Intracranial migration of iophendylate four decades after conventional myelography.

Iophendylate is an oil-based contrast agent used in conventional myelography before the 1980s. We report an unusual case of an 82-year-old woman with iophendylate migration into the intracranial cerebrospinal fluid space after myelography 40 years ago. The patient was treated conservatively and followed up regularly.

Functional mechanotransduction is required for cisplatin-induced hair cell death in the zebrafish lateral line.

Cisplatin, one of the most commonly used anticancer drugs, is known to cause inner ear hair cell damage and hearing loss. Despite much investigation into mechanisms of cisplatin-induced hair cell death, little is known about the mechanism whereby cisplatin is selectively toxic to hair cells. Using hair cells of the zebrafish lateral line, we found that chemical inhibition of mechanotransduction with quinine and EGTA protected against cisplatin-induced hair cell death. Furthermore, we found that the zebrafish mutants mariner (myo7aa) and sputnik (cad23) that lack functional mechanotransduction were resistant to cisplatin-induced hair cell death. Using a fluorescent analog of cisplatin, we found that chemical or genetic inhibition of mechanotransduction prevented its uptake. These findings demonstrate that cisplatin-induced hair cell death is dependent on functional mechanotransduction in the zebrafish lateral line.

Multiple mechanisms of aminoglycoside ototoxicity are distinguished by subcellular localization of action.

Mechanosensory hair cells of the inner ears and lateral line of vertebrates display heightened vulnerability to environmental insult, with damage resulting in hearing and balance disorders. An important example is hair cell loss due to exposure to toxic agents including therapeutic drugs such as the aminoglycoside antibiotics such as neomycin and gentamicin and antineoplastic agents. We describe two distinct cellular pathways for aminoglycoside-induced hair cell death in zebrafish lateral line hair cells. Neomycin exposure results in death from acute exposure with most cells dying within 1 hour of exposure. By contrast, exposure to gentamicin results primarily in delayed hair cell death, taking up to 24 hours for maximal effect. Washout experiments demonstrate that delayed death does not require continuous exposure, demonstrating two mechanisms where downstream responses differ in their timing. Acute damage is associated with mitochondrial calcium fluxes and can be alleviated by the mitochondrially-targeted antioxidant mitoTEMPO, while delayed death is independent of these factors. Conversely delayed death is associated with lysosomal accumulation and is reduced by altering endolysosomal function, while acute death is not sensitive to lysosomal manipulations. These experiments reveal the complexity of responses of hair cells to closely related compounds, suggesting that intervention focusing on early events rather than specific death pathways may be a successful therapeutic strategy.

Trans-arterial embolization for intractable primary postpartum hemorrhage caused by arterial aneurysms with arteriovenous fistulas in the lower vagina bilaterally: a case report.

Failure of conservative management for controlling postpartum hemorrhage (PPH) is not uncommon, particularly when PPH is caused by vascular lesions. Awareness of this possibility and initiating timely trans-arterial embolization (TAE) are essential for improving the outcome. Herein, we describe the case of a 34-year-old woman presenting with arterial aneurysms with arteriovenous fistulas in the lower vagina bilaterally, which caused intractable PPH. Conservative management failed to resolve the PPH; however, TAE successfully controlled the bleeding, and the patient recovered smoothly. Knowledge of this possible etiology for intractable PPH is crucial for timely TAE. This case report aims to highlight the pivotal role of TAE in detecting and treating this unusual cause of PPH.

Effects of High-Resolution CT Changes on Prognosis Predictability in Acute Respiratory Distress Syndrome with Diffuse Alveolar Damage.

