Immune responses and safety of COVID-19 vaccination in atypical hemolytic uremic syndrome patients in Taiwan.

Atypical hemolytic uremic syndrome is a rare, life-threatening disorder which can be triggered by COVID 19 infection and COVID 19 vaccination then induce multiple organ failure. Our study is the first to evaluate immune responses to COVID-19 vaccination and safety in a cohort of patients in a local single-center study in Taiwan.. Results indicate that vaccines effectively shield aHUS patients from severe COVID-19 complications without significant safety concerns. A double booster dose for the third vaccine is essential for optimal efficacy. Anti-complement therapy did not influence vaccination effectiveness. Transplant aHUS patients had the lowest immune response titers, indicating a need for additional vaccine doses. Compared to healthcare workers, aHUS patients had poor T-cell responses. We noted a superior trend with mixed-type COVID-19 vaccinations in aHUS patients, while fixed-type mRNA demonstrated better results in healthcare workers. Our findings endorse COVID-19 vaccination as a potent strategy to safeguard aHUS patients from severe complications, emphasizing the importance of vigilant monitoring pre- and post-vaccination.

Dysregulation of Immune Cell Subpopulations in Atypical Hemolytic Uremic Syndrome.

Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening thrombotic microangiopathy. Definitive biomarkers for disease diagnosis and activity remain elusive, making the exploration of molecular markers paramount. We conducted single-cell sequencing on peripheral blood mononuclear cells from 13 aHUS patients, 3 unaffected family members of aHUS patients, and 4 healthy controls. We identified 32 distinct subpopulations encompassing 5 B-cell types, 16 T- and natural killer (NK) cell types, 7 monocyte types, and 4 other cell types. Notably, we observed a significant increase in intermediate monocytes in unstable aHUS patients. Subclustering analysis revealed seven elevated expression genes, including NEAT1, MT-ATP6, MT-CYB, VIM, ACTG1, RPL13, and KLRB1, in unstable aHUS patients, and four heightened expression genes, including RPS27, RPS4X, RPL23, and GZMH genes, in stable aHUS patients. Additionally, an increase in the expression of mitochondria-related genes suggested a potential influence of cell metabolism on the clinical progression of the disease. Pseudotime trajectory analysis revealed a unique immune cell differentiation pattern, while cell-cell interaction profiling highlighted distinctive signaling pathways among patients, family members, and controls. This single-cell sequencing study is the first to confirm immune cell dysregulation in aHUS pathogenesis, offering valuable insights into molecular mechanisms and potential new diagnostic and disease activity markers.

Indirect assessment of biomass accumulation in a wastewater-based Chlorella vulgaris photobioreactor by pH variation.

Algae bloom in coastal waters is partly supported by residual nutrients in treated wastewater (WW) released from coastally located treatment plants. In response, a Chlorella vulgaris-based photobioreactor was recently proposed for lowering nutrient levels in WW prior to release. However, the solution requires maintaining biomass accumulation to within a photobioreactor capacity for optimum operation. For high density Chlorella vulgaris suspensions, this is easily done by monitoring turbidity increase, a property directly related to biomass accumulation. For low density suspensions however, direct turbidity measurement would require a cumbersome process of concentrating large volumes of Chlorella vulgaris suspensions. Here, we demonstrate that by measuring pH of the suspensions, turbidity (T) can be estimated indirectly by the following wastewater-dependent expression: pH = aT + pH0, hence avoiding the need to concentrate large volumes. The term pH0 is the initial pH of the suspensions and a, a wastewater-dependent constant, can be computed independently from a = - 0.0061*pH0 + 0.052. In the event %WW is unknown, the following wastewater-independent Gaussian expression can be used to estimate T: pH = 8.71*exp(- [(T - 250)2]/[2*1.26E05]). These three equations should offer an avenue for monitoring the turbidity of dilute Chlorella vulgaris suspensions in large, stagnant municipal Chlorella vulgaris-based wastewater treatment system via pH measurements.

Applying multivariate analysis to characterize waragi spirits from Acoli, Uganda, by their metal contents.

