Preoperative Fluoroscopically Guided Regional Erector Spinae Plane Blocks Reduce Opioid Use, Increase Mobilization, and Reduce Length of Stay Following Lumbar Spine Fusion.

STUDY DESIGN: Retrospective review. OBJECTIVE: To determine the effectiveness of erector spinae plane (ESP) blocks at improving perioperative pain control and function following lumbar spine fusions. METHODS: A retrospective analysis was performed on patients undergoing < 3 level posterolateral lumbar fusions. Data was stratified into a control group and a block group. We collected postop MED (morphine equivalent dosages), physical therapy ambulation, and length of stay. PROMIS pain interference (PI) and physical function (PF) scores, ODI, and VAS were collected preop and at the first postop visit. Chi-square and student's t-test (P = .05) were used for analysis. We also validated a novel fluoroscopic technique for ESP block delivery. RESULTS: There were 37 in the block group and 39 in the control group. There was no difference in preoperative opioid use (P = .22). On postop day 1, MED was reduced in the block group (32 vs 51, P < .05), and more patients in the block group did not utilize any opioids (22% vs 5%, P < .05). The block group ambulated further on postop day 1 (312 ft vs 204 ft, P < .05), and had reduced length of stay (2.4 vs 3.2 days, P < .05). The block group showed better PROMIS PI scores postoperatively (58 vs 63, P < .05). The novel delivery technique was validated and successful in targeting the correct level and plane. CONCLUSIONS: ESP blocks significantly reduced postop opioid use following lumbar fusion. Block patients ambulated further with PT, had reduced length of stay, and had improved PROMIS PI postoperatively. Validation of the block demonstrated the effectiveness of a novel fluoroscopic delivery technique. ESP blocks represent an underutilized method of reducing opioid consumption, improving postoperative mobilization and reducing length of stay following lumbar spine fusion.

PROMIS correlation with NDI and VAS measurements of physical function and pain in surgical patients with cervical disc herniations and radiculopathy.

OBJECTIVE: The aim of this study was to compare the patient-reported outcome measures Neck Disability Index (NDI) and visual analog scale (VAS) with the Patient Reported Outcomes Measurement Information System (PROMIS) physical function (PF) and pain interference (PI) measures, respectively, and to determine their correlations in a surgical population longitudinally.Legacy outcome measures such as NDI and VAS are essential for analyzing treatments in spine surgery for cervical disc herniations with radiculopathy. Despite their usefulness, administrative burdens impose limits on completion of these measures. PROMIS was developed as a patient outcome measure in order to improve reporting of patient symptoms and function and to reduce administrative burden. Despite early positive results of PROMIS in orthopedics, NDI and VAS scores have not been compared with PROMIS scores in patients with cervical disc herniations with radiculopathy. METHODS: Eighty patients undergoing surgery for cervical disc herniations with radiculopathy were included. All patients were treated at the same tertiary spine center. Patients were seen and PROMIS PF and PI, NDI, and VAS arm and neck pain scores were collected preoperatively and at 1 year postoperatively. Correlations between NDI, VAS, and PROMIS PF and PI were quantified using Pearson correlation coefficients. Two-tailed Student t-tests were used to demonstrate correlation significance, with alpha = 0.05. RESULTS: All 80 (100%) patients completed all preoperative questionnaires. Fifty-seven (72%) and 75 (94%) patients completed all questionnaires at baseline and at the 6-month and 1-year follow-ups, respectively. PROMIS PF and NDI scores demonstrated a strong negative correlation, with Pearson r values of -0.81, -0.77, and -0.75 at baseline, 6 months, and 1 year. PROMIS PI and VAS neck pain scores demonstrated a moderately positive correlation, with Pearson r values of 0.51, 0.61, and 0.6. PROMIS PI and VAS arm pain scores demonstrated a moderately positive correlation, with Pearson r values of 0.46, 0.47, and 0.45. CONCLUSIONS: PROMIS PF scores have a strong negative correlation with NDI scores at baseline and in the postoperative course in patients undergoing surgery for cervical disc herniations with radiculopathy. PROMIS PI scores have a moderately positive correlation with VAS neck and arm pain scores at baseline and in the postoperative course. Surgeons may factor these correlation results into the interpretation of patient-reported outcome measures in patients with cervical radiculopathy. Use of PROMIS PF and PI for this patient population may reduce administrative burden while providing reliable outcomes data.