Diffuse alveolar damage (DAD) is the pathological hallmark of acute respiratory distress syndrome (ARDS). DAD is independently correlated with higher mortality compared with the absence of DAD. Traction bronchiectasis in areas of ground-glass opacity or consolidation is associated with the late fibroproliferative or fibrotic phase of DAD. This study examined whether the 60-day mortality related to DAD could be predicted using high-resolution computed tomography (HRCT) findings and HRCT scores. A total of 34 patients with DAD who received HRCT within 7 days of ARDS diagnosis were enrolled; they were divided into a 60-day survival group and a nonsurvival group, with 17 patients in each group. Univariate and multivariate binary regression analyses and the receiver operating characteristic curve revealed that only the total percentage of the area with traction bronchiectasis or bronchiolectasis was an independent predictor of 60-day mortality (odds ratio, 1.067; 95% confidence interval (CI), 1.011-1.126) and had favorable predictive performance (area under the curve (AUC): 0.784; 95% CI, 0.621-0.946; cutoff, 21.7). Physiological variables, including age, days from ARDS to HRCT, the sequential organ failure assessment (SOFA) score, the PaO2/fraction of inspired oxygen (FiO2) ratio, dynamic driving pressure, and dynamic mechanical power, were not discriminative between 60-day survival and nonsurvival. In conclusion, the extent of fibroproliferation on HRCT in early ARDS, presented as the total percentage of area with bronchiectasis or bronchiolectasis, is an independent positive predictor with a favorable predictive ability for the 60-day mortality of DAD.

An in vivo Biomarker to Characterize Ototoxic Compounds and Novel Protective Therapeutics.

There are no approved therapeutics for the prevention of hearing loss and vestibular dysfunction from drugs like aminoglycoside antibiotics. While the mechanisms underlying aminoglycoside ototoxicity remain unresolved, there is considerable evidence that aminoglycosides enter inner ear mechanosensory hair cells through the mechanoelectrical transduction (MET) channel. Inhibition of MET-dependent uptake with small molecules or modified aminoglycosides is a promising otoprotective strategy. To better characterize mammalian ototoxicity and aid in the translation of emerging therapeutics, a biomarker is needed. In the present study we propose that neonatal mice systemically injected with the aminoglycosides G418 conjugated to Texas Red (G418-TR) can be used as a histologic biomarker to characterize in vivo aminoglycoside toxicity. We demonstrate that postnatal day 5 mice, like older mice with functional hearing, show uptake and retention of G418-TR in cochlear hair cells following systemic injection. When we compare G418-TR uptake in other tissues, we find that kidney proximal tubule cells show similar retention. Using ORC-13661, an investigational hearing protection drug, we demonstrate in vivo inhibition of aminoglycoside uptake in mammalian hair cells. This work establishes how systemically administered fluorescently labeled ototoxins in the neonatal mouse can reveal important details about ototoxic drugs and protective therapeutics.

Added Value of Computed Tomography Virtual Intravascular Endoscopy in the Evaluation of Coronary Arteries with Stents or Plaques.

Coronary computed tomography angiography (CCTA) is a widely used imaging modality for diagnosing coronary artery disease (CAD) but is limited by a high false positive rate when evaluating coronary arteries with stents and heavy calcifications. Virtual intravascular endoscopy (VIE) images generated from CCTA can be used to qualitatively assess the vascular lumen and might be helpful for overcoming this challenge. In this study, one hundred subjects with coronary stents underwent both CCTA and invasive coronary angiography (ICA). A total of 902 vessel segments were analyzed using CCTA and VIE. The vessel segments were first analyzed on CCTA alone. Then, using VIE, the segments were classified qualitatively as either negative or positive for in-stent restenosis (ISR) or CAD. These results were compared, using ICA as the reference, to determine the added diagnostic value of VIE. Of the 902 analyzed vessel segments, CCTA/VIE had sensitivity, specificity, accuracy, positive predictive value, and negative predictive value (shown in %) of 93.9/90.2, 96.2/98.2, 96.0/97.7, 70.0/83.1, and 99.4/99.0, respectively, in diagnosing ISR or CAD, with significantly improved specificity (p = 0.025), accuracy (p = 0.046), and positive predictive value (p = 0.047). VIE can be a helpful addition to CCTA when evaluating coronary arteries.

