British Neuropathological Society and International Society of Forensic Radiology and Imaging expert consensus statement for post mortem neurological imaging.

AIMS: To develop an expert consensus statement regarding appropriate clinical and forensic post mortem neurological imaging. METHODS: An expert panel of clinicians were recruited from registered members of the British Neuropathological Society (BNS) and the International Society of Forensic Radiology and Imaging (ISFRI) with post mortem expertise. Following a focus group meeting, 16 core statements were incorporated into an online modified Delphi survey and each panellist was asked to score their level of agreement. Following the first iteration, two statements that failed to reach consensus were modified and re-rated. Consensus was predefined as 75% agreement across responders. RESULTS: Seventeen experts joined the panel and 12 (70.6%) attended the focus group meeting; 14 (82%) completed both iterations of the survey. Consensus was reached for need of adequate clinical history, multidisciplinary discussion, establishment of special interest groups to discuss cases, gathering further evidence to inform imaging choices, establishment of methods for quality assessment in reporting standards and adequate funding for imaging services. The panel agreed that pathologists should be responsible for neuroimaging referrals, collating results of ancillary tests, and producing the final post mortem report. Areas requiring further discussion include the impact of double reporting, indications for neuroimaging and utilities of three-dimensional printing. CONCLUSION: The BNS/ISFRI statement represents current views of an expert panel of health professionals engaged in post-mortem neuroimaging. We hope this provides a working guideline for less experienced operators, stimulates discussion and highlights the most pressing clinical and research questions.

Local bisphosphonate reduces migration and formation of radiolucent lines adjacent to cemented acetabular components.

AIMS: Post-operative migration of cemented acetabular components as measured by radiostereometric analysis (RSA) has a strong predictive power for late, aseptic loosening. Also, radiolucent lines predict late loosening. Migration has been reduced by systemic bisphosphonate treatment in randomised trials of hip and knee arthroplasty. Used as a local treatment, a higher local dose of bisphosphonate can be achieved without systemic exposure. We wished to see if this principle could be applied usefully in total hip arthroplasty (THA). PATIENTS AND METHODS: In this randomised placebo-controlled, double-blinded trial with 60 participants, we compressed gauze soaked in bisphosphonate solution (ibandronate) or saline against the acetabular bone bed immediately before cementing the acetabular component. RSA, classification of radiolucent lines, the Harris Hip Score (HHS) and the Western Ontario McMasters Universities Osteoarthritis Index (WOMAC) were carried out at three-, six-, 12-, and 24-month follow-up. RESULTS: Migration of the cemented acetabular component relative to the pelvis was reduced by movement almost half in the ibandronate group, when measured as maximum total point or as movement of the femoral head (p = 0.001 and 0.004, respectively). Radiolucent lines after one year were classified as absent, partial or complete, and correlated with treatment (rho 0.37; p = 0.004). Only three of 30 patients in the ibandronate group had complete lines, compared with 13 of 28 in the placebo group (p = 0.002). There were no significant effects on HHS or WOMAC score. CONCLUSION: Considering the power of RSA to predict loosening of cemented acetabular components, and the likelihood that radiolucent lines indicate risk of loosening, these data suggest that local treatment with a bisphosphonate can reduce the risk of late aseptic loosening. Cite this article: Bone Joint J 2017;99-B:317-24.

Using daily syndrome-specific absence data for early detection of school outbreaks: a pilot study in rural China.

