[Instabilities of the Thumb Carpometacarpal Joint: Our Surgical Outcomes]. / Nestability karpometakarpálního kloubu palce ruky: nase výsledky operacního resení.

PURPOSE OF THE STUDY Carpometacarpal (CMC) instabilities of the thumb joint occur after injuries or due to joint overload in patients with congenital joint hypermobility. They are often undiagnosed and, if left untreated, are the basis for the development of rhizarthrosis in young individuals. The authors present the results of the Eaton-Littler technique. MATERIAL AND METHODS The authors present a set of 53 CMC joints of patients with an average age of 26.8 years (15-43 years) operated on in the years 2005-2017. Post-traumatic conditions were found in 10 patients and in 43 cases instability was caused by hyperlaxity, also demonstrated in other joints. The operation was performed from the Wagner's modified anteroradial approach. After the operation, a plaster splint was applied for 6 weeks, after which rehabilitation (magnetotherapy, warm-up) began. Patients were evaluated using the VAS (pain at rest and during exercise), DASH score in the work module, and subjective evaluation (no difficulties, difficulties not limiting normal activities, and difficulties limiting normal activities) before surgery and 36 months after surgery. RESULTS During the preoperative assessment, the average VAS value was 5.6 at rest and 8.3 during exercise. During the VAS assessment at rest, the values at 6, 12, 24 and 36 months after surgery were 5.6, 2.9, 0.9, 1, 2 and 1.1. When evaluated in the given intervals under load, the detected values were 4.1, 2, 2.2 and 2.4. The DASH score in the work module was 81.2 before surgery, 46.3 at 6 months, 15.2 at 12 months, 17.3 at 24 months, and 18.4 at 36 months after surgery. In the subjective self-assessment made at 36 months after surgery, 39 patients (74%) assessed their condition as having no difficulties, ten patients (19%) reported difficulties that did not limit normal activities, and four patients (7%) reported difficulties limiting normal activities. DISCUSSION Most authors present the results of their surgeries in patients with post-traumatic joint instability, and they report excellent results at two to six years after surgery. There is a negligible number of studies addressing instabilities in patients with instability caused by hypermobility. When using the conventional method described by the authors in 1973, our results of the evaluation performed at 36 months after surgery are comparable to those reported by other authors. We are well aware of the fact that this is a short-term follow-up and that this method does not prevent developing degenerative changes in the case of long-term follow-up, but reduces clinical difficulties and may delay the development of severe rhizarthrosis in young individuals. CONCLUSIONS CMC instability of the thumb joint is a relatively common disorder, although not all individuals experience clinical difficulties. In the case of difficulties, the instability needs to be diagnosed and treated as this is how the development of early rhizarthrosis in the predisposed individuals can be prevented. Our conclusions suggest a possibility of a surgical solution with good results. Key words: carpometacarpal thumb joint, thumb CMC joint, carpometacarpal thumb instability, joint laxity, rhizarthrosis.

Combined percutaneous approach for aortic valve implantation in poor vascular access.

Transcatheter aortic valve implantation (TAVI) is a well-established management option for symptomatic patients with severe aortic stenosis. The minimally invasive transfemoral approach is considered to be superior to non-transfemoral accesses; however, its use is often limited by concomitant peripheral artery disease (PAD). Percutaneous transluminal angioplasty with stent implantation (PTA) is a gold-standard therapy for symptomatic PAD. We present 2 cases from our cohort of patients with severe aortic stenosis and PAD previously contraindicated for TAVI because of poor peripheral vascular access. However, the patients were eventually treated either by staged PTA and TAVI through an endothelialized stent or PTA and TAVI though a newly implanted peripheral stent during one procedure. We provide recommendations based on our experience of how to select the optimal patients for such a combined minimally invasive transfemoral approach (Fig. 2, Ref. 9). Keywords: transcatheter valve implantation, peripheral arterial disease, aortic valve disease, percutaneous intervention, atherosclerosis.

[Peroneal Nerve Palsy Management by Tibialis Posterior Muscle Transposition - Anatomical and Clinical Study]. / Resení peroneální parézy transpozicí musculus tibialis posterior ­ anatomická a klinická studie.

