Direct targeting of host microtubule and actin cytoskeletons by a chlamydial pathogenic effector protein.

To propagate within a eukaryotic cell, pathogenic bacteria hijack and remodulate host cell functions. The Gram-negative obligate intracellular Chlamydiaceae, which pose a serious threat to human and animal health, attach to host cells and inject effector proteins that reprogram host cell machineries. Members of the conserved chlamydial TarP family have been characterized as major early effectors that bind to and remodel the host actin cytoskeleton. We now describe a new function for the Chlamydia pneumoniae TarP member CPn0572, namely the ability to bind and alter the microtubule cytoskeleton. Thus, CPn0572 is unique in being the only prokaryotic protein that directly modulates both dynamic cytoskeletons of a eukaryotic cell. Ectopically expressed GFP-CPn0572 associates in a dose-independent manner with either cytoskeleton singly or simultaneously. In vitro, CPn0572 binds directly to microtubules. Expression of a microtubule-only CPn0572 variant resulted in the formation of an aberrantly thick, stabilized microtubule network. Intriguingly, during infection, secreted CPn0572 also colocalized with altered microtubules, suggesting that this protein also affects microtubule dynamics during infection. Our analysis points to a crosstalk between actin and microtubule cytoskeletons via chlamydial CPn0572.

A Functional Yeast-Based Screen Identifies the Host Microtubule Cytoskeleton as a Target of Numerous Chlamydia pneumoniae Proteins.

Bacterial pathogens have evolved intricate ways to manipulate the host to support infection. Here, we systematically assessed the importance of the microtubule cytoskeleton for infection by Chlamydiae, which are obligate intracellular bacteria that are of great importance for human health. The elimination of microtubules in human HEp-2 cells prior to C. pneumoniae infection profoundly attenuated the infection efficiency, demonstrating the need for microtubules for the early infection processes. To identify microtubule-modulating C. pneumoniae proteins, a screen in the model yeast Schizosaccharomyces pombe was performed. Unexpectedly, among 116 selected chlamydial proteins, more than 10%, namely, 13 proteins, massively altered the yeast interphase microtubule cytoskeleton. With two exceptions, these proteins were predicted to be inclusion membrane proteins. As proof of principle, we selected the conserved CPn0443 protein, which caused massive microtubule instability in yeast, for further analysis. CPn0443 bound and bundled microtubules in vitro and co-localized partially with microtubules in vivo in yeast and human cells. Furthermore, CPn0443-transfected U2OS cells had a significantly reduced infection rate by C. pneumoniae EBs. Thus, our yeast screen identified numerous proteins encoded using the highly reduced C. pneumoniae genome that modulated microtubule dynamics. Hijacking of the host microtubule cytoskeleton must be a vital part of chlamydial infection.

Moral Injury during the COVID-19 pandemic: A delphi model survey of family medicine residents.

OBJECTIVES: The objective is to investigate the primary factors that created experiences leading to moral injury in family medicine residents during the COVID-19 pandemic and also to identify any barriers keeping these residents from seeking or receiving help when they experienced moral injury. METHOD: A DELPHI model study utilizing three rounds of surveys was conducted at four family medicine residency programs in the United States. Resident responses to Survey 1 generated factors perceived to be causing them moral injury or constituting barriers to their seeking help. Thematic analysis identified common themes which were presented to residents in Survey 2 for rating and justification. Results and feedback from Survey 2 were shared with residents in Survey 3, where residents were prompted to reevaluate their ratings for factors and barriers for the purpose of generating consensus among themselves. A ranked list of factors and barriers was thereby created for the participating sites. RESULTS: Residents shared several stories about the factors that most pressured them to violate their moral values. The most severe and frequent factors contributing to moral injury involved disruptions to doctor-patient relationships, patient-family relationships, and relationships with other healthcare professionals. Time was the major barrier to residents seeking help. CONCLUSION: During times of crisis, moral injury among residents may be minimized by protecting and promoting important clinical and professional relationships with patients, colleagues, and other medical professionals. While residents report that lack of time was the most significant barrier to seeking help, it is unclear how this complicated and ubiquitous problem would be resolved or mitigated.

