Bacterial production of recombinant contraceptive vaccine antigen from CatSper displayed on a human papilloma virus-like particle.

CatSper is a voltage dependent calcium ion channel present in the principal piece of sperm tail. It plays a crucial role in sperm hyperactivated motility and so in fertilization. Extracellular loops of mouse sperm CatSper were used to develop a vaccine to achieve protection from pregnancy. These loops were inserted at one of the three hypervariable regions of Human Papilloma Virus (HPV) capsid protein (L1). Recombinant vaccines were expressed in E.coli as inclusion body (IB), purified, refolded and assembled into virus-like particles (VLP) in vitro, and adsorbed on alum. Four vaccine candidates were tested in Balb/C mice. All the constructs proved immunogenic, one showed contraceptive efficacy. This recombinant contraceptive vaccine is a non-hormonal intervention and is expected to give long-acting protection from undesired pregnancies.

Deep-learning model associating lateral cervical radiographic features with Cormack-Lehane grade 3 or 4 glottic view.

Unanticipated difficult laryngoscopy is associated with serious airway-related complications. We aimed to develop and test a convolutional neural network-based deep-learning model that uses lateral cervical spine radiographs to predict Cormack-Lehane grade 3 or 4 direct laryngoscopy views of the glottis. We analysed the radiographs of 5939 thyroid surgery patients at our hospital, 253 (4%) of whom had grade 3 or 4 glottic views. We used 10 randomly sampled datasets to train a model. We compared the new model with six similar models (VGG, ResNet, Xception, ResNext, DenseNet and SENet). The Brier score (95%CI) of the new model, 0.023 (0.021-0.025), was lower ('better') than the other models: VGG, 0.034 (0.034-0.035); ResNet, 0.033 (0.033-0.035); Xception, 0.032 (0.031-0.033); ResNext, 0.033 (0.032-0.033); DenseNet, 0.030 (0.029-0.032); SENet, 0.031 (0.029-0.032), all p < 0.001. We calculated mean (95%CI) of the new model for: R2 , 0.428 (0.388-0.468); mean squared error, 0.023 (0.021-0.025); mean absolute error, 0.048 (0.046-0.049); balanced accuracy, 0.713 (0.684-0.742); and area under the receiver operating characteristic curve, 0.965 (0.962-0.969). Radiographic features around the hyoid bone, pharynx and cervical spine were associated with grade 3 and 4 glottic views.

The effect of cricoid and paralaryngeal force on upper oesophageal occlusion during induction of anaesthesia: a randomised, crossover study.

The aim of this study was to evaluate the effectiveness of cricoid and paralaryngeal force for oesophageal entrance occlusion during induction of anaesthesia. Seventy-four patients were included in this randomised, crossover study. The relative position of the glottis and outer anteroposterior diameter of the upper oesophageal entrance were assessed at baseline, after the application of 30 N cricoid and paralaryngeal force, and after induction of anaesthesia. The occlusion rate of the oesophageal entrance with cricoid and paralaryngeal force was assessed during direct laryngoscopy. The relative position of the upper oesophageal entrance to the glottis changed in 45 out of 74 patients after induction of anaesthesia and during direct laryngoscopy compared with the awake state. The application of cricoid and paralaryngeal force decreased the mean (SD) diameter of the upper oesophageal entrance to a similar degree in awake (8.5 (2.1) mm to 6.4 (1.7) mm and 6.5 (1.6) mm, respectively; p < 0.001) and anaesthetised (8.7 (2.2) mm to 6.5 (1.7) mm and (6.7 (1.9) mm, respectively; p < 0.001) states. During direct laryngoscopy, the occlusion rate of the oesophageal entrance was greater with cricoid compared with paralaryngeal force (46/74 vs. 26/74, respectively; p = 0.002). The relative position of the upper oesophageal entrance to the glottis may change after induction of anaesthesia and during direct laryngoscopy. Cricoid and paralaryngeal force both decrease the diameter of the upper oesophageal entrance in awake and anaesthetised states. Occlusion of the oesophageal entrance is achieved more frequently with cricoid force compared with paralaryngeal force during direct laryngoscopy.

