Transumbilical single-incision hybrid pyeloplasty for infant ureteropelvic junction obstruction.

Ureteropelvic junction obstruction (UPJO) can be treated by various pyeloplasty techniques. We present a hybrid technique incorporating elements of laparoendoscopic single-site surgery and open pyeloplasty through a single umbilical incision. As a result, seven infants with UPJO underwent the hybrid pyeloplasty smoothly. The mean operative time was 131.9 min. At a follow-up of 11.8-50.0 months, all infants showed significant improvement and no symptoms except for one febrile urinary tract infection. The cosmetic results were very satisfactory without obvious visible scars. Therefore, the hybrid pyeloplasty appears to be a simple and effective minimally invasive surgery for treating infant UPJO.

Genomic epidemiology of hypervirulent carbapenem-resistant Klebsiella pneumoniae at Jinshan local hospital, Shanghai, during 2014-2018.

BACKGROUND: Hypervirulent carbapenem-resistant Klebsiella pneumoniae (Hv-CRKP) triggered a significant public health challenge. This study explored the prevalence trends and key genetic characteristics of Hv-CRKP in one Shanghai suburbs hospital during 2014-2018. METHODS: During five years, Hv-CRKP strains identified from 2579 CRKP by specific PCR, were subjected to performed short- and long-read sequencing technology; epidemiological characteristics, antimicrobial-resistance genes (ARGs), virulence determinants, detailed plasmid profiles and conjugation efficiency were comprehensively investigated. RESULTS: 155 Hv-CRKP and 31 non-Hv-CRKP strains were sequenced. Hv-CRKP strains exhibited significant resistance to six common antibiotic classes (>92%). ST11 steadily increased and became the most prevalent ST (85.2%), followed by ST15 (8.5%), ST65 (2.6%), ST23 (1.9%), and ST86 (0.6%). ST11-KL64 (65.2%) rapidly increased from 0 in 2014 to 93.9% in 2018. blaKPC-2 was the primary carbapenemase gene (97.4%). Other ARGs switched from aac(3)-IId to aadA2 in aminoglycoside and from sul1 to sul2 in sulfanilamide. The time-dated phylogenetic tree was divided into four independent evolutionary clades. Clade 1 and 3 strains were mostly limited in the ICU, whereas Clade 2 strains were distributed among multiple departments. Compared to ybt14 in ICEKp12 in Clade 1, Clade 3 strains harbored ybt9 in ICEKp3 and blaCTX-M-65. Hv-CRKP infected more wards than non-Hv-CRKP and showed greater transmission capacity. Three plasmids containing crucial carbapenemase genes demonstrated their early transmission across China. CONCLUSION: The Hv-CRKP ST11-KL64 has rapidly replaced ST11-KL47 and emerged as the predominant epidemic subtype in various hospital wards, highlighting the importance of conducting comprehensive early surveillance for Hv-CRKP, especially in respiratory infections.

The association between dietary patterns, plasma lipid profiles, and inflammatory potential in a vascular dementia cohort.

Background: Inflammation and altered lipid dyshomeostasis have been implicated in the pathogenesis of Alzheimer's disease and vascular dementia. Objective: To determine if there are any associations between dietary patterns, plasma lipid profiles, and inflammatory potential in a vascular dementia cohort. Methods: One hundred fifty participants (36 subjects with Vascular Dementia and 114 healthy controls) from two Australian teaching hospitals completed a cross-sectional survey examining their dietary and lifestyle patterns. Each participant's diet was further evaluated using the Empirical Dietary Inflammatory Index. Some participants also donated blood samples for lipidomic analysis. Results: After adjusting for age, education, and socioeconomic status, participants with vascular dementia tend to have higher lipid profiles, do less exercise, and engage less frequently in social interaction, educational, or reading activities. They also tend to consume more deep-fried food and full-fat dairy compared to control subjects. However, there was no difference in Empirical Dietary Inflammatory Index between the two groups after adjusting for age, education, and socioeconomic status. Conclusion: Our findings suggest a graded inverse association between healthy lifestyle factors and vascular dementia.

Involvement of single nucleotide polymorphisms of junction adhesion molecule with small vessel vascular dementia.

