Genome-wide CRISPR screens identify novel regulators of wild-type and mutant p53 stability.

Tumor suppressor p53 (TP53) is frequently mutated in cancer, often resulting not only in loss of its tumor-suppressive function but also acquisition of dominant-negative and even oncogenic gain-of-function traits. While wild-type p53 levels are tightly regulated, mutants are typically stabilized in tumors, which is crucial for their oncogenic properties. Here, we systematically profiled the factors that regulate protein stability of wild-type and mutant p53 using marker-based genome-wide CRISPR screens. Most regulators of wild-type p53 also regulate p53 mutants, except for p53 R337H regulators, which are largely private to this mutant. Mechanistically, FBXO42 emerged as a positive regulator for a subset of p53 mutants, working with CCDC6 to control USP28-mediated mutant p53 stabilization. Additionally, C16orf72/HAPSTR1 negatively regulates both wild-type p53 and all tested mutants. C16orf72/HAPSTR1 is commonly amplified in breast cancer, and its overexpression reduces p53 levels in mouse mammary epithelium leading to accelerated breast cancer. This study offers a network perspective on p53 stability regulation, potentially guiding strategies to reinforce wild-type p53 or target mutant p53 in cancer.

IL7 in combination with radiotherapy stimulates a memory T-cell response to improve outcomes in HNSCC models.

Clinically approved head and neck squamous cell carcinoma (HNSCC) immunotherapies manipulate the immune checkpoint blockade (ICB) axis but have had limited success outside of recurrent/metastatic disease. Interleukin-7 (IL7) has been shown to be essential for effector T-cell survival, activation, and proliferation. Here, we show that IL7 in combination with radiotherapy (RT) is effective in activating CD8 + T-cells for reducing tumor growth. Our studies were conducted using both human papillomavirus related and unrelated orthotopic HNSCC murine models. Immune populations from the tumor, draining lymph nodes, and blood were compared between treatment groups and controls using flow cytometry, proteomics, immunofluorescence staining, and RNA sequencing. Treatment with RT and IL7 (RT + IL7) resulted in significant tumor growth reduction, high CD8 T-cell tumor infiltration, and increased proliferation of T-cell progenitors in the bone marrow. IL7 also expanded a memory-like subpopulation of CD8 T-cells. These results indicate that IL7 in combination with RT can serve as an effective immunotherapy strategy outside of the conventional ICB axis to drive the antitumor activity of CD8 T-cells.

Practical applications of robots in prosthodontics for tooth preparation and denture tooth arrangement: A scoping review.

STATEMENT OF PROBLEM: With the increasing interest in using robots in dentistry and the widespread dissemination of information on this topic and its applications, a comprehensive review of robot applications in prosthodontics is needed. PURPOSE: The purpose of this scoping review was to assess the current status of prosthodontic robotic applications, their achievements to date, and the barriers hindering their broader adoption and further advancement. MATERIAL AND METHODS: The checklist for Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) was used to conduct this review. A comprehensive search methodology was developed to identify relevant studies on the use of robots in prosthodontic procedures in the PubMed, Scopus, Web of Science, and Google Scholar databases. The inclusion criteria were studies that specifically outlined the application of robots in the field of prosthodontics. RESULTS: Eighteen relevant studies were found. Of these, 10 studies focused on assessing the effectiveness of robotic systems through in vitro testing using phantom models for tooth preparation. These studies specifically explored the processes involved in creating complete crowns and veneers. The remaining 8 studies investigated the use of robotics in tooth alignment, with a specific focus on complete dentures. CONCLUSIONS: Robots have the potential to improve precision and accuracy in prosthetic dentistry. However, clinical studies are needed to confirm the widespread use of robots in prosthodontics, as their clinical application is still in its early stages.

The Ste20-like kinase - a Jack of all trades?

