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The purpose of this study was to determine the relationship between peak VO2 and the 1-mile walk test (WALK) performance of forty 12-17-year-old males (mean age = 14.13 years) with mental retardation (mean IQ = 50). Test-retest reliability of the WALK was high for WALK times (R =.97), WALK End-HR (R =.88), and WALK HRpeak (R =.92). Test-retest reliability of relative peak VO2 was.90. Partial correlation analysis indicated that when weight and various combinations of variables with weight were held constant, the relationship between WALK time and peak VO2 was strengthened. Multiple regression analysis of WALK performance variables and peak VO2 measures indicated the best model for estimating relative peak VO2: VO2peak = 95.56 - 3.345 (walk time) - 0.174 (WT) and the best model for estimating absolute peak VO2: VO2peak = 2.90 - .176 (walk time) +.031 (WT). Results indicated the WALK as a reliable field test for the sample tested. [ABSTRACT FROM AUTHOR]

Introduction: Jugulotympanic paraganglioma (JTP) refers to paraganglioma arising from jugular bulb, which can invade surrounding structures such as the bones, blood vessels, meninges, and cranial nerves. The authors conducted a study to find surgical indications to avoid a serious cranial nerve complications by analyzing the medical records of patients who underwent surgical management for JTP., Methods: We performed a single-institution, retrospective review of patients who underwent resection of JTP from 2004 to 2022. Patients underwent either Fisch infratemporal fossa approach type A (ITFA-A) or modification of ITFA-A with partial rerouting of the facial nerve. Preoperative and postoperative lower cranial nerve (LCN) function and facial function using the House-Brackmann (H-B) grade were evaluated., Results: The study included 19 patients with a mean age of 43.1 years (standard deviation [SD], 16.1 years). The average tumor size was 28.6 mm (SD 12.6 mm). In patients with Fisch classes C1 and C2 tumors, there were 3 and 11 patients, respectively. Gross total tumor removal (GTR) was performed in all patients with classes C1 and C2. GTR was achieved in 2 out of the 5 patients with class C3 tumor. Seventeen patients underwent ITFA-A and 2 patients underwent partial rerouting. Facial function before surgery was normal in all but 3 cases. Among 16 patients with preoperative normal facial function, 13 had H-B grade I to II and 3 had H-B grade III at 1 year after surgery. Total and partial rerouting did not significantly affect facial function immediately after surgery or at the postoperative 1-year evaluation (p = 1.00). Preoperative LCN function was normal in all patients. LCN palsy lasting more than 1 year occurred in 7 patients after surgery. Patients with Fisch class C1 tumor did not develop postoperative LCN palsy. Among the patients with class C2 tumor, none of 5 patients with medial invasion depth less than 9.5 mm developed LCN palsy, whereas 5 of 6 patients (83.3%) with invasion depth of 9.5 mm or greater developed LCN palsy (p = 0.02)., Conclusion: JTPs with deep medial invasion should be managed conservatively to prevent LCN palsy., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Objective: To examine the clinical characteristics and auditory performance of patients with CHARGE syndrome following cochlear implantation (CI), as well as the prognostic factors affecting auditory outcomes., Study Design: Retrospective cohort., Setting: Tertiary academic center., Methods: A retrospective chart review was performed in patients with CHARGE syndrome who underwent CI from 2007 to 2022. The category of auditory performance (CAP) score was used to assess the CI outcomes, and factors that may affect the speech outcomes were also evaluated., Results: In 14 children with CHARGE syndrome, 22 CIs were performed, 6 unilaterally and 8 bilaterally. The mean age at CI was 25.9 months (range: 10-62). All patients had ear abnormalities and developmental delays, and cochlear nerve deficiency (CND) was present in all ears. At the last follow-up (mean: 49.6 months), the mean CAP score improved significantly compared to the preoperative measure (from 0.36 ± 0.81 to 3.21 ± 1.70, P = .001), with 6 patients (42.9%) achieving a CAP score of 4 points or higher. However, between the unilateral and bilateral CI groups, the final CAP score or change in CAP score was similar. Factors including age, coloboma, and CND did not significantly affect speech outcomes (all P > .05)., Conclusion: Even though CHARGE syndrome features challenging anomalies, CI can be conducted safely and can offer effective contribution to significant speech improvement. Patients with CHARGE syndrome should be given the opportunity to undergo CI to maximize their audiological progress., (© 2024 American Academy of Otolaryngology‐Head and Neck Surgery Foundation.)