PURPOSE OF THE STUDY Transposition of tibialis posterior muscle ranks among the methods of dorsiflexion restoration in patients with peroneal nerve palsy. Even though this method is commonly used, anatomical variations are still encountered which make us modify the established procedures. The purpose of this study is to evaluate the functional outcomes of operated patients and based on the clinical experience to define by cadaver preparation the anatomical causes preventing the use of the standard transposition technique. MATERIAL AND METHODS The clinical group includes 21 patients (15 men, 6 women) with the mean age of 34.2 years and with common peroneal nerve palsy confirmed by EMG. In 20 patients, transposition of the tendon of the tibialis posterior muscle (MTP) through the interosseous membrane of the leg was performed. In one patient the tendon was transposed ventrally to the distal end of the tibia and fixed in the lateral cuneiform bone due to an extremely narrow space of the interosseous membrane of the leg distally between the lower limb bones. In 18 patients the tendon was fixed by osteosuture to the base of 3rd metatarsal bone, in three patients to the lateral cuneiform bone. The outcomes were evaluated at 6 months after the surgery, when active ankle dorsiflexion (DF) range of motion greater than 5° was considered an excellent outcome, active position at 90° up to DF less than 5° a satisfactory outcome, and any plantigrade position as a poor outcome. The anatomical study included 20 extremities fixed by formalin (10 cadavers, 5 men and 5 women with the mean age of 71.3 years). The length of the individual parts of tibialis posterior muscle was measured and the variations of the muscle attachment were evaluated. The measurement was concluded by a simulation of surgical procedure. RESULTS When evaluating the clinical group, an excellent outcome was reported in 12 patients (57%), a satisfactory outcome in 8 patients (38%) and a poor outcome in one patient (5%). When evaluating the anatomical group, a division of the attaching part of the tendon into three main strips was observed. The thickest middle strip attached to the tuberosity of navicular bone and medial cuneiform bone was reported in all the specimens. The thinner lateral strip (originating from the tendon in 90% of specimens) was attached to the intermediate and lateral cuneiform bone, the cuboid bone, metatarsal bones II-V, and moreover it grows into the origin of the flexor hallucis brevis muscle. The third strip of the tendon attached to the sustentaculum tali, plantar calcaneonavicular ligament and fibrocartilago navicularis was missing in one specimen (5%). When the passing the tendon through the interosseous space between the lower limb bones was simulated in order for the tendon to go in the direction of the planned traction, in two specimens (10%) the pulling through was impossible due to the tendon being thicker than the interosseous space. In two specimens (10%) it was not the tendon, but already the muscular belly which passed through the given space. DISCUSSION In our group, 95% of the functional outcomes were excellent or satisfactory. A poor result was reported in one patient, in whom the EMG examination was not performed as a standard procedure and in whom the muscular strength was insufficient to achieve full dorsiflexion of the ankle. The anatomical study indicates that the narrow space between the lower limb bones can prevent the pulling through of the tendon, which can be addressed intraoperatively by the transposition of the tendon ventrally to tibia. The study reveals that the tendon necessary for transposition can be elongated by the strips of the tendon attached to the sole of the foot. CONCLUSIONS The knowledge of the anatomical conditions may help us better manage potential complications intraoperatively. Key words: tibialis posterior muscle, peroneal nerve palsy, transposition of tibialis posterior muscle, anatomy of tibialis posterior muscle, common fibular nerve palsy.

Treatment of supragastric belching with cognitive behavioral therapy improves quality of life and reduces acid gastroesophageal reflux.

