Nurses' Attitudes Concerning Analgesia Administration for Pediatric Patients with Sickle Cell Disease in Jordan: A Cross-Sectional Study.

BACKGROUND: Pain management of vaso-occlusive crises is a fundamental priority in the lifelong care of children and adolescents with sickle cell disease. AIM: This study examined nurses' attitudes towards caring for children with sickle cell disease (SCD) and SCD pain management in those with vaso-occlusive pain. METHOD: A structured, self-reporting survey was provided to a convenience sample of 298 nurses across 10 hospitals serving Jordan's northern and middle regions. Descriptive and inferential statistics were applied for data analysis. RESULTS: Most nurses (77%) perceived their experience caring for children with SCD as positive. Many nurses (65%) felt frustrated about caring for these children during painful episodes. Participants identified workload and inadequate time as limiting their ability to address the analgesic needs of children with SCD. Receiving structured education specialized in pain management and more years of experience in nursing significantly predicted less hesitancy in administering opioid-based analgesia. CONCLUSIONS: The results of this study provided further insight into factors that potentially contribute to vaso-occlusive pain crises frequently being poorly managed and inadequately addressed among pediatric patients. Nurses' attitudes and understanding of SCD pain management must be addressed to advance the clinical practice of managing pain in children with SCD.

Nurses' beliefs and perceptions regarding family-centered care services in acute pediatric healthcare settings.

OBJECTIVES: To describe pediatrics nurses' beliefs about family-centered services (FCS) as a model of providing healthcare to children in acute care settings in Jordan. DESIGN AND METHODS: This is a cross-sectional descriptive study. Nurses who provide direct acute care to children (n = 246) completed the 'Measure of Beliefs about Participation in Family-Centered Service' questionnaire. Descriptive statistics were used to describe nurses' beliefs about participation, practical feasibility, implementation self-efficacy, principles, and potential adverse outcomes of FCS. RESULTS: Many nurses feel confident (70%) about their ability to work with others in providing FCS and perceive having the ability to operate according to family-centered care (FCC) principles (68%). Many (75%) nurses believed parents should be encouraged to decide how much they want to be involved in the child's care. However, only 46% of the nurses valued attending to family priorities if the health decisions made by the family differed from the healthcare providers' priorities. Many nurses (70%) believed that healthcare professionals' competencies and capacities to work utilizing FCC are more important than their personal preferences and opinion. CONCLUSIONS: The findings of this study clearly indicate that nurses positively viewed providing children's care within a FCS. This supports the efforts to reasonably integrate FCC as an operating model in the pediatric healthcare settings in Jordan. PRACTICE IMPLICATIONS: FCS is a complex task requiring integrating multidisciplinary effort and healthcare providers' positive attitudes toward families as care partners. Steps should help maximize the organizational resources to facilitate family presence and create opportunities for professional-families partnerships for children's care.

Discordant prognosis of mismatch repair deficiency in colorectal and endometrial cancer reflects variation in antitumour immune response and immune escape.

