. There was no significant impact of EF versus DF on all outcomes. In conclusion, current data are limited and do not provide evidence on the optimal time to start fortification. The definition of EF and DF needs to be agreed upon and further larger randomized controlled trials are required

An extremely rare complete bilateral duplication of Inferior vena cava in a male cadaver: anatomy, embryology and clinical relevance

The study presented an extremely rare case of real complete bilateral duplication of inferior vena cava (IVC) in a male cadaver which has never been reported before. Both IVC had approximately the same diameter. The right IVC drained into the right atrium; the left IVC continued as hemiazygos vein and drained into the superior vena cava. Three anastomotic venous channels, a cranial preaortic, a middle and a caudal retroaortic, joined both vessels. Multiple variations in the way of drainage of posterior intercostal veins, on both sides, were also present. The present report invalidates an old classification defining the two vessels when joined at the level of the renal veins as complete bilateral duplication of IVC. Although the presence of combination of venous variations is extremely rare, awareness of such variations is essential for clinical and surgical procedures to avoid misdiagnosis and surgical complications