OBJECTIVES: Excessive supragastric belching (SGB) manifests as troublesome belching, and can be associated with reflux and significant impact on quality of life (QOL). In some GERD patients, SGB-associated reflux contributes to up to 1/3 of the total esophageal acid exposure. We hypothesized that a cognitive-behavioral intervention (CBT) might reduce SGB, improve QOL, and reduce acid gastroesophageal reflux (GOR). We aimed to assess the effectiveness of CBT in patients with pathological SGB. METHODS: Patients with SGB were recruited at the Royal London Hospital. Patients attended CBT sessions focused on recognition of warning signals and preventative exercises. Objective outcomes were the number of SGBs, esophageal acid exposure time (AET), and proportion of AET related to SGBs. Subjective evaluation was by patient-reported questionnaires. RESULTS: Of 51 patients who started treatment, 39 completed the protocol, of whom 31 had a follow-up MII-pH study. The mean number of SGBs decreased significantly after CBT (before: 116 (47-323) vs. after 45 (22-139), P<0.0003). Sixteen of 31 patients were shown to have a reduction in SGB by >50%. In patients with increased AET at baseline, AET after CBT was decreased: 9.0-6.1% (P=0.005). Mean visual analog scale severity scores decreased after CBT (before: 260 (210-320) mm vs. after: 140 (80-210) mm, P<0.0001). CONCLUSIONS: Cognitive behavioral therapy reduced the number of SGB and improved social and daily activities. Careful analysis of MII-pH allows identification of a subgroup of GERD patients with acid reflux predominantly driven by SGB. In these patients, CBT can reduce esophageal acid exposure.

Rs6922269 marker at the MTHFD1L gene predict cardiovascular mortality in males after acute coronary syndrome.

Myocardial infarction (MI) is the leading cause of death in industrialized countries. All the traditional risk factors for MI are responsible for approximately 50% of cases of MI cases. Attention therefore has recently focused on genetic variants that are not associated with conventional risk factors. One of them is the marker rs6922269, which has been suggested as a risk factor for development of MI in Western populations. We analyzed the relationship between rs6922269 variant on MTHFD1L gene and (i) risk of the acute coronary syndrome (ACS) in the Czech population and (ii) mortality in 7 years follow up. Rs6922269 (G>A) variant was analyzed (CR 99.3% for patients and 98.0% for controls) by PCR-RFLP in consecutively examined 1614 men and 503 women with ACS (age below 65 years) and in population-based controls--1191 men and 1368 women (aged up to 65 years). ANOVA and Chi square were used for statistical analysis. The genotype frequencies were almost identical (P=0.87) in the ACS patients and in controls and no differences were observed, if males (P=0.73) and females (P=0.93) were analysed separately. In addition, rs6922269 polymorphism was not associated with the classical risk factors (dyslipidemia, hypertension, obesity, smoking, diabetes) in control population. Cardiovascular mortality was significantly higher in males, carriers of the AA genotype (P<0.001, OR 2.52, 95% CI 1.40-4.55, for AA vs. +G). We conclude, that rs6922269 variant at MTHFD1L gene could be an important prognostic factor for cardiovascular mortality in patients after ACS.

Turgor loss point explains climate-driven growth reductions in trees in Central Europe.

As climate change thrives, and the frequency of intense droughts is affecting many forested regions, a mechanistic understanding of the factors conferring drought tolerance in trees is increasingly important. However, studies linking the observed growth reduction to mechanistic traits are still rare. We compared the median growth anomalies of 16 native tree species, gathered across a network of study plots in Bavaria, with the mean species-specific turgor loss point (πtlp) measured at five locations in Central Europe πtlp explained 37% of the growth anomalies observed in response to the intense droughts between 2018 and 2020 compared to the pre-drought period between 2006 and 2017 across sites. πtlp constitutes an important leaf drought tolerance trait and influences the growth response of native tree species during extraordinary dry periods. As climate change-induced droughts intensify, tree species with drought-tolerant leaves will be less vulnerable to growth reductions. πtlp provides a useful indicator for selecting tree species to adapt forest management systems to climate change.

Association between a marker on chromosome 9 and acute coronary syndrome. confirmatory study on Czech population.

Myocardial infarction (MI) is the leading cause of death in industrialized countries. All the classical risk factors for MI are responsible for approximately 50 % of MI cases. Attention has therefore recently been attracted to those genetic variants that are not associated with conventional risk factors. One of them is the marker rs10757274 in the "genefree" zone on chromosome 9, which has been repeatedly recognized as a risk factor for development of MI in Western populations. We analysed the relationship between the rs10757274 variant on chromosome 9 and risk of the acute coronary syndrome (ACS) in Czech population. The rs10757274 (A > G) variant was successfully analysed (CR = 99.4 % for patients and 98.4 % for controls) by PCR-RFLP in consecutively examined 1,046 men and 281 women with ACS (age below 65 years) and in population-based controls - 1,162 men and 1,355 women (aged up to 65 years). ANOVA and χ2 were used for statistical analysis. We confirmed that GG homozygotes are more frequent (codominant model of analysis) among patients with myocardial infarction than in the control group both in men (28.5 % vs. 22.0 %, P = 0.0001, OR 1.73, 95 % CI 1.36-2.19) and women (32.0 % vs. 24.6 %, P = 0.02, OR 1.62, 95 % CI 1.13-2.34). However, rs10757274 polymorphism was not associated with the classical risk factors either in control population or in ACS patients. We conclude that the rs10757274 variant at 9p23.1 is an important genetic risk factor for ACS development in the Czech population.