PROMIS Physical Function Correlation With NDI and mJOA in the Surgical Cervical Myelopathy Patient Population.

STUDY DESIGN: Retrospective review. OBJECTIVE: To determine the correlation of Patient-Reported Outcomes Measurement Information System (PROMIS) physical function with Neck Disability Index (NDI) and Modified Japanese Orthopedic Association (mJOA) scores in the surgical cervical myelopathy patient population. SUMMARY OF BACKGROUND DATA: Outcome measures such as NDI and mJOA are essential for analyzing treatments for cervical myelopathy. Administrative burdens impose limits on completion of these measures. The PROMIS group developed an outcome measure to improve reporting of patient symptoms and function and to reduce administrative burden. Despite early success, NDI and mJOA have not been compared with PROMIS in patients with cervical myelopathy. This study determines the correlation of NDI and mJOA with PROMIS in surgical patients with cervical myelopathy. METHODS: A total of 60 patients with cervical myelopathy undergoing surgery were included. PROMIS, NDI, and mJOA were collected preoperatively, and in the first 6 months postoperatively. Correlations between NDI, mJOA, and PROMIS were quantified using Pearson correlation coefficients. Students t tests were used to test significance. RESULTS: All 60 (100%) of patients completed preoperative questionnaires. Fifty-five (92%) of patients completed initial follow-up questionnaires within the first 6 months. PROMIS physical function and NDI demonstrated a strong negative correlation at baseline and in initial follow-up (R = -0.69, -0.76). PROMIS and mJOA demonstrated a strong positive correlation at baseline and in initial follow-up (R = 0.61, 0.72). CONCLUSION: PROMIS physical function has a strong negative correlation with NDI and a strong positive correlation with mJOA at baseline and in the early postoperative course in patients undergoing surgery for cervical myelopathy. Surgeons may factor these outcomes into the delivery and interpretation of patient-reported outcome measures in this population. Use of PROMIS may improve completion of outcome measures in the office and reduce administrative burden while still providing reliable outcomes data. LEVEL OF EVIDENCE: 3.

Use of a Novel Pathway for Early Discharge Was Associated With a 48% Shorter Length of Stay After Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis.

INTRODUCTION: Hospital stay after posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS) has decreased only modestly over time despite a healthy patient population. The purpose of this study was to evaluate the impact of a novel postoperative pathway on length of stay (LOS) and complications. METHODS: A retrospective review of patients undergoing PSF for AIS in 2011 to 2012 was performed at 2 institutions evaluating demographics, preoperative Cobb angles, surgical duration, blood loss, LOS, and postoperative complications. Patients at one center were managed using an accelerated discharge (AD) pathway emphasizing early transition to oral pain medications mobilization with physical therapy 2 to 3 times/d, and discharge regardless of return of bowel function. Expectations were set with the family before surgery for early discharge. Patients at the other center were managed without a standardized pathway. RESULTS: One hundred five patients underwent PSF and were treated by an AD pathway, whereas 45 patients were managed using a traditional discharge (TD) pathway. There was no difference in proximal thoracic and main thoracic Cobb magnitudes and a small difference in thoracolumbar curve magnitudes (35.2±13.0 degrees AD vs. 40.6±11.4 degrees TD, P=0.004) between groups. Surgical time was slightly shorter in AD patients (median 3.1 vs. 3.9 h, P=0.0003) with no difference in estimated blood loss. LOS was 48% shorter in the AD group (2.2 vs. 4.2 d, P<0.0001). There was no difference in readmissions or wound complications between groups. CONCLUSIONS: Hospital stay was nearly 50% shorter in patients managed by the AD pathway without any increase in readmissions or early complications. SIGNIFICANCE: Discharge after PSF for AIS may be expedited using a coordinated postoperative pathway. No increase in complications was seen using the AD pathway. Earlier discharge may reduce health care costs and allow an earlier return to normalcy for families. LEVEL OF EVIDENCE: Level III-case control study.

