Miracle-dz/UniFAR-FTUs huggingface dataset:
Resolution of hyperacusis associated with depression, following lithium administration and directive counselling

Abstract Introduction: Hyperacusis may be described as a decreased threshold for discomfort from sound. It may have a serious impact on an individual's lifestyle, as a result of decreased sociability and inability to spend time with family and friends due to intolerance of sound. Subject: We present a case of hyperacusis associated with depression, with no other audiological abnormality. The patient reported greater difficulty during the depressive episode. Method: Audiological investigation was undertaken, followed by counselling and medication for depression. Results and conclusion: The pathophysiological mechanism of hyperacusis in depression is discussed. Outcomes following treatment with directive counselling and lithium (an antidepressant) are described. Research indicates that both hyperacusis and depression can be caused by hypoactivity of 5-hydroxytryptamine (also known as serotonin) in the brain. The patient reported improvement which cannot be explained solely on the basis of counselling. Enhancement of serotonin activity due to lithium, prescribed for depression, may also play a role in alleviation of hyperacusis.
Identification of a core TP53 transcriptional program with highly distributed tumor suppressive activity

The tumor suppressor TP53 is the most frequently mutated gene product in human cancer. Close to half of all solid tumors carry inactivating mutations in the TP53 gene, while in the remaining cases, TP53 activity is abrogated by other oncogenic events, such as hyperactivation of its endogenous repressors MDM2 or MDM4. Despite identification of hundreds of genes regulated by this transcription factor, it remains unclear which direct target genes and downstream pathways are essential for the tumor suppressive function of TP53. We set out to address this problem by generating multiple genomic data sets for three different cancer cell lines, allowing the identification of distinct sets of TP53-regulated genes, from early transcriptional targets through to late targets controlled at the translational level. We found that although TP53 elicits vastly divergent signaling cascades across cell lines, it directly activates a core transcriptional program of ∼100 genes with diverse biological functions, regardless of cell type or cellular response to TP53 activation. This core program is associated with high-occupancy TP53 enhancers, high levels of paused RNA polymerases, and accessible chromatin. Interestingly, two different shRNA screens failed to identify a single TP53 target gene required for the anti-proliferative effects of TP53 during pharmacological activation in vitro. Furthermore, bioinformatics analysis of thousands of cancer genomes revealed that none of these core target genes are frequently inactivated in tumors expressing wild-type TP53. These results support the hypothesis that TP53 activates a genetically robust transcriptional program with highly distributed tumor suppressive functions acting in diverse cellular contexts.
Lordose lombar: estudo dos valores angulares e da participação dos corpos vertebrais e discos intervertebrais

The angular value of lumbar lordosis and the role of vertebral bodies and intervertebral discs in its constitution were studied in normal individuals. X-Ray images of lumbar spine were studied in 350 normal and asymptomatic individuals, ages ranging from 18 to 50 years old (average 29.0 years old ± 8.24), being 143 males and 207 females. The lumbosacral (L1S1) and the lumbolumbar (L1L5) curves were measured. Measurements for lumbar curves and their components presented a large variation. Average values of -61o were seen for lumbosacral curve and of -45o for lumbolumbar curve. Vertebral bodies measurements presented kyphotic values for L1, neutral for L2, and progressively lordotic for L3 - L5. Intervertebral discs presented a progressive lordotic angulation from L1-L2. Caudal elements of curvature, intervertebral discs L4-L5 and L5-S1 and the vertebral body L5 accounted for nearly 60% of the angular measurement of lumbosacral curvature. A significant difference was seen between males and females for lumbar curvature measurements, and for vertebral bodies L2 and L4, with females presenting higher values. Age-related differences were found in lumbar curvature and vertebral bodies measurements.
Diretrizes para cessação do tabagismo - 2008

These guidelines are an up-to-date and comprehensive tool to aid health professionals in treating smokers, recommending measures and strategies for managing each case based on clinical evidence. Written in a simplified and objective manner, the text is divided into two principal sections: Evaluation and Treatment. The sections both present comments on and levels of evidence represented by the references cited, as well as some proposals for the reduction of damage and for intervening in specific and still poorly explored situations, such as relapse, passive smoking, physician smoking, and tobacco use in specific environments.
NNK reduction pathway gene polymorphisms and risk of lung cancer

