Randomised controlled trial of three burns dressings for partial thickness burns in children

BACKGROUND This study compared the effects of three silver dressing combinations on small to medium size acute partial thickness burns in children, focusing on re-epithelialization time, pain and distress during dressing changes. METHOD Children (0-15 years) with clean, ≤ 10% total body surface area (TBSA) partial thickness burns who met the inclusion criteria were included in the study. Children received either (1) Acticoat™; (2) Acticoat™ with Mepitel™; or (3) Mepilex Ag™ dressings. Measures of burn re-epithelialization, pain, and distress were recorded at dressing changes every 3-5 days until full re-epithelialization occurred. RESULTS One hundred and three children were recruited with 96 children included for analysis. No infections were detected for the course of the study. When adjusted for burn depth, Acticoat™ significantly increased the expected days to full re-epithelialization by 40% (IRR = 1.40; 95% CI: 1.14-1.73, p < 0.01) and Acticoat™ with Mepitel™ significantly increased the expected days to full re-epithelialization by 33% (IRR = 1.33; 95% CI: 1.08-1.63, p ≤ 0.01) when compared to Mepilex Ag™. Expected FLACC scores in the Mepilex Ag™ group were 32% lower at dressing removal (p = 0.01) and 37% lower at new dressing application (p = 0.04); and scores in the Acticoat™ with Mepitel™ group were 23% lower at dressing removal (p = 0.04) and 40% lower at new dressing application (p < 0.01), in comparison to the Acticoat™ group. Expected Visual Analog Scale-Pain (VAS-P) scores were 25% lower in the Mepilex Ag™ group at dressing removal (p = 0.04) and 34% lower in the Acticoat™ with Mepitel™ group (p = 0.02) at new dressing application in comparison to the Acticoat™ group. There was no significant difference between the Mepilex Ag™ and the Acticoat™ with Mepitel™ groups at all timepoints and with any pain measure. CONCLUSION Mepilex Ag™ is an effective silver dressing, in terms of accelerated wound re-epithelialization time (compared to Acticoat™ and Acticoat™ with Mepitel™) and decreased pain during dressing changes (compared to Acticoat™), for clean, < 10% TBSA partial thickness burns in children.

Which patients with chronic kidney disease have the greatest symptom burden? A comparative study of advanced CKD stage and dialysis modality

Background Chronic kidney disease (CKD) leads to a range of symptoms, which are often under-recognised and little is known about the multidimensional symptom experience in advanced CKD. Objectives To examine (1) symptom burden at CKD stages 4 and 5, and dialysis modalities, and (2) demographic and renal history correlates of symptom burden. Methods Using a cross-sectional design, a convenience sample of 436 people with CKD was recruited from three hospitals. The CKD Symptom Burden Index (CKD-SBI) was used to measure the prevalence, severity, distress and frequency of 32 symptoms. Demographic and renal history data were also collected. Results Of the sample, 75.5 % were receiving dialysis (haemodialysis, n = 287; peritoneal dialysis, n = 42) and 24.5 % were not undergoing dialysis (stage 4, n = 69; stage 5, n = 38). Participants reported an average of 13.01 ± 7.67 symptoms. Fatigue and pain were common and burdensome across all symptom dimensions. While approximately one-third experienced sexual symptoms, when reported these symptoms were frequent, severe and distressing. Haemodialysis, older age and being female were independently associated with greater symptom burden. Conclusions In CKD, symptom burden is better understood when capturing the multidimensional aspects of a range of physical and psychological symptoms. Fatigue, pain and sexual dysfunction are key contributors to symptom burden, and these symptoms are often under-recognised and warrant routine assessment. The CKD-SBI offers a valuable tool for renal clinicians to assess symptom burden, leading to the commencement of timely and appropriate interventions.