Neoadjuvant Vismodegib and Mohs Micrographic Surgery for Locally Advanced Periocular Basal Cell Carcinoma.

INTRODUCTION: Vismodegib has shown a significant response rate in locally advanced periocular basal cell carcinoma. Long-term monotherapy is very difficult to accomplish due to primary or secondary resistance and side effects that limit the length of treatment. The use of Vismodegib as neoadjuvant followed by Mohs micrographic surgery is an option. PURPOSE: To report the use of neoadjuvant Vismodegib as an option for operable locally advanced basal cell carcinoma followed by Mohs surgery. PATIENTS AND METHODS: The authors treated 8 locally advanced periocular basal cell carcinomas. Mean age was 76, and 6 of 8 were women. Mean size was 18 mm (12-30). Three were recurrent after surgery. Maximal clinical response was obtained at 4.8 months. Patients were operated at the mean time of 7.3 months. RESULTS: Seven patients (87.5%) had a complete response and 1 (12.5%) progressed. Mohs micrographic surgery allowed to confirm a complete histologic response in 5 of 6 (83.3%) cases, and 1 patient refused surgery. All 7 patients are disease free after a mean follow-up of 12.4 months. All patients experienced adverse events. The most common included dysgeusia (100%) and muscle spasms (100%). Weight loss was present in 75% of the patients with a mean loss of 12.6 pounds and hair loss was seen in 50%. Only 1 (12.5%) patient withdraw from treatment because of intolerable muscle spasms. CONCLUSIONS: The authors believe there is a clear role for Vismodegib as neoadjuvant in locally advanced periocular basal cell carcinoma, even in operable cases. Specific indications beyond those already approved should be further discussed. Prospective studies to assess the combination of neoadjuvant Vismodegib followed by Mohs micrographic surgery in locally advanced periocular basal cell carcinoma with long-term follow-up are needed.

The Dbp5 cycle at the nuclear pore complex during mRNA export II: nucleotide cycling and mRNP remodeling by Dbp5 are controlled by Nup159 and Gle1.

Essential messenger RNA (mRNA) export factors execute critical steps to mediate directional transport through nuclear pore complexes (NPCs). At cytoplasmic NPC filaments, the ATPase activity of DEAD-box protein Dbp5 is activated by inositol hexakisphosphate (IP(6))-bound Gle1 to mediate remodeling of mRNA-protein (mRNP) complexes. Whether a single Dbp5 executes multiple remodeling events and how Dbp5 is recycled are unknown. Evidence suggests that Dbp5 binding to Nup159 is required for controlling interactions with Gle1 and the mRNP. Using in vitro reconstitution assays, we found here that Nup159 is specifically required for ADP release from Dbp5. Moreover, Gle1-IP(6) stimulates ATP binding, thus priming Dbp5 for RNA loading. In vivo, a dbp5-R256D/R259D mutant with reduced ADP binding bypasses the need for Nup159 interaction. However, NPC spatial control is important, as a dbp5-R256D/R259D nup42Δ double mutant is temperature-sensitive for mRNA export. Further analysis reveals that remodeling requires a conformational shift to the Dbp5-ADP form. ADP release factors for DEAD-box proteins have not been reported previously and reflect a new paradigm for regulation. We propose a model wherein Nup159 and Gle1-IP(6) regulate Dbp5 cycles by controlling its nucleotide-bound state, allowing multiple cycles of mRNP remodeling by a single Dbp5 at the NPC.

The Dbp5 cycle at the nuclear pore complex during mRNA export I: dbp5 mutants with defects in RNA binding and ATP hydrolysis define key steps for Nup159 and Gle1.

