Very low energy diets in the treatment of obesity : studies of obstructive sleep apnoea, side-effects, and treatment discontinuation

Background: The prevalence of obesity has increased dramatically during the last decades worldwide. Obesity is associated with increased risk of morbidity and mortality, leading to an increased suffering for the individual patient and an increased burden on the health care system. Currently, the most effective treatment is bariatric surgery. Since bariatric surgery cannot be provided to all obese patients, other non-surgical obesity treatment methods are needed. Aim: The overall objective of this thesis was to evaluate effects and side-effects of very low energy diets (VLEDs), as well as to characterise treatment discontinuation. Specific objectives were to evaluate weight loss as treatment option for patients with obstructive sleep apnoea (OSA; Study I&II); to assess the risk of gallstones requiring hospital care, and cholecystectomy, in a commercial weight loss programme using VLED or low energy diet (LED; Study III); and to characterise discontinuation patterns in obesity treatment programmes by analysing data from anti-obesity drug trials (Study IV). Methods: The study on OSA and weight loss (Study I&II) consisted of a randomised controlled trial (RCT) followed by an observational follow-up for a total duration of one year. Included were obese men (n=63, BMI 30-40, aged 30-65 years) with moderate to severe OSA (apnoea-hypopnoea index (AHI) ≥15) treated with CPAP. The intervention consisted of a hospital-based weight loss programme, using VLED (554 kcal/day) to promote weight loss for nine weeks After the RCT was finished the controls also received VLED. The VLED, in both groups, was followed by a 43-week weight loss maintenance phase. Study III was a one-year matched cohort study of consecutively enrolled adults in a commercial weight loss programme in Sweden between 2006 and 2009 (n=6,640; mean age 46y; 83% women; mean BMI 33). The intervention included a three-month weight loss phase, consisting of either VLED (500 kcal/day) or LED (1,200-1,500 kcal/day), followed by a nine-month weight loss maintenance phase. Gallstones requiring hospital care and cholecystectomies during the one-year programme were collected from the National Patient Register. Study IV was a systematic review and meta-analysis including published placebo-controlled anti-obesity trials of orlistat, sibutramine and rimonabant (n=13,457). Results: Study I&II: After the nine-week RCT the intervention group’s mean body weight was 20 kg lower than that of the control group, and its mean AHI was 23 events/h lower. In total 70% (44/63) completed the one-year pooled observational follow-up. The AHI changes after nine weeks of VLED (-58%) were largely maintained at one-year (-47%) following the initial weight loss of 18 kg, and 12 kg at one year. Study III: The absolute risks of gallstones requiring hospital care and cholecystectomy were found to be low, but three times higher in the VLED than the LED programme (hazard ratio 3.4 and 3.1, respectively; both P<0.001). While the risks were greater in the VLED compared to LED group, the benefits in terms of one-year weight loss was also greater (11 vs 8 kg; P<0.001), and the proportion remaining in the programme (82% vs 78%; P<0.001). Study IV: The overall combined one-year dropout rates were high in both the drug (30-39%) and placebo arms (37%) of placebo-controlled anti-obesity drug trials, but marginally lower in the drug arms (pooled risk ratio 0.9; P=0.001). Conclusion: VLED-induced weight loss resulted in a significant reduction of moderate to severe OSA, with the majority of the initial improvement maintained at one year. Albeit low, the risks of gallstones and cholecystectomy were greater with VLED than LED treatment, as was weight loss. Treatment discontinuation was lower both in the hospital-based weight loss programme and in the commercial weight loss programme, as compared to pooled data from the placebo arms in anti-obesity drug trials

Interpretations of the book of Ruth : a critical study

https://place.asburyseminary.edu/ecommonsatsdissertations/1979/thumbnail.jp

Rekneark på ungdomstrinnet

Problemstillinga i oppgåva var korleis opplever elevane bruk av rekneark i matematikk på ungdomstrinnet. Gjennom eitt år vart ulike reknearkoppgåver prøvd ut i 9./10. klasse. I etterkant henta eg inn data ved hjelp av spørjeskjema, opptaksoppgåver av to og to elevar som løyste utvalde oppgåver og eit gruppeintervju. Eg la vekt på kva fordelar og problem elevane opplevde, og kva ulike typar oppgåver som er relevante for elevane.VID-MAUMATMAUMAT65

[2,6-Bis(di-tert-butyl­phosphinometh­yl)phenyl-κ3 P,C 1,P′](trifluoro­acetato)palladium(II)

The PdII atom in the title compound, [Pd(C2F3O2)(C24H43P2)], adopts a distorted square-planar geometry with the P atoms in a trans arrangement, forming two five-membered chelate rings. Four intra­molecular C—H⋯O hydrogen bonds occur. The crystal packing reveals one weak inter­molecular C—H⋯O hydrogen bond, which self-assembles the mol­ecules into infinite chains parallel to the b axis

