The Early Clinical Features of Dengue in Adults: Challenges for Early Clinical Diagnosis

Dengue infection in adults has become increasingly common throughout the world. As most of the clinical features of dengue have been described in children, we undertook a prospective study to determine the early symptoms and signs of dengue in adults. We show here that, overall, dengue cases presented with high rates of symptoms listed in the WHO 1997 or 2009 classification schemes for probable dengue fever thus resulting in high sensitivities of these schemes when applied for early diagnosis. However, symptoms such as myalgia, arthralgia, retro-orbital pain and mucosal bleeding were less frequently reported in older adults. This trend resulted in reduced sensitivity of the WHO classification schemes in older adults even though they showed increased risks of hospitalization and severe dengue. Instead, we suggest that older adults who present with fever and leukopenia should be tested for dengue, even in the absence of other symptoms. This could be useful for early clinical diagnosis in older adults so that they can be monitored and treated for severe dengue, which is especially important when an antiviral drug becomes available

Ethnic differences in body fat distribution among Asian pre-pubertal children: A cross-sectional multicenter study

Background Ethnic differences in body fat distribution contribute to ethnic differences in cardiovascular morbidities and diabetes. However few data are available on differences in fat distribution in Asian children from various backgrounds. Therefore, the current study aimed to explore ethnic differences in body fat distribution among Asian children from four countries. Methods A total of 758 children aged 8-10 y from China, Lebanon, Malaysia and Thailand were recruited using a non-random purposive sampling approach to enrol children encompassing a wide BMI range. Height, weight, waist circumference (WC), fat mass (FM, derived from total body water [TBW] estimation using the deuterium dilution technique) and skinfold thickness (SFT) at biceps, triceps, subscapular, supraspinale and medial calf were collected. Results After controlling for height and weight, Chinese and Thai children had a significantly higher WC than their Lebanese and Malay counterparts. Chinese and Thais tended to have higher trunk fat deposits than Lebanese and Malays reflected in trunk SFT, trunk/upper extremity ratio or supraspinale/upper extremity ratio after adjustment for age and total body fat. The subscapular/supraspinale skinfold ratio was lower in Chinese and Thais compared with Lebanese and Malays after correcting for trunk SFT. Conclusions Asian pre-pubertal children from different origins vary in body fat distribution. These results indicate the importance of population-specific WC cut-off points or other fat distribution indices to identify the population at risk of obesity-related health problems

Role of ER Stress Response in Photodynamic Therapy: ROS Generated in Different Subcellular Compartments Trigger Diverse Cell Death Pathways

We have analyzed the molecular mechanisms of photoinduced cell death using porphyrins with similar structure differing only in the position of the ethylene glycol (EG) chain on the phenyl ring. Meta- and para-positioned EG chains targeted porphyrins to different subcellular compartments. After photoactivation, both types of derivatives induced death of tumor cells via reactive oxygen species (ROS). Para derivatives pTPP(EG)4 and pTPPF(EG)4 primarily accumulated in lysosomes activated the p38 MAP kinase cascade, which in turn induced the mitochondrial apoptotic pathway. In contrast, meta porphyrin derivative mTPP(EG)4 localized in the endoplasmic reticulum (ER) induced dramatic changes in Ca2+ homeostasis manifested by Ca2+ rise in the cytoplasm, activation of calpains and stress caspase-12 or caspase-4. ER stress developed into unfolded protein response. Immediately after irradiation the PERK pathway was activated through phosphorylation of PERK, eIF2α and induction of transcription factors ATF4 and CHOP, which regulate stress response genes. PERK knockdown and PERK deficiency protected cells against mTPP(EG)4-mediated apoptosis, confirming the causative role of the PERK pathway

Measuring the Evolutionary Rewiring of Biological Networks

We have accumulated a large amount of biological network data and expect even more to come. Soon, we anticipate being able to compare many different biological networks as we commonly do for molecular sequences. It has long been believed that many of these networks change, or “rewire”, at different rates. It is therefore important to develop a framework to quantify the differences between networks in a unified fashion. We developed such a formalism based on analogy to simple models of sequence evolution, and used it to conduct a systematic study of network rewiring on all the currently available biological networks. We found that, similar to sequences, biological networks show a decreased rate of change at large time divergences, because of saturation in potential substitutions. However, different types of biological networks consistently rewire at different rates. Using comparative genomics and proteomics data, we found a consistent ordering of the rewiring rates: transcription regulatory, phosphorylation regulatory, genetic interaction, miRNA regulatory, protein interaction, and metabolic pathway network, from fast to slow. This ordering was found in all comparisons we did of matched networks between organisms. To gain further intuition on network rewiring, we compared our observed rewirings with those obtained from simulation. We also investigated how readily our formalism could be mapped to other network contexts; in particular, we showed how it could be applied to analyze changes in a range of “commonplace” networks such as family trees, co-authorships and linux-kernel function dependencies