Objective: To examine the clinical features and surgical outcomes in patients with congenital absence of the oval window (CAOW), and to investigate the potential factors that affect audiologic results., Study Design: A retrospective chart review., Setting: A tertiary academic center., Patients and Intervention: A total of 17 ears among 16 patients were confirmed to have CAOW. Among them, 13 ears underwent vestibulotomy for hearing reconstruction. Clinical parameters associated with the hearing outcomes were analyzed., Main Outcome Measures: A mean air-bone gap (ABG) after 6-month and long-term follow-up was compared with preoperative measurements., Results: Intraoperative findings showed that anomalies of the malleus or incus were observed in 11 ears (64.7%), stapes anomalies were present in all ears (100%), and facial nerve anomalies were present in 10 ears (58.8%). Because of unfavorable facial nerve anomalies, hearing reconstruction was aborted in four cases (23.5%). In the hearing reconstruction group, the mean ABG at 6 months postoperation was significantly reduced after compared with the preoperative value (44.0 ± 8.4 dB versus 58.8 ± 9.1 dB, p = 0.006). After dividing ears into a success subgroup (ABG ≤ 30 dB, seven ears) and non-success subgroup (ABG > 30 dB, six ears), the use of a drill during vestibulotomy was significantly related to a poor hearing outcome (100% versus 16.7%, p = 0.015). The long-term follow-up result (mean, 60 mo) revealed no deterioration compared with the 6-month postoperative result. Five ears (29.4%) underwent revision surgery, and three of them showed ABG improvements. No serious complications were reported., Conclusion: Vestibulotomy is an effective and safe option for hearing restoration in patients with CAOW, particularly when the use of a drill is not required. The long-term audiologic outcome is also reliable., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2024, Otology & Neurotology, Inc.)

Introduction: Natural killer/T cell lymphoma (NKTL) is an aggressive malignancy associated with poor prognosis. This is largely due to limited treatment options, especially for relapsed patients. Immunotherapies like immune checkpoint inhibitors (ICI) and anti-CD38 therapies have shown promising but variable clinical efficacies. Combining these therapies has been suggested to enhance efficacy., Methods: We conducted a case study on a relapsed NKTL patient treated sequentially with anti-CD38 followed by ICI (anti-PD1) using cytometry analyses., Results and Discussion: Our analysis showed an expected depletion of peripheral CD38+ B cells following anti-CD38 treatment. Further analysis indicated that circulating anti-CD38 retained their function for up to 13 weeks post-administration. Anti-PD1 treatment triggered re-activation and upregulation of CD38 on the T cells. Consequently, these anti-PD1-activated T cells were depleted by residual circulating anti-CD38, rendering the ICI treatment ineffective. Finally, a meta-analysis confirmed this counterproductive effect, showing a reduced efficacy in patients undergoing combination therapy. In conclusion, our findings demonstrate that sequential anti-CD38 followed by anti-PD1 therapy leads to a counterproductive outcome in NKTL patients. This suggests that the treatment sequence is antithetic and warrants re-evaluation for optimizing cancer immunotherapy strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lee, Lim, Tang, Tan, Koh, Puan, Wang, Lim, Tan, Chng, Lim, Ong and Rotzschke.)

Mature tropical urban trees are susceptible to root and trunk rot caused by pathogenic fungi. A metagenomic survey of such fungi was carried out on 210 soil and tissue samples collected from 134 trees of 14 common species in Singapore. Furthermore, 121 fruiting bodies were collected and barcoded. Out of the 22,067 OTUs (operational taxonomic units) identified, 10,646 OTUs had annotation information, and most were either ascomycetes (63.4%) or basidiomycetes (22.5%). Based on their detection in the diseased tissues and surrounding soils and/or the presence of fruiting bodies, fourteen basidiomycetes (nine Polyporales , four Hymenochaetales , one Boletales ) and three ascomycetes (three species of Scytalidium ) were strongly associated with the diseased trees. Fulvifomes siamensis affected the largest number of tree species surveyed. The association of three fungi was further supported by in vitro wood decay studies. Genetic heterogeneity was common in the diseased tissues and fruiting bodies ( Ganoderma species especially). This survey identified the common pathogenic fungi of tropical urban trees and laid the foundation for early diagnosis and targeted mitigation efforts. It also illustrated the complexity of fungal ecology and pathogenicity.

