r-Process elements from magnetorotational hypernovae.

Neutron-star mergers were recently confirmed as sites of rapid-neutron-capture (r-process) nucleosynthesis1-3. However, in Galactic chemical evolution models, neutron-star mergers alone cannot reproduce the observed element abundance patterns of extremely metal-poor stars, which indicates the existence of other sites of r-process nucleosynthesis4-6. These sites may be investigated by studying the element abundance patterns of chemically primitive stars in the halo of the Milky Way, because these objects retain the nucleosynthetic signatures of the earliest generation of stars7-13. Here we report the element abundance pattern of the extremely metal-poor star SMSS J200322.54-114203.3. We observe a large enhancement in r-process elements, with very low overall metallicity. The element abundance pattern is well matched by the yields of a single 25-solar-mass magnetorotational hypernova. Such a hypernova could produce not only the r-process elements, but also light elements during stellar evolution, and iron-peak elements during explosive nuclear burning. Hypernovae are often associated with long-duration γ-ray bursts in the nearby Universe8. This connection indicates that similar explosions of fast-spinning strongly magnetized stars occurred during the earliest epochs of star formation in our Galaxy.

Core-binding factor leukemia hijacks the T-cell-prone PU.1 antisense promoter.

The blood system serves as a key model for cell differentiation and cancer. It is orchestrated by precise spatiotemporal expression of crucial transcription factors. One of the key master regulators in the hematopoietic systems is PU.1. Reduced levels of PU.1 are characteristic for human acute myeloid leukemia (AML) and are known to induce AML in mouse models. Here, we show that transcriptional downregulation of PU.1 is an active process involving an alternative promoter in intron 3 that is induced by RUNX transcription factors driving noncoding antisense transcription. Core-binding factor (CBF) fusions RUNX1-ETO and CBFß-MYH11 in t(8;21) and inv(16) AML, respectively, activate the PU.1 antisense promoter that results in a shift from sense toward antisense transcription and myeloid differentiation blockade. In patients with CBF-AML, we found that an elevated antisense/sense transcript and promoter accessibility ratio represents a hallmark compared with normal karyotype AML or healthy CD34+ cells. Competitive interaction of an enhancer with the proximal or the antisense promoter forms a binary on/off switch for either myeloid or T-cell development. Leukemic CBF fusions thus use a physiological mechanism used by T cells to decrease sense transcription. Our study is the first example of a sense/antisense promoter competition as a crucial functional switch for gene expression perturbation by oncogenes. Hence, this disease mechanism reveals a previously unknown Achilles heel for future precise therapeutic targeting of oncogene-induced chromatin remodeling.

Trends, determinants and differences in antibiotic use in 68 residential aged care homes in Australia, 2014-2017: a longitudinal analysis of electronic health record data.

BACKGROUND: Internationally, point prevalence surveys are the main source of antibiotic use data in residential aged care (RAC). Our objective was to describe temporal trends in antibiotic use and antibiotics flagged for restricted use, resident characteristics associated with use, and variation in use by RAC home, using electronic health record data. METHODS: We conducted a retrospective cohort study of 9793 unique residents aged ≥65 years in 68 RAC homes between September 2014 and September 2017, using electronic health records. We modelled the primary outcome of days of antibiotic therapy /1000 resident days (DOT/1000 days), and secondary outcomes of number of courses/1000 days and the annual prevalence of antibiotic use. Antibiotic use was examined for all antibiotics and antibiotics on the World Health Organization's (WHO) Watch List (i.e. antibiotics flagged for restricted use). RESULTS: In 2017, there were 85 DOT/1000 days (99% CI: 79, 92), 8.0 courses/1000 days (99% CI: 7.6, 8.5), and 63.4% (99% CI: 61.9, 65.0) of residents received at least one course of antibiotics. There were 7.7 DOT/1000 days (99% CI: 6.69, 8.77) of antibiotics on the WHO Watch List administered in 2017. Antibiotic use increased annually by 4.09 DOT/1000 days (99% CI: 1.18, 6.99) before adjusting for resident factors, and 3.12 DOT/1000 days (99% CI: - 0.05, 6.29) after adjustment. Annual prevalence of antibiotic use decreased from 68.4% (99% CI: 66.9, 69.9) in 2015 to 63.4% (99% CI: 61.9, 65.0) in 2017, suggesting fewer residents were on antibiotics, but using them for longer. Resident factors associated with higher use were increasing age; chronic respiratory disease; a history of urinary tract infections, and skin and soft tissue infections; but dementia was associated with lower use. RAC home level antibiotic use ranged between 44.0 to 169.2 DOT/1000 days in 2016. Adjusting for resident factors marginally reduced this range (42.6 to 155.5 DOT/1000 days). CONCLUSIONS: Antibiotic course length and RAC homes with high use should be a focus of antimicrobial stewardship interventions. Practices in RAC homes with low use could inform interventions and warrant further investigation. This study provides a model for using electronic health records as a data source for antibiotic use surveillance in RAC.

