Healthcare Burden in Greenland of Gastrointestinal Symptoms in Adults with Inherited Loss of Sucrase-Isomaltase Function.

Background: Congenital sucrase isomaltase deficiency (CSID) is in general a very rare disease. However, 2-3% of the Greenlandic population are homozygous (HO) carriers of an Arctic-specific loss-of-function (LoF) variant in the sucrase-isomaltase (SI) encoding gene, causing CSID. The condition is characterized by gastrointestinal symptoms such as stomachache, diarrhea, and weight loss when consuming sucrose, the most common dietary sugar. However, the awareness of the condition in the population and the healthcare system seems to be limited, potentially leading to a higher healthcare burden. Hence, we aimed to investigate whether HO-carriers visit the healthcare system more with gastrointestinal symptoms compared to the control groups by using registry data. Methods: We performed a case-control study identifying cases and controls using genotype information from the 1999-2001 and 2005-2010 Greenlandic health population cohorts. The cases were defined as HO LoF SI-carriers and controls were defined as non-carriers and were matched (1:1) on sex, age, place of residence, and European genetic admixture. We used electronic medical records to assess the number of electronic medical record contacts (EMRc) related to gastrointestinal symptoms and the number of gastrointestinal-related diagnostic procedures. Results: A total of 80 HO-carriers and 80 non-carriers were included. The HO-carriers had 19% more EMRc related to gastrointestinal symptoms (IRR, 1.19, 95% CI [1.02;1.40], p=0.02) and had a 41% higher incidence of gastrointestinal related diagnostic procedures compared to controls (IRR, 1.41, 95% CI [1.05-1.92], p=0.02). Only one HO-carrier was aware of the condition according to the electronic medical records. Conclusion: HO-carriers of the LoF SI-variant had both significantly more gastrointestinal-related EMRc and significantly more diagnostic procedures conducted due to gastrointestinal symptoms. Only one HO-carrier was aware of the condition. Given the high prevalence of HO-carriers in the Greenlandic population, we anticipate that diagnosing more patients with CSID and providing dietary advice could potentially reduce symptom burden and healthcare visits among HO-carriers.

The effect of sucrase-isomaltase deficiency on metabolism, food intake and preferences: protocol for a dietary intervention study.

In Greenland, traditional marine foods are increasingly being replaced by sucrose- and starch-rich foods. A knock-out c.273_274delAG variant in the sucrase-isomaltase (SI) gene is relatively common in Greenland, with homozygous carriers being unable to digest sucrose and some starch. The variant is associated with a healthier metabolic phenotype in Greenlanders, which is confirmed by SI-knockout mice. We aim to assess if the healthy phenotype is explained by metabolic and microbial differences and if food and taste preferences differ between SI-genotypes. This paper describes the protocol for a randomised cross-over trial conducted in Greenland in 2022 with two dietary interventions of three days; a traditional meat- and fish-rich diet and a starch-rich Western diet with 11 energy% sucrose. The power calculation showed that 22 homozygous SI-carriers and 22 non-carriers were sufficient to detect a 0.5 mmol/L difference in glycaemic variability (80% power, α=0.05). We enrolled 18 carriers and 20 non-carriers. We examined food preferences at baseline and collected samples before and after each intervention for metabolic, metabolome, and microbiome profiling. Analyses of samples have not been completed yet. The Ethics Committee of Greenland approved the study. Results will be disseminated in international peer-reviewed journals and to the general Greenlandic population. NCT05375656.

Sleep is required to consolidate odor memory and remodel olfactory synapses.

Animals with complex nervous systems demand sleep for memory consolidation and synaptic remodeling. Here, we show that, although the Caenorhabditis elegans nervous system has a limited number of neurons, sleep is necessary for both processes. In addition, it is unclear if, in any system, sleep collaborates with experience to alter synapses between specific neurons and whether this ultimately affects behavior. C. elegans neurons have defined connections and well-described contributions to behavior. We show that spaced odor-training and post-training sleep induce long-term memory. Memory consolidation, but not acquisition, requires a pair of interneurons, the AIYs, which play a role in odor-seeking behavior. In worms that consolidate memory, both sleep and odor conditioning are required to diminish inhibitory synaptic connections between the AWC chemosensory neurons and the AIYs. Thus, we demonstrate in a living organism that sleep is required for events immediately after training that drive memory consolidation and alter synaptic structures.