Comparison of image quality of abdominopelvic CT in paediatric patients: low osmolar contrast media versus less iodine-containing iso-osmolar contrast media at different peak kilovoltages.

AIM: To evaluate the effect of iso-osmolar contrast media (IOCM) at different tube voltages on image quality for abdominal computed tomography (CT) in paediatric patients. MATERIALS AND METHODS: The low osmolar contrast media (LOCM) group and IOCM group consisted of 101 and 102 CT examinations, respectively, in patients <18 years old. Images were reviewed retrospectively. Objective measurement of the contrast enhancement and noise were analysed and contrast-to-noise ratios (CNRs) of the abdominal aorta, portal vein, and liver were calculated. Four radiologists participated in subjective analysis using a four-point scale system to evaluate degrees of contrast enhancement, image noise, beam-hardening artefact, and overall image quality. Reader performance for correctly differentiating the two kinds of contrast media was evaluated. RESULTS: Regarding the objective measurement, contrast enhancement was significantly higher in the LOCM group (p<0.05). In subjective analysis, only CT using 120 kVp showed significantly stronger enhancement in the LOCM group (p=0.002), and sensitivity to differentiate the IOCM was 80.6%. Overall sensitivity and specificity for correctly differentiating IOCM were 57.1%, and 56.9%, respectively. CONCLUSION: The application of IOCM was found to be feasible for performing paediatric abdominopelvic CT with a low tube voltage protocol. Although objective measurements of contrast enhancement were significantly lower in the IOCM group, subjective contrast enhancement and image quality assessments were not statistically different between groups.

High-Frequency Ultrasound Imaging for Examination of Early Dental Caries.

The extent of dental tissue destruction during the treatment of white spot lesions (WSLs) increases with the severity of the lesion. If the depth and shape of WSLs can be predicted with a noninvasive diagnostic method before dental caries treatment, more conservative interventions can be planned. Given the superiority of high-frequency ultrasound (HFUS) imaging in observing the internal structures of the body, the present study aimed to verify the possibility of HFUS imaging to examine the depth and shape of WSLs. We prepared tooth samples and developed a biomicroscopic system with a HFUS transducer to obtain images of normal and WSL regions. HFUS images were compared with conventional ultrasound images and micro-computed tomography images. HFUS distinctly differentiated demineralization within WSL and normal regions. WSL depth calculated in the micro-computed tomography image was similar to that in HFUS. This study revealed that HFUS imaging has the potential to detect early dental caries and offer information on the invasion depth of early dental caries quantitatively.

Devising negative pressure within intercuff space reduces microaspiration.

BACKGROUND: Microaspiration past the tracheal tube cuffs causes ventilator-associated pneumonia. The objective of the current study was to evaluate whether creating negative pressure between the tracheal double cuffs could block the fluid passage past the tracheal tube cuffs. METHODS: A new negative pressure system was devised between the double cuffs through a suction hole in the intercuff space. Blue-dyed water was instilled above the cuff at negative suction pressures of - 54, - 68, - 82, - 95, - 109, - 122, and - 136 cmH2O, and the volume leaked was measured in an underlying water trap after 10 min. Leakage tests were also performed during positive pressure ventilation, and using higher-viscosity materials. The actual negative pressures delivered at the hole of double cuffs were obtained by placing microcatheter tip between the intercuff space and the artificial trachea. RESULTS: No leakage occurred past the double cuff at - 136 cmH2O suction pressure at all tracheal tube cuff pressures. The volume leaked decreased significantly as suction pressure increased. When connected to a mechanical ventilator, no leakage was found at - 54 cmH2suction pressure. Volume of the higher-viscosity materials (dynamic viscosity of 63-108 cP and 370-430 cP) leaked was small compared to that of normal saline (0.9-1.1 cP). The pressures measured in the intercuff space corresponded to 3.8-5.9% of those applied. CONCLUSIONS: A new prototype double cuff with negative pressure in the intercuff space completely prevented water leakage. The negative pressure transmitted to the tracheal inner wall was a small percentage of that applied.

Dynamic assembly of liquid crystalline graphene oxide gel fibers for ion transport.