Defective DNA mismatch repair (dMMR) causes elevated tumour mutational burden (TMB) and microsatellite instability (MSI) in multiple cancer types. dMMR/MSI colorectal cancers (CRCs) have enhanced T-cell infiltrate and favourable outcome; however, this association has not been reliably detected in other tumour types, including endometrial cancer (EC). We sought to confirm this and explore the underpinning mechanisms. We first meta-analysed CRC and EC trials that have examined the prognostic value of dMMR/MSI and confirmed that dMMR/MSI predicts better prognosis in CRC, but not EC, with statistically significant variation between cancers (hazard ratio [HR] = 0.63, 95% confidence interval [CI] = 0.54-0.73 versus HR = 1.15, 95% CI = 0.72-1.58; PINT = 0.02). Next, we studied intratumoural immune infiltrate in CRCs and ECs of defined MMR status and found that while dMMR was associated with increased density of tumour-infiltrating CD3+ and CD8+ T-cells in both cancer types, the increases were substantially greater in CRC and significant only in this group (PINT = 4.3e-04 and 7.3e-03, respectively). Analysis of CRC and EC from the independent Cancer Genome Atlas (TCGA) series revealed similar variation and significant interactions in proportions of tumour-infiltrating lymphocytes, CD8+ , CD4+ , NK cells and immune checkpoint expression, confirming a more vigorous immune response to dMMR/MSI in CRC than EC. Agnostic analysis identified the IFNγ pathway activity as strongly upregulated by dMMR/MSI in CRC, but downregulated in EC by frequent JAK1 mutations, the impact of which on IFNγ response was confirmed by functional analyses. Collectively, our results confirm the discordant prognosis of dMMR/MSI in CRC and EC and suggest that this relates to differences in intratumoural immune infiltrate and tumour genome. Our study underscores the need for tissue-specific analysis of cancer biomarkers and may help inform immunotherapy use. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

The Yeast Permease Agp2 Senses Cycloheximide and Undergoes Degradation That Requires the Small Protein Brp1-Cellular Fate of Agp2 in Response to Cycloheximide.

The Saccharomyces cerevisiae Agp2 is a plasma membrane protein initially reported to be an uptake transporter for L-carnitine. Agp2 was later rediscovered, together with three additional proteins, Sky1, Ptk2, and Brp1, to be involved in the uptake of the polyamine analogue bleomycin-A5, an anticancer drug. Mutants lacking either Agp2, Sky1, Ptk2, or Brp1 are extremely resistant to polyamines and bleomycin-A5, suggesting that these four proteins act in the same transport pathway. We previously demonstrated that pretreating cells with the protein synthesis inhibitor cycloheximide (CHX) blocked the uptake of fluorescently labelled bleomycin (F-BLM), raising the possibility that CHX could either compete for F-BLM uptake or alter the transport function of Agp2. Herein, we showed that the agp2Δ mutant displayed striking resistance to CHX as compared to the parent, suggesting that Agp2 is required to mediate the physiological effect of CHX. We examined the fate of Agp2 as a GFP tag protein in response to CHX and observed that the drug triggered the disappearance of Agp2 in a concentration- and time-dependent manner. Immunoprecipitation analysis revealed that Agp2-GFP exists in higher molecular weight forms that were ubiquitinylated, which rapidly disappeared within 10 min of treatment with CHX. CHX did not trigger any significant loss of Agp2-GFP in the absence of the Brp1 protein; however, the role of Brp1 in this process remains elusive. We propose that Agp2 is degraded upon sensing CHX to downregulate further uptake of the drug and discuss the potential function of Brp1 in the degradation process.

Selective Killing of BRCA2-Deficient Ovarian Cancer Cells via MRE11 Blockade.

The MRE11 nuclease is essential during DNA damage recognition, homologous recombination, and replication. BRCA2 plays important roles during homologous recombination and replication. Here, we show that effecting an MRE11 blockade using a prototypical inhibitor (Mirin) induces synthetic lethality (SL) in BRCA2-deficient ovarian cancer cells, HeLa cells, and 3D spheroids compared to BRCA2-proficient controls. Increased cytotoxicity was associated with double-strand break accumulation, S-phase cell cycle arrest, and increased apoptosis. An in silico analysis revealed Mirin docking onto the active site of MRE11. While Mirin sensitises DT40 MRE11+/- cells to the Top1 poison SN-38, it does not sensitise nuclease-dead MRE11 cells to this compound confirming that Mirin specifically inhibits Mre11 nuclease activity. MRE11 knockdown reduced cell viability in BRCA2-deficient PEO1 cells but not in BRCA2-proficient PEO4 cells. In a Mirin-resistant model, we show the downregulation of 53BP1 and DNA repair upregulation, leading to resistance, including in in vivo xenograft models. In a clinical cohort of human ovarian tumours, low levels of BRCA2 expression with high levels of MRE11 co-expression were linked with worse progression-free survival (PFS) (p = 0.005) and overall survival (OS) (p = 0.001). We conclude that MRE11 is an attractive SL target, and the pharmaceutical development of MRE11 inhibitors for precision oncology therapeutics may be of clinical benefit.