Over the past 20 years, the Ste20-like kinase (SLK; also known as STK2) has emerged as a central regulator of cytoskeletal dynamics. Reorganization of the cytoskeleton is necessary for a plethora of biological processes including apoptosis, proliferation, migration, tissue repair and signaling. Several studies have also uncovered a role for SLK in disease progression and cancer. Here, we review the recent findings in the SLK field and summarize the various roles of SLK in different animal models and discuss the biochemical mechanisms regulating SLK activity. Together, these studies have revealed multiple roles for SLK in coupling cytoskeletal dynamics to cell growth, in muscle repair and in negative-feedback loops critical for cancer progression. Furthermore, the ability of SLK to regulate some systems appears to be kinase activity independent, suggesting that it may be an important scaffold for signal transduction pathways. These various findings reveal highly complex functions and regulation patterns of SLK in development and disease, making it a potential therapeutic target.

Pentoxifylline for treatment of sepsis and necrotising enterocolitis in neonates.

BACKGROUND: Mortality and morbidity due to neonatal sepsis and necrotising enterocolitis (NEC) remain high despite the use of potent antimicrobial agents. Agents that modulate inflammation may improve outcomes. Pentoxifylline (PTX), a phosphodiesterase inhibitor, is one such agent. This is an update of a review first published in 2003 and updated in 2011 and 2015. OBJECTIVES: To assess the effectiveness and safety of intravenous PTX as an adjunct to antibiotic therapy on mortality and morbidity in neonates with suspected or confirmed sepsis and neonates with NEC. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, and trial registries in July 2022. We also searched the reference lists of identified clinical trials and handsearched conference abstracts.   SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs assessing the efficacy of PTX with antibiotics (any dose or duration) for treatment of suspected or confirmed sepsis or NEC in neonates. We included three comparisons: (1) PTX with antibiotics compared to placebo or no intervention with antibiotics; (2) PTX with antibiotics compared to PTX with antibiotics and adjunct treatments such as immunoglobulin M-enriched intravenous immunoglobulin (IgM-enriched IVIG); (3) PTX with antibiotics compared to adjunct treatments such as IgM-enriched IVIG with antibiotics. DATA COLLECTION AND ANALYSIS: We reported typical risk ratio (RR) and risk difference (RD) with 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) for continuous outcomes derived from a fixed-effect model of meta-analysis. We calculated the number needed to treat for an additional beneficial outcome (NNTB) if there was a statistically significant reduction in RD. MAIN RESULTS: We identified no new studies for this update. We included six RCTs (416 neonates). All of the included studies examined neonates with sepsis; we identified no studies on neonates with NEC. Four of the six trials had high risk of bias for at least one risk of bias domain. Comparison 1: PTX with antibiotics compared to placebo with antibiotics, or antibiotics alone, in neonates with sepsis may reduce all-cause mortality during hospital stay (typical RR 0.57, 95% CI 0.35 to 0.93; typical RD -0.08, 95% CI -0.14 to -0.01; NNTB 13, 95% CI 7 to 100; 6 studies, 416 participants, low-certainty evidence) and may decrease length of hospital stay (LOS) (MD -7.74, 95% CI -11.72 to -3.76; 2 studies, 157 participants, low-certainty evidence). The evidence is very uncertain that PTX with antibiotics compared to placebo or no intervention results in any change in chronic lung disease (CLD) (RR 1.50, 95% CI 0.45 to 5.05; 1 study, 120 participants, very low-certainty evidence), severe intraventricular haemorrhage (sIVH) (RR 0.75, 95% CI 0.28 to 2.03; 1 study, 120 participants, very low-certainty evidence), periventricular leukomalacia (PVL) (RR 0.50, 95% CI 0.10 to 2.63; 1 study, 120 participants, very low-certainty evidence), NEC (RR 0.56, 95% CI 0.29 to 1.06; 6 studies, 405 participants, very low-certainty evidence), or retinopathy of prematurity (ROP) (RR 0.40, 95% CI 0.08 to 1.98; 1 study, 120 participants, very low-certainty evidence) in neonates with sepsis. Comparison 2: the evidence is very uncertain that PTX with antibiotics compared to PTX with antibiotics and IgM-enriched IVIG has any effect on mortality (RR 0.71, 95% CI 0.24 to 2.10; 102 participants, 1 study, very low-certainty evidence) or development of NEC in neonates with sepsis (RR 1.33, 95% CI 0.31 to 5.66; 1 study, 102 participants, very low-certainty evidence). The outcomes of CLD, sIVH, PVL, LOS, and ROP were not reported. Comparison 3: the evidence is very uncertain that PTX with antibiotics compared to IgM-enriched IVIG with antibiotics has any effect on mortality (RR 1.25, 95% CI 0.36 to 4.39; 102 participants, 1 study, very low-certainty evidence) or development of NEC (RR 1.33, 95% CI 0.31 to 5.66; 102 participants, 1 study, very low-certainty evidence) in neonates with sepsis. The outcomes of CLD, sIVH, PVL, LOS, and ROP were not reported. All of the included studies evaluated adverse effects due to PTX, but none were reported in the intervention group in any of the comparisons. AUTHORS' CONCLUSIONS: Low-certainty evidence suggests that adjunct PTX therapy in neonatal sepsis may decrease mortality and length of hospital stay without any adverse effects. The evidence is very uncertain if PTX with antibiotics compared to PTX with antibiotics and IgM-enriched IVIG, or PTX with antibiotics compared to IgM-enriched IVIG with antibiotics, has any effect on mortality or development of NEC. We encourage researchers to undertake well-designed multicentre trials to confirm or refute the effectiveness and safety of pentoxifylline in reducing mortality and morbidity in neonates with sepsis or NEC.