Nuclear export of messenger RNA (mRNA) occurs by translocation of mRNA/protein complexes (mRNPs) through nuclear pore complexes (NPCs). The DEAD-box protein Dbp5 mediates export by triggering removal of mRNP proteins in a spatially controlled manner. This requires Dbp5 interaction with Nup159 in NPC cytoplasmic filaments and activation of Dbp5's ATPase activity by Gle1 bound to inositol hexakisphosphate (IP(6)). However, the precise sequence of events within this mechanism has not been fully defined. Here we analyze dbp5 mutants that alter ATP binding, ATP hydrolysis, or RNA binding. We found that ATP binding and hydrolysis are required for efficient Dbp5 association with NPCs. Interestingly, mutants defective for RNA binding are dominant-negative (DN) for mRNA export in yeast and human cells. We show that the DN phenotype stems from competition with wild-type Dbp5 for Gle1 at NPCs. The Dbp5-Gle1 interaction is limiting for export and, importantly, can be independent of Nup159. Fluorescence recovery after photobleaching experiments in yeast show a very dynamic association between Dbp5 and NPCs, averaging <1 sec, similar to reported NPC translocation rates for mRNPs. This work reveals critical steps in the Gle1-IP(6)/Dbp5/Nup159 cycle, and suggests that the number of remodeling events mediated by a single Dbp5 is limited.

[Risk factors for the development of rotator cuff tears in individuals with paraplegia : A cross-sectional study]. / Risikofaktoren für Rotatorenmanschettenrupturen bei Paraplegikern : Eine Querschnittstudie.

QUESTION: Shoulder pain and rotator cuff tears are highly prevalent among wheelchair dependent individuals with paraplegia. The purpose of this study was to identify potential risk factors associated with the development of rotator cuff tears in this population. METHODS: A total of 217 wheelchair dependent individuals with paraplegia were included in this cross-sectional study (level of evidence III). The mean age of this population was 47.9 years and the mean duration of wheelchair dependence was 24.1 years. Each individual was asked to complete a questionnaire designed to identify risk factors for rotator cuff tears and underwent a standardized clinical examination with the documentation of the Constant-Murley shoulder outcome score and magnetic resonance imaging (MRI) of both shoulder joints. RESULTS: MRI analysis revealed at least one rotator cuff tear in 93 patients (43%). Multiple logistic regression analysis identified the following factors to be associated with the presence of rotator cuff tear: patient age, duration of spinal cord injury/wheelchair dependence, gender, and wheelchair athletic activity. Neither BMI nor the level of spinal cord injury was found to pose a risk factor in the population studied. With respect to patient age, the risk of developing a rotator cuff tear increased by 11% per annum. In terms of duration of spinal cord injury, the analysis revealed a 6% increased risk per year of wheelchair dependence (OR = 1.06). Females had a 2.6-fold higher risk of developing rotator cuff tears than males and wheelchair sport activity increased the risk 2.3-fold. DISCUSSION: There is a high prevalence of rotator cuff tears in wheel-chair dependent persons with paraplegia. Risk factors such as age, gender, duration of paraplegia, and wheel chair sport activity seem to play an important role in the development of rotator cuff tears.

Spinal cord ability ruler: an interval scale to measure volitional performance after spinal cord injury.

