Type F congenital quadricuspid aortic valve: A very rare case diagnosed by 3-dimenional transoesophageal echocardiography

Congenital quadricuspid aortic valve (QAV) is a rare cardiac anomaly. Several different anatomical variations of a quadricuspid aortic valve have been described. Aortic regurgitation is the predominant valvular dysfunction associated with QAV and patients tend to present in their 5(th) or 6(th) decade of life. This anomaly is rarely picked up by transthoracic echocardiogram (TTE). A comprehensive transoesophageal echocardiography (TOE) study is more likely to diagnose it. We describe a very rare type of QAV - Type F in a 52-year-old lady who presented with symptoms of shortness of breath and pre-syncope. We include TOE images and intra-operative valve images

Does inter-vertebral range of motion increase after spinal manipulation? A prospective cohort study.

Background: Spinal manipulation for nonspecific neck pain is thought to work in part by improving inter-vertebral range of motion (IV-RoM), but it is difficult to measure this or determine whether it is related to clinical outcomes. Objectives: This study undertook to determine whether cervical spine flexion and extension IV-RoM increases after a course of spinal manipulation, to explore relationships between any IV-RoM increases and clinical outcomes and to compare palpation with objective measurement in the detection of hypo-mobile segments. Method: Thirty patients with nonspecific neck pain and 30 healthy controls matched for age and gender received quantitative fluoroscopy (QF) screenings to measure flexion and extension IV-RoM (C1-C6) at baseline and 4-week follow-up between September 2012-13. Patients received up to 12 neck manipulations and completed NRS, NDI and Euroqol 5D-5L at baseline, plus PGIC and satisfaction questionnaires at follow-up. IV-RoM accuracy, repeatability and hypo-mobility cut-offs were determined. Minimal detectable changes (MDC) over 4 weeks were calculated from controls. Patients and control IV-RoMs were compared at baseline as well as changes in patients over 4 weeks. Correlations between outcomes and the number of manipulations received and the agreement (Kappa) between palpated and QF-detected of hypo-mobile segments were calculated. Results: QF had high accuracy (worst RMS error 0.5o) and repeatability (highest SEM 1.1o, lowest ICC 0.90) for IV-RoM measurement. Hypo-mobility cut offs ranged from 0.8o to 3.5o. No outcome was significantly correlated with increased IV-RoM above MDC and there was no significant difference between the number of hypo-mobile segments in patients and controls at baseline or significant increases in IV-RoMs in patients. However, there was a modest and significant correlation between the number of manipulations received and the number of levels and directions whose IV-RoM increased beyond MDC (Rho=0.39, p=0.043). There was also no agreement between palpation and QF in identifying hypo-mobile segments (Kappa 0.04-0.06). Conclusions: This study found no differences in cervical sagittal IV-RoM between patients with non-specific neck pain and matched controls. There was a modest dose-response relationship between the number of manipulations given and number of levels increasing IV-RoM - providing evidence that neck manipulation has a mechanical effect at segmental levels. However, patient-reported outcomes were not related to this

Symptomatic reactions, clinical outcomes and patient satisfaction associated with upper cervical chiropractic care: A prospective, multicenter, cohort study