Management of pediatric blunt abdominal trauma with split liver or spleen injuries: a retrospective study.

BACKGROUND: Blunt abdominal trauma is a prevailing cause of pediatric morbidity and mortality. It constitutes the most frequent type of pediatric injuries. Contrast-enhanced sonography (CEUS) and contrast-enhanced computed tomography (CECT) are considered pivotal diagnostic modalities in hemodynamically stable patients. AIM: To report the experience in management of pediatric split liver and spleen injuries using CEUS and CECT. PATIENTS AND METHODS: This study included 246 children who sustained blunt abdominal trauma, and admitted and treated at three tertiary hospitals in the period of 5 years. Primary resuscitation was offered to all children based on the advanced trauma and life support (ATLS) protocol. A special algorithm for decision-making was followed. It incorporated the FAST, baseline ultrasound (US), CEUS, and CECT. Patients were treated according to the imaging findings and hemodynamic stability. RESULTS: All 246 children who sustained a blunt abdominal were studied. Patients' age was 10.5 ± 2.1. Road traffic accidents were the most common cause of trauma; 155 patients (63%). CECT showed the extent of injury in 153 patients' spleen (62%) and 78 patients' liver (32%), while the remaining 15 (6%) patients had both injuries. CEUS detected 142 (57.7%) spleen injury, and 67 (27.2%) liver injury. CONCLUSIONS: CEUS may be a useful diagnostic tool among hemodynamically stable children who sustained low-to-moderate energy isolated blunt abdominal trauma. It may be also helpful for further evaluation of uncertain CECT findings and follow-up of conservatively managed traumatic injuries.

Knowledge of Strategies to Teach Reading Components among Teachers of Hard of Hearing Students.

This study investigated Saudi Arabian elementary school teachers' knowledge of strategies to teach reading components to hard of hearing students. The study focused on four of the five reading components the National Reading Panel (NPR, 2000) identified: phonemic awareness; phonics; vocabulary; and reading comprehension, and explored the relation between teachers' demographic characteristics and their knowledge of the strategies as well. An explanatory sequential mixed methods design was used that included two phases. The quantitative phase examined the knowledge of these Arabic reading components among 89 elementary school teachers of hard of hearing students, and the qualitative phase consisted of interviews with 10 teachers. The results indicated that the teachers have a great deal of knowledge (above the mean score) of strategies to teach reading components. Specifically, teachers' knowledge of strategies to teach the vocabulary component was the highest. The results also showed no significant association between teachers' demographic characteristics and their knowledge of strategies to teach reading components. The qualitative analysis revealed two themes: (1) teachers' lack of basic knowledge of strategies to teach reading components, and (2) the absence of in-service courses and training programs in reading for teachers.

Prognosticating outcome using magnetic resonance imaging in patients with moderate to severe traumatic brain injury: a machine learning approach.

