Crystal Containing Membrane Bound Intracellular Inclusion Bodies in the Epithelium of Experimentally Infected Sinus Mucosa

The sinus mucosa of 16 rabbits was experimentally infected with Bacteroides fragilis. This paper describes and discusses large inclusion bodies, which were found in abundance by light and electron microscopy inside ciliated cells of the sinus epithelium in 3 of the studied animals. The spindle-shaped inclusions were located in the apical portion of the cytoplasm. They were bound by a trilaminar membrane with several coils to the interior as well as to the exterior. The interior of an inclusion body consisted to a large extent of electron-lucent, floccular substance, but fibrogranular aggregates and rod-shaped crystals with a line periodicity center-to-center of about 15 nm were also conspicuous. These peculiar formations may be constituted by abnormally stored material from defective synthesis of cilia.     

The use of proteomics in biomarker discovery in neurodegenerative diseases

Biomarkers for neurodegenerative diseases should reflect the central pathogenic processes of the diseases. The field of clinical proteomics is especially well suited for discovery of biomarkers in cerebrospinal fluid (CSF), which reflects the proteins in the brain under healthy conditions as well as in several neurodegenerative diseases. Known proteins involved in the pathology of neurodegenerative diseases are, respectively, normal tau protein, beta-amyloid (1-42), synaptic proteins, amyloid precursor protein (APP), apolipoprotein E (apoE), which previously have been studied by protein immunoassays. The objective of this paper was to summarize results from proteomic studies of differential protein patterns in neurodegenerative diseases with focus on Alzheimer's disease (AD). Today, discrimination of AD from controls and from other neurological diseases has been improved by simultaneous analysis of both beta-amyloid (1-42), total-tau, and phosphorylated tau, where a combination of low levels of CSF-beta-amyloid 1-42 and high levels of CSF-tau and CSF-phospho-tau is associated with an AD diagnosis. Detection of new biomarkers will further strengthen diagnosis and provide useful information in drug trials. The combination of immunoassays and proteomic methods show that the CSF proteins express differential protein patterns in AD, FTD, and PD patients, which reflect divergent underlying pathophysiological mechanisms and neuropathological changes in these diseases.     

Sarcopenia Definitions as Predictors of Fracture Risk Independent of FRAX®, Falls,and BMD in the Osteoporotic Fractures in Men (MrOS) Study: A Meta-Analysis

Dual-energy X-ray absorptiometry (DXA)-derived appendicular lean mass/height² (ALM/ht²) is the most commonly used estimate of muscle mass in the assessment of sarcopenia, but its predictive value for fracture is substantially attenuated by femoral neck (fn) bone mineral density (BMD). We investigated predictive value of 11 sarcopenia definitions for incident fracture, independent of fnBMD, fracture risk assessment tool (FRAX^®) probability, and prior falls, using an extension of Poisson regression in US, Sweden, and Hong Kong Osteoporois Fractures in Men Study (MrOS) cohorts. Definitions tested were those of Baumgartner and Delmonico (ALM/ht² only), Morley, the International Working Group on Sarcopenia, European Working Group on Sarcopenia in Older People (EWGSOP1 and 2), Asian Working Group on Sarcopenia, Foundation for the National Institutes of Health (FNIH) 1 and 2 (using ALM/body mass index [BMI], incorporating muscle strength and/or physical performance measures plus ALM/ht²), and Sarcopenia Definitions and Outcomes Consortium (gait speed and grip strength). Associations were adjusted for age and time since baseline and reported as hazard ratio (HR) for first incident fracture, here major osteoporotic fracture (MOF; clinical vertebral, hip, distal forearm, proximal humerus). Further analyses adjusted additionally for FRAX-MOF probability (n = 7531; calculated ± fnBMD), prior falls (y/n), or fnBMD T-score. Results were synthesized by meta-analysis. In 5660 men in USA, 2764 Sweden and 1987 Hong Kong (mean ages 73.5, 75.4, and 72.4 years, respectively), sarcopenia prevalence ranged from 0.5% to 35%. Sarcopenia status, by all definitions except those of FNIH, was associated with incident MOF (HR = 1.39 to 2.07). Associations were robust to adjustment for prior falls or FRAX probability (without fnBMD); adjustment for fnBMD T-score attenuated associations. EWGSOP2 severe sarcopenia (incorporating chair stand time, gait speed, and grip strength plus ALM) was most predictive, albeit at low prevalence, and appeared only modestly influenced by inclusion of fnBMD. In conclusion, the predictive value for fracture of sarcopenia definitions based on ALM is reduced by adjustment for fnBMD but strengthened by additional inclusion of physical performance measures. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

De novo biosynthesis of the aggregation pheromone components ipsenol and ipsdienol by the pine bark beetles Ips paraconfusus Lanier and Ips pini (Say) (Coleoptera: Scolytidae)

The California five-spined ips, Ips paraconfusus Lanier, produces the myrcene-derived acyclic monoterpene alcohols ipsenol (2-methyl-6-methylene-7-octen-4-ol) and ipsdienol (2-methyl-6-methylene-2,7-octadien-4-ol) as components of its aggregation pheromone. The pine engraver beetle, Ips pini (Say), produces only ipsdienol. Previous studies have shown that myrcene, a monoterpene in the pines colonized by these beetles, is a direct precursor to these pheromone components. In vivo radiolabeling studies reported here showed that male I. paraconfusus incorporated [1-14C]acetate into ipsenol, ipsdienol, and amitinol (trans-2-methyl-6-methylene-3,7-octadien-2-ol), while male I. pini incorporated [1-14C]acetate into ipsdienol and amitinol. Females of these species produced neither labeled nor unlabeled pheromone components. The purified radiolabeled monoterpene alcohols from-males were identified by comparison of their HPLC and GC retention times with those of unlabeled standards. HPLC-purified fractions containing the individual radiolabeled components were analyzed by GC-MS and were shown to include only the pure alcohols. To further confirm that ipsdienol and ipsenol were radiolabeled, diastereomeric ester derivatives of the isolated alcohols were synthesized and analyzed by HPLC and GC-MS. After derivatization of the radiolabeled alcohols, the HPLC analysis demonstrated expected shifts in retention times with conservation of naturally occurring stereochemistry. The results provide direct evidence for de novo biosynthesis of ipsenol, ipsdienol, and amitinol by bark beetles.     