GPRA and the asthma locus on chromosome 7p14-p15

The basis of this work was the identification of a genomic region on chromosome 7p14-p15 that strongly associated with asthma and high serum total immunoglobulin E in a Finnish founder population from Kainuu. Using a hierarchical genotyping approach the linkage region was narrowed down until an evolutionary collectively inherited 133-kb haplotype block was discovered. The results were confirmed in two independent data sets: Asthma families from Quebec and allergy families from North-Karelia. In all the three cohorts studied, single nucleotide polymorphisms tagging seven common gene variants (haplotypes) were identified. Over half of the asthma patients carried three evolutionary closely related susceptibility haplotypes as opposed to approximately one third of the healthy controls. The risk effects of the gene variants varied from 1.4 to 2.5. In the disease-associated region, there was one protein-coding gene named GPRA (G Protein-coupled Receptor for Asthma susceptibility also known as NPSR1) which displayed extensive alternative splicing. Only the two isoforms with distinct intracellular tail sequences, GPRA-A and -B, encoded a full-length G protein-coupled receptor with seven transmembrane regions. Using various techniques, we showed that GPRA is expressed in multiple mucosal surfaces including epithelial cells throughout the respiratory tract. GPRA-A has additional expression in respiratory smooth muscle cells. However, in bronchial biopsies with unknown haplotypes, GPRA-B was upregulated in airways of all patient samples in contrast to the lack of expression in controls. Further support for GPRA as a common mediator of inflammation was obtained from a mouse model of ovalbumin-induced inflammation, where metacholine-induced airway hyperresponsiveness correlated with elevated GPRA mRNA levels in the lung and increased GPRA immunostaining in pulmonary macrophages. A novel GPRA agonist, Neuropeptide S (NPS), stimulated phagocytosis of Esterichia coli bacteria in a mouse macrophage cell line indicating a role for GPRA in the removal of inhaled allergens. The suggested GPRA functions prompted us to study, whether GPRA haplotypes associate with respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) in infants sharing clinical symptoms with asthma. According to the results, near-term RDS and asthma may also share the same susceptibility and protective GPRA haplotypes. As in asthma, GPRA-B isoform expression was induced in bronchial smooth muscle cells in RDS and BPD suggesting a role for GPRA in bronchial hyperresponsiveness. In conclusion, the results of the present study suggest that the dysregulation of the GPRA/NPS pathway may not only be limited to the individuals carrying the risk variants of the gene but is also involved in the regulation of immune functions of asthma.

Vocalizations of wild Asian elephants (Elephas maximus): Structural classification and social context

Elephants use vocalizations for both long and short distance communication. Whereas the acoustic repertoire of the African elephant (Loxodonta africana) has been extensively studied in its savannah habitat, very little is known about the structure and social context of the vocalizations of the Asian elephant (Elephas maximus), which is mostly found in forests. In this study, the vocal repertoire of wild Asian elephants in southern India was examined. The calls could be classified into four mutually exclusive categories, namely, trumpets, chirps, roars, and rumbles, based on quantitative analyses of their spectral and temporal features. One of the call types, the rumble, exhibited high structural diversity, particularly in the direction and extent of frequency modulation of calls. Juveniles produced three of the four call types, including trumpets, roars, and rumbles, in the context of play and distress. Adults produced trumpets and roars in the context of disturbance, aggression, and play. Chirps were typically produced in situations of confusion and alarm. Rumbles were used for contact calling within and among herds, by matriarchs to assemble the herd, in close-range social interactions, and during disturbance and aggression. Spectral and temporal features of the four call types were similar between Asian and African elephants.

