№ 46. Із щотижневого зведення Секретного відділу ДПУ УСРР № 46/56 за час з 13 до 19 листопада 1927 р.

Classifications of the Campylobacter fetus subspecies fetus and venerealis were first described in 1959 and were based on the source of isolation (intestinal versus genital) and the ability of the strains to proliferate in the genital tract of cows. Two phenotypic assays (1% glycine tolerance and H2S production) were described to differentiate the subspecies. Multiple molecular assays have been applied to differentiate the C. fetus subspecies, but none of these tests is consistent with the phenotypic identification methods. In this study, we defined the core genome and accessory genes of C. fetus, which are based on the closed genomes of five C. fetus strains. Phylogenetic analysis of the core genomes of 23 C. fetus strains of the two subspecies showed a division into two clusters. The phylogenetic core genome clusters were not consistent with the phenotypic classifications of the C. fetus subspecies. However, they were consistent with the molecular characteristics of the strains, which were determined by multilocus sequence typing, sap typing, and the presence/absence of insertion sequences and a type I restriction modification system. The similarity of the genome characteristics of three of the phenotypically defined C. fetus subsp. fetus strains to C. fetus subsp. venerealis strains, when considering the core genome and accessory genes, requires a critical evaluation of the clinical relevance of C. fetus subspecies identification by phenotypic assays

Reduced Angiopoietin-Like 4 Expression in Multiple Sclerosis Lesions Facilitates Lipid Uptake by Phagocytes via Modulation of Lipoprotein-Lipase Activity

Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system (CNS) characterized by the presence of focal demyelinated plaques. Sufficient clearance of myelin and cellular debris is one of the requirements for proper tissue repair and remyelination. The mechanisms underlying the clearance of such debris by phagocytes are not fully understood, but recent findings suggest a prominent role for lipoprotein-lipase (LPL) in this process. Here, we demonstrate that angiopoietin-like 4 (ANGPTL4), a potent inhibitor of LPL, is abundantly expressed in astrocytes in control white matter tissue and its expression is markedly reduced in active MS lesions. We provide evidence that ANGPTL4 inhibits the uptake of myelin-derived lipids by LPL-immunoreactive phagocytes. Taken together, our data suggest that the strong reduction in astrocytic ANGPTL4 expression in active demyelinating MS lesions enables phagocytes to adequately clear myelin debris, setting the stage for remyelination

Subclinical thyroid dysfunction and cognitive decline in old age

<p>Background: Subclinical thyroid dysfunction has been implicated as a risk factor for cognitive decline in old age, but results are inconsistent. We investigated the association between subclinical thyroid dysfunction and cognitive decline in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER).</p> <p>Methods: Prospective longitudinal study of men and women aged 70–82 years with pre-existing vascular disease or more than one risk factor to develop this condition (N = 5,154). Participants taking antithyroid medications, thyroid hormone supplementation and/or amiodarone were excluded. Thyroid function was measured at baseline: subclinical hyper- and hypothyroidism were defined as thyroid stimulating hormones (TSH) <0.45 mU/L or >4.50 mU/L respectively, with normal levels of free thyroxine (FT4). Cognitive performance was tested at baseline and at four subsequent time points during a mean follow-up of 3 years, using five neuropsychological performance tests.</p> <p>Results: Subclinical hyperthyroidism and hypothyroidism were found in 65 and 161 participants, respectively. We found no consistent association of subclinical hyper- or hypothyroidism with altered cognitive performance compared to euthyroid participants on the individual cognitive tests. Similarly, there was no association with rate of cognitive decline during follow-up.</p> <p>Conclusion: We found no consistent evidence that subclinical hyper- or hypothyroidism contribute to cognitive impairment or decline in old age. Although our data are not in support of treatment of subclinical thyroid dysfunction to prevent cognitive dysfunction in later life, only large randomized controlled trials can provide definitive evidence.</p&gt