<p>Abstract</p> <p>Background</p> <p>Observational studies have previously shown that adverse events following manipulation to the neck and/or back are relatively common, although these reactions tend to be mild in intensity and self-limiting. However, no prospective study has examined the incidence of adverse reactions following spinal adjustments using upper cervical techniques, and the impact of this care on clinical outcomes.</p> <p>Methods</p> <p>Consecutive new patients from the offices of 83 chiropractors were recruited for this practice-based study. Clinical outcome measures included 1) Neck pain disability index (100-point scale), 2) Oswestry back pain index (100-point scale), 3) 11-point numerical rating scale (NRS) for neck, headache, midback, and low back pain, 4) treatment satisfaction, and 5) Symptomatic Reactions (SR). Data were collected at baseline, and after approximately 2 weeks of care. A patient reaching sub-clinical status for pain and disability was defined as a follow-up score <3 NRS and <10%, respectively. A SR is defined as a new complaint not present at baseline or a worsening of the presenting complaint by >30% based on an 11-point numeric rating scale occurring <24 hours after any upper cervical procedure.</p> <p>Results</p> <p>A total of 1,090 patients completed the study having 4,920 (4.5 per patient) office visits requiring 2,653 (2.4 per patient) upper cervical adjustments over 17 days. Three hundred thirty- eight (31.0%) patients had SRs meeting the accepted definition. Intense SR (NRS ≥8) occurred in 56 patients (5.1%). Outcome assessments were significantly improved for neck pain and disability, headache, mid-back pain, as well as lower back pain and disability (<it>p </it><0.001) following care with a high level (mean = 9.1/10) of patient satisfaction. The 83 chiropractors administered >5 million career upper cervical adjustments without a reported incidence of serious adverse event.</p> <p>Conclusions</p> <p>Upper cervical chiropractic care may have a fairly common occurrence of mild intensity SRs short in duration (<24 hours), and rarely severe in intensity; however, outcome assessments were significantly improved with less than 3 weeks of care with a high level of patient satisfaction. Although our findings need to be confirmed in subsequent randomized studies for definitive risk-benefit assessment, the preliminary data shows that the benefits of upper cervical chiropractic care may outweigh the potential risks.</p

A demographic and epidemiological study of a Mexican chiropractic college public clinic

<p>Abstract</p> <p>Background</p> <p>Descriptive studies of chiropractic patients are not new, several have been performed in the U.S., Australia, Canada, and Europe. None have been performed in a Latin American country. The purpose of this study is to describe the patients who visited a Mexican chiropractic college public clinic with respect to demographics and clinical characteristics.</p> <p>Methods</p> <p>This study was reviewed and approved by the IRB of Parker College of Chiropractic and the Universidad Estatal del Valle de Ecatepec (UNEVE). Five hundred patient files from the UNEVE public clinic from May 2005 to May 2007 were selected from an approximate total number of 3,700. Information was collected for demographics, chief complaints, associated complaints, and previous care sought.</p> <p>Results</p> <p>The sample comprised 306 (61.2%) female. Most files (44.2%) were in the age range of 40–59 years (mean of 43.4 years). The most frequent complaints were lumbar pain (29.2%) and extremity pain (28.0%), most commonly the knee. Most (62.0%) described their complaints as greater than one year. Trauma (46.6%) was indicated as the initial cause. Mean VAS score was 6.26/10 with 20% rated at 8/10.</p> <p>Conclusion</p> <p>Demographic results compared closer to studies conducted with private clinicians (females within the ages of 40–59). The primary complaint and duration was similar to previous studies (low back pain and chronic), except in this population the cause was usually initiated by trauma. The most striking features were the higher number of extremity complaints and the marked increased level of VAS score (20% rated as 8/10).</p

Bacterial porin disrupts mitochondrial membrane potential and sensitizes host cells to apoptosis

The bacterial PorB porin, an ATP-binding beta-barrel protein of pathogenic Neisseria gonorrhoeae, triggers host cell apoptosis by an unknown mechanism. PorB is targeted to and imported by host cell mitochondria, causing the breakdown of the mitochondrial membrane potential (delta psi m). Here, we show that PorB induces the condensation of the mitochondrial matrix and the loss of cristae structures, sensitizing cells to the induction of apoptosis via signaling pathways activated by BH3-only proteins. PorB is imported into mitochondria through the general translocase TOM but, unexpectedly, is not recognized by the SAM sorting machinery, usually required for the assembly of beta-barrel proteins in the mitochondrial outer membrane. PorB integrates into the mitochondrial inner membrane, leading to the breakdown of delta psi m. The PorB channel is regulated by nucleotides and an isogenic PorB mutant defective in ATP-binding failed to induce delta psi m loss and apoptosis, demonstrating that dissipation of delta psi m is a requirement for cell death caused by neisserial infection

Temporary exclusion of ill children from childcare centres in Switzerland: practice, problems and potential solutions.