A psychosocial analysis of parent's decisions for limiting their young child's screen time: An examination of attitudes, social norms and roles, and control perceptions

- Objectives Preschool-aged children spend substantial amounts of time engaged in screen-based activities. As parents have considerable control over their child's health behaviours during the younger years, it is important to understand those influences that guide parents' decisions about their child's screen time behaviours. - Design A prospective design with two waves of data collection, 1 week apart, was adopted. - Methods Parents (n = 207) completed a Theory of Planned Behaviour (TPB)-based questionnaire, with the addition of parental role construction (i.e., parents' expectations and beliefs of responsibility for their child's behaviour) and past behaviour. A number of underlying beliefs identified in a prior pilot study were also assessed. - Results The model explained 77% (with past behaviour accounting for 5%) of the variance in intention and 50% (with past behaviour accounting for 3%) of the variance in parental decisions to limit child screen time. Attitude, subjective norms, perceived behavioural control, parental role construction, and past behaviour predicted intentions, and intentions and past behaviour predicted follow-up behaviour. Underlying screen time beliefs (e.g., increased parental distress, pressure from friends, inconvenience) were also identified as guiding parents' decisions. - Conclusion Results support the TPB and highlight the importance of beliefs for understanding parental decisions for children's screen time behaviours, as well as the addition of parental role construction. This formative research provides necessary depth of understanding of sedentary lifestyle behaviours in young children which can be adopted in future interventions to test the efficacy of the TPB mechanisms in changing parental behaviour for their child's health.

Systemic Inflammation in Preterm Infants

Even though mortality among preterm infants has decreased, their risk for chronic complications such as bronchopulmonary dysplasia (BPD) and neurological disability remains significant. One common risk factor for these is exposure to inflammation. The fetus may be exposed prenatally during maternal chorioamnionitis. Pre-eclampsia is also associated with low-grade maternal inflammation. Postnatally, local and systemic inflammation is present during respiratory distress syndrome (RDS). Furthermore, septic infections in the preterm infant are an important source of inflammatory stimuli and can lead to death in only a few hours. The diagnosis of septic infection is difficult, since reliable diagnostic markers are unavailable. This thesis evaluates peri- and postnatal systemic inflammation in preterm infants in septic infections, in RDS treated with mechanical ventilation and surfactant treatment, and in preterm infants prenatally exposed to chorioamnionitis and pre-eclampsia. Surface expressions of the activation markers CD11b, CD54, and CD62L, determined by flow cytometry on circulating phagocytes and T lymphocytes, serve as indicators of systemic inflammation. The main findings: I) In preterm infants with developing late-onset sepsis and fulminant necrotizing enterocolitis, a significant increase in CD11b expression on circulating phagocytes is already present on the day of onset of clinical symptoms. II) In preterm infants with RDS, circulating phagocytes become activated within hours after start of mechanical ventilation. In preterm infants treated for RDS with nasal continuous positive airway pressure, no such activation occurs. III) In preterm infants, RDS is associated during the first days of life with fewer circulating helper and cytotoxic T lymphocytes, of which the greater proportions are activated. Even greater proportions of circulating T cells are activated in infants subsequently developing BPD. IV) In preterm infants born after maternal pre-eclampsia, RDS-associated phagocyte CD11b up-regulation is greater than in preterm infants not exposed to pre-eclampsia during the first week of life. These findings suggest that I) an increase in CD11b expression on circulating phagocytes can identify preterm infants with late-onset sepsis as early as at sampling for blood culture and may thus aid in the diagnosis. II) In preterm infants with RDS, initiation of mechanical ventilation, but not the use of nasal continuous positive airway pressure, promotes a systemic inflammatory reaction; exogenous surfactant does not seem to promote inflammation. III) In addition to activation of circulating cells of the innate immunity in preterm infants with RDS, the circulating cells of the adaptive immunity are activated. The activation of adaptive immunity may link acute inflammation and development of chronic inflammation-associated problems such as BPD. IV) Maternal pre-eclampsia may prime neonatal immunity to react more strongly to postnatal stimuli. In conclusion, the preterm infant is exposed to numerous potentially injurious events such as intrauterine inflammation, respiratory distress syndrome (RDS), and systemic infections, all evoking systemic inflammation. Due to ongoing development of the lung and the brain, this may, in addition to acute injury, lead to aberrant lung and brain development and to clinical syndromes of BPD and neurologic sequelae.