OBJECTIVES: This paper describes and preliminarily evaluates the usefulness of the daily syndrome-specific absenteeism surveillance system (DSSASS) as an early warning system of school outbreaks in rural China. STUDY DESIGN: We conducted an experimental study in rural areas of Hubei Province from September 19, 2011 to December 31, 2011. METHODS: Nine public elementary schools from two counties were selected as pilot sentinel schools. Daily monitoring data of the absent date and reason, sex, age and class of each absent student was collected and entered into a web database. Reported data were checked daily and field investigation was carried out when there was abnormal absentee aggregation. Descriptive analysis and preliminary evaluation were then conducted after the pilot study. RESULTS: The findings showed that the total average of daily absenteeism rate was 3%, and the absenteeism rate differed by county, school level and grade level. The daily absenteeism rate in illness absentees was highest (2.74%), followed by business absentees (0.13%) and injury absentees (0.09%). The total timeliness report rate was 64.84% and the total incident report rate was 29.22%. One varicella outbreak and one influenza B outbreak were identified, but neither of them was detected by China Information System for Diseases Control and Prevention (CISDCP). The study shows syndrome-specific absenteeism data would be useful for early detection of unusual public health events or outbreaks in school. However, more efforts are needed to enhance the quality of surveillance data, and longer follow-up and more analysis are required to evaluate the system comprehensively. Our study might provide useful experience and evidence for other developing regions or counties establishing similar systems.

Myopathies associated with ß-tropomyosin mutations.

Mutations in TPM2, encoding ß-tropomyosin, have recently been found to cause a range of muscle disorders. We review the clinical and morphological expression of the previously reported mutations illustrating the heterogeneity of ß-tropomyosin-associated diseases and describe an additional case with a novel mutation. The manifestations of mutations in TPM2 include non-specific congenital myopathy with type 1 fibre predominance, nemaline myopathy, cap disease and distal arthrogryposis. In addition, Escobar syndrome with nemaline myopathy is a manifestation of homozygous truncating ß-tropomyosin mutation. Cap disease appears to be the most common morphological manifestation. A coarse intermyofibrillar network and jagged Z lines are additional frequent changes. The dominant ß-tropomyosin mutations manifest either as congenital myopathy or distal arthrogryposis. The various congenital myopathies are usually associated with moderate muscle weakness and no congenital joint contractures. The distal arthrogryposis syndromes associated with TPM2 mutations include the less severe forms, with congenital contractures mainly of the hands and feet and mild or no muscle weakness. The dominant TPM2 mutations include amino acid deletions/insertions and missense mutations. There is no clear relation between the type of mutations or the localisation of the mutated residue in the ß-tropomyosin molecule and the clinical and morphological phenotype.

Students' anxiety in a senior thesis course.

The State-Trait Anxiety Inventory was administered on Weeks 8, 12, and 15 of a semester to 16 students enrolled in a senior thesis course. State anxiety scores were elevated when oral presentations began and declined following the presentations. Trait anxiety scores remained constant across test administrations. The influence of situational variables on students' anxiety was discussed.

Long-term effects of a primary health care intervention program for women: lower blood pressure and stable weight.

BACKGROUND: In Strömstad, with 10,000 inhabitants, a cardiovascular prevention program was launched during 1985-1987 because of high rates of cardiovascular disease. To study long-term effects in women, an 8-year follow-up was conducted. METHODS: Participants (n = 114) and nonparticipants (n = 269) in the lifestyle intervention program in 1985-1987 (both groups with cardiovascular risk factors) were compared regarding risk factor levels after 8 years. Effects were also compared to another community not exposed to intervention. RESULTS: After 8 years, intervention participants showed significant reduction of mean systolic blood pressure compared to the control group and had higher intake of dietary fibers and more-positive attitudes to and better knowledge of healthy diets. There was no increase of mean body weight or serum triglyceride levels whatsoever in the intervention group. Compared with another female population not exposed to intervention, body weight and systolic blood pressure changed in a significantly more favorable way. CONCLUSIONS: Results from the prevention program could be discerned after 8 years. Advantages in risk factor changes could also be found when comparing with another female population. Given the high level of stroke in women within the community, the blood pressure advantage in the intervention group is particularly encouraging.

[Sleep disorders in healthy children follows often a "learnt" behavioral pattern. Diurnal rhythm disturbances are dominating among children with functional disabilities]. / Sömnstörningar hos friska barn är ofta ett "inlärt" beteende. Hos barn med funktionshinder dominerar rubbningar i dygnsrytmen.