Quality control during spirits production and means of authenticating or verifying sources of spirits in the sub-Saharan region of Africa are limited due to lack of resources and the scientific acumen required to develop methodologies for characterizing spirits. However, the increasing needs to protect consumers from negligence, or willful contamination of spirits in this region underscores the urgency with which growth in this area must happen. In this paper, we describe a multivariate statistical framework upon which characterization, identification and authentication of spirits could be developed. The framework exploits the unique chemical fingerprints of spirits with the goal of accomplishing three functions simultaneously: the detection of class differences, the authentication of spirits and the verification of sources. In a test case using the metal contents of 17 Ugandan spirits, this framework shows (i) that a class of unrecorded spirits known locally as Lira-Lira can be singled out from other spirits by their Cu contents, (ii) that localities from where the Lira-Lira spirits were purchased can be resolved to within 8 km by cluster analysis and principal component analysis, (iii) that cluster analysis loadings and scores, placed side-by-side, can pair spirits and their unique discriminating contaminants directly, (iv) that the most important metals for authenticating 13 spirits, source verification and production methods are Al, Sr, Ba, Mn, Zn and Cu (high concentration variability across samples is the qualifying factor), (v) that common sources of contamination can be detected by Pearson correlation analysis (this study finds that Sn/Cd, Pb/Cr, Tl/Cr, Pb/Ni or Cu/Ag as well as the triad Se/As/Ni in the 13 Ugandan spirits are from similar sources), and (vi) that inconsistency in spirits production can be detected with empirical data. Such rudimentary solutions to characterizing spirits have never been offered to the sub-Saharan countries.

Association of inflammatory cytokines with mortality in peritoneal dialysis patients.

AIMS: Previous study on association between pro-inflammatory cytokines and mortality in PD population is limited. We aimed to investigate here. METHODS: Total 50 patients who underwent incident PD were enrolled in this study. We measured the titers of pro-inflammatory cytokines Interleukin-18(IL-18), Interleukin-6 (IL-6), and Interleukin-1ß (IL-1ß). Study outcomes were all-cause mortality, cardiovascular-related mortality, and infection-caused mortality. Cox-regression model was used. RESULTS: In this 7 year prospective study, IL-18 ≥ 804.3pg/ml, IL-6 ≥ 3.92 pg/ml, IL-1ß ≥ 0.86pg/ml, age ≥ 50 years-old, and existence of diabetes could be used as individual significant predictors for mortality in PD patients. Higher titers of IL-6 were associated with lower averaging albumin levels within 1st year of PD. Increasing numbers of these risk markers of mortality was associated with decreasing survival advantages (P = 0.001). CONCLUSION: Age ≥ 50 years-old, diabetes, and inflammatory cytokines profiles at the start of PD therapy could predict for 7-year mortality in PD population.

Diagnosis of bacterial pathogens in the dialysate of peritoneal dialysis patients with peritonitis using surface-enhanced Raman spectroscopy.

BACKGROUND: Bacterial peritonitis is the most common cause of peritoneal dialysis (PD) therapy drop-out. A quick and accurate diagnosis of the bacterial pathogen can reduce the PD drop-out rate. Surface-enhanced Raman spectroscopy (SERS) can rapidly identify bacteria using chips coated with nano-sized metal particles. METHODS: Known bacteria were loaded in the SERS-chips and illuminated with laser light to establish a reference Raman spectra library. Dialysate from PD peritonitis patients was concentrated by centrifuge and examined with the same SERS, and the resulting Raman spectra were compared with library spectra for bacteria identification. Principal component analysis was used for further confirmation. The same batches of dialysate were sent to routine culture as a reference bacteria identification method. The results of the 2 identification methods were compared. RESULTS: A total of 43 paired-samples were sent for study. There were 37 samples with bacteria identified but 6 were culture-negative by the reference method. 31 bacteria were identified in paired-samples by SERS, among which, 29 bacteria were exactly the same as those identified by the reference method. Bacteria not included in the reference library spectra cannot be identified. CONCLUSIONS: SERS techniques can rapidly identify bacterial pathogens in the dialysate of PD peritonitis patients.

Loss of Residual Renal Function is Associated With Vascular Calcification in Hemodialysis Patients.

Vascular calcification is common in chronic hemodialysis (HD) patients and can be measured using abdominal aortic calcification (AAC). Loss of residual renal function (RRF) is associated with increased mortality in HD patients. However, the association between loss of RRF and vascular calcification is unknown. The aim of the study was to analyze the association between loss of RRF and VC in HD patients. All chronic HD (HD for more than 3 months) patients of China Medical University Hospital in 2014 were included. AAC scores were measured semi-quantitatively based on later lumbar radiographs. Loss of RRF was defined as urine output less than 200 mL per day. The association between loss of RRF and AAC was analyzed using logistic regression. Four hundred and thirty-eight chronic HD patients with a mean age of 63 ± 12 years were analyzed. The median (interquartile range) AAC score of all patients was 7 (2-13). The AAC score of patients with loss of RRF was 9 (3-22), significantly higher than that of patients with RRF 5 (0-17) (P = 0.004). Loss of RRF, independent of patients' age, diabetes, C-reactive protein, calcium-phosphorus product and vintage of dialysis was associated with higher AAC scores. Loss of RRF was associated with vascular calcification in HD patients.

Association of walking with survival and RRT among patients with CKD stages 3-5.