Clinical Validation of a Predictive Model for the Presence of Cervical Lymph Node Metastasis in Papillary Thyroid Cancer.

BACKGROUND AND PURPOSE: Ultrasound is a standard technique to detect lymph node metastasis in papillary thyroid cancer. Cystic changes and microcalcifications are the most specific features of metastasis, but with low sensitivity. This prospective study compared the diagnostic accuracy of a predictive model for sonographic evaluation of lymph nodes relative to the radiologist's standard assessment in detecting papillary thyroid cancer metastasis in patients after thyroidectomy. MATERIALS AND METHODS: Cervical lymph node sonographic images were reported by a radiologist (R method) per standard practice. The same images were independently evaluated by another radiologist using a sonographic predictive model (M method). A test was considered positive for metastasis if the R or M method suggested lymph node biopsy. The result of lymph node biopsy or surgical pathology was used as the reference standard. We estimated relative true-positive fraction and relative false-positive fraction using log-linear models for correlated binary data for the M method compared with the R method. RESULTS: A total of 237 lymph nodes in 103 patients were evaluated. Our analysis of relative true-positive fraction and relative false-positive fraction included 54 nodes with pathologic results in which at least 1 method (R or M) was positive. The M method had a higher relative true-positive fraction of 1.46 (95% CI, 1.12-1.91; P = .006) and a lower relative false-positive fraction of 0.58 (95% CI, 0.36-0.92; P = .02) compared with the R method. CONCLUSIONS: The sonographic predictive model outperformed the standard assessment to detect lymph node metastasis in patients with papillary thyroid cancer and may reduce unnecessary biopsies.

A Cluster-Randomized, Community-Based, Tribally Delivered Oral Health Promotion Trial in Navajo Head Start Children.

The authors tested the effectiveness of a community-based, tribally delivered oral health promotion (OHP) intervention (INT) at reducing caries increment in Navajo children attending Head Start. In a 3-y cluster-randomized trial, we developed an OHP INT with Navajo input that was delivered by trained Navajo lay health workers to children attending 52 Navajo Head Start classrooms (26 INT, 26 usual care [UC]). The INT was designed as a highly personalized set of oral health-focused interactions (5 for children and 4 for parents), along with 4 fluoride varnish applications delivered in Head Start during academic years of 2011 to 2012 and 2012 to 2013. The authors evaluated INT impact on decayed, missing, and filled tooth surfaces (dmfs) increment compared with UC. Other outcomes included caries prevalence and caregiver oral health-related knowledge and behaviors. Modified intention-to-treat and per-protocol analyses were conducted. The authors enrolled 1,016 caregiver-child dyads. Baseline mean dmfs/caries prevalence equaled 19.9/86.5% for the INT group and 22.8/90.1% for the UC group, respectively. INT adherence was 53% (i.e., ≥3 child OHP events, ≥1 caregiver OHP events, and ≥3 fluoride varnish). After 3 y, dmfs increased in both groups (+12.9 INT vs. +10.8 UC; P = 0.216), as did caries prevalence (86.5% to 96.6% INT vs. 90.1% to 98.2% UC; P = 0.808) in a modified intention-to-treat analysis of 897 caregiver-child dyads receiving 1 y of INT. Caregiver oral health knowledge scores improved in both groups (75.1% to 81.2% INT vs. 73.6% to 79.5% UC; P = 0.369). Caregiver oral health behavior scores improved more rapidly in the INT group versus the UC group (P = 0.006). The dmfs increment was smaller among adherent INT children (+8.9) than among UC children (+10.8; P = 0.028) in a per-protocol analysis. In conclusion, the severity of dental disease in Navajo Head Start children is extreme and difficult to improve. The authors argue that successful approaches to prevention may require even more highly personalized approaches shaped by cultural perspectives and attentive to the social determinants of oral health (ClinicalTrials.gov NCT01116739).