The synbiotic mixture of Bacillus licheniformis and Saccharomyces cerevisiae extract aggravates dextran sulfate sodium induced colitis in rats.

BACKGROUND: Uncertain effects of probiotics and/or prebiotics have been reported in experimental and clinical colitis. This study aims to examine the effects of a synbiotic combination comprising Bacillus licheniformis DSM 17236 and Saccharomyces cerevisiae cell wall extract on dextran sulfate sodium (DSS)-induced colitis in Sprague Dawley rats. METHODS: Acute colitis was induced in rats by oral administration of DSS 3.5% for 7 days. Fifty rats were divided equally into five groups; one control group and the other groups were induced with colitis and treated with or without the tested synbiotic, mixed with diet, for 28 days and sulfasalazine (100 mg/kg) via intragastric tube once daily for 14 days. RESULTS: Symptomatically, the synbiotic administration raised the disease activity index (DAI) to comparable scores of the DSS group, specially from the 2nd to 7th days post DSS intoxication. It also induced a significant (p < 0.05) amplification of WBCs, myeloperoxidase (MPO), malondialdehyde (MDA), nuclear factor kappa B (NF-kB) expression and proinflammatory cytokines tumor necrosis factor alpha (TNFα), interferon gamma (INFγ), and interleukin-1 beta (IL-1ß) while depressed the antioxidant enzymes glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) when compared with the DSS and control groups. The DSS intoxicated and Synbiotic+DSS groups showed desquamations of the covering epithelium, noticeable diffuse leukocytic infiltrations, sever catarrhal enteritis, ischemic colitis with diffuse coagulative necrosis of the entire colonic mucosa. Contrarily, sulfasalazine proved to be effective in the reduction of the tested inflammatory markers and the pathological degenerative changes of the DSS ulcerative colitis. CONCLUSION: The examined synbiotic did not ameliorate but aggravated the DSS-induced colitis, so it should be subjected to intensive experimental and clinical testing before their use in animals and human.

Correlates of parental knowledge about smartphone exposure among young children.

BACKGROUND: Unhealthy smartphone habits use can impair the health of young children. Smartphone use among young children is affected by several factors of which the most important is parental knowledge pertains to smartphone exposure among young children. In Jordan, no studies have focused on this factor. METHOD: A nation-wide cross-sectional survey was distributed to parents of children aged <6 years to assess parental knowledge of smartphone exposure among young children and examine its correlates in Jordan. An online self-reporting questionnaire was administered via Survey Monkey and posted on social media platforms in June 2020. RESULTS: A total of 2,781 Jordanian parents completed the survey. During the pandemic the daily hours of Smartphone use among children were significantly higher than prior the coronavirus-2019 (COVID-19) pandemic (2.12 vs. 1.7 h). More than half the children exceeded the recommended daily hours of use. These results were positively associated with increased smartphone use among parents. Overall, the parents proved knowledgeable regarding the effects of excessive smartphone exposure on the health of their children. However, a knowledge deficit was evident in two areas: parental controls on smartphone and safe levels of infant smartphone exposure. The mothers possessed a significantly higher level of knowledge than the fathers. CONCLUSION: The results suggest that, in the context Jordan, increasing parental knowledge has the potential to reduce smartphone exposure among young children. Awareness campaigns are needed to enhance parental knowledge of smartphone exposure among young children and the use of parental controls on smartphones.

Can Cisplatin Therapy Be Improved? Pathways That Can Be Targeted.