BACKGROUND AND OBJECTIVES: Patients with CKD can benefit from an increase in physical activity. Walking is one of the most common exercises in patients with CKD; however, the association of walking with outcomes in patients with CKD is not clear. This study investigated the association of walking with overall mortality and RRT in patients with CKD stages 3-5. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: All patients with CKD stages 3-5 in the CKD program of China Medical University Hospital from June 2003 to May 2013 were enrolled. The risks of overall mortality and RRT were analyzed using competing-risks regressions. RESULTS: A total of 6363 patients (average age, 70 years) during a median of 1.3 (range=0.6-2.5) years of follow-up were analyzed. There were 1341 (21.1%) patients who reported walking as their most common form of exercise. The incidence density rate of overall mortality was 2.7 per 100 person-years for walking patients and 5.4 for nonwalking ones. The incidence density rate of RRT was 22 per 100 person-years for walking patients and 32.9 for nonwalking ones. Walking, independent of patients' age, renal function, and comorbidity, was linked to lower overall mortality and lower RRT risk in the multivariate competing-risks regression. The adjusted subdistribution hazard ratio (SHR) of walking was 0.67 (95% confidence interval [95% CI], 0.53 to 0.84; P<0.001) for overall mortality and 0.79 (95% CI, 0.73 to 0.85; P<0.001) for the risk of RRT. The SHRs of overall mortality were 0.83, 0.72, 0.42, and 0.41 for patients walking 1-2, 3-4, 5-6, and ≥7 times per week, and the SHRs of RRT were 0.81, 0.73, 0.57, and 0.56, respectively. CONCLUSIONS: Walking is the most popular form of exercise in patients with CKD and is associated with lower risks of overall mortality and RRT. The benefit of walking is independent of patients' age, renal function, and comorbidity.

Stereo-specific inhibition of acetyl- and butyryl-cholinesterases by enantiomers of cis,cis-decahydro-2-naphthyl-N-n-butylcarbamate.

Enantiomers of cis,cis-decahydro-2-naphthyl-N-n-butylcarbamate show stereo-specific inhibition for acetylcholinesterase and butyrylcholinesterase. For both inhibition reaction, (2S,4aR,8aS)-cis,cis-decahydro-2-naphthyl-N-n- butylcarbamate is more potent than (2R,4aS,8aR)-cis,cis-decahydro-2-naphthyl-N-n-butylcarbamate. Optically pure (2S,4aR,8aS)-(-)- and (2R,4aS,8aR)-(+)-cis,cis-decahydro-2-naphthols are resolved by the porcine pancreatic lipase-catalyzed acetylation of decahydro-2-naphthols with vinyl acetate. Absolute configurations and the enantiomeric excess values of (2S,4aR,8aS)-(-)- and (2R,4aS,8aR)-(+)-cis,cis-decahydro-2-naphthols are determined from the (19)F NMR spectra of their Mosher's ester derivatives. We fail to resolve (2S,4aR,8aR)- and (2R,4aS,8aS)-trans,cis-decahydro-2-naphthols from the porcine pancreatic lipase-catalyzed acetylation of decahydro-2-naphthols with vinyl acetate.

Stereoselective inhibition of cholesterol esterase by enantiomers of exo- and endo-2-norbornyl-N-n-butylcarbamates.

Four stereoisomers of 2-norbornyl-N-n-butylcarbamates are characterized as the pseudo substrate inhibitors of cholesterol esterase. Cholesterol esterase shows enantioselective inhibition for enantiomers of exo- and endo-2-norbornyl-N-n-butylcarbamates. For the inhibitions by (R)-(+)- and (S)-(-)-exo-2-norbornyl-N-n-butylcarbamates, the R-enantiomer is 6.8 times more potent than the S-enantiomer. For the inhibitions by (R)-(+)- and (S)-(-)-endo-2-norbornyl-N-n-butyl-carbamates, the S-enantiomer is 4.6 times more potent than the R-enantiomer. The enzyme-inhibitor complex models have been proposed to explain these different enantioselectivities.

Synthesis of enantiomers of exo-2-norbornyl-N-n-butylcarbamate and endo-2-norbornyl-N-n-butylcarbamate for stereoselective inhibition of acetylcholinesterase.

The acetylcholinesterase inhibition by enantiomers of exo- and endo-2-norbornyl-N-n-butylcarbamates shows high stereoselelectivity. For the acetylcholinesterase inhibitions by (R)-(+)- and (S)-(-)-exo-2-norbornyl-N-n-butylcarbamates, the R-enantiomer is more potent than the S-enantiomer. But, for the acetylcholinesterase inhibitions by (R)-(+)- and (S)-(-)-endo-2-norbornyl-N-n-butylcarbamates, the S-enantiomer is more potent than the R-enantiomer. Optically pure (R)-(+)-exo-, (S)-(-)-exo-, (R)-(+)-endo-, and (S)-(-)-endo-2-norbornyl-N-n-butylcarbamates are synthesized from condensations of optically pure (R)-(+)-exo-, (S)-(-)-exo-, (R)-(+)-endo-, and (S)-(-)-endo-2-norborneols with n-butyl isocyanate, respectively. Optically pure norborneols are obtained from kinetic resolutions of their racemic esters by lipase catalysis in organic solvent.