INTRODUCTION: Over the last decade advancements in computer processing have enabled the application of machine learning (ML) to complex medical problems. Convolutional neural networks (CNN), a type of ML, have been used to interrogate medical images for variety of purposes. In this study, we aimed to investigate the potential application of CNN in prognosticating patients with traumatic brain injury (TBI). METHODS: Patients with moderate to severe TBI and evidence of diffuse axonal injury (DAI) were selected retrospectively. A CNN model was developed using a training subgroup and a holdout subgroup was used as a testing dataset. We reported the model characteristics including area under the receiver operating characteristic curve (AUC). RESULTS: We included a total of 38 patient, of which we generated 725 MRI sections. We developed a CNN model based on a modified AlexNet architecture that interpreted the brain stem injury to generate outcome predictions. The model was able to predict GOS outcomes with a specificity of 0.43 and a sensitivity of 0.997. It showed an AUC of 0.917. CONCLUSION: The utilization of machine learning MRI analysis for prognosticating patients with TBI is a valued method that require further investigation. This will require multicentre collaboration to generate large datasets.

Association of periodontal therapy, with inflammatory biomarkers and complications in COVID-19 patients: a case control study.

BACKGROUND: In previous studies, COVID-19 complications were reported to be associated with periodontitis. Accordingly, this study was designed to test the hypothesis that a history of periodontal therapy could be associated with lower risk of COVID-19 complications. METHODS: A case-control study was performed using the medical health records of COVID-19 patients in the State of Qatar between March 2020 and February 2021 and dental records between January 2017 and December 2021. Cases were defined as COVID-19 patients who suffered complications (death, ICU admissions and/or mechanical ventilation); controls were COVID-19 patients who recovered without major complications. Associations between a history of periodontal therapy and COVID-19 complications were analysed using logistic regression models adjusted for demographic and medical factors. Blood parameters were compared using Kruskal-Wallis test. RESULTS: In total, 1,325 patients were included. Adjusted odds ratio (AOR) analysis revealed that non-treated periodontitis was associated with significant risk of need for mechanical ventilation (AOR = 3.91, 95% CI 1.21-12.57, p = 0.022) compared to periodontally healthy patients, while treated periodontitis was not (AOR = 1.28, 95% CI 0.25-6.58, p = 0.768). Blood analyses revealed that periodontitis patients with a history of periodontal therapy had significantly lower levels of D-dimer and Ferritin than non-treated periodontitis patients. CONCLUSION: Among COVID-19 patients with periodontal bone loss, only those that have not received periodontal therapy had higher risk of need for assisted ventilation. COVID-19 patients with a history of periodontal therapy were associated with significantly lower D-dimer levels than those without recent records of periodontal therapy. CLINICAL RELEVANCE: The fact that patients with treated periodontitis were less likely to suffer COVID-19 complications than non-treated ones further strengthen the hypothesis linking periodontitis to COVID-19 complications and suggests that managing periodontitis could help reduce the risk for COVID-19 complications, although future research is needed to verify this.

Prevalence and Risk Factors of Dental Trauma in Ha'il, Saudi Arabia.

AIM: This study will aid in determining the prevalence and risk factors for dental trauma. This will assist in developing a treatment budget plan, thereby, fend off complications. MATERIALS AND METHODS: This study was an observational study, having a cross-sectional design, in which information was obtained from 555 participants. Data were obtained using a non-probability convenient sampling technique. A validated questionnaire was used as a study tool. Data were analyzed using the statistical package for the social sciences (SPSS, version 20). Descriptive and inferential statistics were used. Data were displayed as numbers and percentages, and the Chi-squared test was used to measure the association. RESULTS: Dental trauma was found to be 44% prevalent. Most of the injuries occurred in the 6-9-years age-group (19.1%) and were more common in boys (54.13%) than in girls. The majority of respondents (61%) identified "falls" as the most common cause of dental trauma, and the frequent location for the occurrence of dental injuries was found to be "home" (64.44%). Only 18% of parents reported that their kid's experienced nail-biting concerns, with the majority claimed that their kids never developed oral habits. Most dental injuries occurred during the summer season (48%). CONCLUSION: Young aged group and male gender group were more prone to dental injuries; dental injuries along with fall were found as the most common cause of dental trauma, whereas most of the dental traumas were reported to have occurred at home. CLINICAL SIGNIFICANCE: The study evaluated risk factors and the prevalence of dental trauma in the population of Ha'il, Saudi Arabia. It will be an effective tool for determining the need for treatment facilities.