Diagnosis of a single gallbladder with double cystic ducts and dominant accessory duct draining into the right hepatic duct: a case report.

Biliary anomalies are a high risk for biliary injury during surgery, and although a biliary anomaly is occasionally encountered, variations in cystic ducts are rare. A preoperative diagnosis is highly valuable in facilitating surgical procedures and avoiding surgical complications. Herein, the case of a 67-year-old female patient with acute cholecystitis, in which preoperative fluoroscopic cholangiography clearly demonstrated a single gallbladder with double cystic ducts, is presented. The accessory duct was found to be dominant, draining into the otherwise normal right intrahepatic bile duct, and laparoscopic cholecystectomy was performed smoothly and successfully. Fluoroscopic cholangiography is a powerful tool that may clearly depict the anomaly of a single gallbladder with double cystic ducts. Through appropriate preoperative knowledge and demonstration of this biliary anomaly in the present case, laparoscopic cholecystectomy was safely performed, and the patient was symptom-free at the 3-year follow-up assessment.

Measuring Progress of Regulatory Convergence and Cooperation Among Asia-Pacific Economic Cooperation (APEC) Member Economies in the Context of the COVID-19 Pandemic.

PURPOSE: Regulatory convergence and cooperation among medical product regulatory authorities are essential to delivering safe and efficacious products quickly to patients. The COVID-19 pandemic highlights the urgent need for streamlined regulatory approval processes-which can be achieved in part through regulatory convergence and cooperation-both to accelerate availability of COVID-19 vaccines, treatments and diagnostics and to maintain the availability of the existing medical products unrelated to COVID-19. METHODS: The Asia-Pacific Economic Cooperation (APEC) Life Sciences Innovation Forum (LSIF) established the Regulatory Harmonization Steering Committee (RHSC) in 2008 to advance regulatory convergence among APEC's 21 member economies. Key performance indicators (KPIs) were developed in 2018 to measure convergence. RESULTS: This paper reports survey results collected from KPI tracking in March 2020 from medical product regulatory authorities in all 21 APEC economies concerning areas of regulatory practice in which they could converge and cooperate. For example, from 2008 to 2020, there was a 14.3% increase in the number of APEC member economy regulatory authorities sharing Good Manufacturing Practices (GMP) Certificates and a 28% increase in the number of regulatory authorities accepting multisite licenses in that same period. In addition, this paper explores how APEC economies could realize a maximum level of regulatory convergence and cooperation. CONCLUSIONS: Convergence efforts within APEC can accelerate availability of medical products including that related to COVID-19 vaccines, treatments and diagnostics, while maintaining the availability of the existing medical products unrelated to COVID-19 vaccines and treatment. New KPIs and capability building are to be considered to enable a new era of innovation ushered in by COVID-19.

Point-of-Care Ultrasound May Reduce Misdiagnosis of Pediatric Intussusception.

