The effect of a six-month home-based HIIT intervention on cardiorespiratory fitness and lung function in older adults between 60-85 years

Sammendrag Introduksjon: Høy-intensitets intervall trening (HIIT) har blitt demonstrert som en gunstig metode for å forbedre kardiorespiratorisk kondisjon (KRF, målt som VO2peak) hos eldre voksene (Wu et al., 2021). Det er imidlertid få studier som har undersøkt effekten av HIIT utenfor laboratoriske forhold. Målet med denne studien var derfor for å undersøke effekten av ett seks måneders hjemmebasert HIIT program på KRF og lungefunksjon hos friske eldre voksene (68.5±5.3 år). Metode: 139 eldre menn og kvinner ble randomisert til enten en hjemmebasert HIIT intervensjons gruppe (IG) (n=73) eller en passiv kontrollgruppe (KG) (n=66). Målinger ble utført ved bruk av en oksygenanalysator for undersøkelse av lungefunksjon (MVV, FVC og FEV1) og CRF. CRF ble målt ved å bruke en modifisert inkrementell tredemølleprotokoll (Balke) for å avgjøre deltakerens VO2peak. Intervensjonsgruppen fulgte ett standardisert HIIT-program bestående av 3 økter per uke, to HIIT-gå-økter og en HIIT-styrkesirkel (kroppsvekts øvelser) (>80% av HRpeak). Resultat: IG forbedret VO2peak innad i gruppen, i tillegg til forbedring sammenliknet med kontrollgruppen fra pre- til post-intervensjon (6.22±7.84% versus -1.29±7.07%, p<.001). Det var ingen endring i lungefunksjon innad i intervensjonsgruppen, bortsett fra en økning i MVV (IG 2.92±8.43%, p<.05 and IG menn 4.73±8.07%, p<.05). Det var ingen endring i lungefunksjonsmålinger i intervensjonsgruppen sammenliknet med kontrollgruppen fra pre- til post-intervensjon. Konklusjon: Den gjennomførte studien viste at ett seks måneders hjemmebasert HIIT-regime forbedret kardiorespiratorisk kondisjon hos friske eldre voksene. Intervensjonsgruppen forbedret VO2peak sammenliknet med den passive kontrollgruppen, men ingen forbedring i lungefunksjon ble påvist fra pre- til post-intervensjon. Nøkkelord: Aldring, KRF, VO2peak, Maksimal voluntær ventilasjon, Forsert vitalkapasite

Unveiling Angiotensin II and Losartan-Induced Gene Regulatory Networks Using Human Urine-Derived Podocytes

Podocytes are highly specialized cells that play a pivotal role in the blood filtration process in the glomeruli of the kidney, and their dysfunction leads to renal diseases. For this reason, the study and application of this cell type is of great importance in the field of regenerative medicine. Hypertension is mainly regulated by the renin–angiotensin–aldosterone system (RAAS), with its main mediator being angiotensin II (ANG II). Elevated ANG II levels lead to a pro-fibrotic, inflammatory, and hypertrophic milieu that induces apoptosis in podocytes. The activation of RAAS is critical for the pathogenesis of podocyte injury; as such, to prevent podocyte damage, patients with hypertension are administered drugs that modulate RAAS signaling. A prime example is the orally active, non-peptide, selective angiotensin-II-type I receptor (AGTR1) blocker losartan. Here, we demonstrate that SIX2-positive urine-derived renal progenitor cells (UdRPCs) and their immortalized counterpart (UM51-hTERT) can be directly differentiated into mature podocytes. These podocytes show activation of RAAS after stimulation with ANG II, resulting in ANG II-dependent upregulation of the expression of the angiotensin-II-type I receptor, AGTR1, and the downregulated expression of the angiotensin-II-type II receptor 2 (AGTR2). The stimulation of podocytes with losartan counteracts ANG II-dependent changes, resulting in a dependent favoring of the specific receptor from AGTR1 to AGTR2. Transcriptome analysis revealed 94 losartan-induced genes associated with diverse biological processes and pathways such as vascular smooth muscle contraction, the oxytocin signaling pathway, renin secretion, and ECM-receptor interaction. Co-stimulation with losartan and ANG II induced the exclusive expression of 106 genes associated with DNA methylation or demethylation, cell differentiation, the developmental process, response to muscle stretch, and calcium ion transmembrane transport. These findings highlight the usefulness of UdRPC-derived podocytes in studying the RAAS pathway and nephrotoxicity in various kidney diseases

Correction: Nguyen et al. The Nephrotoxin Puromycin Aminonucleoside Induces Injury in Kidney Organoids Differentiated from Induced Pluripotent Stem Cells. Cells 2022, 11, 635

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Gjenbruk av gråvann i internasjonale operasjoner. En kvalitativ litteraturstudie