Tailoring Antireflux Surgery: A Randomized Clinical Trial

A hypothesis has been formulated that mandates the adjustment of antireflux surgery to either a total or a partial wrap depending on the motor function of the esophagus to avoid dysphagia and other obstructive complaints. This hypothesis has been tested in a randomized, clinical trial where 106 chronic gastroesophageal reflux patients were allocated to either a total Nissen-Rossetti (n= 53) or a Toupet partial posterior (n= 53) fundoplication, irrespective of their preoperative esophageal motor function. All patients were followed at least 3 years, during which time none had a relapse of moderate to severe reflux symptoms. Motor dysfunctions defined as peristaltic amplitude ≤ 30 mmHg in the distal third and failed primary peristalsis with or without > 20% simultaneous contractions were noted in 67 patients preoperatively, but these patients did not have a specific symptom profile (e.g., dominated by obstructive symptoms) nor did seven patients with “aperistaltic esophagus.” The incidence of dysphagia decreased from 20% preoperatively to 8% (mild) at 3 years after the operation with no difference between the surgical procedures. We were unable to demonstrate a relation between preoperative manometric findings and postoperative symptoms when assessed in the total group or when subdivided by the type of fundoplication (r < 0.3). Flatulence occurred more frequently among those with a total fundic wrap (p < 0.01). When patients representing motor dysfunction (see above) were specifically analyzed, we again observed no difference in outcome between those having a total or a partial fundic wrap. In conclusion, the concept of tailoring antireflux surgery based on the preoperative motor function of the esophagus in patients with chronic gastroesophageal reflux disease was not supported by the results of this clinical trial.     

Day care attendance, recurrent respiratory tract infections and asthma

OBJECTIVE: Our objective was to use a causal model for childhood asthma to determine whether the effect of day care attendance on asthma was mediated by recurrent respiratory tract infections. DESIGN: A cross-sectional survey among 1447 children aged 6-16 years in Oslo. Their parents completed written questionnaires. A recursive logit model was used to estimate direct effects in terms of adjusted odds ratios (aOR). RESULTS: Year of birth, number of siblings and length of maternal education were significantly associated with day care attendance. Attendance at day care increased the risk of early infections, aOR = 1.8 (1.3-2.5), and infections were associated with asthma, aOR = 4.9 (3.4-7.3). The crude association between day care and asthma was cOR = 1.5 (1.0-2.2), whereas the estimated direct effect was small and nonsignificant, aOR = 1.2 (0.8-1.9). The results may be influenced by overreporting of infections among parents of children with asthma. CONCLUSIONS: Our results suggest that children who attend day care have an increased risk of asthma with early infections as a mediator of risk.     

The self-employed and the self-driven: two coronary-prone subpopulations from the Zeist study

In four Dutch communities, Zeist, De Bilt, Driebergen, and Doorn (total population, 111,000 inhabitants), all patients who suffered acute coronary events between July 1970 and March 1974 were recorded. By combining data from this study with data from the 1971 national census of the Netherlands, it was possible to demonstrate that the incidence of acute coronary events is twice as high for self-employed men as for employed men and as much as seven times as high for self-employed women as for housewives. The incidence of acute coronary events is practically the same for self-employed women aged 45-69 years as for men of the same age in the general population. Men aged 35-64 years whose nature is such that they feel driven to do all their work with great intensity and against the clock ("self-driven men") suffer myocardial infarction seven times as frequently as others and are 2.4 times as likely to die of fatal coronary attack. Only 10% of the self-employed male referents, but 50% of the self-employed male cases, consider themselves self-driven. On the other hand, experiences of excessive working hours and time pressures are not related to the incidence of acute coronary events. These results were not influenced by and were independent of other known risk indicators.     

Lesion pattern in patients with multiple sclerosis and depression

To assess if a specific lesion pattern or changes of the basal limbic system as seen in primary depression and depression associated with neurodegenerative disorders might be identified in depressive multiple sclerosis (MS) patients, we submitted 78 MS patients to a MRI examination consisting of a quantitative measurement of lesions and of hyperintense signals from the pontomesencephalic midline (raphe). Furthermore relaxometry of the pontomesencephalic midline, a transcranial ultrasound examination rating its echogenicity semiquantitatively and a standardized neurological, neuropsychiatric and neuropsychological assessment were obtained. Thirty-one patients fulfilled the DSM-IV criteria for depression. Depressed MS patients had a significantly larger temporal lesion load than non-depressed MS patients, especially on the right side. A trend of difference was detected for lesions of the right parietal lobe, the right frontal lobe, the cerebellum and the total lesion load. Neither hyperintense signals or relaxometry nor echogenicity of the region at the level of the pontomesencephalic midline were significantly different between the groups. We conclude that depression in MS patients is not associated with an alteration of the basal limbic system at the brainstem as seen in Parkinson's disease or unipolar depression but with an increased lesion load of the projection areas of the basal limbic system.