Lats2 kinase potentiates Snail1 activity by promoting nuclear retention upon phosphorylation.

Snail1 is a central regulator of epithelial cell adhesion and movement in epithelial-to-mesenchymal transitions (EMTs) during embryo development; a process reactivated during cancer metastasis. While induction of Snail1 transcription precedes EMT induction, post-translational regulation of Snail1 is also critical for determining Snail1's protein level, subcellular localization, and capacity to induce EMT. To identify novel post-translational regulators of Snail1, we developed a live cell, bioluminescence-based screen. From a human kinome RNAi screen, we have identified Lats2 kinase as a novel regulator of Snail1 protein level, subcellular localization, and thus, activity. We show that Lats2 interacts with Snail1 and directly phosphorylates Snail1 at residue T203. This occurs in the nucleus and serves to retain Snail1 in the nucleus thereby enhancing its stability. Lats2 was found to positively influence cellular EMT and tumour cell invasion, in a Snail1-dependent manner. Indeed during TGFß-induced EMT Lats2 is activated and Snail1 phosphorylated at T203. Analysis in mouse and zebrafish embryo development confirms that Lats2 acts as a positive modulator of Snail1 protein level and potentiates its in vivo EMT activity.

Neutrophil elastase mediates pathogenic effects of anthrax lethal toxin in the murine intestinal tract.

Neutrophils isolated from BALB/c or C57BL/6 mice and treated in vitro with anthrax lethal toxin release bioactive neutrophil elastase, a proinflammatory mediator of tissue destruction. Similarly, neutrophils isolated from mice treated with anthrax lethal toxin in vivo and cultured ex vivo release greater amounts of elastase than neutrophils from vehicle-treated controls. Direct measurements from murine intestinal tissue samples demonstrate an anthrax lethal toxin-dependent increase in neutrophil elastase activity in vivo as well. These findings correlate with marked lethal toxin-induced intestinal ulceration and bleeding in neutrophil elastase(+/+) animals, but not in neutrophil elastase(-/-) animals. Moreover, neutrophil elastase(-/-) mice have a significant survival advantage over neutrophil elastase(+/+) animals following exposure to anthrax lethal toxin, thereby establishing a key role for neutrophil elastase in mediating the deleterious effects of anthrax lethal toxin.

Host association of Campylobacter genotypes transcends geographic variation.

Genetic attribution of bacterial genotypes has become a major tool in the investigation of the epidemiology of campylobacteriosis and has implicated retail chicken meat as the major source of human infection in several countries. To investigate the robustness of this approach to the provenance of the reference data sets used, a collection of 742 Campylobacter jejuni and 261 Campylobacter coli isolates obtained from United Kingdom-sourced chicken meat was established and typed by multilocus sequence typing. Comparative analyses of the data with those from other isolates sourced from a variety of host animals and countries were undertaken by genetic attribution, genealogical, and population genetic approaches. The genotypes from the United Kingdom data set were highly diverse, yet structured into sequence types, clonal complexes, and genealogical groups very similar to those seen in chicken isolates from the Netherlands, the United States, and Senegal, but more distinct from isolates obtained from ruminant, swine, and wild bird sources. Assignment analyses consistently grouped isolates from different host animal sources regardless of geographical source; these associations were more robust than geographic associations across isolates from three continents. We conclude that, notwithstanding the high diversity of these pathogens, there is a strong signal of association of multilocus genotypes with particular hosts, which is greater than the geographic signal. These findings are consistent with local and international transmission of host-associated lineages among food animal species and provide a foundation for further improvements in genetic attribution.