Studien er, etter ønske fra Hærens Våpenskole Ingeniør, en undersøkelse av hvordan et anlegg for rensing og gjenbruk av gråvann i internasjonale operasjoner kan se ut, og hvilke økonomiske effekter dette vil kunne ha. I studien blir ulik teknologi og løsninger vurdert opp mot faktorer som er viktige i internasjonale operasjoner. resultatet av dette fører til anlegget som videre blir vurdert opp mot økonomi og innsparinger. Det konkluderes med at teknologien har kommet tilstrekkelig langt til at rensing og gjenbruk av gråvann har potensiale for å redusere uttak av grunnvann, og at dette er en kapasitet Forsvaret bør tilstrebe å implementere i sine basesett.Forsvaret opererer i dag i flere områder i verden hvor det er mangel på tilgang til rent vann, i tillegg har FOH oppfordret alt militært personell til å redusere sitt forbruk av naturressurser. For å bidra mot dette målet er et av tiltakene som kan gjøres rensing og gjenbruk av gråvann, på denne måten kan forbruket av naturressursen vann reduseres, uten at dette påvirker forbruket. Dagens teknologi har kommet langt, og det finnes eksiterende løsninger som gjør det mulig å rense gråvann til drikkevannskvalitet. Dette er viktig, da det tilstrebes at alt vann som benyttes i INTOPS tilfredsstiller drikkevannskvalitet, dette for å unngå sykdom eller lignende. Selv om vannet tilfredsstiller drikkevannskvalitet er det ikke sikkert det er ønskelig fra brukerens side å benytte dette som drikkevann, og vannet bør derfor først og fremst benyttes i dusj eller klesvask, som er to av de største forbrukspostene for vann i INTOPS. En løsning som tar vann fra dusj og klesvask, og renser dette til bruk i dusj og klesvask har potensiale til å mer enn halvere uttaket fra en vannkilde. Dette fører til større robusthet for leiren, da den ikke er like avhengig av vannkilden, og kan også bidra positivt i fredsbevarende eller opprørsbekjempende operasjoner, hvor det er viktig å ha lokalbefolkningen på sin side. Ved gjenbruk av gråvann reduseres også produksjonen av avløpsvann tilsvarende, og denne reduksjonen kan gi en positiv økonomisk effekt ved at mengden vann som må kjøres bort og deponeres reduseres. Dette gir mulighet for at anskaffelsen av et anlegg i sin helhet kan spares inn etter 3 års drift. Gråvann er en relativt konstant mengde vann, og forurensningen som kan forventes i gråvann skiller seg ikke mye fra dag til dag. Dette gjør gråvann til en god vannkilde, og gjør det mulig å lage et generisk system for rensing og gjenbruk av gråvann. Systemet som presenteres i oppgaven anbefales anskaffet for Forsvaret, da det tilfredsstiller kravene til enkelhet og størrelse, som er viktige i INTOPS. Dette i tillegg til muligheten for at anskaffelsen kan spares inn gjennom drift og at systemet allerede eksisterer og slik sett er «hyllevare» er viktige faktorer.Summary: Today the Norwegian Armed Forces are operating in several areas of the world where access to potable water is limited. In addition, there is a strong directive issued from the Norwegian Joint Headquarters that encourages all military personnel to limit their usage of natural resources. One of the measures that can to contribute to this goal, is grey water treatment and recycling. By doing this, it should be possible to reduce the usage of natural resources, without influencing overall water consumption. In the last decades, technology has allowed great advances in the field of grey water treatment, meaning that there are efficient solutions to turning grey water into potable water. This is important since the military strives to maximise the use of potable water in international contingency operations, in order to reduce the likelihood of sickness among its personnel. Even though treated water currently meets the criteria for its potability, it is not recognized as such, generally among the soldiers, with the result that treated water is mainly used for showers or laundry. These are also the two biggest contributors of water usage in military contingency operations. By treating grey water from showers and laundry, and reusing it in showers and laundry, it is possible to reduce the usage of raw water to more than half of today’s use. This again will lead to a higher level of military resilience, by being less dependent on water resources. In counter insurgency or peacekeeping operations, less use of raw water could prove positive in trying to gain the goodwill of local populations. Reusing grey water also reduces the amount of wastewater produced, which again reduces the cost of depositing sewage. This reduction in cost makes it possible for the treatment system to pay for itself in less than 3 years. Grey water is a relatively consistent stream of water which contains similar pollutions from day to day. This makes grey water an ideal source for a generic solution to its treatment and reuse. The greywater treatment system presented in this thesis meets the requirements for simplicity and size, which are important factors in contingency operations. It is therefore recommended that the Norwegian Armed Forces acquire this system. In addition, the fact that the system has the potential to recover its initial cost within a three-year period, and that it is an already existing and tried system, makes it a good addition to the Norwegian force provider system

Activation of the Renin–Angiotensin System Disrupts the Cytoskeletal Architecture of Human Urine-Derived Podocytes

