Fighting vessel dysmorphia to improve glioma chemotherapy

High-grade gliomas are aggressive and abundantly vascular tumors, and as in most cancer types, blood vessels in advanced lesions are highly abnormal. Poor perfusion and vascular leakage in tumor tissue resulting in hypoxia, necrosis, and high interstitial fluid pressure can hamper the efficient delivery of chemotherapy. Tumor angiogenesis is known to be supported by host leukocytes recruited to the tumor microenvironment, but the mechanisms leading to dysfunctional vascular network formation are incompletely understood. In this issue of EMBO Molecular Medicine, Mathivet et al (2017) present an elegant study, where longitudinal intravital imaging gives new insight on how recruitment and polarization of tumor-associated macrophages regulate aberrant angiogenesis in experimental gliomas. They show that macrophage targeting results in vessel normalization and improved chemotherapy response, suggesting that the combination of these therapeutic modalities could improve the outcome of glioma treatment in the clinic.Non peer reviewe

Prevention of low back pain: effect, cost-effectiveness, and cost-utility of maintenance care - study protocol for a randomized clinical trial

BACKGROUND: Low back pain (LBP) is a prevalent condition and a socioeconomic problem in many countries. Due to its recurrent nature, the prevention of further episodes (secondary prevention), seems logical. Furthermore, when the condition is persistent, the minimization of symptoms and prevention of deterioration (tertiary prevention), is equally important. Research has largely focused on treatment methods for symptomatic episodes, and little is known about preventive treatment strategies. METHODS/DESIGN: This study protocol describes a randomized controlled clinical trial in a multicenter setting investigating the effect and cost-effectiveness of preventive manual care (chiropractic maintenance care) in a population of patients with recurrent or persistent LBP. Four hundred consecutive study subjects with recurrent or persistent LBP will be recruited from chiropractic clinics in Sweden. The primary outcome is the number of days with bothersome pain over 12 months. Secondary measures are self-rated health (EQ-5D), function (the Roland Morris Disability Questionnaire), psychological profile (the Multidimensional Pain Inventory), pain intensity (the Numeric Rating Scale), and work absence. The primary utility measure of the study is quality-adjusted life years and will be calculated using the EQ-5D questionnaire. Direct medical costs as well as indirect costs will be considered. Subjects are randomly allocated into two treatment arms: 1) Symptom-guided treatment (patient controlled), receiving care when patients feel a need. 2) Preventive treatment (clinician controlled), receiving care on a regular basis. Eligibility screening takes place in two phases: first, when assessing the primary inclusion/exclusion criteria, and then to only include fast responders, i.e., subjects who respond well to initial treatment. Data are collected at baseline and at follow-up as well as weekly, using SMS text messages. DISCUSSION: This study investigates a manual strategy (chiropractic maintenance care) for recurrent and persistent LBP and aims to answer questions regarding the effect and cost-effectiveness of this preventive approach. Strict inclusion criteria should ensure a suitable target group and the use of frequent data collection should provide an accurate outcome measurement. The study utilizes normal clinical procedures, which should aid the transferability of the results. TRIAL REGISTRATION: Clinical trials.gov; NCT01539863, February 22, 2012. The first patient was randomized into the study on April 13th 2012

Spatio-temporal Models of Lymphangiogenesis in Wound Healing

Several studies suggest that one possible cause of impaired wound healing is failed or insufficient lymphangiogenesis, that is the formation of new lymphatic capillaries. Although many mathematical models have been developed to describe the formation of blood capillaries (angiogenesis), very few have been proposed for the regeneration of the lymphatic network. Lymphangiogenesis is a markedly different process from angiogenesis, occurring at different times and in response to different chemical stimuli. Two main hypotheses have been proposed: 1) lymphatic capillaries sprout from existing interrupted ones at the edge of the wound in analogy to the blood angiogenesis case; 2) lymphatic endothelial cells first pool in the wound region following the lymph flow and then, once sufficiently populated, start to form a network. Here we present two PDE models describing lymphangiogenesis according to these two different hypotheses. Further, we include the effect of advection due to interstitial flow and lymph flow coming from open capillaries. The variables represent different cell densities and growth factor concentrations, and where possible the parameters are estimated from biological data. The models are then solved numerically and the results are compared with the available biological literature.Comment: 29 pages, 9 Figures, 6 Tables (39 figure files in total

