The Grizzly, February 3, 1984

Chancellor Helfferich Dies At 85 • Book Situation Better But Not Great • First Year Job Seminar Held • Workshops To Be Held • Gibson To Speak • Electron Scope: DOA • Richter Proud Of Ursinus College • Remembering Helfferich • Lantern Enters National Competition • Letter To The Editor • Wellness Week At Ursinus • Forum Starts Semester • Allen Flick Is No Sleeper • UC Appoints New Vice Presidents • Red and Gold Days Prove Successful • Coffee-House Blues • Evening Of The Absurd At Ursinus • Buddy Holly 25 Years Ago Today • French Film Tickles Viewers • Evening Course At Ursinus • WRUC Increases Audience • Old Men\u27s Gets New Machines • Bears Hoopsters Hit a Cold Spell • Aquabears Crush Opponents As They Roll to MAC • Winning Streak in Fencing Continues • Aquabearettes Drown Widener • Lady Bears Bid For Strong Finish • Gymnasts Show Potential • Wrestlers Vie For MAC Championshiphttps://digitalcommons.ursinus.edu/grizzlynews/1111/thumbnail.jp

Communication, inclusion and psychological wellbeing among deaf and hard of hearing children: A qualitative study in the Gaza Strip.

Deaf and hard of hearing children are at risk of exclusion from community life and education, which may increase their risk of mental health conditions. This study explores the experience of deaf and hard of hearing children in the Gaza Strip, with particular focus on the factors that contribute to psychological wellbeing and distress. In-depth interviews were conducted with 17 deaf and hard of hearing children, 10 caregivers of deaf and hard of hearing children and eight teachers of deaf and hard of hearing children in mainstream and special schools, across the Gaza Strip. Further, three focus group discussions were held with deaf and hard of hearing adults and disability leaders, mental health specialists and other teachers of deaf and hard of hearing children. Data collection was completed in August 2020. Key themes identified in the analysis included lack of accessible communication, community exclusion, negative attitudes towards hearing impairment and deafness and the impact on deaf and hard of hearing children's sense of self, and limited family knowledge on hearing impairment and deafness. Further findings focused on strategies to improve the inclusion of deaf and hard of hearing children and how to promote wellbeing. In conclusion, participants in this study believed that deaf and hard of hearing children in the Gaza Strip are at increased risk of mental health conditions. Changes are needed across community and government structures, including education systems, to promote the inclusion of deaf and hard of hearing children and to support their psychological wellbeing. Recommendations from the findings include increasing efforts to improve awareness and reduce stigma, providing better access to sign language for deaf and hard of hearing children, and offering training for teachers of deaf and hard of hearing children, especially in mainstream environments

Coronary CT Angiography and 5-Year Risk of Myocardial Infarction.

BACKGROUND: Although coronary computed tomographic angiography (CTA) improves diagnostic certainty in the assessment of patients with stable chest pain, its effect on 5-year clinical outcomes is unknown. METHODS: In an open-label, multicenter, parallel-group trial, we randomly assigned 4146 patients with stable chest pain who had been referred to a cardiology clinic for evaluation to standard care plus CTA (2073 patients) or to standard care alone (2073 patients). Investigations, treatments, and clinical outcomes were assessed over 3 to 7 years of follow-up. The primary end point was death from coronary heart disease or nonfatal myocardial infarction at 5 years. RESULTS: The median duration of follow-up was 4.8 years, which yielded 20,254 patient-years of follow-up. The 5-year rate of the primary end point was lower in the CTA group than in the standard-care group (2.3% [48 patients] vs. 3.9% [81 patients]; hazard ratio, 0.59; 95% confidence interval [CI], 0.41 to 0.84; P=0.004). Although the rates of invasive coronary angiography and coronary revascularization were higher in the CTA group than in the standard-care group in the first few months of follow-up, overall rates were similar at 5 years: invasive coronary angiography was performed in 491 patients in the CTA group and in 502 patients in the standard-care group (hazard ratio, 1.00; 95% CI, 0.88 to 1.13), and coronary revascularization was performed in 279 patients in the CTA group and in 267 in the standard-care group (hazard ratio, 1.07; 95% CI, 0.91 to 1.27). However, more preventive therapies were initiated in patients in the CTA group (odds ratio, 1.40; 95% CI, 1.19 to 1.65), as were more antianginal therapies (odds ratio, 1.27; 95% CI, 1.05 to 1.54). There were no significant between-group differences in the rates of cardiovascular or noncardiovascular deaths or deaths from any cause. CONCLUSIONS: In this trial, the use of CTA in addition to standard care in patients with stable chest pain resulted in a significantly lower rate of death from coronary heart disease or nonfatal myocardial infarction at 5 years than standard care alone, without resulting in a significantly higher rate of coronary angiography or coronary revascularization. (Funded by the Scottish Government Chief Scientist Office and others; SCOT-HEART ClinicalTrials.gov number, NCT01149590 .)

