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This study compared the accuracy and efficiency of fully guided static and dynamic computer-assisted surgical navigation techniques for osteotomy and root-end resection (RER). Fifty roots from cadaver heads were divided into two groups: fully guided static computer-assisted endodontic microsurgery (FG sCAEMS) and dynamic computer-assisted endodontic microsurgery (dCAEMS) (all, n = 25). Cone-beam computed tomography scans were taken pre and postoperatively. The osteotomy and RER were planned virtually in the preoperative cone-beam computed tomography scan and guided using 3D-printed surgical guides in the FG sCAEMS and 3D-dynamic navigation system in the dCAEMS. The 2D and 3D deviations and angular deflection were calculated. The osteotomy volume, resected root length, and resection angle were measured. The osteotomy and RER time and the number of procedural mishaps were recorded. FG sCAEMS was as accurate as dCAEMS, with no difference in the 2D and 3D deviation values or angular deflection (P >.05). The osteotomy and RER time were shortened using FG sCAEMS (P <.05). The FG sCAEMS showed a greater number of incomplete RERs than dCAEMS. Osteotomy volume, RER angle, and root length resected were similar in both groups (P >.05). FG sCAEMS and dCAEMS were feasible for osteotomy and RER. Within the limitations of this cadaver-based study, FG sCAEMS was as accurate as dCAEMS. Both FG sCAEMS and dCAEMS were time-efficient for osteotomy and RER. [ABSTRACT FROM AUTHOR]

Accidents with venomous bees are a serious worldwide health concern. Since the kidney has been reported as the main venomtarget organ, the present study was undertaken to investigate the in vivo nephrotoxic effect of Algerian bee venom (ABV) (Apis mellifera intermissa) collected in the middle east of Algeria. A preliminary study was performed on ABV to identify the ABV using SDS-PAGE analysis and to determine the in vivo intraperitoneal median lethal dose (LD50) using the Probit analysis test. In vivo nephrotoxic effect was assessed through the determination of physiological and kidney biochemical markers in mice intraperitoneally injected with ABV at doses of 0.76 (D1); 1.14 (D2) and 2.29 mg/kg body weight (bwt) (D3), corresponding respectively to LD50/15, LD50/10, and LD50/5 (i.p. LD50=11.48 mg/kg bwt) for seven consecutive days. Results revealed a marked decrease in body weight gain and food intake, and an increase in absolute and relative kidney weights in ABV D2 and D3 treated mice compared with controls. Furthermore, ABV D2 and D3 resulted in a significant increase in serum creatinine, urea, and uric acid. ABV-induced oxidative stress was evidenced by a significant increase in kidney MDA level, and a significant depletion in kidney GSH level, and catalase activity. Meanwhile, no marked changes in the above-mentioned parameters were noticed in ABV D1. Accordingly, the adverse nephrotoxic effect of ABV was proved by the dose-dependent kidney histological changes. In summary, the results of the present study evidence that ABV at doses of 1.14 (D2) and 2.28 mg/kg body weight (bwt) can cause marked changes in kidney biochemical and major antioxidant markers, and histological architecture. [ABSTRACT FROM AUTHOR]

Rooibos (Aspalathus linearis Brum. f) can directly influence female reproduction, but whether rooibos can influence the response of ovarian cells to FSH and whether the rooibos effects are due to the presence of quercetin remain unknown. We compared the influence of rooibos extract and quercetin (both at 10 µg/ml-1) on porcine ovarian granulosa cells cultured with and without FSH (0, 1, 10 or 100 ng/ml-1). The expression of intracellular proliferation (PCNA, cyclin B1) and apoptosis (bax, caspase 3) markers in the cells was detected by immunocytochemistry. The release of progesterone (P), testosterone (T) and estradiol (E) were evaluated with ELISAs. Administration of both rooibos and quercetin reduced the accumulation of proliferation markers and promoted the accumulation of apoptosis markers and the release of T and E. Rooibos stimulated, but quercetin inhibited, P output. Administration of FSH increased the accumulation of proliferation markers, decreased the accumulation of apoptosis markers, promoted the release of P and T, and had a biphasic effect on E output. The addition of both rooibos and quercetin mitigated or prevented the main effects of FSH. The present observations suggest a direct influence of both rooibos and quercetin on basic ovarian functions - proliferation, apoptosis, steroidogenesis and response to FSH. The similarity in the major effects of rooibos and its constituent quercetin indicates that quercetin could be the molecule responsible for the main rooibos effects on the ovary. The potential anti-reproductive effects of rooibos and rooibos constituent quercetin, should be taken into account in animal and human nutrition. [ABSTRACT FROM AUTHOR]

Colon cancer (CC) is a common form of cancer worldwide. According to growing incidence of cancer and little information about the possible protective role of Ivermectin (IVM) on colon cancer, this study aimed to investigate the chemoprotective role of IVM against colon cancer induced by Dimethylhydrazine (DMH) in Male Wistar Rats. Based on LD 50, three doses of IVM (0.25, 0.5, and 1 mg/kg) were applied before assayingthe antioxidant status, apoptotic markers, and microscopic analysis. Our result showed that glutathione (GSH) level was significantly increased in low dose of IVM-treated rats. Hight levels of oxidative stress and tissue damage consumed GSH and catalase (CAT), and dismutase (SOD) as indicated by significant drop in the treated groups. mRNA levels of Bax and caspase-3 were upregulated in rats treated with the high dose. Contrastingly, the expression of Bcl-2 was significantly downregulated with high dose. Changes in genes expression proved that IVM triggered apoptosis in treated groups compared to untreated control group. Microscopic analysis showed that rats treated with DMH exhibited high development of colorectal tumor. After induction of colorectal tumor, medium and high dose of DMH induced reduction in medullary carcinoma with great incidence of lymphoid nodules and desmoplastic reaction. In conclusion, this study demonstrates the potential of IVM as an anticancer drug against colon cancer in male Wistar rats. [ABSTRACT FROM AUTHOR]