The tobacco‐specific nitrosamine NNK is a potent carcinogen found in tobacco smoke and implicated in the development of lung cancer. The major route of NNK metabolism is carbonyl reduction by AKR1C1, AKR1C2, CBR1, and 11β‐HSD1 to form NNAL. This study investigated the potential role of variants in this pathway on lung cancer risk by examining 53 tag‐SNPs representing the common variations in AKR1C1, AKR1C2, CBR1, and HSD11B1 in 456 lung cancer cases and 807 controls. One SNP in CBR1 (rs2835267) was significantly associated with overall risk of lung cancer, but did not pass multiple testing adjustment (OR: 0.76 95% CI: 0.58–0.99, P = 0.048, FDR P = 0.20). After stratification and multiple testing correction, three SNPs showed significance. One SNP (rs2835267) in CBR1 showed a significant decreased risk for smokers with a high pack‐years (OR: 0.3595% CI: 0.17–0.69, P = 0.018) and in SCC (OR: 0.4895% CI: 0.29–0.76, P = 0.018). Another SNP located in CBR1 (rs3787728) also showed a significant decreased risk in SCC (OR: 0.4695% CI: 0.26–0.80, P = 0.024) and small cell carcinoma (only in current smokers) (OR: 0.06895% CI: 0.01–0.42, P = 0.028). The HSD11B1 SNP (rs4844880) showed a significant increased risk for adenocarcinoma within former smokers (OR: 3.9495% CI: 1.68–9.22, P = 0.011). Haplotype analysis found significance with six haplotypes and lung cancer risk. These findings indicate that select variants in genes in the carbonyl reduction pathway of NNK may alter the risk of lung cancer. © 2014 Wiley Periodicals, Inc.
Perioperative Blood Management Strategies for Total Knee Arthroplasty

Total knee arthroplasty (TKA) often causes a significant amount of blood loss with an accompanying decline in hemoglobin and may increase the frequency of allogeneic blood transfusion rates. Unfortunately, allogeneic blood transfusions have associated risks including postoperative confusion, infection, cardiac arrhythmia, fluid overload, increased length of hospital stay, and increased mortality. Other than reducing the need for blood transfusions, reducing perioperative blood loss in TKA may also minimize intra‐articular hemorrhage, limb swelling, and postoperative pain, and increase the range of motion during the early postoperative period. These benefits improve rehabilitation success and increase patients’ postoperative satisfaction. Preoperative anemia, coupled with intraoperative and postoperative blood loss, is a major factor associated with higher rates of blood transfusion in TKA. Thus, treatment of preoperative anemia and prevention of perioperative blood loss are the primary strategies for perioperative blood management in TKA. This review, combined with current evidence, analyzes various methods of blood conservation, including preoperative, intraoperative, and postoperative methods, in terms of their effectiveness, safety, and cost. Because many factors can be controlled to reduce blood loss and transfusion rates in TKA, a highly efficient, safe, and cost‐effective blood management strategy can be constructed to eliminate the need for transfusions associated with TKA.
Does Specialized Inpatient Rehabilitation Affect Whether or Not People with Traumatic Spinal Cord Injury Return Home?