Cisplatin (cis-diamminedichloroplatinum (II)) is the oldest known chemotherapeutic agent. Since the identification of its anti-tumour activity, it earned a remarkable place as a treatment of choice for several cancer types. It remains effective against testicular, bladder, lung, head and neck, ovarian, and other cancers. Cisplatin treatment triggers different cellular responses. However, it exerts its cytotoxic effects by generating inter-strand and intra-strand crosslinks in DNA. Tumour cells often develop tolerance mechanisms by effectively repairing cisplatin-induced DNA lesions or tolerate the damage by adopting translesion DNA synthesis. Cisplatin-associated nephrotoxicity is also a huge challenge for effective therapy. Several preclinical and clinical studies attempted to understand the major limitations associated with cisplatin therapy, and so far, there is no definitive solution. As such, a more comprehensive molecular and genetic profiling of patients is needed to identify those individuals that can benefit from platinum therapy. Additionally, the treatment regimen can be improved by combining cisplatin with certain molecular targeted therapies to achieve a balance between tumour toxicity and tolerance mechanisms. In this review, we discuss the importance of various biological processes that contribute to the resistance of cisplatin and its derivatives. We aim to highlight the processes that can be modulated to suppress cisplatin resistance and provide an insight into the role of uptake transporters in enhancing drug efficacy.

The frequency and clinical significance of DNA polymerase beta (POLß) expression in breast ductal carcinoma in situ (DCIS).

BACKGROUND: The prediction of clinical behaviour of breast ductal carcinoma in situ (DCIS) and its progression to invasive disease remains a challenge. Alterations of DNA damage repair mechanisms are associated with invasive breast cancer (BC). This study aims to assess the role of base excision repair (BER) DNA Polymerase Beta (POLß) in DCIS. METHODS: A cohort of DCIS comprising pure DCIS (n = 776) and DCIS coexisting with invasive BC (n = 239) were prepared as tissue microarrays. POLß protein expression was assessed using immunohistochemistry and correlated with clinicopathological parameters and patient outcome. Preclinically, we investigated the impact of POLß depletion on stem cell markers in representative DCIS cell line models. RESULTS: Reduced POLß expression was associated with aggressive DCIS features including high nuclear grade, comedo necrosis, larger tumour size, hormonal receptor negativity, HER2 overexpression and high Ki67 index. Combined low nuclear/low cytoplasmic POLß expression showed the strongest association with the features' characteristics of aggressive behaviour. There was a gradual reduction in the POLß expression from normal breast tissue, to DCIS, with the lowest expression observed in the invasive BC. Low POLß expression was an independent predictor of recurrence in DCIS patients treated with breast conserving surgery (BCS). POLß knockdown was associated with a significant increase in cell stemness markers including SOX2, NANOG and OCT4 levels in MCF10-DCIS cell lines. CONCLUSION: Loss of POLß in DCIS is associated with aggressive behaviour and it can predict recurrence. POLß expression in DCIS provides an additional feature for patients' risk stratification for personalised therapy.

"Resumption of Sexuality and Health Education in Postpartum Period: From Jordanian Health Care Professionals' Perspectives".

Objective: to explore Jordanian health care professionals' perspectives about sexual education after giving birth. Methods: a descriptive qualitative approach was used to address the study aim. A purposive sampling method was used to recruit seven midwives, 13 nurses and two obstetricians from three Primary Health Centres. The inclusion criteria were: midwives, nurses or obstetricians with at least two years' experience and currently working at a maternity health centre. Focus group discussions were used to collect data. A manual Thematic Content Analysis Tool was used to analyse the data. Results: five major themes emerged. Silence; resumption of sexuality after giving birth/area of conflict; men's authority in resumption of sexuality; the importance of sexual education (what, when and whom) and suggestions for sexual education approaches. Conclusions: Healthcare professionals were hesitant to open sexuality topic with the women during antenatal and postnatal visits due to cultural limitations and lack of knowledge. Therefore, in a time of global migration, the healthcare professionals have the need to understand cultural differences in attitude towards health care issues involving sexuality.