AKT-mediated phosphorylation of Sox9 induces Sox10 transcription in a murine model of HER2-positive breast cancer.

BACKGROUND: Approximately 5-10% of HER2-positive breast cancers can be defined by low expression of the Ste20-like kinase, SLK, and high expression of SOX10. Our lab has observed that genetic deletion of SLK results in the induction of Sox10 and significantly accelerates tumor initiation in a HER2-induced mammary tumor model. However, the mechanism responsible for the induction of SOX10 gene expression in this context remains unknown. METHODS: Using tumor-derived cell lines from MMTV-Neu mice lacking SLK and biochemical approaches, we have characterized the signaling mechanisms and relevant DNA elements driving Sox10 expression. RESULTS: Biochemical and genetic analyses of the SOX10 regulatory region in SLK-deficient mammary tumor cells show that Sox10 expression is dependent on a novel -7kb enhancer that harbors three SoxE binding sites. ChIP analyses demonstrate that Sox9 is bound to those elements in vivo. Our data show that AKT can directly phosphorylate Sox9 in vitro at serine 181 and that AKT inhibition blocks Sox9 phosphorylation and Sox10 expression in SLK(-/-) tumor cells. AKT-mediated Sox9 phosphorylation increases its transcriptional activity on the Sox10 -7kb enhancer without altering its DNA-binding activity. Interestingly, analysis of murine and human mammary tumors reveals a direct correlation between the levels of active phospho-Sox9 S181 and Sox10 expression. CONCLUSIONS: Our results have identified a novel Sox10 enhancer and validated Sox9 as a direct target for AKT. As Sox10 is a biomarker for triple-negative breast cancers (TNBC), these findings might have major implications in the targeting and treatment of those cancers.

Periostin gene expression in neu-positive breast cancer cells is regulated by a FGFR signaling cross talk with TGFß/PI3K/AKT pathways.

BACKGROUND: Breast cancer is a highly heterogeneous disease with multiple drivers and complex regulatory networks. Periostin (Postn) is a matricellular protein involved in a plethora of cancer types and other diseases. Postn has been shown to be involved in various processes of tumor development, such as angiogenesis, invasion, cell survival and metastasis. The expression of Postn in breast cancer cells has been correlated with a more aggressive phenotype. Despite extensive research, it remains unclear how epithelial cancer cells regulate Postn expression. METHODS: Using murine tumor models and human TMAs, we have assessed the proportion of tumor samples that have acquired Postn expression in tumor cells. Using biochemical approaches and tumor cell lines derived from Neu+ murine primary tumors, we have identified major regulators of Postn gene expression in breast cancer cell lines. RESULTS: Here, we show that, while the stromal compartment typically always expresses Postn, about 50% of breast tumors acquire Postn expression in the epithelial tumor cells. Furthermore, using an in vitro model, we show a cross-regulation between FGFR, TGFß and PI3K/AKT pathways to regulate Postn expression. In HER2-positive murine breast cancer cells, we found that basic FGF can repress Postn expression through a PKC-dependent pathway, while TGFß can induce Postn expression in a SMAD-independent manner. Postn induction following the removal of the FGF-suppressive signal is dependent on PI3K/AKT signaling. CONCLUSION: Overall, these results reveal a novel regulatory mechanism and shed light on how breast tumor cells acquire Postn expression. This complex regulation is likely to be cell type and cancer specific as well as have important therapeutic implications.

Association between periodontitis and severity of COVID-19 infection: A case-control study.