Accelerating repaired basement membrane after bevacizumab treatment on alkali-burned mouse cornea

To understand the corneal regeneration induced by bevacizumab,we investigated the structure changes of stroma andbasement membrane regeneration. A Stick soaked in 0.5 NNaOH onto the mouse cornea and 2.5 mg/ml of bevacizumabwas delivered into an alkali-burned cornea (2 μl) by subconjunctivalinjections at 1 hour and 4 days after injury. At 7 daysafter injury, basement membrane regeneration was observedby transmission electron microscope. Uneven and thin epithelialbasement membrane, light density of hemidesmosomes,and edematous collagen fibril bundles are shown in thealkali-burned cornea. Injured epithelial basement membraneand hemidesmosomes and edematous collagen fibril bundlesresulting from alkali-burned mouse cornea was repaired bybevacizumab treatment. This study demonstrates that bevacizumabcan play an important role in wound healing in thecornea by accelerating the reestablishment of basementmembrane integrity that leads to barriers for scar formation.[BMB Reports 2013; 46(4): 195-200

Predicting factor analysis of postoperative complications after robot-assisted radical cystectomy: Multicenter KORARC database study

© 2022 The Japanese Urological Association.Objectives: To evaluate postoperative complications following robot-assisted radical cystectomy in patients diagnosed with bladder cancer and reveal if there are predictors for postoperative complications. Methods: Prospectively collected medical records of 730 robot-assisted radical cystectomy patients between 2007/04 and 2019/05 in 13 tertiary referral centers were reviewed. Perioperative outcomes were compared between two groups by postoperative complications (complication vs non-complication). We assessed recurrence-free survival, cancer-specific survival, and overall survival between groups. Regression analyses were implemented to identify factors associated with postoperative complications. Results: Any total and high-grade complication (Clavien–Dindo grade ≥3) rates were 57.8% and 21.1%, respectively. Patients in complication group had significantly higher proportion of diabetes mellitus (P = 0.048), chronic kidney disease (P = 0.011), dyslipidemia (P < 0.001), longer operation time (P = 0.001), more estimated blood loss (P = 0.001), and larger intraoperative fluid volume (P < 0.001). There was a significant difference in cancer-specific survival (log-rank P = 0.038, median cancer-specific survival: both groups not reached). Dyslipidemia (odds ratio 2.59, P = 0.002) and intraoperative fluid volume (odds ratio 1.0002, P = 0.040) were significantly associated with high-grade postoperative complications. Diabetes mellitus (odds ratio 1.97, P = 0.028), chronic kidney disease (odds ratio 1.89, P = 0.046), dyslipidemia (odds ratio 5.94, P = 0.007), and intraoperative fluid volume (odds ratio 1.0002, P = 0.009) were significantly associated with any postoperative complications. Conclusions: Patients with diabetes mellitus, chronic kidney disease, dyslipidemia, or a relatively large intraoperatively infused fluid volume are more likely to develop postoperative complications. Patients with postoperative complications might have a possibility of lower cancer-specific survival rate.N

Preoperative smoking and robot-assisted radical cystectomy outcomes & complications in multicenter KORARC database

Abstract To investigate the influence of preoperative smoking history on the survival outcomes and complications in a cohort from a large multicenter database. Many patients who undergo radical cystectomy (RC) have a history of smoking; however, the direct association between preoperative smoking history and survival outcomes and complications in patients with muscle-invasive bladder cancer (MIBC) who undergo robot-assisted radical cystectomy (RARC) remains unexplored. We conducted a retrospective analysis using data from 749 patients in the Korean Robot-Assisted Radical Cystectomy Study Group (KORARC) database, with an average follow-up duration of 30.8 months. The cohort was divided into two groups: smokers (n = 351) and non-smokers (n = 398). Propensity score matching was employed to address differences in sample size and baseline demographics between the two groups (n = 274, each). Comparative analyses included assessments of oncological outcomes and complications. After matching, smoking did not significantly affect the overall complication rate (p = 0.121). Preoperative smoking did not significantly increase the occurrence of complications based on complication type (p = 0.322), nor did it increase the readmission rate (p = 0.076). There were no perioperative death in either group. Furthermore, preoperative smoking history showed no significant impact on overall survival (OS) [hazard ratio (HR) = 0.87, interquartile range (IQR): 0.54–1.42; p = 0.589] and recurrence-free survival (RFS) (HR = 1.12, IQR: 0.83–1.53; p = 0.458) following RARC for MIBC. The extent of preoperative smoking (≤ 10, 10–30, and ≥ 30 pack-years) had no significant influence on OS and RFS in any of the categories (all p > 0.05). Preoperative smoking history did not significantly affect OS, RFS, or complications in patients with MIBC undergoing RARC