Examining the associations between smartphone use and mother-infant bonding and family functioning: A survey design.

Excessive smartphone use has been found to be associated with dysfunctional social and family relations. While most studies of this phenomenon have focused on adolescent and adult addiction, none has yet to focus on mothers with infants. This study examined the association of excessive smartphone use with mother-infant bonding, maternal mental health, and family functioning in Jordan. The predictive value of the study variables with respect to the level of smartphone use was evaluated. A descriptive correlational cross-sectional survey design was used. A sample of 114 mothers with infants was interviewed in person and completed a web-based questionnaire. Approximately 16% reported using smartphones 5 to 14 hours per day; 6.7% described themselves as smartphone addicts. The results suggest that excessive smartphone use may be linked to unhealthy family functioning. No associations were found between smartphone use and mother-infant bonding or maternal mental health. Raising awareness of this linkage and limiting smartphone use are recommended as precautionary measures. Although this study failed to find any association between smartphone use and mother-infant bonding, further studies using empirical methods might have better success.

Clinicopathological significance of ataxia telangiectasia-mutated (ATM) kinase and ataxia telangiectasia-mutated and Rad3-related (ATR) kinase in MYC overexpressed breast cancers.

PURPOSE: MYC transcription factor has critical roles in cell growth, proliferation, metabolism, differentiation, transformation and angiogenesis. MYC overexpression is seen in about 15% of breast cancers and linked to aggressive phenotypes. MYC overexpression also induces oxidative stress and replication stress in cells. ATM signalling and ATR-mediated signalling are critical for MYC-induced DNA damage response. Whether ATM and ATR expressions influence clinical outcomes in MYC overexpressed breast cancers is unknown. METHODS: We investigated ATM, ATR and MYC at the transcriptional level [Molecular Taxonomy of Breast Cancer International Consortium cohort (n = 1950)] and at the protein level in the Nottingham series comprising 1650 breast tumours. We correlated ATM, ATR and MYC expressions to clinicopathological features and survival outcomes. RESULTS: In MYC over expressed tumours, high ATR or low ATM levels were associated with aggressive breast cancer features such as higher tumour grade, de-differentiation, pleomorphism, high mitotic index, high-risk Nottingham Prognostic Index, triple negative and basal-like breast cancers (all adjusted p values < 0.05). Tumours with low ATM or high ATR levels in conjunction with MYC overexpression also have worse overall breast cancer-specific survival (BCSS) (p value < 0.05). CONCLUSIONS: We conclude that ATR/ATM-directed stratification and personalisation of therapy may be feasible in MYC overexpressed breast cancer.

Predictors of breakfast skipping among 14 to 16 years old adolescents in Jordan: The influential role of mothers.

AIM: To assess the prevalence and identify the predictors of breakfast skipping among 14- to 16-year-old adolescents in Jordan, focusing on mother-related variables. BACKGROUND: Breakfast is an essential meal across one's entire lifespan and especially important during the adolescent years. The practice of skipping breakfast has become so prevalent among adolescents that it is now a well-documented nutritional problem. DESIGN: A descriptive cross-sectional correlational design. METHODS: A proportional cluster stratified sampling protocol was used to select 1896 adolescents and their mothers (1013) during the period of March to June 2016. A self-reported questionnaire was used to collect data on breakfast-skipping rates, the perceived reasons for this behavior, the perceived importance of consuming breakfast, and maternal encouragement of breakfast consumption. RESULTS: The prevalence of breakfast skipping was 34.3% among adolescents and 21.5% among their mothers. A significant association was found between breakfast skipping among adolescents and their mothers (χ2 [1, n = 998] = 37.90, P = .001). Maternal encouragement of breakfast consumption, gender, and adolescent perception of the importance of this meal were found to be significant predictors of adolescent breakfast skipping. CONCLUSION: The findings highlight the importance of involving mothers in developing nutritional health plans aimed at promoting regular breakfast consumption among adolescents.

