Mother's education and perinatal problems in Finland.

This study using nationwide data expands a previous study from one area in Finland. The purpose was to study how perinatal problems (mortality, short gestation, low birthweight and low Apgar scores) vary by mother's social class, which is measured by level of education. Outcomes of all births in the 1987 Medical Birth Register were linked to the 1988 National Education Register with gives the estimated number of years of completed education. In unadjusted analyses, the lowest educational groups (less than 9 years) had the worst results for outcomes other than neonatal mortality. Results in the two highest educational groups (greater than or equal to 13 and 12 years of education) were similar and if anything, better in the second highest group. Excluding twins and adjusting for confounding variables (age, parity, county, urbanization of residence) by logistic regression analysis did not alter the results much. Adjustment for possible mechanisms correlated with social class (marital status, smoking, time of first antenatal visit) decreased the higher occurrence of low birthweight infants in the low educational groups. Reported previous miscarriages were more common in the higher educational groups. Based on the available background characteristics one would expect to have found the usual social gradient in perinatal problems to have persisted between the two highest educational groups. Further studies on factors causing the plateau in the gradient between these groups might be useful.     

L-selectin ligands in rat high endothelium: multivalent sialyl Lewis x glycans are high-affinity inhibitors of lymphocyte adhesion

Lymphocyte homing is initiated by their tethering to and rolling on the high endothelium and is followed by extravasation into the lymph nodes. We show here that glycosylated cell adhesion molecule-1 (GlyCAM-1), CD34, and sialyl Lewis x (sLex) are present on rat lymph node high endothelium analyzed by using monoclonal antibodies. α(1,3)fucosyltransferase VII (Fuc-TVII), the last enzyme involved in the synthesis of the sLex sequence is also expressed on the rat lymph node high endothelium. We have synthesized a family of sLex-decorated oligosaccharide structures and used them to inhibit lymphocyte binding to high endothelium in the Stamper-Woodruff assay. Monovalent sLex, branched di- and tetravalent sLex, as well as a linear tetravalent sLex significantly reduce lymphocyte binding to endothelium. The branched and linear forms of tetravalent sLex were clearly superior inhibitors of the L-selectin-dependent lymphocyte adhesion, with IC50 values in low nanomolar range. In contrast, the fucose-free analogs having the same charge and approximately the same size as the corresponding sLex glycans had no effect on lymphocyte binding and served as negative controls. Taken together, these data show the crucial importance of sLex in the endothelial ligands for L-selectin. Furthermore, we suggest that L-selectin acts as an oligomer on the lymphocyte surface as it binds multivalent sLex glycans.     

Impact of enteral nutrition on intestinal bacterial translocation and mortality in burned mice

The aim of these experiments was to study the effect of early enteral nutrition with either standard or enriched (arginine, n-3 fatty acids, RNA) enteral formulas on translocation of bacteria from the gut and acute mortality rate following thermal injury. In the first experiment 60 Balb c mice were gavaged with 10(10)Escherichia coli and received a 20% burn injury. In 40 mice enteral nutrition (20 standard, 20 enriched) was started immediately after injury and stopped 36 h later. In the control group (n = 20) aliquotes of Ringer's solution was administered intragastrically. Mortality rate was observed for 10 days post-injury. In the second experiment 60 Balb c mice were gavaged with 10(10)E. coli labelled with biotin(111) Indium and then burned. In 40 mice enteral nutrition (20 standard, 20 enriched) was started immediately after burn. The control group (n = 20) received aliquotes of Ringer's solution. 4 h after injury all animals were sacrificed and liver, lungs, kidneys, spleen and systemic blood were harvested, and radionuclide counts were measured. No animal died after day 3 post-burn. The mortality rate was significantly lower at day 1 in the groups infused with both enteral solutions (15%) compared to controls (30%; p = 0.05). At day 3 the animals fed with the enriched diets showed a lower mortality (5%) versus the standard and control groups (10%). Bacterial translocation to the liver and lungs was significantly higher in Ringer's group than in both enterally fed groups. Early post-burn enteral nutrition reduces both translocation and acute mortality. Supplementation of the diets with specific nutrients appears to exert additional advantages on outcome.     

Gender differences in illhealth in Finland: patterns, magnitude and change

The common wisdom about gender differences in illhealth has been encapsulated in the phrase "women are sicker, but men die quicker". Recently this wisdom has been increasingly questioned. The purpose of this study is first to analyse the patterns and magnitude of gender differences across various indicators of illhealth; second to examine changes over time in these differences and third to assess whether sociodemographic and socioeconomic, family status and social network determinants have any bearing on the differences. The data derive from nationally representative 1986 and 1994 Surveys on Living Conditions in Finland. Women showed poorer health for five out of eight indicators analysed; that is somatic symptoms, mental symptoms, disability among those 50 years or older, long-standing illness and limiting long-standing illness were more prevalent among women than men. Male excess was found for perceived health below good and extremely limiting long-standing illness among those 50 years or older. However, the male excess was statistically significant only for poor perceived health among those 50 years or older. Adjusting for a number of suggested determinants of health had a negligible effect on gender differences. Further analyses showed that gender differences in illhealth remained largely stable over the eight year study period which saw a steep increase of unemployment for both genders. Only in the case of mental and somatic symptoms have gender differences declined, with a simultaneous increase in the prevalence of such symptoms. Otherwise gender differences in illhealth turned out to be resistant to the deep labour market crisis over this relatively short period of time. Although women had poorer health than men for a number of health indicators, we also find gender equality and even male excess for some indicators. Furthermore, the results suggest that a male excess in illhealth is likely to be found with more severe domains of illhealth among elderly people.     