Balance of growth factors in the human perinatal lung : Implications for physiological lung development and link to bronchopulmonary dysplasia

The aims of this Thesis was to evaluate the role of proangiogenic placental growth factor (PlGF), antiangiogenic endostatin and lymphangiogenic vascular endothelial growth factor (VEGF) -C as well as the receptors vascular endothelial growth factor receptor (VEGFR) -2 and VEGFR-3 during lung development and in development of lung injury in preterm infants. The studied growth factors were selected due to a close relationship with VEGF-A; a proangiogenic growth factor important in normal lung angiogenesis and lung injury in preterm infants. The thesis study consists of three analyses. I: Lung samples from fetuses, preterm and term infants without lung injury, as well as preterm infants with acute and chronic lung injury were stained by immunohistochemistry for PlGF, endostatin, VEGF-C, VEGFR-2 and VEGFR-3. II: Tracheal aspirate fluid (TAF) was collected in the early postnatal period from a patient population consisting of 59 preterm infants, half developing bronchopulmonary dysplasia (BPD) and half without BPD. PlGF, endostatin and VEGF-C concentrations were measured by commercial enzyme-linked immunosorbent assay (ELISA). III: Cord plasma was collected from very low birth weight (VLBW) (n=92) and term (n=48) infants in conjuncture with birth and endostatin concentrations were measured by ELISA. I: All growth factors and receptors studied were consistently stained in immunohistochemistry throughout development. For endostatin in early respiratory distress syndrome (RDS), no alveolar epithelial or macrophage staining was seen, whereas in late RDS and BPD groups, both alveolar epithelium and macrophages stained positively in approximately half of the samples. VEGFR-2 staining was fairly consistent, except for the fact that capillary endothelial staining in the BPD group was significantly decreased. II: During the first postnatal week in TAF mean PlGF concentrations were stable whereas mean endostatin and VEGF-C concentrations decreased. Higher concentrations of endostatin and VEGF-C correlated with lower birth weight (BW) and associated with administration of antenatal betamethasone. Parameters reflecting prenatal lung inflammation associated with lower PlGF, endostatin and VEGF-C concentrations. A higher mean supplemental fraction of inspired oxygen during the first 2 postnatal weeks (FiO2) correlated with higher endostatin concentrations. III: Endostatin concentrations in term infants were significantly higher than in VLBW infants. In VLBW infants higher endostatin concentrations associated with the development of BPD, this association remained significant after logistic regression analysis. We conclude that PlGF, endostatin and VEGF-C all have a physiological role in the developing lung. Also, the VEGFR-2 expression profile seems to reflect the ongoing differentiation of endothelia during development. Both endostatin and VEGFR-2 seem to be important in the development of BPD. During the latter part of the first postnatal week, preterm infants developing BPD have lower concentrations of VEGF-A in TAF. Our findings of disrupted VEGFR-2 staining in capillary and septal endothelium seen in the BPD group, as well as the increase in endostatin concentrations both in TAF and cord plasma associated with BPD, seem to strengthen the notion that there is a shift in the angiogenic balance towards a more antiangiogenic environment in BPD. These findings support the vascular hypothesis of BPD.

Epithelial sodium channel in airway epithelium of the newborn infant : Implications for postnatal pulmonary adaptation