Targeting ataxia telangiectasia-mutated- and Rad3-related kinase (ATR) in PTEN-deficient breast cancers for personalized therapy.

PURPOSE: Phosphate and tensin homolog (PTEN), a negative regulator of PI3K signaling, is involved in DNA repair. ATR is a key sensor of DNA damage and replication stress. We evaluated whether ATR signaling has clinical significance and could be targeted by synthetic lethality in PTEN-deficient triple-negative breast cancer (TNBC). METHODS: PTEN, ATR and pCHK1Ser345 protein level was evaluated in 1650 human breast cancers. ATR blockade by VE-821 was investigated in PTEN-proficient- (MDA-MB-231) and PTEN-deficient (BT-549, MDA-MB-468) TNBC cell lines. Functional studies included DNA repair expression profiling, MTS cell-proliferation assay, FACS (cell cycle progression & γH2AX accumulation) and FITC-annexin V flow cytometry analysis. RESULTS: Low nuclear PTEN was associated with higher grade, pleomorphism, de-differentiation, higher mitotic index, larger tumour size, ER negativity, and shorter survival (p values < 0.05). In tumours with low nuclear PTEN, high ATR and/or high pCHK1ser345 level was also linked to higher grade, larger tumour size and poor survival (all p values < 0.05). VE-821 was selectively toxic in PTEN-deficient TNBC cells and resulted in accumulation of double-strand DNA breaks, cell cycle arrest, and increased apoptosis. CONCLUSION: ATR signalling adversely impact survival in PTEN-deficient breast cancers. ATR inhibition is synthetically lethal in PTEN-deficient TNBC cells.

Maternal Sociodemographic Characteristics and Behaviors as Correlates of Preadolescent's Breakfast Habits.

PURPOSE: To explore factors affecting skipping breakfast rate, and to identify its perceived reasons among preadolescent students and their mothers in Jordan. DESIGN AND METHODS: Using cluster stratified sampling, preadolescent (10-11years) students (N=1915) and their mothers (N=1299) from 26 public and private schools completed a self-reported questionnaire. Breakfast skipping and its related habits were described. Children's and mothers' perceptions of regular breakfast eating and sociodemographic factors were analyzed in relation to breakfast skipping in children. RESULTS: Although the majority of both children and mothers perceived breakfast as very important, 23% of the children and mothers reported skipping breakfast. Male students skipped breakfast more than female students. Students whose mothers had a low level of education and students with a low value of breakfast consumption had a higher likelihood of skipping breakfast. Mothers' high value of breakfast and encouragement of children to eat breakfast were directly related to an increase in children's perceived importance of breakfast consumption. Preadolescents' and mothers' perceptions of the importance of breakfast and mothers' encouragement to eat breakfast were significant predictors of breakfast consumption among students. CONCLUSION: The high prevalence of breakfast skipping among students, and knowledge about association between mothers' perceived importance of breakfast consumption and encouragement highlighted the pivotal role of mothers in preadolescent's breakfast consumption. PRACTICAL IMPLICATIONS: The findings suggest that health care providers, including school health practitioners, are recommended to assess children's and mothers' perceived value of breakfast and to include mothers in health promotion interventions on breakfast consumption.

The Association Between Maternal Factors and Preadolescent Breakfast Skipping: The Mediating Role of Preadolescent Attitudes Toward Breakfast.

