Pediatric obstructive sleep apnea - evaluation of questionnaire and surgical treatment

Obstructive sleep apnea (OSA) is a major pediatric health problem and is associated with potentially severe consequences if left untreated. Diagnosing OSA in children can be challenging since the clinical symptoms are very non-specific. A full-night polysomnography is recommended as the gold standard to establish the diagnosis, but it is not possible to perform this for every child where suspicion of OSA has arisen. Other diagnostic instruments such as questionnaires have been used, and one of these, the OSA-18, was evaluated in Paper I. The dominant cause of OSA in children is tonsil hypertrophy and treatment is surgical with removal of tonsils. Tonsillectomy is one of the most common surgical procedures performed on children throughout the world. The trends of Swedish tonsil surgery in recent decades were described in Paper II. In recent years, tonsillotomy (partial tonsillectomy) has gained popularity as an option for surgery in Sweden. It has been unclear whether tonsillotomy is as effective as tonsillectomy in treating OSA, and this was investigated in a randomized study. The overall aim of the thesis was to contribute to the improvement of the diagnostic process and surgical treatment of OSA for children. Paper I considers the diagnostic process of pediatric OSA and evaluates the disease-specific questionnaire OSA-18. 225 children were included. They all performed a full-night PSG and their parents responded to OSA-18. The scores of the OSA-18 were compared to the apneahypopnea index from PSG, and the results showed poor predictivity of the OSA-18 to detect and correctly grade the severity of OSA. Paper II is a longitudinal description of the trends in the clinical practice of tonsil surgery in Sweden between 1987 and 2013. The study was based on the Swedish National Patient Register, and all children aged 1-17 years who were registered with a tonsil surgery procedure were included, totaling 167 894 individuals. The results demonstrated substantial shifts in the trends of tonsil surgery over the period, with an overall increase in incidence of tonsil procedures, consisting mainly of tonsil surgery due to sleep disordered breathing/OSA, especially among the youngest children (1-3 years). Moreover, a gradual increase in the incidence of tonsillotomy since it was introduced in the late 1990s was observed, and since 2011 tonsillotomy has been more common than tonsillectomy. Papers III and IV are a randomized trial with the aim of comparing adenotonsillotomy (ATT) with adenotonsillectomy (ATE) regarding the effect of treating pediatric OSA measured by polysomnography(Paper III). The RCT included 79 children aged 2-6 years, with moderate to severe OSA, randomized to either ATT or ATE. All children performed a PSG at baseline, with follow-up one year after surgery. Paper III primarily evaluated the polysomnographic outcomes, showing that ATT was non-inferior to ATE. However, five cases in the ATT-group needed repeated surgery due to re-growth of tonsils and return of OSA-symptoms, and thus considered as failures of ATT. All children were also evaluated concerning postoperative pain and bleeding (Paper IV), showing that ATT is associated with less postoperative pain than ATE, but the differences were modest. Two cases of postoperative bleeding were seen in the ATE group and no cases of postoperative bleeding in the ATT group, indicating a lower risk of bleeding after ATT than ATE, but a larger study population would have been needed for better evaluation

A novel multiplex qPCR targeting 23S rDNA for diagnosis of swine dysentery and porcine intestinal spirochaetosis

Figure S1. Consensus sequence alignment of the target DNA region within 23S ribosomal DNA. Primers (Brachy primer for. and Brachy primer rev.) on the target DNA are marked in grey. The probe for B. hyodysenteriae (Probe_hyo) is highlighted in yellow, the probe for B. pilosicoli (Probe_pilo) in purple, and the probe for the B. intermedia/B. innocens/B. murdochii (probe inter) in green. Differences in single residues are marked in red. (PDF 112 kb

Small Molecular Inhibitors Block TRPM4 Currents in Prostate Cancer Cells, with Limited Impact on Cancer Hallmark Functions.

Transient receptor potential melastatin 4 (TRPM4) is a broadly expressed Ca2+ activated monovalent cation channel that contributes to the pathophysiology of several diseases. For this study, we generated stable CRISPR/Cas9 TRPM4 knockout (K.O.) cells from the human prostate cancer cell line DU145 and analyzed the cells for changes in cancer hallmark functions. Both TRPM4-K.O. clones demonstrated lower proliferation and viability compared to the parental cells. Migration was also impaired in the TRPM4-K.O. cells. Additionally, analysis of 210 prostate cancer patient tissues demonstrates a positive association between TRPM4 protein expression and local/metastatic progression. Moreover, a decreased adhesion rate was detected in the two K.O. clones compared to DU145 cells. Next, we tested three novel TRPM4 inhibitors with whole-cell patch clamp technique for their potential to block TRPM4 currents. CBA, NBA and LBA partially inhibited TRPM4 currents in DU145 cells. However, none of these inhibitors demonstrated any TRPM4-specific effect in the cellular assays. To evaluate if the observed effect of TRPM4 K.O. on migration, viability, and cell cycle is linked to TRPM4 ion conductivity, we transfected TRPM4-K.O. cells with either TRPM4 wild-type or a dominant-negative mutant, non-permeable to Na+. Our data showed a partial rescue of the viability of cells expressing functional TRPM4, while the pore mutant was not able to rescue this phenotype. For cell cycle distribution, TRPM4 ion conductivity was not essential since TRPM4 wild-type and the pore mutant rescued the phenotype. In conclusion, TRPM4 contributes to viability, migration, cell cycle shift, and adhesion; however, blocking TRPM4 ion conductivity is insufficient to prevent its role in cancer hallmark functions in prostate cancer cells