Cancer continues to be a prominent global threat, and current chemotherapy options often involve tubulin-targeting compounds disrupting microtubule function. Autophagy's role in cancer varies across cell types, tumor stages, and carcinogenic stimuli. Recent attention has focused on autophagy as a response to antimitotic drugs. Our study spotlights TubA, a myxobacteria-derived peptide with potent antimitotic properties, demonstrating notable antiproliferative effects on diverse cancer cell lines at low concentrations. Remarkably, TubA proved more effective than TubB, another myxobacterial compound. In MCF-7 cells, TubA induced autophagy, increasing LC3-I lipidation to LC3-II and enhancing lysosomal activity and acidity. Intriguingly, TubA triggered an intrinsic apoptotic pathway mediated by autophagy, evidenced by increased cathepsin B activity, cytosolic leakage, and subsequent apoptosis through cytochrome c release. In summary, our findings indicate that TubA promotes cell death via cytotoxic autophagic activity in the MCF-7 cancer cell line. [ABSTRACT FROM AUTHOR]

The advent of online social networks (OSNs) has catalyzed the formation of novel learning communities. Identifying experts within OSNs has become a critical component for facilitating knowledge exchange and enhancing self-awareness, particularly in contexts such as rumor verification processes. Research efforts aimed at locating authorities in OSNs are scant, largely due to the scarcity of annotated datasets. This work represents a contribution to the domain of unsupervised learning to address the challenge of authorities' identification in Twitter. We have employed advanced natural language processing technique to transfer knowledge concerning topics in the Arabic language and to discern the semantic connections among candidates within Twitter in zero-shot learning. We take advantage of the Single-labeled Arabic News Articles Dataset (SANAD) to perform the process of extracting domain features and applying these features in finding authorities using the Authority Finding in Arabic Twitter (AuFIN) dataset. Our evaluation assessed the extent of extracted topical features transferred and the efficacy of authorities' retrieval in comparison to the latest unsupervised models in this domain. Our approach successfully extracted and integrated the limited available topical semantic features of the language into the representation of candidates. The findings indicate that our hybrid model surpasses those that rely solely on lexical features of language and network topology, as well as other contemporary approaches to topic-specific expert finding. [ABSTRACT FROM AUTHOR]

The action of the medicinal plant Tribulus terrestris (TT) on bovine ovarian cell functions, as well as the protective potential of TT against xylene (X) action, remain unknown. The aim of the present in vitro study was to elucidate the influence of TT, X and their combination on basic bovine ovarian cell functions. For this purpose, we examined the effect of TT (at doses of 0, 1, 10, and 100 ng/ml), X (at 20 µg/ml) and the combination of TT + X (at these doses) on proliferation, apoptosis and hormone release by cultured bovine ovarian granulosa cells. Markers of proliferation (accumulation of PCNA), apoptosis (accumulation of Bax) and the release of hormones (progesterone, testosterone and insulin-like growth factor I, IGF-I) were analyzed by quantitative immunocytochemistry and RIA, respectively. TT addition was able to stimulate proliferation and testosterone release and inhibit apoptosis and progesterone output. The addition of X alone stimulated proliferation, apoptosis and IGF-I release and inhibited progesterone and testosterone release by ovarian cells. TT was able to modify X effects: it prevented the antiproliferative effect of X, induced the proapoptotic action of X, and promoted X action on progesterone but not testosterone or IGF-I release. Taken together, our observations represent the first demonstration that TT can be a promoter of ovarian cell functions (a stimulator of proliferation and a suppressor of apoptosis) and a regulator of ovarian steroidogenesis. X can increase ovarian cell proliferation and IGF-I release and inhibit ovarian steroidogenesis. These effects could explain its antireproductive and cancer actions. The ability of TT to modify X action on proliferation and apoptosis indicates that TT might be a natural protector against some ovarian cell disorders associated with X action on proliferation and apoptosis, but it can also promote its adverse effects on progesterone release. [ABSTRACT FROM AUTHOR]

Global warming-induced environmental changes have resulted in salinity fluctuations that markedly impact aquatic organisms. Consequently, the salinization of freshwater has become a major concern. Among these organisms, planarians are highly sensitive to environmental changes, especially Dugesia bursagrossa , the first freshwater planarian species identified in Saudi Arabia, which reproduces both sexually and asexually through fission. This study examined the reproductive response of sexual and asexual D. bursagrossa specimens to salinity changes. Asexual reproduction rates were found to increase with elevated salinity, whereas sexual reproduction was sensitive to high salinity, evidenced by the absence of cocoons in treated groups. This phenomenon was further explored by investigating the microtubular cytoskeleton's organization in the sexual form's ovary using immunolabeled α-tubulin and confocal microscopy. Results revealed a significant decline in the tubulin cytoskeleton with rising salinity levels, supporting the notion that increased salinity restricts sexual reproduction. Given that heightened salinity induces stress, the activities of malondialdehyde (MDA) and various antioxidant indicators, including glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT), were evaluated. Elevated salinity led to a notable increase in MDA levels as well as reduced GSH, SOD, and CAT levels in both sexual and asexual specimens, with sexual organisms exhibiting more pronounced effects. In conclusion, salinity directly impacts the homeostasis and reproduction of D. bursagrossa , with sexual specimens facing greater challenges than their asexual counterparts. [ABSTRACT FROM AUTHOR]