Colloidal dispersions with liquid crystallinity hold great promise for fabricating their superstructures. As an example, when graphene oxide (GO) sheets are assembled in the liquid crystalline state, they can turn into ordered macroscopic forms of GO such as fibers via the wet spinning process. Here, we report that by reinforcing intersheet interactions, GO liquid crystals (LCs) turn into mechanically robust hydrogels that can be readily drawn into highly aligned fibrillar structures. GO hydrogel fibers with highly aligned sheets (orientation factor, f = 0.71) exhibit more than twice the ionic conductivity compared to those with partially aligned structures (f = 0.01). The hierarchically interconnected two-dimensional nanochannels within these neatly aligned GOLC hydrogel fibers may facilitate controlled transport of charge carriers and could be potentially explored as cables for interconnecting biosystems and/or human-made devices.

Rational Design of Low Cost and High Energy Lithium Batteries through Tailored Fluorine-free Electrolyte and Nanostructured S/C Composite.

We report a new Li-S cell concept based on an optimized F-free catholyte solution and a high loading nanostructured C/S composite cathode. The Li2 S8 present in the electrolyte ensures both buffering against active material dissolution and Li+ conduction. The high S loading is obtained by confining elemental S (≈80 %) in the pores of a highly ordered mesopores carbon (CMK3). With this concept we demonstrate stabilization of a high energy density and excellent cycling performance over 500 cycles. This Li-S cell has a specific capacity that reaches over 1000 mA h g-1 , with an overall S loading of 3.6 mg cm-2 and low electrolyte volume (i.e., 10 µL cm-2 ), resulting in a practical energy density of 365 Wh kg-1 . The Li-S system proposed thus meets the requirements for large scale energy storage systems and is expected to be environmentally friendly and have lower cost compared with the commercial Li-ion battery thanks to the removal of both Co and F from the overall formulation.

Percutaneous nephrostomy placement in infants and young children.

PURPOSE: The purpose of this study was to evaluate the feasibility, safety, and clinical effectiveness of ultrasound and fluoroscopy-guided percutaneous nephrostomy (PCN) placement in infants and young children. MATERIALS AND METHODS: Between January 2000 and December 2015, 57 patients had a total of 66 fluoroscopically guided PCN placement procedures. There were 37 boys and 20 girls with a mean age 8.6±15.3 (SD) months (range: 1 day-75.5months). The most common underlying disease was upper-urinary-tract obstruction, including ureteropelvic-junction stenosis (27/66, 40.9%) and ureterovesical-junction stenosis (16/66, 24.2%). Technical success, complications, clinical effectiveness, and radiation exposure were retrospectively analyzed. Technical success was defined as completion of PCN catheter in the renal calyx or proximal ureter. Complications were graded in severity using the Common Terminology Criteria for Adverse Event (version 4.03). Clinical effectiveness was evaluated with presence of decompression of the hydronephrosis on follow-up ultrasonography. RESULTS: All PCN placement procedures were technically successful. A total of 37 complications were identified in 33/37 procedures (89.2%), with transient gross hematuria (n=28) being most common (mean hematuria duration 2.2±1.4 [range: 1-6] days), which were grade 1 Postprocedural fever occurred after eight procedures; four and three patients were graded 1 and 2, respectively. Complete hydronephrosis decompression was achieved in 35/53 kidneys (66%), incomplete hydronephrosis decompression in 17/55 kidneys (32.1%), and progression of hydronephrosis was noted in 1/55 kidney (1.9%). Dose-area-product (DAP) was 44.86±89 (SD) (range: 3.7-464) µGycm2 and cumulative dose was 10.3±20.4 (SD) (range: 0.3-97.9) mGy. CONCLUSION: PCN is a feasible and effective treatment option to relieve urinary obstruction, and can serve as a bridging procedure until definitive corrective surgery in pediatric patients.

Image quality of CT angiography in young children with congenital heart disease: a comparison between the sinogram-affirmed iterative reconstruction (SAFIRE) and advanced modelled iterative reconstruction (ADMIRE) algorithms.