Subclinical thyroid dysfunction and cognitive decline in old age

<p>Background: Subclinical thyroid dysfunction has been implicated as a risk factor for cognitive decline in old age, but results are inconsistent. We investigated the association between subclinical thyroid dysfunction and cognitive decline in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER).</p> <p>Methods: Prospective longitudinal study of men and women aged 70–82 years with pre-existing vascular disease or more than one risk factor to develop this condition (N = 5,154). Participants taking antithyroid medications, thyroid hormone supplementation and/or amiodarone were excluded. Thyroid function was measured at baseline: subclinical hyper- and hypothyroidism were defined as thyroid stimulating hormones (TSH) <0.45 mU/L or >4.50 mU/L respectively, with normal levels of free thyroxine (FT4). Cognitive performance was tested at baseline and at four subsequent time points during a mean follow-up of 3 years, using five neuropsychological performance tests.</p> <p>Results: Subclinical hyperthyroidism and hypothyroidism were found in 65 and 161 participants, respectively. We found no consistent association of subclinical hyper- or hypothyroidism with altered cognitive performance compared to euthyroid participants on the individual cognitive tests. Similarly, there was no association with rate of cognitive decline during follow-up.</p> <p>Conclusion: We found no consistent evidence that subclinical hyper- or hypothyroidism contribute to cognitive impairment or decline in old age. Although our data are not in support of treatment of subclinical thyroid dysfunction to prevent cognitive dysfunction in later life, only large randomized controlled trials can provide definitive evidence.</p&gt

Interpreting Overdiagnosis Estimates in Population-based Mammography Screening

Estimates of overdiagnosis in mammography screening range from 1% to 54%. This review explains such variations using gradual implementation of mammography screening in the Netherlands as an example. Breast cancer incidence without screening was predicted with a micro-simulation model. Observed breast cancer incidence (including ductal carcinoma in situ and invasive breast cancer) was modeled and compared with predicted incidence without screening during various phases of screening program implementation. Overdiagnosis was calculated as the difference between the modeled number of breast cancers with and the predicted number of breast cancers without screening. Estimating overdiagnosis annually between 1990 and 2006 illustrated the importance of the time at which overdiagnosis is measured. Overdiagnosis was also calculated using several estimators identified from the literature. The estimated overdiagnosis rate peaked during the implementation phase of screening, at 11.4% of all predicted cancers in women aged 0–100 years in the absence of screening. At steady-state screening, in 2006, this estimate had decreased to 2.8%. When different estimators were used, the overdiagnosis rate in 2006 ranged from 3.6% (screening age or older) to 9.7% (screening age only). The authors concluded that the estimated overdiagnosis rate in 2006 could vary by a factor of 3.5 when different denominators were used. Calculations based on earlier screening program phases may overestimate overdiagnosis by a factor 4. Sufficient follow-up and agreement regarding the chosen estimator are needed to obtain reliable estimates

Hemostasis and ageing

On March 19, 2008 a Symposium on Pathophysiology of Ageing and Age-Related Diseases was held in Palermo, Italy. The lecture of D. Mari on Hemostasis and ageing is summarized herein. Physiological ageing is associated with increased plasma levels of many proteins of blood coagulation together with fibrinolysis impairment. This may be of great concern in view of the known association between vascular and thromboembolic diseases and ageing. On the other hand, centenarians are characterized by a state of hypercoagulability and possession of several high-risk alleles and well-known atherothrombotic risk markers but this appears to be compatible with longevity and/or health. Parameters considered risk factors for atherosclerotic vascular diseases in young people may lose their biological significance in advanced age and assume a different role

How I report breast magnetic resonance imaging studies for breast cancer staging and screening

Magnetic resonance imaging (MRI) of the breast is the most sensitive imaging technique for the diagnosis and local staging of primary breast cancer and yet, despite the fact that it has been in use for 20 years, there is little evidence that its widespread uncritical adoption has had a positive impact on patient-related outcomes. This has been attributed previously to the low specificity that might be expected with such a sensitive modality, but with modern techniques and protocols, the specificity and positive predictive value for malignancy can exceed that of breast ultrasound and mammography. A more likely explanation is that historically, clinicians have acted on MRI findings and altered surgical plans without prior histological confirmation. Furthermore, modern adjuvant therapy for breast cancer has improved so much that it has become a very tall order to show a an improvement in outcomes such as local recurrence rates. In order to obtain clinically useful information, it is necessary to understand the strengths and weaknesses of the technique and the physiological processes reflected in breast MRI. An appropriate indication for the scan, proper patient preparation and good scan technique, with rigorous quality assurance, are all essential prerequisites for a diagnostically relevant study. The use of recognised descriptors from a standardised lexicon is helpful, since assessment can then dictate subsequent recommendations for management, as in the American College of Radiology BI-RADS (Breast Imaging Reporting and Data System) lexicon (Morris et al., ACR BI-RADS® Atlas, Breast Imaging Reporting and Data System, 2013). It also enables audit of the service. However, perhaps the most critical factor in the generation of a meaningful report is for the reporting radiologist to have a thorough understanding of the clinical question and of the findings that will influence management. This has never been more important than at present, when we are in the throes of a remarkable paradigm shift in the treatment of both early stage and locally advanced breast cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40644-016-0078-0) contains supplementary material, which is available to authorized users