Background: Hypertriglyceridemia is an important feature of dyslipidemia in type 1 and type 2 diabetic patients and associated with the development of atherosclerotic cardiovascular disease. Recently, variability of lipid profile has been suggested as a residual risk factor for cardiovascular disease. This study compared the clinical impact of serum triglyceride variability, and their cumulative exposure estimates on cardiovascular prognosis in diabetic patients., Methods: A total of 25,933 diabetic patients who had serum triglyceride levels measured at least 3 times and did not have underlying malignancy, myocardial infarction (MI), and stroke during the initial 3 years (modeling phase) were selected from three tertiary hospitals. They were divided into a high/low group depending on their coefficient of variation (CV) and cumulative exposure estimate (CEE). Incidence of major adverse event (MAE), a composite of all-cause death, MI, and stroke during the following 5 years were compared between groups by multivariable analysis after propensity score matching., Results: Although there was a slight difference, both the high CV group and the high CEE group had a higher cardiovascular risk profile including male-dominance, smoking, alcohol, dyslipidemia, and chronic kidney disease compared to the low groups. After the propensity score matching, the high CV group showed higher MAE incidence compared to the low CV group (9.1% vs 7.7%, p = 0.01). In contrast, there was no significant difference of MAE incidence between the high CEE group and the low CEE group (8.6% vs 9.1%, p = 0.44). After the multivariable analysis with further adjustment for potential residual confounding factors, the high CV was suggested as an independent risk predictor for MAE (HR 1.19 [95% CI 1.03-1.37])., Conclusion: Visit-to-visit variability of triglyceride rather than their cumulative exposure is more strongly related to the incidence of MAE in diabetic patients., (© 2022. The Author(s).)

Objectives: Arytenoid adduction (AA) and injection laryngoplasty (IL) are major surgical options for the treatment of unilateral vocal fold paralysis (UVFP). AA is a laryngeal framework surgery and IL is a soft-tissue augmentation procedure. Therefore, the effect of each intervention will not be substitutive but complementary to the other., Methods: Patients who received AA and IL were enrolled (N = 43). Mean age was 60.1 ± 12.7 years. Objective and subjective voice parameters including maximum phonation time (MPT), jitter, shimmer, noise to harmonic ratio (NHR), grade of dysphonia (G), and voice handicap index (VHI)-30 were collected preoperatively and 6 months postoperatively. AA and IL were sequentially performed with time interval; 28 (65.1%) patients received IL first followed by AA (IL+AA group) and 15 (34.9%) had AA followed by IL (AA+IL group). Time interval between first and second procedures was 9.9 ± 14.6 months., Results: MPT, jitter, shimmer, NHR, G and VHI-30 significantly improved by both first and second procedures (P < 0.001). When we evaluated IL+AA group and AA+IL group separately, the final outcomes of MPT, jitter, G, and VHI-30 between the two groups were not significantly different. When the overall effects of IL and AA were compared, MPT significantly improved with AA than with IL (P < 0.001)., Conclusion: In patients with unilateral vocal fold paralysis, sequential AA and IL (or IL and AA) provided additional improvement of subjective and objective voice parameters. Final outcomes of the two combined procedures resulted in similar degree of voice improvement regardless of the order of procedure., (Copyright © 2020 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The aim of this study is to investigate the clinical effectiveness of Ponto in Korea, a recently released percutaneous bone-anchored hearing implant., Methods: 16 patients with single-sided deafness (SSD) and mixed or conductive hearing loss who underwent Ponto implantation from December 2018 to September 2020 were enrolled in the study. Puretone audiometry, the Korean version of the Hearing in Noise Test (K-HINT), sound localization test (SLT), and Pupillometry were performed pre- and three months post-operation. Standardized questionnaires, the Hearing Handicap Inventory for the Elderly (HHIE) and Speech, Spatial and Qualities of Hearing Scale (SSQ), were administered., Results: The mean age of subjects was 55.5 (range, 48-67) years. Four males and 12 females participated in the study. The mean puretone average was 73.17 dB hearing level (HL) before surgery and significantly improved to 36.72 dB HL three months after surgery. The mean word recognition score improved from 26.0% to 90.75% after implantation. In the case of K-HINT, there was a significant difference in summation (Z = -2.250, P = 0.024) and head shadow effects (Z = -3.103, P = 0.002). There was no significant difference in root mean square error degree (RMSE) and hemifield identification scores for SLT testing. Pupillometry was performed to measure listening effort and the results revealed that the degree of pupillary dilatation decreased under the condition of quiet, 0 dB signal to noise ratio (SNR) and 3 dB SNR. The total score for HHIE decreased significantly ( Z = -3.130, P = 0.002) while the SSQ score increased significantly ( Z = -2.216, P = 0.027)., Conclusions: The Ponto bone-anchored hearing system showed significant clinical benefit in Korean patients with conductive and mixed hearing loss and SSD., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