Extremely metal-poor stars from the cosmic dawn in the bulge of the Milky Way.

The first stars are predicted to have formed within 200 million years after the Big Bang, initiating the cosmic dawn. A true first star has not yet been discovered, although stars with tiny amounts of elements heavier than helium ('metals') have been found in the outer regions ('halo') of the Milky Way. The first stars and their immediate successors should, however, preferentially be found today in the central regions ('bulges') of galaxies, because they formed in the largest over-densities that grew gravitationally with time. The Milky Way bulge underwent a rapid chemical enrichment during the first 1-2 billion years, leading to a dearth of early, metal-poor stars. Here we report observations of extremely metal-poor stars in the Milky Way bulge, including one star with an iron abundance about 10,000 times lower than the solar value without noticeable carbon enhancement. We confirm that most of the metal-poor bulge stars are on tight orbits around the Galactic Centre, rather than being halo stars passing through the bulge, as expected for stars formed at redshifts greater than 15. Their chemical compositions are in general similar to typical halo stars of the same metallicity although intriguing differences exist, including lower abundances of carbon.

Type III interferons are expressed by Coxsackievirus-infected human primary hepatocytes and regulate hepatocyte permissiveness to infection.

Hepatitis is a common and potentially fatal manifestation of severe Coxsackievirus infections, particularly in newborn children. Little is known of the immune-mediated mechanisms regulating permissiveness to liver infection. It is well established that type I interferons (IFNs) play an important role in the host innate immune response to Coxsackievirus infections. Recent studies have highlighted a role for another IFN family, the type III IFNs (also called IFN-λ), in anti-viral defence. Whether type III IFNs are produced by hepatocytes during a Coxsackievirus infection remains unknown. Moreover, whether or not type III IFNs protects hepatocytes from a Coxsackievirus infection has not been addressed. In this study, we show that primary human hepatocytes respond to a Coxsackievirus B3 (CVB3) infection by up-regulating the expression of type III IFNs. We also demonstrate that type III IFNs induce an anti-viral state in hepatocytes characterized by the up-regulated expression of IFN-stimulated genes, including IFN-stimulated gene (ISG15), 2'-5'-oligoadenylate synthetase 2 (OAS2), protein kinase regulated by dsRNA (PKR) and myxovirus resistance protein 1 (Mx1). Furthermore, our study reveals that type III IFNs attenuate CVB3 replication both in hepatocyte cell lines and primary human hepatocytes. Our studies suggest that human hepatocytes express type III IFNs in response to a Coxsackievirus infection and highlight a novel role for type III IFNs in regulating hepatocyte permissiveness to this clinically relevant type of virus.

A single low-energy, iron-poor supernova as the source of metals in the star SMSS J031300.36-670839.3.

The element abundance ratios of four low-mass stars with extremely low metallicities (abundances of elements heavier than helium) indicate that the gas out of which the stars formed was enriched in each case by at most a few--and potentially only one--low-energy supernova. Such supernovae yield large quantities of light elements such as carbon but very little iron. The dominance of low-energy supernovae seems surprising, because it had been expected that the first stars were extremely massive, and that they disintegrated in pair-instability explosions that would rapidly enrich galaxies in iron. What has remained unclear is the yield of iron from the first supernovae, because hitherto no star has been unambiguously interpreted as encapsulating the yield of a single supernova. Here we report the optical spectrum of SMSS J031300.36-670839.3, which shows no evidence of iron (with an upper limit of 10(-7.1) times solar abundance). Based on a comparison of its abundance pattern with those of models, we conclude that the star was seeded with material from a single supernova with an original mass about 60 times that of the Sun (and that the supernova left behind a black hole). Taken together with the four previously mentioned low-metallicity stars, we conclude that low-energy supernovae were common in the early Universe, and that such supernovae yielded light-element enrichment with insignificant iron. Reduced stellar feedback both chemically and mechanically from low-energy supernovae would have enabled first-generation stars to form over an extended period. We speculate that such stars may perhaps have had an important role in the epoch of cosmic reionization and the chemical evolution of early galaxies.

