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Coming dissertations at MedFak

  • Diet and Sarcopenia : Swedish Cohort Studies in Aging Populations Author: Mikael Karlsson Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-454314 Publication date: 2021-11-11 08:23

    Sarcopenia is a growing public health concern, involving a loss of muscle mass and function, thus resulting in functional impairment. The role of diet in sarcopenia is unknown.

    Paper I identified equations by Mifflin-St Jeor and Harris-Benedict as accurate predictive equations for resting energy expenditure among 22 octogenarian men, from the Uppsala Longitudinal Study of Adult Men (ULSAM), using indirect calorimetry as a reference. Our results address the importance of validating the equation in the study population.

    Papers II, III, and IV aimed to increase the understanding of the role of dietary patterns (DP) in sarcopenia and its individual components. Lean muscle mass index (LMI) was determined using dual-energy X-ray absorptiometry (DXA).

    In Papers II and III, DPs were defined at baseline using a 7-day food record from ULSAM (mean age 71 years). Sarcopenia was defined 16 years later. In Paper IV, DPs were defined at baseline using a food frequency questionnaire in women from the Swedish Mammography Cohort Clinical (SMCC; mean age 67 years). Sarcopenia was defined 12 years later.

    Paper II used the old definition by the European Working Group on Sarcopenia in Older People (EWGSOP1) (prevalence of sarcopenia: 21% of 254). Papers III and IV used the new definition (EWGSOP2) (prevalence of sarcopenia: 19% of 257, and incidence of sarcopenia 4% of 1,212, respectively).

    Paper II used two a priori DPs (modified Mediterranean Diet Score and modified Healthy Diet Indicator). Higher adherence to a Mediterranean-like diet was associated with a lower prevalence of sarcopenia at follow-up.

    Paper III defined four a posteriori DPs. Higher adherence to DP2 (characterized by high intake of vegetables, fruits, poultry, rice, and pasta) was associated with a lower prevalence of sarcopenia at follow-up.

    In Paper IV, the associations between DPs (an a priori defined Mediterranean-like and three a posteriori) and sarcopenia displayed no clear associations. However, a DP characterized by a high intake of vegetables, fruits, nuts, grains, poultry, fatty fish, and fermented milk was associated with a higher appendicular LMI at baseline, better muscle function at follow-up, and displayed non-linear associations with changes in appendicular LMI. A DP characterized by a high intake of boiled potatoes, dairy, grains, pancake, and sweet bakery, and a low intake of wine/spirits and poultry displayed non-linear associations with changes in appendicular LMI.

    Thus, dietary patterns with a common feature of being considered a healthy choice may be important for muscle function, muscle mass, and sarcopenia.

  • Superparamagnetic iron oxide nanoparticles, a novel tracer in breast cancer surgery Author: Abdi-Fatah Hersi Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-455673 Publication date: 2021-11-10 10:17

    The most common surgical choice of treatment in breast cancer is breast-conserving surgery (BCS) together with sentinel lymph node biopsy (SNB). Around 10% of breast cancer diagnosis are ductal carcinoma in situ (DCIS). Superparamagnetic iron oxide nanoparticles (SPIO) are a novel tracer for sentinel lymph node (SN) detection. The aim of this thesis was to investigate the unique applications and functionality of a magnetic approach in breast cancer surgery.

    Paper I was a two-centre pilot study of 32 patients with non-palpable breast cancer who were scheduled for BCS together with SNB. They received SPIO for SNB and a magnetic seed (Magseed®) for localization of the breast tumour. All 32 patients underwent microscopically radical resection and SNB was successfully performed in all included patients.

    Paper II was a multicentre prospective single-cohort study. It was a pre-planned interim analysis of 189 patients with “high-risk” DCIS who received SPIO at primary surgery but without performing SNB. If an invasive breast cancer was shown by the final histopathology report, the patient was scheduled for second surgery to undergo SNB. Because SPIO has a much longer half-life than the radioisotope, the magnetic signal at the second surgery was sufficient for detecting SNs; in fact, in patients with DCIS, it reduced from around 50% to 22%. 

    Paper III was a multicentre prospective trial. Two consecutive cohorts of patients with breast cancer scheduled for SNB (n = 328) were included. Lower doses of a refined SPIO suspension were tested in different time frames and injection sites. Analyses were performed as a one-step individual patient-level meta-analysis using patient-level data from a similar previous cohort (n = 206) as a third reference group. In 534 patients, the SPIO SN detection rates were comparable (97.5% vs. 100% vs. 97.6%, p = 0.11) and were noninferior to the dual technique. 

    Paper IV was a multicentre randomized pilot trial aimed to compare tumour localization in nonpalpable breast cancers using either Magseed® or guidewire in patients scheduled for BCS + SNB. All patients received SPIO for the SNB preoperatively. Patients who were randomized to the magnetic seed cohort received their Magseed® at the same time as the SPIO injection preoperatively while the guidewire placement was performed on the same day as surgery. In 207 patients, there were no significant differences in reoperation rate (3% in the magnetic seed cohort vs 7% in the guidewire cohort, p = 0.35). 

  • Diving into the zebrafish locomotor network : A study on dI6 interneurons Author: Ana Belen Iglesias Gonzalez Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-455896 Publication date: 2021-11-10 09:09

    The generation and coordination of locomotion comprise of inhibitory and excitatory interneurons that govern motor neuron output to muscles. This neuronal network is known as the central pattern generator (CPG). Spinal inhibitory interneurons that originate from the dI6 population play a crucial role in the coordination of locomotor output. This thesis provides new insights into the role of two subsets of interneurons within the dI6 population, marked by the expression of Doublesex and mab-3 related transcription factor 3 (dmrt3a) or Wilms tumor 1 (wt1a). 

    We showed that dmrt3a neurons play an important role during zebrafish locomotion by using a transgenic line lacking dmrt3a expression. The absence of Dmrt3a generated acceleration and coordination problems in larvae and reduced the maximum speed in juveniles. Analysis of the transcriptome of the dmrt3a subpopulation in both mice and zebrafish established their characteristics as well as revealed unique markers for novel dI6 subpopulations. The knock-down of Wt1a protein resulted in impaired left-right alternation and a reduction of fast swims. On a cellular level, we found alterations in dmrt3a-, wt1a- and evx2- interneuron composition, indicating a link between the two dI6 populations and changes in their fate assignments affecting cell type composition within the locomotor network. Moreover, we linked the absence of specific subtypes of dI6 interneurons with the observed locomotor phenotype in knock-down animals.

    While searching for unique markers genes within dmrt3a-expressing interneurons, we observed calb2b (encoding for calretinin) expression in one specific subpopulation. Following the generation of a calb2b transgenic line, we found it expressed in interneurons and motor neurons. Knock-down of calretinin generated a development disorder of dmrt3a interneurons and motor neurons, leading to a disruption of the left-right alternation and escape responses performance. 

    Together, the work presented here provides new cellular, molecular, and behavioral information related to the dI6 population, helping us to better understand their role within the CPG of zebrafish specifically and vertebrates as a whole.

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