Role of Pht Proteins in Attachment of Streptococcus pneumoniae to Respiratory Epithelial Cells

Pneumococcal adherence to mucosal surfaces is a critical step in nasopharyngeal colonization, but so far few pneumococcal adhesins involved in the interaction with host cells have been identified. PhtA, PhtB, PhtD, and PhtE are conserved pneumococcal surface proteins that have proven promising as vaccine candidates. One suggested virulence function of Pht proteins is to mediate adherence at the respiratory mucosa. In this study, we assessed the role of Pht proteins in pneumococcal binding to respiratory epithelial cells. Pneumococci were incubated with human nasopharyngeal epithelial cells (Detroit-562) and lung epithelial cells (A549 and NCI-H292), and the proportion of bound bacteria was measured by plating viable counts. Strains R36A (unencapsulated), D39 (serotype 2), 43 (serotype 3), 4-CDC (serotype 4), and 2737 (serotype 19F) with one or more of the four homologous Pht proteins deleted were compared with their wild-type counterparts. Also, the effect of anti-PhtD antibodies on the adherence of strain 2737 to the respiratory epithelial cells was studied. Our results suggest that Pht proteins play a role in pneumococcal adhesion to the respiratory epithelium. We also found that antibody to PhtD is able to inhibit bacterial attachment to the cells, suggesting that antibodies against PhtD present at mucosal surfaces might protect from pneumococcal attachment and subsequent colonization. However, the relative significance of Pht proteins to the ability of pneumococci to bind in vitro to epithelial cells depends on the genetic background and the capsular serotype of the strain.     

White adipose tissue mitochondrial metabolism in health and in obesity

White adipose tissue is one of the largest organs of the body. It plays a key role in whole‐body energy status and metabolism; it not only stores excess energy but also secretes various hormones and metabolites to regulate body energy balance. Healthy adipose tissue capable of expanding is needed for metabolic well‐being and to prevent accumulation of triglycerides to other organs. Mitochondria govern several important functions in the adipose tissue. We review the derangements of mitochondrial function in white adipose tissue in the obese state. Downregulation of mitochondrial function or biogenesis in the white adipose tissue is a central driver for obesity‐associated metabolic diseases. Mitochondrial functions compromised in obesity include oxidative functions and renewal and enlargement of the adipose tissue through recruitment and differentiation of adipocyte progenitor cells. These changes adversely affect whole‐body metabolic health. Dysfunction of the white adipose tissue mitochondria in obesity has long‐term consequences for the metabolism of adipose tissue and the whole body. Understanding the pathways behind mitochondrial dysfunction may help reveal targets for pharmacological or nutritional interventions that enhance mitochondrial biogenesis or function in adipose tissue.     

Early seroconversion and rapidly increasing autoantibody concentrations predict prepubertal manifestation of type 1 diabetes in children at genetic risk

Aims/hypothesis  

The aim of the study was to investigate the timing of the appearance of autoantibodies associated with type 1 diabetes between birth and puberty, the natural fate of these autoantibodies and the predictive power of autoantibody concentrations for early progression to clinical diabetes.     

Salience network integrity predicts default mode network function after traumatic brain injury

Efficient behavior involves the coordinated activity of large-scale brain networks, but the way in which these networks interact is uncertain. One theory is that the salience network (SN)--which includes the anterior cingulate cortex, presupplementary motor area, and anterior insulae--regulates dynamic changes in other networks. If this is the case, then damage to the structural connectivity of the SN should disrupt the regulation of associated networks. To investigate this hypothesis, we studied a group of 57 patients with cognitive impairments following traumatic brain injury (TBI) and 25 control subjects using the stop-signal task. The pattern of brain activity associated with stop-signal task performance was studied by using functional MRI, and the structural integrity of network connections was quantified by using diffusion tensor imaging. Efficient inhibitory control was associated with rapid deactivation within parts of the default mode network (DMN), including the precuneus and posterior cingulate cortex. TBI patients showed a failure of DMN deactivation, which was associated with an impairment of inhibitory control. TBI frequently results in traumatic axonal injury, which can disconnect brain networks by damaging white matter tracts. The abnormality of DMN function was specifically predicted by the amount of white matter damage in the SN tract connecting the right anterior insulae to the presupplementary motor area and dorsal anterior cingulate cortex. The results provide evidence that structural integrity of the SN is necessary for the efficient regulation of activity in the DMN, and that a failure of this regulation leads to inefficient cognitive control.     