[Outcome after a shaken baby syndrome]. / « Le syndrome du bébé secoué : les séquelles ? ¼

The Shaken Baby Syndrome (SBS) is a severe inflicted brain injury due to an adult violently shaking an infant. Diagnostic guidelines have been recently published by the "Haute Autorité de santé". The mortality rate after SBS is 21.6 % and the long-term outcome is good for only 8 to 36 % patients followed over more than 5 years. The aim of this article is to describe sequelae after a SBS, their mechanisms, prognostic factors and recommendations for a better long-term care of the patients.

Immunology in the clinic review series; focus on type 1 diabetes and viruses: the innate immune response to enteroviruses and its possible role in regulating type 1 diabetes.

Type 1 diabetes (T1D) is an autoimmune disease arising as a consequence of a misdirected T cell response to the pancreatic beta cell. In recent years, there has been a growing interest in the innate immune system as a regulator of disease development. Genome-wide association studies have identified diabetes-associated polymorphisms in genes encoding proteins with functions related to the innate immune response. Moreover, enteroviruses, known to activate a strong innate immune response, have been implicated in the disease pathogenesis. In this review, we discuss the innate immune response elicited by enteroviruses and how this response may regulate T1D development.

Frequent loss of RAF kinase inhibitor protein expression in acute myeloid leukemia.

RAF kinase inhibitor protein (RKIP) is a negative regulator of the RAS-mitogen-activated protein kinase/extracellular signal-regulated kinase signaling cascade. We investigated its role in acute myeloid leukemia (AML), an aggressive malignancy arising from hematopoietic stem and progenitor cells (HSPCs). Western blot analysis revealed loss of RKIP expression in 19/103 (18%) primary AML samples and 4/17 (24%) AML cell lines but not in 10 CD34+ HSPC specimens. In in-vitro experiments with myeloid cell lines, RKIP overexpression inhibited cellular proliferation and colony formation in soft agar. Analysis of two cohorts with 103 and 285 AML patients, respectively, established a correlation of decreased RKIP expression with monocytic phenotypes. RKIP loss was associated with RAS mutations and in transformation assays, RKIP decreased the oncogenic potential of mutant RAS. Loss of RKIP further related to a significantly longer relapse-free survival and overall survival in uni- and multivariate analyses. Our data show that RKIP is frequently lost in AML and correlates with monocytic phenotypes and mutations in RAS. RKIP inhibits proliferation and transformation of myeloid cells and decreases transformation induced by mutant RAS. Finally, loss of RKIP seems to be a favorable prognostic parameter in patients with AML.

Progression from mild to pronounced MCI is not associated with cerebrospinal fluid biomarker deviations.

BACKGROUND/AIM: Detection of cerebrospinal fluid (CSF) biomarker deviations improve prediction of progression from mild cognitive impairment (MCI) to dementia. However, it is not settled whether the same pattern exists in patients progressing from very mild to more pronounced MCI. Given that neurodegenerative processes occur very early in the disease course, we also expected to find biomarker deviations in these patients. METHODS: A total of 246 memory clinic patients with non-progressive (n = 161), progressive (n = 19), or converting (n = 66) MCI, 67 with stable dementia, and 80 controls were followed for 24 months. At baseline, CSF total tau (T-tau), ß-amyloid 1-42 (Aß42) and the light subunit of neurofilament protein (NFL) were determined. RESULTS: Patients with converting MCI and stable dementia had lower CSF Aß42 concentrations and higher T-tau concentrations and NFL in comparison with controls and non-progressive/progressive MCI (p < 0.0005). No differences were found between progressive and non-progressive MCI. CONCLUSION: As expected, biomarker deviations predicted progression from MCI to dementia. Contrary to our hypothesis, progression from very mild MCI to more pronounced MCI was not reflected by biomarker deviations. The results suggest that the measured biomarkers are not early disease markers, or alternatively Alzheimer or vascular pathology is not the underlying cause in this patient group.

Cerebrospinal fluid biomarkers of white matter lesions - cross-sectional results from the LADIS study.