BACKGROUND: In childcare centres, temporary exclusion of ill children, if their illness poses a risk of spread of harmful diseases to others, is a central approach to fight disease transmission. However, not all ill children need to be excluded. Previous studies suggested that childcare centre staff have difficulties in deciding whether or not to exclude an ill child, even when official ill-child guidelines are used. We aimed to describe, quantify and analyse these ambiguities and discuss potential solutions. METHODS: For this cross-sectional study, we sent postal surveys to 488 childcare centre directors in the Swiss Canton of Zurich, where no official ill-child guideline is in place. We asked for exclusion criteria for ill children and ambiguities faced when dealing with ill children. We checked whether existing guidelines provided solutions to the ambiguities identified. RESULTS: 249/488 (51%) directors responded to the survey. The most common exclusion criteria were fever (87.4%) and contagiousness (52.2%). Ambiguities were mostly caused by conjunctivitis (23.7%) and use of antipyretic drugs (22.9%). Roughly one third of the ambiguities identified could have been resolved with existing guidelines, another third if existing guidelines contained additional information. For the last third, clear written directives are difficult to formulate. CONCLUSIONS: Written recommendations may help to clarify when an ill child should temporarily be excluded. However, such a guideline should cover the topics antipyretic drugs and teething and have room for modification to local circumstances. Collaboration with a paediatrician may be of additional benefit

Efficacy of manipulation for non-specific neck pain of recent onset: design of a randomised controlled trial

BACKGROUND: Manipulation is a common treatment for non-specific neck pain. Neck manipulation, unlike gentler forms of manual therapy such as mobilisation, is associated with a small risk of serious neurovascular injury and can result in stroke or death. It is thought however, that neck manipulation provides better results than mobilisation where clinically indicated. There is long standing and vigorous debate both within and between the professions that use neck manipulation as well as the wider scientific community as to whether neck manipulation potentially does more harm than good. The primary aim of this study is to determine whether neck manipulation provides more rapid resolution of an episode of neck pain than mobilisation. METHODS/DESIGN: 182 participants with acute and sub-acute neck pain will be recruited from physiotherapy, chiropractic and osteopathy practices in Sydney, Australia. Participants will be randomly allocated to treatment with either manipulation or mobilisation. Randomisation will occur after the treating practitioner decides that manipulation is an appropriate treatment for the individual participant. Both groups will receive at least 4 treatments over 2 weeks. The primary outcome is number of days taken to recover from the episode of neck pain. Cox regression will be used to compare survival curves for time to recovery for the manipulation and mobilisation treatment groups. DISCUSSION: This paper presents the rationale and design of a randomised controlled trial to compare the effectiveness of neck manipulation and neck mobilisation for acute and subacute neck pain

SLI-1 Cbl Inhibits the Engulfment of Apoptotic Cells in C. elegans through a Ligase-Independent Function

The engulfment of apoptotic cells is required for normal metazoan development and tissue remodeling. In Caenorhabditis elegans, two parallel and partially redundant conserved pathways act in cell-corpse engulfment. One pathway, which includes the small GTPase CED-10 Rac and the cytoskeletal regulator ABI-1, acts to rearrange the cytoskeleton of the engulfing cell. The CED-10 Rac pathway is also required for proper migration of the distal tip cells (DTCs) during the development of the C. elegans gonad. The second pathway includes the receptor tyrosine kinase CED-1 and might recruit membranes to extend the surface of the engulfing cell. Cbl, the mammalian homolog of the C. elegans E3 ubiquitin ligase and adaptor protein SLI-1, interacts with Rac and Abi2 and modulates the actin cytoskeleton, suggesting it might act in engulfment. Our genetic studies indicate that SLI-1 inhibits apoptotic cell engulfment and DTC migration independently of the CED-10 Rac and CED-1 pathways. We found that the RING finger domain of SLI-1 is not essential to rescue the effects of SLI-1 deletion on cell migration, suggesting that its role in this process is ubiquitin ligase-independent. We propose that SLI-1 opposes the engulfment of apoptotic cells via a previously unidentified pathway.National Cancer Institute (U.S.) (Award K08CA104890