Antisense RNA directed to the human papillomavirus type 16 E7 mRNA from herpes simplex virus type 1 derived vectors is expressed in CaSki cells and downregulates E7 mRNA

<p>Abstract</p> <p>Background</p> <p>Human papillomavirus (HPV) infection is known to be the most important etiologic factor of cervical cancer. There is no HPV specific therapy available for treatment of invasive squamous cell carcinoma of the cervix and its precursor lesions. The present study elucidates the potential to use herpes simplex virus (HSV) derived vectors for expression of antisense RNA to HPV -16 E7 oncogene.</p> <p>Results</p> <p>We have constructed replication competent, nonneuroinvasive HSV-1 vectors, deleted of the γ₁34.5 gene. The vectors express RNA antisense to the first 100 nucleotides of the HPV-16 E7 gene. We assayed the ability of the antisense E7 vectors R5225 (<it>tk</it>-) and R5226 (<it>tk+</it>), to produce antisense RNA, as well as the consequent effects on E7 mRNA and protein levels in HPV-16 positive CaSki cells. Anti-E7 RNA was expressed by both constructs in a dose-dependent manner. Expression of HPV-16 E7 mRNA was downregulated effectively in CaSki cells infected with the <it>tk- </it>recombinant R5225 or with R5226. The <it>tk+ </it>recombinant R5226 was effective in downregulating E7 protein expression.</p> <p>Conclusion</p> <p>We have shown that anti-E7 RNA expressed from an HSV vector could efficiently downregulate HPV-16 E7 mRNA and E7 protein expression in CaSki cells. We conclude that HSV vectors may become a useful tool for gene therapy of HPV infections.</p

Light-Activated Liposomes Coated with Hyaluronic Acid as a Potential Drug Delivery System

Light-activated liposomes permit site and time-specific drug delivery to ocular and systemic targets. We combined a light activation technology based on indocyanine green with a hyaluronic acid (HA) coating by synthesizing HA–lipid conjugates. HA is an endogenous vitreal polysaccharide and a potential targeting moiety to cluster of differentiation 44 (CD44)-expressing cells. Light-activated drug release from 100 nm HA-coated liposomes was functional in buffer, plasma, and vitreous samples. The HA-coating improved stability in plasma compared to polyethylene glycol (PEG)-coated liposomes. Liposomal protein coronas on HA- and PEG-coated liposomes after dynamic exposure to undiluted human plasma and porcine vitreous samples were hydrophilic and negatively charged, thicker in plasma (~5 nm hard, ~10 nm soft coronas) than in vitreous (~2 nm hard, ~3 nm soft coronas) samples. Their compositions were dependent on liposome formulation and surface charge in plasma but not in vitreous samples. Compared to the PEG coating, the HA-coated liposomes bound more proteins in vitreous samples and enriched proteins related to collagen interactions, possibly explaining their slightly reduced vitreal mobility. The properties of the most abundant proteins did not correlate with liposome size or charge, but included proteins with surfactant and immune system functions in plasma and vitreous samples. The HA-coated light-activated liposomes are a functional and promising alternative for intravenous and ocular drug delivery

Responses to projected changes in climate and UV-B at the species level

Environmental manipulation experiments showed that species respond individualistically to each environmental-change variable. The greatest responses of plants were generally to nutrient, particularly nitrogen, addition. Summer warming experiments showed that woody plant responses were dominant and that mosses and lichens became less abundant. Responses to warming were controlled by moisture availability and snow cover. Many invertebrates increased population growth in response to summer warming, as long as desiccation was not induced. CO2 and UV-B enrichment experiments showed that plant and animal responses were small. However, some microorganisms and species of fungi were sensitive to increased UV-B and some intensive mutagenic actions could, perhaps, lead to unexpected epidemic outbreaks. Tundra soil heating, CO 2 enrichment and amendment with mineral nutrients generally accelerated microbial activity. Algae are likely to dominate cyanobacteria in milder climates. Expected increases in winter freeze-thaw cycles leading to ice-crust formation are likely to severely reduce winter survival rate and disrupt the population dynamics of many terrestrial animals. A deeper snow cover is likely to restrict access to winter pastures by reindeer/caribou and their ability to flee from predators while any earlier onset of the snow-free period is likely to stimulate increased plant growth. Initial species responses to climate change might occur at the sub-species level: an Arctic plant or animal species with high genetic/racial diversity has proved an ability to adapt to different environmental conditions in the past and is likely to do so also in the future. Indigenous knowledge, air photographs, satellite images and monitoring show that changes in the distributions of some species are already occurring: Arctic vegetation is becoming more shrubby and more productive, there have been recent changes in the ranges of caribou, and "new" species of insects and birds previously associated with areas south of the treeline have been recorded. In contrast, almost all Arctic breeding bird species are declining and models predict further quite dramatic reductions of the populations of tundra birds due to warming. Species-climate response surface models predict potential future ranges of current Arctic species that are often markedly reduced and displaced northwards in response to warming. In contrast, invertebrates and microorganisms are very likely to quickly expand their ranges northwards into the Arctic