The aim of the present thesis was to study the role of the epithelial sodium channel (ENaC) in clearance of fetal lung fluid in the newborn infant by measurement of airway epithelial expression of ENaC, of nasal transepithelial potential difference (N-PD), and of lung compliance (LC). In addition, the effect of postnatal dexamethasone on airway epithelial ENaC expression was measured in preterm infants with bronchopulmonary dysplasia (BPD). The patient population was formed of selected term newborn infants born in the Department of Obstetrics (Studies II-IV) and selected preterm newborn infants treated in the neonatal intensive care unit of the Hospital for Children and Adolescents (Studies I and IV) of the Helsinki University Central Hospital in Finland. A small population of preterm infants suffering from BPD was included in Study I. Studies I, III, and IV included airway epithelial measurement of ENaC and in Studies II and III, measurement of N-PD and LC. In Study I, ENaC expression analyses were performed in the Research Institute of the Hospital for Sick Children in Toronto, Ontario, Canada. In the following studies, analyses were performed in the Scientific Laboratory of the Hospital for Children and Adolescents. N-PD and LC measurements were performed at bedside in these hospitals. In term newborn infants, the percentage of amiloride-sensitive N-PD, a surrogate for ENaC activity, measured during the first 4 postnatal hours correlates positively with LC measured 1 to 2 days postnatally. Preterm infants with BPD had, after a therapeutic dose of dexamethasone, higher airway epithelial ENaC expression than before treatment. These patients were subsequently weaned from mechanical ventilation, probably as a result of the clearance of extra fluid from the alveolar spaces. In addition, we found that in preterm infants ENaC expression increases with gestational age (GA). In preterm infants, ENaC expression in the airway epithelium was lower than in term newborn infants. During the early postnatal period in those born both preterm and term airway epithelial βENaC expression decreased significantly. Term newborn infants delivered vaginally had a significantly smaller airway epithelial expression of αENaC after the first postnatal day than did those delivered by cesarean section. The functional studies showed no difference in N-PD between infants delivered vaginally and by cesarean section. We therefore conclude that the low airway epithelial expression of ENaC in the preterm infant and the correlation of N-PD with LC in the term infant indicate a role for ENaC in the pathogenesis of perinatal pulmonary adaptation and neonatal respiratory distress. Because dexamethasone raised ENaC expression in preterm infants with BPD, and infants were subsequently weaned from ventilator therapy, we suggest that studies on the treatment of respiratory distress in the preterm infant should include the induction of ENaC activity.

Depressive Disorders in Primary Health Care

The Vantaa Primary Care Depression Study (PC-VDS) is a naturalistic and prospective cohort study concerning primary care patients with depressive disorders. It forms a collaborative research project between the Department of Mental and Alcohol Research of the National Public Health Institute, and the Primary Health Care Organization of the City of Vantaa. The aim is to obtain a comprehensive view on clinically significant depression in primary care, and to compare depressive patients in primary care and in secondary level psychiatric care in terms of clinical characteristics. Consecutive patients (N=1111) in three primary care health centres were screened for depression with the PRIME-MD, and positive cases interviewed by telephone. Cases with current depressive symptoms were diagnosed face-to-face with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I/P). A cohort of 137 patients with unipolar depressive disorders, comprising all patients with at least two depressive symptoms and clinically significant distress or disability, was recruited. The Structured Clinical Interview for DSM-IV Axis II Disorders (SCID-II), medical records, rating scales, interview and a retrospective life-chart were used to obtain comprehensive cross-sectional and retrospective longitudinal information. For investigation of suicidal behaviour the Scale for Suicidal Ideation (SSI), patient records and the interview were used. The methodology was designed to be comparable to The Vantaa Depression Study (VDS) conducted in secondary level psychiatric care. Comparison of major depressive disorder (MDD) patients aged 20-59 from primary care in PC-VDS (N=79) was conducted with new psychiatric outpatients (N =223) and inpatients (N =46) in VDS. The PC-VDS cohort was prospectively followed up at 3, 6 and 18 months. Altogether 123 patients (90%) completed the follow-up. Duration of the index episode and the timing of relapses or recurrences were examined using a life-chart. The retrospective investigation revealed current MDD in most (66%), and lifetime MDD in nearly all (90%) cases of clinically significant depressive syndromes. Two thirds of the “subsyndromal” cases had a history of major depressive episode (MDE), although they were currently either in partial remission or a potential prodromal phase. Recurrences and chronicity were common. The picture of depression was complicated by Axis I co-morbidity in 59%, Axis II in 52% and chronic Axis III disorders in 47%; only 12% had no co-morbidity. Within their lifetimes, one third (37%) had seriously considered suicide, and one sixth (17%) had attempted it. Suicidal behaviour clustered in patients with moderate to severe MDD, co-morbidity with personality disorders, and a history of treatment in psychiatric care. The majority had received treatment for depression, but suicidal ideation had mostly remained unrecognised. The comparison of patients with MDD in primary care to those in psychiatric care revealed that the majority of suicidal or psychotic patients were receiving psychiatric treatment, and the patients with the most severe symptoms and functional limitations were hospitalized. In other clinical aspects, patients with MDD in primary care were surprisingly similar to psychiatric outpatients. Mental health contacts earlier in the current MDE were common among primary care patients. The 18-month prospective investigation with a life-chart methodology verified the chronic and recurrent nature of depression in primary care. Only one-quarter of patients with MDD achieved and maintained full remission during the follow-up, while another quarter failed to remit at all. The remaining patients suffered either from residual symptoms or recurrences. While severity of depression was the strongest predictor of recovery, presence of co-morbid substance use disorders, chronic medical illness and cluster C personality disorders all contributed to an adverse outcome. In clinical decision making, beside severity of depression and co-morbidity, history of previous MDD should not be ignored by primary care doctors while depression there is usually severe enough to indicate at least follow-up, and concerning those with residual symptoms, evaluation of their current treatment. Moreover, recognition of suicidal behaviour among depressed patients should also be improved. In order to improve outcome of depression in primary care, the often chronic and recurrent nature of depression should be taken into account in organizing the care. According to literature management programs of a chronic disease, with enhancement of the role of case managers and greater integration of primary and specialist care, have been successful. Optimum ways of allocating resources between treatment providers as well as within health centres should be found.