Calcified canals present a challenge during endodontic treatments. The purpose of this study was to compare the accuracy and efficiency of a dynamic navigation system (DNS) to the freehand (FH) method for locating calcified canals in human teeth. Sixty human single-rooted teeth with canal obliteration were selected and mounted in dry cadaver jaws. Based on cone-beam computed tomographic scans of the jaws, the drilling path and depth were virtually planned to use X-Guide software (X-Nav Technologies, LLC, Lansdale, PA). Access preparation was made with navigation in the DNS group and without guidance in the FH group by 2 operators with different levels of experience. Postoperative cone-beam computed tomographic scans were taken of all teeth. Linear and angular deviations and reduced dentin thickness at 2 levels were measured. The time for locating the canal, the number of mishaps, and the unsuccessful attempts were determined and analyzed. The mean linear and angular deviations, reduced dentin thickness (at both levels), the time for access cavity preparation, and the number of mishaps in the DNS group were significantly less than the FH group (P ≤.05). The unsuccessful attempts were not different between the 2 groups (P >.05). The time for access preparation was significantly shorter for the board-certified endodontist in the FH group (P ≤.05). The DNS was more accurate and more efficient than the FH technique in locating calcified canals in human teeth. This novel DNS can help clinicians avoid catastrophic mishaps during access preparation in calcified teeth. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is a highly aggressive brain tumor associated with a high mortality rate, with an average survival time of less than two years. GBM treatment faces significant challenges due to its infiltrative nature, genetic diversity, protection by the blood–brain barrier (BBB), drug resistance, and post-treatment side effects. Transcription factors (TFs) play a crucial role in regulating gene expression during cancer initiation and progression. This study aimed to investigate the impact of altering the function of ONECUT-2 (OC-2) in GBM cells, focusing on metabolic activity, proliferation, cell cycle, and apoptosis. To confirm the successful reduction of OC-2 expression in U251 and U87 cells compared to the control cells (wild types; WT), quantitative real-time polymerase chain reaction (qPCR) was performed. The downregulation of OC-2 resulted in a significant decrease in metabolic activity (MTT) of U251 cells by 47 % (P = 0.0056) and U87 cells by 36.4 % (P = 0.0003) compared to WT cells. In U251 cells, OC-2 downregulation caused cell cycle arrest in both the G0/G1 phase (13.6 %) and the S/G2 phase (52.52 %) compared to WT cells. Similarly, in U87 cells, downregulation of OC-2 led to cell cycle arrest in the G0/G1 phase (90.5 %) and the G2 phase (76.61 %) compared to WT cells. Furthermore, OC-2 downregulation significantly affected early-stage apoptosis in U251 cells (95.46 %, P = 0.0005) and U87 cells (19.64 %, P = 0.0004). Conversely, upregulation of OC-2 significantly increased the metabolic activity (MTT) of U251 cells by 94 % (P = 0.0067) and U87 cells by 58 % (P = 0.0028) compared to WT cells. These findings highlight the essential role of OC-2 in regulating the progression of GBM cells. Consequently, OC-2 represents a potential therapeutic target for inhibiting GBM. Overall, this study demonstrates that OC-2 plays a significant role in cell progression, suggesting its potential as a therapeutic target for GBM treatment. [ABSTRACT FROM AUTHOR]

Dentists and physicians alike often prescribe opioids for dental pain management. The purpose of this study was to identify the common practices among United States endodontists for prescribing opioids to their patients. A descriptive, cross-sectional survey was developed to query 1000 American Association of Endodontists members from all 7 districts in the United States. The 20-question survey addressed provider demographics, types and frequency of medications prescribed, and clinical scenarios that compelled prescription-writing habits. The anonymous survey was electronically mailed. There was a preference to prescribe nonsteroidal anti-inflammatory drugs and/or acetaminophen followed by hydrocodone to manage endodontic pain. The majority of respondents limited an opioid prescription to ≤4 days. Different demographics played a role in the response to direct questions if they ever felt or succumbed to pressure toward prescribing opioids. Opioids are the second most prescribed medication to manage endodontic postoperative pain. Practice background was a significant factor in feeling pressure to prescribe an opioid. [ABSTRACT FROM AUTHOR]

This paper presents a content analytic approach to research related to in-service science teachers’ professional development. The research under consideration was published in four international science education journals and three international conference proceedings specialized in science education from 2012 through 2016. A total of 204 articles (44 published in journals and 160 published in conference proceedings) were examined to identify the fields of concentration within continuous professional development (CPD) programmes, which are; focus of professional development, Types of Professional development, research purposes, research tools, Types of the data, the context of the in-service CPD programmes. The result indicated that there is increasing emphasis on pedagogical content knowledge (PCK), inquiry, problem-solving and thinking. Most of the journals and conferences provide CPD as in-school and long-term training programmes subject to systematic evaluation. [ABSTRACT FROM AUTHOR]

Tubulin is still a highly valued target in cancer chemotherapy. Agents that target tubulin and microtubule dynamic are considered to be of high therapeutic potential. We conducted a study to assess the effects of TAM1344, a synthetic cytolysin that is derived from the natural tubulysins on the proliferation of cancer cell lines. Tubulysins are a group of naturally occurring cytotoxic compounds that are produced by Myxobacteria. Our results show that TAM1344 exhibit strong antiproliferative activity against different cancer cell lines at low nanomolar concentration. The measured IC 50 values in HCT116, A549 and MCF7 cancer cell lines were 0.14 nM, 0.24 nM & 0.09 nM, respectively. In a direct comparison, the three cell lines were more sensitive to the drugs than the myxobacterial natural products tubulysin-A and –B. Additionally, in HCT116 cells, TAM1344 induces destabilization and depletion of the interphase microtubules as indicated by Immunofluorescence staining. Furthermore, the spindle pools of dividing cells show unusual, condensed phenotyping, a characteristic phenotype of many anti-tubulin agents. The nuclei of treated cells look fragmented in comparison to control cells, as detected with DAPI or PI staining. Furthermore, at low concentrations, TAM1344 induces an accumulation of the cells in the G 2 /M phase of the cell cycle, and therefore apoptotic induction, as indicated with flow cytometry analysis. In addition, it provoked an apoptotic process, marked by elevated caspase-3 activity. To conclude, the results indicate that TAM1344 is a novel, highly effective microtubule-targeting agent. [ABSTRACT FROM AUTHOR]

