Pretransplant BKV-IgG serostatus and BKV-specific ELISPOT assays to predict BKV infection after kidney transplantation

IntroductionPolyomavirus (BKV) infection can lead to major complications and damage to the graft in kidney transplant recipients (KTRs). We investigated whether pretransplant BK serostatus and BK-specific cell-mediated immunity (CMI) predicts post-transplant BK infection.MethodsA total of 93 donor-recipient pairs who underwent kidney transplantation (KT) and 44 healthy controls were examined. Assessment of donor and recipient BKV serostatus and BKV-CMI in recipients was performed prior to transplantation using BKV-IgG ELISA and BKV-specific IFN-g ELISPOT assays against five BK viral antigens (LT, St, VP1, VP2, and VP3). BK viremia was diagnosed when blood BKV-DNA of 104 copies/mL or more was detected during follow-up periods. ResultsAnti-BKV IgG antibody was detected in 74 (79.6%) of 93 KTRs and in 68 (73.1%) of 93 KT donors. A greater percentage of KTRs who received allograft from donors with high levels of anti-BKV IgG had posttransplant BK viremia (+) than KTRs from donors with low anti-BKV IgG (25.5% [12/47] vs. 4.3% [2/46], respectively; P = 0.007). Pretransplant total BKV-ELISPOT results were lower in BK viremia (+) patients than in patients without viremia (-) 20.5 [range 9.9−63.6] vs. 72.0 [43.2 - 110.8]; P = 0. 027). The sensitivity and specificity of the total BKV-ELISPOT assay (cut-off ≤ 53 spots/3×105 cells) for prediction of posttransplant BK viremia were 71.4 (95% CI: 41.9–91.6) and 54.4 (42.8–65.7), respectively. The combination of high donor BKV-IgG, low recipient BKV-IgG, and low total BKV-ELISPOT results improved specificity to 91.1%.DiscussionOur study highlights the importance of pretransplant BKV-IgG serostatus and BKV-specific CMI in predicting posttransplant BKV infection in KTRs. The combination of high donor BKV-IgG, low recipient BKV-IgG, and low total BKV-ELISPOT results predicted BK viremia after KT. Pretransplant identification of patients at highrisk for BK viremia could enable timely interventions and improve clinical outcomes of KTRs

What Drives Task Performance During Animal Fluency in People With Alzheimer's Disease?

Background Animal fluency is a widely used task to assess people with Alzheimer's disease (AD) and other neurological disorders. The mechanisms that drive performance in this task are argued to rely on language and executive functions. However, there is little information regarding what specific aspects of these cognitive processes drive performance on this task. Objective To understand which aspects of language (i.e., semantics, phonological output lexicon, phonological assembly) and executive function (i.e., mental set shifting; information updating and monitoring; inhibition of possible responses) are involved in the performance of animal fluency in people with AD. Methods Animal fluency data from 58 people with probable AD from the DementiaBank Pittsburgh Corpus were analyzed. Number of clusters and switches were measured and nine word properties (e.g., frequency, familiarity) for each of the correct words (i.e., each word counting toward the total score, disregarding non-animals and repetitions) were determined. Random forests were used to understand which variables predicted the total number of correct words, and conditional inference trees were used to search for interactions between the variables. Finally, Wilcoxon tests were implemented to cross-validate the results, by comparing the performance of participants with scores below the norm in animal fluency against participants with scores within the norm based on a large normative sample. Results Switches and age of acquisition emerged as the most important variables to predict total number of correct words in animal fluency in people with AD. Cross-validating the results, people with AD whose animal fluency scores fell below the norm produced fewer switches and words with lower age of acquisition than people with AD with scores in the normal range. Conclusion The results indicate that people with AD rely on executive functioning (information updating and monitoring) and language (phonological output lexicon, not necessarily semantics) to produce words on animal fluency

Cutaneous Schwannoma Presented as a Pedunculated Protruding Mass

Schwannoma is a benign neoplasm of the nerve sheath origin. It arises from the nerve sheath of large peripheral or cranial nerves and occurs at the level of the subcutaneous fat layer or deeper layer. Cutaneous schwannoma occurs more superficially and usually presents as a solitary dermal or subcutaneous nodule. We describe a case of cutaneous schwannoma that presented as an erythematous pedunculated protruding mass on the left flank of a 19-year-old female. It was clinically diagnosed as a granuloma pyogenicum. Shaving biopsy was conducted and histological examination revealed an encapsulated tumor mass containing dense, spindle-shaped cells whose nuclei are arranged back to back representing Verocay body, and a diagnosis of schwannoma was made. This is an unusual case of cutaneous schwannoma that presented as a pedunculated protruding mass

Renormalization group theory for percolation in time-varying networks

Motivated by multi-hop communication in unreliable wireless networks, we present a percolation theory for time-varying networks. We develop a renormalization group theory for a prototypical network on a regular grid, where individual links switch stochastically between active and inactive states. The question whether a given source node can communicate with a destination node along paths of active links is equivalent to a percolation problem. Our theory maps the temporal existence of multi-hop paths on an effective two-state Markov process. We show analytically how this Markov process converges towards a memory-less Bernoulli process as the hop distance between source and destination node increases. Our work extends classical percolation theory to the dynamic case and elucidates temporal correlations of message losses. Quantification of temporal correlations has implications for the design of wireless communication and control protocols, e.g. in cyber-physical systems such as self-organized swarms of drones or smart traffic networks.Comment: 8 pages, 3 figure

Acute Viral Myopericarditis Presenting as a Transient Effusive-Constrictive Pericarditis Caused by Coinfection with Coxsackieviruses A4 and B3