Stereoselective inhibition of butyrylcholinesterase by enantiomers of exo- and endo-2-norbornyl-N-n-butylcarbamates.

Enantiomers of exo- and endo-2-norbornyl-N-n-butylcarbamates were characterized as pseudo substrate inhibitors of butyrylcholinesterase. These inhibitions discriminate enantiomers of the inhibitors and therefore show stereoselectivity for the enzyme. For inhibitions by (R)-(+)- and (S)-(-)-exo-2-norbornyl-N-n-butylcarbamates, R-enantiomer is a more potent inhibitor than S-enantiomer. But, for inhibitions by (R)-(+)- and (S)-(-)-endo-2-norbornyl-N-n-butylcarbamates, S-enantiomer is a more potent inhibitor than R-enantiomer. Optically pure (R)-(+)-exo-, (S)-(-)-exo-, (R)-(+)-endo-, and (S)-(-)-endo-2-norbornyl-N-n-butylcarbamates were synthesized from condensations of optically pure (R)-(+)-exo-, (S)-(-)-exo-, (R)-(+)-endo-, and (S)-(-)-endo-2-norborneols with n-butyl isocyanate, respectively. Optically pure norborneols were obtained from kinetic resolution of their racemic esters by lipase catalysis in organic solvent.

Disc height and lumbar index as independent predictors of degenerative spondylolisthesis in middle-aged women with low back pain.

STUDY DESIGN: A age- and sex-matched case-control radiographic study. OBJECTIVE: To identify the predisposing factors of degenerative spondylolisthesis (DS). SUMMARY OF BACKGROUND DATA: None of the radiologic methods for predicting the development of DS are very reliable or readily accessible. The methods commonly used are computed tomography or magnetic resonance imaging. METHODS: Data were gathered retrospectively on middle-aged women with degenerative lumbar spondylolisthesis. RESULTS: The most common slipped vertebra was L4 (63.64%) and the second was L5 (13.64%). Most parameters, including the disc height, body height, and angle measurements, for the case group tended to be lower than the control group, whereas the transverse process were larger than control group. The differences in disc height, lumbar index (LI), sacral inclination angle (SIA), sacral horizontal angle (SHA), and transverse process between the 2 groups were statistically significant (P < 0.05). Multivariate logistic regression analysis confirmed that anterior inferior disc height (DHIA) and LI were independent variables of predisposing factor to DS and both could explain a 50% variation of DS. Further analysis of the different levels of spondylolisthesis (L4 on L5 vs. L5 on S1 DS) revealed that there was a significant difference in the width of L5 transverse process in L4 on L5 spondylolisthesis (P = 0.03) but insignificant on disc height (P = 0.86). CONCLUSION: There are 2 independent predictors of DS, decreased anterior disc height and increased lumbar index. The iliolumbar ligament also contributes to the stability of lumbosacral junction, especially in L5 on S1 DS.

Complex decongestive physiotherapy for patients with chronic cancer-associated lymphedema.

BACKGROUND AND PURPOSE: Lymphedema of the limbs after cancer therapy is the most common cause of lymphedema in developed countries. There is no cure for chronic cancer-associated lymphedema. Multidisciplinary complex decongestive physiotherapy (CDP) is commonly used as a primary treatment. This prospective study assessed the efficacy of intensive CDP treatment in chronic cancer-associated lymphedema. METHODS: Thirty women who had unilateral upper or lower limb chronic lymphedema after breast or pelvic cancer therapy were enrolled in the study. All patients received CDP once per day, in consecutive full treatment sessions, which took place between 4 and 21 times. Assessment of the results of therapy included measuring the circumference, calculated volume, and edema ratio (excess volume/unaffected side volume) of the limb volume. The main outcome measure was the percentage reduction in excess limb volume. RESULTS: The pretreatment edema ratio demonstrated a high correlation with the patient's age (r = 0.508, p = 0.004) and the duration of the lymphedema (r = 0.634, p < 0.000). After the intensive CDP, the limb circumference, calculated volume, and edema ratio were significantly reduced compared with their pretreatment values (p < 0.000). The mean percentage reduction of excess volume was 67.8 +/- 33.2% in all patients. CONCLUSIONS: Intensive CDP was effectively able to reduce the limb volume of patients with chronic cancer-associated lymphedema. Further follow-up study is needed to confirm the effectiveness of CDP in the maintenance phase, and its long-term effectiveness in Taiwanese.