The goal of this study was to analyse international journals and conference proceedings published from 2012 to 2016. The main results indicated that the gap between the Arab Gulf Countries (GC) and the rest of the world regarding the amounts and trends of professional development (PD) research is too wide. At the global level, the initial scanning analysis showed the publication of 161 articles on math teacher PD, including 121 articles or abstracts published in conference proceedings and 40 articles published in journals. The number of articles on math teacher PD in the GC conference proceedings and journals was only 11. The results indicated that there is growing interest in research on PD in math and pedagogical content knowledge (PCK). The results also showed that descriptive research received the most attention, followed by developmental and evaluative research. Most of the English-language research used qualitative methodology and mixed methodology, and hence, used observations and interviews to collect their data. At the level of Arabic-Language, GC, research, the results indicated that developmental research received the greatest attention; however, all the data collected were quantitative because the survey was the most commonly used tool in these research studies. [ABSTRACT FROM AUTHOR]

Adult human bone marrow stromal cells (hBMSC) cultured for cell therapy require evaluation of potency and stability for safe use. Chromosomal aberrations upsetting genomic integrity in such cells have been contrastingly described as “Limited” or “Significant”. Previously reported stepwise acquisition of a spontaneous neoplastic phenotype during three-year continuous culture of telomerized cells (hBMSC-TERT20) didn't alter a diploid karyotype measured by spectral karyotype analysis (SKY). Such screening may not adequately monitor abnormal and potentially tumorigenic hBMSC in clinical scenarios. We here used array comparative genomic hybridization (aCGH) to more stringently compare non-tumorigenic parental hBMSC-TERT strains with their tumorigenic subcloned populations. Confirmation of a known chromosome 9p21 microdeletion at locus CDKN2A/B , showed it also impinged upon the adjacent MTAP gene. Compared to reference diploid human fibroblast genomic DNA, the non-tumorigenic hBMSC-TERT4 cells had a copy number variation (CNV) in at least 14 independent loci. The pre-tumorigenic hBMSC-TERT20 cell strain had further CNV including 1q44 gain enhancing SMYD3 expression and 11q13.1 loss downregulating MUS81 expression. Bioinformatic analysis of gene products reflecting 11p15.5 CNV gain in tumorigenic hBMSC-TERT20 cells highlighted networks implicated in tumorigenic progression involving cell cycle control and mis-match repair. We provide novel biomarkers for prospective risk assessment of expanded stem cell cultures. [ABSTRACT FROM AUTHOR]

We have previously reported that human neonatal foreskin stromal cells (hNSSCs) promote angiogenesis in vitro and in chick embryo chorioallantoic membrane (CAM) assay in vivo. To examine the in vivo relevance of this observation, we examined in the present study the differentiation potential of hNSSCs in ex vivo organotypic cultures of embryonic chick femurs. Isolated embryonic chick femurs (E10 and E11) were cultured for 10 days together with micro-mass cell pellets of hNSSCs, human umbilical vein endothelial cells (HUVEC) or a combination of the two cell types. Changes in femurs gross morphology and integration of the cells within the femurs were investigated using standard histology and immunohistochemistry. After 10 days, the femurs that were cultured in the presence of hNSSCs alone or hNSSC + HUVEC cells grew longer, exhibited thicker diaphysis and an enlarged epiphyseal region compared to control femurs cultured in the absence of cells. Analysis of cell–femur interactions, revealed intense staining for CD31 and enhanced deposition of collagen rich matrix along the periosteum in femurs cultured with hNSSCs alone or hNSSCs + HUVEC and the most pronounced effects were observed in hNSSC + HUVEC cultures. Our data suggest that organotypic cultures can be employed to test the differentiation potential of stem cells and demonstrate the importance of stem cell interaction with 3D-intact tissue microenvironment for their differentiation. [ABSTRACT FROM AUTHOR]

Understanding the regulatory networks underlying lineage differentiation and fate determination of human bone marrow stromal cells (hBMSC) is a prerequisite for their therapeutic use. The goal of the current study was to unravel the novel role of the low-density lipoprotein receptor-related protein 3 (LRP3) in regulating the osteogenic and adipogenic differentiation of immortalized hBMSCs. Gene expression profiling revealed significantly higher LRP3 levels in the highly osteogenic hBMSC clone imCL1 than in the less osteogenic clone imCL2, as well as a significant upregulation of LRP3 during the osteogenic induction of the imCL1 clone. Data from functional and gene expression assays demonstrated the role of LRP3 as a molecular switch promoting hBMSC lineage differentiation into osteoblasts and inhibiting differentiation into adipocytes. Interestingly, microRNA (miRNA) expression profiling identified miR-4739 as the most under-represented miRNA (− 36.11 fold) in imCL1 compared to imCL2. The TargetScan prediction algorithm, combined with functional and biochemical assays, identified LRP3 mRNA as a novel target of miR-4739, with a single potential binding site for miR-4739 located in the LRP3 3′ UTR. Regulation of LRP3 expression by miR-4739 was subsequently confirmed by qRT-PCR, western blotting, and luciferase assays. Over-expression of miR-4739 mimicked the effects of LRP3 knockdown on promoting adipogenic and suppressing osteogenic differentiation of hBMSCs. Hence, we report for the first time a novel biological role for the LRP3/hsa-miR-4739 axis in balancing osteogenic and adipocytic differentiation of hBMSCs. Our data support the potential utilization of miRNA-based therapies in regenerative medicine. [ABSTRACT FROM AUTHOR]

This study compared the accuracy and efficiency of a novel static computer-aided surgical technique using a 3-dimensional (3D)-printed surgical guide (3D-SG) with a fully guided drill protocol (3D-SG FG) to the freehand (FH) osteotomy and root-end resection (RER). Forty-six roots from 2 cadaver heads were divided into 2 groups: 3D-SG FG (n = 23) and FH (n = 23). Cone-beam computed tomographic scans were taken preoperatively and postoperatively. The endodontic microsurgery was planned in Blue Sky Bio software, and the 3D-SG was designed and 3D printed. The osteotomy and RER were conducted using a guided twist drill diameter of 2 mm and an ascending tapered drill with diameters of 2.8/3.2, 3.2/3.6, 3.8/4.2, and 4.2 mm with respective guided drill guides. Two-dimensional and three-dimensional virtual deviations and angular deflection were calculated. Linear osteotomy measures and root resection angle were obtained. The osteotomy and RER time and the number of mishaps were recorded. Two-dimensional and three-dimensional accuracy deviations and angular deflection were lower in the 3D-SG FG protocol than in the FH technique (P <.05). The height, length, and depth of the osteotomy and root resection angle were less in the 3D-SG FG protocol than in the FH technique (P <.05). The osteotomy and RER time with the 3D-SG FG protocol were less than the FH method (P <.05). Within the limitations of this cadaver-based study using denuded maxillary and mandibular jaws, 3D-SG FG protocol showed higher accuracy than FH osteotomy and RER. Moreover, the 3D-SG FG drill protocol significantly reduced the surgical time. [ABSTRACT FROM AUTHOR]