A children's sleep disorders clinic was started as a project supported by the Swedish National Board for Health and Welfare in 1994. During the first three years 71 children, 21 girls and 50 boys aged 0.5-26 years, were clinically examined by a child neurologist/somnologist and a child psychologist. Psychological follow-up was offered. Twenty-five children were healthy, in the others several types of medical conditions were found. Twenty-five children were mentally retarded. In children with physical impairments the most common sleep problems were circadian sleep disturbances, in the healthy ones habitual insomnias were the most common finding. Taking a detailed history was important for correct sleep diagnosis and was often therapeutic. In healthy children with habitual insomnia psychological support was often successful. Melatonin was of benefit in circadian sleep disorders, and only in these. Other medications were used in a restrictive way, mostly as a temporary support.

Anticardiolipin antibodies and their associations with cerebrovascular risk factors.

OBJECTIVE: To investigate associations between cerebrovascular risk factors and anticardiolipin (aCL) immunoreactivity. BACKGROUND: High titers of aCL immunoreactivity, mainly the immunoglobulin (Ig) G isotype, were shown to predict aCL-related thrombo-occlusive complications. METHODS: aCL antibodies, and IgG and IgM isotypes were measured by a validated assay in a single laboratory, run in duplicate, in 749 individuals with first ischemic stroke (n = 300) and patients with other CNS disease or undergoing diagnostic procedures. RESULTS: Age varied according to aCL categories, with a mean of 61.8 years among patients with negative aCL (< 10 IgG phospholipid units [GPL]) to 62.3, 64.9, and 69.9 years in patients with immunoreactivity 10 to 20, 20 to 40, and >40 GPL respectively (p = 0.02). History of atrial fibrillation, congestive heart failure, or valvular heart disease was associated with significantly higher rates of positive IgG aCL (>10 GPL) and with higher immunoreactivity. IgG aCL immunoreactivity increased significantly, in a dose-response manner, as a function of the number of cerebrovascular risk factors present. In patients with first ischemic stroke, rates of 10 to 20, 20 to 40, and >40 GPL were 14%, 7%, and 0% among those with no risk factors versus 20%, 12%, and 12% respectively among patients with four or more risk factors (p = 0.007). No significant associations were identified, however, between IgM isotype aCL and any of the risk factors or increasing number of risk factors. CONCLUSION: The presence of multiple cerebrovascular risk factors is associated with substantially higher rates of positive IgG isotype aCL, and with higher immunoreactivity. These findings should caution against overdiagnosis of the antiphospholipid syndrome, and consequent changes in management among patients with multiple cerebrovascular risk factors.

Oxidation of methionine residues in coagulation factor VIIa.

The oxidation of the activated form of recombinant coagulation factor VII (FVIIa) by hydrogen peroxide has been studied. The three predominant oxidation products observed at pH 7.5 have been characterized as methionine sulfoxide derivatives of the parent protein involving two of the four methionine residues of the protein, Met298 and Met306. We conclude that oxidation of FVIIa with hydrogen peroxide only affects methionine residues and selectively oxidizes those which are readily accessible to the solvent. The oxidation process has been studied in the pH range 3.5-9.5. The total rate of oxidation of FVIIa as well as the formation of the three oxidation products is consistent over the pH interval 7.5-9.5. However, under acidic conditions, significant variations have been observed indicating a conformational change of FVIIa. Oxidized FVIIa had the same amidolytic activity as the native protein. The binding to soluble tissue factor (TF) was weaker after oxidation as manifested by a threefold increase in dissociation constant and the amidolytic activity in complex with soluble TF was 80% compared to that of native FVIIa. In complex with lipid surface TF, the rate of factor X activation catalyzed by oxidized FVIIa was also reduced by approximately 20% compared to that of native FVIIa. However, native and oxidized FVIIa appeared to bind lipidated TF with indistinguishable affinities.

The influence of cuff pathology on shoulder function after arthroscopic subacromial decompression: a 3- and 6-year follow-up study.