Parkinson’s disease (PD) is a debilitating movement disorder characterised by the loss of dopaminergic neurons in the substantia nigra. As neuroprotective agents mitigating the rate of neurodegeneration are unavailable, the current therapies largely focus only on symptomatic relief. Here, we identified stress-inducible phosphoprotein 1 (STIP1) as a putative neuroprotective factor targeted by PD-specific autoantibodies. STIP1 is a co-chaperone with reported neuroprotective capacities in mouse Alzheimer’s disease and stroke models. With human dopaminergic neurons derived from induced pluripotent stem cells, STIP1 was found to alleviate staurosporine-induced neurotoxicity. A case-control study involving 50 PD patients (average age = 62.94 ± 8.48, Hoehn and Yahr >2 = 55%) and 50 age-matched healthy controls (HCs) (average age = 63.1 ± 8) further revealed high levels of STIP1 autoantibodies in 20% of PD patients compared to 10% of HCs. Using an overlapping peptide library covering the STIP1 protein, we identified four PD-specific B cell epitopes that were not recognised in HCs. All of these epitopes were located within regions crucial for STIP1’s chaperone function or prion protein association. Our clinical and neuro-immunological studies highlight the potential of the STIP1 co-chaperone as an endogenous neuroprotective agent in PD and suggest the possible involvement of autoimmune mechanisms via the production of autoantibodies in a subset of individuals.

Intravenous gadolinium-enhanced inner-ear magnetic resonance imaging (IV-Gd inner-ear MRI) has been used to visualize endolymphatic hydrops (EH) in clinical diagnosis of Ménière's disease (MD). However, lack of histological validation has led to several concerns regarding how best to interpret the resulting images. Here, we compared hydropic changes in temporal bone specimens with the results of IV-Gd inner-ear MRI in patients with MD. Histopathologic images of temporal bones from 37 patients with MD and 10 healthy controls were collected from the National Temporal Bone Bank of the Massachusetts Eye and Ear Infirmary in the United States. The EH ratios in the vestibule and cochlea were calculated from temporal bones using the methods used for IV-Gd inner-ear MRI, and the degree to which the saccular and utricular hydrops contributed to vestibular hydrops was measured. The presence of hydropic change in each semicircular canal was assessed using temporal bone images and compared with IV-Gd inner-ear MRI scans of 74 patients with MD. Based on human temporal bone imagery, the EH ratios in the cochlea and the vestibule on the affected side were 0.314 and 0.757, respectively. In the healthy control group, the ratio was 0.064 for the cochlea and 0.289 for the vestibule; these values were significantly different from those for the affected side of MD patients. The values for the affected ear were similar to the ratios from the IV-Gd inner-ear MRI scans in MD patients. In the vestibule, saccular hydrops were more common than utricular hydrops. The average EH ratios in the saccule and utricle were 0.513 and 0.242, respectively. No significant hydropic change from each of three semicircular canals was evident in temporal bone histopathology. However, herniation of otolithic organs (saccule or utricle) into the lateral semicircular canal was found in 44.4% of the patients, with saccular herniation (24.8%) more common than utricular herniation (16.7%). Although IV-Gd inner-ear MRI might not reflect fully the results of actual histopathology due to the limited resolution of MRI and image-processing techniques, the measured EH ratios from temporal bone specimens and IV-Gd inner-ear MRI scans were similar. Hydropic change in the three semicircular canals was not significant at either the ampullated or nonampullated end. Canal invasion of vestibular hydrops seen on MRI also appeared in temporal bone histopathology, and saccular invasion was dominant., (© 2021. The Author(s).)