The goal of the current study was to determine the effects of the allethrin, as a pyrethroid-based insecticide, on kidney function in rat offspring. Sixty-day-old Wistar albino female rats were randomly allocated to three groups: control group and two allethrin-treated groups that were intragastrically administered with 34.2 or 68.5 mg/kg b.w. of allethrin starting from the day 6 of pregnancy until delivery. The results revealed that the high dose of allethrin (68.5 mg/kg) reduced the number of glomeruli. Results showed that the glomeruli diameter in animals treated with 34.2 mg/kg of allethrin significantly decreased when compared to the controls (p < 0.001) whereas at the dose of 68.5 mg/kg the glomeruli diameter was significantly higher than those of the control group (p < 0.05). Interestingly, the expression of the autophagic markers Beclin-1 and LC-3 was increased when compared to control indicating an induction of the autophagic mechanism. Furthermore, allethrin administration downregulated in a dose-dependent manner the expression of the epithelial sodium channel (ENaC) gene. The mRNA levels of Na+/K+- ATPase gene were significantly higher in the group treated with the low dose and significantly lower with the high dose, when compared to control. However, there was no effect of allethrin on the gene expression of NHE3 in both treated groups. Taken together, the findings of this study suggested that the exposure to allethrin might contribute to the nephrotoxicity by affecting the number and the diameter of glomeruli, causing histopathological alterations and inducing autophagic-related markers and affecting the mRNA levels of ENaC and Na+/ K + ATPase genes. [ABSTRACT FROM AUTHOR]

Osteopetrosis is a monogenic disorder represented by disturbed osteoclast resorption or osteoclastogenesis differentiation. Clinical symptoms are intensive and brittle bones, recurrent fractures, thrombocytopenia, impaired immune function, optic nerve compression, and anemia. Several osteopetrosis-causing genes have been identified and reported. The present study describes two consanguineous Saudi families segregating a severe autosomal recessive osteopetrosis disease. A single proband (II-2) in family A and two probands (II-2; II-4) in family B exhibited increased bone density, multiple fractures, teeth abnormalities, bilateral optic atrophy with nystagmus, and progressive blindness. DNA of the affected individuals was exposed to whole-exome sequencing (WES) and Sanger sequencing. Further, reverse transcriptase-polymerase chain reaction (RT-PCR) and western blotting analysis were done to investigate the impact of the identified mutation. WES revealed a novel homozygous splice site variant (c.739-18G > A) in the CLCN7 gene on chromosome 16p13.3, segregating perfectly with the disorder phenotype. RT-PCR resulted in the retention of a 50 bp sequence of intron 8 in the mutated sequence. As a result, this variant resulted in a large size exon 9 compared to the wild type. In addition, the western blot revealed the heteromeric form of ClC-7 disappeared in the patient's fibroblasts versus the control, indicating identified variant pathogenicity. The present research provides certain proof that homozygous variants in the CLCN7 gene are responsible for intense osteopetrosis disorders with diverse phenotypes. These findings have significant implications for decisions regarding the clinical therapeutic regimen, prognosis assessment, and antenatal diagnosis. [ABSTRACT FROM AUTHOR]

Placental insufficiency causes fetal adaptation, leading to fetal programming of chronic diseases. Placentas with intrauterine growth restriction (IUGR) are smaller than average and may contribute to low birth weight of the newborn. The number of patients with IUGR in the Saudi population is increasing; however, little is known about their placentas. The aim of this study was to assess morphometric and histopathological placental changes in Saudi patients with IUGR. Overall, 20 healthy pregnant Saudi women (control group) and 20 pregnant Saudi women with IUGR were enrolled. Maternal and fetal morphometric measurements were recorded. The placentas from both groups were processed for histopathological examination using stereological techniques. The IUGR group had lower placental weight, volume, length, breadth, and surface area than the control group. The total volume of villi and surface area of the terminal villi were significantly reduced in the IUGR placentas. IUGR group had a reduction in birth weight; length; and circumference of the head, chest, abdomen, and thigh compared to control group. The reduction in placental mass, specifically the reduction in the volume and surface area of villi, the functional units, may have reduced the capacity for nutrient transport. This led to a significant reduction in neonatal measurements. The fetus rearranged nutrient distribution in favor of the brain and other essential organs; however, at the expense of thigh development and growth. This fetal trade-off strategy increases the risk of developing chronic diseases in adulthood. Therefore, IUGR infants may require more clinical attention. [ABSTRACT FROM AUTHOR]

Considering that lead caused a lot of health problems in the world, the present study was carried out to investigate the protective effect of captopril as antioxidants to reduce liver and spleen toxicity induced by lead. Animals were divided into 3 groups, the 1st group served as control group, the 2nd group received 20 mg/kg of lead acetate and the 3rd group received 50 mg/kg of captopril one hour prior to lead administration for 5 days. Results showed that lead intake caused severe alterations in the liver and spleen manifested by hepatocytes degeneration, leukocytic infiltration, fibrosis in liver and moderate to severe liver pathological score. Spleen showed ill-defined architecture, presence of large macrophages and lymphoid necrosis. Administration of captopril reduced hepatotoxicity, liver fibrosis and decrease in pathological scoring system. Moreover, reduced toxicity in spleen is represented by reduction in necrotic areas, more or less healthy lymphoid follicles and decreasing in pathological scoring system. [ABSTRACT FROM AUTHOR]