Quality of care and access to care at birth in low- and middle-income countries

Over two million newborns die at birth or during their first week of life every year. The majority of early neonatal deaths occur in low- and middle-income countries (LMICs) and could be prevented with high-quality care at birth. This thesis studied quality of care and geographic and socioeconomic inequalities in access to care at birth in LMICs. Furthermore, the aim was to elucidate whether birth in a facility improves newborn survival. Quality of emergency obstetric and newborn care, routine care and non-medical care were studied through a health facility assessment in seven districts of Brong Ahafo region in Ghana. Clinical vignettes were used to assess competence of health professionals in managing obstetric emergencies. The effects of two distal determinants (distance to a health facility and socioeconomic inequalities) on early neonatal mortality and on facility delivery were studied; Distance effects were studied using Demographic and Health Survey (DHS) data from rural Malawi and Zambia and Health Facility Census data from both countries. Socioeconomic inequalities were quantified using DHS data on 679,818 live births from 72 LMICs. Hospitals and large health centres provided the highest quality of care, managed the most patients and employed the most competent staff among the 64 delivery facilities in Brong Ahafo region. Quality of care was poor in the smallest facilities. Although coverage of facility delivery was fairly high at 68%, coverage of high-quality care was only 18%. Lack of health provider competence limited emergency care more than shortages of necessary drugs and equipment for management of these emergencies. Although distance to a health facility was a strong barrier to delivery care in rural Malawi and Zambia, proximity to a delivery facility was not associated with lower early neonatal mortality. Similarly, while socioeconomic inequalities in coverage of delivery care were found to be large in the 72 countries studied, inequalities in early neonatal mortality by wealth and education were small in most countries and compared with inequalities in facility delivery and postneonatal infant mortality. The findings of this thesis point to insufficient quality of care at birth in the seven districts of Brong Ahafo region in Ghana, in Malawi and Zambia and in many DHS countries. Early neonatal mortality remains a global health problem that has not been solved by increasing coverage with institutional deliveries. Improving quality of care should be prioritised in the future.Maailmassa kuolee vuosittain yli kaksi miljoonaa lasta synnytyksen tai ensimmäisen elinviikon aikana. Kuolleisuus on suurinta matalan tulotason ja keskitulotason maissa Afrikassa ja Aasiassa. Suurin osa varhaisen vastasyntyneisyyskauden kuolemista voitaisiin kuitenkin estää, jos synnytyksen hoito olisi korkealaatuista. Väitöskirjassa tutkittiin synnytyksen hoidon laatua ja saatavuutta 64 synnytyssairaalassa Brong Ahafon alueella Ghanassa, Malawissa ja Sambiassa sekä laajassa 72 matalan ja keskitulotason maata kattavassa analyysissä, jossa oli mukana yhteensä 679 818 syntymää. Väitöskirjassa verrattiin sosioekonomisia ja maantieteellisiä eroja hoidon saatavuudessa ja varhaisessa vastasyntyneisyyskuolleisuudessa. Tavoitteena oli arvioida, pelastaako synnytyksen hoito synnytyssairaalassa vastasyntyneiden henkiä. Synnytysten hoidon laatu oli matala kaikilla hoidon neljällä osa-alueella eli perushoidossa, synnyttäjän ja vastasyntyneen hätätilanteiden hoidossa sekä ei-lääketieteellisessä hoidossa Brong Ahafon alueella. Lääkärit, kätilöt ja sairaanhoitajat saivat korkeammat pisteet hätätilanteiden hoidon osaamista kartoittavissa potilastapauksissa kuin pienissä sairaaloissa työskentelevät henkilöt. Puutteet henkilökunnan osaamisessa saattoivatkin rajoittaa hätätilanteiden hoitoa enemmän kuin puutteet hoitovälineiden tai lääkkeiden saatavuudessa. Lyhyt maantieteellinen etäisyys kotoa synnytyssairaalaan lisäsi laitossynnytyksen todennäköisyyttä Malawissa ja Sambiassa. Lyhyempi etäisyys ei kuitenkaan vähentänyt varhaista vastasyntyneisyyskuolleisuutta. Analyysit koskien 72 matalan tulotason ja keskitulotason maata osoittivat, että sosioekonomiset erot vastasyntyneisyyskuolleisuudessa olivat pieniä verrattuna eroihin laitossynnytyksissä ja vastasyntyneisyyskauden jälkeisessä imeväiskuolleisuudessa. Tulokset viittaavat siihen, että syntymä sairaalassa ei useimmiten parantanut vastasyntyneen ennustetta kotona syntyneeseen lapseen verrattuna. Synnytyksen hoidon laatu oli puutteellista valtaosassa tutkimukseen osallistuneista synnytyssairaaloista Brong Ahafon alueella Ghanassa, Malawissa ja Sambiassa sekä useissa matalan tulotason ja keskitulotason maassa. Varhainen vastasyntyneisyyskuolleisuus on maailmanlaajuinen ongelma, jota synnytyssairaaloiden ja laitossynnytysten määrän lisääminen ei ole valitettavasti ratkaissut. Tämän vuoksi maiden, joissa on korkea vastasyntyneiden kuolleisuus, tulisi laitossynnytysten määrän lisäämisen sijaan keskittyä synnytysten hoidon laadun varmistamiseen ja parantamiseen