Relative effectiveness and adverse effects of cervical manipulation, mobilisation and the activator instrument in patients with sub-acute non-specific neck pain: results from a stopped randomised trial

<p>Abstract</p> <p>Background</p> <p>Neck pain of a mechanical nature is a common complaint seen by practitioners of manual medicine, who use a multitude of methods to treat the condition. It is not known, however, if any of these methods are superior in treatment effectiveness. This trial was stopped due to poor recruitment. The purposes of this report are (1) to describe the trial protocol, (2) to report on the data obtained from subjects who completed the study, (3) to discuss the problems we encountered in conducting this study.</p> <p>Methods</p> <p>A pragmatic randomised clinical trial was undertaken. Patients who met eligibility criteria were randomised into three groups. One group was treated using specific segmental high velocity low amplitude manipulation (diversified), another by specific segmental mobilisation, and a third group by the Activator instrument. All three groups were also treated for any myofascial distortions and given appropriate exercises and advice. Participants were treated six times over a three-week period or until they reported being pain free. The primary outcome measure for the study was Patient Global Impression of Change (PGIC); secondary outcome measures included the Short-Form Health Survey (SF-36v₂), the neck Bournemouth Questionnaire, and the numerical rating scale for pain intensity. Participants also kept a diary of any pain medication taken and noted any perceived adverse effects of treatment. Outcomes were measured at four points: end of treatment, and 3, 6, and 12 months thereafter.</p> <p>Results</p> <p>Between January 2007 and March 2008, 123 patients were assessed for eligibility, of these 47 were considered eligible, of which 16 were allocated to manipulation, 16 to the Activator instrument and 15 to the mobilisation group. Comparison between the groups on the PGIC adjusted for baseline covariants did not show a significant difference for any of the endpoints. Within group analyses for change from baseline to the 12-month follow up for secondary outcomes were significant for all groups on the Bournemouth Questionnaire and for pain, while the mobilisation group had a significant improvement on the PCS and MCS subscales of the SF-36_v2. Finally, there were no moderate, severe, or long-lasting adverse effects reported by any participant in any group.</p> <p>Conclusions</p> <p>Although the small sample size must be taken into consideration, it appears that all three methods of treating mechanical neck pain had a long-term benefit for subacute neck pain, without moderate or serious adverse events associated with any of the treatment methods. There were difficulties in recruiting subjects to this trial. This pragmatic trial should be repeated with a larger sample size.</p

Crystal Structure of PrgI-SipD: Insight into a Secretion Competent State of the Type Three Secretion System Needle Tip and its Interaction with Host Ligands

Many infectious Gram-negative bacteria, including Salmonella typhimurium, require a Type Three Secretion System (T3SS) to translocate virulence factors into host cells. The T3SS consists of a membrane protein complex and an extracellular needle together that form a continuous channel. Regulated secretion of virulence factors requires the presence of SipD at the T3SS needle tip in S. typhimurium. Here we report three-dimensional structures of individual SipD, SipD in fusion with the needle subunit PrgI, and of SipD:PrgI in complex with the bile salt, deoxycholate. Assembly of the complex involves major conformational changes in both SipD and PrgI. This rearrangement is mediated via a π bulge in the central SipD helix and is stabilized by conserved amino acids that may allow for specificity in the assembly and composition of the tip proteins. Five copies each of the needle subunit PrgI and SipD form the T3SS needle tip complex. Using surface plasmon resonance spectroscopy and crystal structure analysis we found that the T3SS needle tip complex binds deoxycholate with micromolar affinity via a cleft formed at the SipD:PrgI interface. In the structure-based three-dimensional model of the T3SS needle tip, the bound deoxycholate faces the host membrane. Recently, binding of SipD with bile salts present in the gut was shown to impede bacterial infection. Binding of bile salts to the SipD:PrgI interface in this particular arrangement may thus inhibit the T3SS function. The structures presented in this study provide insight into the open state of the T3SS needle tip. Our findings present the atomic details of the T3SS arrangement occurring at the pathogen-host interface