Specific language impairment in pre-adolescence, adolescence, and adulthood with special emphasis on health-related quality of life

This clinical study focused on effects of childhood specific language impairment (SLI) on daily functioning in late life. SLI is a neurobiological disorder with genetic predisposition and manifests as poor language production or comprehension or both in a child with age-level non-verbal intelligence and no other known cause for deficient language development. The prevalence rate of around 7% puts it among the most prevalent developmental disorders in childhood. Negative long-term effects, such as problems in learning and behavior, are frequent. In follow-up studies the focus has seldom been on self-perception of daily functioning and participation, which are considered important in the International Classification of Functioning, Disability, and Health (ICF). To investigate the self-perceived aspects of everyday functioning in individuals with childhood receptive SLI compared with age- and gender-matched control populations, the 15D, 16D, and 17D health-related quality of life (HRQoL) questionnaires were applied. These generic questionnaires include 15, 16, and 17 dimensions, respectively, and give both a single index score and a profile with values on each dimension. Information on different life domains (rehabilitation, education, employment etc.) from each age-group was collected with separate questionnaires. The study groups comprised adults, adolescents (12-16 years), and pre-adolescents (8-11 years) who had received a diagnosis of receptive SLI and had been examined, usually before school age, at the Department of Phoniatrics of Helsinki University Central Hospital, where children with language deficits caused by various etiologies are examined and treated by a multidisciplinary team. The adult respondents included 33 subjects with a mean age of 34 years. Measured with 15D, the subjects perceived their HRQoL to be nearly as good as that of their controls, but on the dimensions of speech, usual activities, mental functioning, and distress they were significantly worse off. They significantly more often lived with their parents (19%) or were pensioned (26%) than the adult Finnish population on average. Adults with self-perceived problems in finding words and in remembering instructions, manifestations of persistent language impairment, showed inferior every day functioning to the rest of the study group. Of the adolescents and pre-adolescents, 48 and 51, respectively, responded. The majority in both groups had received special education or extra educational support at school. They all had attended speech therapy at some point; at the time of the study only one adolescent, but every third pre-adolescent still received speech therapy. The 16D score of the adolescent or the 17D score of the pre-adolescents did not differ from that of their controls. The 16D profiles differed on some dimensions; subjects were significantly worse off on the dimension of mental functioning, but better off on the dimension of vitality than controls. Of the 17D dimensions, the study group was significantly worse off on speech, whereas the control group reported significantly more problems in sleeping. Of the childhood performance measures investigated, low verbal intelligence quotient (VIQ), which is often considered to reflect receptive language impairment, was in adults subjects significantly associated with some of the self-perceived problems, such as problems in usual activities and mental functioning. The 15D, 16D, and 17D questionnaires served well in measuring self-perceived HRQoL. Such standardized measures with population values are especially important in confirming with the ICF guidelines. In the future these questionnaires could perhaps be used on a more individual level in follow-up of children in clinics, and even in special schools and classes, to detect those children at greatest risk of negative long-term effects and perhaps diminished well-being regarding daily functioning and participation.