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Diabetes mellitus is one of the major health problems. This study was designed to investigate the effect of biotin to regulate blood glucose level, reduced toxicity and oxidative stress in liver of diabetic mice STZ-induced type 1. Male mice were divided into three groups, the first one served as the control group, the second and the third groups received single ip dose of 150 mg/kg of STZ, the second group served as the untreated diabetic group, the third group received daily oral dose of 15 mg/kg of biotin, livers and liver index showed insignificant difference among groups. Blood glucose level showed a significant decrease in treated diabetic mice compared to untreated diabetic mice. Biochemical analysis showed a significant decrease in liver enzymes AST and ALT compared to the control group. Histopathological examination showed severe changes in untreated diabetic liver tissue manifested by dilated portal vein, leukocytic infiltration, fatty degeneration and moderate to severe histopathological score, whereas, treated diabetic mice with biotin showed reduction in hepatotoxicity represented by appearance of relative healthy hepatocytes and normal histopathological score. Immunohistochemistry of acrolein showed intense immunoreactions in liver section of untreated diabetic mice and faint immunoreactions in treated diabetic mice with biotin as evidence to oxidative stress reduction. [ABSTRACT FROM AUTHOR]

Cancer is emerging as one of the most significant challenges to the human health. Ivermectin (IVM) is one of the most effective drugs in veterinary and human medicine. The purpose of this study was to evaluate the potential preventative effect of IVM against cytotoxicity induced by dimethylhydrazine (DMH) in Male Wistar rats. Three concentrations of IVM (0.25, 0.5 and 1 mg/kg) were utilized in this study. Liver function enzymes, inflammatory markers and histopathological alterations in liver and kidney tissues were investigated. Obtained data showed that the combination of DMH with each concentration of IVM increased the activity of liver enzymes (ALT, ALP, AST, and GGT) compared to control and DMH alone. RT-PCR findings showed upregulation in the level of INF-γ, IL-6, IL-1β, Cox1, and Cox2 genes compared to control. In contrast, IL-6 gene was down-regulated. The levels of genes expression were down-regulated with combined DMH with medium and high concentrations compared to DMH alone. Microscopic analysis demonstrated histological alterations in the liver and kidney of rats treated with DMH. Combinations of DMH either with medium or high concentration resulted in less pathological features in both liver and kidney tissues. In conclusion, this study showed that IVM mitigated the toxic effects of DMH on the liver and kidney of male Wistar rats. [ABSTRACT FROM AUTHOR]

The aim of the study is to investigate whether the 3-dimensional dynamic navigation system (3D-DNS) can improve experienced endodontists' (EEs') and novice endodontists' (NEs') accuracy and efficiency in osteotomy and root-end resection (RER) and to verify that the 3D-DNS enables NEs to perform osteotomy and RER as accurately and efficiently as EEs. Seventy-six roots in cadaver heads were randomly divided into 4 groups: 3D-DNS-NE, 3D-DNS-EE, freehanded (FH)-NE, and FH-EE (all, n = 19). Cone-beam computed tomography scans were taken preoperatively and postoperatively. Osteotomy and RER were planned virtually in the X-guided software (X-Nav Technologies, Lansdale). Accuracy was calculated by measuring the 2-dimensional and 3D virtual deviations and angular deflection using superimposing software (X-Nav technologies). Efficiency was determined by the time of operation and the number of mishaps. Accuracy deviations were significantly fewer in the 3D-DNS-EE group than those in the FH-EE group (P <.05). We found less 2-dimensional and 3D accuracy deviations comparing the 3D-DNS-NE group to the FH-NE group (P <.05). The time required for osteotomy and RER with the 3D-DNS was ∼ ½ of that required for the FH method for both EEs and NEs (P <.05). We found no difference in the number of mishaps between the 3D-DNS and FH groups for EEs and NEs (P >.05). The 3D-DNS improved EEs' and NEs' accuracy and efficiency in osteotomy and RER. The NEs were as efficient as the EEs using the 3D-DNS. Notably, the 3D-DNS improved the NEs' accuracy compared to the FH method, but the 3D-DNS did not enable the NEs to perform osteotomy and RER as accurately as the EEs. [ABSTRACT FROM AUTHOR]

Human embryonic stem cells (hESCs) have the ability to differentiate into all human cells, however controlling the differentiation has always been a challenge. In the present study we have investigated the direct differentiation of hESCs on MEFs by using TGF-β signaling pathway activators Activin A and Activin B. Activation of the TGF-β pathway with Activin B in low serum highly induced primitive streak and mesendoderm formation after 24 h, which included up-regulation of SOX 17 and BRACHYURY protein and gene expression. Continuous stimulation with Activin B in 2% serum further induced mesendoderm formation by increased gene expression of Brachyury, SOX17, MEOX and FOX at the same time we found down-regulation of neuroectodermal marker genes. Further, by stimulating the mesodermal cells by BMP-2 we succeeded to induce mesenchymal like cells with high expression of mesenchymal markers including; MEOX, FOX, RUNX2, COL1 and OSTEOPONTIN. In conclusion we have directed the differentiation of hESCs as monolayer to primitive streak like cells with Activin B and further into pure mesoderm and mesenchymal like cells by BMP-2. [ABSTRACT FROM AUTHOR]