Aim: Intussusception, the most common abdominal emergency in early childhood, is frequently misdiagnosed at initial presentation. The effect of using point-of-care ultrasonography (POCUS) by emergency medicine physicians on pediatric intussusception misdiagnosis rate remains unclear. Here, we summarize outcomes and misdiagnoses before and after training junior and senior physicians on using POCUS for diagnosing intussusception and compared their performance levels. Materials and Methods: This observational cohort analysis included patients with suspected intussusception who visited a pediatric emergency department (ED) between January 2017 and December 2019. All enrolled patients were evaluated by junior (<10-year experience) or senior attending physicians. Misdiagnosis was defined as a finding of negative air reduction or confirmation of diagnosis on ED revisit or admission. The misdiagnosis rates and outcomes before and after POCUS training for intussusception diagnosis were evaluated and performance of the junior and senior physicians was compared. Results: Of the 167 enrolled patients, 130 were confirmed to have intussusception by air reduction. Misdiagnosis rate was significantly lower in the post-training patient group after training than in the pre-training patient group (43.7 vs. 12.7%, P < 0.001). After training, fewer misdiagnoses were made by the junior (59.1 vs. 25.9%, P = 0.003) and senior (31.7 vs. 0%, P < 0.001) physicians. In the post-training patient group, the door-to-reduction time and rate of ultrasonography consultation with an expert also decreased significantly (118.2 ± 124.5 vs. 198 ± 250.2 min, P = 0.006). Abdominal pain (80.9%) was the most common symptom of intussusception, followed by vomiting (58.3%), fever (17.8%), bloody stool (15.4%), and diarrhea (14.2%). Even after training, the presenting symptoms of intussusception often leading junior physicians to misdiagnosis were diarrhea and fever. Conclusions: A brief POCUS training leads to decreased misdiagnosis rates in both the senior and junior physicians. Junior physicians should increase their awareness regarding diarrhea and fever being the presenting symptoms of intussusception, particularly in early childhood. Combining clinical judgment and POCUS results forms the core principle of the evaluation of children with intussusception.

Chloroquine kills hair cells in zebrafish lateral line and murine cochlear cultures: Implications for ototoxicity.

Hearing and balance deficits have been reported during and following treatment with the antimalarial drug chloroquine. However, experimental work examining the direct actions of chloroquine on mechanoreceptive hair cells in common experimental models is lacking. This study examines the effects of chloroquine on hair cells using two common experimental models: the zebrafish lateral line and neonatal mouse cochlear cultures. Zebrafish larvae were exposed to varying concentrations of chloroquine phosphate or hydroxychloroquine for 1 h or 24 h, and hair cells assessed by antibody staining. A significant, dose-dependent reduction in the number of surviving hair cells was seen across conditions for both exposure periods. Hydroxychloroquine showed similar toxicity. In mouse cochlear cultures, chloroquine damage was specific to outer hair cells in tissue from the cochlear basal turn, consistent with susceptibility to other ototoxic agents. These findings suggest a need for future studies employing hearing and balance monitoring during exposure to chloroquine and related compounds, particularly with interest in these compounds as therapeutics against viral infections including coronavirus.

Subtracted Computed Tomography Angiography in the Evaluation of Coronary Arteries With Severe Calcification or Stents Using a 320-Row Computed Tomography Scanner.

PURPOSE: Coronary computed tomography angiography (CCTA) has its limitations in evaluating arteries with stents or heavy calcification. This study compares the diagnostic performance of subtracted coronary computed tomography angiography (SCCTA) and nonsubtracted coronary computed tomography angiography (NSCCTA) in evaluating coronary artery disease (CAD) and in-stent restenosis (ISR). MATERIALS AND METHODS: Twelve patients with stents and 20 patients with heavy coronary calcifications (total Agatston's score >400) underwent both SCCTA and invasive coronary angiography (ICA) with an interval of <3 months. Four subjects in the stented group also had heavy calcifications. Overall, 30 stented segments and 202 calcified segments were assessed to compare the diagnostic performance of SCCTA and NSCCTA in detecting ISR and CAD. RESULTS: For the 30 stented segments, SCCTA/NSCCTA had a sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) (shown in %) of 66.7/100, 100/55.6, 96.7/60, 100/20, and 96.4/100 in diagnosing ISR, respectively. For the 202 calcified segments, SCCTA/NSCCTA had a sensitivity, specificity, accuracy, PPV, and NPV of 68.8/84.4, 97.6/76.5, 93.1/77.7, 84.6/40.3, and 94.3/96.3 in diagnosing CAD, respectively. For both stented and calcified segments, SCCTA was significantly superior to NSCCTA in specificity and accuracy. For the calcified segments, SCCTA was significantly superior to NSCCTA in PPV. There was no significant difference in the diagnostic performance of SCCTA between the stented and calcified segments. CONCLUSIONS: The diagnostic accuracy and specificity of SCCTA are significantly superior to those of NSCCTA in evaluating CAD and ISR. SCCTA shows no statistical difference in its diagnostic performance between the stented and calcified segments.