AIM: To compare the image quality of computed tomography angiography (CTA) reconstructed by sinogram-affirmed iterative reconstruction (SAFIRE) with that of advanced modelled iterative reconstruction (ADMIRE) in children with congenital heart disease (CHD). MATERIAL AND METHODS: Thirty-one children (8.23±13.92 months) with CHD who underwent CTA were enrolled. Images were reconstructed using SAFIRE (strength 5) and ADMIRE (strength 5). Objective image qualities (attenuation, noise) were measured in the great vessels and heart chambers. Two radiologists independently calculated the contrast-to-noise ratio (CNR) by measuring the intensity and noise of the myocardial walls. Subjective noise, diagnostic confidence, and sharpness at the level prior to the first branch of the main pulmonary artery were also graded by the two radiologists independently. RESULTS: The objective image noise of ADMIRE was significantly lower than that of SAFIRE in the right atrium, right ventricle, and myocardial wall (p<0.05); however, there were no significant differences observed in the attenuations among the four chambers and great vessels, except in the pulmonary arteries (p>0.05). The mean CNR values were 21.56±10.80 for ADMIRE and 18.21±6.98 for SAFIRE, which were significantly different (p<0.05). In addition, the diagnostic confidence of ADMIRE was significantly lower than that of SAFIRE (p<0.05), while the subjective image noise and sharpness of ADMIRE were not significantly different (p>0.05). CONCLUSION: CTA using ADMIRE was superior to SAFIRE when comparing the objective and subjective image quality in children with CHD.

The association between whole body sagittal balance and risk of falls among elderly patients seeking treatment for back pain.

OBJECTIVES: The objective of this study was to assess the association between whole body sagittal balance and risk of falls in elderly patients who have sought treatment for back pain. Balanced spinal sagittal alignment is known to be important for the prevention of falls. However, spinal sagittal imbalance can be markedly compensated by the lower extremities, and whole body sagittal balance including the lower extremities should be assessed to evaluate actual imbalances related to falls. METHODS: Patients over 70 years old who visited an outpatient clinic for back pain treatment and underwent a standing whole-body radiograph were enrolled. Falls were prospectively assessed for 12 months using a monthly fall diary, and patients were divided into fallers and non-fallers according to the history of falls. Radiological parameters from whole-body radiographs and clinical data were compared between the two groups. RESULTS: A total of 144 patients (120 female patients and 24 male patients) completed a 12-month follow-up for assessing falls. A total of 31 patients (21.5%) reported at least one fall within the 12-month follow-up. In univariate logistic regression analysis, the risk of falls was significantly increased in older patients and those with more medical comorbidities, decreased lumbar lordosis, increased sagittal vertical axis, and increased horizontal distance between the C7 plumb line and the centre of the ankle (C7A). Increased C7A was significantly associated with increased risk of falls even after multivariate adjustment. CONCLUSION: Whole body sagittal balance, measured by the horizontal distance between the C7 plumb line and the centre of the ankle, was significantly associated with risk of falls among elderly patients with back pain.Cite this article: J. Kim, J. Y. Hwang, J. K. Oh, M. S. Park, S. W. Kim, H. Chang, T-H. Kim. The association between whole body sagittal balance and risk of falls among elderly patients seeking treatment for back pain. Bone Joint Res 2017;6:-344. DOI: 10.1302/2046-3758.65.BJR-2016-0271.R2.

Whole-exome sequencing study reveals common copy number variants in protocadherin genes associated with childhood obesity in Koreans.

Recently, the prevalence of childhood obesity has significantly increased in industrialized countries, including Korea, and now controlling obesity is becoming an economic burden. However, knowledge of the risk factors associated with obesity is still limited. In this study, we aimed to discover additional obesity-associated loci in children. To achieve this, we conducted an exome-wide association analysis of copy number variation (CNV) using whole-exome sequencing (WES) data from a total of 102 cases and 86 controls. We newly identified a CNV locus that overlapped two protocadherin genes, PCDHB7 and PCDHB8, which are brain function-related genes (P-value=6.40 × 10-4, odds ratio=2.2189). A subsequent replication analysis using WES data from 203 obese and 291 normal weight children showed that this CNV region satisfied the genome-wide significance standard (Fisher's combined P-value=3.76 × 10-5). Moreover, correlation test using 199 additional samples supported significant association between CNV and increased body mass index. This region also showed a meaningful association with 273 cases and 2596 controls in adult samples. Our findings suggest that differences in the common CNV region at 5q31.3 may have an impact on the pathophysiology of obesity.