Return to living at home is an important patient-reported outcome following traumatic spinal cord injury (tSCI). Specialized inpatient rehabilitation assists such patients in maximizing function and independence. Our project aim was to describe those patients receiving specialized rehabilitation after tSCI in Canada, and to determine if such rehabilitation improved the likelihood of returning home. This cohort study utilized data from the Rick Hansen Spinal Cord Injury Registry (RHSCIR) to identify patients with tSCI discharged from 1 of 18 participating acute specialized spine facilities between 2011 and 2015 to either 1 of 13 participating specialized rehabilitation facilities, or to another discharge destination. To determine if specialized rehabilitation affected likelihood of returning home, multiple logistic regressions and propensity score matchings were performed to account for age at injury, gender, neurological severity and level, acute length of stay (LOS), and region of residence. The χ2 test was used to compare rate of return home between matched groups. Of the 1599 patients included, 71% received specialized rehabilitation. Receiving specialized rehabilitation was a significant and strong predictor of return to home after controlling for covariates (adjusted odds ratio = 3.1; 95% confidence interval [CI], 1.6-5.9). The rate of return to home was significantly higher in the matched rehabilitation group than the no rehabilitation group (98% vs. 87%, p = 0.0004). For the matched patients, an extra 11 patients returned home for every 100 patients receiving specialized rehabilitation. However, effect of age on returning home requires further investigation. Improving access to specialized rehabilitation could potentially reduce discharges to nursing homes or other non-home destinations.
Neuronal correlates of fear conditioning in the bed nucleus of the stria terminalis

Lesion and inactivation studies indicate that the central amygdala (CeA) participates in the expression of cued and contextual fear, whereas the bed nucleus of the stria terminalis (BNST) is only involved in the latter. The basis for this functional dissociation is unclear because CeA and BNST form similar connections with the amygdala and brainstem fear effectors. To address this question, we recorded neurons in the anterolateral (AL) and anteromedial (AM) regions of BNST in rats subjected to auditory fear conditioning. During habituation, few neurons were responsive to the conditioned stimulus (CS). After fear conditioning, 20% of BNST-AL neurons developed inhibitory responses to the CS. In BNST-AM, 26% of neurons developed positive CS responses. The behavior of BNST-AM and -AL neurons during contextual fear paralleled their CS responsiveness: More BNST-AM neurons fired at higher rates during contextual freezing than movement, whereas the opposite was seen in BNST-AL cells. These findings point to regional differences in the activity of BNST-AL and -AM in relation to learned fear, raising the possibility that they exert opposite influences on fear output networks. However, given the similar behavior of BNST-AM and -AL neurons in relation to cued and contextual fear, it remains unclear why lesion and inactivation of BNST differentially affect these two types of fear. Either neurons in a different BNST sector, not explored here, show a different activity profile in relation to the two forms of fear or inactivation/lesion studies inadvertently affected a structure adjacent to BNST, which is involved in contextual fear.
PAC exhibits potent anti‐colon cancer properties through targeting cyclin D1 and suppressing epithelial‐to‐mesenchymal transition

Colorectal cancer (CRC) is a major cause of cancer morbidity and mortality worldwide. Although response rates and overall survival have been improved in recent years, resistance to multiple drug combinations is inevitable. Therefore, the development of more efficient drugs, with fewer side effects is urgently needed. To this end, we have investigated in the present report the effect of PAC, a novel cucumin analogue, on CRC cells both in vitro and in vivo. We have shown that PAC induces apoptosis, mainly via the internal mitochondrial route, and inhibits cell proliferation through delaying the cell cycle at G2/M phase. Interestingly, the pro‐apoptotic effect was mediated through STAT3‐dependent down‐regulation of cyclin D1 and its downstream target survivin. Indeed, change in the expression level of cyclin D1 modulated the expression of survivin and the response of CRC cells to PAC. Furthermore, using the ChIP assay, we have shown PAC‐dependent reduction in the binding of STAT3 to the cyclin D1 promoter in vivo. Additionally, PAC suppressed the epithelial‐to‐mesenchymal process through down‐regulating the mesenchymal markers (N‐cadherin, vimentin and Twist1) and inhibiting the invasion/migration abilities of the CRC cells via repressing the pro‐migration/invasion protein kinases AKT and ERK1/2. In addition, PAC inhibited tumor growth and repressed the JAK2/STAT3, AKT/mTOR and MEK/ERK pathways as well as their common downstream effectors cyclin D1 and survivin in humanized CRC xenografts. Collectively, these results indicate that PAC has potent anti‐CRC effects, and therefore could constitute an effective alternative chemotherapeutic agent, which may consolidate the adjuvant treatment of colon cancer. © 2015 Wiley Periodicals, Inc.
Audit of handover in an ENT unit.