Hengitysvajauspotilaan hoitotyö: verkkokurssin laatiminen Skhole Oy:lle

Tämän opinnäytetyön tarkoituksena on tuottaa Skhole Oy:n oppimisympäristöön verkkomateriaalia hengitysvajauspotilaan hoitotyöstä. Verkkokurssit Skhole Oy:llä ovat myös oppimisympäristö hoitoalan ammattilaisille, jotka hakevat täydennyskoulutusta hoitoalan aiheista. Skhole Oy:llä oli kysyntää juuri hengitysvajauspotilaan hoitotyöstä ja halusivat, että siitä tehdään heille verkkokurssimateriaali. Verkkokoulutuksen avulla voidaan antaa opiskelijalle lisätietoa, miten hengitysvajauspotilasta hoidetaan ja mitä apuvälineitä voidaan hoidossa käyttää. Opinnäytetyö on toteutettu toiminnallisena työnä. Verkkokurssin aihe oli hengitysvajauspotilaan hoitotyö. Opinnäytetyön keskeiset käsitteet ovat hengitysvajaus, hoitotyö ja hoidon tukena käytettävät menetelmät. Opinnäytetyön tietoperusta koostui hengitysvajauksesta ja hoidon tukena olevista menetelmistä. Opinnäytetyöhön hankin aineistoa kirjoista, tieteellisistä artikkeleista ja käytin myös tiedonhankinnassa Terveysporttia. Opinnäytetyön tietoperusta koostuu jo olemassa olevan tiedon käytöstä. Opinnäytetyön tuotos oli verkkokurssimateriaali Skhole Oy:lle, he loivat materiaalin pohjalta verkkokurssin internettiin, johon opiskelija voi kirjautuu omilla tunnuksilla. Verkkokurssi on jaettu aihealueisiin ja aihealueen jälkeen opiskelija voi testata omaa osaamista kysymysten avulla. Kurssista muodostui tiivis kurssimateriaali, jossa opiskelijat voivat opiskella hengitysvajauspotilaan hoito-työstä ja testata omaa osaamista eri osioiden lopussa olevien kysymysten avulla

"Tuutti selvä!": Liisa Koskisen haastattelu

Turun kieli-instituutin ensimmäiseltä vuosikurssilta (1966–1968) valmistuneen Liisa Koskisen haastattelu.Turun kieli-instituutin ensimmäiseltä vuosikurssilta (1966–1968) valmistuneen Liisa Koskisen haastattelu

Aneurysmaattiseen lukinkalvonalaiseen verenvuotoon sairastuneen potilaan tehohoito

Teema : neuroanestesiologi

Healthy workplaces : Factors of importance for employee health and organizational production