STUDY DESIGN: Retrospective statistical analysis of database. OBJECTIVE: Spinal cord injury (SCI) clinical trials are challenged to enroll participants, and early trial outcomes have often been equivocal. We hypothesized that a specifically designed novel true linear interval-scaled outcome measure targeted to simultaneously track a broad range of SCI will enable more inclusive enrollment of participants and valid comparisons of functional changes after SCI. METHODS: To define a single SCI measurement framework, we used items from existing measures. To evaluate linearity and validity of the measure, we used rigorous psychometric Rasch analysis on two data sets from over 2500 traumatic SCI participants (all levels and severities of SCI) within the EMSCI (European Multicenter study about SCI) database. RESULTS: Volitional performance was found to be the unidimensional construct that would detect and track a treatment effect from a central nervous system-directed therapeutic. Along with early evidence for voluntary neurological control of upper-extremity muscle contractions, volitional performance is best described by goal-directed activities of daily living that are increasingly difficult to re-acquire when activity within more caudal spinal segments is required. Validity of the Spinal Cord Ability Ruler (SCAR) as a linear interval construct was confirmed with Rasch analysis. All measurement items were properly ordered, as well as being precise and stable across clinically relevant groups. Only 5/24 items had some misfit. Targeting was excellent over time after SCI, with few gaps and only modest floor and ceiling effects (3% each). CONCLUSIONS: SCAR is a quantitative linear measure of volitional performance across an inclusive range of tetraplegic and paraplegic SCI.

International standards for neurological classification of spinal cord injury: classification skills of clinicians versus computational algorithms.

STUDY DESIGN: This is a retrospective analysis. OBJECTIVES: The objective of this study was to describe and quantify the discrepancy in the classification of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) by clinicians versus a validated computational algorithm. SETTINGS: European Multicenter Study on Human Spinal Cord Injury (EMSCI). METHODS: Fully documented ISNCSCI data sets from EMSCI's first years (2003-2005) classified by clinicians (mostly spinal cord medicine residents, who received in-house ISNCSCI training by senior SCI physicians) were computationally reclassified. Any differences in the scoring of sensory and motor levels, American Spinal Injury Association Impairment Scale (AIS) or the zone of partial preservation (ZPP) were quantified. RESULTS: Four hundred and twenty ISNCSCI data sets were evaluated. The lowest agreement was found in motor levels (right: 62.1%, P=0.002; left: 61.8%, P=0.003), followed by motor ZPP (right: 81.6%, P=0.74; left 80.0%, P=0.27) and then AIS (83.4%, P=0.001). Sensory levels and sensory ZPP showed the best concordance (right sensory level: 90.8%, P=0.66; left sensory level: 90.0%, P=0.30; right sensory ZPP: 91.0%, P=0.18; left sensory ZPP: 92.2%, P=0.03). AIS B was most often misinterpreted as AIS C and vice versa (AIS B as C: 29.4% and AIS C as B: 38.6%). CONCLUSION: Most difficult classification tasks were the correct determination of motor levels and the differentiation between AIS B and AIS C/D. These issues should be addressed in upcoming ISNCSCI revisions. Training is strongly recommended to improve classification skills for clinical practice, as well as for clinical investigators conducting spinal cord studies. SPONSORSHIP: This study is partially funded by the International Foundation for Research in Paraplegia, Zurich, Switzerland.

Challenges for defining minimal clinically important difference (MCID) after spinal cord injury.

STUDY DESIGN: This is a review article. OBJECTIVES: This study discusses the following: (1) concepts and constraints for the determination of minimal clinically important difference (MCID), (2) the contrasts between MCID and minimal detectable difference (MDD), (3) MCID within the different domains of International Classification of Functioning, disability and health, (4) the roles of clinical investigators and clinical participants in defining MCID and (5) the implementation of MCID in acute versus chronic spinal cord injury (SCI) studies. METHODS: The methods include narrative reviews of SCI outcomes, a 2-day meeting of the authors and statistical methods of analysis representing MDD. RESULTS: The data from SCI study outcomes are dependent on many elements, including the following: the level and severity of SCI, the heterogeneity within each study cohort, the therapeutic target, the nature of the therapy, any confounding influences or comorbidities, the assessment times relative to the date of injury, the outcome measurement instrument and the clinical end-point threshold used to determine a treatment effect. Even if statistically significant differences can be established, this finding does not guarantee that the experimental therapeutic provides a person living with SCI an improved capacity for functional independence and/or an increased quality of life. The MDD statistical concept describes the smallest real change in the specified outcome, beyond measurement error, and it should not be confused with the minimum threshold for demonstrating a clinical benefit or MCID. Unfortunately, MCID and MDD are not uncomplicated estimations; nevertheless, any MCID should exceed the expected MDD plus any probable spontaneous recovery. CONCLUSION: Estimation of an MCID for SCI remains elusive. In the interim, if the target of a therapeutic is the injured spinal cord, it is most desirable that any improvement in neurological status be correlated with a functional (meaningful) benefit.