AIM: COVID-19 is associated with an exacerbated inflammatory response that can result in fatal outcomes. Systemic inflammation is also a main characteristic of periodontitis. Therefore, we investigated the association of periodontitis with COVID-19 complications. MATERIALS AND METHODS: A case-control study was performed using the national electronic health records of the State of Qatar between February and July 2020. Cases were defined as patients who suffered COVID-19 complications (death, ICU admissions or assisted ventilation), and controls were COVID-19 patients discharged without major complications. Periodontal conditions were assessed using dental radiographs from the same database. Associations between periodontitis and COVID 19 complications were analysed using logistic regression models adjusted for demographic, medical and behaviour factors. RESULTS: In total, 568 patients were included. After adjusting for potential confounders, periodontitis was associated with COVID-19 complication including death (OR = 8.81, 95% CI 1.00-77.7), ICU admission (OR = 3.54, 95% CI 1.39-9.05) and need for assisted ventilation (OR = 4.57, 95% CI 1.19-17.4). Similarly, blood levels of white blood cells, D-dimer and C Reactive Protein were significantly higher in COVID-19 patients with periodontitis. CONCLUSION: Periodontitis was associated with higher risk of ICU admission, need for assisted ventilation and death of COVID-19 patients, and with increased blood levels of biomarkers linked to worse disease outcomes.

Double Double to Double Perovskite Transformations in Quaternary Manganese Oxides.

Control of cation ordering in ABX3 perovskites is important to structural, physical and chemical properties. Here we show that thermal transformations of AA'BB'O6 double double perovskites, where both A and B sites have 1:1 cation order, to (A0.5 A'0.5 )2 BB'O6 double perovskites with fully disordered A/A' cations can be achieved under pressure in CaMnMnWO6 and SmMnMnTaO6 , enabling both polymorphs of each material to be recovered. This leads to a dramatic switch of magnetic properties from ferrimagnetic order in double double perovskite CaMnMnWO6 to spin glass behaviour in the highly frustrated double perovskite polymorph. Comparison of double double and double perovskite polymorphs of other materials will enable effects of cation order and disorder on other properties such as ferroelectricity and conductivity to be explored.

An approach for adaptive automatic threat recognition within 3D computed tomography images for baggage security screening.

BACKGROUND: The screening of baggage using X-ray scanners is now routine in aviation security with automatic threat detection approaches, based on 3D X-ray computed tomography (CT) images, known as Automatic Threat Recognition (ATR) within the aviation security industry. These current strategies use pre-defined threat material signatures in contrast to adaptability towards new and emerging threat signatures. To address this issue, the concept of adaptive automatic threat recognition (AATR) was proposed in previous work. OBJECTIVE: In this paper, we present a solution to AATR based on such X-ray CT baggage scan imagery. This aims to address the issues of rapidly evolving threat signatures within the screening requirements. Ideally, the detection algorithms deployed within the security scanners should be readily adaptable to different situations with varying requirements of threat characteristics (e.g., threat material, physical properties of objects). METHODS: We tackle this issue using a novel adaptive machine learning methodology with our solution consisting of a multi-scale 3D CT image segmentation algorithm, a multi-class support vector machine (SVM) classifier for object material recognition and a strategy to enable the adaptability of our approach. Experiments are conducted on both open and sequestered 3D CT baggage image datasets specifically collected for the AATR study. RESULTS: Our proposed approach performs well on both recognition and adaptation. Overall our approach can achieve the probability of detection around 90% with a probability of false alarm below 20%. CONCLUSIONS: Our AATR shows the capabilities of adapting to varying types of materials, even the unknown materials which are not available in the training data, adapting to varying required probability of detection and adapting to varying scales of the threat object.

Upregulation of Orai1 and STIM1 expression as well as store-operated Ca2+ entry in ovary carcinoma cells by placental growth factor.