Induced swelling of kaolinitic soil in alkali solution

Unexpected swelling induced in foundation soils can cause distress to structures founded on them. In this paper, the swelling of kaolinitic soils due to interaction with alkali solution has been reported. The induced swelling is attributed to the formation of new minerals, which has been confirmed by X-ray diffraction patters and SEM studies. To understand the effect of alkali concentration and duration of interaction, two series of consolidation experiments have been carried out. In series 1, the specimen were remoulded with water and inundated with alkali solutions and in series 2, the specimen were remoulded and inundated with same alkali solutions. A steep compression during loading cycle and no abnormal swelling during unloading cycle has been noticed for the specimen remoulded with water and inundated with 1 N NaOH solutions. The steep compression is due to the segregation or break down of clay minerals due to alkali interactions. In case of specimen inundated with 4 N NaOH solutions, abnormal swelling has been observed during unloading cycle of the consolidation test. New minerals are formed on interaction of soil with 4 N solution as confirmed by X-ray diffraction patterns. These minerals are known to have very fine pores and possess high water holding capacity. The differences in the amount of swelling of samples remoulded with water and remoulded with alkali solution are due to variations in the concentration of alkali and duration of interaction.

Matrix proteinases in lung injury in the preterm infant

During inflammation, excess production and release of matrix proteinases, including matrix metalloproteinases (MMPs) and serine proteinases, may result in dysregulated extracellular proteolysis leading to development of tissue damage. Pulmonary inflammation may play an important role in the pathogenesis of lung injury in the preterm infant. The aims of this study were to evaluate involvement of MMPs and serine proteinase trypsin in acute and chronic lung injury in preterm infants and to study the role of these enzymes in acute lung injury by means of an animal model of hyperoxic lung injury. Molecular forms and levels of MMP-2, -8, and -9, and their specific inhibitor, tissue inhibitor of metalloproteinases (TIMP)-2, as well as trypsin were studied in tracheal aspirate fluid (TAF) samples collected from preterm infants with respiratory distress. Expression and distribution of trypsin-2 and proteinase-activated receptor 2 (PAR2) was examined in autopsy lung specimens from fetuses, from preterm infants with respiratory distress syndrome (RDS) or bronchopulmonary dysplasia (BPD), and from newborn infants without lung injury. We detected higher MMP-8 and trypsin-2 and lower TIMP-2 in TAF from preterm infants with more severe acute respiratory distress. Infants subsequently developing BPD had higher levels of MMP-8 and trypsin-2 early postnatally than did those who survived without this chronic lung injury. Immunohistochemically, trypsin-2 was mainly detectable in bronchial epithelium, but also in alveolar epithelium, and its expression was strongest in prolonged RDS. Since trypsin-2 is potent activator of PAR2, a G-protein coupled receptor involved in inflammation, we studied PAR2 expression in the lung. PAR2 co-localized with trypsin-2 in bronchoalveolar epithelium and its expression was significantly higher in bronchoalveolar epithelium in preterm infants with prolonged RDS than in newborn controls. In the experimental study, rats were exposed to >95% oxygen for 24, 48, and 60 hours, or room air. At 48 hours of hyperoxia, MMP-8 and trypsin levels sharply increased in bronchoalveolar lavage fluid, and expression of trypsin appeared in alveolar epithelium, and MMP-8 predominantly in macrophages. In conclusion, high pulmonary MMP-8 and trypsin-2 early postnatally are associated with severity of acute lung injury and subsequent development of BPD in preterm infants. In the injured preterm lung, trypsin-2 co-localizes with PAR2 in bronchoalveolar epithelium, suggesting that PAR2 activated by high levels of trypsin-2 is involved in lung inflammation associated with development of BPD. Marked increase in MMP-8 and trypsin early in the course of experimental hyperoxic lung injury suggests that these enzymes play a role in the pathogenesis of acute lung injury. Further exploration of the roles of trypsin and MMP-8 in lung injury may offer new targets for therapeutic intervention.