BACKGROUND: Although skipping breakfast is common among children and adolescents, daily breakfast consumption is a healthy habit that is particularly important in childhood. There is a link between children's attitudes toward breakfast, breakfast-skipping behaviors, and maternal factors. Evidence demonstrating a clear relationship between maternal factors and preadolescent attitudes and behaviors toward breakfast skipping is scarce. AIMS: This study aims to examine the mediation effect of preadolescent attitudes toward breakfast on the associations between maternal involvement (encouragement and control of breakfast eating) and preadolescent breakfast skipping. METHODS: A cross-sectional descriptive study was conducted across Jordan in public and private primary schools in 2015. A sample of 1,915 preadolescent students (10-11 years) and their mothers (N = 1,299) was generated through proportional cluster stratification sampling. The interrelationships were examined among the participants' demographics, the number of preadolescent skipped breakfasts during a given week, self-reported attitudes toward breakfast, and perceived maternal encouragement and control of breakfast-eating variables. RESULTS: Analysis revealed that preadolescent attitudes toward breakfast and mothers' involvement in preadolescent breakfast were negatively correlated with preadolescent breakfast skipping. Linear regressions revealed that maternal involvement (i.e., encouragement and control of breakfast eating, and educational attainment levels) was predictive of preadolescent attitudes toward breakfast consumption. Multiple regressions using bootstrapping analysis showed that preadolescent attitudes partially mediated the effect of mothers' control and encouragement of breakfast consumption over preadolescent breakfast-skipping behavior. LINKING EVIDENCE TO ACTION: Results suggest that preadolescent attitudes, maternal encouragement, and control of breakfast eating influenced preadolescent breakfast skipping. These findings emphasize the importance of carefully assessing preadolescent attitudes toward breakfast, maternal encouragement, and control of breakfast consumption when developing interventions aimed at reducing breakfast-skipping behavior.

Antioxidant activity of simvastatin prevents ifosfamide-induced nephrotoxicity.

Ifosfamide is an anticancer agent used largely in treatment of solid tumors. The mainstay dose-limiting toxicity of ifosfamide is nephrotoxicity. This is largely believde to be a result of ifosfamide-induced oxidative stress. In this study, we investigated the antioxidant activity of simvastatin and the possible protective role of simvastatin against ifosfamide induced nephrotoxicity. Thirty Sprague-Dawely rats were divided into five groups and given orally different drug combinations. Group I and II were regarded as control groups and received 0.1% DMSO and normal saline, respectively. Group III received ifosfamide at 50 mg/kg, group IV received simvastatin at 0.3 mg/kg and group V received both ifosfamide and simvastatin. All animals were decapitated 2 days after the last ifosfamide administration. Findings revealed that ifosfamide induced nephrotoxicity as indicated by a significant increase in plasma creatinine and lipid per oxidation. This increase was significantly inhibited in animals pretreated with simvastatin. Histopathological observations were in correlation with the biochemical parameters in that simvastatin minimized ifosfamide-induced renal tubular damage. The above results promote a future use of simvastatin in combination with ifosfamide in treatment of cancer patients to indicate that simvastatin protectics against ifosfamide-induced nephrotoxicity in terms of oxidative stress and might be given in combination.

Zizyphus jujuba protects against ibuprofen-induced nephrotoxicity in rats.

CONTEXT: Zizyphus jujuba Mill. (Rhamnaceae) has long been used for the treatment of anxiety and insomnia in Chinese traditional medicine. The edible part is the fruit. Different parts of Z. jujuba possess medicinal properties such as anti-inflammatory, anticancer and antifertility. OBJECTIVES: This study evaluated the therapeutic effect of Z. jujuba fruit aqueous extract (ZE) on nephrotoxicity induced by ibuprofen (IBP) in rats. MATERIALS AND METHODS: Male Sprague-Dawley rats were grouped as normal saline (control), ZE (500 mg/kg), IBP (400 mg/kg) and ZE + IBP-treated groups. After five days of oral administration, rats were sacrificed. The protective effect of ZE was evaluated by measuring kidney biomarkers, and histopathological changes of kidney were observed. Kidney antioxidant enzymes such as superoxide dismutase, catalase (CAT), glutathione S-transferase (GST) and lipid peroxidase were investigated. RESULTS: Administration of IBP resulted in a significant increase in urea and creatinine (p < 0.05) and a significant decrease in albumin and total protein (p < 0.05). Damage in glomeruli and proximal convoluted tubules was observed. IBP also increased CAT (p < 0.05) and GST (p < 0.001) activities compared to the control group. Administration of ZE with IBP significantly decreased serum urea and creatinine (p < 0.05) and reduced the severity of kidney damage. There was also a significant increase in the activities of CAT (p < 0.05) and GST (p < 0.001). DISCUSSION AND CONCLUSION: These results indicated that Z. jujuba aqueous extract could have a therapeutic role in reducing nephrotoxicity induced by ibuprofen.