In the literature operative management of rotator cuff ruptures in the shoulder varies, from tendon repair to debridement of the cuff lesion combined with subacromial decompression. This study was made to evaluate whether patients with intact rotator cuff differed from patients with rotator cuff ruptures regarding functional outcome after arthroscopic subacromial decompression. We performed a clinical review of 39 patients with subacromial impingement who all underwent arthroscopic subacromial decompression; no other surgery was performed. There were 13 patients with intact cuff, 13 patients with partial-thickness supraspinatus ruptures, and 13 patients with full-thickness supraspinatus ruptures < 2 cm. Selection was based solely on the status of the supraspinatus tendon. Patients with other pathologic conditions were excluded. Follow-up was performed after 3 and 6 years. The clinical evaluation was performed with the Constant score and the visual analog pain score. The 3- and 6-year follow-up (100% follow-up rate) revealed no significant difference between the groups regarding the Constant scores and the visual analog scale values. Also, no significant difference was seen among the 3 groups in active range of motion or strength, and the patients had no appreciable pain. We conclude that the functional outcome 6 years after arthroscopic subacromial decompression is not obviously related to the preoperative degree of cuff pathology, even if a total rupture of small size is present.

Cloning and characterization of the gene encoding the highly expressed ribosomal protein l3 of the ciliated protozoan Tetrahymena thermophila. Evidence for differential codon usage in highly expressed genes.

We have cloned and characterized the cDNA and the macronuclear genomic copy of the highly conserved ribosomal protein (r-protein) L3 of Tetrahymena thermophila. The r-protein L3 is encoded by a single copy gene interrupted by one intron. The organization of the promoter region exhibits features characteristic of ribosomal protein genes in Tetrahymena. The codon usage of the L3 gene is highly biased. A thorough analysis of codon usage in Tetrahymena genes revealed that genes could be categorized into two classes according to codon usage bias. Class A comprises r-protein genes and a number of other highly expressed genes. Class B comprises weakly expressed genes such as the conjugation induced CnjB and CnjC genes, but surprisingly, this class also contains abundantly expressed genes such as the genes encoding the surface antigens SerH3 and SerH1. Codon usage is slightly more restricted in class A than in class B, but both classes exhibit distinct and different codon usage biases. Class A genes preferentially use C and U in the silent third codon positions, whereas class B genes preferentially use A and U in the silent third codon positions. The analysis suggests that two different strategies have been employed for optimization of codon usage in the A+T-rich genome of Tetrahymena.

Specificity, isotype, and titer distribution of anticardiolipin antibodies in CNS diseases.

BACKGROUND AND PURPOSE: There is an association between anticardiolipin antibodies (aCL) and ischemic stroke. There are, however, also occasional reports linking aCL with other CNS diseases (OND), particularly with multiple sclerosis (MS). Hence, we studied the specificity of aCL for ischemic stroke. METHODS: Prospective, consecutively identified patients evaluated for aCL (immunoglobulin G [IgG] and immunoglobulin M [IgM] isotypes) were divided into two groups: ischemic stroke (first ever) and OND (stroke-free subjects affected by OND). RESULTS: The ischemic stroke group (n = 300) and the OND (n = 149) differed in the following risk factors: age (64 +/- 14 versus 58 +/- 15 years; p < 0.001) and proportions of African Americans (67% versus 29%; p < 0.001); current cigarette smoker (26% versus 17%; p = 0.028); hypertensive (69% versus 34%; p < 0.001); diabetic (18% versus 7%; p = 0.001); history of angina (16% versus 8%; p = 0.015) or myocardial infarction (15% versus 3%; p < 0.001). There were higher rates of aCL positivity (26% versus 17%; p = 0.050), IgG-aCL > 10 GPL (23% versus 11%; p = 0.003) or IgG aCL > 20 GPL (12% versus 4%; p = 0.012) among the stroke group than among the OND group. No differences in IgG-aCL positivity were found between the MS group and the rest of the OND group but the MS patients had a higher rate of IgM-aCL positivity than the other OND patients. CONCLUSION: IgG-aCL positivity does not appear to be a marker for CNS disease generally but of ischemic stroke.