Acute myopericarditis is usually caused by viral infections, and the most common cause of viral myopericarditis is coxsackieviruses. Diagnosis of myopericarditis is made based on clinical manifestations of myocardial (such as myocardial dysfunction and elevated serum cardiac enzyme levels) and pericardial (such as inflammatory pericardial effusion) involvement. Although endomyocardial biopsy is the gold standard for the confirmation of viral infection, serologic tests can be helpful. Conservative management is the mainstay of treatment in acute myopericarditis. We report here a case of a 24-year-old man with acute myopericarditis who presented with transient effusive-constrictive pericarditis. Echocardiography showed transient pericardial effusion with constrictive physiology and global regional wall motion abnormalities of the left ventricle. The patient also had an elevated serum troponin I level. A computed tomogram of the chest showed pericardial and pleural effusion, which resolved after 2 weeks of supportive treatment. Serologic testing revealed coxsackievirus A4 and B3 coinfection. The patient received conservative medical treatment, including nonsteroidal anti-inflammatory drugs, and he recovered completely with no complications

Polymer Micelle Formulation for the Proteasome Inhibitor Drug Carfilzomib: Anticancer Efficacy and Pharmacokinetic Studies in Mice

Carfilzomib (CFZ) is a peptide epoxyketone proteasome inhibitor approved for the treatment of multiple myeloma (MM). Despite the remarkable efficacy of CFZ against MM, the clinical trials in patients with solid cancers yielded rather disappointing results with minimal clinical benefits. Rapid degradation of CFZ in vivo and its poor penetration to tumor sites are considered to be major factors limiting its efficacy against solid cancers. We previously reported that polymer micelles (PMs) composed of biodegradable block copolymers poly(ethylene glycol) (PEG) and poly(caprolactone) (PCL) can improve the metabolic stability of CFZ in vitro. Here, we prepared the CFZ-loaded PM, PEG-PCL-deoxycholic acid (CFZ-PM) and assessed its in vivo anticancer efficacy and pharmacokinetic profiles. Despite in vitro metabolic protection of CFZ, CFZ-PM did not display in vivo anticancer efficacy in mice bearing human lung cancer xenograft (H460) superior to that of the clinically used cyclodextrin-based CFZ (CFZ-CD) formulation. The plasma pharmacokinetic profiles of CFZ-PM were also comparable to those of CFZ-CD and the residual tumors that persisted in xenograft mice receiving CFZ-PM displayed an incomplete proteasome inhibition. In summary, our results showed that despite its favorable in vitroperformances, the current CFZ-PM formulation did not improve in vivo anticancer efficacy and accessibility of active CFZ to solid cancer tissues over CFZ-CD. Careful consideration of the current results and potential confounding factors may provide valuable insights into the future efforts to validate the potential of CFZ-based therapy for solid cancer and to develop effective CFZ delivery strategies that can be used to treat solid cancers

The Relationship between the Level of Fatness and Fitness during Adolescence and the Risk Factors of Metabolic Disorders in Adulthood

BACKGROUND: The purpose of the current study was to investigate the association between the level of obesity and physical fitness (PF) during adolescence and the risk factors of metabolic disorders during adulthood. METHODS: In the current analysis, 3,993 Korean adults (mean age, 38.70 +/- 1.69 years) were recruited. The level of body index (BI) and PF were examined during adolescence through high school record, and their health examination data, including systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glucose (FG), total cholesterol (TC), and current body mass index (BMI) were obtained from National Health Insurance Corporation Data. Gender-specific analyses were administered to compare health exam data across the level of BI, the level of PF, and a mixed level of BI and PF. RESULTS: Most obese males during high school had statistically higher SBP, DBP, FG, and BMI in adulthood, and most obese females had higher BMI, as compared to most lean males or females. Least fit males during high school had statistically higher BMI in adulthood, and least fit females had statistically higher SBP, DBP, FG, TC, and BMI, as compared to most fit males or females. There was a significant relationship between the mixed level of BI and PF and SBP, DBP, TC and current BMI in both genders. CONCLUSION: Maintaining a healthy level of body weight and PF during adolescence is recommended to prevent the development of metabolic diseases in adulthood.ope

B-cell Complement Dependent Cytotoxic Crossmatch Positivity is an Independent Risk Factor for Long-term Renal Allograft Survival

The clinical significance of positive B-cell complement-dependent cytotoxicity crossmatching (B-CDC) in renal transplant recipients remains unclear. We reviewed 20 recipients with isolated B-CDC positivity at the time of transplantation. We compared the clinical characteristics, acute rejection and long-term graft survival between positive and negative B-CDC patients (n = 602). The number of retransplant recipients and positivity for T- and B-flowcytometric crossmatch was greater in positive B-CDC patients than in negative B-CDC patients. The overall acute rejection rate of positive B-CDC patients was significantly higher (P < 0.001), and Banff grade II or III cellular rejection was more frequently observed in positive B-CDC patients (P = 0.037). Compared with negative B-CDC patients, acute cellular rejection as a cause of graft loss was more prevalent (P = 0.020) and rescue rejection therapy was more frequently needed in positive B-CDC patients (P = 0.007). The allograft survival rate of positive B-CDC patients was significantly lower than that of negative B-CDC patients (P < 0.001), and B-CDC positivity independently increased the risk of allograft failure 2.31-fold (95% CI 1.15-4.67; P = 0.019) according to multivariate analysis. In conclusion, isolated B-CDC positivity is an independent long-term prognostic factor for allograft survival