BACKGROUND AND PURPOSE: White matter lesions (WMLs) caused by small vessel disease are common in elderly people and contribute to cognitive impairment. There are no established biochemical markers for WMLs. We aimed to study the relation between degree of WMLs rated on magnetic resonance imaging of the brain and cerebrospinal fluid (CSF) levels of structural biomarkers associated with Alzheimer's disease (AD) and subcortical vascular dementia. METHODS: Fifty-three non-demented elderly individuals with WMLs were subjected to lumbar puncture. Degree of WMLs was rated using the Fazekas scale. Volumetric assessment of WMLs was performed. CSF samples were analyzed for the 40 and 42 amino acid fragments of amyloid beta, alpha- and beta-cleaved soluble amyloid precursor protein, total tau (T-tau), hyperphosphorylated tau (P-tau(181)), neurofilament light protein (NFL), sulfatide and CSF/Serum-albumin ratio. RESULTS: Fifteen subjects had mild, 23 had moderate and 15 had severe degree of WMLs. CSF-NFL levels differed between the groups (P < 0.001) and correlated with the volume of WMLs (r = 0.477, P < 0.001). CSF sulfatide concentration displayed similar changes but less strongly. T-tau, P-tau(181) and the different amyloid markers as well as CSF/S-albumin ratio did not differ significantly between the groups. CONCLUSIONS: The association of increased CSF-NFL levels with increasing severity of WMLs in non-demented subjects suggests that NFL is a marker for axonal damage in response to small vessel disease in the brain. This manifestation may be distinct from or earlier than the neurodegenerative process seen in AD, as reflected by the lack of association between WMLs and AD biomarkers.

Apathy is a prominent neuropsychiatric feature of radiological white-matter changes in patients with dementia.

OBJECTIVE: Cerebral white-matter changes (WMCs) are frequently found in dementia and have been proposed to be related to vascular factors and a certain symptomatological profile. However, few studies have included both vascular factors and a broad spectrum of cognitive, neurological and psychiatric symptoms, easily detectable by the physician in the everyday clinical work. The objective was to study the relationships between WMCs on MRI/CT and neuropsychiatric symptoms and vascular factors in patients with cognitive impairment. METHODS: One hundred and seventy-six patients with Alzheimer's disease, vascular dementia, mixed dementia, and mild cognitive impairment were included. All patients underwent a standardized examination including medical history, clinical examinations, laboratory tests and brain imaging (CT or MRI). The identification and severity degree of WMCs was assessed blindly to clinical findings, using a semi-quantitative scale. For statistical analyses, patients were grouped based on absence or presence of WMCs. Significant variables in bivariate analyses were included as predictors in stepwise multiple logistic regression analyses. RESULTS: Bivariate analyses showed significant associations between WMCs and age, gender, blood pressure, hypertension, ischaemic heart disease and TIA/RIND. Furthermore, there were significant associations between WMCs and apathy, mental slowness, disinhibition, gait disturbance and focal neurologic symptoms. The multivariate logistic model revealed apathy, mental slowness and age as the most consistent predicting factors for WMCs, together with MRI as a radiological method for the detection of WMCs. CONCLUSIONS: The findings indicate that WMCs in patients with dementia are associated with a dysexecutive-related behavioural symptom profile, vascular factors related to small and large vessel diseases and age.

No evidence for the presence of tissue factor in high-purity preparations of immunologically isolated eosinophils.

BACKGROUND: To date, there is no unequivocal opinion on whether human eosinophils express tissue factor (TF). Therefore, we studied the expression of TF protein and activity in resting or stimulated immunologically purified human eosinophils. METHODS AND RESULTS: By use of immunologic isolation, we achieved over 96% purity of eosinophil preparations, and contamination by CD14-positive cells was below 0.3%. Flow cytometric [fluorescence-activated cell sorting (FACS)] analysis of eosinophils revealed no surface expression of TF antigen in resting or stimulated eosinophils. Immunoblotting of eosinophil lysates did not show any TF protein under resting or stimulated conditions. The lysates of resting or stimulated eosinophils contained no detectable levels of TF procoagulant activity. In contrast, monocytes, stimulated in plasma or medium, possessed readily detectable TF levels on the cell surface and in cell lysates as detected by FACS and immunoblotting. This was active TF antigen, as confirmed by TF activity assay (19.2 +/- 4.2 and 28.6 +/- 3.1 mU per 10(6) cells, stimulated in medium or plasma, respectively). We found no detectable TF mRNA levels in resting or stimulated eosinophils by real-time polymerase chain reaction (PCR), whereas in monocytes TF mRNA levels were significantly increased after stimulation. CONCLUSIONS: Our data indicate that there is no evidence for TF expression in high-purity preparations of immunologically isolated eosinophils.