Genetic relationships among reptilian and mammalian Campylobacter fetus strains determined by multilocus sequence typing.

Reptile Campylobacter fetus isolates and closely related strains causing human disease were characterized by multilocus sequence typing. They shared approximately 90% nucleotide sequence identity with classical mammalian C. fetus, and there was evidence of recombination among members of these two groups. The reptile group represents a possible separate genomospecies capable of infecting humans.

Amoxicillin therapy of poultry flocks: effect upon the selection of amoxicillin-resistant commensal Campylobacter spp.

BACKGROUND: The aim of this study was to investigate the effect of amoxicillin therapy of poultry flocks upon the persistence of commensal Campylobacter spp. and the incidence of antibiotic resistance. METHODS: Four poultry flocks naturally colonized with Campylobacter were treated with amoxicillin and monitored before, during and up to 4 weeks post-treatment. The numbers of Campylobacter were determined and the isolates speciated and typed by flaA short variable region (SVR) sequence analysis and PFGE. The susceptibility of the isolates to antibiotics, presence of the Cj0299 gene encoding a beta-lactamase and beta-lactamase production (nitrocefin hydrolysis) were also determined. RESULTS: Amoxicillin-resistant Campylobacter were isolated from Flock 1 before and during treatment, but Campylobacter were not detected afterwards. Flock 2 was colonized by amoxicillin-susceptible strains throughout sampling. No amoxicillin-resistant isolates arose during or after treatment. Flock 3 contained amoxicillin-susceptible and -resistant types pre-treatment. Resistant isolates were detected during treatment, while antibiotic-susceptible isolates re-emerged at 3 weeks post-treatment. All Campylobacter isolates from Flock 4 were amoxicillin resistant, irrespective of sampling time. All but one of the 82 amoxicillin-resistant (MICs 16 to >128 mg/L) Campylobacter jejuni and Campylobacter coli tested for the presence of Cj0299 carried the gene and all of these produced beta-lactamase. Co-amoxiclav remained active against amoxicillin-resistant isolates. CONCLUSIONS: Amoxicillin therapy had little effect on the numbers of amoxicillin-resistant commensal Campylobacter except for one flock where amoxicillin-resistant Campylobacter temporarily dominated. Amoxicillin therapy did not select amoxicillin-resistant isolates from a previous susceptible strain. Co-amoxiclav remained active against amoxicillin-resistant isolates.

Rapid identification of Salmonella enterica subsp. arizonae and S. enterica subsp. diarizonae by real-time polymerase chain reaction.

Reptiles are popular as pets, leading to an increased risk of human infections due to uncommon Salmonella strains including the Arizona group (subspecies arizonae and diarizonae). We present a real-time Arizona-specific polymerase chain reaction demonstrating 100% specificity and 99.6% sensitivity, offering savings in time and labor over traditional identification methods.

Frequency and molecular characteristics of ciprofloxacin- and rifampicin-resistant Helicobacter pylori from gastric infections in the UK.

Treatment failure with standard Helicobacter pylori eradication regimes may require the use of 'rescue' therapies containing fluoroquinolones or rifamycins. The susceptibilities of H. pylori in the UK to such antimicrobials are unknown; therefore, this study aimed to determine the frequencies and molecular markers of resistance. Ciprofloxacin and rifampicin susceptibilities were determined by Etest and/or disc diffusion for 255 isolates of H. pylori, including 171 isolates from adult dyspeptic patients with refractive infections. Mutations in known resistance-determining regions of gyrA and rpoB were determined. The ciprofloxacin resistance rate was 7.5 %, and gyrA mutations, predominantly at codon position 91, were identified in most resistant isolates. One isolate (<1 %) had an unequivocal rifampicin-resistant phenotype by Etest yet had no associated mutations in the rpoB gene. As resistance rates were low in H. pylori isolates, including those from patients with refractive infections, it was concluded that fluoroquinolones or rifamycins might be considered in the UK for inclusion in 'rescue' therapies.

p38delta Mitogen-activated protein kinase is essential for skin tumor development in mice.

