Introduction: Type 2 diabetes (T2D) increases in prevalence and generates significant diseaseburden, where impairment in hormonal systems, such as glucagon, is suspected to contribute to T2Ddevelopment. Covariates such as obesity is a known risk factor for T2D development. Additionally,higher fasting insulin and glucagon concentrations, stronger adrenocorticotrophic hormone- (ACTH)and cortisol-response during hypoglycemia have been demonstrated in obese individuals. In contrast,bariatric surgery has shown to result in diabetes remission, independent of weight loss. The effect ofglucose and insulin on glucagon, ACTH and cortisol have been well studied, but not modelledduring hypoglycemia. Aim: To develop a population model of glucagon, ACTH and cortisol response during hypo- andhyperglycemia by characterizing the relationship between glucagon and glucose/insulin as well asACTH and glucose, connected with cortisol and explore impact of covariates. Followed byinvestigating changes in the concentration-response relationships after Roux-en-Y gastric bypass(RYGB). Methods: Data from a cross-over study with one arm being hyperinsulinemic-eu/hypoglycemicclamp, and the second arm being a hyperglycemic clamp was combined with data from two crossoverdesign studies with arms being hyperinsulineamic-eu/hypoglycemic clamps, conducted beforeand after RYGB. The pre-surgical combined data was used to create a population model throughnon-linear mixed effect modelling where additional delay mediating through an effect compartmentwas investigated on all response variables. Various structural models were explored in order todescribe glucose and/or insulins effect on glucagon response. Glucose inhibition on ACTH production was described through a sigmoidal Imax-model, which was combined with a surge modelto describe ACTH production caused by circadian rhythm. Cortisol production was modelled asbeing driven solely by ACTH concentrations and covariate relationships were investigated through astepwise covariate model. The models were validated with statistical and graphical analysis. Results and discussion: Glucagon production was dependent on an individuals’ insulin sensitivityand fasting glucose and insulin concentration. Glucose inhibition on glucagon productioncontributed with 77 % of the total inhibition in comparison to insulin, which contributed with 23 %.Glucose concentration had a steeper exposure-response relationship in comparison to insulinconcentration on glucagon production. Despite insulin concentrations having smaller effect incomparison to glucose on glucagon production, insulin had significant impact on the models fit tothe data. ACTH and cortisol responses were accurately described, despite some misspecificationswhich were independent of glucose concentrations. Production of ACTH was dependent on insulinsensitivity and fasting glucose. Alteration in glucagon and ACTH production, together with insulinsensitivity was sufficient to describe changes after RYGB. This model can be used in optimal designgenerations where clamping technique is used as guidance of appropriate hypoglycemic clamplevels. Conclusion: A population model of glucagon, ACTH and cortisol response was developed using datafrom hypo- and hyperglycemic studies. Glucagon production was described as dependent onglucose and insulin and ACTH production was described as dependent on glucose, with the ACTHconcentration driving the cortisol production. Insulin sensitivity was found to affect baselineglucose and the sensitivity of ACTH to glucose. The model could describe post-bariatric surgerydata when adjusting the estimating of baseline glucagon and ACTH.