Proteolytic degradation and potential role of onconeural protein cdr2 in neurodegeneration.

Cerebellar degeneration-related protein 2 (cdr2) is expressed in the central nervous system, and its ectopic expression in tumor cells of patients with gynecological malignancies elicits immune responses by cdr2-specific autoantibodies and T lymphocytes, leading to neurological symptoms. However, little is known about the regulation and function of cdr2 in neurodegenerative diseases. Because we found that cdr2 is highly expressed in the midbrain, we investigated the role of cdr2 in experimental models of Parkinson's disease (PD). We found that cdr2 levels were significantly reduced after stereotaxic injection of 1-methyl-4-phenylpyridinium (MPP(+)) into the striatum. cdr2 levels were also decreased in the brains of post-mortem PD patients. Using primary cultures of mesencephalic neurons and MN9D cells, we confirmed that MPP(+) reduces cdr2 in tyrosine hydroxylase-positive dopaminergic neuronal cells. The MPP(+)-induced decrease of cdr2 was primarily caused by calpain- and ubiquitin proteasome system-mediated degradation, and cotreatment with pharmacological inhibitors of these enzymes or overexpression of calcium-binding protein rendered cells less vulnerable to MPP(+)-mediated cytotoxicity. Consequently, overexpression of cdr2 rescued cells from MPP(+)-induced cytotoxicity, whereas knockdown of cdr2 accelerated toxicity. Collectively, our findings provide insights into the novel regulatory mechanism and potentially protective role of onconeural protein during dopaminergic neurodegeneration.

Strengthening behavior of carbon/metal nanocomposites.

Nanocomposites reinforced with nano-scale reinforcements exhibit excellent mechanical properties with low volume fraction of the reinforcement. For instance, only an addition of 0.7 vol.% few-layer graphene (FLG) into the pure titanium shows strength of ~1.5 GPa, obviously much superior to that of the monolithic titanium. The strengthening efficiency of composites is determined by several factors such as reinforcement geometrical/spatial characteristics and interfacial features between the matrix and the reinforcement. For the metal-matrix nanocomposites (MMNCs), since the nano-scale reinforcement has significantly high specific surface area, interfacial feature is more important and has to be clearly evaluated in understanding property of MMNCs. Although many researchers suggested the theoretical work using continuum mechanics in order to estimate the mechanical properties of the metallic composites, a clear determination has yet not to be proven by systematic experimental works. Here, we provide a new model to predict strength and stiffness of MMNCs based on quantitative analysis of efficiency parameters in which interface feature is strongly emphasized. To validate the model, we select multi-walled carbon nanotube (MWCNT) and FLG for reinforcement, and titanium (Ti) and aluminum (Al) for the matrix to modify bonding strength and specific surface area in the MMNCs.

Involvement of the Nrf2/HO-1 signaling pathway in sulfuretin-induced protection against amyloid beta25-35 neurotoxicity.

Sulfuretin, one of the major flavonoid glycosides found in the stem bark of Albizzia julibrissin and heartwood of Rhus verniciflua, is a known anti-oxidant. We previously demonstrated that sulfuretin inhibits neuronal death via reactive oxygen species (ROS)-dependent mechanisms in human SH-SY5Y cells, although other relevant mechanisms of action of this compound remain largely uncharacterized. As part of our ongoing exploration of the pharmacological actions of sulfuretin, we studied the neuroprotective effects of sulfuretin against amyloid beta (Aß)-induced neurotoxicity in human SH-SY5Y and primary hippocampal neuron cells and investigated the possible mechanisms involved. Specifically, we found in the present study that sulfuretin significantly attenuates the decrease in cell viability, release of lactate dehydrogenase, and accumulation of ROS associated with Aß25-35-induced neurotoxicity in neuronal cells. Furthermore, sulfuretin stimulated the activation of nuclear factor erythroid 2-related factor 2 (Nrf2), a downstream target of phosphatidylinositol 3-kinases (PI3K)/Akt. We demonstrated that sulfuretin induces the expression of heme oxygenase-1 (HO-1), an anti-oxidant response gene. Notably, we found that the neuroprotective effects of sulfuretin were diminished by an Nrf2 small interfering RNA (siRNA), the HO-1 inhibitor zinc protoporphyrin IX (ZnPP), as well as the PI3K/Akt inhibitor LY294002. Taken together, these results indicated that sulfuretin protects neuronal cells from Aß25-35-induced neurotoxicity through activation of Nrf/HO-1 and PI3K/Akt signaling pathways. Our results also indicate that sulfuretin-induced induction of Nrf2-dependent HO-1 expression via the PI3K/Akt signaling pathway has preventive and/or therapeutic potential for the management of Alzheimer's disease.

