Site and Strain-Specific Variation in Gut Microbiota Profiles and Metabolism in Experimental Mice

The gastrointestinal tract microbiota (GTM) of mammals is a complex microbial consortium, the composition and activities of which influences mucosal development, immunity, nutrition and drug metabolism. It remains unclear whether the composition of the dominant GTM is conserved within animals of the same strain and whether stable GTMs are selected for by host-specific factors or dictated by environmental variables.The GTM composition of six highly inbred, genetically distinct strains of mouse (C3H, C57, GFEC, CD1, CBA nu/nu and SCID) was profiled using eubacterial -specific PCR-DGGE and quantitative PCR of feces. Animals exhibited strain-specific fecal eubacterial profiles that were highly stable (c. >95% concordance over 26 months for C57). Analyses of mice that had been relocated before and after maturity indicated marked, reproducible changes in fecal consortia and that occurred only in young animals. Implantation of a female BDF1 mouse with genetically distinct (C57 and Agoutie) embryos produced highly similar GTM profiles (c. 95% concordance) between mother and offspring, regardless of offspring strain, which was also reflected in urinary metabolite profiles. Marked institution-specific GTM profiles were apparent in C3H mice raised in two different research institutions.Strain-specific data were suggestive of genetic determination of the composition and activities of intestinal symbiotic consortia. However, relocation studies and uterine implantation demonstrated the dominance of environmental influences on the GTM. This was manifested in large variations between isogenic adult mice reared in different research institutions

Changes in Human Fecal Microbiota Due to Chemotherapy Analyzed by TaqMan-PCR, 454 Sequencing and PCR-DGGE Fingerprinting

BACKGROUND: We investigated whether chemotherapy with the presence or absence of antibiotics against different kinds of cancer changed the gastrointestinal microbiota. METHODOLOGY/PRINCIPAL FINDINGS: Feces of 17 ambulant patients receiving chemotherapy with or without concomitant antibiotics were analyzed before and after the chemotherapy cycle at four time points in comparison to 17 gender-, age- and lifestyle-matched healthy controls. We targeted 16S rRNA genes of all bacteria, Bacteroides, bifidobacteria, Clostridium cluster IV and XIVa as well as C. difficile with TaqMan qPCR, denaturing gradient gel electrophoresis (DGGE) fingerprinting and high-throughput sequencing. After a significant drop in the abundance of microbiota (p = 0.037) following a single treatment the microbiota recovered within a few days. The chemotherapeutical treatment marginally affected the Bacteroides while the Clostridium cluster IV and XIVa were significantly more sensitive to chemotherapy and antibiotic treatment. DGGE fingerprinting showed decreased diversity of Clostridium cluster IV and XIVa in response to chemotherapy with cluster IV diversity being particularly affected by antibiotics. The occurrence of C. difficile in three out of seventeen subjects was accompanied by a decrease in the genera Bifidobacterium, Lactobacillus, Veillonella and Faecalibacterium prausnitzii. Enterococcus faecium increased following chemotherapy. CONCLUSIONS/SIGNIFICANCE: Despite high individual variations, these results suggest that the observed changes in the human gut microbiota may favor colonization with C. difficile and Enterococcus faecium. Perturbed microbiota may be a target for specific mitigation with safe pre- and probiotics

Long-Term Persistance of the Pathophysiologic Response to Severe Burn Injury

Main contributors to adverse outcomes in severely burned pediatric patients are profound and complex metabolic changes in response to the initial injury. It is currently unknown how long these conditions persist beyond the acute phase post-injury. The aim of the present study was to examine the persistence of abnormalities of various clinical parameters commonly utilized to assess the degree hypermetabolic and inflammatory alterations in severely burned children for up to three years post-burn to identify patient specific therapeutic needs and interventions. Nine-hundred seventy-seven severely burned pediatric patients with burns over 30% of the total body surface admitted to our institution between 1998 and 2008 were enrolled in this study and compared to a cohort non-burned, non-injured children. Demographics and clinical outcomes, hypermetabolism, body composition, organ function, inflammatory and acute phase responses were determined at admission and subsequent regular intervals for up to 36 months post-burn. Statistical analysis was performed using One-way ANOVA, Student's t-test with Bonferroni correction where appropriate with significance accepted at p<0.05. Resting energy expenditure, body composition, metabolic markers, cardiac and organ function clearly demonstrated that burn caused profound alterations for up to three years post-burn demonstrating marked and prolonged hypermetabolism, p<0.05. Along with increased hypermetabolism, significant elevation of cortisol, catecholamines, cytokines, and acute phase proteins indicate that burn patients are in a hyperinflammatory state for up to three years post-burn p<0.05. Severe burn injury leads to a much more profound and prolonged hypermetabolic and hyperinflammatory response than previously shown. Given the tremendous adverse events associated with the hypermetabolic and hyperinflamamtory responses, we now identified treatment needs for severely burned patients for a much more prolonged time