High blood pressure is one of the major public health problems that causes severe disorders in several tissues including the human kidney. One of the most important signaling pathways associated with the regulation of blood pressure is the renin–angiotensin system (RAS), with its main mediator angiotensin II (ANGII). Elevated levels of circulating and intracellular ANGII and aldosterone lead to pro-fibrotic, -inflammatory, and -hypertrophic milieu that causes remodeling and dysfunction in cardiovascular and renal tissues. Furthermore, ANGII has been recognized as a major risk factor for the induction of apoptosis in podocytes, ultimately leading to chronic kidney disease (CKD). In the past, disease modeling of kidney-associated diseases was extremely difficult, as the derivation of kidney originated cells is very challenging. Here we describe a differentiation protocol for reproducible differentiation of sine oculis homeobox homolog 2 (SIX2)-positive urine-derived renal progenitor cells (UdRPCs) into podocytes bearing typical cellular processes. The UdRPCs-derived podocytes show the activation of the renin–angiotensin system by being responsive to ANGII stimulation. Our data reveal the ANGII-dependent downregulation of nephrin (NPHS1) and synaptopodin (SYNPO), resulting in the disruption of the podocyte cytoskeletal architecture, as shown by immunofluorescence-based detection of α-Actinin. Furthermore, we show that the cytoskeletal disruption is mainly mediated through angiotensin II receptor type 1 (AGTR1) signaling and can be rescued by AGTR1 inhibition with the selective, competitive angiotensin II receptor type 1 antagonist, losartan. In the present manuscript we confirm and propose UdRPCs differentiated to podocytes as a unique cell type useful for studying nephrogenesis and associated diseases. Furthermore, the responsiveness of UdRPCs-derived podocytes to ANGII implies potential applications in nephrotoxicity studies and drug screening

Derivation of the Immortalized Cell Line UM51-PrePodo-hTERT and Its Responsiveness to Angiotensin II and Activation of the RAAS Pathway

Recent demographic studies predict there will be a considerable increase in the number of elderly people within the next few decades. Aging has been recognized as one of the main risk factors for the world’s most prevalent diseases such as neurodegenerative disorders, cancer, cardiovascular disease, and metabolic diseases. During the process of aging, a gradual loss of tissue volume and organ function is observed, which is partially caused by replicative senescence. The capacity of cellular proliferation and replicative senescence is tightly regulated by their telomere length. When telomere length is critically shortened with progressive cell division, cells become proliferatively arrested, and DNA damage response and cellular senescence are triggered, whereupon the “Hayflick limit” is attained at this stage. Podocytes are a cell type found in the kidney glomerulus where they have major roles in blood filtration. Mature podocytes are terminal differentiated cells that are unable to undergo cell division in vivo. For this reason, the establishment of primary podocyte cell cultures has been very challenging. In our present study, we present the successful immortalization of a human podocyte progenitor cell line, of which the primary cells were isolated directly from the urine of a 51-year-old male. The immortalized cell line was cultured over the course of one year (~100 passages) with high proliferation capacity, endowed with contact inhibition and P53 expression. Furthermore, by immunofluorescence-based expression and quantitative real-time PCR for the podocyte markers CD2AP, LMX1B, NPHS1, SYNPO and WT1, we confirmed the differentiation capacity of the immortalized cells. Finally, we evaluated and confirmed the responsiveness of the immortalized cells on the main mediator angiotensin II (ANGII) of the renin–angiotensin system (RAAS). In conclusion, we have shown that it is possible to bypass cellular replicative senescence (Hayflick limit) by TERT-driven immortalization of human urine-derived pre-podocyte cells from a 51-year-old African male

Type 2 diabetes and risk of diverticular disease:a Danish cohort study

OBJECTIVES: To investigate the association between type 2 diabetes and risk of diverticular disease. Unlike previous studies, which have found conflicting results, we aimed to distinguish between diabetes types and adjust for modifiable risk factors. DESIGN: Observational cohort study. SETTING: Population-based Danish medical databases, covering the period 2005–2018. PARTICIPANTS: Respondents of the 2010 or the 2013 Danish National Health Survey, of which there were 15 047 patients with type 2 diabetes and 210 606 patients without diabetes. PRIMARY AND SECONDARY OUTCOME MEASURES: Hazard ratios (HRs) for incident hospital diagnosis of diverticular disease adjusted for survey year, sex, age, body mass index (BMI), physical activity intensity, smoking behaviour, diet and education based on Cox regression analysis. As latency may affect the association between type 2 diabetes and diverticular disease, patients with type 2 diabetes were stratified into those with <2.5, 2.5–4.9 and ≥5 years duration of diabetes prior to cohort entry. RESULTS: For patients with and without diabetes the incidence rates of diverticular disease were 0.76 and 0.54 events per 1000 person years, corresponding to a crude HR of 1.08 (95% CI 1.00 to 1.16) and an adjusted HR of 0.88 (95% CI 0.80 to 0.96). The HR was lower among patients with ≥5 years duration of diabetes (adjusted HR: 0.76, 95% CI 0.67 to 0.87) than among those with 2.5–4.9 years or <2.5 years duration. CONCLUSION: We found that patients with type 2 diabetes had a higher incidence rate of diverticular disease compared with patients without diabetes. However, after adjustment for modifiable risk factors, driven by BMI, type 2 diabetes appeared to be associated with a slightly lower risk of diverticular disease. Lack of adjustment for BMI may partially explain the conflicting findings of previous studies