Importance: Septoplasty is used to correct nasal obstructions caused by a deviated septum. In some patients, septal deviation is also associated with external nasal deformity, which suggests that proper septoplasty can improve external deformities as well. However, objective studies of the esthetic outcome of septoplasty are limited. Objective: To investigate the potential esthetic outcome of correction of septal in addition to its functional purpose of treating nasal obstructions. Design, Setting, and Participants: Retrospective chart analysis of prospectively collected data was conducted for patients who underwent septoplasty performed by a single surgeon at our clinic. Ninety-five patients who had preoperative and postoperative medical photographs were enrolled. Main Outcomes and Measures: We measured the mid-vault dorsum angle (MDA) from a bird's eye view to evaluate the objective esthetic outcome. The nasofrontal angle and the nasolabial angle were also included in our analysis. Differences in preoperative anthropometric measurements and application of specific surgical techniques were additionally analyzed. Results: The mean age of the participants was 39.1 years (male: 85.2%, female: 14.8%). The average preoperative MDA was 3.41° ± 3.05°, and the postoperative MDA was 1.88° ± 1.09° ( p  < 0.001). In the severe dorsum deviation group (MDA >4°, N  = 31), angle measure improvement was prominent (3.82° ± 2.97°, p  < 0.001). The correlation analysis revealed that a higher preoperative MDA had a significant correlation with a higher angle improvement postoperatively ( r  = 0.7, p  < 0.001); this outcome was also observed in the severe dorsal deviation group ( r  = 0.6, p  = 0.003). In addition, we found a positive correlation between the bony septal deviation angle on computed tomography and preoperative MDA ( r  = 0.51, p  = 0.003). Conclusions and Relevance: In some cases with significant external dorsum deviation, septoplasty via an endonasal approach can yield positive esthetic outcomes in addition to functional improvements. This finding will benefit patient counseling and also provide important surgical concepts in rhinoplasty with an emphasis on a gradual surgical approach to correcting external nasal deformity.

Background: After the year 2000, kidney transplants with high immunologic risk and deceased donors increased rapidly in Korea. At the same time, the medical community developed special pretransplant and early posttransplantation management protocols. Our team evaluated the effect of early graft stabilization on long-term graft survival and functional status using databases from a high-volume kidney transplantation center., Methods: We included 1,895 kidney transplant patients from a total of 1,976 performed between 2005 and 2018. Early graft failure within 1 month (n=9), loss to follow-up (n=2), pediatric recipient or donor (n=37), and combined organ transplantation (n=33) cases were excluded. We grouped the cases at 1-month posttransplantation by serum creatinine quantiles (1.0 mg%, 1.23 mg%, and 1.52 mg%)., Results: After an average of 95 months of follow-up (maximum 189 months), the high-serum creatinine group (4th quantile) showed significantly poorer graft survival than other groups (1st to 3rd quantile) (P<0.05). In multiple Cox regression analysis, a high serum creatinine level (4th quantile) at 1-month posttransplant is an independent risk factor for graft failure with a hazard ratio of 1.799 (P=0.013). The quantile group by serum creatinine shows a persistent, significant difference of functional graft status (glomerular filtration rate by Modification of Diet in Renal Disease method) among quantile groups beyond ten years posttransplant., Conclusions: Serum creatinine level at 1-month posttransplant is a strong independent predictor of graft survival and functional graft status beyond ten years posttransplant., Competing Interests: Conflict of Interest No potential conflict of interest relevant to this article was reported., (Copyright © 2020 The Korean Society for Transplantation.)

Purpose: Osteoarthritis (OA) of the knee is a multifactorial degenerative disease typically defined as the 'wear and tear' of articular joint cartilage. However, recent studies suggest that OA is a disease arising from chronic low-grade inflammation. We conducted a study to investigate the relationship between chronic inflammatory mediators present in both the systemic peripheral blood system and localised inflammation in synovial fluid (SF) of OA and non-OA knees; and subsequently made direct comparative analyses to understand the mechanisms that may underpin the processes involved in OA., Methods: 20-Plex proteins were quantified using Human Magnetic Luminex® assay (R&D Systems, USA) from plasma and SF of OA (n = 14) and non-OA (n = 14) patients. Ingenuity Pathway Analysis (IPA) software was used to predict the relationship and possible interaction of molecules pertaining to OA., Results: There were significant differences in plasma level for matrix metalloproteinase (MMP)-3, interleukin (IL)-27, IL-8, IL-4, tumour necrosis factor-alpha, MMP-1, IL-15, IL-21, IL-10, and IL-1 beta between the groups, as well as significant differences in SF level for IL-15, IL-8, vascular endothelial growth factor (VEGF), MMP-1, and IL-18. Our predictive OA model demonstrated that toll-like receptor (TLR) 2, macrophage migration inhibitory factor (MIF), TLR4 and IL-1 were the main regulators of IL-1B, IL-4, IL-8, IL-10, IL-15, IL-21, IL-27, MMP-1 and MMP-3 in the plasma system; whilst IL-1B, TLR4, IL-1, and basigin (BSG) were the regulators of IL-4, IL-8, IL-10, IL-15, IL-18, IL-21, IL-27, MMP-1, and MMP-3 in the SF system., Conclusion: The elevated plasma IL-8 and SF IL-18 may be associated with the pathogenesis of OA via the activation of MMP-3., (Copyright © 2019. Published by Elsevier B.V.)