Short-term health-related quality of life consequences in a lung cancer CT screening trial (NELSON)

Item does not contain fulltextBACKGROUND: In lung cancer CT screening, participants often have an indeterminate screening result at baseline requiring a follow-up CT. In subjects with either an indeterminate or a negative result after screening, we investigated whether health-related quality of life (HRQoL) changed over time and differed between groups in the short term. METHODS: A total of 733 participants in the NELSON trial received four questionnaires: T0, before randomisation; T1, 1 week before the baseline screening; T2, 1 day after the screening; and T3, 2 months after the screening results but before the 3-month follow-up CT. HRQoL was measured as generic HRQoL (the 12-item Short Form, SF-12; the EuroQol questionnaire, EQ-5D), anxiety (the Spielberger State-Trait Anxiety Inventory, STAI-6), and lung-cancer-specific distress (the Impact of Event Scale, IES). For analyses, repeated-measures analysis of variance was used, adjusted for covariates. RESULTS: Response to each questionnaire was 88% or higher. Scores on SF-12, EQ-5D, and STAI-6 showed no clinically relevant changes over time. At T3, IES scores that were clinically relevant increased after an indeterminate result, whereas these scores showed a significant decrease after a negative result. At T3, differences in IES scores between the two baseline result groups were both significant and clinically relevant (P<0.01). CONCLUSION: This longitudinal study among participants of a lung cancer screening programme showed that in the short term recipients of an indeterminate result experienced increased lung-cancer-specific distress, whereas the HRQoL changes after a negative baseline screening result may be interpreted as a relief

Rising incidence of breast cancer among female cancer survivors: implications for surveillance

The number of female cancer survivors has been rising rapidly. We assessed the occurrence of breast cancer in these survivors over time. We computed incidence of primary breast cancer in two cohorts of female cancer survivors with a first diagnosis of cancer at ages 30+ in the periods 1975–1979 and 1990–1994. Cohorts were followed for 10 years through a population-based cancer registry. Over a period of 15 years, the incidence rate of breast cancer among female cancer survivors increased by 30% (age-standardised rate ratio (RR-adj): 1.30; 95% CI: 1.03–1.68). The increase was significant for non-breast cancer survivors (RR-adj: 1.41, 95% CI: 1.04–2.75). During the study period, the rate of second breast cancer stage II tripled (RR-adj: 3.10, 95% CI: 1.73–5.78). Non-breast cancer survivors had a significantly (P value=0.005) more unfavourable stage distribution (62% stage II and III) than breast cancer survivors (32% stage II and III). A marked rise in breast cancer incidence among female cancer survivors was observed. Research to optimise follow-up strategies for these women to detect breast cancer at an early stage is warranted

Impact of screening for breast cancer in high-risk women on health-related quality of life

The effectiveness of intensive surveillance in women at high risk for breast cancer due to a familial or genetic predisposition is uncertain and is currently being evaluated in a Dutch magnetic resonance imaging (MRI) screening (MRISC) study, in which annual imaging consists of mammography and MRI. Unfavourable side effects on health-related quality of life may arise from this screening process. We examined the short-term effects of screening for breast cancer in high-risk women on generic health-related quality of life and distress. A total of 519 participants in the MRISC study were asked to complete generic health-status questionnaires (SF-36, EQ-5D) as well as additional questionnaires for distress and items relating to breast cancer screening, at three different time points around screening. The study population showed significantly better generic health-related quality of life scores compared to age-/sex-adjusted reference scores from the general population. Neither generic health-related quality of life scores nor distress scores among the study sample (n = 334) showed significant changes over time. The impact of the screening process on generic health status did not differ between risk categories. Relatively more women reported mammography as quite to very painful (30.1%) compared to MRI. Anxiety was experienced by 37% of the women undergoing MRI. We conclude that screening for breast cancer in high-risk women does not have an unfavourable impact on short-term generic health-related quality of life and general distress. In this study, high-risk women who opted for regular breast cancer screening had a better health status than women from the general population