Dyslipidemia and the preventive potential in the Greenlandic population.

Background: Low-density lipoprotein cholesterol (LDL-C) is a well-established risk factor for development of cardiovascular diseases. Based on available clinical data, we aimed to investigate the plasma lipid profile in the Greenlandic population, the proportion on cholesterol-lowering treatment and the adherence to local indications for cholesterol-lowering therapy. Methods: This is an observational cross-sectional study of the adult (≥21 years) Greenlandic population with focus on clinically determined lipid levels from 2017 to early 2022. We investigated levels of dyslipidemia and assessed cholesterol-lowering medication usage in individuals with an indication according to current Greenlandic guidelines, which include a) LDL-C >5 mmol/l, b) diabetes, c) diagnosed atherosclerotic disease and 4) a SCORE2 >7.5%. Results: In the adult Greenlandic population of 40,565 individuals a lipid profile was available in 13,895 with a mean LDL-C of 3.0 mmol/L and 976 (7%) had a LDL-C >5 mmol/l. One or more indications for cholesterol-lowering medication was present in 3988 individuals and a total of 5464 adult Greenlanders either fulfilled local criteria for statin therapy or received a statin (some without current indication) and among these, 2232 (41%) individuals received no statin. Conclusion: These findings indicate that clinically significant dyslipidemia is common in the adult Greenlandic population and that the cardiovascular preventive potential of cholesterol-lowering therapy is currently underutilized.

Association between neonatal homecare for preterm infants and incidence of severe postpartum depression in mothers.

BACKGROUND: Understanding the association between neonatal homecare and postpartum depression could contribute to the design of evidence-based interventions to prevent postpartum depression. We aimed to determine whether the change from inpatient stays in neonatal intensive care units to offering neonatal homecare was associated with a reduced incidence rate of severe postpartum depression among mothers who gave birth prematurely. METHODS: We conducted a register-based population-wide study of all mothers who gave birth prematurely 1994-2017 to live-born infants and spent at least one night in the Neonatal Intensive Care Unit. We performed an interrupted time series analysis to investigate the incidence rate ratio of severe postpartum depression before and after the implementation of neonatal homecare. Neonatal homecare was implemented between 1994 and 2016. RESULTS: The total population consisted of 46,456 mothers and the median age was 30 years and interquartile range of 27-34 years. Overall 4.5 % of the mothers were diagnosed with severe postpartum depression. Prior to neonatal homecare no change in the incidence of severe postpartum depression was found; (incidence rate ratio=1.01 [95 % confidence interval: 0.97-1.05] every half year, p=0.69). The implementation was associated with a level change with an incidence rate ratio reduction of 23 % (incidence rate ratio=0.77 [95 % confidence interval: 0.64-0.93], p=0.007). LIMITATIONS: Limitations include potential underdiagnosis in early periods, lack of randomization, and different periods of implementation of neonatal homecare. CONCLUSIONS: We found a possible association between the implementation of neonatal homecare and a 23 % reduced incidence rate of severe postpartum depression among mothers of preterm infants.

Using a Robust and Sensitive GFP-Based cGMP Sensor for Real-Time Imaging in Intact Caenorhabditis elegans.