Paediatric airway management is a challenging area of anaesthesia practice to learn. Techniques and skills required need modification from adult practice and gaining experience through exposure takes considerable time. Preparation to manage airway emergencies can be particularly difficult as these events are rare in paediatric practice. This study aimed to examine what educational approaches health professionals of varying backgrounds find useful when learning or teaching paediatric airway management. This qualitative study involved the conduct of five interdisciplinary focus groups; each group consisted of four to six health professionals from nursing, anaesthetic, simulation and critical care backgrounds. After transcription, focus group content was analysed using a qualitative method to identify common themes expressed within the interviews. Five themes were most prominent. These included the high value of hands-on learning, the challenges created by variability in exposure, the importance of developing basic airway skills, the potential for simulation to cover rare situations, and the problems of current airway models. These themes were evident in comments from both experienced and novice practitioners, clinicians with different subspecialty backgrounds and both medical and nursing staff. Learners and educators have similar priorities in airway education. This includes a strong recognition of the importance of spending time mastering basic airway techniques, a role for simulation in building non-technical skills and noted deficiencies in current airway models.

The sirtuin family of proteins consists of nicotinamide adenine dinucleotide-dependent deacetylases that are involved in the response to calorie restriction and various physiological phenomena, such as aging and cognition. One of these proteins, sirtuin 3 (SIRT3), is localized in the mitochondria and protects the cell against oxidative or metabolic stress. Sirtuin protein deficiencies have been shown to accelerate neurodegeneration in neurotoxic conditions. The mechanisms underlying the involvement of SIRT3 in cognition remain unclear. Interestingly, SIRT1, another member of the sirtuin family, has been reported to modulate synaptic plasticity and memory formation. To learn more about these proteins, we examined the behavior and cognitive functions of Sirt3-knockout mice. The mice exhibited poor remote memory. Consistent with this, long-term potentiation was impaired in the Sirt3-knockout mice, and they exhibited decreased neuronal number in the anterior cingulate cortex, which seemed to contribute to their memory deficiencies.

Purpose: To demonstrate that vasoactive intestinal peptide (VIP), a corneal endothelial (CE) cell autocrine factor, maintains the integrity of corneal endothelium in human donor corneoscleral explants precut for endothelial keratoplasty., Methods: Twelve paired human donor corneoscleral explants used as control versus VIP-treated explants (10 nM, 30 minutes, 37°C) were shipped (4°C) to the Lions Eye Institute for Transplantation and Research for precutting (Moria CBM-ALTK Keratome), shipped back to the laboratory, and cultured in ciliary neurotrophic factor (CNTF, 0.83 nM, 37°C, 24 hours). Trephined endothelial discs (8-8.5 mm) were analyzed for differentiation markers (N-cadherin, CNTF receptor α subunit [CNTFRα], and connexin 43) by Western blot after a quarter of the discs from 4 paired explants were cut away and stained with alizarin red S for microscopic damage analysis. Two additional paired explants (6 days in culture) were stained for panoramic view of central CE damage., Results: VIP treatment increased N-cadherin and CNTFRα levels (mean ± SEM) to 1.38 ± 0.11-fold (P = 0.003) and 1.46 ± 0.22-fold (P = 0.03) of paired controls, respectively, whereas CE cell CNTF responsiveness in upregulation of connexin 43 increased to 2.02 ± 0.5 (mean ± SEM)-fold of the controls (P = 0.04). CE damage decreased from (mean ± SEM) 10.0% ± 1.2% to 1.6% ± 0.3% (P < 0.0001) and 9.1% ± 1.1% to 2.4% ± 1.0% (P = 0.0006). After 6 days in culture, the damage in whole CE discs decreased from 20.0% (control) to 5.5% (VIP treated)., Conclusions: VIP treatment before precut enhanced the preservation of corneal endothelium.