Summer temperatures reach the thermal tolerance threshold of photosynthetic decline in temperate conifers.

Climate change-related environmental stress has been recognized as a driving force in accelerating forest mortality over the last decades in Central Europe. Here, we aim to elucidate the thermal sensitivity of three native conifer species, namely Norway spruce (Picea abies), Scots pine (Pinus sylvestris) and silver fir (Abies alba), and three non-native species, namely Austrian pine (Pinus nigra), Douglas fir (Pseudotsuga menziesii) and Atlas cedar (Cedrus atlantica). Thermal sensitivity, defined here as a decline of the maximum quantum yield of photosystem II (Fv /Fm ) with increasing temperature, was measured under varying levels of heat stress and compared with the turgor loss point (πtlp ) as a drought resistance trait. We calculated three different leaf thermotolerance traits: the temperature at the onset (5%) of the Fv /Fm decline (T5), the temperature at which Fv /Fm was half the maximum value (T50) and the temperature at which only 5% Fv /Fm remained (T95). T5 ranged from 38.5 ± 0.8 °C to 43.1 ± 0.6 °C across all species, while T50 values were at least 9 to 11 degrees above the maximum air temperatures on record for all species. Only Austrian pine had a notably higher T5 value than recorded maximum air temperatures. Species with higher T5 values were characterized by a less negative πtlp compared to species with lower T5. The six species could be divided into 'drought-tolerant heat-sensitive' and 'drought-sensitive heat-tolerant' groups. Exposure to short-term high temperatures thus exhibits a considerable threat to conifer species in Central European forest production systems.

Comparison of 30-Day Outcomes after Carotid Artery Stenting in Patients with Near-Occlusion and Severe Stenosis: A Propensity Score Matching Analysis.

BACKGROUND AND PURPOSE: Carotid artery near-occlusion is a type of severe stenosis with complete or partial distal luminal collapse and intracranial collaterals. This study aimed to compare 30-day outcomes and 10-year survival in patients undergoing carotid artery stenting for near-occlusion with a control group of patients with severe stenosis. MATERIALS AND METHODS: We used data from a registry of 639 patients who underwent 789 carotid artery stenting procedures between 2005 and 2021. The primary end point was any stroke or death within 30 days after carotid artery stenting. Patients were matched using propensity scores based on 6 variables. RESULTS: Propensity score matching yielded 84 subjects in the near-occlusion group matched with 168 subjects in the control group. In the matched cohort, the primary end point occurred in 7 (8.3%) and 11 (6.6%) patients in the near-occlusion and control groups, respectively (P = .611). In the unmatched cohort, the primary end point occurred in 7 (8.3%) and 19 (4.1%) patients (P = .101). Survival in the near-occlusion group versus the control group in the matched cohort at 5 and 10 years was 69.8% (95% CI, 58.0%-78.8%) versus 77.3% (95% CI, 70.0%-83.1%) and 53.3% (95% CI, 39.9%-65.0%) versus 53.3% (95% CI, 44.5%-61.4%) (log-rank, P = .798). CONCLUSIONS: Carotid stent placement in patients with ICA near-occlusion was not associated with an increased 30-day risk of stroke or death compared with severe stenosis. Survival up to 10 years after carotid artery stenting was similar in both groups.

[Comparison of various methods of body fat analysis in overweight and obese women]. / Srovnání ruzných meted pro stanovení mnozství tuku v tele u zen s nadváhou a obezitou.