Biomarker candidates of neurodegeneration in Parkinson’s disease for the evaluation of disease-modifying therapeutics

Reliable biomarkers that can be used for early diagnosis and tracking disease progression are the cornerstone of the development of disease-modifying treatments for Parkinson’s disease (PD). The German Society of Experimental and Clinical Neurotherapeutics (GESENT) has convened a Working Group to review the current status of proposed biomarkers of neurodegeneration according to the following criteria and to develop a consensus statement on biomarker candidates for evaluation of disease-modifying therapeutics in PD. The criteria proposed are that the biomarker should be linked to fundamental features of PD neuropathology and mechanisms underlying neurodegeneration in PD, should be correlated to disease progression assessed by clinical rating scales, should monitor the actual disease status, should be pre-clinically validated, and confirmed by at least two independent studies conducted by qualified investigators with the results published in peer-reviewed journals. To date, available data have not yet revealed one reliable biomarker to detect early neurodegeneration in PD and to detect and monitor effects of drug candidates on the disease process, but some promising biomarker candidates, such as antibodies against neuromelanin, pathological forms of α-synuclein, DJ-1, and patterns of gene expression, metabolomic and protein profiling exist. Almost all of the biomarker candidates were not investigated in relation to effects of treatment, validated in experimental models of PD and confirmed in independent studies

Experimental Investigation of the Thermal Performance and Pressure Loss in Additively Manufactured mini-channels

Industrial gas turbines reach temperatures of 1500-2000K at high rotational velocities which means that much effort is spent on the design of an efficient cooling system. With the recent advances of the additive manufacturing (AM) industry, new design opportunities have open up for many industries and applications, including the design of cooling systems. However, a significant surface roughness will be present in AM components compared to traditionally manufactured components. An increased surface roughness inside a channel will affect both the heat transfer and pressure loss. The performance of AM channels are therefore not fully known and needs to be examined experimentally on the actual material to fully capture the effects of the increased surface roughness. The aim with this project is to experimentally investigate the thermal performance and pressure losses experienced in AM channels due to surface roughness. This was done by using a Steady State Heat Transfer rig which was assembled and verified. AM and aluminium test channels were mounted in a copper block which was insulated and heated up by electrical heaters. The test channels were then subjected to an air flow of constant mass flow. Temperature and pressure measurements were made at the inlet and outlet together with mass flow measurements and copper block temperature measurements. The Nusselt number and Darcy friction factor were used to evaluate the heat transfer and pressure losses experienced in the channels. The results showed that the heat transfer and friction factor increased significantly for the AM channels compared to smooth channels. Both the heat transfer and friction factor increased when the relative roughness of the channels increased. This project was executed at Siemens Energy in Finspång at the Fluid Dynamic Laboratory and is a part of the work of obtaining thermal performance data for mini-channels manufactured by AM