Posterior cortical brain dysfunction in cognitively impaired patients with Parkinson's disease--a rCBF scintigraphy study.

OBJECTIVES: The aim of the study was to visualize cortical function in Parkinson's patients with various degrees of cognitive impairment. MATERIALS AND METHODS: Thirty-seven patients with Parkinson's disease and three with Parkinson plus syndromes underwent cognitive assessment and rCBF using (99m)TC-HMPAO-SPECT. RESULTS: Almost no regional reductions in cerebral blood flow were seen in patients without cognitive impairment (n = 16). Limited, mainly posterior, blood flow reductions were seen in patients with mild cognitive impairment (n = 14), whereas the reductions were extensive and bilaterally symmetric, involving both anterior and posterior brain regions in patients with dementia (n = 10). CONCLUSIONS: The findings suggest a widespread cortical, mainly posterior type of dysfunction and a relationship between the degree of cognitive impairment and the magnitude of the dysfunction.

Several new considerations in mitral valve repair.

BACKGROUND AND AIM OF THE STUDY: A retrospective evaluation was made of a small personal series of patients undergoing mitral valve repair in order to address four contemporary questions: (i) What is the best method of achieving a stable repair in mitral valve prolapse?; (ii) How should patients with pure annular dilatation without prolapse or antecedent ischemia be categorized?; (iii) Are valve procedures in ischemic mitral regurgitation (MR) still associated with less satisfactory early and late outcomes?; and (iv) Is prophylactic amiodarone therapy safe and effective in reducing postoperative arrhythmias? METHODS: Between 1993 and 2002, a total of 118 patients with non-rheumatic MR undergoing isolated mitral valve repair with or without coronary bypass was analyzed retrospectively: of these patients, 66 had prolapse (Group I), 21 had pure annular dilatation (Group II), and 31 had ischemic MR (Group III). All three groups routinely underwent Carpentier ring annuloplasty. Twenty-three patients in Group I were managed with leaflet resection and reconstruction (LRR), but in 1996 the technique for Group I was changed to uniform artificial chordal replacement (ACR) and no leaflet resection (n = 43). Also in 1996, prophylactic amiodarone therapy was first used routinely, and postoperative arrhythmia data were compared to those from prior patients. Baseline and outcome variables were assessed for each group and compared between the three groups. Survival data were evaluated using the Cox proportional hazards model. RESULTS: Significant differences in baseline characteristics were observed: Group II was predominantly female; Group III more often experienced acute presentation; and Groups II and III had more comorbid disorders and left ventricular dysfunction (all p < 0.01). ACR was highly successful for repair of prolapse, and no ACR patient exhibited significant residual MR or outflow tract obstruction. Operative mortality and morbidity were low in all groups, and ischemic etiology failed to be an independent predictor of early or late adverse outcome (p > 0.10). Cox model analysis to nine years of follow up (median 4 years) identified only advanced age and number of comorbidities as influencing late mortality (both p < 0.03). Over the follow up period, 8.7% of LRR patients required reoperation for valve failure due to late chordal rupture, whereas none of the ACR patients failed. Finally, prophylactic amiodarone significantly reduced postoperative arrhythmias (p = 0.03) with no observed complications, and also eliminated death due to arrhythmia. CONCLUSION: Ischemic etiology may be diminishing as an independent risk factor in Group III, at least partially because of uniform valve repair. Group II comprised a distinct entity of females with higher comorbidity, and prophylactic amiodarone therapy seemed useful as a routine measure. Finally, ACR appeared to produce a stable repair in virtually all Group I patients, suggesting that prolapse might be appropriately managed with ring annuloplasty and uniform ACR. However, future studies are suggested for further consideration of these hypotheses.