INTRODUCTION: Body composition assessment and determination of the amount and distribution of body fat, respectively, form an essential part of the basic clinical assessment of an obese patient. However, there are no recommended methods to determine the amount of fat in obese population. The aim of our study was to compare the methods most frequently used to determine the amount of body fat in overweight and obese women in clinical practice (multi-frequency bio-electrical impedance analysis--BIA using the Bodystat, Omron and Tanita machines and the skinfold test using a calliper) with a reference method (DEXA). The study further aimed to compile prediction formulae enabling clinicians to calculate the percentage of body fat when using the available body fat measurement techniques. METHODS: The study included 61 overweight and obese women (mean age 48.6 years +/- 13.9 years). Four practice-based body fat assessment methods were used - bioimpedance technique with tetra-polar electrode arrangement (Bodystat machine), bioimpedance technique with bi-pedal electrode arrangement (Tanita machine), hand-held bioimpedance technique (Omron machine) and the anthropometry assessment--the skinfold calliper technique. These methods were compared to the method considered as the reference--the whole body densinometry (DEXA). RESULTS: The results obtained using the listed body fat assessment methods suggest that the resulting body fat measurements differ importantly depending on the method used. The highest correlation with DEXA was found for the Bodystat BIA (r = 0.9096, p < 0.001). Prediction formulae were constructed for a more accurate calculation of body fat content when using the techniques evaluated in the present study. CONCLUSION: When the newly compiled formulae are employed, the body fat assessment obtained with any of the methods applied in the present study will approximate DEXA. The BIA techniques were found to be particularly precise. Therefore, further evaluation of these techniques is recommendable to support their use as methods for monitoring the efficacy of weight reduction programmes in overweight and obese patients.

A cluster-randomised controlled trial of a brief training session to facilitate general practitioner referral to smoking cessation treatment.

OBJECTIVES: General practitioners (GPs) are the main source of referrals to specialist smoking cessation services (SSCS), but the referral rates are low. We evaluated effects of a brief GP training session on the number of referrals received by their local SSCS. METHODS: A cluster-randomised controlled trial was undertaken across three East London primary care trusts. A total of 91 GPs were randomly allocated to a training session or usual care. Participants in the intervention arm were offered a 40-min training session addressing the rationale and skills for referral of smokers for treatment. Participants in the usual care arm received referral guidance by post. The main outcome measure was the number of referrals recorded by the SSCS over 3 months after the intervention. RESULTS: Over the 3-month baseline period the average number of referrals per GP was 1.0 and 0.6 in the intervention and usual care arms, respectively. During the post-intervention period the mean number of referrals was 6.4 and 1.8 per GP. When adjusting for baseline variables the incidence rate ratio for the referrals from the intervention arm compared to usual care was 4.9 (p<0.001; 95% CI 1.7 to 14.7). CONCLUSION: A brief training session can significantly increase GP referral to smoking cessation services. TRIAL REGISTRATION: National Research Register, Department of Health, UK N0261148824 (available online at: http://www.nrr.nhs.uk/ViewDocument.asp?ID = N0261148824).

Pregnancy-associated plasma protein A and proform eosinophilic major basic protein in the detection of different types of coronary artery disease.

Kryptor system was proven to be a rapid, standard method for pregnancy-associated plasma protein A and proform eosinophilic major basic protein (PAPP-A/proMBP) complex detection in coronary artery disease (CAD). No age and/or gender differences in 51 controls and 110 stable coronary artery disease (SCAD) patients were found. SCAD patients did not differ from controls and no difference in PAPP-A/proMBP levels with regards to the number of affected vessels was found. In 21 unstable angina pectoris (UAP), in 35 without and 66 with ST elevation acute myocardial infarctions (NSTEMI, STEMI respectively) patients PAPP-A/proMBP levels were increased (P=0.004 and P<0.0005, respectively). PAPP-A/proMBP levels did not correlate with cardiac troponin I (cTnI) in STEMI and NSTEMI patients. PAPP-A/ proMBP increase was more frequent than cTnI (P=0.036) within the early phase of STEMI. In NSTEMI patients PAPP-A/proMBP positivity was present in 50% of cTnI negative cases. Receiver operating characteristic (ROC) analysis revealed the highest diagnostic accuracy of PAPP-A/proMBP (0.919) in STEMI cTnI positive cases. The highest specificity/sensitivity PAPP-A/proMBP levels for particular acute coronary syndrome (ACS) types were 10.65-14.75 mIU/l. Combination of PAPP-A/proMBP with cTnI increases their diagnostic efficacy within the early phase of ACS. Our results suggest that PAPP-A/proMBP complex is involved in processes preceding vulnerable plaque development in ACS.