OBJECTIVES To analyse the completeness and accuracy of the written handover in our ENT department, in line with Royal College of Surgeons of England guidance, and to improve standards. SETTING University Hospital, Cumberland Infirmary, Carlisle, UK. METHODS AND RESULTS We prospectively analysed the written handover over two periods (of 30 and 18 days each). In the first period, the morning handover was present and complete on 77 per cent of days, present but incomplete or illegible on 6 per cent of days, and absent on 17 per cent of days; the evening handover was present and complete on 30 per cent of days, and absent on 67 per cent of days. To improve standards, we emphasised the importance of accurate handover to the ENT team and to junior doctors who cross-covered ENT. A reminder of the Royal College of Surgeons of England guidance was included in the handover book, and junior doctors received regular feedback. CONCLUSION We demonstrated a substantial improvement in the quality and completeness of written handover, comparing the second and first audit periods.
Adiponectin induces CXCL1 secretion from cancer cells and promotes tumor angiogenesis by inducing stromal fibroblast senescence

Adiponectin is an adipocyte‐specific adipocytokine with proliferative and pro‐angiogenic effects that regulates many biological processes, including immunity, insulin resistance, and inflammation. The oncogenic role of adiponectin has been implicated in several cancer types. Stromal cells within tumor contribute tumor growth and angiogenesis; however, it is not clear that how adiponectin regulates stromal cell‐mediated tumorigenesis. In this study, using the tumor xenograft models, we demonstrated that tumor development was severely impaired in mouse subcutaneous cancer tissue and metastasis tumor tissue in adiponectin knockout mice. Our results indicated adiponectin deficiency resulted in decrease of blood vessel and stromal senescent fibroblasts in subcutaneous and metastasis tumor tissue. These observations were confirmed in vitro, in which co‐cultured tumor cells and fibroblasts treated with adiponectin promoted ECs tube formation. A secretion of CXCL1 by adiponectin‐treated tumor cells was observed during the process of inducing stromal fibroblast senescence. Furthermore, stromal cells senescence was through p53 and p16 pathways. Taken together, our results indicate that adiponectin promotes stromal cell senescence within invasive colon cancer contributing to angiogenesis and tumor growth in part through the production of CXCL1 and may serve as a therapeutic target for tumor patients. © 2015 Wiley Periodicals, Inc.
δ Subunit-containing GABAA receptor prevents overgeneralization of fear in adult mice

The role of δ subunit-containing GABAA receptor (GABAA(δ)R) in fear generalization is uncertain. Here, by using mice with or without genetic deletion of GABAA(δ)R and using protocols in which the conditioned tone stimuli were cross presented with different nonconditioned stimuli, we observed that when the two tone stimuli were largely similar, both genotypes froze similarly to either of them. However, when they differed markedly, the knockout mice froze much more than their wild-type littermates to the nonconditioned but not conditioned stimuli. Thus, GABAA(δ)R may prevent inappropriate fear generalization when the incoming stimuli differ clearly from the learned threat.
A Study of the NASPA Journal (1967-1996): A 30-Year Reflection of Scholarship in Student Affairs Focusing on Race and Ethnicity

The purpose of this study is to present a comprehensive picture of the student affairs scholarship published in the NASPA Journal from 1967 to 1996 that focused on racial and ethnic topics. A thematic analysis suggested the published articles moved from themes of “concern and assessment” to themes of ethnic and racial minority students as multi-dimensional rather than a population in need of “adjustment,” and “campus environmental change” as a way to support a more racially and ethnically diverse student body. While the scholarship addressed racial and ethnic topics, the writings most often focused on concerns related to the Black student. Few articles related to Native American, Hispanic or Latino, and Asian groups. Encouragement by all levels of the profession, including associations, training programs, and journals for additional scholarship in these underrepresented areas is recommended, including using the historical strategy of the “special issues” format.
Thicker carotid intima layer, thinner media layer and higher intima/media ratio in women with recurrent depressive disorders: A pilot study using non-invasive high frequency ultrasound