Objectives: It is now recognized that blood brain barrier (BBB) leakage occurs in cerebral small vascular disease (CSVD) and plays a significant role in the pathophysiology of vascular dementia. We hypothesized that genetic polymorphisms of junctional adhesion molecule-A (JAM-A) (which may result in compromised structure of tight junction proteins that form the BBB) in combination with cerebrovascular risk factors hypertension, lipid disorders, and type 2 diabetes may result in BBB leakage and increase the individual's risk of CSVD-related dementia. Methods: In this case-control study, 97 controls with a mean Mini-Mental State Exam (MMSE) score of 29 and 38 CSVD-related vascular dementia participants (mean MMSE score of 19) were recruited. Bloods were collected for the analysis of two common single nucleotide polymorphisms (SNPs) of the JAM-A genotypes rs790056 and rs2481084 using real-time polymerase chain reaction (PCR) assay. Medical history of hypertension, hyperlipidemia, and diabetes was collected for all participants. Results: Polymorphisms of genotype JAM-A SNP rs790056 showed statistically significant result when the subgroup with hyperlipidemia was analyzed (OR = 3.130, p = 0.042 for TC + CC genotypes with hyperlipidaemia vs controls). Similar result was found with diabetes (OR = 4.670, p = 0.031 for TC + CC genotypes vs controls). No significant result was found with hypertension. Borderline results of statistical significance were found for JAM-A SNP rs2481084 with hyperlipidemia (OR = 3.210, p = 0.054 for TC + CC genotypes vs controls) and with diabetes (OR = 3.620, p = 0.069 for TC + CC genotypes vs controls) but not for hypertension. The borderline results might have been due to lack of statistical power because of small sample size. Conclusions: These results lend further support that cerebrovascular risk factors interact with genetic polymorphisms of BBB proteins to increase the risk of vascular dementia.

Plasma biomarkers inclusive of α-synuclein/amyloid-beta40 ratio strongly correlate with Mini-Mental State Examination score in Parkinson's disease and predict cognitive impairment.

Plasma biomarkers for Parkinson's disease (PD) diagnosis that carry predictive value for cognitive impairment are valuable. We explored the relationship of Mini-Mental State Examination (MMSE) score with plasma biomarkers in PD patients and compared results to vascular dementia (VaD) and normal controls. The predictive accuracy of an individual biomarker on cognitive impairment was evaluated using area under the receiver operating characteristic curve (AUROC), and multivariate logistic regression was applied to evaluate predictive accuracy of biomarkers on cognitive impairment; 178 subjects (41 PD, 31 VaD and 106 normal controls) were included. In multiple linear regression analysis of PD patients, α-synuclein, anti-α-synuclein, α-synuclein/Aß40 and anti-α-synuclein/Aß40 were highly predictive of MMSE score in both full model and parsimonious model (R2 = 0.838 and 0.835, respectively) compared to non-significant results in VaD group (R2 = 0.149) and in normal controls (R2 = 0.056). Α-synuclein and anti-α-synuclein/Aß40 were positively associated with MMSE score, and anti-α-synuclein, α-synuclein/Aß40 were negatively associated with the MMSE score among PD patients (all Ps < 0.005). In the AUROC analysis, anti-α-synuclein (AUROC = 0.788) and anti-α-synuclein/Aß40 (AUROC = 0.749) were significant individual predictors of cognitive impairment. In multivariate logistic regression, full model of combined biomarkers showed high accuracy in predicting cognitive impairment (AUROC = 0.890; 95%CI 0.796-0.984) for PD versus controls, as was parsimonious model (AUROC = 0.866; 95%CI 0.764-0.968). In conclusion, simple combination of biomarkers inclusive of α-synuclein/Aß40 strongly correlates with MMSE score in PD patients versus controls and is highly predictive of cognitive impairment.

Characteristics of childhood-onset systemic lupus erythematosus in pregnancy and its association with pregnancy outcomes: a retrospective comparative cohort study.