Knowledge of stroke and the window period for thrombolytic therapy in ischemic stroke among South Indians: A hospital-based survey with educational intervention.

Objectives: The objective of this study was to determine the awareness of stroke in regards to the risk factors, warning symptoms, and knowledge of the therapeutic window period among varied strata of non-medical people attending a tertiary care center. Materials and Methods: The interventional study involved the collection of data regarding awareness of stroke using a structured questionnaire with a total score of 16. Pre-intervention assessment was followed by intervention in the form of education regarding awareness of stroke administered one-on-one for personalized and effective comprehension by subjects. Then, subjects were asked to recall the information that was delivered to them and were scored accordingly. Results: Among the 500 subjects included, 51% were female. About 76.8% of participants were young (age <50 years), and 83.4% were literate. Only 25.4% of participants were aware of the brain as the site of stroke. About 32.2% of candidates were aware of a few risk factors for stroke. Among them, the majority of participants were aware of hypertension (24%) as a risk factor. The most known warning symptom was "Numbness" or weakness of arm. The majority of the subjects (97.8%) were unaware of a therapeutic window period for stroke being 4.5 h or below. The mean pre-intervention score was 2.52 ± 1.65 while the mean post-intervention score was 15.10 ± 1.79 (P < 0.0001). Conclusion: The study showed that even among literate participants, only a meager number of subjects were aware of the golden window period of intravenous thrombolysis. Educational intervention by means of an in-person and one-on-one explanation achieved significant levels of understanding of stroke. The study could be used to formulate large-scale educational programs that focus on spreading awareness of symptoms and risk factors while also instilling the importance of timely medical intervention for efficient thrombolytic therapy.

Magnetically Integrated Tumor-Vascular Interface System to Mimic Pro-angiogenic Endothelial Dysregulations for On-Chip Drug Testing.

The tumor-vascular interface is a critical component of the tumor microenvironment that regulates all of the dynamic interactions between a growing tumor and the endothelial lining of the surrounding vasculature. In this paper, we report the design and development of a custom-engineered tumor-vascular interface system for investigating the early stage tumor-mediated pro-angiogenic dysfunctional behavior of the endothelium. Using representative endothelial cells and triple negative breast cancer cell lines, we established a biomimetic interface between a three-dimensional tumor tissue across a mature, functional endothelial barrier using a magnetically hybrid-integrated tumor-vascular interface system, wherein vasculature-like features containing a monolayer of endothelial cell culture on porous microfluidic channel surfaces were magnetically attached to tumor spheroids generated on a composite polymer-hydrogel microwell plate and embedded in a collagen matrix. Tumor-mediated endothelial microdynamics were characterized by their hallmark behavior such as loss of endothelial adherens junctions, increased cell density, proliferation, and changes in cell spreading and corroborated with endothelial YAP/TAZ nuclear translocation. We further confirm the feasibility of drug-mediated reversal of this pro-angiogenic endothelial organization through two different signaling mechanisms, namely, inhibition of the vascular endothelial growth factor pathway and the Notch signaling pathway, thereby demonstrating the utility of the tumor-vascular interface platform for rapid, early stage prediction of antiangiogenic drug efficacy. Overall, our work emphasizes the importance of our strategic engineering approach for identifying some unique, physiologically relevant aspects of the tumor-vascular interface, which are otherwise difficult to implement using standard in vitro approaches.