All-trans retinoic acid (ATRA)-induced TFEB expression is required for myeloid differentiation in acute promyelocytic leukemia (APL)

© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Objective: In acute promyelocytic leukemia (APL), normal retinoid signaling is disrupted by an abnormal PML-RARα fusion oncoprotein, leading to a block in cell differentiation. Therapeutic concentrations of all-trans-retinoic acid (ATRA) can restore retinoid-induced transcription and promote degradation of the PML-RARα protein. Autophagy is a catabolic pathway that utilizes lysosomal machinery to degrade intracellular material and facilitate cellular re-modeling. Recent studies have identified autophagy as an integral component of ATRA-induced myeloid differentiation. Methods: As the molecular communication between retinoid signaling and the autophagy pathway is not defined, we performed RNA sequencing of NB4 APL cells treated with ATRA and examined autophagy-related transcripts. Results: ATRA altered the expression of >80 known autophagy-related transcripts, including the key transcriptional regulator of autophagy and lysosomal biogenesis, TFEB (11.5-fold increase). Induction of TFEB and its transcriptional target, sequestosome 1 (SQSTM1, p62), is reduced in ATRA-resistant NB4R cells compared to NB4 cells. TFEB knockdown in NB4 cells alters the expression of transcriptional targets of TFEB and reduces CD11b transcript levels in response to ATRA. Conclusions: We show for the first time that TFEB plays an important role in ATRA-induced autophagy during myeloid differentiation and that autophagy induction potentiates leukemic cell differentiation (Note: this study includes data obtained from NCT00195156, https://clinicaltrials.gov/show/NCT00195156)

All-Trans-Retinoic Acid Combined With Valproic Acid Can Promote Differentiation in Myeloid Leukemia Cells by an Autophagy Dependent Mechanism

Acute myeloid leukemia (AML) is an aggressive blood cancer with an overall survival of 30%. One form of AML, acute promyelocytic leukemia (APL) has become more than 90% curable with differentiation therapy, consisting of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO). Application of differentiation therapy to other AML subtypes would be a major treatment advance. Recent studies have indicated that autophagy plays a key role in the differentiation of ATRA-responsive APL cells. In this study, we have investigated whether differentiation could be enhanced in ATRA resistant cells by promoting autophagy induction with valproic acid (VPA). ATRA sensitive (NB4) and resistant leukemia cells (NB4R and THP-1) were co-treated with ATRA and valproic acid, followed by assessment of autophagy and differentiation. The combination of VPA and ATRA induced autophagic flux and promoted differentiation in ATRA-sensitive and -resistant cell lines. shRNA knockdown of ATG7 and TFEB autophagy regulators impaired both autophagy and differentiation, demonstrating the importance of autophagy in the combination treatment. These data suggest that ATRA combined with valproic acid can promote differentiation in myeloid leukemia cells by mechanism involving autophagy

A large-scale and PCR-referenced vocal audio dataset for COVID-19

The UK COVID-19 Vocal Audio Dataset is designed for the training and evaluation of machine learning models that classify SARS-CoV-2 infection status or associated respiratory symptoms using vocal audio. The UK Health Security Agency recruited voluntary participants through the national Test and Trace programme and the REACT-1 survey in England from March 2021 to March 2022, during dominant transmission of the Alpha and Delta SARS-CoV-2 variants and some Omicron variant sublineages. Audio recordings of volitional coughs, exhalations, and speech were collected in the 'Speak up to help beat coronavirus' digital survey alongside demographic, self-reported symptom and respiratory condition data, and linked to SARS-CoV-2 test results. The UK COVID-19 Vocal Audio Dataset represents the largest collection of SARS-CoV-2 PCR-referenced audio recordings to date. PCR results were linked to 70,794 of 72,999 participants and 24,155 of 25,776 positive cases. Respiratory symptoms were reported by 45.62% of participants. This dataset has additional potential uses for bioacoustics research, with 11.30% participants reporting asthma, and 27.20% with linked influenza PCR test results.Comment: 37 pages, 4 figure

Consensus Guidelines for Delineation of Clinical Target Volume for Intensity-Modulated Pelvic Radiotherapy in Postoperative Treatment of Endometrial and Cervical Cancer

To develop an atlas of the clinical target volumes (CTV) definitions for the post-operative radiotherapy of endometrial and cervical cancer to be utilized for planning pelvic Intensity Modulated Radiation Therapy (IMRT)

Induction of autophagy is a key component of all-trans-retinoic acid-induced differentiation in leukemia cells and a potential target for pharmacological modulation