BACKGROUND: Disease situations are more aggressive in patients with childhood-onset systemic lupus erythematosus (cSLE) than in those with adult-onset SLE (aSLE). However, information on pregnant women with cSLE and its association with pregnancy outcomes is limited. This study aimed to compare pregnancies in patients with cSLE vs. aSLE, and further analyse the characteristics of cSLE in pregnant women and explore its association with adverse pregnancy outcomes. METHODS: Altogether, data of 167 pregnancies from 150 women, including 22 pregnancies with cSLE and 145 pregnancies with aSLE, were retrospectively analysed. Characteristics and disease activity were compared between the cSLE and aSLE groups during pregnancy. Associations between cSLE and the risk of active SLE (SLEPDAI > 4), active lupus nephritis (LN), and adverse pregnancy outcomes were analysed using logistic regression. RESULTS: The cSLE group had a higher incidence of active SLE (12/22 vs. 30/145, P = 0.001) and active LN (11/22 vs. 26/145, P = 0.001) than the aSLE group. In the multivariable analysis, cSLE was a risk factor for active SLE and active LN during pregnancy, with ORs of 4.742 (95%CI 1.678-13.405, P = 0.003) and 4.652 (95%CI 1.630-13.279, P = 0.004), respectively. No significant association between cSLE and the risk of composite adverse gestational outcomes was identified after sequentially adjusting pre-pregnancy characteristics and pregnancy factors (P > 0.05). CONCLUSION: Disease activity of women with cSLE in pregnancy was more aggressive than that of women with aSLE, which was similar to the characteristics of non-pregnant women with SLE. cSLE might have indirect effects on the risk of adverse pregnancy outcomes through LN and active disease. Therefore, closely monitoring patients with cSLE during pregnancy is crucial.

Strong Predictive Algorithm of Pathogenesis-Based Biomarkers Improves Parkinson's Disease Diagnosis.

Easily accessible and accurate biomarkers can aid Parkinson's disease diagnosis. We investigated whether combining plasma levels of α-synuclein, anti-α-synuclein, and/or their ratios to amyloid beta-40 correlated with clinical diagnosis. The inclusion of amyloid beta-40 (Aß40) is novel. Plasma levels of biomarkers were quantified with ELISA. Using receiver operating characteristic (ROC) curve analysis, levels of α-synuclein, anti-α-synuclein, and their ratios with Aß40 were analyzed in an initial training set of cases and controls. Promising biomarkers were then used to build a diagnostic algorithm. Verification of the results of biomarkers and the algorithm was performed in an independent set. The training set consisted of 50 cases (age 65.2±9.3, range 44-83, female:male=21:29) with 50 age- and gender-matched controls (67.1±10.0, range 45-96 years; female:male=21:29). ROC curve analysis yielded the following area under the curve results: anti-α-synuclein=0.835, α-synuclein=0.738, anti-α-synuclein/Aß40=0.737, and α-synuclein/Aß40=0.663. A 2-step diagnostic algorithm was built: either α-synuclein or anti-α-synuclein was ≥2 times the means of controls (step-1), resulting in 74% sensitivity; and adding α-synuclein/Aß40 or anti-α-synuclein/Aß40 (step-2) yielded better sensitivity (82%) while using step-2 alone yielded good specificity in controls (98%). The results were verified in an independent sample of 46 cases and 126 controls, with sensitivity reaching 91.3% and specificity 90.5%. The algorithm was equally sensitive in Parkinson's disease of ≤5-year duration with 92.6% correctly identified in the training set and 90% in the verification set. With two independent samples totaling 272 subjects, our study showed that combination of biomarkers of α-synuclein, anti-α-synuclein, and their ratios to Aß40 showed promising sensitivity and specificity.

Macrophage- and Microglia-Related Chemokines Are Associated with Small Vessel (White Matter) Vascular Dementia: A Case-Control Study.

INTRODUCTION: Little is known about the role of inflammation in the process of small vessel vascular dementia (VaD). Recently, the notion that small vessel VaD is caused solely by vascular pathology has been challenged by new evidence of concomitant breakdown of the blood-brain barrier and dysregulation of neuroinflammation in the white matter. METHODS: We examined selected inflammatory cytokines and chemokines in the plasma from patients with small vessel VaD (n = 41) and from age-matched controls (n = 131) using multiplex bead-based assays. Participants were recruited from a memory disorder clinic and from a hospital or community. RESULTS: When compared to controls, patients with small vessel VaD had a highly significant increase in the plasma interferon-γ-inducible protein 10 (IP-10) level (p < 0.0001) and a highly significant decrease in plasma macrophage inflammatory protein 1-beta (MIP-1ß) level (p < 0.0001). We also observed a significant increase in patients' levels of interleukin-10 (IL-10) (p = 0.022) as well as decreases in interleukin-8 (IL-8) (p = 0.004) and interleukin-7 (IL-7) (p = 0.011) when compared to age-matched controls. CONCLUSION: Both IP-10 and MIP-1ß are macrophage-related chemokines. The significant differences between cases and controls suggest a potential role for macrophages in small vessel VaD neuroinflammation. Although it remains unclear whether there is a causal effect of their alteration for small vessel VaD, a better understanding of these molecules in the pathogenesis of small vessel VaD may lead to improved diagnosis and future treatment outcomes against this disease.