Bone marrow stromal cells (BMSCs, also known as bone marrow-derived mesenchymal stem cells) and their progenitors have been identified based on retrospective functional criteria. CD markers are employed to define cell populations with distinct functional characteristics. However, defining and prospective isolation of BMSCs and committed progenitors are lacking. Here, we compared the transcriptome profile of CD markers expressed at baseline and during the course of osteoblast and adipocyte differentiation of two well-characterized osteogenic-committed murine BMSCs (mBMSC Bone ) and adipogenic-committed mBMSCs (mBMSC Adipo ), respectively. Bioinformatic analysis revealed the presence of a core set of canonical mBMSC CD markers with comparable expression levels in mBMSC Bone and mBMSC Adipo at baseline and during their differentiation. We identified 11 CD markers that are differentially expressed between mBMSC Adipo and mBMSC Bone . Among these, we identified osteoprogenitor-associated CD markers expressed only in mBMSC Bone : CD34, CD54, CD73, CD132, CD200, CD227 and adipoprogenitor-associated CD markers expressed only in mBMSC Adipo : CD53, CD80, CD134, CD141 and CD212. FACS analysis confirmed these results. We selected CD34 for further analysis. CD34 was expressed at baseline of mouse stromal cell line ST2, primary mBMSCs, mBMSC Bone and its expression decreased during osteoblast differentiation. FACS-sorted CD34 + primary mBMSCs exhibited higher expression of 70% osteoblast-associated genes, and formed significantly higher heterotopic bone in vivo when implanted subcutaneously in immune-deficient mice compared with CD34 − primary mBMSCs. Our results demonstrate that a set of CD markers can distinguish osteoprogenitor versus adipoprogenitor populations of mBMSCs. CD34 is suitable for prospective isolation of mouse bone marrow osteoprogenitors. [ABSTRACT FROM AUTHOR]

The current study was carried out to investigate the protective role of biotin in kidney injury and oxidative stress in diabetic mice type 1. Male Swiss albino mice were randomly divided into 3 groups. Control group received saline. Diabetes type 1 was induced in second and third groups by intraperitoneal injection of streptozotocin as a single dose (150 mg/kg). Second group remained as the untreated diabetic group and the third group received 15 mg/kg daily oral dose of biotin for 12 successive days. Biochemical results showed significant elevation in blood glucose and urea levels in both diabetic groups. Also, there is an increase in glomerular areas and decrease in glomerular cellularity in both diabetic groups. Histopathological results showed severe alterations in the untreated diabetic group represented by distorted glomeruli, inflammatory cells, and giant macrophages. In addition, there was an intense immune-reaction response toward acrolein indicator of oxidative damage. Upon biotin administration of diabetic mice, the above mentioned histopathological changes were reduced and also acroline reaction of oxidative damage was diminished. Our findings prove that biotin has a protective role against streptozotocin-induced oxidative damage in kidneys of laboratory mice. [ABSTRACT FROM AUTHOR]

Abstract: There may be regional specialisation in structure and function across the placental surface. In Riyadh, Saudi Arabia, the length and the breadth of the placental surface at birth were highly correlated, but the breadth was more closely associated with the size of the baby. To replicate this we studied 321 pregnant Saudi women in the town of Baish. We measured the size of the newborn babies and their placentas. The association of the length and breadth of the placental surface on the baby's body size differed in boys and girls. Among boys the breadth had a stronger association with all birth measurements except crown–heel length. This was similar to the findings in Riyadh. Placental surface length was related to crown–heel length. For each centimetre in surface length, crown–heel length increased by 0.27 cm (95% CI 0.09–0.44, p = 0.004). Among girls placental surface breadth was related to crown–heel length, whereas surface length was related to birth weight, head and thigh circumferences. For each centimetre in surface breadth, crown–heel length increased by 0.33 cm (0.13–0.53, p = 0.001). We conclude that, within Saudi Arabia, there are both geographical and sex differences in regional specialisation across the placental surface. In the adverse circumstances of Baish, linked to the mothers' short stature, boys were smaller at birth than girls. Boys may have compensated for under-nutrition by increasing the depth of spiral artery invasion rather than by recruiting additional spiral arteries. Girls may have had more effective regional specialisation across the placental surface. [Copyright &y& Elsevier]

Problem Statement: Teacher professional development is a prominent feature in the educational landscapes of both developed and developing countries. Teacher development can be conceptualised as a mechanism for driving change in educational systems and/ or as a strategy for empowering teachers to improve their professional knowledge and pedagogy. To ensure effective teacher professional development, Science teachers need to be more in control of their own PD. More studies of teacher professional needs have been carried out in Western societies rather than Arab societies. In addition, supervisors' voices in regard to the PD of teachers have not been emphasised by international or national studies. Changing the research contexts might introduce a new understanding of the priority of professional needs. Purpose of the Study: This study aimed to identify and explore science teachers' needs for both pedagogical and content knowledge as a first step toward making decisions and recommendations about the elements of CPD programme(s) required for science teachers. The purpose of the study was to determine the professional development needs perceived by science teachers and their supervisors in Saudi Arabia. Methods: The main instrument used was a questionnaire. The validity and reliability of the instrument were systematically established through relevant test procedures. The questionnaire seeks feedback on the main aspects of science teachers' needs, including generic pedagogical knowledge and skills, knowledge and skills in science subjects, managing and delivering science instruction, diagnosing students' needs, evaluating students' work, planning science instruction, administering the use of facilities and equipment, integrating multimedia technology, and informal science learning. Additionally, the questionnaire covers the key science subject domains in which science teachers might need professional development (PD). Findings and Results: This study argues that science teachers' voices concerning their PD needs are the key guide for their CPD. While science teachers may share a number of perceived needs with science supervisors, teachers have distinct pedagogical and content knowledge needs that may differ according to individual interests. Suggestions and Recommendations: Attention should be given to ensure that individual teachers' differing needs are met because providing the same programme for all teachers may not meet the needs of them all. Science teachers, supervisors, policy makers, and in-service and pre-service training planners need to work together to consider the recommendations that have been identified in the teachers' PD research. [ABSTRACT FROM AUTHOR]