Association of sweetened carbonated beverage consumption during pregnancy and ADHD symptoms in the ofspring: a study from the Norwegian Mother, Father and Child Cohort Study (MoBa)

Purpose Intrauterine exposures influence offspring health and development. Here we investigated maternal intake of sweetened carbonated beverages (SCB) during pregnancy and its association with ADHD symptoms in the offspring. Methods This study was based on the Norwegian Mother, Father and Child Cohort Study (MoBa) and the Medical Birth Registry of Norway. Maternal diet mid-pregnancy was assessed using a food frequency questionnaire (FFQ). All mothers who responded to the FFQ and a questionnaire when their child was 8 years of age were included (n = 39,870). The exposure was defined as maternal intake (daily servings) of SCB, using no daily intake as reference. Outcome was offspring ADHD symptoms, evaluated as a continuous standardized ADHD score and as a binary outcome of six or more ADHD symptoms vs. five symptoms or less. Associations were analysed using log-binomial regression and linear mixed regression models with adjustment for covariates. Results The adjusted regression coefficients for the standardized ADHD offspring symptom score were 0.31 [95% confidence intervals (0.001, 0.62)] and 0.46 (0.15, 0.77) for maternal daily intake of ≥ 1 glasses of SCB, when the models included adjustments for total energy intake or energy intake from other sources than SCBs and sweet drinks, respectively. The corresponding adjusted relative risks were 1.16 (1.004, 1.34) and 1.21. (1.05, 1.39) for drinking ≥ 1 glasses daily. Conclusion In a large pregnancy cohort with offspring followed until 8 years of age, we found an association between maternal daily intake of SCB and offspring ADHD symptoms. These results suggest a weak positive relationship between prenatal exposure to SCB and offspring ADHD.publishedVersio

Assessing the Causal Relationship of Maternal Height on Birth Size and Gestational Age at Birth : A Mendelian Randomization Analysis

Background Observational epidemiological studies indicate that maternal height is associated with gestational age at birth and fetal growth measures (i.e., shorter mothers deliver infants at earlier gestational ages with lower birth weight and birth length). Different mechanisms have been postulated to explain these associations. This study aimed to investigate the casual relationships behind the strong association of maternal height with fetal growth measures (i.e., birth length and birth weight) and gestational age by a Mendelian randomization approach. Methods and Findings We conducted a Mendelian randomization analysis using phenotype and genome-wide single nucleotide polymorphism (SNP) data of 3,485 mother/infant pairs from birth cohorts collected from three Nordic countries (Finland, Denmark, and Norway). We constructed a genetic score based on 697 SNPs known to be associated with adult height to index maternal height. To avoid confounding due to genetic sharing between mother and infant, we inferred parental transmission of the height-associated SNPs and utilized the haplotype genetic score derived from nontransmitted alleles as a valid genetic instrument for maternal height. In observational analysis, maternal height was significantly associated with birth length (p = 6.31 x 10(-9)), birth weight (p = 2.19 x 10(-15)), and gestational age (p = 1.51 x 10(-7)). Our parental-specific haplotype score association analysis revealed that birth length and birth weight were significantly associated with the maternal transmitted haplotype score as well as the paternal transmitted haplotype score. Their association with the maternal nontransmitted haplotype score was far less significant, indicating a major fetal genetic influence on these fetal growth measures. In contrast, gestational age was significantly associated with the nontransmitted haplotype score (p = 0.0424) and demonstrated a significant (p = 0.0234) causal effect of every 1 cm increase in maternal height resulting in similar to 0.4 more gestational d. Limitations of this study include potential influences in causal inference by biological pleiotropy, assortative mating, and the nonrandom sampling of study subjects. Conclusions Our results demonstrate that the observed association between maternal height and fetal growth measures (i.e., birth length and birth weight) is mainly defined by fetal genetics. In contrast, the association between maternal height and gestational age is more likely to be causal. In addition, our approach that utilizes the genetic score derived from the nontransmitted maternal haplotype as a genetic instrument is a novel extension to the Mendelian randomization methodology in casual inference between parental phenotype (or exposure) and outcomes in offspring.Peer reviewe