Relationship between depressive symptomatology and the subcortical brain syndrome in dementia.

OBJECTIVES: the aim of the present study was to elucidate a possible relationship between depressive symptomatology and regional brain symptomatology in demented patients. METHODS: 170 consecutive inpatients were studied. They suffered from Alzheimer's disease (103 patients), vascular dementia (48 patients), or frontotemporal dementia (19 patients). The patients underwent a neuropsychiatric investigation, which included assessments of (1) depression, and (2) regional brain symptomatology. Depressive symptomatology was assessed as presence of (a) depressed mood, and (b) anxiety. In the further statistical analysis, the presence of depressed mood and/or anxiety was also evaluated. The principle of the regional symptom analysis was the successive aggregation of observable symptom variables, leading to the final determination of four possible regional brain syndromes (frontal, subcortical, parietal and global), by way of the Stepwise comparative status analysis (STEP). The possible correlations between regional brain symptomatology and depressive symptomatology were analysed by means of (a) chi(2) statistics, and (b) a logistic regression analysis in which confounding factors were included (age, degree of dementia, duration). RESULTS: the subcortical syndrome correlated with depressed mood (chi(2), p = 0.002; logistic regression, p = 0.002). A negative correlation was noted between the parietal syndrome and depressed mood (p = 0.010 and p = 0.013, respectively). No other significant correlations between presence of regional brain syndrome and presence of depressive symptomatology could be seen. CONCLUSIONS: demented patients with a clinically established subcortical dysfunction appear to be more susceptible to depressive symptomatology. The results of this study also suggest that posterior brain dysfunction in dementia is not correlated with depressive symptomatology.

Calf muscle function after Achilles tendon rupture. A prospective, randomised study comparing surgical and non-surgical treatment.

In a prospective, randomised, multicentre study, 112 patients with Achilles tendon rupture (ATR) were allocated to surgical treatment (n=59), followed by early functional rehabilitation using a brace, and non-surgical treatment (n=53), i.e. eight weeks of plaster treatment. In this study, the results of the isokinetic muscle strength evaluation are presented for contractions in both the concentric and the eccentric mode, plantar flexion and dorsiflexion, two angular velocities and three different positions of the subject. The heel-raise test for endurance, maximum calf circumference and tendon width were also evaluated. The re-rupture rate was 20.8% in the non-surgically-treated group and 1.7% in the surgically-treated group. No significant differences were found between the treatment groups in terms of the isokinetic strength measurements and the endurance test among the patients who did not sustain a re-rupture. If a re-rupture is avoided, both surgical and non-surgical treatment for ATR produce good functional outcome; however, the muscle function was not restored after two years in either group.

Neurofilament protein in cerebrospinal fluid: a marker of white matter changes.

The objective of this study was to compare cerebrospinal fluid (CSF) levels of the light subtype of the neurofilament proteins (NFL), tau, and beta-amyloid42 (Abeta42) in individuals with moderate or severe white matter changes (WMC) and in those with mild or no WMC. Twenty-two patients with Alzheimer's disease (AD), nine patients with subcortical vascular dementia (SVD), and 20 normal controls were included in the study. The occurrence of WMC was evaluated by a neuroradiologist using the Blennow-Wallin scale. Thirty-seven subjects had no or only punctate WMC; 14 had moderate to severe WMC. Both diagnostic group and WMC, but not gender or apolipoproteinE E4 inheritance, contributed to the variance in the CSF levels of tau, NFL, and Abeta42. In patients with moderate to severe WMC, CSF NFL (P < 0.01), but not CSF tau or CSF Abeta42, was increased also after correction for age, gender, and degree of cognitive impairment. A comparison between patients and controls with any signs of WMC and those without such signs yielded a similar result: CSF NFL (P < 0.001) was increased in the group with signs of WMC. As in numerous previous studies, we found that CSF tau was increased in AD (P < 0.001) compared with controls. Furthermore, CSF NFL was increased in both AD and SVD compared with controls (P < 0.001 for both). Although diagnostic group seems to be a stronger predictor of the variance found in CSF NFL, a clear association between the presence of WMC and increased CSF NFL was found. Because NFL is located mainly in large myelinated axons, increased CSF NFL in individuals with WMC probably reflects axonal degeneration.