The Use of Artificial Intelligence in the Differentiation of Malignant and Benign Lung Nodules on Computed Tomograms Proven by Surgical Pathology.

The purpose of this work was to evaluate the performance of an existing commercially available artificial intelligence (AI) software system in differentiating malignant and benign lung nodules. The AI tool consisted of a vessel-suppression function and a deep-learning-based computer-aided-detection (VS-CAD) analyzer. Fifty patients (32 females, mean age 52 years) with 75 lung nodules (47 malignant and 28 benign) underwent low-dose computed tomography (LDCT) followed by surgical excision and the pathological analysis of their 75 nodules within a 3 month time frame. All 50 cases were then processed by the AI software to generate corresponding VS images and CAD outcomes. All 75 pathologically proven lung nodules were well delineated by vessel-suppressed images. Three (6.4%) of the 47 lung cancer cases, and 11 (39.3%) of the 28 benign nodules were ignored and not detected by the AI without showing a CAD analysis summary. The AI system/radiologists produced a sensitivity and specificity (shown in %) of 93.6/89.4 and 39.3/82.1 in distinguishing malignant from benign nodules, respectively. AI sensitivity was higher than that of radiologists, though not statistically significant (p = 0.712). Specificity obtained by the radiologists was significantly higher than that of the VS-CAD AI (p = 0.003). There was no significant difference between the malignant and benign lesions with respect to age, gender, pure ground-glass pattern, the diameter and location of the nodules, or nodules <6 vs. ≥6 mm. However, more part-solid nodules were proven to be malignant than benign (90.9% vs. 9.1%), and more solid nodules were proven to be benign than malignant (86.7% vs. 13.3%) with statistical significance (p = 0.001 and <0.001, respectively). A larger cohort and prospective study are required to validate the AI performance.

ORC-13661 protects sensory hair cells from aminoglycoside and cisplatin ototoxicity.

Aminoglycoside (AG) antibiotics are widely used to prevent life-threatening infections, and cisplatin is used in the treatment of various cancers, but both are ototoxic and result in loss of sensory hair cells from the inner ear. ORC-13661 is a new drug that was derived from PROTO-1, a compound first identified as protective in a large-scale screen utilizing hair cells in the lateral line organs of zebrafish larvae. Here, we demonstrate, in zebrafish larvae and in mouse cochlear cultures, that ORC-13661 provides robust protection of hair cells against both ototoxins, the AGs and cisplatin. ORC-13661 also prevents both hearing loss in a dose-dependent manner in rats treated with amikacin and the loading of neomycin-Texas Red into lateral line hair cells. In addition, patch-clamp recordings in mouse cochlear cultures reveal that ORC-13661 is a high-affinity permeant blocker of the mechanoelectrical transducer (MET) channel in outer hair cells, suggesting that it may reduce the toxicity of AGs by directly competing for entry at the level of the MET channel and of cisplatin by a MET-dependent mechanism. ORC-13661 is therefore a promising and versatile protectant that reversibly blocks the hair cell MET channel and operates across multiple species and toxins.

Congenital tuberculosis: case report and review of the literature.

Congenital tuberculosis is rare, even where tuberculosis (TB) is endemic. A 14-day-old girl presented with a 3-day history of fever and respiratory distress. Her mother was diagnosed with a disseminated TB infection immediately after the delivery which was confirmed by a positive TB-polymerase chain reaction (TB-PCR) and subsequent culture from ascites and sputum. The infant was separated from her mother at birth. Her chest radiograph showed bilateral miliary nodules. Congenital TB was strongly suspected because of the symptoms, signs and maternal TB history, and was confirmed by TB-PCR and culture from the gastric lavage. Timely administration of standard anti-TB therapy resulted in a good outcome. The case highlights the importance of maternal TB history and typical miliary pattern on chest radiography for early diagnosis of congenital or neonatal TB which in turn facilitates prompt treatment and the prognosis.