Effects of the jaw-thrust manoeuvre in the semi-sitting position on securing a clear airway during fibreoptic intubation.

Securing a clear airway is important for successful fibreoptic intubation. We investigated whether the jaw-thrust manoeuvre in the 25° semi-sitting position improves airway clearance compared with the supine position in 88 anaesthetised patients randomly assigned to the two positions. After induction of anaesthesia, the fibreoptic bronchoscope was advanced into the mouth along the dorsum of the tongue during the jaw-thrust manoeuvre. Airway clearance was assessed at the level of the soft palate and epiglottis. Patients in the 25° semi-sitting position had clearer airways (judged subjectively by a three-level scale) than those in the supine position at the soft palate level (p = 0.012). At the level of the epiglottis, airway clearance was equally good in both positions. The mean (SD) times to view the vocal cord and carina were shorter in the 25° semi-sitting position (4 (1) s and 8 (1) s, respectively) compared with the supine position (6 (3) s and 11 (3) s; p < 0.001, respectively). The time to achieve intubation was also shorter in the 25° semi-sitting position (21 (5) s) than in the supine position (25 (7) s; p = 0.018).

Post-infectious bronchiolitis obliterans in children: CT features that predict responsiveness to pulse methylprednisolone.

OBJECTIVE: Intravenous pulse methylprednisolone therapy (IPMT) is an important treatment option for post-infectious obliterative bronchiolitis (OB), although it must be used carefully and only in selected patients because of its drawbacks. This study evaluated whether CT and clinical features of children with post-infectious OB can predict their responsiveness to IPMT. METHODS: We searched the medical records for patients (less than 18 years of age) who were diagnosed with post-infectious OB between January 2000 and December 2011. 17 children who received IPMT were included in this study. All underwent chest CT before and after IPMT. The radiological features seen on pre-treatment CT were recorded. The air-trapping area percentages on pre- and post-treatment CT images were determined. The nine patients who exhibited decreased air trapping on post-treatment CT scans relative to pre-treatment scans were classed as responders. The patient ages and time from initial pneumonia to IPMT were recorded. RESULTS: All responders and only four non-responders had thickened bronchial walls before treatment (p = 0.029). The two groups did not differ significantly in terms of bronchiolitis, bronchiectasis or the extent of air trapping, although the responders had a significantly shorter median interval between initial pneumonia and IPMT (4 vs 50 months; p = 0.005) and were significantly younger (median, 2.0 vs 7.5 years; p = 0.048). CONCLUSION: Immediate IPMT may improve the degree of air trapping in children with post-infectious OB if they show a thickened bronchial wall on CT. ADVANCES IN KNOWLEDGE: Children with post-infectious OB may respond favourably to IPMT when pre-treatment CT indicates bronchial-wall thickening.

Relationship of maternal grain intake and serum triglyceride levels with infant birth weight: Mothers and Children's Environmental Health (MOCEH) study.