Harm–benefit analysis – what is the added value?:A review of alternative strategies for weighing harms and benefits as part of the assessment of animal research

Animal experiments are widely required to comply with the 3Rs, to minimise harm to the animals and to serve certain purposes in order to be ethically acceptable. Recently, however, there has been a drift towards adding a so-called harm-benefit analysis as an additional requirement in assessing experiments. According to this, an experiment should only be allowed if there is a positive balance when the expected harm is weighed against the expected benefits. This paper aims to assess the added value of this requirement. Two models, the discourse model and the metric model, are presented. According to the former, the weighing of harms and benefits must be conducted by a committee in which different stakeholders engage in a dialogue. Research into how this works in practice, however, shows that in the absence of an explicit and clearly defined methodology, there are issues about transparency, consistency and fairness. According to the metric model, on the other hand, several dimensions of harms and benefits are defined beforehand and integrated in an explicit weighing scheme. This model, however, has the problem that it makes no real room for ethical deliberation of the sort committees undertake, and it has therefore been criticised for being too technocratic. Also, it is unclear who is to be held accountable for built-in ethical assumptions. Ultimately, we argue that the two models are not mutually exclusive and may be combined to make the most of their advantages while reducing the disadvantages of how harm-benefit analysis in typically undertaken

Early life programming by diet can play a role in risk reduction of otitis in dogs

IntroductionOtitis in dogs is often chronic while local treatment primarily consists of flushing, antibiotics, and/or antifungals. We were interested in finding early life variables that associate with otitis later in life, preferably some that could be modified.MethodsA cross-sectional hypothesis-driven study with longitudinal data was performed to search for associations between pre- and postnatal exposures, and the incidence of owner-reported otitis in dogs at over 1 year of age. The multivariate logistic regression analysis study included data from 3,064 dogs and explored 26 different early life variables at four early life stages: prenatal, neonatal, postnatal, and puppyhood. We compared two feeding patterns, a non-processed meat-based diet (NPMD, raw) and an ultra-processed carbohydrate-based diet (UPCD, dry).ResultsWe report that eating a NPMD diet significantly decreased the risk of otitis later in life, while eating a UPCD diet significantly increased the risk. This was seen in different life stages of mother or puppy: The maternal diet during pregnancy (p=0.011) and the puppies’ diet from 2 to 6 months of age (p=0.019) were both significantly associated with otitis incidence later in life, whereas the puppies’ first solid diet, was associated in the same way, but did not reach significance (p=0.072). Also, analyzing food ratios showed that when puppies were consuming >25% of their food as NPMD it significantly decreased their incidence of otitis later in life, while a ratio of >75% UPCD in their diet significantly increased their risk of otitis. Also, if the dog was born in the current family, was exposed to sunlight for more than 1 hour daily, and was raised on a dirt floor during puppyhood, there was a lower risk of otitis development later in life.DiscussionThe findings only suggest causality, and further studies are required. However, we propose that veterinarians, breeders, and owners can impact otitis risk by modifying factors such as diet and environment

Elevers upplevelser av deltagande i bedömningsarbetet

En undersökning av hur elever upplevelser sig delaktiga i bedömningsarbetet i sex niondeklasser fördelade på tre skolor. Syftet med arbetet var att undersöka hur eleverna upplever sig delaktiga i bedömningsarbetet i ämnena geografi och kemi. Vårt mål har varit att ta reda på:• I vilken utsträckning upplever sig eleverna delaktiga i bedömningsarbetet? • På vilka sätt upplever eleverna att de är delaktiga i bedömningsarbetet? • Hur skiljer sig elevernas upplevelser av delaktighet i bedömningsarbetet åt mellan ämnena? Metod har varit den enkät som vi formade efter våra frågeställningar. Resultaten visar att eleverna genomgående upplever låg delaktighet. Inga signifikanta skillnader hittades mellan ämnena men däremot mellan lärarna. Signifikanta skillnader fanns även mellan vilka olika bedömningsformer eleverna upplever att de arbetat mest med, där självbedömning är den vanligaste formen.En undersökning av hur elever upplevelser sig delaktiga i bedömningsarbetet i sex niondeklasser fördelade på tre skolor. Syftet med arbetet var att undersöka hur eleverna upplever sig delaktiga i bedömningsarbetet i ämnena geografi och kemi. Vårt mål har varit att ta reda på:• I vilken utsträckning upplever sig eleverna delaktiga i bedömningsarbetet? • På vilka sätt upplever eleverna att de är delaktiga i bedömningsarbetet? • Hur skiljer sig elevernas upplevelser av delaktighet i bedömningsarbetet åt mellan ämnena? Metod har varit den enkät som vi formade efter våra frågeställningar. Resultaten visar att eleverna genomgående upplever låg delaktighet. Inga signifikanta skillnader hittades mellan ämnena men däremot mellan lärarna. Signifikanta skillnader fanns även mellan vilka olika bedömningsformer eleverna upplever att de arbetat mest med, där självbedömning är den vanligaste formen