Neonates colonized with pathogenic bacteria in the airways have a low-grade systemic inflammation.

BACKGROUND AND OBJECTIVES: The development of childhood asthma is associated with neonatal colonization with pathogenic bacteria in hypopharynx. Furthermore, established asthma is associated with systemic low-grade inflammation. We here report on the association between neonatal colonization with pathogenic bacteria in hypopharynx and the development of systemic low-grade inflammation. METHODS: Bacterial colonization of the hypopharynx with Moraxella catharralis, Haemophilus influenzae, and/or Streptococcus pneumoniae was assessed in asymptomatic children from the Copenhagen Prospective Studies on Asthma in Childhood2000 (COPSAC2000 ) cohort at age 1 month by culturing technique (N = 238) and by quantitative polymerase chain reaction (qPCR) technique (N = 249) and in the COPSAC2010 cohort by culturing at age 1 month (N = 622) and again at age 3 months (N = 613). Systemic low-grade inflammation was determined in both cohorts at age 6 months by measuring plasma levels of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (lL-6). RESULTS: In both cohorts, bacterial colonization was associated with increased levels of hs-CRP: COPSAC2000 , 1 month culturing (geometric mean ratio of colonized/noncolonized [95% CI]), 1.39 [0.97-2.01], P = .08; 1 month qPCR, 1.55 [1.14-2.10], P < .01; COPSAC2010 , 1 month, 1.52 [1.23-1.87], P < .01; and 3 month, 1.57 [1.30-1.90], P < .01. A multiparametric principal component analysis incorporating hs-CRP, TNF-α, and IL-6 confirmed a systemic inflammatory profile in children colonized with M. catharralis, H. influenzae. and/or S. pneumoniae in the hypopharynx compared to noncolonized children (P-values < .05). CONCLUSION: The composition of the upper airway microbiome in early life may cause systemic low-grade inflammation.

Patients experiences of patient education on psychiatric inpatient wards; a systematic review.

OBJECTIVE: To synthesize the evidence on how patients with serious mental disorders perceived patient education on psychiatric wards and to learn more about the patient perceived benefits and limitations related to patient education and how well patient education meets the perceived needs of inpatients. METHODS: Quantitative and qualitative data were categorized and synthesized. A systematic literature search was conducted. Articles were validated using validated critical appraisal tools. Data were analyzed using inductive content analysis. RESULTS: Five articles met the inclusion criteria. The results concerned the specific population with bipolar disorder or schizophrenia. Two explanatory syntheses were aggregated: (I) Benefits and perceived barriers to receiving education and (II) Educational needs of mental health patients. Patients reported mechanical information dissemination and lack of individual and corporative discussions. Patients preferred patient education from different educational sources with respect to individual needs. CONCLUSION: Patient education were most useful when it could be tailored to an individuals specific needs and match patient preference for how to receive it. The findings did not provide evidence to support any educational methods of preference. PRACTICE IMPLICATIONS: The findings may contribute to the development of educational interventions that are perceived more helpful for in-patients suffering from serious mental disorders.

Wake and light therapy for moderate-to-severe depression - a randomized controlled trial.

OBJECTIVE: To examine the efficacy of using wake and light therapy as a supplement to standard treatment of hospitalized patients with depression. METHOD: In this randomized, controlled study, 64 patients with moderate-to-severe depression were allocated to standard treatment or to the intervention, which additionally consisted of three wake therapy sessions in one week, 30-min daily light treatment and sleep time stabilization over the entire nine-week study period. RESULTS: Patients in the wake therapy group had a significant decrease in depressive symptoms in week one as measured by HAM-D17 , 17.39 (CI 15.6-19.2) vs. 20.19 (CI 18.3-22.09) (P = 0.04), whereas no statistically significant differences were found between the groups in weeks two to nine. At week nine, the wake therapy group had a significantly larger increase in general self-efficacy (P = 0.001), and waking up during nights was a significantly less frequent problem (1.9 times vs. 3.2) (P = 0.0008). In most weeks, significantly fewer patients in the wake therapy group slept during the daytime, and if they slept, their naps were shorter (week three: 66 min vs. 117 min P = 0.02). CONCLUSION: The antidepressant effect initially achieved could not be maintained during the nine-week study period. However, sleep and general self-efficacy improved.

Divergent response profile in activated cord blood T cells from first-born child implies birth-order-associated in utero immune programming.

BACKGROUND: First-born children are at higher risk of developing a range of immune-mediated diseases. The underlying mechanism of 'birth-order effects' on disease risk is largely unknown, but in utero programming of the child's immune system may play a role. OBJECTIVE: We studied the association between birth order and the functional response of stimulated cord blood T cells. METHOD: Purified cord blood T cells were polyclonally activated with anti-CD3-/anti-CD28-coated beads in a subgroup of 28 children enrolled in the COPSAC2010 birth cohort. Expression levels of seven activation markers on helper and cytotoxic T cells as well as the percentage of CD4(+) CD25(+) T cells were assessed by flow cytometry. Production of IFN-γ, TNF-α, IL-17, IL-4, IL-5, IL-13, and IL-10 was measured in the supernatants. RESULTS: IL-10 secretion (P = 0.007) and CD25 expression on CD4(+) helper T cells (P = 0.0003) in the activated cord blood T cells were selectively reduced in first-born children, while the percentage of circulating CD4(+) CD25(+) cord blood T cells was independent of birth order. CONCLUSION: First-born infants display a reduced anti-inflammatory profile in T cells at birth. This possible in utero 'birth-order' T-cell programming may contribute to later development of immune-mediated diseases by increasing overall immune reactivity in first-born children as compared to younger siblings.