[Rehabilitation for paraplegics]. / Rehabilitation nach Querschnittlähmung.

Paraplegia permanently impairs the lives of patients and puts them at risk for other medical complications. Rehabilitation is very complex and has to be adjusted to the specific needs of the patient; it requires an interdisciplinary team with special training. Initial treatment of paraplegic patients aims to enable life at home whenever feasible or a nursing institution that can accommodate the patient's needs. For this, it is necessary that the patient is in stable condition, urinary and bowel continence has been established, ability to communicate is restored, and the patient is mobile within his/her means. Occupational rehabilitation should also have been started or at least offered. Another important element in the comprehensive care of paraplegic patients is lifelong follow-up.

Lowered GnT-I Activity Decreases Complex-Type N-Glycan Amounts and Results in an Aberrant Primary Motor Neuron Structure in the Spinal Cord.

The attachment of sugar to proteins and lipids is a basic modification needed for organismal survival, and perturbations in glycosylation cause severe developmental and neurological difficulties. Here, we investigated the neurological consequences of N-glycan populations in the spinal cord of Wt AB and mgat1b mutant zebrafish. Mutant fish have reduced N-acetylglucosaminyltransferase-I (GnT-I) activity as mgat1a remains intact. GnT-I converts oligomannose N-glycans to hybrid N-glycans, which is needed for complex N-glycan production. MALDI-TOF MS profiles identified N-glycans in the spinal cord for the first time and revealed reduced amounts of complex N-glycans in mutant fish, supporting a lesion in mgat1b. Further lectin blotting showed that oligomannose N-glycans were more prevalent in the spinal cord, skeletal muscle, heart, swim bladder, skin, and testis in mutant fish relative to WT AB, supporting lowered GnT- I activity in a global manner. Developmental delays were noted in hatching and in the swim bladder. Microscopic images of caudal primary (CaP) motor neurons of the spinal cord transiently expressing EGFP in mutant fish were abnormal with significant reductions in collateral branches. Further motor coordination skills were impaired in mutant fish. We conclude that identifying the neurological consequences of aberrant N-glycan processing will enhance our understanding of the role of complex N-glycans in development and nervous system health.

Inositol hexakisphosphate and Gle1 activate the DEAD-box protein Dbp5 for nuclear mRNA export.

Regulation of nuclear mRNA export is critical for proper eukaryotic gene expression. A key step in this process is the directional translocation of mRNA-ribonucleoprotein particles (mRNPs) through nuclear pore complexes (NPCs) that are embedded in the nuclear envelope. Our previous studies in Saccharomyces cerevisiae defined an in vivo role for inositol hexakisphosphate (InsP6) and NPC-associated Gle1 in mRNA export. Here, we show that Gle1 and InsP6 act together to stimulate the RNA-dependent ATPase activity of the essential DEAD-box protein Dbp5. Overexpression of DBP5 specifically suppressed mRNA export and growth defects of an ipk1 nup42 mutant defective in InsP6 production and Gle1 localization. In vitro kinetic analysis showed that InsP6 significantly increased Dbp5 ATPase activity in a Gle1-dependent manner and lowered the effective RNA concentration for half-maximal ATPase activity. Gle1 alone had minimal effects. Maximal InsP6 binding required both Dbp5 and Gle1. It has been suggested that Dbp5 requires unidentified cofactors. We now propose that Dbp5 activation at NPCs requires Gle1 and InsP6. This would facilitate spatial control of the remodelling of mRNP protein composition during directional transport and provide energy to power transport cycles.