Activating Ras mutations occur in a large portion of human tumors. Yet, the signaling pathways involved in Ras-induced tumor formation remain incompletely understood. The mitogen-activated protein kinase pathways are among the best studied Ras effector pathways. The p38 mitogen-activated protein kinase isoforms are important regulators of key biological processes including cell proliferation, differentiation, survival, inflammation, senescence, and tumorigenesis. However, the specific in vivo contribution of individual p38 isoforms to skin tumor development has not been elucidated. Recent studies have shown that p38delta, a p38 family member, functions as an important regulator of epidermal keratinocyte differentiation and survival. In the present study, we have assessed the effect of p38delta deficiency on skin tumor development in vivo by subjecting p38delta knockout mice to a two-stage 7,12-dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol-13-acetate chemical skin carcinogenesis protocol. We report that mice lacking p38delta gene exhibited a marked resistance to development of 7,12-dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol-13-acetate-induced skin papillomas, with increased latency and greatly reduced incidence, multiplicity, and size of tumors compared with wild-type mice. Our data suggest that the underlying mechanism for reduced susceptibility to skin carcinogenesis in p38delta-null mice involves a defect in proliferative response associated with aberrant signaling through the two major transformation-promoting pathways: extracellular signal-regulated kinase 1/2-activator protein 1 and signal transducer and activator of transcription 3. These findings strongly suggest an in vivo role for p38delta in promoting cell proliferation and tumor development in epidermis and may have therapeutic implication for skin cancer.

Prevalence, characterisation and antimicrobial resistance of Campylobacter and Salmonella in raw poultrymeat in the UK, 2003-2005.

This study was conducted to determine the prevalence and antimicrobial resistance of Campylobacter and Salmonella isolates from retail poultrymeat in the UK during 2003-2005. Poultrymeat (n = 2104) were more frequently contaminated with Campylobacter (57.3%) than with Salmonella (6.6%). Chicken exhibited the highest contamination from Campylobacter (60.9%), followed by duck (50.7%), turkey (33.7%) and other poultrymeat (34.2%). Duck had the highest contamination from Salmonella (29.9%), compared with chicken (5.6%), turkey (5.6%), and other poultrymeat (8.6%). C. jejuni predominated in raw chicken, whereas C. coli predominated in turkey and duck. C. coli isolates were more likely to exhibit antimicrobial drug resistance, including quinolones, than C. jejuni. Salmonella Enteritidis was the most frequent Salmonella serotype isolated. Salmonella isolates from turkey exhibited higher rates of multiple drug resistance (55.6%) than isolates from chicken (20.9%) and duck (13.6%). The findings reinforce the importance of thorough cooking of poultrymeat and good hygiene to avoid cross-contamination.

Horizontal versus familial transmission of Helicobacter pylori.