Development of an Aerobic Glycolysis Index for Predicting the Sorafenib Sensitivity and Prognosis of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a deadly tumor with high heterogeneity. Aerobic glycolysis is a common indicator of tumor growth and plays a key role in tumorigenesis. Heterogeneity in distinct metabolic pathways can be used to stratify HCC into clinically relevant subgroups, but these have not yet been well-established. In this study, we constructed a model called aerobic glycolysis index (AGI) as a marker of aerobic glycolysis using genomic data of hepatocellular carcinoma from The Cancer Genome Atlas (TCGA) project. Our results showed that this parameter inferred enhanced aerobic glycolysis activity in tumor tissues. Furthermore, high AGI is associated with poor tumor differentiation and advanced stages and could predict poor prognosis including reduced overall survival and disease-free survival. More importantly, the AGI could accurately predict tumor sensitivity to Sorafenib therapy. Therefore, the AGI may be a promising biomarker that can accurately stratify patients and improve their treatment efficacy.

Re-pigmentation of hair after prolonged cholinesterase inhibitor therapy in a Chinese population.

Eighty consecutive Chinese patients diagnosed with Alzheimer disease were assessed for darkening of grey hair. Of the 62 eligible patients (mean age = 79.3 ± 7.9 years; male: female = 1:1.48), 24/62 (38.7%, 95%CI: 26.6 - 51.9) reported hair darkening after prolonged usage of cholinesterase inhibitor for at least 6 months. Of the 24 patients with hair darkening, 17 (70.9%) experienced hair darkening in the occipital region, 3 (12.5%) in the parietal region, 2 (8.3%) patients in the frontal region and 2 (8.3%) patients experienced hair darkening in multiple regions. Analysis of melanin concentration showed no significant difference between darkened hair of patients after prolonged drug use and the dark hair of controls (P = 0.381).

Key issues to consider and innovative ideas on fall prevention in the geriatric department of a teaching hospital.

Falls in hospital are common and up to 70% result in injury, leading to increased length of stay and accounting for 10% of patient safety-related deaths. Yet, high-quality evidence guiding best practice is lacking. Fall prevention strategies have worked in some trials but not in others. Differences in study setting (acute, subacute, rehabilitation) and sampling of patients (cognitively intact or impaired) may explain the difference in results. This article discusses these important issues and describes the strategies to prevent falls in the acute hospital setting we have studied, which engage the cognitively impaired who are more likely to fall. We have used video clips rather than verbal instruction to educate patients, and are optimistic that this approach may work. We have also explored the option of co-locating high fall risk patients in a close observation room for supervision, with promising results. Further studies, using larger sample sizes are required to confirm our findings.

Mini-review on initiatives to interfere with the propagation and clearance of alpha-synuclein in Parkinson's disease.

In this mini-review, we summarize recent findings relating to the prion-like propagation of α-synuclein (α-syn) and the development of novel therapeutic strategies to target synucleinopathy in Parkinson's disease (PD). We link the Braak's staging hypothesis of PD with the recent evidence from in-vivo and in-vitro studies for the prion-like cell-to-cell propagation of α-syn (via exocytosis and endocytosis). The classical accumulation of aggregated α-syn in PD may result from an increased production or a failure in the mechanisms of clearance of α-syn. We discuss novel agents, currently in clinical trial for PD including the ones that impact the aggregation of α-syn and others that interfere with α-syn endocytosis as a means to target the progression of the disease.

Delirium post-stroke: short- to long-term effect on anxiety and depression compared to effect on cognition.

Background Delirium is common after stroke and has significant negative impact on mortality, morbidity, cognitive function, and institutionalization. Despite these known effects, any impact of delirium on the emotional well-being of stroke survivors is unclear. Methods A post hoc analysis was performed on our prospective cohort study of 156 stroke patients. Hospital Anxiety and Depression (HAD) scale scores were compared between patients with delirium and patients without delirium at 1-month, 6-month, and 12-month post-stroke. Results Contrary to the negative impact of delirium on cognition and functional status, we did not discern any influence on HAD scale scores in the short to long term. The median scores of the HAD anxiety scale were 4 (interquartile range IQR 3) at 1 month, 5.5 (IQR 8.75) at 6 months, and 6 (IQR 5) at 12 months in the delirium group compared to 5 (IQR 7) at 1 month (p = 0.6), 4 (IQR 7) at 6 months (p = 0.4), and 6 (IQR 5.75) at 12 months (p = 0.9) in the non-delirium group, respectively. Similarly, the median scores of the HAD depression scale were 5 (IQR 4) at 1 month, 4 (IQR 6.5) at 6 months, and 3 (IQR 6) at 12 months in the delirium group compared to 6 (IQR 5.75) at 1 month (p = 0.9), 5 (IQR 7) at 6 months (p = 0.9), and 6 (IQR 5) at 12 months (p = 0.5) in the non-delirium group. Conclusion Delirium may not have a significant effect on the development of anxiety or depression after stroke which differs in its effect on cognitive function and functional status.