Det finns sammanlagt 35 sötvattenlevande musselarter nio utav de kategoriseras som stormusslor, arterna lever i sjöar och vattendrag men hittas även i rinnande vatten. Stormusselarterna är idag hotade på grund av faktorer som föroreningar, fysiska förändringar i deras livsmiljöer, igenslammade bottnar och förlust av värdfiskarter. Det kan i sin tur leda till att musselpopulationerna dör ut. Syftet med studien är att undersöka populationsförändringen av samtliga stormusselarter i vattensystem Lidan, Tidan och Mariedalsån som ligger i Västra Götalands län. Arbetet är en återinventering baserad på tidigare studier inom de tre olika vattensystemen.Fältarbetet utfördes april 2021 i sju selektivt valda vattenlokaler. Metoden som tillämpades var vattenkikare med vadarstövlar med provyta på 10 m². De insamlade musslorna räknades, artbestämdes med litteratur, längd mättes och åldern uppskattades utifrån vinterringarna på skalen. Resultatet visade att föryngringen var svår att bedöma på grund att arbetet fokuserade på de adulta musslorna och inte de juvenila därför kan vi inte veta hur föryngringen såg ut i vattendragen. Storleksfördelningen visade däremot att inga livskraftiga populationer fanns i de inventerade lokalerna och att artmångfalden var låg jämfört med tidigare inventeringar. Enbart arterna Spetsig målarmussla (U.tumidus) och allmän dammussla (A. anatina) återfanns i lokalerna. Eftersom de inventerade lokalerna ska representera några av de bästa i de tre vattensystemen är resultaten oroväckande och fortsatta studier bör göras för övervakning av samtliga stormusselarter i Västra Götalands län med fokus på föryngring. Framtida undersökning bör även fokusera mer på musslornas reproduktion och hur förhållanden ser ut i vattendragen. / There are a total of 35 freshwater mussel species, nine of which are categorized as large mussels, the species live in lakes and streams but are also found in running water. The mussel species are today threatened due to factors such as pollution, physical changes in their habitats, clogged bottoms and loss of host fish species. This in turn can lead to the extinction of the mussel populations. The purpose of the study is to investigate the population change of all mussel species in the water systems Lidan, Tidan and Mariedalsån which are located in Västra Götaland County. The work is a re-inventory based on previous studies in the three different water systems.The field work was carried out in April 2021 in seven selectively selected water premises. The method used was water binoculars with wading boots with a sample area of 10 m². The mussels collected were counted, species determined with literature, length was measured and age was estimated based on the winter rings on the shells. The results showed that the rejuvenation was difficult to assess because the work focused on the adult mussels and not the juveniles, therefore we cannot know what the rejuvenation looked like in the watercourses. On the other hand, the size distribution showed that there were no viable populations in the inventoried premises and that the species diversity was low compared with previous inventories. Only the species swollen river mussel (U. tumidus) and common dust mussel (A. anatina) were found in the premises. Since the inventoried premises are to represent some of the best in the three water systems, the results are worrying and further studies should be done to monitor all mussel species in Västra Götaland County with a focus on rejuvenation. Future research should also focus more on mussel reproduction and what conditions look like in watercourses.

No description available.

No description available.

Pancreatic ductal adenocarcinoma (PDAC) yet remains one of the top 10 most prevalent and top five most common cause of cancer-related deaths solely in the United States. Its metastatic deviation from most cancer types rends it one of the most subtle yet perturbating disease. Hope lies within the traces of reproducibly mutated genes which are said to be found in nearly 95% of all PDAC. This study aimed to examine how digitoxin affects glycolysis and gene expression in Panc-1 cell lines. Panc-1 cells were cultured and treated with various concentrations of digitoxin for 24h-48h depending on the analysis and cell viability was then examined via the MTS assay. Lactate assay was conducted in order to investigate the degree to which panc-1 production of lactate was affected by digitoxin. Specific genes of interest (LDHA, C-Myc, PFKM, PDP1, SLC2A and PMM1) that take part in the glycolytic segment of the panc-1 metabolism were analyzed with qPCR in order to study their expression. Cell cycle assay was conducted in order to examine whether digitoxin also affected the panc-1 cell cycle and to what degree. Results from the MTS assay indicated that cell viability was indeed affected with increasing concentrations of digitoxin whereas; the lactate assay indicated that panc-1 cells were sensitive to 25nM digitoxin/higher due to how the decrease in lactate production became evident at that point. The gene expression of PDP1 was significantly increased with high concentrations of digitoxin compared to other genes. The cell cycle assay indicated that most treatment groups did not make it to the G2 and M phase due to apoptosis. All in all, digitoxin showed to have apoptotic effects on panc-1 cells line although this effect was not evident in certain assays.

Background: Diclofenac is an analgesic, antipyretic and anti-inflammatory drug that may have harmful effects on the environment, It has contributed to the death of fish exposed to the substance through discharges into lakes and seas. Even birds, especially vultures, have died after exposure to diclofenac by consuming carcasses that were treated before they died. Aim: The purpose of this study was to assess the sales of diclofenac around Lake Mälaren. Method: Data were obtained from the Swedish eHealth Agencys statistics database Concise, for the time period 2018–2021. The counties studied were Uppsala, Västmanland, Södermanland and Örebro, which have waste water treatment plants with Lake Mälaren as the recipient. The amount sold in kg was calculated using DDD, number of packages and package size and analyzed by season, time, sales method and region. Results: Uppsala accounted for the highest sales of diclofenac of the counties studied and over-the-counter sales at pharmacies sold most of the various sales methods. During the winter there was an increase of sold diclofenac while no other seasonal variations were observed. Following the prescription in June 2020, sales of tablets and capsules decreased, while other forms of preparation were not affected. For each year studied, the number of kg of diclofenac sold has decreased. Conclusion: Sales of diclofenac have declined during the period of 2018-2021, which is positive from an environmental point of view as reduced use means reduced emissions to nature.  This data can be used to investigate farmacies and citys on a lower level.