[Diagnostics of the retrocalcaneal bursitis: possibilities of the use of new anatomical data]. / Diagnostika retrokalkaneárních burzitíd: moznosti vyuzití nových anatomických poznatku.

The anatomy and histology of the normal retrocalcaneal bursa (RB) was studied on both embalmed and fresh cadaverous material. The bursa is a constant structure, its upper and posterior walls are completely covered with the unilayered synovial membrane. Its anterior wall represents the superior facet of the calcaneal tuberosity, the posterior one corresponds to the anterior surface of the insertional part of the Achilles tendon. The superior wall is formed by the adipose tissue of the inferior part of Kager's triangle, extending into the cavity of the bursa in a form of constant large and irregularly shaped synovial fold. The normal anatomical features as well as some pathological changes of the bursa and its neighbourhood were demonstrated on examples of some case reports, by use of the ultrasonography and magnetic resonance investigations. In healthy individuals the space of the bursa was not figured in the ultrasonographic investigations, but was well apparent in the MR images. The pathological changes of the bursa are detectable by using of both methods, but the MR images present substantially precise quality of depiction. The authors recommend the use of presented new anatomical data for the improvement in differential diagnostic of the wide spectrum of achillar enthesopathies.

Overproduction of PDR3 suppresses mitochondrial import defects associated with a TOM70 null mutation by increasing the expression of TOM72 in Saccharomyces cerevisiae.

Most mitochondrial proteins are synthesized with cleavable amino-terminal targeting signals that interact with the mitochondrial import machinery to facilitate their import from the cytosol. We previously reported that the presequence of the F(1)-ATPase beta subunit precursor (pre-F(1)beta) acts as an intramolecular chaperone that maintains the precursor in an import-competent conformation prior to import (P. Hajek, J. Y. Koh, L. Jones, and D. M. Bedwell, Mol. Cell. Biol. 17:7169-7177, 1997). We also found that a mutant form of pre-F(1)beta with a minimal targeting signal (Delta 1,2 pre-F(1)beta) is inefficiently imported into mitochondria because it rapidly folds into an import-incompetent conformation. We have now analyzed the consequences of reducing the pre-F(1)beta targeting signal to a minimal unit in more detail. We found that Delta 1,2 pre-F(1)beta is more dependent upon the Tom70p receptor for import than WT pre-F(1)beta is, resulting in a growth defect on a nonfermentable carbon source at 15 degrees C. Experiments using an in vitro mitochondrial protein import system suggest that Tom70p functions to maintain a precursor containing the Delta 1,2 pre-F(1)beta import signal in an import-competent conformation. We also identified PDR3, a transcriptional regulator of the pleiotropic drug resistance network, as a multicopy suppressor of the mitochondrial import defects associated with Delta 1,2 pre-F(1)beta in a tom70 Delta strain. The overproduction of PDR3 mediated this effect by increasing the import of Delta 1,2 pre-F(1)beta into mitochondria. This increased the mitochondrial ATP synthase activity to the extent that growth of the mutant strain was restored under the selective conditions. Analysis of the transcription patterns of components of the mitochondrial outer membrane import machinery demonstrated that PDR3 overproduction increased the expression of TOM72, a little studied TOM70 homologue. These results suggest that Tom72p possesses overlapping functions with Tom70p and that the pleiotropic drug resistance network plays a previously unappreciated role in mitochondrial biogenesis.

The amino terminus of the F1-ATPase beta-subunit precursor functions as an intramolecular chaperone to facilitate mitochondrial protein import.