Ethylbenzene is a hydrocarbon that is extensively used in both industry and in the home and has been reported as toxic to various tissues. Nevertheless, its effect on ovarian function remains unclear. For this purpose, we assessed ovarian tissue morphology, evaluated protein and gene expression related to folliculogenesis and steroidogenesis, and investigated the involvement of both apoptosis and autophagy processes in this effect. Female Wistar albinos rats were treated with 2000, 4000 and 8000 ppm doses of ethylbenzene by inhalation for 30 min daily for one month. Ovaries were then removed and proceeded for histopathological and molecular analyses. We found that ethylbenzene affected folliculogenesis by decreasing the number of growing follicles and increasing the number of abnormal follicles, leading to faster female reproductive aging. Interestingly, it disrupted female reproductive hormone balance, including progesterone, estradiol, testosterone and IGF-1 plasma levels. The latter protein, along with GDF-9, significantly decreased in all ethylbenzene-treated groups, leading to the disruption of follicular cell proliferation and development. TUNEL assay study showed that ethylbenzene exposure significantly increased the number of apoptotic cells. The mRNA levels of genes involved in granulosa cell proliferation and differentiation, such as INSL3 , CCND2 and ACTB, were significantly decreased. In addition, LC3 protein expression increased, and its encoding gene was upregulated, suggesting that ethylbenzene treatment induced autophagy. In summary, ethylbenzene exposure caused structural and functional disorders of the ovary by disrupting the normal growth of follicles, altering reproductive hormone balance, inhibiting the expression of key reproductive proteins and triggering autophagy as well as apoptosis. • Ethylbenzene caused ovarian histopathological and stereological changes. • Ethylbenzene exposure altered progesterone, testosterone and IGF-1 release. • Ethylbenzene induced both autophagy and apoptosis mechanisms. • Ethylbenzene disrupted folliculogeneic and steroidogenic-related gene expression. [ABSTRACT FROM AUTHOR]

Background: There is growing evidence of the need to consider cultural factors in the design and implementation of digital health interventions. However, there is still inadequate knowledge pertaining to the aspects of the Saudi Arabian culture that need to be considered in the design and implementation of digital health programs, especially in the context of home health care services for patients who are chronically and terminally ill.Objective: This study aims to explore the specific cultural factors related to patients and their caregivers from the perspective of physicians, nurses, and trainers that have influenced the pilot implementation of Remotely Accessible Healthcare At Home, a connected health program in the Home Health Care department at King Saud University Medical City, Riyadh, Saudi Arabia.Methods: A qualitative study design was adopted to conduct a focus group discussion in July 2019 using a semistructured interview guide with 3 female and 4 male participants working as nurses, family physicians, and information technologists. Qualitative data obtained were analyzed using a thematic framework analysis.Results: A total of 2 categories emerged from the focus group discussion that influenced the experiences of digital health program intervention: first, culture-related factors including language and communication, cultural views on using cameras during consultation, nonadherence to web-based consultations, and family role and commitment and second, caregiver characteristics in telemedicine that includes their skills and education and electronic literacy. Participants of this study revealed that indirect contact with patients and their family members may work as a barrier to proper communication through the Remotely Accessible Healthcare At Home program.Conclusions: We recommend exploring the use of interpreters in digital health, creating awareness among the local population regarding privacy in digital health, and actively involving direct family members with the health care providers. [ABSTRACT FROM AUTHOR]

Background: The adoption rate of digital health in the health care sector is low in many countries. A facilitating factor for successful implementation and adoption of digital health is acceptance by current and future health care professionals. Objective: This study was conducted to identify factors associated with willingness to use digital health tools in patient care among health care professionals and students. Methods: This was a quantitative cross-sectional survey study conducted among health care professionals and students at a university hospital in Riyadh, Saudi Arabia. A nonprobability convenience sampling procedure was used to recruit participants. Data were collected using a self-completed e-questionnaire that was distributed by email. Chi-square tests, t tests, and logistic regression were used to analyze the data. Results: We found that 181 out of 218 health care professionals (83.0%; 75.6% [59/78] physicians; 87.1% [122/140] nurses) and 115 out of 154 students (74.7%; 80.0% [76/95] medical students and 66.1% [39/59] nursing students) were willing to use digital tools in patient care. Willingness to use digital tools was significantly associated with attitude (Adjusted Odds Ratios [AOR] 1.96; 95% CI 1.14-3.36) and self-efficacy (AOR 1.64; 95% CI 1.17-2.30) among health care professionals, and with current year of study (AOR 2.08; 95% CI 1.18-3.68) and self-efficacy (AOR 1.77; 95% CI 1.17-2.69) among students. No significant difference in willingness to use digital tools was found between physicians and nurses (P =.113), and between medical and nursing students (P =.079). Conclusions: The findings of this study should encourage policy makers and hospital managers to implement relevant eHealth interventions within routine health care systems in Saudi Arabia. For successful implementation, digital health education programs should be implemented simultaneously, so that current and future health care professionals are able to develop required positive attitudes as well as practical skills and competencies. JMIR Med Educ 2021;7(1):e18590 doi:10.2196/18590 [ABSTRACT FROM AUTHOR]

A microcosm experiment was conducted to evaluate the impacts of the fluoroquinolone antibiotic ciprofloxacin on meiobenthic taxa abundance, nematode genus structure, and functional trait parameters. Sediment samples were experimentally enriched with four different doses of ciprofloxacin [D1 (50 ppm Dry weight 'DW'), D2 (100 ppm DW), D3 (200 ppm DW), and D4 (500 ppm DW)] and were then compared with non-enriched sediments (controls). After one month of exposure, the data showed that ciprofloxacin had altered the meiofaunal taxa abundance. A change in the structure of nematofaunal genera was observed, particularly with the highest dose (D4), which was characterized by the lowest taxonomic diversity. The SIMPER analysis revealed that the average dissimilarity between nematode communities increased with increasing doses of ciprofloxacin. Two dimensional (2D) non-metric multidimensional scaling (nMDS) plots and relative abundances of functional groups of nematode genus assemblages revealed that all functional trait abundances were affected, particularly with the highest dose. However, only the amphid shape and feeding group functions showed a clear distribution separation between the control and ciprofloxacin treatments. The nMDS second-stage ordination of inter-matrix rank correlations for matrices including genus and functional traits showed that the tail shape was the closest functional trait to the generic distribution. Thus, only the curves of cumulative dominance related to the tail shape mirrored discernibly the sedimentary concentrations in ciprofloxacin. • Ciprofloxacin has a high adsorption capacity in aquatic sediments. • Ciprofloxacin reduced the abundance of meiobenthic taxa. • Ciprofloxacin addition led to the restructuring of marine nematodes genera. • Restructuring of morphological and functional traits of genus with the highest dose. [ABSTRACT FROM AUTHOR]