Attributional style, depression, and grade point averages of college students.

91 upper-level undergraduates completed the Attributional Style Questionnaire and the Center for Epidemiologic Studies Depression Scale; scores on these inventories were correlated with students' cumulative grade point averages. Students with pessimistic attributional style scores had higher depression scores than students with optimistic attributional style scores and those with higher depression scores had lower grade point averages. The need for longitudinal evaluation of changes in these associations is discussed.

Analysis of the site-specific asparagine-linked glycosylation of recombinant human coagulation factor VIIa by glycosidase digestions, liquid chromatography, and mass spectrometry.

The two asparagine-linked glycosylation sites of recombinant coagulation factor VIIa have been characterized by glycosidase digestions, size-exclusion chromatography (SEC), and mass spectrometry (MS). Nine structures were characterized as core fucosylated bi-and triantennary structures with 0-3 sialic-acid residues which were alpha 2-3 linked to galactose exclusively. Three of the structures had one or two galactose residues substituted by N-acetylgalactosamine. Significant differences were found between the oligosaccharide profiles for the two glycosylation sites in rFVIIa. At Asn322, the degree of sialylation was lower and higher amounts of structures containing N-acetylgalactosamine were found compared to Asn145.

Analysis of the site-specific asparagine-linked glycosylation of recombinant human coagulation factor VLLa by glycosidase digestions, liquid chromatography, and mass spectrometry.

The two asparagine-linked glycosylation sites of recombinant coagulation factor VIIa have been characterized by glycosidase digestions, size-exclusion chromatography (SEC), and mass spectrometry (MS). Nine structures were characterized as core fucosylated bi- and triantennary structures with 0-3 sialic-acid residues, which were alpha2-3 linked to galactose exclusively. Three of the structures had one or two galactose residues substituted by N-acetylgalactosamine. Significant differences were found between the oligosac-charide profiles for the two glycosylation sites in rFVIIa. At Asn322, the degree of sialylation was lower and higher amounts of structures containing N-acetylgalactosamine were found compared to Asn l45.

IgG anticardiolipin antibody titer > 40 GPL and the risk of subsequent thrombo-occlusive events and death. A prospective cohort study.

BACKGROUND: Anticardiolipin antibodies (aCL) have been associated with an increased risk of stroke and thrombo-occlusive events. Little is known about the influence of aCL on recurrent thrombo-occlusive events. METHODS: Consecutively identified patients (n = 132) with focal cerebral ischemia [stroke = 112, transient ischemic attack (TIA) = 20] harboring aCL of at least 10 GPL units at the time of their index event were prospectively followed to estimate the effect of aCL titer on time to and risk of subsequent thrombo-occlusive events (stroke, TIA, deep venous thrombosis, pulmonary embolism, myocardial infarction) and death. On the basis of prior literature, we divided patients into those with aCL < or = 40 GPL (n = 111; mean age, 63 +/- 14 years; mean follow-up, 1.95 years) and those with aCL > 40 GPL (n = 21; mean age, 54 +/- 20 years; mean follow-up, 1.50 years). RESULTS: There was no difference between groups for prevalence of hypertension, diabetes mellitus, cigarette smoking, atrial fibrillation, prior TIA, or sex. The GPL > 40 group was younger (54 +/- 20 versus 63 +/- 14 years; P = .055), had more prior strokes [9/21 (48%) versus 27/111 (20%); P = .030], more frequent subsequent thrombo-occlusive events and death [15/21 (71%) versus 51/111 (48%); P = .030], and a shorter median time (years) to event (0.15 versus 0.61, log rank P = .005). The risk ratio for recurrent event and death with GPL > 40 obtained from Cox proportional hazards models, adjusted for prior strokes, prior TIAs, hypertension, diabetes mellitus, atrial fibrillation, and cigarette smoking was 1.9 (95% confidence interval, 1.0 to 3.5; P = .051). CONCLUSIONS: Our data suggest that subsequent thrombo-occlusive events and death after focal cerebral ischemia associated with IgG aCL may occur sooner and more frequently with GPL > 40.