cGMP plays a role in sensory signaling and plasticity by regulating ion channels, phosphodiesterases, and kinases. Studies that primarily used genetic and biochemical tools suggest that cGMP is spatiotemporally regulated in multiple sensory modalities. FRET- and GFP-based cGMP sensors were developed to visualize cGMP in primary cell culture and Caenorhabditis elegans to corroborate these findings. While a FRET-based sensor has been used in an intact animal to visualize cGMP, the requirement of a multiple emission system limits its ability to be used on its own as well as with other fluorophores. Here, we demonstrate that a C. elegans codon-optimized version of the cpEGFP-based cGMP sensor FlincG3 can be used to visualize rapidly changing cGMP levels in living, behaving C. elegans We coexpressed FlincG3 with the blue-light-activated guanylyl cyclases BeCyclOp and bPGC in body wall muscles, and found that the rate of change in FlincG3 fluorescence correlated with the rate of cGMP production by each cyclase. Furthermore, we show that FlincG3 responds to cultivation temperature, NaCl concentration changes, and sodium dodecyl sulfate in the sensory neurons AFD, ASEL/R, and PHB, respectively. Intriguingly, FlincG3 fluorescence in ASEL and ASER decreased in response to a NaCl concentration upstep and downstep, respectively, which is opposite in sign to the coexpressed calcium sensor jRGECO1a and previously published calcium recordings. These results illustrate that FlincG3 can be used to report rapidly changing cGMP levels in an intact animal, and that the reporter can potentially reveal unexpected spatiotemporal landscapes of cGMP in response to stimuli.

Cardiotocography interpretation skills and the association with size of maternity unit, years of obstetric work experience and healthcare professional background: a national cross-sectional study.

INTRODUCTION: We aimed to examine whether cardiotocography (CTG) knowledge, interpretation skills and decision-making measured by a written assessment were associated with size of maternity unit, years of obstetric work experience and healthcare professional background. MATERIAL AND METHODS: A national cross-sectional study in the setting of a CTG teaching intervention involving all 24 maternity units in Denmark. Participants were midwives (n = 1260) and specialists (n = 269) and residents (n = 142) in obstetrics and gynecology who attended a 1-day CTG course and answered a 30-item multiple-choice question test. Associations between mean test score and work conditions were analyzed using multivariable robust regression, in which the three variables were mutually adjusted. RESULTS: Participants from units with > 3000 deliveries/year scored higher on the test than participants from units with < 1000 deliveries/year (3000-3999 deliveries/year: mean difference 0.8, p < 0.0001; > 4000 deliveries/year: mean difference 0.5, p = 0.006). Participants with < 15 years of work experience scored higher than participants with > 15 years of experience (15-20 years of experience: mean difference - 0.6, p = 0.007; > 20 years experience: mean difference - 0.9, p < 0.0001). No differences were detected concerning professional background. CONCLUSIONS: CTG knowledge, interpretation skills and decision-making measured by a written assessment were positively associated with working in large maternity units and having < 15 years of obstetric work experience. This might indicate a challenge in maintaining CTG skills in small units and among experienced staff but could also reflect different levels of motivation, test familiarity and learning culture. Whether the findings are transferable to the clinical setting was not examined.

Development of a written assessment for a national interprofessional cardiotocography education program.

BACKGROUND: To reduce the incidence of hypoxic brain injuries among newborns a national cardiotocography (CTG) education program was implemented in Denmark. A multiple-choice question test was integrated as part of the program. The aim of this article was to describe and discuss the test development process and to introduce a feasible method for written test development in general. METHODS: The test development was based on the unitary approach to validity. The process involved national consensus on learning objectives, standardized item writing, pilot testing, sensitivity analyses, standard setting and evaluation of psychometric properties using Item Response Theory models. Test responses and feedback from midwives, specialists and residents in obstetrics and gynecology, and medical and midwifery students were used in the process (proofreaders n = 6, pilot test participants n = 118, CTG course participants n = 1679). RESULTS: The final test included 30 items and the passing score was established at 25 correct answers. All items fitted a loglinear Rasch model and the test was able to discriminate levels of competence. Seven items revealed differential item functioning in relation to profession and geographical regions, which means the test is not suitable for measuring differences between midwives and physicians or differences across regions. In the setting of pilot testing Cronbach's alpha equaled 0.79, whereas Cronbach's alpha equaled 0.63 in the setting of the CTG education program. This indicates a need for more items and items with a higher degree of difficulty in the test, and illuminates the importance of context when discussing validity. CONCLUSIONS: Test development is a complex and time-consuming process. The unitary approach to validity was a useful and applicable tool for development of a CTG written assessment. The process and findings supported our proposed interpretation of the assessment as measuring CTG knowledge and interpretive skills. However, for the test to function as a high-stake assessment a higher reliability is required.