Quantitative estimates of vascularity in solid tumors by non-invasive near-infrared spectroscopy.

We examined the relationship between non-invasive estimates of the tumor hemoglobin concentration by near-infrared spectroscopy (NIRS) and histological scores of tumor vascularity by Chalkley counts in seven tumor lines in nude mice [malignant gliomas: U87, U118, U373; small cell lung cancers (SCLC): 54A, 54B, DMS79; prostate cancer: MatLyLu (MLL)]. We also evaluated the effect of continuous anti-angiogenic treatment with TNP-470 on tumor hemoglobin concentration and tumor vascularity in U87 and MLL tumors. Non-invasive NIRS recordings were performed with a custom-built flash near-infrared spectrometer using light guide-coupled reflectance measurements at 800+/-10 nm. Chalkley counts were obtained from CD31-immunostained cryosections. The NIRS recordings in arbitrary absorbance units increased with tumor size in the individual tumors until a plateau was reached at approximately 150 mm(3). This plateau was relatively tumor line-specific. NIRS recordings at the plateau phase were strongly correlated (P<.001, n=71) to the histological vessel score (Chalkley count) of the same individual tumors excised immediately after the NIRS was performed. Non-invasive NIRS recordings of the highly vascularized gliomas (U87, U118, and U373) plus the MatLyLu tumor line were significantly higher than the three less vascularized SCLC tumor lines (P<.001). Continuous treatment with the anti-angiogenic compound TNP-470, an endothelial cell inhibitor, significantly retarded tumor growth in both U87 and MLL tumors, but all tumors eventually grew. When comparing treated and untreated tumors of similar size, both NIRS recordings and Chalkley counts were significantly lower in TNP-470-treated tumors (P<.05). In conclusion, the NIRS technique provides a non-invasive measure of the degree of vascularization in untreated tumors and the NIRS technique can measure modifications in tumor vascularization by anti-angiogenic therapy.

Quantitative estimates of angiogenic and anti-angiogenic activity by laser Doppler flowmetry (LDF) and near infra-red spectroscopy (NIRS).

The use of laser Doppler flowmetry (LDF) and near-infra-red spectroscopy (NIRS) for non-invasive in vivo measurements of angiogenic and anti-angiogenic activity in nude mice was evaluated. Angiogenic foci were induced in the skin by implantation of slow release pellets containing 200 ng basic fibroblast growth factor (bFGF). LDF and NIRS recordings from induced foci were significantly higher than placebo implants (P<0.05) and controls (P<0.001), proving that LDF and NIRS provide measures of angiogenic activity. Correspondingly, by these methods, an anti-angiogenic activity was significantly demonstrated in bFGF-stimulated animals treated with either the specific anti-angiogenic compound TNP-470 (P<0.05) or the anti-inflammatory agent dexamethasone (P<0.001). We conclude that LDF and NIRS, alone or in combination, are useful non-invasive tools for early evaluation of angiogenic and anti-angiogenic activity in vivo.

Time until initiation of tumor growth is an effective measure of the anti-angiogenic effect of TNP-470 on human glioblastoma in nude mice.

We examined the effect of the anti-angiogenic compound TNP-470 on early tumor growth characteristics following subcutaneous implantation of 1 mm3 tissue blocks of human glioblastoma U87, in nude mice. The mice received daily injections with TNP-470, 7 mg/kg, from one day before until either 3, 7, 11, or 15 days after inoculation. The time from inoculation until initiation of exponential tumor growth was determined along with the post-therapeutic growth delay and the initial tumor doubling time (TD) for each individual tumor (n=103) on the basis of tumor volume growth curves. We found that: i) the onset of growth of U87 xenografts was effectively inhibited by concurrent treatment with TNP-470 beyond the first three days after inoculation, ii) this effect was fully reversible upon termination of therapy, and iii) the post-therapeutic growth delay was independent of the accumulated dose. These findings demonstrate that the in vivo effect of TNP-470 on tumor growth is tumor inhibitory rather than cytotoxic. The lack of effect of the anti-angiogenic compound, TNP-470, in the early 3-day schedule is consistent with the existence of an early avascular phase which precede the angiogenesis-dependent tumor growth.

Cuticular proteins from the lobster, Homarus americanus.

The urea-extractable proteins from calcified regions of intermoult cuticle of the lobster, Homarus americanus, have been separated by two-dimensional electrophoresis, showing that the extracts contain a large number of proteins. The major proteins have isoelectric points between 4 and 9, and their apparent molecular weights are between 5 and 30 kDa. Two of the proteins have been purified by a combination of ion-exchange chromatography, gel-filtration and RP-HPLC, and their complete amino acid sequences were determined by a combination of mass spectrometry and automated Edman degradation. Although they were purified from a single animal, both proteins were obtained as two isoforms. The isoforms of the smaller protein (HaCP4.6) differed only in a single position (phenylalanine/isoleucine), and the isoforms of the larger protein (HaCP11.6) differed in two positions (valine/isoleucine and glutamine/lysine). HaCP11.6 is N-terminally blocked by a pyroglutamate residue. Variants of an 18-residue motif are a characteristic feature of both sequences: it occurs twice in HaCP4.6 and four times in HaCP11.6. Comparison of the sequence to sequences published for cuticular proteins from other arthropods shows that the repeated motif is also present in proteins from the exoskeleton of the Bermuda land crab, Gecarcinus lateralis, but not in the single shrimp protein (Pandalus borealis) sequenced so far. The amino acid compositions of the lobster proteins are similar to that of flexible cuticles in locusts, but no convincing sequence similarities were found between the lobster proteins and cuticular proteins from locusts or other insects.