Acute myeloid leukemia (AML) is characterized by the accumulation of immature blood cell precursors in the bone marrow. Pharmacologically overcoming the differentiation block in this condition is an attractive therapeutic avenue, which has achieved success only in a subtype of AML, acute promyelocytic leukemia (APL). Attempts to emulate this success in other AML subtypes have thus far been unsuccessful. Autophagy is a conserved protein degradation pathway with important roles in mammalian cell differentiation, particularly within the hematopoietic system. In the study described here, we investigated the functional importance of autophagy in APL cell differentiation. We found that autophagy is increased during all-trans-retinoic acid (ATRA)-induced granulocytic differentiation of the APL cell line NB4 and that this is associated with increased expression of LC3II and GATE-16 proteins involved in autophagosome formation. Autophagy inhibition, using either drugs (chloroquine/3-methyladenine) or short-hairpin RNA targeting the essential autophagy gene ATG7, attenuates myeloid differentiation. Importantly, we found that enhancing autophagy promotes ATRA-induced granulocytic differentiation of an ATRA-resistant derivative of the non-APL AML HL60 cell line (HL60-Diff-R). These data support the development of strategies to stimulate autophagy as a novel approach to promote differentiation in AML

UK consensus guidelines for the delivery of unexpected news in obstetric ultrasound: The ASCKS framework

Background: Studies indicate there is a need to improve the delivery of unexpected news via obstetric ultrasound, but there have been few advances in this area. One factor preventing improvement has been a lack of consensus regarding the appropriate phrases and behaviours which sonographers and ultrasound practitioners should use in these situations. Aims: To develop consensus guidelines for unexpected news delivery in Early Pregnancy Unit and Fetal Anomaly Screening Programme NHS settings. Methods: A workshop was conducted to identify priorities and reach consensus on areas of contention. Contributors included interdisciplinary healthcare professionals, policy experts, representatives from third-sector organisations, lay experts and academic researchers (n = 28). Written and verbal feedback was used to draft initial guidance which was then circulated amongst the wider writing group (n = 39). Revisions were undertaken until consensus was reached. Results: Consensus guidelines were developed outlining the behaviours and phrases which should be used during scans where unexpected findings are identified. Specific recommendations included that: honest and clear communication should be prioritised, even with uncertain findings; technical terms should be used, but these should be written down together with their lay interpretations; unless expectant parents use other terminology (e.g. ‘foetus’), the term ‘baby’ should be used as a default, even in early pregnancy; at the initial news disclosure, communication should focus on information provision. Expectant parents should not be asked to make decisions during the scan. Conclusions: These recommendations can be used to develop and improve news delivery interventions in obstetric ultrasound settings. The full guidelines can be accessed online as supplemental material and at https://doi.org/10.5518/100/24

MicroRNA-34a is a potent tumor suppressor molecule in vivo in neuroblastoma

<p>ABSTRACT</p> <p>Background</p> <p>Neuroblastoma is a paediatric cancer which originates from precursor cells of the sympathetic nervous system and accounts for 15% of childhood cancer mortalities. With regards to the role of miRNAs in neuroblastoma, miR-34a, mapping to a chromosome 1p36 region that is commonly deleted, has been found to act as a tumor suppressor through targeting of numerous genes associated with cell proliferation and apoptosis.</p> <p>Methods</p> <p>A synthetic miR-34a (or negative control) precursor molecule was transfected into NB1691^lucand SK-N-AS^lucneuroblastoma cells. Quantitative PCR was used to verify increased miR-34a levels in NB1691^lucand SK-N-AS^luccell lines prior to <it>in vitro </it>and <it>in vivo </it>analysis. <it>In vitro </it>analysis of the effects of miR-34a over expression on cell growth, cell cycle and phosphoprotein activation in signal transduction pathways was performed. Neuroblastoma cells over expressing miR-34a were injected retroperitoneally into immunocompromised CB17-SCID mice and tumor burden was assessed over a 21 day period by measuring bioluminescence (photons/sec/cm²).</p> <p>Results</p> <p>Over expression of miR-34a in both NB1691^lucand SK-N-AS^lucneuroblastoma cell lines led to a significant decrease in cell number relative to premiR-negative control treated cells over a 72 hour period. Flow cytometry results indicated that miR-34a induced cell cycle arrest and subsequent apoptosis activation. Phosphoprotein analysis highlighted key elements involved in signal transduction, whose activation was dysregulated as a result of miR-34a introduction into cells. As a potential mechanism of miR-34a action on phosphoprotein levels, we demonstrate that miR-34a over-expression results in a significant reduction of <it>MAP3K9 </it>mRNA and protein levels. Although <it>MAP3K9 </it>is a predicted target of miR-34a, direct targeting could not be validated with luciferase reporter assays. Despite this fact, any functional effects of reduced MAP3K9 expression as a result of miR-34a would be expected to be similar regardless of the mechanism involved. Most notably, <it>in vivo </it>studies showed that tumor growth was significantly repressed after exogenous miR-34a administration in retroperitoneal neuroblastoma tumors.</p> <p>Conclusion</p> <p>We demonstrate for the first time that miR-34a significantly reduces tumor growth in an <it>in vivo </it>orthotopic murine model of neuroblastoma and identified novel effects that miR-34a has on phospho-activation of key proteins involved with apoptosis.</p