Hexamethylene bisacetamide-inducible protein 1 (HEXIM1) is best known as the inhibitor of positive transcription elongation factor b (P-TEFb) and is recently identified as a novel positive regulator of p53. We previously showed the basic region (BR) of HEXIM1 mediates the binding of HEXIM1 to a nucleolar protein, nucleophosmin (NPM), and can be ubiquitinated by human double minute 2 protein. Here we identify a cytotoxic peptide derived from the BR of HEXIM1. When fused with a cell-penetrating peptide, the HEXIM1 BR peptide triggers rapid cytotoxic effect independent of p53. Similarly, when the BR peptide is linked with a breast cancer cell targeting peptide, LTV, the LTV-BR fusion peptide exhibits specific killing of breast cancer cells, which is not observed with the commonly used cytotoxic peptide, KLA. Importantly, the BR peptide fails to enter cells by itself and does not induce any cytotoxic effects when it is not guided by any cell-penetrating or cancer targeting peptides. We showed that HEXIM1 BR peptide depolarizes mitochondrial membrane potential in a p53-dependent manner and its cell-killing activity is not suppressed by caspase inhibition. Furthermore, we observed an accumulation of the internalized BR peptide in the nucleoli of treated cells and an altered localization of NPM. These results illustrate a novel mechanism which the BR peptide induces cell death and can potentially be used as a novel therapeutic strategy against breast cancer.

Fibreoptic intubation remains an essential skill for anaesthetists to master. In addition to the reusable fibrescope, an alternative disposable videoscope is available (aScope(™)2, Ambu®, Ballerup, Denmark). A total of 60 anaesthetised adult patients were randomised to either having orotracheal intubation using the aScope 2 or a Karl Storz fibrescope. Intubations were performed by experienced operators who were familiar with both devices. The primary outcome was the Global Rating Scale score. Secondary outcomes included intubation success, number of intubation attempts and intubation time. Other subjective outcomes including practicality, useability and image quality were also recorded. There was no significant difference in the Global Rating Scale score, intubation success orintubation time between the aScope 2 or Karl Storz fibrescope. Global Rating Scale scores were three and two in the aScope 2 and Karl Storz groups respectively (P=0.14). All of the other subjective outcomes were similar between the two groups, except that operators found it easier to use the aScope 2 compared to the fibrescope. There was no significant difference in clinical performance between the aScope 2 and the Karl Storz fibreoptic bronchoscope. The aScope's practicality, disposability and recently improved version (aScope(™)3) potentially make it an acceptable alternative to the reusable fibrescope.

Progressive advancements in the fields of medicine, oncology and palliative care have seen significant gains in the life expectancy but have also resulted in patients living longer with the burdens of cancer. It is within the sphere of end-of-life care that the role of palliative rehabilitation comes into its own in addressing the effects of increased physical and psychological morbidity that accompany many of these prognostic gains. Focusing on the cancer journey, we highlight the impact of rehabilitative measures on efforts to preserve the personhood of a patient with metastatic renal cell carcinoma and thus maintain her dignity and quality of life and provide her with appropriate and effective holistic care at the end of life. Through employing the Ring Theory of Personhood, the critical role of the complementary aspects of palliative rehabilitation in end-of-life care is brought to the fore., (2014 BMJ Publishing Group Ltd.)

This study highlights the benefits of carpal tunnel release (CTR) in four patients presenting with complex regional pain syndrome (CRPS) after hand surgery who also had carpal tunnel syndrome (CTS) diagnosed clinically and by nerve conduction studies. Three of the patients underwent pre- and postoperative volumetric, circumference, grip strength and range of motion measurements. The Disabilities of the Arm, Shoulder and Hand (DASH) functional outcome measure and pain scores were also used. There was almost complete resolution of CRPS symptoms in all four patients, with notable reductions in oedema and improvements in grip strength and range of motion. There were also improvements in DASH outcome scores and pain scores after CTR.

This is a validation study of the RT3 accelerometer for measuring physical activities of children in simulated free-living conditions. Twenty-five children age 12-14 years completed indoor testing, and 18 of them completed outdoor testing. Activity counts from the RT3 accelerometer estimated activity energy expenditure (AEE) and the Cosmed K4b2 analyzer measured oxygen uptake. Correlations were found between activity counts and metabolic cost (r = .95, p < .001), metabolic cost and RT3 estimated AEE (r = .96, p < .001) in the indoor test, activity counts and RT3 estimated AEE (r = .97, p < .001) in the outdoor test, and activity counts and metabolic cost when all activities were combined (r = .77, p < .001). Results indicate that the RT3 accelerometer might be used to provide acceptable estimates of free-living physical activity in children.