The overall aim of the thesis was to investigate one aspect of healthy workplaces; namely, how psychosocial work factors affect employees general health and organizational production. The aim of Study I was to identify psychosocial factors at work that promote positive changes in employee health and factors that prevent negative changes in employee health. Specifically, we wanted to see if certain changes in the work environment would have a positive or negative impact on changes in the general health of the employee. The results showed that if employees perception of leadership and social climate improved, their health would also improve. A decrease in employees perception of leadership, organizational commitment and experiencing job strain were related to a decrease in their health. The aim of Study II was to investigate whether there is a relationship between psychosocial work environment factors and production loss, and if a potential relationship is mediated by employee health. Organizational commitment, social climate, job demands, job control and role compatibility were directly or indirectly related to production loss through employee health. The aim of Study III was to further develop a work capacity index including both qualitative and quantitative aspects of the ability to perform at work by including factors in the psychosocial work environment. A further aim was to evaluate the effects of a workplace intervention by estimating the change in the work capacity index. The results showed that the intervention had an effect in terms of more employees who were healthy and healthier employees, measured as improvement in the work capacity index, among the companies that worked actively with the intervention. The company that put less effort into the method did not have the same positive effect as the others did. Improvements in employee health and decreased production loss are related to improvements in psychosocial work factors. A good work environment contributes to improved employee health, which in turn affects organizational production. Creating a healthy workplace is not achieved by a single intervention. Instead, it is a process that needs to be maintained and constantly preserved. This focus must be part of the organizational culture, structure and climate. The results of the research done here, as well as of previous research, suggest that a healthy workplace is not only of value to companies, but also to the people who work for those companies

Differential Prox-1 and CD 31 expression in mucousae, cutaneous and soft tissue vascular lesions and tumors

The study of lymphatic vessels and lymphatic tumors has been hampered with difficulty due to the overlapping morphological features between blood and lymphatic endothelial cells, as well as to the lack of specific lymphatic endothelial markers. Over the last few years, lymphatic vessels and lymphangiogenesis have received great attention owing to their putative implications in terms of metastatic dissemination and the promise of targets for lymphangiogenic therapy. Prox-1 is a nuclear transcription factor that plays a major role during embryonic lymphangiogenesis and is deemed to be a useful marker for differentiating lymphatic endothelial cells from the other blood vessels endothelial cells. Here, we describe a double-immunostaining strategy for formalin-fixed, paraffinembedded tissues that aims at evaluating the distribution of Prox-1 and CD 31 – a cytoplasmic pan-endothelial marker -in a series of 28 mucousae, cutaneous and soft tissue vascular lesions and tumors, including hemangiomas, lymphangiomas, lymphangiectasia, and Kaposi’s sarcomas. Our results showed that in non-lesional mucousae and skin, Prox-1 decorated exclusively the nuclei of endothelial cells in lymphatic vessels. Prox-1 stained almost all the benign lymphatic vascular lesions/tumors (91%) and was absent or only focally positive in 75% of blood vascular tumors. CD 31 stained endothelial cells of blood vessels of superficial and deep dermal plexuses, lymphatics, and all blood vascular lesions/tumors. Kaposi’s sarcomas were all positive for both CD 31 and Prox-1 markers. In conclusion, although Prox-1 expression in vascular lesions/tumors was not entirely restricted to tumors with known lymphatic differentiation, CD 31/Prox-1 double-immunolabeling can be used as an adjunct marker to identify lymphatic vessels in routinely processed formalin-fixed, paraffin-embedded samples

Comparing socioeconomic inequalities between early neonatal mortality and facility delivery: Cross-sectional data from 72 low- and middle-income countries

Facility delivery should reduce early neonatal mortality. We used the Slope Index of Inequality and logistic regression to quantify absolute and relative socioeconomic inequalities in early neonatal mortality (0 to 6 days) and facility delivery among 679,818 live births from 72 countries with Demographic and Health Surveys. The inequalities in early neonatal mortality were compared with inequalities in postneonatal infant mortality (28 days to 1 year), which is not related to childbirth. Newborns of the richest mothers had a small survival advantage over the poorest in unadjusted analyses (−2.9 deaths/1,000; OR 0.86) and the most educated had a small survival advantage over the least educated (−3.9 deaths/1,000; OR 0.77), while inequalities in postneonatal infant mortality were more than double that in absolute terms. The proportion of births in health facilities was an absolute 43% higher among the richest and 37% higher among the most educated compared to the poorest and least educated mothers. A higher proportion of facility delivery in the sampling cluster (e.g. village) was only associated with a small  decrease in early neonatal mortality. In conclusion, while socioeconomically advantaged mothers had much higher use of a health facility at birth, this did not appear to convey a comparable survival advantage