Background: The increased use of medicines in recent decades has affected the environmentand led to negative consequences. Environmental risk for a drug can be classified by using PBTindex and PEC / PNEC-ratio. Environmental risk information can be found on the knowledgesupport websites "medicines and the environment" at Janusinfo.se and in environmentalinformation at Fass.se. The Drug- and Therapeutics Committees (DTCs) ensure that medicinesare used in a correct and cost-effective manner and recommend medicines in annually updatedguidelines. Method: A survey was created and pilot-tested by 10 persons experienced from DTCs. Thequestionnaire consisted of four parts, general questions, questions about the use of theknowledge support "medicines and the environment" on janusinfo, questions about the use ofenvironmental information from Fass.se and other questions about environmental aspects. Result: In total, 9 out of 10 people who were included in the pilot study answered. Threerespondents had only positive feedback on the questionnaires. Some respondents thought thatthere were some questions and answers’ options that were not easy to understand and that somequestions could be answered only by people familiar with the subject.Conclusions: The conclusion is that the pilot study has led to many improvements in surveyquestions and approaches. In the future, further research is needed for knowledge about drugeffects in the environment.

Background:  Generic substitution has resulted in large economical savings for prescription drugs, but there is concern about potential negative consequences such as double medication, altered effect and poor compliance. Such problems would be worst among the elderly since they use many drugs, some have impaired cognitive function and a higher risk of serious consequences. Objective: The purpose of this study is to assess if there are any negative consequences of genetic changes in the elderly. Method: The study was a systematic review where data from scientific articles were collected from the PubMed database. A search strategy was developed using MeSH terms and keywords. The work was carried out according to the PRISMA guidelines for systematic review. A total of 232 papers were screened and 5 papers remained fulfilling inclusion and exclusion critera. Results: Two studies show that generic substitution has no effect on patient compliance. One study on antiepiletics showdes that patients experienced different effects and new side effects after switching to generic drugs. However there was no association between switching and seizure related hospital visits. In another study, the results showed no association between hospitalization and generic substitution Conclusion: There are few studies on the consequences of generic substitution in elderly. Current studies indicate that generic substitution has no effect on the patient's compliance, it may  cause some confusion and anxiety in certain groups, but no increase in hospital admissions been found.

No description available.

This Thesis focuses on the exchange of phosphorus (P) across the sediment–water interface in the Baltic Sea proper, with particular attention to the influence of bioturbating macrofauna and benthic redox conditions. Benthic P fluxes have major influence on P availability in the water column, which in turn regulates growth conditions for dinitrogen fixating cyanobacteria in the Baltic proper. Presently, a very large area of bottom sediment is overlain by oxygen depleted bottom water and is therefore devoid of aerobic organisms. In paper I, anoxic sediment from the Western Gotland Basin was oxygenated and exposed to bioturbation by three macrofauna species in a laboratory experiment. The experimental design allowed for detailed studies of how bioturbating animals influence the P fluxes on a species-specific level. All species (Monoporeia affinis, Mysis mixta, and Macoma balthica) mobilised dissolved organic P from the bottom sediment to the supernatant water. Also, particulate P was released by the two former species. None of these P fractions showed any mobility in control sections of the aquarium system. These animal-dependent P fluxes are a previously largely overlooked but potentially significant source of bioavailable P in coastal marine areas, such as the Baltic Sea. In paper II, we estimate a contemporary reflux of 146 kton dissolved inorganic P (DIP) from bottom sediments in the Baltic proper. This estimate is based on data from a large number of in situ benthic flux measurements using benthic chamber landers along a depth gradient in the Eastern Gotland Basin. DIP effluxes increased with increasing water depth, and decreasing bottom water oxygen concentrations. Bottom water anoxia was identified as a major driver for the mobilisation of DIP from bottom sediments. During such conditions, the DIP efflux was well correlated to carbon oxidation rate, while on oxic bottoms DIP fluxes were low irrespectively of the carbon oxidation rate. Our data support the hypothesis of a positive feedback loop of self-amplifying eutrophication in the Baltic Sea. Thus, both nutrient emission cuts and active mitigation actions to strengthen sedimentary P sinks are warranted for effective remediation of eutrophication in the Baltic Sea.