Abstract Objectives. Growing evidence indicates that depression is an important risk factor for coronary heart disease. Thus, the aim of the present study has been to investigate if young women with adolescent onset and recurrent depressive disorders have signs of carotid intima and media changes already at the age of 30. Methods. Fifteen subjects with adolescent onset recurrent depressive disorders, mean age 31.5 years, were compared to 20 healthy women with a mean age of 39.6 years. The thickness of carotid artery intima and media was assessed, using non-invasive high-frequency ultrasound (25MHz). Results. The subjects with recurrent depressive disorders had significantly thicker carotid intima, significantly thinner carotid media and significantly higher intima/media ratio despite the fact that they were about 10 years younger than the healthy women. Hypertension, obesity or smoking could not explain the results. Conclusion. Already at the age of 30, subjects with recurrent depressive disorders with adolescent onset do have early signs of carotid intima and media changes, indicating a less healthy artery wall, despite otherwise no clinical signs of cardiovascular disease.
A virtual-reality subtotal tonsillectomy simulator.

OBJECTIVES To develop a virtual-reality subtotal tonsillectomy simulation for surgical training. MATERIALS AND METHODS Computer models of a male patient's head and throat, and the surgical instrument, were created. These models were combined with custom-built simulation software. Recently developed tissue simulation technology that exploits recent developments in programmable graphics processing units was used to model tonsillar tissue in a way that allows surgical interaction whilst providing accurate tactile feedback. Current real-time rendering techniques were used to provide realistic visuals. Iterative refinements were made to the simulation, and in particular the tissue simulation, in consultation with relevantly experienced surgeons. RESULTS We have used newly developed tissue simulation technology to developed a novel virtual-reality subtotal tonsillectomy simulation for surgical training, the first of its kind. CONCLUSION Early feedback suggests that this simulator can help surgeons to rapidly acquire subtotal tonsillectomy surgical skills in a risk-free and realistic virtual environment.
The mechanism of CIRP in inhibition of keratinocytes growth arrest and apoptosis following low dose UVB radiation

UV induces CIRP expression and subsequent Stat3 activation, but the biological function and mechanism of CIRP and Stat3 in mediating UVB‐induced skin carcinogenesis have not been fully elucidated. In this study, we demonstrate that CIRP is elevated in all tested melanoma and non‐melanoma skin cancer cell lines; and the expression of CIRP is upregulated in keratinocytes after being irradiated with relatively low dose (<5 mJ/cm2), but not high dose (50 mJ/cm2), UVB acutely and chronically. The increased expression of CIRP, either induced by UVB or through overexpression, leads to resistance of keratinocytes to UVB‐induced growth arrest and death; and reduced expression of CIRP by RNA knockdown sensitizes keratinocyte cells to the low dose UVB radiation. We also demonstrated that CIRP expression is required for the low dose UVB‐induced Tyr705‐phosphorylation, but not total amount, of Stat3. The p‐Stat3 level is correlated with the expression levels of cyclin D1 and VEGF, two known downstream cell growth regulators of Stat3, as well as Bag‐1/S, an apoptosis regulator. Inhibition of Stat3 DNA‐binding activity by S3I‐201 leads to a reduction of the p‐Stat3 and Bag‐1/S along with growth and survival of keratinocytes post‐UVB; and the effect of S3I‐201 on the UVB‐irradiated cells can be partially inhibited by overexpression of CIRP or Bag‐1/S. Furthermore, the overexpression of Bag‐1/S can totally inhibit UVB‐induced PARP cleavage and caspase 3 activation. The results presented above led us to propose that CIRP‐p(705)Stat3 cascade promotes cell proliferation and survival post‐UVB via upregulating the expression of cyclin D1 and Bag‐1/S, respectively. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.
Sudden Arrhythmic Death Syndrome: Diagnostic Yield of Comprehensive Clinical Evaluation of Pediatric First‐Degree Relatives

Sudden arrhythmic death syndrome (SADS) is most often caused by heritable cardiac diseases. Studies in adults have identified evidence of inherited cardiovascular diseases in up to 53% of families, but data on the prevalence of familial disease in children are scarce. The aim of this study was to evaluate the yield of clinical screening in pediatric first‐degree relatives of victims of SADS using a systematic and comprehensive protocol.