European Confederation of Medical Mycology (ECMM) epidemiological survey on invasive infections due to Fusarium species in Europe

In order to better understand the epidemiology of fusariosis in Europe, a survey collecting information on the clinical characteristics of the patients infected by Fusarium as well as on the infecting isolates was launched. A total of 76 cases of invasive fusariosis occurring from January 2007 to June 2012 were collected and Fusarium isolates were identified by sequencing the translation elongation factor 1α (TEF) gene. Also, antifungal susceptibility was tested by broth microdilution according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the Etest. Disseminated disease was considered proven in 46 cases and probable in 17 cases. Localised infection was seen in 13 cases. Gibberella fujikuroi species complex (SC), including Fusarium verticillioides and F. proliferatum, and F. solani SC were the most frequent aetiology of disseminated and localised infections, respectively. The crude mortality rate was 46 %, the highest associated with F. solani SC (67 %) and F. proliferatum (62.5 %). A wide range of antifungal susceptibilities was observed. Amphotericin B was the most potent antifungal in vitro, and itraconazole the least effective. The azoles exhibited lower minimum inhibitory concentrations (MICs) against F. verticillioides strains, with posaconazole having a slightly better performance, while F. solani SC isolates were resistant to all three azoles tested. The essential agreement between the Etest and the EUCAST method was 100 % for itraconazole and voriconazole, and 96 % for amphotericin B and posaconazole. In conclusion, we confirm that fusariosis is a rare but severe event in Europe, that G. fujikuroi SC is the predominant cause of deep infections and that different species have different antifungal in vitro susceptibility patterns.     

Surgical Complications Associated with Arterial Catheterization

Objectives. Atherosclerosis is a systemic disease affecting several vessels of the body. Coronary artery patients requiring bypass surgery have increased prevalence of carotid artery atherosclerosis which is known to increase operative risk in coronary artery bypass surgery (CABG). Radial artery is often screened for grafting purposes preoperatively. Our aim was to find out whether atherosclerotic changes in forearm vessels are correlated and could reveal risk to carotid artery disease. Design. Eighty-five patients planned for elective CABG were examined with ultrasonography preoperatively. Biplane ultrasonographic scanning was performed on forearm arteries and both carotid arteries. Results. Eleven patients had pathologic changes in the wall of forearm vessels. Carotid artery disease was found on 19 patients. Forearm vessel pathology was found to have correlation to carotid artery disease. When forearm arteries show atherosclerotic pathology the risk of having carotid disease is at least five-fold, in subgroups even higher. Conclusions. Forearm arterial pathology is correlated to carotid artery disease. When forearm vessel pathology is evident in preoperative examination, scanning of the carotid vessels should be considered.     

The joint contribution of physical activity,insomnia symptoms,and smoking to the cost of short‐term sickness absence

Physical inactivity has been associated with both insomnia symptoms and smoking. Further, they are all independently associated with increased sickness absence (SA) from work. However, joint contribution of either physical activity (PA) with insomnia symptoms or with smoking to SA and, especially, their direct cost for the employer is poorly understood. Therefore, we aimed to examine these joint associations with short‐term (<15 days) SA cost. The Helsinki Health Study is a cohort of midlife employees of the City of Helsinki, Finland (baseline n = 8960, response rate 67%). During 2000‐2002, the participants were mailed a survey questionnaire that gathered information on health behavior and sociodemographic characteristics. SA, salary, and time of employment were followed up through the employer's personnel register between 2002 and 2016 for those with a written consent to the use of their register data (78% of the participants). Individual salary data were used to calculate the direct cost of short‐term SA. Data were analyzed with a two‐part model. Inactive participants with frequent insomnia symptoms had 2526€ (95% CI 1736€‐3915€) higher cost of short‐term SA than vigorously active participants without insomnia symptoms. Furthermore, inactive smokers had 4166€ (95% CI 2737€‐5595€) higher cost for the employer over the follow‐up than vigorously active non‐smokers. In conclusion, this study showed that PA and insomnia symptoms as well as PA and smoking are jointly associated with short‐term SA cost. The results emphasize encouraging employers to improve work environments so that they promote active lifestyle, good sleep, and non‐smoking in order to reduce the cost of SA.     

Rational excipient selection for co-amorphous formulations

Introduction: For almost two decades there has been intense debate about whether the amorphous solid state form could resolve the solubility problems and subsequent bioavailability issues of many small molecule drugs. Since the amorphous form is a high energy and unstable state of solid matter, any material in that form requires stabilization.

Areas covered: This review examines the technologies being exploited to stabilize the amorphous state in co-amorphous formulations. The review emphasizes the importance of the appropriate selection criteria of stabilizing excipient and focuses on the mechanisms of stabilization.

Expert opinion: An extensive literature review has revealed that the current research seeking to achieve stabilization of an amorphous form tends to be conducted on a case-by-case basis. This kind of approach is very inefficient since it can rarely be transferred to other cases. The greatest weakness in the selection of stabilizing excipient for co-amorphous formulations is that modern computational tools have rarely been utilized as a predictive tool in the selection of the excipient. It is evident that more research needs to be done to study larger datasets with modern in silico tools, chemometrics and advanced statistical tools to achieve a more predictive, and systematic approach for the screening of stabilizing excipients to be incorporated into co-amorphous formulations.