Upplevelser av att leva med en ileostomi : Ett patientperspektiv

Bakgrund: En stomi från tunntarmen benämns ileostomi och är ett resultat av ett kirurgiskt ingrepp där hela eller delar av tjocktarmen tagits bort. Att leva med en ileostomi kan både leda till fysisk och psykisk påverkan på patienter. Syfte: Syftet var att belysa patienters upplevelser av att leva med en ileostomi. Metod: En litteraturstudie har genomförts för att sammanställa aktuell forskning. Totalt har fyra kvalitativa och fyra kvantitativa artiklar inkluderats till resultatet och analyserats med en integrerad analys. Resultat: Resultatet presenteras i fyra kategorier: förändrad självbild, förändrade relationer till andra, komplikationer och behandling samt kontakten med sjukvården. En ileostomi kan ge en försämrad kroppsbild som påverkar patienters upplevelser av sig själva negativt. Osäkerhet uppstod inför att avslöja ileostomin för andra och då upplevde patienter påverkan på relationer. Komplikationer upplevdes försämra välbefinnandet. Sjukvården var viktig för patienters upplevelser av välbefinnande. Slutsats: Patienters upplevelser av att leva med en ileostomi varierar och kan vara både positiva och negativa. Kroppsbilden påverkas och patienter kan känna sig onaturliga. Patienter upplevde osäkerhet när sjuksköterskor visade avsky mot ileostomin, medan välbefinnande uppstod när sjuksköterskor var medkännande. Background: A stoma from the small intestine is called an ileostomy and is a result of a surgical procedure where all or parts of the large intestine has been removed. Living with an ileostomy might entail physical and mental problems for the patient. Aim: The aim was to illuminate patients experiences of living with an ileostomy. Method: A literature study has been conducted to compile current research. In total, four qualitative and four quantitative articles have been included in the results and analyzed with integrated analysis Results: The result is presented in four categories: changed selfimage, changed relationships with others, complications and treatment, contact with healthcare. An ileostomy can cause a deteriorated body image that adversely affects the patient's experiences. Uncertainty arose in order to reveal the ileostomy to others and then patients experienced the impact on relationships. Complications of the ileostomy was found to impair well-beeing. Healthcare was important for patients' experiences of well-being. Conclusion: Patients' experiences of living with an ileostomy vary and may be both positive and negative. The body image is affected and patients may feel unnatural. Patients experienced insecurity when nurses showed disgust towards their ileostomy, while well-beeing aroused when nurses were compassionate

What the patient feels as comforting in life-threatening cancer decease. : A literature study

Bakgrund: I dag överlever fler sin cancerdiagnos till följd av förbättrad biomedicinsk teknik. År 2018 rapporterade socialstyrelsen att 63 000 individer drabbats av malign cancer. Detta är ett stort nationellt hälsoproblem och ställer höga krav på hälso- och sjukvården. Cancer innebär fysiskt och psykiskt lidande för patienten och är grund till tröstande omvårdnad. Tröst har ifrågasatts som en omvårdnadsåtgärd samt om det är en uppgift som sjuksköterskan skall utföra. Syfte: Var att belysa vad patienten upplevde som tröstande vid livshotande cancersjukdom. Metod: En systematisk litteraturstudie med 10 vetenskapliga resultatartiklar varav nio med kvalitativ ansats och en med kvantitativ ansats som har granskats, bearbetats och analyserats med hjälp av Fribergs femstegsmodell (Friberg, 2017). Artiklarna har kvalitetsgranskats med hjälp av Carlsson och Eimans (2003) granskningsmall. Resultat: Tröst är mångdimensionellt och subjektivt. Kommunikation, utbildning och personcentrerad vård var viktiga för att patienten skall kunna erhålla tröst. Andra faktorer som gav patienten tröst var interaktion med sjuksköterskan, spirituell närvaro och hopp. Konklusion:Viktiga relationer gav patienten tröst och hopp. Relationen mellan spirituell närvaro och viktiga relationer stärkte varandra. Kommunikation och interaktion med sjuksköterska och annan hälso- och sjukvårdspersonal var betydelsefull för att erhålla en bättre livskvalitet samt finna en väg till tröst. När patienten upplevde sig komfortabel och ren i sin kropp kunde patienten uppleva sig stark och därigenom få framtidshopp samt behållen värdighet.Background: Today, more people survive their cancer diagnosis as a result of improved biomedical technology. In 2018, the National Board of Health reported that 63,000 individuals were affected by malignant cancer. This is a major national health problem and places high demands on health care and hospitals. Cancer means physical and mental distress for the patient and is the basis for comforting nursing. However, comfort has been questioned as a nursing measure and whether it is a task that the nurse should perform. Aim: The aim was to enlighten what patients experience as comforting in a life-threatening cancer decease. Method: A general literature study with10 scientific articles, nine with qualitative approach and one with quantitative approach. Reviewed and analyzed by using Fribergs five step model (Friberg, 2017). The articles have been reviewed in accordance with Carlsson och Eimans (2003) schedule for review. Result: Consolation is multi-dimensional and subjective. Communication, education and person-centered care were important for the patient to receive comfort. Other factors that allowed the patient comfort was interaction with the nurse, spiritual presence and hope. Conclusion: Important relationships gave the patient consolation and hope. The relationship between spiritual precence and other close relations fortified eachother. Communication and interaction with the nurse and other health care professionals was important in obtaining a better quality of life and finding a way to consolation. When the patient felt comfortable and clean in his or her body, the patient could feel strong and thereby gain future hope and maintained dignity.