Isoflurane promotes glucose metabolism through up-regulation of miR-21 and suppresses mitochondrial oxidative phosphorylation in ovarian cancer cells.

Ovarian cancer is one of the most lethal gynecologic malignancies in women. Isoflurane is one of the volatile anesthetics used extensively for inhalational anesthesia and gynecological surgery. However, the effects of isoflurane on ovarian cancer have not been fully elucidated. It is widely studied that one of the biochemical fingerprints of cancer cells is the altered energy metabolism which is characterized by preferential dependence on glycolysis for energy production in an oxygen-independent manner. In the present study, we explored the roles of isoflurane in the regulation of cellular metabolism of ovarian cancer cells. We observed the glucose uptake, lactate production and extracellular acidification of two ovarian cancer cell lines, SKOV3 and TOV21G were significantly stimulated by isoflurane treatments at 1 and 2 h. The glycolysis enzymes, HK2, PKM2, and LDHA were up-regulated by isoflurane. We report that miR-21 was induced by isoflurane treatments in ovarian cancer cells, leading to the elevated AKT phosphorylation and up-regulation of glycolysis enzymes. In contrast, the mitochondrial functions were suppressed by isoflurane treatments: the oxygen consumption, mitochondrial membrane potential (MMP), and activities of complex I, II, and IV on the electron transport chain were significantly decreased under isoflurane treatments. Importantly, ovarian cancer cells become hypersensitive to glycolysis inhibitors with isoflurane pretreatments. The present study demonstrates that isoflurane treatments drive a metabolic switch of ovarian cancer cells and contributes to the discovery and development of clinical therapeutic agents against ovarian cancer.

Association of genetic polymorphisms of claudin-1 with small vessel vascular dementia.

The most recent hypothesis of the development of small vessel vascular dementia (VaD) emphasises the role of blood-brain barrier (BBB) dysfunction. It is hypothesised that certain genetic polymorphisms of the BBB tight junction claudin-1 protein, in combination with adverse environmental risk factors, increase the risk of BBB dysfunction and small vessel VaD. In this case-control study, 97 control participants, with a mean Mini Mental State Exam (MMSE) score of 29.1, and 38 VaD participants were recruited and completed a questionnaire on their medical history and lifestyle factors. Blood was also collected and two single nucleotide polymorphisms (SNPs), rs17501010 and rs893051 of claudin-1 genotyping, were analysed by real-time polymerase chain reaction (PCR) assay. A significantly higher frequency of all rs893051 SNP genotypes (GC and CC) was found in the VaD population (OR=4.8, P=0.006 and OR=6, P<0.001 respectively). Patients with TT genotype of rs17501010 were also more likely to have VaD (OR=3.25, P=0.022). Stratification analysis revealed that having combined haplotype GC+CC of rs893051 and lipid disorders was associated with higher risk of VaD (OR=9.9, P<0.001). For patients with type 2 diabetes the odds ratio of VaD increased significantly in GC+CC genotypes of rs893051 (OR=12.57, P<0.0001) and GT+TT of rs17501010 (OR=5.33, P=0.01).

Interference of α-Synuclein Uptake by Monomeric ß-Amyloid1-40 and Potential Core Acting Site of the Interference.