The Inner Ear Heat Shock Transcriptional Signature Identifies Compounds That Protect Against Aminoglycoside Ototoxicity.

Mechanosensory hair cells of the inner ear transduce auditory and vestibular sensory input. Hair cells are susceptible to death from a variety of stressors, including treatment with therapeutic drugs that have ototoxic side effects. There is a need for co-therapies to mitigate drug-induced ototoxicity, and we showed previously that induction of heat shock proteins (HSPs) protects against hair cell death and hearing loss caused by aminoglycoside antibiotics in mouse. Here, we utilized the library of integrated cellular signatures (LINCS) to identify perturbagens that induce transcriptional profiles similar to that of heat shock. Massively parallel sequencing of RNA (RNA-Seq) of heat shocked and control mouse utricles provided a heat shock gene expression signature that was used in conjunction with LINCS to identify candidate perturbagens, several of which were known to protect the inner ear. Our data indicate that LINCS is a useful tool to screen for compounds that generate specific gene expression signatures in the inner ear. Forty-two LINCS-identified perturbagens were tested for otoprotection in zebrafish, and three of these were protective. These compounds also induced the heat shock gene expression signature in mouse utricles, and one compound protected against aminoglycoside-induced hair cell death in whole organ cultures of utricles from adult mice.

T1-REDEEM: A Randomized Controlled Trial to Reduce Diabetes Distress Among Adults With Type 1 Diabetes.

OBJECTIVE: To compare the effectiveness of two interventions to reduce diabetes distress (DD) and improve glycemic control among adults with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: Individuals with T1D (n = 301) with elevated DD and HbA1c were recruited from multiple settings and randomly assigned to OnTrack, an emotion-focused intervention, or to KnowIt, an educational/behavioral intervention. Each group attended a full-day workshop plus four online meetings over 3 months. Assessments occurred at baseline and 3 and 9 months. Primary and secondary outcomes were change in DD and change in HbA1c, respectively. RESULTS: With 12% attrition, both groups demonstrated dramatic reductions in DD (effect size d = 1.06; 78.4% demonstrated a reduction of at least one minimal clinically important difference). There were, however, no significant differences in DD reduction between OnTrack and KnowIt. Moderator analyses indicated that OnTrack provided greater DD reduction to those with initially poorer cognitive or emotion regulation skills, higher baseline DD, or greater initial diabetes knowledge than those in KnowIt. Significant but modest reductions in HbA1c occurred with no between-group differences. Change in DD was modestly associated with change in HbA1c (r = 0.14, P = 0.01), with no significant between-group differences. CONCLUSIONS: DD can be successfully reduced among distressed individuals with T1D with elevated HbA1c using both education/behavioral and emotion-focused approaches. Reductions in DD are only modestly associated with reductions in HbA1c. These findings point to the importance of tailoring interventions to address affective, knowledge, and cognitive skills when intervening to reduce DD and improve glycemic control.

Prognostic impact of peritonitis in hemodialysis patients: A national-wide longitudinal study in Taiwan.