Impact of chemotherapy on cancer-related fatigue and cytokines in 1312 patients: A systematic review of quantitative studies

Purpose of review: Cancer-related fatigue (CRF) is the most common psychosomatic distress experienced by cancer patients before, during and after chemotherapy. Its impact on functional status and Health Related Quality of Life is a great concern among patients, healthcare professionals and researchers. The primary objective of this systematic review is to determine whether the different chemotherapies affect the association of CRF with individual pro- and anti-inflammatory cytokines. The PRISMA statement guideline has been followed to systematically search and screen article from PubMed and Embase. Recent findings: This review has examined 14 studies which included a total of 1312 patients. These studies assayed 20 different kinds of cytokines. The cytokines interleukin-6, interleukin-1RA, TGF-[beta] and sTNF-R2 were associated with CRF in patients receiving anthracycline-based chemotherapy. However, only interleukin-13 was identified in the taxane-based chemotherapy. Similarly, different sets of cytokines were linked with CRF in patients with chemotherapy regimens containing platinum, cyclophosphamides, topotecan or bleomycin. Summary: This review has identified that cytokines are differentially linked with CRF according to the various types of chemotherapy regimens.

Law student lifestyle pressures

One significant factor influencing student wellbeing is the degree to which their studies are subject to external lifestyle pressures. These pressures are relieved or exacerbated by choices students make around their approaches to study, and the amount of time they devote to work and leisure. This Chapter considers results from a 2012 survey of law students at the University of New South Wales (UNSW), Sydney, Australia. Those results are compared to results from a similar US law student survey, and comparable data from the UK and Australia more broadly. In addition, the UNSW study compares key lifestyle choices of undergraduate (LLB) and graduate (JD) law students. The significance of the analysis in this Chapter for understanding law students’ wellbeing is that comparing American and Australian law students’ lifestyle patterns provides insights into contextual variation between both groups, which is important to bear in mind when comparing American and Australian research on law students’ wellbeing, and appreciating the limits of such comparisons. In particular, much of the wellbeing literature to date has focused on course-based stressors, but in light of recent research indicating that improvements in students’ course-based experiences may not have a direct effect on law students’ elevated levels of psychological distress, it is important to understand the broader life pressures and stressors that may be impacting law students’ wellbeing.

“Well this is it. Just get on with it”: Pain willingness and activity engagement in people with chronic pain

Pain is recognised as a problem of significant concern worldwide and in the latest Global Burden of Disease Study, low back pain was identified as the biggest contributor worldwide to Years Lived with Disability. There is evidence to suggest that people who accept their chronic pain have a higher quality of life, lower levels of disability and distress, and function better emotionally, socially and physically. Findings on the specific pathways linking pain acceptance to quality of life outcomes are less clear. the two widely accepted pain acceptance factors, pain willingness and activity engagement, have not been well explored in qualitative studies on acceptance of chronic pain. To address this deficit in the literature, the current study has two related aims: 1) to explore pain willingness and activity engagement in the lives of people with chronic pain, and ; 2) to find out what people believe helps them to successfully get on with life in spite of chronic pain.