Long-term melatonin treatment in blind children and young adults with circadian sleep-wake disturbances.

Oral melatonin therapy was used to treat-severe circadian sleep-wake disturbances in eight children and young adults in an open study. All patients were functionally blind, six of them because of defects in the anterior visual pathway. All were mentally retarded. Baseline sleep diaries kept by the caregivers before treatment showed non-24-hour sleep-wake syndrome. Diurnal variations in serum and urinary melatonin were examined. Melatonin secretion peak time was delayed in seven patients. Body temperature variation was out of phase relative to sleep and melatonin in five patients, and thus they had signs of internal desynchronisation. Melatonin given in the evening dramatically improved the sleep-wake pattern in all patients. The effect was maintained during long-term therapy for between 1 and 6 years in six patients. One patient fell back into the earlier sleep pattern after 6 to 8 months, and another had increasing sleep disturbance because of reflux oesophagitis, although the improvement regarding the circadian component remained. No side effects have been noted during the therapy. Oral melatonin is promising as an efficient and seemingly safe alternative for treatment of severe circadian sleep disturbances.

Identification of five hemoglobins in B6C3F1 mice by mass spectrometry and sequence analysis.

The aim of the work is to identify and characterize the hemoglobins found in B6C3F1 mice using mass spectrometry. The primary structures are compared to those reported for BALB/c mice. Individual hemoglobin chains were isolated by reverse-phase high performance liquid chromatography (RP-HPLC). The molecular masses of the globins were determined using electrospray ionization (ESI) and matrix-assisted laser desorption ionization (MALDI). The purified globin chains were enzymatically cleaved and the resulting peptides were separated by RP-HPLC. The chains were identified by N-terminal sequencing and mass spectrometry (MALDI). Selected peptides were analysed by Edman degradation. ESI analysis indicates that B6C3F1 mice have two alpha-globin chains (alpha-1 and alpha-2) and at least three beta-globin chains, beta-1, beta-2 and beta-3. This is one additional alpha- and one additional beta-globin chain than reported in the literature for BALB/c mice. Mass and sequence analysis of enzymatically generated peptides showed variations in the amino acid sequence in the alpha-1, alpha-2, beta-2 and beta-3 chains compared to the BALB/c mouse hemoglobins (alpha, beta (minor) and beta (major)). The study showed that mass spectrometry in combination with traditional protein chemistry is able to identify and locate minor protein sequence variations.

Recurrent stroke and thrombo-occlusive events in the antiphospholipid syndrome.

We prospectively studied 81 consecutively identified patients with antiphospholipid antibodies (aPLs) who developed focal cerebral ischemia over a 7-year period. The mean age of this cohort was approximately a decade younger than the average atherothromboembolic stroke victim and women were more commonly involved than men. The frequency of conventional stroke risk factors was lowest in the group of stroke patients with the highest levels of IgG cardiolipin immunoreactivity. Other serological abnormalities associated with aPL (false-positive Venereal Disease Research Laboratory test, thrombocytopenia, prolonged activated partial thromboplastin time [aPTT]) were more common in the group with over 100 GPL units (high positive). Patients with the highest IgG anticardiolipin titers had the shortest times to subsequent thrombo-occlusive events. The most common recurrent event was cerebral infarction, often occurring within the first year of follow-up during a mean prospective follow-up of 3 years. Over one-half of the cohort had at least one recurrent thrombo-occlusive event during follow-up. This distinct syndrome of cerebral ischemia should be recognized for its younger age at onset, predominance of women, high risk of recurrent thrombo-occlusive events, and the possible use of the IgG anticardiolipin antibody titer for prognosis.