Improved Functional Performance in Geriatric Patients During Hospital Stay.

OBJECTIVE: The aim of this work was to evaluate the time course of changes in strength and functional performance in elderly hospitalized medical patients. DESIGN: This was a prospective observational study in elderly medical patients of age 65 years or older at a geriatric department.Measurements were obtained on days 2 to 4, day 5 to 8, and days 9 to 13. Functional performance was measured with De Morton Mobility Index (DEMMI) test and a 30-second chair stand test (30-s CST). Muscular strength was measured with handgrip strength. Activity level was determined with accelerometry (ActivPAL). RESULTS: Results in DEMMI and 30-s CST gradually improved (P < 0.05), whereas handgrip strength remained unchanged (P > 0.05). Larger functional improvements were observed in patients with "high" compared to "low" and "moderate" activity level (P < 0.05). Changes in DEMMI score correlated with changes in 30-s CST (P < 0.05); however, changes in DEMMI score and 30-s CST were more likely to occur in patients with a low versus high functional level, respectively. CONCLUSIONS: Functional performance of the lower extremities in geriatric patients improves moderately over the time of a hospital stay of less than 14 days, with larger improvements in patients with high activity level. The DEMMI test and the 30-s CST seem to be complementary to each other when evaluating functional changes in a geriatric hospital population. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon completion of this article, the reader should be able to (1) describe changes in mobility and muscle strength of geriatric patients during a hospital stay of less than 14 days, (2) understand the significance of physical activity during hospital admission in geriatric patients, and (3) discuss the potential limitations of measures for assessing mobility and lower extremity strength status and change during a hospital admission. LEVEL: Advanced ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this activity for a maximum of 1.5 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Unannounced in situ simulation of obstetric emergencies: staff perceptions and organisational impact.

AIM: To describe how unannounced in situ simulation (ISS) was perceived by healthcare professionals before and after its implementation, and to describe the organisational impact of ISS. STUDY DESIGN: Ten unannounced ISS involving all staff were scheduled March-August 2007. Questionnaire surveys on staff perceptions were conducted before (2003-2006) and after (2007-2008) implementation of unannounced ISS. Information from the debriefing sessions following each ISS constituted a proxy measure of the organisational impact of the ISS. RESULTS: Five out of ten of the unannounced ISS scheduled were conducted. Twenty-three members of the staff at work on a scheduled day for ISS were randomly selected to participate. Questionnaires before implementation revealed that 137/196 (70%) of staff members agreed or strongly agreed that ISS was a good idea and 52/199 (26%) thought it likely to be stressful and unpleasant. Questionnaires completed after implementation showed significantly more staff members, 135/153 (89%), thought ISS was a good idea. A significantly higher amount of staff members 50/153 (33%) found it to be stressful and unpleasant, and among midwives, 15/59 (25%) were anxious about ISS, whereas none of the obstetricians reported this. Information obtained through debriefing sessions generated learning points. CONCLUSIONS: The number of staff members with a positive perception of multiprofessional unannounced ISS increased after implementation; however, one-third considered ISS to be stressful and unpleasant and midwives more frequently so. The specific perception of ISS by each healthcare profession should be taken into account when planning ISS. The information from the debriefing sessions showed that implementation of ISS had an impact as it provided information required for organisational changes.

The Electronic Structure of Carcinogenic Dibenzopyrenes: Linear Dichroism, Fluorescence Polarization Spectroscopy and Quantum Mechanical Calculations.

Abstract- In studies of polycyclic aromatic hydrocarbon carcinogenicity three dibenzopyrenes have been named as the strongest mutagens together with the frequently studied benzo[a]pyrene. A detailed study of the electronic structure of one of the three compounds, dibenzo [a, i] pyrene, was performed several years ago. Here we present a similar study of the two remaining compounds, dibenzo [a, h] pyrene and dibenzo [a, e] pyrene. The studies include electronic linear dichroism spectra, fluorescence polarization spectra and quantum mechanical calculations for both molecules, as well as vibrational linear dichroism spectra for the former of the two.