Transmission of Helicobacter pylori is thought to occur mainly during childhood, and predominantly within families. However, due to the difficulty of obtaining H. pylori isolates from large population samples and to the extensive genetic diversity between isolates, the transmission and spread of H. pylori remain poorly understood. We studied the genetic relationships of H. pylori isolated from 52 individuals of two large families living in a rural community in South Africa and from 43 individuals of 11 families living in urban settings in the United Kingdom, the United States, Korea, and Colombia. A 3,406 bp multilocus sequence haplotype was determined for a total of 142 H. pylori isolates. Isolates were assigned to biogeographic populations, and recent transmission was measured as the occurrence of non-unique isolates, i.e., isolates whose sequences were identical to those of other isolates. Members of urban families were almost always infected with isolates from the biogeographic population that is common in their location. Non-unique isolates were frequent in urban families, consistent with familial transmission between parents and children or between siblings. In contrast, the diversity of H. pylori in the South African families was much more extensive, and four distinct biogeographic populations circulated in this area. Non-unique isolates were less frequent in South African families, and there was no significant correlation between kinship and similarity of H. pylori sequences. However, individuals who lived in the same household did have an increased probability of carrying the same non-unique isolates of H. pylori, independent of kinship. We conclude that patterns of spread of H. pylori under conditions of high prevalence, such as the rural South African families, differ from those in developed countries. Horizontal transmission occurs frequently between persons who do not belong to a core family, blurring the pattern of familial transmission that is typical of developed countries. Predominantly familial transmission in urban societies is likely a result of modern living conditions with good sanitation and where physical contact between persons outside the core family is limited and regulated by societal rules. The patterns observed in rural South African families may be representative of large parts of the developing world.

A novel real-time PCR assay for the detection of Helicobacter pullorum-like organisms in chicken products.

A novel real-time PCR assay was developed for the direct detection in food of Helicobacter pullorum-like bacteria, which are occasionally associated with human enteric disease. Experiments using control strains showed that the realtime PCR assay was specific and reproducible, with a detection level of 1 colony-forming unit (CFU)/g. The assay was then applied to determine contamination rates in 30 samples of three types of chicken-meat products obtained from five retail outlets in Spain (Valencia); all of the samples were initially considered to be culture-negative for Helicobacter even after an enrichment period. H.pullorum-like DNA was detected in seven out of ten chicken carcasses and in one chicken-burger sample (without enrichment), as well as in one liver sample (after enrichment). Sequencing of three randomly selected PCR products confirmed concordance (99% homology) with the H. pullorum 16S rDNA gene. The advantages of real-time PCR over conventional PCR assays are the improved detection level, speed of testing, and validation of specificity by melting-point analysis. The fact that bacteria are frequently present in chicken carcasses sold in retail stores highlights the importance of more widely monitoring contamination rates. The novel assay described herein allows better assessment of potential human health risks posed by H. pullorum.

A novel real-time PCR assay for the detection of Helicobacter pullorum-like organisms in chicken products

A novel real-time PCR assay was developed for the direct detection in food of Helicobacter pullorum-like bacteria, which are occasionally associated with human enteric disease. Experiments using control strains showed that the realtime PCR assay was specific and reproducible, with a detection level of 1 colony-forming unit (CFU)/g. The assay was then applied to determine contamination rates in 30 samples of three types of chicken-meat products obtained from five retail outlets in Spain (Valencia); all of the samples were initially considered to be culture-negative for Helicobacter even after an enrichment period. H.pullorum-like DNA was detected in seven out of ten chicken carcasses and in one chicken-burger sample (without enrichment), as well as in one liver sample (after enrichment). Sequencing of three randomly selected PCR products confirmed concordance (99% homology) with the H. pullorum 16S rDNA gene. The advantages of real-time PCR over conventional PCR assays are the improved detection level, speed of testing, and validation of specificity by melting-point analysis. The fact that bacteria are frequently present in chicken carcasses sold in retail stores highlights the importance of more widely monitoring contamination rates. The novel assay described herein allows better assessment of potential human health risks posed by H. pullorum (AU)

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Host-pathogen interactions in Campylobacter infections: the host perspective.

Campylobacter is a major cause of acute bacterial diarrhea in humans worldwide. This study was aimed at summarizing the current understanding of host mechanisms involved in the defense against Campylobacter by evaluating data available from three sources: (i) epidemiological observations, (ii) observations of patients, and (iii) experimental observations including observations of animal models and human volunteer studies. Analysis of available data clearly indicates that an effective immune system is crucial for the host defense against Campylobacter infection. Innate, cell-mediated, and humoral immune responses are induced during Campylobacter infection, but the relative importance of these mechanisms in conferring protective immunity against reinfection is unclear. Frequent exposure to Campylobacter does lead to the induction of short-term protection against disease but most probably not against colonization. Recent progress in the development of more suitable animal models for studying Campylobacter infection has opened up possibilities to study the importance of innate and adaptive immunity during infection and in protection against reinfection. In addition, advances in genomics and proteomics technologies will enable more detailed molecular studies. Such studies combined with better integration of host and pathogen research driven by epidemiological findings may truly advance our understanding of Campylobacter infection in humans.