BACKGROUND: Peritonitis has been independently associated with increased morbidity and mortality in peritoneal dialysis patients. However, there are few reports on peritonitis in hemodialysis patients. We aim at investigating both the risk profiles and prognostic impact of peritonitis in hemodialysis patients. METHODS: This nation-wide longitudinal study uses claims data obtained from the Taiwan National Health Insurance Research Database. A total of 80,733 incident hemodialysis patients of age ≥ 20 years without a history of peritonitis were identified between January 1, 1998 and December 31, 2009. Predictors of peritonitis events were estimated using Cox proportional hazard models. Time-dependent Cox proportional hazard models were used to estimate hazard ratio for mortality attributed to peritonitis exposure. RESULTS: Of 80,733 incident hemodialysis patients over a 13-year study period, peritonitis was diagnosed in 935 (1.16%), yielding an incidence rate of 2.91 per 1000 person-years. Female gender, liver cirrhosis and polycystic kidney disease were three of the most significant factors for peritonitis in both non-diabetic and diabetic hemodialysis patients. The cumulative survival rate of patients with peritonitis was 38.8% at 1 year and 10.1% at 5 years. A time-dependent Cox multivariate analysis showed that peritonitis had significantly increased hazard ratio for all cause mortality. Additionally, the risk of mortality remained significantly higher for non-diabetic hemodialysis patients that experienced peritonitis. CONCLUSIONS: The risk of peritonitis in hemodialysis patients is higher in female gender, liver cirrhosis and polycystic kidney disease. Although peritonitis is a rare condition, it is associated with significantly poorer outcome in hemodialysis patients.

Impact of filter convolution and displayed field of view on estimation of coronary Agatston scores in low-dose lung computed tomography.

BACKGROUND: Coronary artery calcification (CAC) may be quantified on low-dose computed tomography (CT) of the lung (LDCT). This study aims to evaluate the effects of filter convolution (FC) and displayed field of view (dFOV) in a Toshiba 320-row CT scanner in quantifying CAC, and to compare the CAC scores obtained by LDCT with standard cardiac CT. METHODS: Fifty subjects (52 to 85years, mean 68.5, 36 males) with visible CAC underwent both standard cardiac CT and LDCT. CAC scores were obtained from standard cardiac CT using conventional FC12(22) (FC12 with 22-cm dFOV) and four different LDCT protocols: FC02(22), FC02(40), FC08(22), and FC08(40). CAC scores obtained by each LDCT protocol were compared with those obtained by standard cardiac CT. RESULTS: CAC scores obtained by all four LDCT protocols were well correlated with those by standard protocol (Pearson's coefficient=0.978 to 0.987, p<0.001; kappa=0.731 to 0.836, p<0.001). CAC scores obtained by FC08(22) showed the best agreement with standard cardiac CT (kappa=0.836, p<0.001). Under fixed dFOV, CAC scores in FC08 were significantly higher than in FC02 (p<0.001). Under fixed FC, CAC scores were significantly higher in 22-cm dFOV than in 40-cm dFOV (p≤0.006). CONCLUSIONS: Both FC and dFOV have significant impact on CAC scoring. To obtain reliable data, consistent parameters should be employed when quantifying CAC using LDCT. In a Toshiba 320-row CT scanner, CAC scores obtained by FC08(22) agree well with standard cardiac CT.

Mitochondrial calcium uptake underlies ROS generation during aminoglycoside-induced hair cell death.

Exposure to aminoglycoside antibiotics can lead to the generation of toxic levels of reactive oxygen species (ROS) within mechanosensory hair cells of the inner ear that have been implicated in hearing and balance disorders. Better understanding of the origin of aminoglycoside-induced ROS could focus the development of therapies aimed at preventing this event. In this work, we used the zebrafish lateral line system to monitor the dynamic behavior of mitochondrial and cytoplasmic oxidation occurring within the same dying hair cell following exposure to aminoglycosides. The increased oxidation observed in both mitochondria and cytoplasm of dying hair cells was highly correlated with mitochondrial calcium uptake. Application of the mitochondrial uniporter inhibitor Ru360 reduced mitochondrial and cytoplasmic oxidation, suggesting that mitochondrial calcium drives ROS generation during aminoglycoside-induced hair cell death. Furthermore, targeting mitochondria with free radical scavengers conferred superior protection against aminoglycoside exposure compared with identical, untargeted scavengers. Our findings suggest that targeted therapies aimed at preventing mitochondrial oxidation have therapeutic potential to ameliorate the toxic effects of aminoglycoside exposure.