Intestinal bacterial translocation and tight junction structure in acute porcine pancreatitis

Background/Aims: To examine whether intestinal bacterial translocation occurs early in acute mild and severe pancreatitis and whether the intestinal expression of tight junction proteins (claudins-2, -3, -4, -5, -7), apoptosis or proliferation would explain the possible translocation. Methodology: Fifteen pigs were randomized to controls (n=5) or to develop mild edematous pancreatitis (n=5, saline infusion to pancreatic duct) or severe necrotic pancreatitis (n=5, taurocholic acid infusion). Translocation was studied by measuring bacterial cultures from portal vein blood and mesenteric lymph nodes. Immunohistochemical expression of the tight junction proteins, apoptosis rate (TUNEL) and Ki-67 were analyzed quantitatively from the epithelium of the jejunum and colon. Results: There was no bacterial translocation during the 6 hours followup, nor changes in the expression of tight junction proteins claudins-2 and -5 in jejunum or colon. Saturation and proportional area of claudin-3 staining decreased in the colon, as did claudins-4 and -7 staining in the jejunum of the necrotic pancreatitis group. Increased apoptosis was found in all samples from controls and the edematous pancreatitis group but not in jejunum in the necrotic pancreatitis group. Ki-67 activity tended to increase in the upper half of the villus in edematous and necrotic pancreatitis. There were no changes in the basic histology. Conclusions: The major finding of this study was that bacterial translocation from the gut is not present at the beginning of acute pancreatitis. Tight junction proteins claudin-2 and -5 do not become altered in the early stages of pancreatitis. Claudin-3 decreases in the colon and claudins-4 and -7 in the jejunum in necrotic pancreatitis. Laparotomy itself causes increased apoptosis in the colon and the jejunum.     

Association Between Symptoms of Temporomandibular Disorders and Depression: An Epidemiological Study of the Northern Finland 1966 Birth Cohort

Facial pain and other symptoms of temporomandibular disorders (TMD) are rather common in the adult population. According to clinical studies, psychological factors play an important role in the etiology and maintenance of these symptoms. On the other hand, chronic pain can cause depression. The aim of this study was to evaluate the association between symptoms of TMD and depression in a large population sample of young adults. The study was a part of the 31-year follow-up study of the Northern Finland Birth Cohort consisting of 12,058 live births from the year 1966. Questionnaire information concerning TMD symptoms was collected from a subsample of 5,696 subjects. Depression was measured with a question about reported depression (diagnosed by a doctor) and with the Symptom Checklist depression subscale (SCL-25 DS). Of the TMD symptoms, those related to pain had the most significant relations to indicators of depression. In both genders, the proportion of depression indicated with the SCL-25 DS was significantly higher in subjects with pain-related symptoms of TMD, i.e., facial pain and “pain at jaw rest”, and in men with “pain on jaw movement”, compared with non-pain subjects (p<0.05). Other symptoms of TMD also associated significantly with SCL-25 DS (p>0.05), except “difficulties in mouth opening” among women. Among women, the prevalence of recognized depression was also significantly higher in subjects with pain-related symptoms of TMD, compared with subjects with no pain (p≤0.05). Almost all the associations remained significant after adjusting for marital status, education, and self-rated general health. In conclusion, the results show that depression has an association with TMD symptoms, especially those related to pain. When treating patients with facial pain, dentists should consider the possible presence of psychopathology and, if necessary, consult appropriate mental health professionals.     

Association of Symptoms of TMD and Orofacial Pain with Alexithymia: An Epidemiological Study of the Northern Finland 1966 Birth Cohort

Alexithymia is a term denoting a deficit in the ability to differentiate emotional from physical states and to identify and describe one's feelings, as well as a preference for external oriented thinking. Alexithymia has been linked with various somatic and psychosomatic diseases, especially with chronic pain. The aim of this study was to evaluate the association between alexithymia and symptoms of temporomandibular disorders (TMD) as well as oro-lingual and dental pain, in a large representative population sample of young adults. The study was a part of the 31-year follow-up study of the Northern Finland Birth Cohort originally consisting of 12058 live births in the year 1966. In 1997, 4893 subjects living in northern Finland or in the capital area, who participated in a field study of the project and later returned a postal questionnaire, made up the sample of this study. Information concerning symptoms of TMD and oro-lingual and dental pain was collected from the subjects. To assess alexithymia, the Toronto Alexithymia Scale-20 (TAS-20) was used. In addition, information about depression, marital status and self-rated health was collected. The proportion of alexithymics (TAS score over 60) was higher in subjects with the most orofacial symptoms than in asymptomatic subjects. In men, alexithymia associated significantly with facial pain, difficulties in mouth opening, oro-lingual pain and dental pain, and in women with pain on jaw movement and dental pain. After adjusting for depression, marital status, and self-rated health, a significant association remained between alexithymia and the symptoms mentioned, except for facial pain in men. It can be concluded that alexithymia is connected with orofacial symptoms. Clinicians treating these symptoms should be familiar with the concept of alexithymia.