A Nationwide survey on the natural radioactivity in industrial raw mineral commodities (17 kinds of domestic and 18 kinds of imported) that are representative minerals used in production and consumption in South Korea was conducted. The target industrial minerals can be categorized into two groups. The first group covers non-metallic and metallic raw minerals with low levels of radioactivity such as clay, silica sand, carbonates, bituminous and anthracite coal, iron ores, ilmenite, rutile, and phosphate ore. The other group comprises minerals with high levels of radioactivity including zircon and monazite. One hundred and sixty-four domestic and imported samples were analysed by gamma-ray spectroscopy using an HPGe detector. The (40)K content ranges from <0.00131 to 2.69Bq g(-1), and (226)Ra and (232)Th range over <0.0006 to 0.630 and <0.0008 to 0.474Bq g(-1), respectively. There was no anthropogenic radioactive signal in any of the samples.

Objectives: To document incidences of vestibular dysfunction after cochlear implantation and investigate why it occurs. This work was also motivated by a desire to provide the basis for better preoperative counseling and postoperative vestibular therapy to cochlear implant patients., Setting: Melbourne Cochlear Implant Clinic at a tertiary referral hospital., Study Design: Prospective observational study., Patients: One hundred forty-six adult implant recipients, mean age, 60 years (range, 20-90 yr)., Main Outcome Measures: Postoperative vestibular disturbance was defined as symptoms lasting for 1 week or longer after surgery. The differences in preoperative and postoperative vestibular function were measured from subjective assessments (Dizziness Handicap Inventory and Activity Balance Confidence questionnaires) and objective assessments (bithermal caloric tests). The position of the postoperative electrode was classified as "loose", "regular", or "tight" fitting., Results: Thirty-two percent of patients reported vestibular disturbance and had poorer Dizziness Handicap Inventory, Activity Balance Confidence, and caloric results in the implanted ear after surgery. Patient age, cause, and preoperative caloric result did not predict postoperative vestibular symptoms. Recipients aged 70 years or older had significantly poorer caloric results on the implanted side after surgery that was not related to the intracochlear electrode position or surgical team., Conclusion: One-third of recipients can expect to experience a significant vestibular disturbance after surgery, regardless of age, cause, or preoperative caloric result. "Older" ears seem more prone to permanent injury after cochlear implantation.

The retinal pigment epithelium (RPE) is a single cell layer juxtaposed between the neural retina and the choroid and functions as a blood-retina barrier. The RPE performs functions essential for photoreceptor (PR) survival. Although the regulation of these functions has remained unknown, it is a distinct possibility that the RPE is under constant regulation by signaling molecules coming from the choroid and the retina. Vasoactive intestinal peptide (VIP), a 28-amino acid neuropeptide present in the retina and in the choroid, has been shown to promote the growth and differentiation of a variety of cells in tissue and organ cultures. In cultured RPE cells, VIP is the one most effective stimulator of the cAMP signaling pathway among a long list of neurotransmitters and modulators tested. For example, VIP, at 1 microM, stimulates the intracellular cAMP to 80-100- and 20-fold in 3 min in RPE cells cultured from chick embryos and adult human donor eyes, respectively. In cultured chick embryonic RPE, VIP is also shown to be a potent and effective modulator of pp60(c-src), the non-receptor tyrosine kinase present in differentiating and terminally differentiated cells. VIP stimulates both overall phosphorylation at unknown sites and phosphotyrosine dephosphorylation in pp60(c-src). A 190-kDa microtubule-associated protein is known to be one of the downstream targets in VIP-modulated signaling pathways. At the cellular level, VIP stimulates cell proliferation modestly and melanogenesis pronouncedly in growing chick embryonic RPE cultures. Ultimately, the differentiation goal of RPE cells in vivo is to perform functions that are essential for photoreceptor survival. On bare permeable supports (that is, without biological material coating), the chick embryonic RPE cells grow to become RPE sheets with a cytoarchitecture that allows the display of two of the RPE functions. These cultures demonstrate structural polarity and are functionally polarized, allowing for proper macromolecule secretion and fluid transport. VIP is shown to stimulate macromolecule secretion at the apical surface (retina facing) and the development of the capacity for fluid transport from the apical to the basal surface of the RPE sheet. In conclusion, studies in our laboratory indicate that VIP is a differentiation promotor during the development of a functional RPE. Recent advances in the molecular biology of melanogenesis and the fluid transport-linked Na-K-2Cl cotransporter in other cells will allow future studies of VIP modulated events in the RPE at the molecular level. Finally, identification of RPE differentiation factors may prove essential for the ultimate success of RPE transplantation, thus promoting the rescue of photoreceptor cells in retinal degeneration.