Increasing evidence suggests an important role of alpha-synuclein (α-Syn) in the pathogenesis of Parkinson's disease (PD). The inter-neuronal spread of α-Syn via exocytosis and endocytosis has been proposed as an explanation for the neuropathological findings of PD in sub-clinical and clinical phases. Therefore, interfering the uptake of α-Syn by neurons may be an important step in slowing or modifying the propagation of the disease. The purposes of our study were to investigate if the uptake of α-Syn fibrils can be specifically interfered with monomeric ß-Amyloid1-40 (Aß40) and to characterise the core acting site of interference. Using a radioisotope-labelled uptake assay, we found an 80 % uptake reduction of α-Syn fibrils in neurons interfered with monomeric Aß40, but not ß-Amyloid1-42 (Aß42) as compared to controls. This finding was further confirmed by enzyme-linked immunosorbent assay (ELISA) with α-Syn uptake reduced from about 80 % (Aß42) to about 20 % (Aß40) relative to controls. To define the region of Aß40 peptide capable of the interference, we explored shorter peptides with less amino acid residues from both the C-terminus and N-terminus. We found that the interference effect was preserved if amino acid residue was trimmed to position 11 (from N-terminus) and 36 (from C-terminus), but dropped off significantly if residues were trimmed beyond these positions. We therefore deduced that the "core acting site" lies between amino acid residue positions 12-36. These findings suggest α-Syn uptake can be interfered with monomeric Aß40 and that the core acting site of interference might lie between amino acid residue positions 12-36.

Genetic and environmental factors in vascular dementia: an update of blood brain barrier dysfunction.

Vascular dementia (VaD) describes a combination of both cognitive and behavioural manifestations associated with variable brain lesions of vascular origin. While vascular risk factors have been implicated in VaD, the relationship is most evident when the factors are considered together and not individually. This review will examine the significance of the integrity of blood brain barrier (BBB) tight junction (TJ) proteins - occludin and claudins in the pathophysiology of VaD. Specifically, some of the genetic contributors to VaD, namely those responsible for the integrity of the BBB, will be reviewed in detail. Moreover, environmental factors will be considered in conjunction with these genes to examine how the interaction of environmental and genetic factors contributes to one's susceptibility to VaD.

Mortality trend and predictors of mortality in dysphagic stroke patients postpercutaneous endoscopic gastrostomy.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) feeding is widely used in stroke patients suffering from persistent dysphagia; however, predicting the risks and benefits of PEG insertion in the individual patient is difficult. The aim of our study was to investigate if candidate risk factors could predict short-term mortality risk in poststroke patients who had PEG tube insertion for persistent dysphagia. METHODS: This was a retrospective study of 3504 consecutive stroke patients admitted to two metropolitan hospitals during the period January 2005 to December 2013 and who also underwent PEG insertion for feeding due to persistent dysphagia. RESULTS: A total of 102 patients were included in the study. There were 22 deaths in 6 months after insertion of PEG tubes and 20 deaths of those occurred within 3 months post PEG. Those who survived beyond 6 months showed significantly lower mean age (75.9 ± 9.0 years vs. 83.0 ± 4.9 years, P < 0.001), a lower mean American Society of Anesthesia (ASA) score (3.04 ± 0.63 vs. 3.64 ± 0.58, P < 0.001) compared to nonsurvivors. In multiple Logistic, age (P = 0.004, odds ratio [OR] = 1.144; 95% confidence interval [CI]: 1.044-1.255); ASA (P = 0.002, OR = 5.065; 95% CI: 1.815-14.133) and albumin level pre-PEG insertion (P = 0.033, OR = 0.869; 95% CI: 0.764-0.988) were the independent determinants of mortality respectively. CONCLUSIONS: We propose that age, ASA score and albumin level pre-PEG insertion to be included as factors to assist in the selection of patients who are likely to survive more than 3 months post PEG insertion.

Relationship of immunogenicity to protective potency in acellular pertussis vaccines.

Comparison of the immunogenicity response and resistance to challenge in the modified intracerebral challenge assay induced by various acellular pertussis vaccines showed that these were not closely linked. The immunogenicity assay was effective for confirming the presence of specific antigenic components and was invaluable for detecting minor components present in co-purified vaccines. However, the magnitude of antibody responses was not consistently related to antigen concentration nor did it correlate with protection in the modified intracerebral challenge assay. The immunogenicity assay detected degradation of pertussis toxin and pertactin components but not of filamentous haemagglutinin or fimbriae 2 and 3 in denatured acellular pertussis vaccines. The modified intracerebral challenge assay was effective in detecting antigen degradation in all types of acellular pertussis vaccines including those of European/North American origin but was dominated by the response to pertussis toxin. Aerosol challenge was more sensitive in detecting denaturation of filamentous haemagglutinin or fimbriae. The modified intracerebral challenge assay was the only assay that provided a quantitative indication of protective activity. Both immunogenicity and challenge assays provided useful data on acellular pertussis vaccine properties but were complementary and not alternatives.