Placental growth factor (PlGF) is produced by tumor cells and stimulates tumor growth and metastasis in part by upregulation of hypoxia inducible factor HIF1α. Orchestration of tumor cell proliferation and migration involves oscillations of cytosolic Ca2+ activity ([Ca2+]i). The [Ca2+]i oscillations could be accomplished by triggering of intracellular Ca2+ release followed by store-operated Ca2+-entry (SOCE). Mechanisms accomplishing SOCE include the pore-forming ion channel unit Orai1 and its regulator STIM1. The present study explored whether PlGF influences the expression of Orai1 and STIM1, as well as SOCE and whether this effect impacts on HIF1α expression. To this end, ovary carcinoma cells were cultured for 24 h without and with PlGF (10 ng/ml). Orai1, STIM1 and HIF1α transcript levels were quantified utilizing RT-PCR and Orai1, STIM1 and HIF1α protein levels by Western blotting. [Ca2+]i was estimated from Fura-2-fluorescence and SOCE from increase of [Ca2+]i following Ca2+ re-addition after Ca2+-store depletion with extracellular Ca2+ removal and sarcoendoplasmatic Ca2+-ATPase (SERCA) inhibitor thapsigargin (1 µM). As a result, exposure of ovary carcinoma cells to PlGF was followed by a significant increase of Orai1 as well as STIM1 transcript and protein levels. PlGF significantly increased store-operated Ca2+-entry following re-addition of extracellular Ca2+, an effect virtually abrogated by Orai1 inhibitor MRS1845 (10 µM). PlGF further increased HIF1α transcript and protein levels, an effect again significantly blunted by MRS1845 (10 µM). In conclusion, PlGF upregulates expression of both, Orai1 and STIM1 thus enhancing store-operated Ca2+-entry with subsequent upregulation of HIF1α.

Facile synthesis and antimicrobial activity of CdS-Ag2S nanocomposites.

In this study CdS-Ag2S nanocomposites for antibacterial activity were synthesized via facile co-precipitation method using PVP as capping agent. The prepared nanocomposites have particle sizes in the range of 50-100 nm (SEM) and PVP addition has good influence on the morphology of nanocomposites. The antimicrobial activity of pure Ag2S, CdS and CdS-Ag2S composites was evaluated against Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli. The results demonstrate that antibacterial activity was significantly improved due to increasing ratio of CdS into CdS-Ag2S nanocomposites in comparison to pure Ag2S and CdS.

Management of colonoscopic perforation: a systematic review and treatment algorithm.

BACKGROUND: The aim of this review is to evaluate and summarize the current strategies used in the management of colonoscopic perforations as well as propose a modern treatment algorithm. METHODS: Articles published between January 2004 and January 2019 were screened. A total of 167 reports were identified in combined literature search, of which 61 articles were selected after exclusion of duplicate and unrelated articles. Only studies that reported on the management of endoscopic perforation in an adult population were retrieved for review. Case reports and case series of 8 patients or less were not considered. Ultimately, 19 articles were considered eligible for review. RESULTS: A total of 744 cases of colonoscopic perforations were reported in 19 major articles. The cause of perforation was mentioned in 16 articles. Colonoscopic perforations were reported as a consequence of diagnostic colonoscopies in 222 cases and therapeutic colonoscopies in 248 cases. The site of perforation was mentioned in 486 cases. Sigmoid colon was the predominant site followed by the cecum. The management of colonoscopic perforations was reported in a total of 741 patients. Surgical intervention was employed in 75% of the patients, of these 15% were laparoscopic and 85% required laparotomy. The predominant surgical intervention was primary repair. CONCLUSION: Management strategies of colon perforations depend upon the etiology, size, severity, location, available expertise, and general health status. Usually, peritonitis, sepsis, or hemodynamic compromise requires immediate surgical management. Endoscopic techniques are under continuous evolution. Newer developments have offered high success rate with least amount of post-procedure complications. However, there is a need for further studies to compare the newer endoscopic techniques in terms of success rate, cost, complications, and the affected part of colon.

Non traumatic spinal epidural haematoma.

Spinal epidural haematoma is a rare condition, which may be due to trauma, surgery, epidural catheterisation or disorders of coagulation. We report a case of 60 year old lady who was on warfarin for Atrial fibrillation (AF) presented with history of non-traumatic sudden onset pain in both legs and difficulty in walking. Magnetic resonance imaging (MRI) spine demonstrated epidural haematoma which was treated conservatively. Another dilemma was anticoagulation for AF. We examine the options to manage such case.

Non traumatic spinal epidural haematoma.

Spinal epidural haematoma is a rare condition, which may be due to trauma, surgery, epidural catheterisation or disorders of coagulation. We report a case of 60 year old lady who was on warfarin for Atrial fibrillation (AF) presented with history of non-traumatic sudden onset pain in both legs and difficulty in walking. Magnetic resonance imaging (MRI) spine demonstrated epidural haematoma which was treated conservatively. Another dilemma was anticoagulation for AF. We examine the options to manage such case.