Application of polymerase chain reaction-based assays for rapid identification and antibiotic resistance screening of Helicobacter pylori in gastric biopsies.

The benefits of using a multiplex detection polymerase chain reaction (PCR) assay for Helicobacter pylori speciation and 2 real-time probe hybridization assays determining clarithromycin and tetracycline susceptibilities in gastric biopsies from 171 dyspeptic patients were investigated. Overall, 70 of 71 H. pylori culture-positive biopsies were PCR positive. For the 100 culture-negative biopsies, PCR identified a further 29 H. pylori positives (17% overall) and presence of resistance markers for clarithromycin (20/28) and tetracycline (2/28). The results demonstrated that PCR testing was valuable in providing improved detection rates and antibiotic susceptibility information when H. pylori culture was unsuccessful.

Helicobacter hypothesis for idiopathic parkinsonism: before and beyond.

We challenge the concept of idiopathic parkinsonism (IP) as inevitably progressive neurodegeneration, proposing a natural history of sequential microbial insults with predisposing host response. Proof-of-principle that infection can contribute to IP was provided by case studies and a placebo-controlled efficacy study of Helicobacter eradication. "Malignant" IP appears converted to "benign", but marked deterioration accompanies failure. Similar benefit on brady/hypokinesia from eradicating "low-density" infection favors autoimmunity. Although a minority of UK probands are urea breath test positive for Helicobacter, the predicted probability of having the parkinsonian label depends on the serum H. pylori antibody profile, with clinically relevant gradients between this "discriminant index" and disease burden and progression. In IP, H. pylori antibodies discriminate for persistently abnormal bowel function, and specific abnormal duodenal enterocyte mitochondrial morphology is described in relation to H. pylori infection. Slow intestinal transit manifests as constipation from the prodrome. Diarrhea may flag secondary small-intestinal bacterial overgrowth. This, coupled with genetically determined intense inflammatory response, might explain evolution from brady/hypokinetic to rigidity-predominant parkinsonism.

Geographical conservation of short inserts in the signal and middle regions of the Helicobacter pylori vacuolating cytotoxin gene.

Short nucleotide sequence inserts within the signal (s) and mid (m) regions of the vacuolating cytotoxin gene (vacA) of Helicobacter pylori provide the basis for defining the allelic forms widely used for strain typing and as markers for toxin functionality and severity of interactions with host gastric epithelial cells. Here 484 signal region and 411 mid-region sequences (new and from public databases) from 32 countries were analysed to determine the effect of geographical location on insert diversity, which is currently undefined. Short (27 bp) inserts of 52 mol% G+C from 201 sequences (98 %) of the s2 allelic family encoded a highly conserved nine amino acid sequence irrespective of geographical origin. The longer (75 bp) mid-region insert of 38 mol% G+C in 255 sequences of the m2 allelic family was more diverse and represented by 23 peptide variants, with one predominant sequence (MRI type 4) representing 62 % of inserts. Mid-region inserts were widespread throughout European/North American (Western) sequences in the dataset whereas a lower insert frequency was a geographical feature of East Asian sequences. Each insert was preceded by an associated conserved motif that provided a marker of the insertion sites within vacA, and facilitated identification of the Chinese m2b genotype. It is concluded that the observed sequence conservation supports the continued global use of vacA genotyping, and that inserts could have a functional significance in the mature protein, particularly the s2 form of the toxin, as the same combination of signal and mid-region insert type and preinsert motif was highly conserved.