[Perioperative care of palliative patients by the anesthetist : medical, psychosocial and ethical challenges]. / Perioperative Betreuung von Palliativpatienten durch den Anästhesisten : Medizinische, psychosoziale und ethische Herausforderungen.

Anesthetists will encounter palliative patients in the daily routine as palliative patients undergo operations and interventions as well, depending on the state of the disease. The first challenge for anesthetists will be to recognize the patient as being palliative. In the course of further treatment it will be necessary to address the specific problems of this patient group. Medical problems are optimized symptom control and the patient's pre-existing medication. In the psychosocial domain, good communication skills are expected of anesthetists, especially during the preoperative interview. Ethical conflicts exist with the decision-making process for surgery and the handling of perioperative do-not-resuscitate orders. This article addresses these areas of conflict and the aim is to enable anesthetists to provide the best possible perioperative care to this vulnerable patient group with the goal to maintain quality of life and keep postoperative recovery as short as possible.

[Therapy of septic paraplegia]. / Therapie der septischen Querschnittlähmung.

The frequency of infectious diseases of the spine and associated spinal cord injury are constantly increasing. Affected are multimorbid and elderly patients, mostly after prolonged medical treatment. An acute spinal cord injury due to infection is an emergency. A rapid decision for treatment strategy and if at all possible subtle debridement of the infected tissue with decompression of the spinal cord is paramount. Additionally spinal cord injury necessitates specialized treatment and care of the infection. Spinal cord injured patients in general and these patients in particular are prone to complications and need especially trained nursing personnel. It is therefore recommended that patients with vertebral osteomyelitis associated with spinal cord injury should be transferred to dedicated centres of treatment as soon as possible.Just as in cases of spondylodiscitis without spinal cord injury inconsistent surgical or insufficient antibiotic treatment worsens the prognosis significantly. If it is possible to remit the infection, the prognosis for recovery of motor and sensory function is better than in cases with traumatic spinal cord injury. In many cases at least partial recovery can be observed.

Inositol Pyrophosphate-Controlled Kinetochore Architecture and Mitotic Entry in S. pombe.

Inositol pyrophosphates (IPPs) comprise a specific class of signaling molecules that regulate central biological processes in eukaryotes. The conserved Vip1/PPIP5K family controls intracellular IP8 levels, the highest phosphorylated form of IPPs present in yeasts, as it has both inositol kinase and pyrophosphatase activities. Previous studies have shown that the fission yeast S. pombe Vip1/PPIP5K family member Asp1 impacts chromosome transmission fidelity via the modulation of spindle function. We now demonstrate that an IP8 analogue is targeted by endogenous Asp1 and that cellular IP8 is subject to cell cycle control. Mitotic entry requires Asp1 kinase function and IP8 levels are increased at the G2/M transition. In addition, the kinetochore, the conductor of chromosome segregation that is assembled on chromosomes is modulated by IP8. Members of the yeast CCAN kinetochore-subcomplex such as Mal2/CENP-O localize to the kinetochore depending on the intracellular IP8-level: higher than wild-type IP8 levels reduce Mal2 kinetochore targeting, while a reduction in IP8 has the opposite effect. As our perturbations of the inositol polyphosphate and IPP pathways demonstrate that kinetochore architecture depends solely on IP8 and not on other IPPs, we conclude that chromosome transmission fidelity is controlled by IP8 via an interplay between entry into mitosis, kinetochore architecture, and spindle dynamics.

Control of mRNA export and translation termination by inositol hexakisphosphate requires specific interaction with Gle1.