BACKGROUND/OBJECTIVES: Maternal serum triglyceride (TG) level is known to be associated with neonatal birth weight. Although Koreans traditionally consume relatively high amounts of grain and grain products, mainly in the form of white rice, and the consumption is positively associated with serum TG levels, no study has investigated the relationship between dietary grain intake, serum TG levels and neonatal birth weight in pregnant women. This study was conducted to identify the association between infant birth weight and maternal intake of grain, as well as serum TG levels. SUBJECTS/METHODS: Subjects were 1011 pregnant women at 12-28 weeks' gestational age and their offspring. Maternal serum TG levels, dietary intake and infant birth weight were measured. RESULTS: Serum TG levels were positively related to neonatal birth weight both at mid-pregnancy (P=0.0015) and at late pregnancy (P<0.0001). Such an association only existed in subjects with the highest tertile of grain intake at mid-pregnancy (P=0.0055) but was observed in all tertiles at late pregnancy (1st P=0.0186, 2nd P=0.0146, 3rd P=0.0099). CONCLUSIONS: The relationship between maternal TG levels and infant birth weight may depend on dietary grain intake and stages of pregnancy in Korean pregnant women.

The impact of drug-resistant cytomegalovirus in pediatric allogeneic hematopoietic cell transplant recipients: a prospective monitoring of UL97 and UL54 gene mutations.

BACKGROUND: Cytomegalovirus (CMV) infection is a major cause of morbidity in allogeneic hematopoietic cell transplant (alloHCT) recipients. Little is known about the epidemiology of antiviral resistance in the pediatric population. We performed the prospective study to assess the impact of drug-resistant CMV infections in pediatric alloHCT recipients. METHODS: Pediatric alloHCT recipients who developed CMV infection were consecutively enrolled from May 2009 to April 2012. CMV polymerase chain reaction amplification and sequencing analysis for UL97 and UL54 genes were performed at enrollment and during follow-up. RESULTS: In total, 208 sequence data from viruses in 49 recipients were eligible for the final analysis. Resistant CMV infection caused by UL97 and UL54 mutations occurred in 4.1% (2/49) and 2.0% (1/49), respectively. Known UL97 mutations, M460V and C592G, were observed in each of 2 patients. One patient with the M460V UL97 mutation had an additional T700A UL54 mutation. Drug-resistant CMV attributable mortality was 2.0% (1/49). One or more known sequence variants (drug-sensitive) were observed in all 49 patients. Thirty-one (63.3%) and 28 patients (60.9%) already had known UL97 and UL54 sequence variants before antiviral therapy, respectively. CONCLUSION: This study provides comprehensive information on the epidemiology of both UL97 and UL54 variants and mutations in alloHCT recipients.

Effect of adjunctive dipyridamole to DAPT on platelet function profiles in stented patients with high platelet reactivity. The result of the ACCEL-DIP Study.

Adjunctive use of phosphodiesterase (PDE) inhibitor can enhance antiplatelet and vasoprotective properties in patients with cardiovascular disease. The aim of this study was to evaluate the impact of PDE5 inhibitor dipyridamole on platelet function in stented patients with high platelet reactivity (HPR) during dual antiplatelet therapy (DAPT) with aspirin and clopidogrel. Patients with HPR after 600-mg clopidogrel loading were randomly assigned to adjunctive dipyridamole 75 mg twice daily to standard DAPT (DIP group; n = 45) or double-dose clopidogrel of 150 mg daily (DOUBLE group; n = 46) for 30 days. Platelet function was assessed at baseline and 30-day follow-up with platelet reactivity index (PRI) by vasodilator-stimulated phosphoprotein-phosphorylation (VASP-P) assay and platelet aggregation (PA) by light transmittance aggregometry (LTA). Primary endpoint was PRI at 30-day follow-up. HPR was defined as PRI > 50%. Baseline platelet function did not differ between the groups. Following 30-day therapy, platelet function was significantly reduced in the DIP and DOUBLE groups (all p-values ≤ 0.004 and ≤ 0.068, respectively). PRI values were not significantly different between the two groups (mean difference: 3.1%; 95% confidence interval: -2.8% to 9.0%: p = 0.295). PA values and prevalence of HPR were similar between the groups. However, a significant number of patients still exhibited HPR in the DIP (75.6%) and DOUBLE (67.4%) groups. In conclusion, among stented HPR patients, adding dipyridamole to DAPT does not reduce platelet reactivity and prevalence of HPR compared with double-dose clopidogrel therapy, and therefore both strategies are inadequate to overcome HPR.