Mitochondrial import signals have been shown to function in many steps of mitochondrial protein import. Previous studies have shown that the F1-ATPase beta-subunit precursor (pre-F1beta) of the yeast Saccharomyces cerevisiae contains an extended, functionally redundant mitochondrial import signal at its amino terminus. However, the full significance of this functionally redundant targeting sequence has not been determined. We now report that the extended pre-F1beta signal acts to maintain the precursor in an import-competent conformation prior to import, in addition to its previously characterized roles in mitochondrial targeting and translocation. We found that this extended signal is required for the efficient posttranslational mitochondrial import of pre-F1beta both in vivo and in vitro. To determine whether the pre-F1beta signal directly influences precursor conformation, fusion proteins that contain wild-type and mutant forms of the pre-F1beta import signal attached to the model passenger protein dihydrofolate reductase (DHFR) were constructed. Deletions that reduced the import signal to a minimal functional unit decreased both the half-time of precursor folding and the efficiency of mitochondrial import. To confirm that the reduced mitochondrial import associated with this truncated signal was due to a defect in its ability to maintain DHFR in a loosely folded conformation, we introduced structurally destabilizing missense mutations into the DHFR passenger to block precursor folding independently of the import signal. We found that the truncated signal imported this destabilized form of DHFR as efficiently as the intact targeting signal, indicating that the primary defect associated with the minimal signal is an inability to maintain the precursor in a loosely folded conformation. Our results suggest that the loss of this intramolecular chaperone function leads to defects in the early stages of the import process.

The role of tissue factor in thrombosis and hemostasis.

The tissue factor (TF) is one of the most important regulators of arterial thrombosis. Because arterial thrombosis is the pathophysiologic background of acute coronary syndrome, the possible impact of blocking the arterial thrombosis on its onset is a challenging problem. The investigations of TF brought a new concept of "cell-based coagulation model" which highlighted the question of blood-borne TF as a source of TF in circulating blood. In this review we summarize essential information on the pathophysiology, molecular structure, expression and distribution of TF and we propose a novel concept of blood-borne TF, suggesting the possibilities of inhibition of the coagulation cascade with newly synthetized drugs.

Clinical and demographic characteristics of psychiatric patients seropositive for Borrelia burgdorferi.

PURPOSE: Borrelia burgdorferi (Bb) infection can affect the central nervous system and possibly lead to psychiatric disorders. We compared clinical and demographic variables in Bb seropositive and seronegative psychiatric patients and healthy controls. METHOD: Nine hundred and twenty-six consecutive psychiatric patients were screened for antibodies to Bb and compared with 884 simultaneously recruited healthy subjects. RESULTS: Contrary to healthy controls, seropositive psychiatric patients were significantly younger than seronegative ones. None of the studied psychiatric diagnostic categories exhibited stronger association with seropositivity. There were no differences between seropositive and seronegative psychiatric patients in hospitalization length, proportion of previously hospitalized patients and proportion of subjects with family history of psychiatric disorders. CONCLUSION: These findings elaborate on potential association between Bb infection and psychiatric morbidity, but fail to identify any specific clinical 'signature' of Bb infection.

Evaluation of cerebrovascular reserve in patients undergoing carotid artery stenting and its usefulness in predicting significant hemodynamic changes during temporary carotid occlusion.

We investigated the usefulness of cerebrovascular reserve (CVR) testing to predict severe hemodynamic changes during proximally protected carotid artery stenting. Of 90 patients referred, 63 eligible underwent complete evaluation of the extent of carotid artery disease and transcranial Doppler ultrasound (TCD) assessment of CVR by means of a breath-holding test and ophthalmic artery flow pattern evaluation. Periprocedural TCD monitoring of the ipsilateral middle cerebral artery flow was performed in 24 patients undergoing proximally protected procedure (requiring induction of flow arrest within internal carotid artery). Abnormal CVR was significantly less common in patients with unilateral compared to bilateral carotid artery disease (26.3 % vs. 76.9 %, p=0.02), while ophthalmic artery flow reversal was rare in patients with unilateral carotid artery disease (2.5 % vs. 42.9 %, p<0.01). During the induction of carotid flow arrest, the average mean flow velocity drop following external carotid artery occlusion was low (3.5 %, p=0.67) compared to the induction of complete flow arrest (32.8 %, p<0.01). Six patients had a total mean flow velocity drop >50 %, including 2 patients with normal pre-procedural CVR. Our results suggest that TCD evaluation of CVR is not a reliable predictor of hemodynamic changes induced during proximally protected carotid artery stenting in patients with unilateral carotid artery disease.