The unidirectional translocation of messenger RNA (mRNA) through the aqueous channel of the nuclear pore complex (NPC) is mediated by interactions between soluble mRNA export factors and distinct binding sites on the NPC. At the cytoplasmic side of the NPC, the conserved mRNA export factors Gle1 and inositol hexakisphosphate (IP(6)) play an essential role in mRNA export by activating the ATPase activity of the DEAD-box protein Dbp5, promoting localized messenger ribonucleoprotein complex remodeling, and ensuring the directionality of the export process. In addition, Dbp5, Gle1, and IP(6) are also required for proper translation termination. However, the specificity of the IP(6)-Gle1 interaction in vivo is unknown. Here, we characterize the biochemical interaction between Gle1 and IP(6) and the relationship to Dbp5 binding and stimulation. We identify Gle1 residues required for IP(6) binding and show that these residues are needed for IP(6)-dependent Dbp5 stimulation in vitro. Furthermore, we demonstrate that Gle1 is the primary target of IP(6) for both mRNA export and translation termination in vivo. In Saccharomyces cerevisiae cells, the IP(6)-binding mutants recapitulate all of the mRNA export and translation termination defects found in mutants depleted of IP(6). We conclude that Gle1 specifically binds IP(6) and that this interaction is required for the full potentiation of Dbp5 ATPase activity during both mRNA export and translation termination.

A low carbohydrate Mediterranean diet improves cardiovascular risk factors and diabetes control among overweight patients with type 2 diabetes mellitus: a 1-year prospective randomized intervention study.

BACKGROUND: The appropriate dietary intervention for overweight persons with type 2 diabetes mellitus (DM2) is unclear. Trials comparing the effectiveness of diets are frequently limited by short follow-up times and high dropout rates. AIM: The effects of a low carbohydrate Mediterranean (LCM), a traditional Mediterranean (TM), and the 2003 American Diabetic Association (ADA) diet were compared, on health parameters during a 12-month period. METHODS: In this 12-month trial, 259 overweight diabetic patients (mean age 55 years, mean body mass index 31.4 kg/m(2)) were randomly assigned to one of the three diets. The primary end-points were reduction of fasting plasma glucose, HbA1c and triglyceride (TG) levels. RESULTS: 194 patients out of 259 (74.9%) completed follow-up. After 12 months, the mean weight loss for all patients was 8.3 kg: 7.7 kg for ADA, 7.4 kg for TM and 10.1 kg for LCM diets. The reduction in HbA1c was significantly greater in the LCM diet than in the ADA diet (-2.0 and -1.6%, respectively, p < 0.022). HDL cholesterol increased (0.1 mmol/l +/- 0.02) only on the LCM (p < 0.002). The reduction in serum TG was greater in the LCM (-1.3 mmol/l) and TM (-1.5 mmol/l) than in the ADA (-0.7 mmol/l), p = 0.001. CONCLUSIONS: An intensive 12-month dietary intervention in a community-based setting was effective in improving most modifiable cardiovascular risk factors in all the dietary groups. Only the LCM improved HDL levels and was superior to both the ADA and TM in improving glycaemic control.

[Kyphectomy in myelomeningocele patients. Longterm results, complications and risk analysis]. / Gibbusresektion bei Myelomeningozelepatienten. Langzeitergebnisse, Komplikationen und Risikoanalyse.

BACKGROUND: The conservative and surgical management of lumbar kyphosis is difficult and is a challenge for the orthopaedic surgeon. A kyphotic deformity of the lumbar spine is present in 8% to 20% of these patients. Most curves have very rigid components, often exceed 80 degrees at birth. The options for conservative management are limited. Bracing is extremely difficult, rarely effective, and in advanced stages impossible. We have been using the Warner and Fackler kyphectomy technique at our institution since 1994 as a standard procedure for treating children with lumbar kyphosis due to myelomeningocele. RESULTS: This study was performed for a better understanding of the cause of the complications and optimizing the surgical technique. AIM: The aim of this study was to evaluate the longterm results, technical problems, early and late complications and the complication associated risk factors.